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1.
Nature ; 629(8011): 467-473, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38471529

RESUMO

Prokaryotes have evolved intricate innate immune systems against phage infection1-7. Gabija is a highly widespread prokaryotic defence system that consists of two components, GajA and GajB8. GajA functions as a DNA endonuclease that is inactive in the presence of ATP9. Here, to explore how the Gabija system is activated for anti-phage defence, we report its cryo-electron microscopy structures in five states, including apo GajA, GajA in complex with DNA, GajA bound by ATP, apo GajA-GajB, and GajA-GajB in complex with ATP and Mg2+. GajA is a rhombus-shaped tetramer with its ATPase domain clustered at the centre and the topoisomerase-primase (Toprim) domain located peripherally. ATP binding at the ATPase domain stabilizes the insertion region within the ATPase domain, keeping the Toprim domain in a closed state. Upon ATP depletion by phages, the Toprim domain opens to bind and cleave the DNA substrate. GajB, which docks on GajA, is activated by the cleaved DNA, ultimately leading to prokaryotic cell death. Our study presents a mechanistic landscape of Gabija activation.


Assuntos
Bacillus cereus , Proteínas de Bactérias , Bacteriófagos , Microscopia Crioeletrônica , Imunidade Inata , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/química , Adenosina Trifosfatases/ultraestrutura , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Apoproteínas/química , Apoproteínas/imunologia , Apoproteínas/metabolismo , Apoproteínas/ultraestrutura , Proteínas de Bactérias/química , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/ultraestrutura , Bacteriófagos/imunologia , DNA/metabolismo , DNA/química , Clivagem do DNA , Magnésio/química , Magnésio/metabolismo , Modelos Moleculares , Ligação Proteica , Domínios Proteicos , Viabilidade Microbiana , Bacillus cereus/química , Bacillus cereus/imunologia , Bacillus cereus/metabolismo , Bacillus cereus/ultraestrutura , Estrutura Quaternária de Proteína , DNA Primase/química , DNA Primase/metabolismo , DNA Primase/ultraestrutura , DNA Topoisomerases/química , DNA Topoisomerases/metabolismo , DNA Topoisomerases/ultraestrutura
2.
Mol Cell ; 68(3): 591-604.e5, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29100056

RESUMO

The Hippo pathway is crucial in organ size control and tissue homeostasis, with deregulation leading to cancer. An extracellular nutrition signal, such as glucose, regulates the Hippo pathway activation. However, the mechanisms are still not clear. Here, we found that the Hippo pathway is directly regulated by the hexosamine biosynthesis pathway (HBP) in response to metabolic nutrients. Mechanistically, the core component of Hippo pathway (YAP) is O-GlcNAcylated by O-GlcNAc transferase (OGT) at serine 109. YAP O-GlcNAcylation disrupts its interaction with upstream kinase LATS1, prevents its phosphorylation, and activates its transcriptional activity. And this activation is not dependent on AMPK. We also identified OGT as a YAP-regulated gene that forms a feedback loop. Finally, we confirmed that glucose-induced YAP O-GlcNAcylation and activation promoted tumorigenesis. Together, our data establish a molecular mechanism and functional significance of the HBP in directly linking extracellular glucose signal to the Hippo-YAP pathway and tumorigenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transformação Celular Neoplásica/metabolismo , Glucose/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Neoplasias/enzimologia , Fosfoproteínas/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Regulação Neoplásica da Expressão Gênica , Glicosilação , Células HEK293 , Células HeLa , Humanos , Camundongos Nus , Neoplasias/genética , Neoplasias/patologia , Fosfoproteínas/genética , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Serina , Transdução de Sinais , Fatores de Tempo , Fatores de Transcrição , Transcrição Gênica , Ativação Transcricional , Proteínas de Sinalização YAP
3.
Mol Biol Rep ; 51(1): 338, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393490

RESUMO

Pulmonary fibrosis (PF) is a progressive and fatal lung disease with high incidence and a lack of effective treatment, which is a severe public health problem. PF has caused a huge socio-economic burden, and its pathogenesis has become a research hotspot. SIRT1 is a nicotinamide adenosine dinucleotide (NAD)-dependent sirtuin essential in tumours, Epithelial mesenchymal transition (EMT), and anti-aging. Numerous studies have demonstrated after extensive research that it is crucial in preventing the progression of pulmonary fibrosis. This article reviews the biological roles and mechanisms of SIRT1 in regulating the progression of pulmonary fibrosis in terms of EMT, oxidative stress, inflammation, aging, autophagy, and discusses the potential of SIRT1 as a therapeutic target for pulmonary fibrosis, and provides a new perspective on therapeutic drugs and prognosis prospects.


