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1.
Clin Transl Med ; 14(7): e1749, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38951127

RESUMEN

During myocardial ischaemia‒reperfusion injury (MIRI), the accumulation of damaged mitochondria could pose serious threats to the heart. The migrasomes, newly discovered mitocytosis-mediating organelles, selectively remove damaged mitochondria to provide mitochondrial quality control. Here, we utilised low-intensity pulsed ultrasound (LIPUS) on MIRI mice model and demonstrated that LIPUS reduced the infarcted area and improved cardiac dysfunction. Additionally, we found that LIPUS alleviated MIRI-induced mitochondrial dysfunction. We provided new evidence that LIPUS mechanical stimulation facilitated damaged mitochondrial excretion via migrasome-dependent mitocytosis. Inhibition the formation of migrasomes abolished the protective effect of LIPUS on MIRI. Mechanistically, LIPUS induced the formation of migrasomes by evoking the RhoA/Myosin II/F-actin pathway. Meanwhile, F-actin activated YAP nuclear translocation to transcriptionally activate the mitochondrial motor protein KIF5B and Drp1, which are indispensable for LIPUS-induced mitocytosis. These results revealed that LIPUS activates mitocytosis, a migrasome-dependent mitochondrial quality control mechanism, to protect against MIRI, underlining LIPUS as a safe and potentially non-invasive treatment for MIRI.


Asunto(s)
Modelos Animales de Enfermedad , Daño por Reperfusión Miocárdica , Animales , Ratones , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/terapia , Ondas Ultrasónicas , Masculino , Ratones Endogámicos C57BL , Mitocondrias/metabolismo
2.
Chem Sci ; 15(20): 7643-7650, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38784741

RESUMEN

Attaining meticulous dominion over the binding milieu of catalytic metal sites remains an indispensable pursuit to tailor product selectivity and elevate catalytic activity. By harnessing the distinctive attributes of a Zr4+-anchored thiacalix[4]arene (TC4A) metalloligand, we have pioneered a methodology for incorporating catalytic Ag1+ sites, resulting in the first Zr-Ag bimetallic cluster, Zr2Ag7, which unveils a dualistic configuration embodying twin {ZrAg3(TC4A)2} substructures linked by an {AgSal} moiety. This cluster unveils a trinity of discrete Ag sites: a pair ensconced within {ZrAg3(TC4A)2} subunits and one located between two units. Expanding the purview, we have also crafted ZrAg3 and Zr2Ag2 clusters, meticulously mimicking the two Ag site environment inherent in the {ZrAg3(TC4A)2} monomer. The distinct structural profiles of Zr2Ag7, ZrAg3, and Zr2Ag provide an exquisite foundation for a precise comparative appraisal of catalytic prowess across three Ag sites intrinsic to Zr2Ag7. Remarkably, Zr2Ag7 eclipses its counterparts in the electroreduction of CO2, culminating in a CO faradaic efficiency (FECO) of 90.23% at -0.9 V. This achievement markedly surpasses the performance metrics of ZrAg3 (FECO: 55.45% at -1.0 V) and Zr2Ag2 (FECO: 13.09% at -1.0 V). Utilizing in situ ATR-FTIR, we can observe reaction intermediates on the Ag sites. To unveil underlying mechanisms, we employ density functional theory (DFT) calculations to determine changes in free energy accompanying each elementary step throughout the conversion of CO2 to CO. Our findings reveal the exceptional proficiency of the bridged-Ag site that interconnects paired {ZrAg3(TC4A)2} units, skillfully stabilizing *COOH intermediates, surpassing the stabilization efficacy of the other Ag sites located elsewhere. The invaluable insights gleaned from this pioneering endeavor lay a novel course for the design of exceptionally efficient catalysts tailored for CO2 reduction reactions, emphatically underscoring novel vistas this research unshrouds.

3.
Sensors (Basel) ; 24(10)2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38793975

RESUMEN

Multistatic synthetic aperture radar (SAR) is a special mode of SAR system. The radar transmitter and receiver are located on different satellites, which brings many advantages, such as flexible baseline configuration, diverse receiving modes, and more detailed ground object classification information. The multistatic SAR has been widely used in interferometry, moving target detection, three-dimensional imaging, and other fields. The frequency offset between different oscillators will cause a modulation phase error in the signal. Therefore, phase synchronization is one of the most critical problems to be addressed in distributed SAR systems. This article reviews phase synchronization techniques, which are mainly divided into two methods: synchronization by direct microwave link and synchronization by a data-based estimation algorithm. Furthermore, the future development of synchronization technology is anticipated.

