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1.
Chem Asian J ; : e202400211, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38709109

RESUMEN

The growing demand for wearable electronics has driven the development of flexible thermoelectric (TE) generators which can harvest waste body heat as a renewable power source. Despite carbon nanotube (CNT) yarns have attracted significant attention as a promising candidate for TE materials, challenges still exist in improving their TE efficiency for commercial applications. Herein, we developed high performance CNT/polyaniline (PANI) yarns by engineering the coating of polyaniline emeraldine base (PANIeb), in which CNT yarns were firstly coated by PANIeb layer and further doped by HCl vapor treatment. With the incorporation of PANIeb, σ and S were simultaneously increased to 1796 S cm-1 and 74.8 µV K-1 for CNT/PANIeb 4-2d fibers, respectively. Further HCl vapor treatment induced greatly increased σ to 3194 S cm-1, but maintained be 83 % value before doping, giving rise to the highest power factor of 1224 µW m-1K-2, higher than pristine CNT yarns of 576 µW m-1K-2. Combining outstanding high TE performance and bending durability, a flexible TE generator was constructed to deliver high out power of 187 nW with temperature gradients of about 30 K. These results demonstrate the potential promise of high-performance CNT/PANI-HCl yarns to harvest waste body heat for sustainable power supply.

2.
Sci Adv ; 10(21): eadj8184, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38781332

RESUMEN

Sinking particles are a critical conduit for the transport of surface microbes to the ocean's interior. Vertical connectivity of phylogenetic composition has been shown; however, the functional vertical connectivity of microbial communities has not yet been explored in detail. We investigated protein and taxa profiles of both free-living and particle-attached microbial communities from the surface to 3000 m depth using a combined metaproteomic and 16S rRNA amplicon sequencing approach. A clear compositional and functional vertical connectivity of microbial communities was observed throughout the water column with Oceanospirillales, Alteromonadales, and Rhodobacterales as key taxa. The surface-derived particle-associated microbes increased the expression of proteins involved in basic metabolism, organic matter processing, and environmental stress response in deep waters. This study highlights the functional vertical connectivity between surface and deep-sea microbial communities via sinking particles and reveals that a considerable proportion of the deep-sea microbes might originate from surface waters and have a major impact on the biogeochemical cycles in the deep sea.


Asunto(s)
Microbiota , Océanos y Mares , Filogenia , ARN Ribosómico 16S , Agua de Mar , ARN Ribosómico 16S/genética , Agua de Mar/microbiología , Bacterias/genética , Bacterias/clasificación
3.
Artículo en Inglés | MEDLINE | ID: mdl-38737375

RESUMEN

Released mitochondrial DNA (mtDNA) in cells activates cGAS-STING pathway, which induces expression of interferon-stimulated genes (ISGs) and thereby promotes inflammation, as frequently seen in asthmatic airways. However, whether the genetic determinant, Gasdermin B (GSDMB), the most replicated asthma risk gene, regulates this pathway remains unknown. We set out to determine whether and how GSDMB regulates mtDNA-activated cGAS-STING pathway and subsequent ISGs induction in human airway epithelial cells. Using qPCR, ELISA, native polyacrylamide gel electrophoresis, co-immunoprecipitation and immunofluorescence assays, we evaluated the regulation of GSDMB on cGAS-STING pathway in both BEAS-2B cells and primary normal human bronchial epithelial cells (nHBEs). mtDNA was extracted in plasma samples from human asthmatics and the correlation between mtDNA levels and eosinophil counts was analyzed. GSDMB is significantly associated with RANTES expression in asthmatic nasal epithelial brushing samples from the Genes-environments and Admixture in Latino Americans (GALA) II study. Over-expression of GSDMB promotes DNA-induced IFN and ISGs expression in bronchial epithelial BEAS-2B cells and nHBEs. Conversely, knockout of GSDMB led to weakened induction of interferon (IFNs) and ISGs in BEAS-2B cells. Mechanistically, GSDMB interacts with the C-terminus of STING, promoting the translocation of STING to Golgi, leading to the phosphorylation of IRF3 and induction of IFNs and ISGs. mtDNA copy number in serum from asthmatics was significantly correlated with blood eosinophil counts especially in male subjects. GSDMB promotes the activation of mtDNA and poly (dA:dT)-induced activation of cGAS-STING pathway in airway epithelial cells, leading to enhanced induction of ISGs.