Assuntos
Neoplasias , Fibrose Pulmonar , Sirtuína 1 , Humanos , Transição Epitelial-Mesenquimal , Fibrose , Estresse Oxidativo , Sirtuína 1/genética , Sirtuína 1/metabolismo
4.
J Nanobiotechnology ; 22(1): 318, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38849914

RESUMO

Mitochondria occupy a central role in the biology of most eukaryotic cells, functioning as the hub of oxidative metabolism where sugars, fats, and amino acids are ultimately oxidized to release energy. This crucial function fuels a variety of cellular activities. Disruption in mitochondrial metabolism is a common feature in many diseases, including cancer, neurodegenerative conditions and cardiovascular diseases. Targeting tumor cell mitochondrial metabolism with multifunctional nanosystems emerges as a promising strategy for enhancing therapeutic efficacy against cancer. This review comprehensively outlines the pathways of mitochondrial metabolism, emphasizing their critical roles in cellular energy production and metabolic regulation. The associations between aberrant mitochondrial metabolism and the initiation and progression of cancer are highlighted, illustrating how these metabolic disruptions contribute to oncogenesis and tumor sustainability. More importantly, innovative strategies employing nanomedicines to precisely target mitochondrial metabolic pathways in cancer therapy are fully explored. Furthermore, key challenges and future directions in this field are identified and discussed. Collectively, this review provides a comprehensive understanding of the current state and future potential of nanomedicine in targeting mitochondrial metabolism, offering insights for developing more effective cancer therapies.


Assuntos
Mitocôndrias , Nanomedicina , Neoplasias , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Nanomedicina/métodos , Animais , Metabolismo Energético/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos
5.
J Nanobiotechnology ; 22(1): 171, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38610017

RESUMO

Salivary extracellular vesicles (EVs) have emerged as key tools for non-invasive diagnostics, playing a crucial role in the early detection and monitoring of diseases. These EVs surpass whole saliva in biomarker detection due to their enhanced stability, which minimizes contamination and enzymatic degradation. The review comprehensively discusses methods for isolating, enriching, quantifying, and characterizing salivary EVs. It highlights their importance as biomarkers in oral diseases like periodontitis and oral cancer, and underscores their potential in monitoring systemic conditions. Furthermore, the review explores the therapeutic possibilities of salivary EVs, particularly in personalized medicine through engineered EVs for targeted drug delivery. The discussion also covers the current challenges and future prospects in the field, emphasizing the potential of salivary EVs in advancing clinical practice and disease management.


Assuntos
Vesículas Extracelulares , Neoplasias Bucais , Humanos , Medicina de Precisão , Sistemas de Liberação de Medicamentos , Saliva
6.
Ecotoxicol Environ Saf ; 270: 115948, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38184976

RESUMO

The increasing production and prevalence of antimony (Sb)-related products raise concerns regarding its potential hazards to reproductive health. Upon environmental exposure, Sb reportedly induces testicular toxicity during spermatogenesis; moreover, it is known to affect various testicular cell populations, particularly germline stem cell populations. However, the cell-cell communication resulting from Sb exposure within the testicular niche remains poorly understood. To address this gap, herein we analyzed testicular single-cell RNA sequencing data from Sb-exposed Drosophila. Our findings revealed that the epidermal growth factor receptor (EGFR) and WNT signaling pathways were associated with the stem cell niche in Drosophila testes, which may disrupt the homeostasis of the testicular niche in Drosophila. Furthermore, we identified several ligand-receptor pairs, facilitating the elucidation of intercellular crosstalk involved in Sb-mediated reproductive toxicology. We employed scRNA-seq analysis and conducted functional verification to investigate the expression patterns of core downstream factors associated with EGFR and WNT signatures in the testes under the influence of Sb exposure. Altogether, our results shed light on the potential mechanisms of Sb exposure-mediated testicular cell-lineage communications.


