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1.
Nature ; 567(7747): 234-238, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30814736

RESUMO

Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification1. However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth1,2, but this model has never been proved. Here, using clonal genetic tracing with multicolour reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondroprogenitors, whereas later in life, coinciding with the formation of the secondary ossification centre, chondroprogenitors acquire the capacity for self-renewal, resulting in the formation of large, stable monoclonal columns of chondrocytes. Simultaneously, chondroprogenitors begin to express stem cell markers and undergo symmetric cell division. Regulation of the pool of self-renewing progenitors involves the hedgehog and mammalian target of rapamycin complex 1 (mTORC1) signalling pathways. Our findings indicate that a stem cell niche develops postnatally in the epiphyseal growth plate, which provides a continuous supply of chondrocytes over a prolonged period.


Assuntos
Condrócitos/citologia , Células Clonais/citologia , Lâmina de Crescimento/citologia , Nicho de Células-Tronco/fisiologia , Envelhecimento , Animais , Cartilagem/citologia , Autorrenovação Celular , Células Clonais/metabolismo , Feminino , Lâmina de Crescimento/metabolismo , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos
2.
Cytokine ; 175: 156483, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38159472

RESUMO

PURPOSE: The purpose of this research study was to investigate the impact of schaftoside on Aspergillus fumigatus (A. fumigatus) keratitis and elucidate its underlying mechanisms. METHODS: In order to establish safe experimental concentrations of schaftoside in human corneal epithelial cells (HCECs), RAW264.7 cells, and mouse models, various techniques were employed including cytotoxicity assay (CCK-8) assay, cell scratch assay, and Draize test. The therapeutic effect of schaftoside was assessed using slit-lamp biomicroscopy, clinical scores, as well as determination of neutrophil infiltration through hematoxylin and eosin (HE) staining, immunofluorescence (IF) staining, and myeloperoxidase (MPO) assay. The levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), pro-inflammatory mediators interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6 were determined using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and IF techniques. RESULTS: Schaftoside at a concentration of 160 µM displayed no harmful side effects on HCECs, RAW cells, and mouse corneas, rendering it suitable for further experiments. In a murine fungal keratitis model, schaftoside mitigated the severity of fungal keratitis by inhibiting neutrophil infiltration and reducing MPO activity. Both in vitro and in vivo experiments demonstrated that schaftoside treatment suppressed the upregulation of IL-1ß, TNF-α, and IL-6 expression, while also downregulating the expressions of TLR4 as well as MyD88 at both mRNA and protein levels. CONCLUSIONS: Schaftoside demonstrated a protective effect against A. fumigatus keratitis by reducing corneal damage through inhibition of neutrophil recruitment and downstream inflammatory cytokines. The anti-inflammatory properties of schaftoside in A. fumigatus keratitis may involve modulation of the TLR4/MyD88 pathway.


Assuntos
Aspergilose , Glicosídeos , Ceratite , Animais , Camundongos , Humanos , Aspergillus fumigatus , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/metabolismo , Aspergilose/tratamento farmacológico , Interleucina-6/metabolismo , Ceratite/tratamento farmacológico , Ceratite/metabolismo , Ceratite/microbiologia , Inflamação/tratamento farmacológico , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Camundongos Endogâmicos C57BL
3.
Cell Commun Signal ; 22(1): 116, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347540