4.
J Ethnopharmacol ; : 118357, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38763374

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. MATERIALS AND METHODS: The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-Ⅰ in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. RESULTS: The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-Ⅰ (35.34 kDa), and the structural characterization indicated that CVP-AP-Ⅰ was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-Ⅰ attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. CONCLUSION: The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases.

5.
J Ethnopharmacol ; 331: 118299, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38729539

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM), Yigong San (YGS) is mainly used to treat dyspepsia caused by deficiency of spleen and stomach qi. Although the chemical composition and bioactivity of YGS has been well studied, the main in vivo compounds and their distribution in tissues still need to be made clearer. AIM OF THE STUDY: To elucidate the pharmacokinetic profiles and tissue distribution of eight main compounds of YGS in rats, and provide a reference for clinical application and new drug development. MATERIALS AND METHODS: UPLC-Q-Exactive-Orbitrap-MS was used to qualitatively characterize the parent compounds and their metabolites in the plasma of rats after oral administration of YGS. A sensitive, reliable, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method using UPLC-AB Sciex QTRAP 5500 MS was established to quantitatively determine eight main compounds of YGS in rat plasma and tissues, including liquiritin, isoliquiritin, hesperidin, ginsenosides Rb1, Re and Rg1, atractylenolides I and II. RESULTS: The mean area under the concentration-time curve (AUC) values of ginsenoside Rb1, hesperidin, and liquiritin at low, medium, and high doses were greater than 150 ng h/mL. The elimination half-life (t1/2) values of ginsenoside Rb1, atractylenolides I and II (low and medium doses) were longer than 10 h. Peak time (Tmax) values of all compounds were shorter than 10 h. Except for atractylenolides, the maximum concentration (Cmax) values of the compounds were greater than 10 ng/mL. The eight compounds were detected in the heart, brain, liver, spleen and kidney at 0.25 h after oral administration. Liquiritin and isoliquiritin had higher exposure in the liver and heart. Hesperidin and ginsenosides Rb1, Re, and Rg1 are mainly distributed in the spleen and kidney. Atractylenolides I and II are mainly distributed in spleen, liver and kidney. CONCLUSIONS: All main compounds of YGS, i.e., liquiritin, isoliquiritin, hesperidin, ginsenosides Rb1, Re, and Rg1, and atractylenolides I and II are absorbed into plasma and widely distributed in various tissues. Among them, hesperidin, ginsenoside Rb1, and atractylenolide I are main in vivo compounds. They are mainly distributed in spleen, liver and kidney. The results of this study provide a basis for further in-depth development and application of YGS.

6.
Bioinformatics ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730554

RESUMEN

MOTIVATION: Enhanced by contemporary computational advances, the prediction of drug-target interactions (DTIs) has become crucial in developing de novo and effective drugs. Existing deep learning approaches to DTI prediction are frequently beleaguered by a tendency to overfit specific molecular representations, which significantly impedes their predictive reliability and utility in novel drug discovery contexts. Furthermore, existing DTI networks often disregard the molecular size variance between macro molecules (targets) and micro molecules (drugs) by treating them at an equivalent scale that undermines the accurate elucidation of their interaction. RESULTS: We propose a novel DTI network with a differential-scale scheme to model the binding site for enhancing DTI prediction, which is named as BindingSiteDTI. It explicitly extracts multiscale substructures from targets with different scales of molecular size and fixed-scale substructures from drugs, facilitating the identification of structurally similar substructural tokens, and models the concealed relationships at the substructural level to construct interaction feature. Experiments conducted on popular benchmarks, including DUD-E, human and BindingDB, shown that BindingSiteDTI contains significant improvements compared with recent DTI prediction methods. AVAILABILITY: The source code of BindingSiteDTI can be accessed at https://github.com/MagicPF/BindingSiteDTI. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