Assuntos
Drosophila , Testículo , Masculino , Animais , Testículo/metabolismo , Drosophila/metabolismo , Antimônio/toxicidade , Antimônio/metabolismo , Comunicação Celular , Receptores ErbB/metabolismo , Análise de Sequência de RNA
7.
Phytother Res ; 38(2): 797-838, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38083970

RESUMO

Obesity has become a serious global public health problem, affecting over 988 million people worldwide. Nevertheless, current pharmacotherapies have proven inadequate. Natural compounds have garnered significant attention due to their potential antiobesity effects. Over the past three decades, ca. 50 natural compounds have been evaluated for the preventive and/or therapeutic effects on obesity in animals and humans. However, variations in the antiobesity efficacies among these natural compounds have been substantial, owing to differences in experimental designs, including variations in animal models, dosages, treatment durations, and administration methods. The feasibility of employing these natural compounds as pharmacotherapies for obesity remained uncertain. In this review, we systematically summarized the antiobesity efficacy and mechanisms of action of each natural compound in animal models. This comprehensive review furnishes valuable insights for the development of antiobesity medications based on natural compounds.


Assuntos
Fármacos Antiobesidade , Obesidade , Humanos , Animais , Obesidade/tratamento farmacológico , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico
8.
Int J Mol Sci ; 25(6)2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38542160

RESUMO

Protein serine/threonine phosphatase 2A (PP2A) regulates diverse cellular processes via the formation of ~100 heterotrimeric holoenzymes. However, a scarcity of knowledge on substrate recognition by various PP2A holoenzymes has greatly prevented the deciphering of PP2A function in phosphorylation-mediated signaling in eukaryotes. The review summarized the contribution of B56 phosphorylation to PP2A-B56 function and proposed strategies for intervening B56 phosphorylation to treat diseases associated with PP2A-B56 dysfunction; it especially analyzed recent advancements in LxxIxEx B56-binding motifs that provide the molecular details of PP2A-B56 binding specificity and, on this basis, explored the emerging role of PP2A-B56 in the mitosis process, virus attack, and cancer development through LxxIxE motif-mediated PP2A-B56 targeting. This review provides theoretical support for discriminatingly targeting specific PP2A holoenzymes to guide PP2A activity against specific pathogenic drivers.


Assuntos
Proteína Fosfatase 2 , Transdução de Sinais , Fosforilação , Proteína Fosfatase 2/metabolismo , Ligação Proteica , Holoenzimas/metabolismo
9.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1406-1414, 2024 Mar.
Artigo em Zh | MEDLINE | ID: mdl-38621989

RESUMO

The clinical data of coronary heart disease(CHD) patients treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine and Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to March 2023 were retrospectively collected. This study involved the descriptive analysis of demographic characteristics, clinical symptoms, and tongue and pulse features. The χ~2 test was conducted to analyze the distribution of syndrome elements and their combinations at diffe-rent stages of CHD, so as to reveal the clinical characteristics and syndrome patterns at various pathological stages of CHD. This study extracted 28 symptom entries, 10 tongue manifestation entries, and 7 pulse manifestation entries, summarized the 5 main disease locations of the heart, lung, liver, spleen, and kidney, and the 8 main disease natures of blood stasis, phlegm turbidity, Qi stagnation, heat(fire), fluid retention, Qi deficiency, Yin deficiency, and Yang deficiency and 8 combinations of disease natures. The χ~2 test showed significant differences in the distribution of syndrome elements including the lung, liver, spleen, kidney, blood stasis, heat(fire), Qi stagnation, heat syndrome, water retention, Qi deficiency, Yin deficiency, and Yang deficiency between different disease stages. Specifically, the liver, blood stasis, heat(fire), and Qi stagnation accounted for the highest proportion during unstable stage, and the lung, spleen, kidney, water retention, Qi deficiency, Yin deficiency, and Yang deficiency accounted for the highest proportion at the end stage. The distribution of Qi deficiency varied in the different time periods after percutaneous coronary intervention(PCI). As shown by the χ~2 test of the syndrome elements combination, the distribution of single disease location, multiple disease locations, single disease nature, double disease natures, multiple natures, excess syndrome, and mixture of deficiency and excess varied significantly at different stages of CHD. Specifically, single disease location, single disease nature, and excess syndrome accounted for the highest proportion during the stable stage, and double disease natures accounted for the highest proportion during the unstable stage. Multiple disease locations, multiple disease natures, and mixture of deficiency and excess accounted for the highest proportion during the end stage. In conclusion, phlegm turbidity and blood stasis were equally serious during the stable stage, and a pathological mechanism caused by blood stasis and toxin existed during the unstable stage. The overall Qi deficiency worsened after PCI, and the end stage was accompanied by the Yin and Yang damage and the aggravation of water retention. There were significant differences in the distribution of clinical characteristics and syndrome elements at different stages of CHD. The pathological process of CHD witnessed the growth and decline of deficiency and excess and the combination of phlegm turbidity and blood stasis, which constituted the basic pathogenesis.