4.
Front Pharmacol ; 15: 1362857, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38567356

RESUMEN

Introduction: Ischemic stroke is the second most common chronic disease worldwide and is associated with high morbidity and mortality. Thromboembolism and platelet aggregation are the most characteristic features of stroke. Other than aspirin, no standard, accepted, or effective treatment for acute ischemic stroke has been established. Consequently, it is essential to identify novel therapeutic compounds for this condition. Methods: In this study, novel ozagrel/paeonol-containing codrugs were synthesized and characterized using 1H-NMR, 13C-NMR, and mass spectroscopy. Their antiplatelet aggregation activity was evaluated, with compound PNC3 found to exhibit the best effect. Subsequently, studies were conducted to assess its neuroprotective effect, pharmacokinetic properties and model its binding mode to P2Y12 and TXA2, two proteins critical for platelet aggregation. Results: The results indicated that PNC3 has good bioavailability and exerts protective effects against oxygen-glucose deprivation injury in PC12 cells. Molecular docking analysis further demonstrated that the compound interacts with residues located in the active binding sites of the target proteins. Conclusion: The codrugs synthesized in this study display promising pharmacological activities and have the potential for development as an oral formulation.

5.
Ecol Evol ; 14(4): e11279, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38633519

RESUMEN

Wolbachia, one of the most ubiquitous heritable symbionts in lepidopteran insects, can cause mitochondrial introgression in related host species. We recently found mito-nuclear discordance in the Lepidopteran tribe Tagiadini Mabille 1878 from which Wolbachia has not been reported. In this study, we found that 13 of the 46 species of Tagiadini species tested were positive for Wolbachia. Overall, 14% (15/110) of Tagiadini specimens were infected with Wolbachia and nine new STs were found from 15 isolates. A co-phylogenetic comparison, divergence time estimation and Wolbachia recombination analysis revealed that mito-nuclear discordance in Tagiadini species is not mediated by Wolbachia, but Wolbachia acquisition in Tagiadini appears to have occurred mainly through horizontal transmission rather than codivergence.

6.
Mol Immunol ; 169: 37-49, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38493580

RESUMEN

BACKGROUND: Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) lead to severe irritation and impaired sperm quality in males. However, current therapeutic options often fail to achieve satisfactory effects. Consequently, the investigation of novel treatment strategies or remedies holds substantial clinical importance. As a flavonoid monomer, isoliquiritigenin (ISL) has been shown to possess anti-inflammatory activity, especially in several chronic nonspecific-inflammatory conditions. Thus, an exploration of the possible anti-inflammatory effects of ISL on CP/CPPS, a chronic aseptic inflammation of the prostate, has significant potential. METHODS: An experimental autoimmune prostatitis (EAP) model was used for the evaluation of the anti-inflammatory effects of ISL. It was found that ISL treatment could reduce the secretion and invasion of pro-inflammatory cytokines in prostate tissue. In EAP mice, ISL treatment also reduced oxidative stress (OS) and activation of the NLRP3 inflammasome. In vitro, ISL upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibited NLRP3 inflammasome activation in RAW264.7 macrophages exposed to lipopolysaccharide (LPS). RESULTS: Treatment with ISL treatment relieved prostate inflammation and pelvic pain in EAP mice. Both in vivo and in vitro, ISL treatment activated Nrf2/HO-1 signaling, which in turn inhibited oxidative stress and activation of the NLRP3 inflammasome. Blockade of Nrf2/HO-1 signaling abolished the inhibitory effects of ISL on oxidative stress and NLRP3 inflammasome activation. CONCLUSIONS: Isoliquiritigenin reduced experimental autoimmune prostatitis by facilitating Nrf2 activation and suppressing the NLRP3 inflammasome pathway.