7.
bioRxiv ; 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38559185

RESUMEN

A major challenge in microbiome research is understanding how natural communities respond to environmental change. The ecological, spatial, and chemical complexity of soils makes understanding the metabolic response of these communities to perturbations particularly challenging. Here we measure the dynamics of respiratory nitrate utilization in >1,500 soil microcosms from 20 soil samples subjected to pH perturbations. Despite the complexity of the soil microbiome a minimal mathematical model with two parameters, the quantity of active biomass and the availability of a limiting nutrient, quantifies observed nitrate utilization dynamics across soils and pH perturbations. Across environmental perturbations, the model reveals the existence of three functional phases each with distinct qualitative dynamics of nitrate utilization over time: a phase where acidic perturbations induce cell death that limits metabolic activity, a nutrient-limiting phase where nitrate uptake is performed by dominant taxa that utilize nutrients released from the soil matrix, and a resurgent growth phase in basic conditions, where nutrients are in excess and rare taxa rapidly outgrow dominant populations. The underlying mechanism of each phase is predicted by our interpretable model and tested via amendment experiments, nutrient measurements, and sequencing. Finally, our data suggest that how soils transition between functional phases depends on the long-term history of environmental variation in the wild. Therefore, quantitative measurements and a minimal mathematical formalism reveal the existence of qualitative phases that capture the mechanisms and dynamics of a community responding to environmental change.

8.
J Med Virol ; 96(4): e29592, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38587184

RESUMEN

The role of human papillomavirus 16 (HPV 16) in esophageal squamous cell carcinoma (ESCC) remains uncertain. Therefore, this study aimed to investigate the prevalence of HPV 16 in patients with ESCC and its impact on theirprognosis. HPV 16 was detected using FISH, and TP53 status was evaluated via immunohistochemistry. The factors influencing prognosis were ananalyzed using the Log-rank test and Cox regression analyses. Among 178 patients with ESCC, 105 and 73 patients were categorized into concurrent chemoradiotherapy (CCRT) and postoperative chemoradiotherapy (POCRT) cohorts, respectively. Among 178 patients, 87 (48.87%) tested positive for HPV 16. Log-rank tests revealed that the overall survival (OS) of patients with ESCC who were HPV 16-positive was longer than that of those who were HPV 16-negative (median OS: 57 months vs. 27 months, p < 0.01**). HPV 16 infection and TP53 mutation status were identified as independent events. The OS of patients with mutant TP53 who were HPV 16-positive was longer than that of those who were HPV 16-negative in both CCRT and POCRT cohorts (p = 0.002** for CCRT cohorts and p = 0.0023** for POCRT cohorts). Conversely, HPV 16 infection had no effect on OS in the wild-type TP53 subgroup (p = 0.13 and 0.052 for CCRT and POCRT cohorts, respectively). As a conclusion, the positive rate of HPV 16 in ESCC in this study was 48.87% (87/178). Among the patients with ESCC who had TP53 mutation, those who were HPV 16-positive exhibited a better prognosis than those who were HPV 16-negative.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Infecciones por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Esófago/radioterapia , Papillomavirus Humano 16/genética , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patología , Estudios Retrospectivos , Quimioradioterapia , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología
9.
Heliyon ; 10(7): e28637, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38571627

RESUMEN

Chinese medicinal materials (CMMs) are important strategic resource in China. The cultivation process of medicinal plants is the key link which directly affect the quality and efficacy. The literatures of CMMs cultivation were acquired from China National Knowledge Infrastructure (CNKI) database and State Intellectual Property Office (SIPO) patent database for the years between 2001 and 2021. All the articles found were subjected to bibliometric analysis. The development trends and key topics were analyzed and visualized by VOSviewer and CiteSpace software. The results indicate that ecological planting, under-forest economy, intercropping patterns and industrialization production are the research hotspots in this field; cultivation technology and nutritional fertilization technology are the main areas addressed in recent years. Therefore, the high-quality and sustainable development of CMMs cultivation should be examined in terms of theoretical approaches, technical innovation, multi-cooperation, and intellectual property protection.