RESUMO

BACKGROUND: R140Q mutation in isocitrate dehydrogenase 2 (IDH2) promotes leukemogenesis. Targeting IDH2/R140Q yields encouraging therapeutic effects in the clinical setting. However, therapeutic resistance occurs in 12% of IDH2/R140Q inhibitor treated patients. The IDH2/R140Q mutant converted TF-1 cells to proliferate in a cytokine-independent manner. This study investigated the signaling pathways involved in TF-1(R140Q) cell proliferation conversion as alternative therapeutic strategies to improve outcomes in patients with acute myeloid leukemia (AML) harboring IDH2/R140Q. METHODS: The effects of IDH2/R140Q mutation on TF-1 cell survival induced by GM-CSF withdrawal were evaluated using flow cytometry assay. The expression levels of apoptosis-related proteins, total or phosphorylated STAT3/5, ERK, and AKT in wild-type TF-1(WT) or TF-1(R140Q) cells under different conditions were evaluated using western blot analysis. Cell viability was tested using MTT assay. The mRNA expression levels of GM-CSF, IL-3, IL-6, G-CSF, leukemia inhibitory factor (LIF), oncostatin M (OSM), and IL-11 in TF-1(WT) and TF-1(R140Q) cells were quantified via RT-PCR. The secretion levels of GM-CSF, OSM, and LIF were determined using ELISA. RESULTS: Our results showed that STAT3 and STAT5 exhibited aberrant constitutive phosphorylation in TF-1(R140Q) cells compared with TF-1(WT) cells. Inhibition of STAT3/5 phosphorylation suppressed the cytokine-independent proliferation of TF-1(R140Q) cells. Moreover, the autocrine GM-CSF, LIF and OSM levels increased, which is consistent with constitutive STAT5/3 activation in TF-1(R140Q) cells, as compared with TF-1(WT) cells. CONCLUSIONS: The autocrine cytokines, including GM-CSF, LIF, and OSM, contribute to constitutive STAT3/5 activation in TF-1(R140Q) cells, thereby modulating IDH2/R140Q-mediated malignant proliferation in TF-1 cells. Targeting STAT3/5 phosphorylation may be a novel strategy for the treatment of AML in patients harboring the IDH2/R140Q mutation. Video Abstract.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos , Leucemia Mieloide Aguda , Humanos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Fator de Transcrição STAT5/metabolismo , Fosforilação , Leucemia Mieloide Aguda/genética , Mutação , Proliferação de Células , Fator de Transcrição STAT3/metabolismo
4.
Phys Chem Chem Phys ; 26(19): 14329-14335, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38695750

RESUMO

Ligands have been known to profoundly affect the chemical transformations of methane, yet significant challenges remain in shedding light on the underlying mechanisms. Here, we demonstrate that the conversion of methane can be regulated by Ru centered cations with a series of ligands (C, CH, CNH, CHCNH). Gas-phase experiments complemented by theoretical dynamic analysis were performed to explore the essences and principles governing the ligand effect. In contrast to the inert Ru+, [RuC]+, and [RuCNH]+ toward CH4, the dehydrogenation dominates the reaction of ligand-regulated systems [RuCH]+/CH4 and [RuCHCNH]+/CH4. In active cases, CH acts as active sites, and regulates the activation of CH4 assisted by the "seemingly inert" CNH ligand.

5.
Nanomedicine ; 59: 102754, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38797223

RESUMO

Exocytosis is a critical factor for designing efficient nanocarriers and determining cytotoxicity. However, the research on the exocytosis mechanism of nanoparticles, especially the role of long non-coding RNAs (lncRNAs), has not been reported. In this study, the exocytosis of AuNPs in the KYSE70 cells and the involved molecular pathways of exocytosis are analyzed. It demonstrates that nanoparticles underwent time-dependent release from the cells by exocytosis, and the release of ß-hexosaminidase confirms that AuNPs are excreted through lysosomes. Mechanistic studies reveal that lncRNA ESCCAL-1 plays a vital role in controlling the exocytosis of AuNPs through activation of the MAPK pathway, including the phosphorylation of ERK and JNK. The study implies that the ESCCAL-1-mediated pathway plays an important role in the exocytosis of AuNPs in KYSE70 cells. This finding has implications for the role of ESCCAL-1 on the drug resistance of esophagus cancer by controlling lysosome-mediated exocytosis.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Exocitose , Ouro , Nanopartículas Metálicas , RNA Longo não Codificante , Exocitose/efeitos dos fármacos , Humanos , Ouro/química , Nanopartículas Metálicas/química , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Linhagem Celular Tumoral , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Lisossomos/metabolismo , Lisossomos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética
6.
Artigo em Inglês | MEDLINE | ID: mdl-38430150