Asunto(s)
Chalconas , Prostatitis , Animales , Humanos , Masculino , Ratones , Antiinflamatorios/farmacología , Inflamasomas , Inflamación , Factor 2 Relacionado con NF-E2/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Dolor Pélvico , Prostatitis/tratamiento farmacológico
7.
Nat Commun ; 15(1): 671, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38253634

RESUMEN

The offshore ocean heat supplied to the Antarctic continental shelves by warm eddies has the potential to greatly impact the melting rates of ice shelves and subsequent global sea level rise. While featured in modeling and some observational studies, the processes around how these warm eddies form and overcome the dynamic sub-surface barrier of the Antarctic Slope Front over the upper continental slope has not yet been clarified. Here we report on the detailed observations of persistent eddies carrying warm modified Circumpolar Deep Water (CDW) onto the continental shelf of Prydz Bay, East Antarctica, using subsurface mooring and hydrographic section data from 2013-2015. We show the warm-eddy transport is most active when the summer westerlies strengthen, which promotes the upwelling of CDW and initiates eddy formation and intrusions. Our study highlights the important role of warm eddies in the melting of Antarctica's ice shelves, both now and into the future.

8.
BMC Microbiol ; 24(1): 5, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172684

RESUMEN

BACKGROUND: Harmonia axyridis is an effective natural enemy insect to a variety of phloem-sucking pests and Lepidopteran larvae, such as aphids, scabies, and phylloxera, while its industrial production is limited due to unmature artificial diet. Insect intestinal microbiota affect host development and reproduction. The aim of this study is to understand intestinal microbiota composition of H. axyridis and screen effective probiotics on artificial diet. Considering the role of the components and composition of the diet on the structure and composition of the intestinal microbiome, four kinds of diets were set up: (1) aphid; (2) basic diet; (3) basic diet + glucose; (4) basic diet + trehalose. The gut microbiota of H. axyridis was detected after feeding on different diets. RESULTS: Results showed that the gut microbiota between artificial diet group and aphid groups were far apart, while the basic and glucose groups were clearly clustered. Besides, the glucose group and trehalose group had one unique phylum, Cryptophyta and Candidatus Saccharibacteria, respectively. The highest abundance of Proteobacteria was found in the aphid diet. The highest abundance of Firmicutes was found in the basic diet. However, the addition of glucose or trehalose alleviated the change. In addition, the relative abundance of Enterobacter, Klebsiella, Enterobacteriaceae_unclassified, Enterobacteriales_unclassified and Serratia in the aphid group was higher than other groups. Moreover, the function of gut genes in each group also showed clear differences. CONCLUSION: These results have offered a strong link between artificial diets and gut microbes, and also have provided a theoretical basis for the screening of synergistic probiotics in artificial diet.


Asunto(s)
Áfidos , Escarabajos , Microbioma Gastrointestinal , Animales , Trehalosa , Insectos , Dieta , Enterobacter , Glucosa
9.
Cancer Biomark ; 39(1): 49-62, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37545215

RESUMEN

BACKGROUND: Abelson interactor 1 (ABI1) is associated with the metastasis and prognosis of many malignancies. The association between ABI1 transcript spliced variants, their molecular constitutive exons and exon-exon junctions (EEJs) in 14 cancer types and clinical outcomes remains unsolved. OBJECTIVE: To identify novel cancer metastatic and prognostic biomarkers from ABI1 total mRNA, TSVs, and molecular constitutive elements. METHODS: Using data from TCGA and TSVdb database, the standard median of ABI1 total mRNA, TSV, exon, and EEJ expression was used as a cut-off value. Kaplan-Meier analysis, Chi-squared test (X2) and Kendall's tau statistic were used to identify novel metastatic and prognostic biomarkers, and Cox regression analysis was performed to screen and identify independent prognostic factors. RESULTS: A total of 35 ABI1-related factors were found to be closely related to the prognosis of eight candidate cancer types. A total of 14 ABI1 TSVs and molecular constitutive elements were identified as novel metastatic and prognostic biomarkers in four cancer types. A total of 13 ABI1 molecular constitutive elements were identified as independent prognostic biomarkers in six cancer types. CONCLUSIONS: In this study, we identified 14 ABI1-related novel metastatic and prognostic markers and 21 independent prognostic factors in total 8 candidate cancer types.