10.
Clin Proteomics ; 21(1): 29, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594611

RESUMEN

BACKGROUND: Adamantinomatous craniopharyngiomas (ACPs) are rare benign epithelial tumours with high recurrence and poor prognosis. Biological differences between recurrent and primary ACPs that may be associated with disease recurrence and treatment have yet to be evaluated at the proteomic level. In this study, we aimed to determine the proteomic profiles of paired recurrent and primary ACP, gain biological insight into ACP recurrence, and identify potential targets for ACP treatment. METHOD: Patients with ACP (n = 15) or Rathke's cleft cyst (RCC; n = 7) who underwent surgery at Sanbo Brain Hospital, Capital Medical University, Beijing, China and received pathological confirmation of ACP or RCC were enrolled in this study. We conducted a proteomic analysis to investigate the characteristics of primary ACP, paired recurrent ACP, and RCC. Western blotting was used to validate our proteomic results and assess the expression of key tumour-associated proteins in recurrent and primary ACPs. Flow cytometry was performed to evaluate the exhaustion of tumour-infiltrating lymphocytes (TILs) in primary and recurrent ACP tissue samples. Immunohistochemical staining for CD3 and PD-L1 was conducted to determine differences in T-cell infiltration and the expression of immunosuppressive molecules between paired primary and recurrent ACP samples. RESULTS: The bioinformatics analysis showed that proteins differentially expressed between recurrent and primary ACPs were significantly associated with extracellular matrix organisation and interleukin signalling. Cathepsin K, which was upregulated in recurrent ACP compared with that in primary ACP, may play a role in ACP recurrence. High infiltration of T cells and exhaustion of TILs were revealed by the flow cytometry analysis of ACP. CONCLUSIONS: This study provides a preliminary description of the proteomic differences between primary ACP, recurrent ACP, and RCC. Our findings serve as a resource for craniopharyngioma researchers and may ultimately expand existing knowledge of recurrent ACP and benefit clinical practice.

11.
J Hazard Mater ; 471: 134273, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38653137

RESUMEN

This study employs five UV-AOPs (PMS, PDS, H2O2, NaClO and NaClO2) to produce radicals (•OH, SO4•-, ClO•, O2•- and 1O2) and further comparatively studies their activity sequence and activity difference cause in toluene degradation. The toluene mineralization efficiency as a descending order is 73 % (UV-PMS) > 71 % (UV-PDS) > 70 % (acidified-UV-NaClO) > 55 % (UV-H2O2) > 36 % (UV-NaClO) > 35 % (UV-NaClO2); that of conversion efficiency is 99 % (acidified-UV-NaClO) > 95 % (UV-PMS) > 90 % (UV-PDS) > 74 % (UV-H2O2) > 44 % (UV-NaClO) > 41 % (UV-NaClO2). Acidic pretreatment significantly boosts the reactivity of UV-NaClO. ESR combined with radical quenching tests reveals the radicals' generation and evolution, and their contribution rates to toluene conversion, i.e. ClO• > SO4•- > O2•- > 1O2 > â€¢OH. Theoretical calculations further unveil the ring-opening reaction routes and the nature of the activity difference of different radicals. The minimum energy required for ring-opening reaction is 116.77, 150.63, 168.29 and 191.92 kJ/mol with respect to ClO•, SO4•-, 1O2 and •OH, and finding that the ClO•-HO• pair is the best for toluene mineralization. The difficulty for eliminating typical VOCs by using UV-AOPs method is determined as toluene > chlorobenzene > benzene > ethyl acetate.

12.
Int Immunopharmacol ; 133: 112012, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38657501

RESUMEN

Alveolar macrophages (AMs) seed in lung during embryogenesis and become mature in perinatal period. Establishment of acclimatization to environmental challenges is important, whereas the detailed mechanisms that drive metabolic adaptation of AMs remains to be elucidated. Here, we showed that energy metabolism of AMs was transformed from glycolysis prenatally to oxidative phosphorylation (OXPHOS) postnatally accompanied by up-regulated expression of mitochondrial transcription factor A (TFAM). TFAM deficiency disturbed mitochondrial stability and decreased OXPHOS, which finally impaired AM maintenance and function, but not AM embryonic development. Mechanistically, Tfam-deletion resulted in impaired mitochondrial respiration and decreased ATP production, which triggered endoplasmic reticulum (ER) stress to cause B cell lymphoma 2 ovarian killer (BOK) accumulation and abnormal distribution of intracellular Ca2+, eventually led to induce AM apoptotic death. Thus, our data illustrated mitochondrial-dependent OXPHOS played a key role in orchestrating AM postnatal metabolic adaptation.