RESUMO

Objective: Gaucher disease (GD) is a clinically rare single-gene recessive lysosomal storage disease mainly divided into three subtypes I to III. This report aims to present a case of type IIIb GD in a Chinese child with a focus on the manifestation of hearing loss and the importance of early diagnosis and monitoring. Methods: The patient underwent a routine physical examination upon admission, followed by CT scans of the chest and abdomen, MRI of the brain, and bone marrow smear examination. The patient's GBA enzyme activity, Lyso-GL-1 levels, and GBA gene expression were analyzed using tandem mass spectrometry (MS/MS) and next-generation sequencing technology. Finally, auditory brainstem response (ABR) testing was conducted. Results: This report presented a case of a Chinese boy with hematological manifestations as the first symptom, followed by hepatosplenomegaly, and the bilateral femurs showed obvious Erlenmeyer flask-like changes. Combined with GBA enzyme activity, Lyso-GL-1 and GBA genotype analysis results, the boy was initially diagnosed as type I GD. During the follow-up, the boy developed nystagmus, bilateral ABR V wave threshold increased, V/I amplitude ratio <0.5, accompanied by delayed growth and development, and finally diagnosed as type IIIb. Conclusions: This case suggests the necessity of neuropathy monitoring in patients with type I GD during the early stages of the disease. This includes EEG, neuro-ophthalmological examination, and auditory function assessment, which can help reflect the progression of neuropathy and facilitate the early diagnosis of type III GD.

7.
Alzheimers Dement ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38895994

RESUMO

INTRODUCTION: Arterial stiffness is linked to age-related cognitive dysfunction. Estimated pulse wave velocity (ePWV) is associated with cerebrovascular disease. We sought to determine whether ePWV was associated with cognition in a multiethnic population. METHODS: We included 1257 participants enrolled in a Northern Manhattan Study magnetic resonance imaging MRI-cognitive study (mean age 64 ± 8 years, 61% women, 67% Hispanic, 18% non-Hispanic Black, 15% non-Hispanic white) and analyzed cognitive performance at two time points, at enrollment and on an average 5.0 ± 0.6 years later. ePWV was calculated using baseline age and blood pressure. Cognition and cognitive change scores were regressed on ePWV in multivariable linear regression models. RESULTS: In adjusted models, ePWV (mean 11 ± 2 m/s) was significantly associated with cognition (b = -0.100, 95% CI, -0.120, -0.080) and cognitive change over time (b = -0.063, 95% CI, -0.082, -0.045). Effect modification by race and sex was found. DISCUSSION: In this multiethnic population, the associations of ePWV with cognitive performance underline the role of vascular stiffness in age-related cognitive decline. HIGHLIGHTS: ePWV is a modest but independent predictor of cognitive function and cognitive decline among older individuals. After adjustment, the ePWV measure was inversely associated with performance and decline in global cognition, processing speed, episodic memory, executive function, and semantic memory. After adjustment, modification of the association between ePWV and change in episodic memory and executive function by race and ethnicity was suggested by a significant interaction term. The association between ePWV and episodic memory decline was stronger in females.