Asunto(s)
Neoplasias , Humanos , Pronóstico , Neoplasias/genética , Perfilación de la Expresión Génica , Biomarcadores , ARN Mensajero/genética , Biomarcadores de Tumor/genética , Proteínas del Citoesqueleto/genética , Proteínas Adaptadoras Transductoras de Señales/genética
10.
Cancer Med ; 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38083905

RESUMEN

BACKGROUND: Increasing evidence suggests that lncRNA (Long non-coding RNA, lncRNA)-mediated ceRNA (competing endogenous RNA, ceRNA) networks are involved in the occurrence and progression of colorectal cancer (CRC). However, the roles of the lncRNA-miRNA-mRNA ceRNA network in distant metastasis of CRC are still unclear. METHODS: In this study, we constructed a specific ceRNA network to identify potential biomarkers and therapeutic targets for distant metastasis of CRC. Specifically, RNA-Seq data from The Cancer Genome Atlas (TCGA) were used to screen for differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) related to metastasis. After validation and selection by qRT-PCR and univariate and multivariate analysis of the metastasis- and prognosis-related lncRNAs, the regulated microRNAs (miRNAs) and coexpressed mRNAs were used to construct a ceRNA network for distant metastasis of CRC. RESULTS: Two key distant metastasis-related DElncRNAs, AP002498.1 and LINC01871, were identified by univariate and multivariate analysis in combination with analyses of clinical data and expression levels. Furthermore, lncRNA-associated ceRNA subnetworks were constructed from the predicted miRNAs and 13 coexpressed DEmRNAs (SERPINA1, ITLN1, REG4, L1TD1, IGFALS, MUC5B, CIITA, CXCL9, CXCL10, GBP4, GNLY, IDO1, and NOS2). The AP002498.1- and LINC01871-associated ceRNA subnetworks regulated the expression of the target genes SERPINA1 and MUC5B and GNLY, respectively, through the associated miRNAs. CONCLUSION: The DElncRNA AP002498.1 and the LINC01871/miR-4644 and miR-185-5p/GNLY axes were identified as being closely associated with distant metastasis and could represent independent prognostic biomarkers or therapeutic targets in colorectal adenocarcinoma.

11.
Biomedicines ; 11(12)2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38137472

RESUMEN

Histone acetylation and mitochondrial function contribute importantly to neural differentiation, which is critically associated with neurodevelopmental disorders such as Down Syndrome (DS). However, whether and how histone acetylation regulates mitochondrial function and further affects neural differentiation has not been well described. In this study, when treated with retinoid acid (RA), the human neuroblastoma SH-SY5Y cell line was used as a neural differentiation model. We found that the acetylation of histone H3, especially H3 lysine 14 acetylation (H3K14ac), and mitochondrial function, including biogenesis and electron transport chain, were enhanced during neural differentiation. Specific inhibition of histone acetyltransferases (HATs) induced neural differentiation deficits, accompanied by downregulation of mitochondrial function. Furthermore, RA receptors (RARs) interacting with HATs were involved in the increased H3K14ac and the enhanced mitochondrial function during the neural differentiation process. Finally, receptor-interacting protein 140 (RIP140), a co-repressor of RARs, was also involved in regulating histone acetylation. RIP140 overexpression inhibited histone acetylation and mediated negative feedback on target genes which are involved in RA signaling. These findings evidenced that when interacting with RARs which had been negatively regulated by RIP140, RA promoted neural differentiation by promoting H3K14ac and enhanced mitochondrial function. This provides a molecular foundation for further investigations into abnormal neural development.

12.
Chem Sci ; 14(48): 14280-14289, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38098712

RESUMEN

Skillfully engineering surface ligands at specific sites within robust clusters presents both a formidable challenge and a captivating opportunity. Herein we unveil an unprecedented titanium-oxo cluster: a calix[8]arene-stabilized metallamacrocycle (Ti16L4), uniquely crafted through the fusion of four "core-shell" {Ti4@(TBC[8])(L)} subunits with four oxalate moieties. Notably, this cluster showcases an exceptional level of chemical stability, retaining its crystalline integrity even when immersed in highly concentrated acid (1 M HNO3) and alkali (20 M NaOH). The macrocycle's surface unveils four specific, customizable µ2-bridging sites, primed to accommodate diverse carboxylate ligands. This adaptability is highlighted through deliberate modifications achieved by alternating crystal soaking in alkali and carboxylic acid solutions. Furthermore, Ti16L4 macrocycles autonomously self-assemble into one-dimensional nanotubes, which subsequently organize into three distinct solid phases, contingent upon the specific nature of the four µ2-bridging ligands. Notably, the Ti16L4 exhibit a remarkable capacity for photocatalytic activity in selectively reducing CO2 to CO. Exploiting the macrocycle's modifiable shell yields a significant boost in performance, achieving an exceptional maximum CO release rate of 4.047 ± 0.243 mmol g-1 h-1. This study serves as a striking testament to the latent potential of precision-guided surface ligand manipulation within robust clusters, while also underpinning a platform for producing microporous materials endowed with a myriad of surface functionalities.