Assuntos
Doença das Coronárias , Insuficiência Cardíaca , Intervenção Coronária Percutânea , Humanos , Medicina Tradicional Chinesa , Deficiência da Energia Yang , Deficiência da Energia Yin , Estudos Transversais , Estudos Retrospectivos , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Síndrome , Água
10.
Angew Chem Int Ed Engl ; 63(18): e202401880, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38407419

RESUMO

Cytisine (CTS) is a useful medicine for treating nervous disorders and smoking addiction, and exploring a convenient method to detect CTS is of great significance for long-term/home medication to avoid the risk of poisoning, but it is full of challenges. Here, a modified metal-organic framework sensor Tb@Zn-TDA-80 with dual emission centers was prepared using a post-modified luminescence center strategy. The obtained Tb@Zn-TDA-80 can serve as a CTS sensor with high sensitivity and selectivity. To achieve portable detection, Tb@Zn-TDA-80 was further fabricated as a membrane sensor, M-Tb@Zn-TDA-80, which displayed an obvious CTS-responsive color change by simply dropping a CTS solution onto its surface. Benefiting from this unique functionality, M-Tb@Zn-TDA-80 successfully realized the visual detection and quantitative monitoring of CTS in the range of 5.26-52.6 mM by simply scanning the color with a smartphone. The results of nuclear magnetic resonance spectroscopy and theoretical computation illustrated that the high sensing efficiency of Tb@Zn-TDA-80 for CTS was attributed to the N-H⋅⋅⋅π and π⋅⋅⋅π interactions between the ligand and CTS. And luminescence quenching may result from the intramolecular charge transfer. This study provides a convenient method for ensuring long-term medication safety at home.


Assuntos
Alcaloides , Estruturas Metalorgânicas , Alcaloides Quinolizidínicos , Luminescência , Smartphone , Zinco , Estruturas Metalorgânicas/química
11.
Funct Integr Genomics ; 23(2): 79, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36882550

RESUMO

As a well-known behavioral risk factor for human health, smoking is involved in carcinogenesis, tumor progression, and therapeutic interventions of head and neck squamous cell carcinoma (HNSCC). The stratification of disease subtypes according to tobacco use is expressively needed for HNSCC precision therapy. High-throughput transcriptome profiling by RNA sequencing (RNA-seq) from The Cancer Genome Atlas (TCGA) was collected and collated for differential expression analysis and pathway enrichment analysis to characterize the molecular landscape for non-smoking HNSCC patients. Molecular prognostic signatures specific to non-smoking HNSCC patients were identified by the least absolute shrinkage and selection operator (LASSO) analysis and were then verified via internal and external validation cohorts. While proceeding to immune cell infiltration and after drug sensitivity analysis was further carried out, a proprietary nomogram was finally developed for their respective clinical applications. In what it relates to the non-smoking cohort, the enrichment analysis pointed to human papillomavirus (HPV) infection and PI3K-Akt signaling pathway, with the prognostic signature consisting of another ten prognostic genes (COL22A1, ADIPOQ, RAG1, GREM1, APBA2, SPINK9, SPP1, ARMC4, C6, and F2RL2). These signatures showed to be independent factors, and the related nomograms were, thus, constructed for their further and respective clinical applications. While the molecular landscapes and proprietary prognostic signature were characterized based on non-smoking HNSCC patients, a clinical nomogram was constructed to provide better HNSCC patient classification and guide treatment for non-smoking HNSCC patients. Nonetheless, there are still significant challenges in the recognition, diagnosis, treatment, and understanding of the potentially efficient mechanisms of HNSCC with no tobacco use.