8.
J Environ Manage ; 350: 119652, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38016235

RESUMO

Renewable energy (RE) plays a crucial role in global energy transformation, and a thorough study of the potential impact of RE on regional carbon emissions is of great significance. This is particularly relevant to China, which needs to clarify its path to carbon reduction. Using the sample data of 30 provinces in China from 2000 to 2021, this paper uses the Granger causality test to verify the causal relationship between carbon emission intensity (CEI) and other factors. It builds a mediation effect model on this basis to explore the direct impact effect and indirect transmission path of renewable energy utilization (REU) on CEI. The results show that REU has a one-way causal relationship with CEI. REU can directly and indirectly reduce CEI by improving social wealth and changing the direction of energy investment. In addition, REU indirectly increases CEI through the transmission paths of investment in the energy industry - social affluence and industrial level-social affluence. The CEI is indirectly reduced through the conduction paths of (social affluence-Urbanization rate), (Investment in the energy industry-Urbanization rate), (Industrial level-Urbanization rate), and (Industrial level-Investment in the energy industry). These conclusions will assist policymakers in exploring targeted pathways for low-carbon power development, providing a reference for strategic and sustainable carbon reduction policies.


Assuntos
Dióxido de Carbono , Carbono , Carbono/análise , Dióxido de Carbono/análise , Urbanização , Energia Renovável , China , Desenvolvimento Econômico
9.
Molecules ; 29(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38542875

RESUMO

BACKGROUND: Trapa bispinosa shells (TBs) and its flesh (TBf) have been recognized for their medicinal properties, including antioxidant, antitumor, and immunomodulatory effects. Despite these benefits, TBs are often discarded as waste material, and their applications remain to be further explored. METHODS: In this study, we optimized the solid-state fermentation process of Ganoderma sinense (GS) with TBs using a response surface experiment methodology to obtain the fermented production with the highest water extract rate and DPPH free radical scavenging activity. We prepared and characterized pre-fermentation purified polysaccharides (P1) and post-fermentation purified polysaccharides (P2). Alcoholic extracts before (AE1) and after (AE2) fermentation were analyzed for active components such as polyphenols and flavonoids using UPLC-QTOF-MS/MS (ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry). Mouse macrophages (RAW 264.7) were employed to compare the immune-stimulating ability of polysaccharides and the antioxidant activity of AE1 and AE2. RESULTS: Optimal fermentation conditions comprised a duration of 2 days, a temperature of 14 °C, and a humidity of 77%. The peak water extract yield and DPPH free radical scavenging rate of the water extract from TBs fermented by GS were observed under these conditions. The enhanced activity may be attributed to changes in the polysaccharide structure and the components of the alcoholic extract. The P2 treatment group indicated more secretion of RAW 264.7 cells of NO, iNOS, IL-2, IL-10, and TNF-α than P1, which shows that the polysaccharides demonstrated increased immune-stimulating ability, with their effect linked to the NF-кB pathway. Moreover, the results of the AE2 treatment group indicated that secretion of RAW 264.7 cells of T-AOC and T-SOD increased and MDA decreased, which shows that the alcoholic extract demonstrated enhanced antioxidant activity, with its effect linked to the Nrf2/Keap1-ARE pathway. CONCLUSIONS: Biphasic fermentation of Trapa bispinosa shells by Ganoderma sinense could change the composition and structure of the polysaccharides and the composition of the alcoholic extract, which could increase the products' immunomodulatory and antioxidant activity.


Assuntos
Antioxidantes , Ganoderma , Lythraceae , Animais , Camundongos , Antioxidantes/análise , Fermentação , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Espectrometria de Massas em Tandem , Fator 2 Relacionado a NF-E2/metabolismo , Polissacarídeos/química , Ganoderma/química , Água/metabolismo , Radicais Livres/metabolismo
10.
Molecules ; 29(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38792058

RESUMO

The 1092 bp F3H gene from Trapa bispinosa Roxb., which was named TbF3H, was cloned and it encodes 363 amino acids. Bioinformatic and phylogenetic tree analyses revealed the high homology of TbF3H with flavanone 3-hydroxylase from other plants. A functional analysis showed that TbF3H of Trapa bispinosa Roxb. encoded a functional flavanone 3-hydroxylase; it catalyzed the formation of dihydrokaempferol (DHK) from naringenin in S. cerevisiae. The promoter strengths were compared by fluorescence microscopy and flow cytometry detection of the fluorescence intensity of the reporter genes initiated by each constitutive promoter (FITC), and DHK production reached 216.7 mg/L by the promoter adjustment strategy and the optimization of fermentation conditions. The results presented in this study will contribute to elucidating DHK biosynthesis in Trapa bispinosa Roxb.