13.
Front Chem ; 11: 1296712, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38025052

RESUMEN

Introduction: Ginger (Zingiber officinale Roce.) is a widely consumed food item and a prominent traditional Chinese medicinal herb. The intrinsic quality of ginger may differ due to variations in its origin and processing techniques. To evaluate the quality of ginger, a straightforward and efficient discriminatory approach has been devised, utilizing 6-gingerol, 8-gingerol, and 10-gingerol as benchmarks. Methods: In order to categorize ginger samples according to their cultivated origins with different longitude and latitude (Shandong, Anhui, and Yunnan provinces in China) and processing methods (liquid nitrogen pulverization, ultra-micro grinding, and mortar grinding), similarity analysis (SA), hierarchical cluster analysis (HCA), and principal component analysis (PCA) were employed. Furthermore, there was a quantitative determination of the significant marker compounds gingerols, which has considerable impact on maintaining quality control and distinguishing ginger products accurately. Moreover, discrimination analysis (DA) was utilized to further distinguish and classify samples with unknown membership degrees based on the eigenvalues, with the aim of achieving optimal discrimination between groups. Results: The findings obtained from the high-performance liquid chromatography (HPLC) data revealed that the levels of various gingerols present in all samples exhibited significant variations. The study confirmed that the quality of ginger was primarily influenced by its origin and processing method, with the former being the dominant factor. Notably, the sample obtained from Anhui province and subjected to liquid nitrogen pulverization demonstrated the highest content of gingerols. Conclusion: The results obtained from the analysis of SA, HCA, PCA, and DA were consistent and could be employed to evaluate the quality of ginger. As such, the combination of HPLC fingerprints and chemo metric techniques provided a dependable approach for comprehensively assessing the quality and processing of ginger.

14.
Neuropharmacology ; 239: 109691, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37625690

RESUMEN

Dysfunctional glutamatergic neurotransmission contributes importantly to the pathophysiology of depression. However, the underlying neural mechanisms of glutamatergic dysfunction remain poorly understood. Here, we employed chronic unpredictable mild stress (CUMS) to induce depression-like behavior in male mice and to assess the alterations of glutamatergic system within the ventromedial prefrontal cortex (vmPFC). Male mice subjected to CUMS showed an increase in levels of glutamate content, synaptosomal GluN2B-NMDA receptors (GluN2B-NMDARs) and phosphorylated synaptosomal associated protein 25 KD of Ser187 (pSer187-SNAP25), which is involved in synaptic vesicular fusion processes in the vmPFC. Downregulation of pSer187-SNAP25 via the TAT-S187 fusion peptide efficiently alleviated CUMS-induced depressive-like behaviors in male mice by reversing the increase of glutamate content and synaptosomal GluN2B-NMDARs. These findings demonstrated a critical role for pSer187-SNAP25-mediated glutamatergic dysfunction in CUMS-induced depressive-like behaviors, suggesting the potential of pS187-SNAP25 inhibitors for further investigation on depression management.


Asunto(s)
Corteza Prefrontal , Transmisión Sináptica , Masculino , Animales , Ratones , Proteína 25 Asociada a Sinaptosomas , Regulación hacia Abajo , Ácido Glutámico
15.
J Appl Toxicol ; 43(10): 1499-1510, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37127545