Assuntos
Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Transcriptoma , Humanos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , Fosfatidilinositol 3-Quinases/genética , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
12.
J Gene Med ; 25(7): e3495, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36894497

RESUMO

Immunogenic cell death (ICD) is one of the mechanisms regulating cell death, which activates adaptive immunity in immunocompetent hosts and is associated with tumor progression, prognosis and therapeutic response. Endometrial cancer (EC) is one of the most common malignancies of the female genital tract, and the potential role of immunogenic cell death-related genes (IRGs) in the tumor microenvironment (TME) remains unclear. We describe the variation of IRGs and assess the expression patterns in EC samples from The Cancer Genome Atlas and Gene Expression Omnibus cohorts. Based on the expression of 34 IRGs, we identified two different ICD-related clusters and subsequently differentially expressed genes between the two ICD-related clusters were used for the identification of two ICD gene clusters. We identified the clusters and found that alterations in the multilayer IRG were associated with patient prognosis and TME cell infiltration characteristics. On this basis, ICD score risk scores were calculated, and ICD signatures were constructed and validated for their predictive power in EC patients. To help clinicians better apply the ICD signature, an accurate nomogram was constructed. The low ICD risk group was characterized by high microsatellite instability, high tumor mutational load, high IPS score and stronger immune activation. Our comprehensive analysis of IRGs in EC patients suggested a potential role in the tumor immune interstitial microenvironment, clinicopathological features and prognosis. These findings may improve our understanding of the role of ICDs, and provide a new basis for assessing prognosis and developing more effective immunotherapeutic strategies in EC.


Assuntos
Neoplasias do Endométrio , Morte Celular Imunogênica , Humanos , Feminino , Microambiente Tumoral/genética , Neoplasias do Endométrio/genética , Família Multigênica , Mutação
13.
J Transl Med ; 21(1): 211, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949458

RESUMO

The human body is colonized by abundant and diverse microorganisms, collectively known as the microbiome. The oral cavity has more than 700 species of bacteria and consists of unique microbiome niches on mucosal surfaces, on tooth hard tissue, and in saliva. The homeostatic balance between the oral microbiota and the immune system plays an indispensable role in maintaining the well-being and health status of the human host. Growing evidence has demonstrated that oral microbiota dysbiosis is actively involved in regulating the initiation and progression of an array of autoimmune diseases.Oral microbiota dysbiosis is driven by multiple factors, such as host genetic factors, dietary habits, stress, smoking, administration of antibiotics, tissue injury and infection. The dysregulation in the oral microbiome plays a crucial role in triggering and promoting autoimmune diseases via several mechanisms, including microbial translocation, molecular mimicry, autoantigen overproduction, and amplification of autoimmune responses by cytokines. Good oral hygiene behaviors, low carbohydrate diets, healthy lifestyles, usage of prebiotics, probiotics or synbiotics, oral microbiota transplantation and nanomedicine-based therapeutics are promising avenues for maintaining a balanced oral microbiome and treating oral microbiota-mediated autoimmune diseases. Thus, a comprehensive understanding of the relationship between oral microbiota dysbiosis and autoimmune diseases is critical for providing novel insights into the development of oral microbiota-based therapeutic approaches for combating these refractory diseases.


Assuntos
Doenças Autoimunes , Microbioma Gastrointestinal , Microbiota , Probióticos , Humanos , Disbiose/microbiologia , Boca/microbiologia
14.
Glycoconj J ; 40(5): 541-549, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37542637

RESUMO

Alpha-1,6 fucosylation of N-glycans (core fucosylation, CF) represents a unique form of N-glycans and is widely involved in disease progression. In order to accurately identify CF glycoproteins, several approaches have been developed based on sequential cleavage with different glycosidases to truncate the N-glycans. Since multi-step sample treatments may introduce quantitation bias and affect the practicality of these approaches in large-scale applications. Here, we systematically evaluated the performance of the single-step treatment of intact glycopeptides by endoglycosidase F3 for CF glycoproteome. The single-step truncation (SST) strategy demonstrated higher quantitative stability and higher efficiency compared with previous approaches. The strategy was further practiced on both cell lines and serum samples. The dysregulation of CF glycopeptides between preoperative and postoperative serum from patients with pancreatic ductal adenocarcinoma was revealed, and the CF modifications of BCHE_N369, CDH5_N112 and SERPIND1_N49 were found to be potential prognostic markers. This study thus provides an efficient solution for large-scale quantitative analysis of the CF glycoproteome.