Assuntos
Flavanonas , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Flavanonas/biossíntese , Flavanonas/metabolismo , Filogenia , Regiões Promotoras Genéticas , Clonagem Molecular/métodos , Flavonoides/biossíntese , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fermentação
11.
Angew Chem Int Ed Engl ; 63(7): e202318043, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38135669

RESUMO

A key task in today's inorganic synthetic chemistry is to develop effective reactions, routes, and associated techniques aiming to create new functional materials with specifically desired multilevel structures and properties. Herein, we report an ultrathin two-dimensional layered composite of graphene ribbon and silicate via a simple and scalable one-pot reaction, which leads to the creation of a novel carbon-metal-silicate hybrid family: carbosilicate. The graphene ribbon is in situ formed by unzipping carbon nanotubes, while the ultrathin silicate is in situ obtained from bulk silica or commercial glass; transition metals (Fe or Ni) oxidized by water act as bridging agent, covalently bonding the two structures. The unprecedented structure combines the superior properties of the silicate and the nanocarbon, which triggers some specific novel properties. All processes during synthesis are complementary to each other. The associated synergistic chemistry could stimulate the discovery of a large class of more interesting, functionalized structures and materials.

12.
Curr Issues Mol Biol ; 45(2): 820-837, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36825999

RESUMO

Conflicting phylogenetic signals are pervasive across genomes. The potential impact of such systematic biases may be reduced by phylogenetic approaches accommodating for heterogeneity or by the exclusive use of homoplastic sites in the datasets. Here, we present the complete mitogenome of Lynceus grossipedia as the first representative of the suborder Laevicaudata. We employed a phylogenomic approach on the mitogenomic datasets representing all major branchiopod groups to identify the presence of conflicts and concordance across the phylogeny. We found pervasive phylogenetic conflicts at the base of Diplostraca. The homogeneity of the substitution pattern tests and posterior predictive tests revealed a high degree of compositional heterogeneity among branchiopod mitogenomes at both the nucleotide and amino acid levels, which biased the phylogenetic inference. Our results suggest that Laevicaudata as the basal clade of Phyllopoda was most likely an artifact caused by compositional heterogeneity and conflicting phylogenetic signal. We demonstrated that the exclusive use of homoplastic site methods combining the application of site-heterogeneous models produced correct phylogenetic estimates of the higher-level relationships among branchiopods.

13.
Small ; 19(44): e2303887, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37392054

RESUMO

Wound healing, known as a fundamental healthcare issue worldwide, has been attracting great attention from researchers. Here, novel bioactive gellan gum microfibers loaded with antibacterial peptides (ABPs) and vascular endothelial growth factor (VEGF) are proposed for wound healing by using microfluidic spinning. Benefitting from the high controllability of microfluidics, bioactive microfibers with uniform morphologies are obtained. The loaded ABPs are demonstrated to effectively act on bacteria at the wound site, reducing the risk of bacterial infection. Besides, sustained release of VEGF from microfibers helps to accelerate angiogenesis and further promote wound healing. The practical value of woven bioactive microfibers is demonstrated via animal experiments, where the wound healing process is greatly facilitated because of the excellent circulation of air and nutritious substances. Featured with the above properties, it is believed that the novel bioactive gellan gum microfibers would have a remarkable effect in the field of biomedical application, especially in promoting wound healing.