Asunto(s)
Pulmón , Macrófagos Alveolares , Mitocondrias , Fosforilación Oxidativa , Animales , Macrófagos Alveolares/metabolismo , Mitocondrias/metabolismo , Ratones , Pulmón/metabolismo , Adaptación Fisiológica , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Estrés del Retículo Endoplásmico , Ratones Noqueados , Apoptosis , Ratones Endogámicos C57BL , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Femenino , Glucólisis , Adenosina Trifosfato/metabolismo , Proteínas del Grupo de Alta Movilidad
13.
Biomolecules ; 14(4)2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38672475

RESUMEN

The skin is the outer layer of the human body, and it is crucial in defending against injuries and damage. The regenerative capacity of aging and damaged skin caused by exposure to external stimuli is significantly impaired. Currently, the rise in average life expectancy and the modern population's aesthetic standards have sparked a desire for stem-cell-based therapies that can address skin health conditions. In recent years, mesenchymal stem cells (MSCs) as therapeutic agents have provided a promising and effective alternative for managing skin regeneration and rejuvenation, attributing to their healing capacities that can be applied to damaged and aged skin. However, it has been established that the therapeutic effects of MSC may be primarily mediated by paracrine mechanisms, particularly the release of exosomes (Exos). Exosomes are nanoscale extracellular vesicles (EVs) that have lipid bilayer and membrane structures and can be naturally released by different types of cells. They influence the physiological and pathological processes of recipient cells by transferring a variety of bioactive molecules, including lipids, proteins, and nucleic acids such as messenger RNAs (mRNAs) and microRNAs (miRNAs) between cells, thus playing an important role in intercellular communication and activating signaling pathways in target cells. Among them, miRNAs, a type of endogenous regulatory non-coding RNA, are often incorporated into exosomes as important signaling molecules regulating protein biosynthesis. Emerging evidence suggests that exosomal miRNAs from MSC play a key role in skin regeneration and rejuvenation by targeting multiple genes and regulating various biological processes, such as participating in inflammatory responses, cell migration, proliferation, and apoptosis. In this review, we summarize the recent studies and observations on how MSC-derived exosomal miRNAs contribute to the regeneration and rejuvenation of skin tissue, with particular attention to the applications of bioengineering methods for manipulating the miRNA content of exosome cargo to improve their therapeutic potential. This review can provide new clues for the diagnosis and treatment of skin damage and aging, as well as assist investigators in exploring innovative therapeutic strategies for treating a multitude of skin problems with the aim of delaying skin aging, promoting skin regeneration, and maintaining healthy skin.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , MicroARNs , Piel , Humanos , Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , MicroARNs/metabolismo , MicroARNs/genética , Piel/metabolismo , Animales , Regeneración , Trasplante de Células Madre Mesenquimatosas/métodos
14.
Eur J Pharmacol ; 974: 176601, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38677534