RESUMEN

Compound diclofenac sodium chlorphenamine maleate tablets (CDCT) are widely used for the cold in Asia. However, CDCT can cause hematuria symptoms in clinical, and the underlying mechanism is unknown. This study aims to investigate the CDCT-induced changes of morphology in kidney and metabolites and further explore the possible mechanisms of CDCT-induced nephrotoxicity. Sprague-Dawley rats were exposed to the CDCT at a clinical equivalent dose for 6 days. CDCT exposure can induce kidney injury and death. Pathological changes, including creatinine, urea nitrogen, and histopathology, were observed in rats. Furthermore, metabolomic-driven energy and glycerophospholipid metabolism pathway disorders, accompanied by remarkably changed key metabolites, such as succinate, leukotriene B4 (LTB4 ), and cardiolipin (CL), are observed in the CDCT-induced nephrotoxicity. Functionally, succinate accumulation leads to mitochondrial damage, as evidence by the imbalance of complex I and complex II and an increase in mitochondrial reactive oxygen species (mito SOX). Meanwhile, LTB4 activated the NF-κB signaling, as shown by increased protein of p65, phosphor-p65, and decreased protein of IκBα and phosphor-IκBα. Eventually, the apoptosis pathway was triggered in response to reduced CL, inflammation, and mito SOX, as demonstrated by the expression of cyt c, Bax, Bcl-2, caspase-3, and caspase-9. This study indicated that CDCT-induced metabolic disorders triggered nephrotoxicity and provided a comprehensive information to elucidate the mechanism of CDCT induced nephrotoxicity.


Asunto(s)
Riñón , Estrés Oxidativo , Ratas , Animales , Ratas Sprague-Dawley , Inhibidor NF-kappaB alfa/metabolismo , Riñón/metabolismo , Apoptosis , FN-kappa B/metabolismo
16.
Dalton Trans ; 52(21): 7071-7078, 2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37161840

RESUMEN

In the field of metallo-supramolecular assemblies, supramolecular macrocycles have attracted considerable attention due to their guest recognition and catalytic properties. Herein, we report a novel strategy for the construction of giant hollow macrocyclic structures using a bi-directional geometric constraint strategy. We investigated the structural design of two terpyridine-based tetratopic organic ligands, whose inner and outer rims have different angles. Compared to conventional strategies of self-assembly using single angular orientation building blocks that typically generate small macrocyclic objects or polymers, the mutual interaction between the different angles of the ligands could promote the formation of giant hollow macrocyclic supramolecular architectures. The self-assembly mechanism and hierarchical self-assembly of giant supramolecular macrocycles have been characterized by NMR, ESI-MS and TEM experiments. The strategy used in this study not only advances the design of giant 2D macrocycles with large inner diameters but also gives insights into the mechanism of formation of large structures.

17.
Sleep Breath ; 27(6): 2469-2478, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37213066

RESUMEN

PURPOSE: Down syndrome (DS) is linked to a higher prevalence of obstructive sleep apnea (OSA) than in the general population, which in turn contributes to worse cognitive impairment in DS. However, the shared pathogenic mechanisms for DS and OSA remain incompletely illustrated. This study was designed to decipher the genetic cross-talk between DS and OSA by bioinformatics approach. METHODS: Transcriptomic datasets of DS (GSE59630) and OSA (GSE135917) were accessed from the Gene Expression Omnibus (GEO) repository. After screening out the common differentially expressed genes (DEGs) for DS and OSA, gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were carried out. A protein-protein interaction (PPI) network was then constructed to determine essential modules and hub genes. Finally, based on hub genes, transcriptional factor (TF)-gene interaction and TF-miRNA regulatory networks were constructed. RESULTS: DS and OSA showed 229 DEGs. Functional analyses revealed how oxidative stress and inflammatory response were critical in the progression of DS and OSA. Ten significant hub genes were identified, including TLR4, SOD1, IGF1, FGF2, NFE2L2, PECAM1, S100A8, S100A9, FCGR3A, and KCNA1, which were candidate targets for DS and OSA. CONCLUSIONS: We found that DS and OSA display similarities in their pathogenesis. Key genes and signaling pathways revealed to be in common between the two conditions could lead us to new therapeutic targets for DS and OSA.