Assuntos
Microfluídica , Fator A de Crescimento do Endotélio Vascular , Animais , Cicatrização , Polissacarídeos Bacterianos/farmacologia , Polissacarídeos Bacterianos/química
14.
Small ; 19(41): e2301633, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37329203

RESUMO

Atomically precise copper nanoclusters (Cu NCs) have attracted tremendous attention for their huge potential in many applications. However, the uncertainty of the growth mechanism and complexity of the crystallization process hinder the in-depth understanding of their properties. In particular, the ligand effect has been rarely explored at the atomic/molecular level due to the lack of feasible models. Herein, three isostructural Cu6 NCs ligated with diverse mono-thiol ligands (2-mercaptobenzimidazole, 2-mercaptobenzothiazole, and 2-mercaptobenzoxazole, respectively) are successfully synthesized, which provide an ideal platform to unambiguously address the intrinsic role of ligands. The overall atom-by-atom structural evolution process of Cu6 NCs is mapped out with delicate mass spectrometry (MS) for the first time. It is intriguingly found that the ligands, albeit only atomic difference (NH, O, and S), can profoundly affect the building-up processes, chemical properties, atomic structures, as well as catalytic activities of Cu NCs. Furthermore, ion-molecule reactions combined with density functional theory (DFT) calculations demonstrate that the defective sites formed on ligand can significantly contribute to the activation of molecular oxygen. This study provides fundamental insights into the ligand effect, which is vital for the delicate design of high-efficient Cu NCs-based catalysts.

15.
Planta ; 257(3): 63, 2023 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-36807538

RESUMO

MAIN CONCLUSION: Four types of cells were engineered from Artemisia annua to produce approximately 17 anthocyanins, four of which were elucidated structurally. All of them expressed the artemisinin pathway. Artemisia annua is the only medicinal crop to produce artemisinin for the treatment of malignant malaria. Unfortunately, hundreds of thousands of people still lose their life every year due to the lack of sufficient artemisinin. Artemisinin is considered to result from the spontaneous autoxidation of dihydroartemisinic acid in the presence of reactive oxygen species (ROS) in an oxidative condition of glandular trichomes (GTs); however, whether increasing antioxidative compounds can inhibit artemisinin biosynthesis in plant cells is unknown. Anthocyanins are potent antioxidants that can remove ROS in plant cells. To date, no anthocyanins have been structurally elucidated from A. annua. In this study, we had two goals: (1) to engineer anthocyanins in A. annua cells and (2) to understand the artemisinin biosynthesis in anthocyanin-producing cells. Arabidopsis Production of Anthocyanin Pigment 1 was used to engineer four types of transgenic anthocyanin-producing A. annua (TAPA1-4) cells. Three wild-type cell types were developed as controls. TAPA1 cells produced the highest contents of total anthocyanins. LC-MS analysis detected 17 anthocyanin or anthocyanidin compounds. Crystallization, LC/MS/MS, and NMR analyses identified cyanidin, pelargonidin, one cyanin, and one pelargonin. An integrative analysis characterized that four types of TAPA cells expressed the artemisinin pathway and TAPA1 cells produced the highest artemisinin and artemisinic acid. The contents of arteannuin B were similar in seven cell types. These data showed that the engineering of anthocyanins does not eliminate the biosynthesis of artemisinin in cells. These data allow us to propose a new hypothesis that enzymes catalyze the formation of artemisinin from dihydroartemisinic acid in non-GT cells. These findings show a new platform to increase artemisinin production via non-GT cells of A. annua.


Assuntos
Artemisia annua , Artemisininas , Artemisia annua/química , Antocianinas/metabolismo , Vias Biossintéticas , Engenharia Metabólica , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Massas em Tandem , Artemisininas/química , Artemisininas/metabolismo
16.
Pediatr Blood Cancer ; 70(10): e30545, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37438860