RESUMEN

BACKGROUND: Hypoxia disrupts glucose metabolism in hepatocellular carcinoma (HCC). Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) plays an ontogenetic role. Thus, we aimed to explore the regulation of TRPM7 by hypoxia-induced factor (HIF) and its underlying mechanisms in HCC. METHODS: hypoxia was induced in multiple HCC cells using 1% O2 or CoCl2 treatment, and subsequently blocked using siRNAs targeting HIF-1α or HIF-2α as well as a HIF-1α protein synthesis inhibitor. The levels of HIF-1α and TRPM7 were assessed using quantitative PCR (qPCR) and Western blot analysis. Chromatin immunoprecipitation (ChIP) and luciferase assays were performed to observe the regulation of TRPM7 promoter regions by HIF-1α. A PCR array was utilized to screen glucose metabolism-related enzymes in HEK293 cells overexpressing TRPM7 induced by tetracycline, and then verified in TRPM7-overexpressed huh7 cells. Finally, CCK-8, transwell, scratch and tumor formation experiments in nude mice were conducted to examine the effect of TRPM7 on proliferation and metastasis in HCC. RESULTS: Exposure to hypoxia led to increase the levels of TRPM7 and HIF-1α in HCC cells, which were inhibited by HIF-1α siRNA or enhanced by HIF-1α overexpression. HIF-1α directly bound to two hypoxia response elements (HREs) in the TRPM7 promoter. Several glycolytic metabolism-related enzymes, were simultaneously upregulated in HEK293 and huh7 cells overexpressing TRPM7 during hypoxia. In vitro and in vivo experiments demonstrated that TRPM7 promoted the proliferation and metastasis of HCC cells. CONCLUSIONS: TRPM7 was directly transcriptionally regulated by HIF-1α, leading to glycolytic metabolic reprogramming and the promotion of HCC proliferation and metastasis in vitro and in vivo. Our findings suggest that TRPM7 might be a potential diagnostic indicator and therapeutic target for HCC.


Asunto(s)
Carcinoma Hepatocelular , Proliferación Celular , Glucólisis , Subunidad alfa del Factor 1 Inducible por Hipoxia , Neoplasias Hepáticas , Canales Catiónicos TRPM , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Glucólisis/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Animales , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Ratones , Células HEK293 , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Progresión de la Enfermedad , Hipoxia de la Célula , Movimiento Celular/efectos de los fármacos , Regiones Promotoras Genéticas
15.
Phytother Res ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38685750

RESUMEN

The escalating incidence of nonalcoholic fatty liver disease (NAFLD) is closely associated with a high-fat diet, leading to a decline in quality of life and significant health impairment. 7-Hydroxyflavone (7-HY) is a flavonoid known for its anti-inflammatory, anticarcinogenic, and antioxidant effects. This study aims to assess the ameliorative effects of 7-HY on NAFLD induced by a high-fat diet and elucidate underlying mechanisms. Oleic acid/palmitic acid-induced HepG2 cells and C57BL/6 mice on a high-fat diet were utilized as in vitro and in vivo models. In animal experiments, 7-HY was utilized as a dietary supplement. The 15-week in vivo experiment monitored body weight, body fat percentage, glucose tolerance, insulin tolerance, and metabolic indexes. Commercial kits assessed triglyceride (TG) and total cholesterol levels in cells, liver tissue, and blood. Discovery Studio identified potential targets of 7-HY, compared with NAFLD-associated targets in the GeneCards database. Results indicated 7-HY mitigated fat accumulation, hepatic steatosis, and oxidative stress induced by a high-fat diet. Furthermore, 7-HY showed potential efficacy in ameliorating abnormal glucose metabolism and promoting energy metabolism. Reverse target finding and molecular docking demonstrated a robust interaction between 7-HY and serine/threonine kinase 24 (STK24). Subsequent experimental results confirmed 7-HY's ability to inhibit TG deposition in HepG2 cells through interaction with STK24. In conclusion, 7-HY demonstrated the capacity to alleviate high-fat diet-induced NAFLD, presenting a novel strategy for the prevention and treatment of NAFLD.

16.
BMC Chem ; 18(1): 72, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609951

RESUMEN

Toluene, a prominent member of volatile organic compounds (VOCs), exerts a substantial adverse influence on both human life and the environment. In the context of advanced oxidation processes, the ·OH radical emerges as a highly efficient oxidant, pivotal in the elimination of VOCs. This study employs computational quantum chemistry methods (G4MP2//B3LYP/6-311++G(d,p)) to systematically investigate the degradation of toluene by ·OH radicals in an implicit solvent model, and validates the rationale of choosing a single-reference method using T1 diagnostics. Our results suggest three possible reaction mechanisms for the oxidation of toluene by ·OH: firstly, the phenyl ring undergoes a hydrogen abstraction reaction followed by direct combination with ·OH to form cresol; secondly, ·OH directly adds to the phenyl ring, leading to ring opening; thirdly, oxidation of sidechain to benzoic acid followed by further addition and ring opening. The last two oxidation pathways involve the ring opening of toluene via the addition of ·OH, significantly facilitating the process. Therefore, both pathways are considered feasible for the degradation of toluene. Subsequently, the UV-H2O2 system was designed to induce the formation of ·OH for toluene degradation and to identify the optimal reaction conditions. It was demonstrated that ·OH and 1O2 are the primary active species for degrading toluene, with their contribution ranking as ·OH > 1O2. The intermediates in the mixture solution after reactions were characterized using GC-MS, demonstrating the validity of theoretical predictions. A comparative study of the toluene consumption rate revealed an experimental comprehensive activation energy of 10.33 kJ/mol, which is consistent with the preliminary activation energies obtained via theoretical analysis of these three mechanisms (0.56 kJ/mol to 13.66 kJ/mol), indicating that this theoretical method can provide a theoretical basis for experimental studies on the oxidation of toluene by ·OH.