Assuntos
Glicopeptídeos , Glicoproteínas , Humanos , Glicosilação , Glicoproteínas/metabolismo , Glicopeptídeos/análise , Polissacarídeos
15.
Int J Mol Sci ; 24(13)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37445889

RESUMO

The instability and volatility of iodine is high, however, effective iodine biocidal species can be readily stored in iodinated azoles and then be released upon decomposition or detonation. Iodine azoles with high iodine content and high thermal stability are highly desired. In this work, the strategy of methylene bridging with asymmetric structures of 3,4,5-triiodo-1-H-pyrazole (TIP), 2,4,5-triiodo-1H-imidazol (TIM), and tetraiodo-1H-pyrrole (TIPL) are proposed. Two highly stable fully iodinated methylene-bridged azole compounds 3,4,5-triiodo-1-((2,4,5-triiodo-1H-imidazol-1-yl)methyl)-1H-pyrazole (3) and 3,4,5-triiodo-1-((tetraiodo-1H-pyrrol-1-yl)methyl)-1H-pyrazole (4) were obtained with high iodine content and excellent thermal stability (iodine content: 84.27% for compound 3 and 86.48% for compound 4; Td: 3: 285 °C, 4: 260 °C). Furthermore, their composites with high-energy oxidant ammonium perchlorate (AP) were designed. The combustion behavior and thermal decomposition properties of the formulations were tested and evaluated. This work may open a new avenue to develop advanced energetic biocidal materials with well-balanced energetic and biocidal properties and versatile functionality.


Assuntos
Azóis , Iodo , Azóis/farmacologia , Iodo/farmacologia , Iodo/química , Pirróis , Fenômenos Químicos , Pirazóis
16.
Int J Mol Sci ; 24(17)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37686320

RESUMO

Fungal pathogens of the Cryptococcus neoformans species complex (C. neoformans SC) are a major cause of fungal meningitis in immunocompromised individuals. As with other melanotic microorganisms associated with human diseases, the cell-wall-associated melanin of C. neoformans SC is a major virulence factor that contributes to its ability to evade host immune responses. The levels of melanin substrate and the regulation of melanin formation could be influenced by the microbiota-gut-brain axis. Moreover, recent studies show that C. neoformans infections cause dysbiosis in the human gut microbiome. In this review, we discuss the potential association between cryptococcal meningitis and the gut microbiome. Additionally, the significant potential of targeting the gut microbiome in the diagnosis and treatment of this debilitating disease is emphasized.


Assuntos
Criptococose , Cryptococcus neoformans , Microbioma Gastrointestinal , Meningite Criptocócica , Humanos , Melaninas , Eixo Encéfalo-Intestino
17.
Molecules ; 28(24)2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38138437

RESUMO

To explore the feasibility of the mechanochemical-assisted extraction (MCAE) of phenolic compounds from lotus seedpod (Receptaculum Nelumbinis), a single-factor experiment combined with response-surface methodology (RSM) was used to optimize the extraction process. The results showed the optimal extraction conditions as follows: Li2CO3 as a solid reagent (25%), an extraction time of 80 min, liquid/solid ratio of 42.8 mL/g, and extraction temperature of 80.7 °C; and the maximum value of total phenolic content (TPC) was 106.15 ± 1.44 gallic acid equivalents (GAE)/g dry weight (DW). Additionally, the 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) were 279.75 ± 18.71, 618.60 ± 2.70, and 634.14 ± 7.17 µmol TE/g, respectively. Ultra-high pressure liquid chromatography combined with triple-time-of-flight mass spectrophotometry (UPLC-Triple-TOF/MS) analysis identified eight phenolic compounds mainly consisting of polyphenols and flavonoids. Moreover, the phenolic compounds showed potent inhibitory effects on both α-amylase and α-glucosidase, with inhibition rates of over 80%. Furthermore, the results showed different degrees of inhibition activity against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli, among which the inhibitory effect on the growth of B. subtilis was the best. This paper shows that the phenolic compounds have good biological activities, which provides a reference for the further exploitation of LSP.