RESUMO

BACKGROUND: Dysregulation of microRNAs (miRNAs) targeting genes in the PI3K/Akt pathway has been implicated in the pathogenesis of childhood acute lymphoblastic leukemia (ALL). However, the impact of genetic variants in these miRNAs on ALL susceptibility has not been extensively explored in the Chinese population. METHODS: To address this gap, we conducted a case-control study to evaluate the association between genetic variants in five PI3K/AKT pathway-related miRNAs (miR-149, miR-126, miR-492, miR-612, and miR-423) and childhood ALL susceptibility in the Chinese population. Additionally, we investigated the effects of the rs2292832 mutation on ALL cell proliferation and apoptosis. RESULTS: Our analyses revealed that the miR-149 rs2292832 mutant heterozygous CT genotype was more frequent in the control group than in the ALL cases, indicating a protective effect against ALL (adjusted odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.63-0.97, p = .024). Stratification analyses further revealed that the miR-149 rs2292832 CC genotype was associated with an increased risk of childhood ALL in subgroups of older children, females, those with parents who never smoked or drank alcohol, those living in painted houses, those with B-ALL, and those with high-risk ALL. Finally, we observed that the rs2292832 mutation inhibited ALL cell proliferation and induced apoptosis (p = .001), providing a potential mechanism by which this genetic variant may influence ALL susceptibility. CONCLUSION: Our study highlights the significant association between the miR-149 rs2292832 genetic variant and childhood ALL susceptibility in the Chinese population. These findings expand our understanding of the complex genetic landscape underlying ALL and have implications for the development of personalized therapeutic strategies.


Assuntos
MicroRNAs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Feminino , Humanos , Adolescente , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Genótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Predisposição Genética para Doença
17.
Macromol Rapid Commun ; 44(19): e2300268, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37402482

RESUMO

Photodynamic therapy (PDT) has emerged as a promising cancer treatment modality; however, its therapeutic efficacy is greatly limited by tumor hypoxia. In this study, a metal-organic framework (MOF)-based hydrogel (MOF Gel) system that synergistically combines PDT with the supply of oxygen is designed. Porphyrin-based Zr-MOF nanoparticles are synthesized as the photosensitizer. MnO2 is decorated onto the surface of the MOF, which can effectively convert H2O2 into oxygen. Simultaneously, the incorporation of MnO2 -decorated MOF (MnP NPs) into a chitosan hydrogel (MnP Gel) serves to enhance its stability and retention at the tumor site. The results show that this integrated approach significantly improves tumor inhibition efficiency by relieving tumor hypoxia and enhancing PDT. Overall, the findings underscore the potential for employing nano-MOF-based hydrogel systems as promising agents for cancer therapy, thus advancing the application of multifunctional MOFs in cancer treatment.

18.
Environ Res ; 222: 115376, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36736755

RESUMO

Cadmium (Cd) and chromium (Cr) are widespread contaminants with a high risk to the environment and humans. Herein we isolated a novel strain of Serratia marcescens, namely strain S27, from soil co-contaminated with Cd and Cr. This strain showed strong resistance to Cd as well as Cr. S27 cells demonstrated Cd adsorption rate of 45.8% and Cr reduction capacity of 84.4% under optimal growth conditions (i.e., 30 °C, 200 rpm, and pH 7.5). Microscopic characterization of S27 cells revealed the importance of the functional groups C-O-C, C-H-O, C-C, C-H, and -OH, and also indicated that Cr reduction occurred on bacterial cell membrane. Cd(II) and Cr(VI) bioaccumulation on S27 cell surface was mainly in the form of Cd(OH)2 and Cr2O3, respectively. Further, metabolomic analyses revealed that N-arachidonoyl-l-alanine was the key metabolite that promoted Cd and Cr complexation by S27; it primarily promotes γ-linolenic acid (GLA) metabolism, producing siderophores and coordinating with organic acids to enhance metal bioavailability. To summarize, our results suggest that S27 is promising for the bioremediation of environments contaminated with Cd and Cr in tropical regions.