17.
Chem Sci ; 15(15): 5746-5756, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38638236

RESUMEN

The variety of highly efficient red/near-infrared (NIR) materials with thermally activated delayed fluorescence (TADF) feature is extremely limited so far, and it is necessary to expand the candidate pool of excellent red/deep-red emitters. However, how to control the energy level alignment of the 1CT (singlet charge transfer) state and the 3LE (triplet local excitation) state to improve the emission efficiency of materials remains a challenge. Herein, based on our previously reported green fluorescent material 67dTPA-FQ, three new donor-acceptor type TADF materials (TQ-oMeOTPA, TsQ-oMeOTPA and SQ-oMeOTPA) were designed by introducing 4,4'-dimethoxy triphenylamine (MeOTPA) as the donor, and introduced S atoms on the acceptors to enhance the spin-orbit coupling (SOC) and CT effects. The theoretical calculations showed that the newly introduced MeOTPA and S atom successfully enhanced the CT effect of the materials, not only shifting the luminescence peak to the deep red region but also effectively adjusting the energy level alignment of the excited state, accelerating the reverse intersystem crossing process. Finally, the organic light-emitting diodes based on SQ-oMeOTPA exhibit an external quantum efficiency of 19.1%, with an emission peak at 619 nm. This work not only expands the candidate inventory of red TADF materials, but also proves the feasibility of designing emitters by adjusting the excited state energy levels, greatly broadening the diversity of TADF emitters in design, and providing a powerful means for rapidly screening efficient emitters in the future.

18.
Eur Respir J ; 63(5)2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38514093

RESUMEN

RATIONALE: Respiratory virus-induced inflammation is the leading cause of asthma exacerbation, frequently accompanied by induction of interferon-stimulated genes (ISGs). How asthma-susceptibility genes modulate cellular response upon viral infection by fine-tuning ISG induction and subsequent airway inflammation in genetically susceptible asthma patients remains largely unknown. OBJECTIVES: To decipher the functions of gasdermin B (encoded by GSDMB) in respiratory virus-induced lung inflammation. METHODS: In two independent cohorts, we analysed expression correlation between GSDMB and ISG s. In human bronchial epithelial cell line or primary bronchial epithelial cells, we generated GSDMB-overexpressing and GSDMB-deficient cells. A series of quantitative PCR, ELISA and co-immunoprecipitation assays were performed to determine the function and mechanism of GSDMB for ISG induction. We also generated a novel transgenic mouse line with inducible expression of human unique GSDMB gene in airway epithelial cells and infected the mice with respiratory syncytial virus to determine the role of GSDMB in respiratory syncytial virus-induced lung inflammation in vivo. RESULTS: GSDMB is one of the most significant asthma-susceptibility genes at 17q21 and acts as a novel RNA sensor, promoting mitochondrial antiviral-signalling protein (MAVS)-TANK binding kinase 1 (TBK1) signalling and subsequent inflammation. In airway epithelium, GSDMB is induced by respiratory viral infections. Expression of GSDMB and ISGs significantly correlated in respiratory epithelium from two independent asthma cohorts. Notably, inducible expression of human GSDMB in mouse airway epithelium led to enhanced ISGs induction and increased airway inflammation with mucus hypersecretion upon respiratory syncytial virus infection. CONCLUSIONS: GSDMB promotes ISGs expression and airway inflammation upon respiratory virus infection, thereby conferring asthma risk in risk allele carriers.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Asma , Gasderminas , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Animales , Humanos , Asma/metabolismo , Asma/genética , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Ratones Transgénicos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Predisposición Genética a la Enfermedad , Infecciones por Virus Sincitial Respiratorio/metabolismo , Infecciones por Virus Sincitial Respiratorio/genética , Células Epiteliales/metabolismo , Línea Celular , Bronquios/metabolismo , Bronquios/patología , Neumonía/metabolismo , Neumonía/genética , Neumonía/virología , Femenino , Pulmón/metabolismo , Pulmón/patología
19.
Int J Food Microbiol ; 416: 110660, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38460236