Assuntos
Fenóis , Extratos Vegetais , Extratos Vegetais/química , Fenóis/química , Antioxidantes/química , Sementes/química
18.
Angew Chem Int Ed Engl ; 62(34): e202305213, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37170958

RESUMO

Thermocatalysis of CO2 into high valuable products is an efficient and green method for mitigating global warming and other environmental problems, of which Noble-metal-free metal-organic frameworks (MOFs) are one of the most promising heterogeneous catalysts for CO2 thermocatalysis, and many excellent researches have been published. Hence, this review focuses on the valuable products obtained from various CO2 conversion reactions catalyzed by noble-metal-free MOFs, such as cyclic carbonates, oxazolidinones, carboxylic acids, N-phenylformamide, methanol, ethanol, and methane. We classified these published references according to the types of products, and analyzed the methods for improving the catalytic efficiency of MOFs in CO2 reaction. The advantages of using noble-metal-free MOF catalysts for CO2 conversion were also discussed along the text. This review concludes with future perspectives on the challenges to be addressed and potential research directions. We believe that this review will be helpful to readers and attract more scientists to join the topic of CO2 conversion.

19.
Acc Chem Res ; 54(2): 332-343, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33300791

RESUMO

For a very long time, frequent occurrences of biocrises have wreaked havoc on human beings, animals, and the environment. As a result, it is necessary to develop biocidal agents to destroy or neutralize active agents by releasing large amounts of strong biocides which are obtained upon detonation. Iodine is an efficient biocidal agent for bacteria, fungi, yeasts, viruses, spores, and protozoan parasites, and it is the sole element in the periodic table that can destroy microbes without contaminating the environment. Based on chemical biology, the mechanism of iodine as a bactericide may arise from oxidation and iodination reactions of cellular proteins and nucleic acids. However, because of the high vapor pressure causing elemental iodine to sublime readily at room temperature, it is inconvenient to use this material in its normal solid state directly as a biocidal agent under ambient conditions. Iodine-rich compounds where iodine is firmly bonded in molecules as a C-I or I-O moiety have been observed to be among the most promising energetic biocidal compounds. Gaseous products comprised of large amounts of iodine or iodine-containing components as strong biocides are released in the decomposition or explosion of iodine-rich compounds. Because of the detonation pressure, the iodine species are distributed over a large area greatly improving the efficacy of the system and requiring considerably less effort compared to traditional biocidal methods. The commercially available tetraiodomethane and tetraiodoethene, which possess superb iodine content also have the disadvantages of volatility, light sensitivity, and chemically reactivity, and therefore, are not suitable for use directly as biocidal agents. It is absolutely critical to synthesize new iodine-rich compounds with good thermal and chemical stabilities.In this Account, we describe our strategies for the syntheses of energetic iodine-rich compounds while maintaining the maximum iodine content with concomitant stability and routes for the synthesis of oxygen-containing iodine-rich compounds to improve the oxygen balance and achieve both high-energy and high-iodine content. In the other work, which involves cocrystals, iodine-containing polymers were also summarized. It is hoped that this Account will provide guidelines for the design and syntheses of new iodine-rich compounds and a route for the development of inexpensive, more efficient, and safer iodine-rich antibiological warfare agents of the future.


Assuntos
Desinfetantes/química , Compostos de Iodo/química , Bactérias/efeitos dos fármacos , Desinfetantes/síntese química , Desinfetantes/farmacologia , Compostos de Iodo/síntese química , Compostos de Iodo/farmacologia , Estruturas Metalorgânicas , Oxirredução , Triazóis/química
20.
Health Qual Life Outcomes ; 20(1): 98, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35725609

RESUMO

PURPOSE: Mapping the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to SF-6Dv2 in Chinese patients with chronic heart failure, and to obtain the health utility value for health economic assessment. METHODS: Four statistical algorithms, including ordinary least square method (OLS), Tobit model, robust MM estimator (MM) and censored least absolute deviations (CLAD), were used to establish the alternative model. Models were validated by using a tenfold cross-validation technique. The mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate the prediction performance of the model. The Spearman correlation coefficient and Intraclass Correlation Coefficients (ICC) were used to examine the relationship between the predicted and observed SF-6Dv2 values. RESULTS: A total of 195 patients with chronic heart failure were recruited from 3 general hospitals in Beijing. The MLHFQ summary score and domain scores of the study sample were negatively correlated with SF-6Dv2 health utility value. The OLS regression model established based on the MLHFQ domain scores was the optimal fitting model and the predicted value was highly positively correlated with the observed value. CONCLUSION: The MLHFQ can be mapped to SF-6Dv2 by OLS, which can be used for health economic assessment of cardiovascular diseases such as chronic heart failure.


Assuntos
Insuficiência Cardíaca , Qualidade de Vida , China , Doença Crônica , Humanos , Análise dos Mínimos Quadrados , Inquéritos e Questionários
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