Asunto(s)
Síndrome de Down , Apnea Obstructiva del Sueño , Humanos , Transcriptoma/genética , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Perfilación de la Expresión Génica , Apnea Obstructiva del Sueño/genética , Apnea Obstructiva del Sueño/diagnóstico , Cruzamientos Genéticos
18.
Dalton Trans ; 52(17): 5438-5442, 2023 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-37083046

RESUMEN

Accurate manipulation of ligands at specific sites in robust clusters is attractive but difficult, especially for those ligands that coordinate in intricate binding patterns. By linking the shuttlecock-like {Cu4(µ4-Cl)TC4A} motif and the phenylphosphate (PhPO32-) ligand, we elaborately design and synthesize two Cu(II)-thiacalix[4]arene metallamacrocycles (MMCs), namely Cu12L3 and Cu16L4, which have regular triangular and quadrilateral topologies, respectively. While keeping the core intact, the Cl- and PhPO32- in those two MMCs, which coordinated in a µ4-bridging fashion, can be accurately substituted with salicylate ligands. Theoretical calculations have been carried out to reveal the effect of ligand tailoring on the electronic structure of clusters. Structural regulation can affect the catalytic activity of these clusters, which has been verified by using the clusters as catalysts for selective sulfide oxidation.

19.
Biochem Genet ; 61(5): 2042-2055, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36929358

RESUMEN

Streptomyces are one of the most prolific sources of bioactive and structurally diverse secondary metabolites for natural product drug discovery. Genome sequencing and bioinformatics analysis revealed that the genomes of Streptomyces harbor a wealth of cryptic secondary metabolite biosynthetic gene clusters that could encode novel compounds. In this work, a genome mining approach was employed to investigate the biosynthetic potential of Streptomyces sp. HP-A2021, isolated from rhizosphere soil of Ginkgo biloba L. The complete genome of HP-A2021 was sequenced and contained the 9,607,552 base pair linear chromosome with a GC content of 71.07%. The annotation results revealed the presence of 8534 CDSs, 76 tRNA genes, and 18 rRNA genes in HP-A2021. The highest dDDH and ANI values based on genome sequences between HP-A2021 and the most closely related type strain, Streptomyces coeruleorubidus JCM 4359, were 64.2% and 92.41%, respectively. In total, 33 secondary metabolite biosynthetic gene clusters with an average length of 105,594 bp were identified, including the putative thiotetroamide, alkylresorcinol, coelichelin, and geosmin. The antibacterial activity assay confirmed that the crude extracts of HP-A2021 showed potent antimicrobial activity against human pathogenic bacteria. Our study demonstrated that Streptomyces sp. HP-A2021 will propose a potential use in biotechnological and novel bioactive secondary metabolite biosynthetic applications.


Asunto(s)
Productos Biológicos , Streptomyces , Humanos , Genoma Bacteriano , Productos Biológicos/metabolismo , Biología Computacional , Antibacterianos/metabolismo , Streptomyces/genética , Streptomyces/metabolismo , Familia de Multigenes
20.
Front Cell Infect Microbiol ; 13: 1109889, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36844413

RESUMEN

Introduction: Down syndrome (DS), the presence of a supernumerary chromosome 21, is associated with cognitive dysfunction caused by early neurodegenerative processes. Alterations in the gut microbiota were observed in Chinese children with DS, and the genus Blautia was associated with cognitive function in these children. Therefore, it is crucial to understand the detailed composition of this group at the species level and to explore the effect of specific species on cognitive function. Methods: In this study, Blautia-specific amplicon sequencing was conducted to identify the specific Blautia species in 15 children with DS and 15 matched healthy children. Results: The taxonomic analyses suggested that the Blautia taxa were clustered by disease status. The diversity of Blautia at the species level differed between DS patients and healthy controls, with the abundances of Blautia massiliensis and Blautia argi decreasing in DS children, while Blautia faecis was increased. Acetic acid, one of the metabolites of Blautia, was significantly reduced in the DS group. Of particular interest, Kyoto Encyclopaedia of Genes and Genomes analysis revealed decreased modules related to starch and sucrose metabolism and glycolysis. In addition, B. argi was positively related to DS cognitive scores, and B. faecis was negatively related to cognitive function, implying its role on the DS cognitive impairments. Discussion: Our study has important implications for understanding the important effects of specific species of Blautia on cognitive function and thus possibly provides a new strategy for future studies of cognitive improvement in individuals with DS.


Asunto(s)
Clostridiales , Disfunción Cognitiva , Síndrome de Down , Microbioma Gastrointestinal , Niño , Humanos , Cognición , Síndrome de Down/microbiología , Síndrome de Down/psicología , Pueblos del Este de Asia , Clostridiales/clasificación
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