Assuntos
Cádmio , Cromo , Humanos , Cromo/metabolismo , Serratia marcescens/metabolismo , Biodegradação Ambiental , Adsorção
19.
Environ Res ; 238(Pt 1): 117158, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37726031

RESUMO

Volatile organic compounds (VOCs) undergo substantial photochemical losses during their transport from emission sources to receptor sites, resulting in serious implications for their source apportionment and ozone (O3) formation. Based on the continuous measurements of VOCs in suburban Jinan in August 2022, the effects of photochemical losses on VOC source contributions and O3 formation were evaluated in this study. The observed and initial concentrations of total VOCs (TVOC) were 12.0 ± 5.1 and 16.0 ± 7.4 ppbv, respectively. Throughout the observation period, alkenes had the most prominent photochemical losses (58.2%), followed by aromatic hydrocarbons (23.1%), accounting for 80.6% and 6.9% of the total losses, respectively. During high O3 episodes, the photochemical loss of VOCs was 6.9 times higher than that during the cleaning period. Alkene losses (exceeding 67.3%), specifically losses of isoprene, propylene, ethylene, and n-butene, dominated the total losses of VOCs during the O3 increase period. Eight sources of VOCs were identified by positive matrix factorization (PMF) based on the observed and initial concentration data (OC-PMF and IC-PMF, respectively). Concentrations of all emission sources in the OC-PMF were underestimated by 2.4%-57.1%. Moreover, the contribution of each emission source was over- or underestimated compared with that in case of the IC-PMF. The contributions of biogenic and motor vehicle exhaust emissions were underestimated by 5.3 and 2.8 percentage points, respectively, which was associated with substantial oxidation of the emitted high-reactive species. The contributions of coal/biomass burning and natural gas were overestimated by 2.4 and 3.9 percentage points, respectively, which were related to the emission of low-reactive species (acetylene, ethane, and propane). Based on our results, the photochemical losses of VOCs grossly affect their source apportionment and O3 formation. Thus, photochemical losses of VOCs must be thoroughly accounted to establish a precise scientific foundation for air-pollution control strategies.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Ozônio/análise , Poluentes Atmosféricos/análise , Compostos Orgânicos Voláteis/análise , China , Emissões de Veículos/análise , Monitoramento Ambiental
20.
Surg Endosc ; 37(7): 5129-5136, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36941411

RESUMO

BACKGROUND: Total thoracoscopic segmentectomy (TTS) is a technically challenging procedure in children but results in more parenchyma preservation, better pain control, better cosmetic results, and a shorter hospital stay. However, definitive data describing the learning curve of TTS has yet to be obtained. Here, we review the safety and efficiency of our initial experiences with pediatric TTS and evaluate our learning curve. METHODS: This was a retrospective study of all pediatric patients undergoing TTS between December 2016 and January 2020. Pediatric patients who underwent TTS were included, while those undergoing lobectomy or wedge resection were excluded. RESULTS: One hundred and twelve patients were retrospectively analyzed to evaluate the learning curve and were divided chronologically into three phases, the ascending phase (A), plateau phase (B) and descending phase (C), through cumulative summation (CUSUM) of the operative time (OT). Phases A, B, and C comprised 28, 51, and 33 cases, respectively. OT decreased significantly from phases A to B (p < 0.001) and from phase B to C (p = 0.076). No significant differences were observed in the demographic factors among the three phases. The conversion rate was zero, and the complication rate was 0.9%. Differences in technical parameters, such as length of stay and chest tube duration, were statistically insignificant between phases A and B or B and C. There were no mortalities. CONCLUSION: CUSUMOT indicates that the learning curve of at least 79 cases is required for TTS in our institute. We emphasize that the learning curve should be cautiously interpreted because many factors in different institutions may influence the exact parabola and actual learning curve.


Assuntos
Pneumopatias , Neoplasias Pulmonares , Humanos , Criança , Estudos Retrospectivos , Pneumonectomia/métodos , Curva de Aprendizado , Resultado do Tratamento , Tempo de Internação , Pulmão/cirurgia , Neoplasias Pulmonares/cirurgia
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