RESUMEN

The spoilage bacterium Bacillus licheniformis has been identified as a quick and strong biofilm former in the dairy industry. In our previous study, intra-species variation in bacterial biofilms has been observed in diverse B. licheniformis strains from different genetic backgrounds; however, the mechanisms driving the observed heterogeneity of biofilms remain to be determined. In this study, the genotype-phenotype evaluation of the heterogeneity in biofilm formation of four B. licheniformis strains were examined. The heterogeneity in biofilm phenotype was accessed in aspects of bacterial growth and motility, cell viability, biofilm matrix production, and biofilm architectures. The underlying mechanisms of the intra-species variability in biofilms were also explored by whole genome resequencing (WGR). Results from bacterial motility tests showed a diverse motility among the strains, but there was no clear correlation between bacterial motility and biofilm formation. The cell viability results showed a different number of live cells in biofilms at the intra-species level. Analysis of chemical components in biofilm matrix demonstrated the great intra-species differences regarding extracellular matrix composition, and a negative correlation between biofilm formation on stainless steel and the protein: carbohydrate ratio in biofilm matrix was observed. Confocal laser scanning microscopy analysis also revealed the intra-species variability by showing great differences in general properties of B. licheniformis biofilms. WGR results identified important pathways involved in biofilm formation, such as two-component systems, quorum sensing, starch and sucrose metabolism, ABC transporters, glyoxylate and dicarboxylate metabolism, purine metabolism, and a phosphotransferase system. Overall, the above results emphasize the necessity of exploring the intra-species variation in biofilms, and would provide in-depth knowledge for designing efficient biofilm control strategies in the dairy industry.


Asunto(s)
Bacillus licheniformis , Productos Lácteos/microbiología , Biopelículas , Bacterias , Genotipo
20.
Environ Sci Pollut Res Int ; 31(17): 26170-26181, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38498134

RESUMEN

The wet flue gas desulfurization (WFGD) system of coal-fired power plants shows a good removal effect on condensable particulate matter (CPM), reducing the dust removal pressure for the downstream flue gas purification devices. In this work, the removal effect of a WFGD system on CPM and its organic pollutants from a coal-fired power plant was studied. By analyzing the organic components of the by-products emitted from the desulfurization tower, the migration characteristics of organic pollutants in gas, liquid, and solid phases, as well as the impact of desulfurization towers on organic pollutants in CPM, were discussed. Results show that more CPM in the flue gas was generated by coal-fired units at ultra-low load, and the WFGD system had a removal efficiency nearly 8% higher than that at full load. The WFGD system had significant removal effect on two typical esters, especially phthalate esters (PAEs), with the highest removal efficiency of 49.56%. In addition, the WFGD system was better at removing these two esters when the unit was operating at full load. However, it had a negative effect on n-alkanes, which increased the concentration of n-alkanes by 8.91 to 19.72%. Furthermore, it is concluded that the concentration distribution of the same type of organic pollutants in desulfurization wastewater was similar to that in desulfurization slurry, but quite different from that in coal-fired flue gas. The exchange of three organic pollutants between flue gas and desulfurization slurry was not significant, while the concentration distribution of organic matters in gypsum was affected by coal-fired flue gas.


Asunto(s)
Contaminantes Atmosféricos , Contaminantes Ambientales , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Gases , Centrales Eléctricas , Carbón Mineral , Alcanos
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