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Saline-alkali soils have poor N storage capacity, high N loss and inadequate nutrient supply potential, which are the main limiting factors for crop yields. Vermicompost can increase organic nutrient content, improve soil structure, and enhance microbial activity and function, and the Ca2+ in flue gas desulfurization (FGD) gypsum can replace Na+ and neutralize alkalinity in saline-alkali soils though chemical improvement. This study aimed to determine if vermicompost and FGD gypsum addition could improve the N storage capacity through decreasing NH3 volatilization and 15N/NO3- leaching from saline-alkali soils. The results indicate that the combined application of vermicompost and FGD gypsum led to the displacement and leaching Na+ in the upper soil layer (0-10 cm), as well as the neutralization of HCO3- by the reaction with Ca2+. This treatment also improved soil organic matter content and macroaggregate structure. Also, these amendments significantly increased the abundance of nifH and amoA genes, while concurrently decreasing the abundance of nirK gene. The structural improvements and the lowering of Na + concentration in and alkalinity decreased cumulative NH3 volatilization, and leaching of 15N and NO3- to the deep soil layer (20-30 cm). FGD gypsum increased the 15N stocks and inorganic N stocks of saline-alkali soil, whereas vermicompost not only increased the 15N and inorganic N stocks, but also increased the total N stocks, the combination of vermicompost and FGD gypsum can not only increase the available N storage capacity, but also enhance the potential for N supply. Therefore, vermicompost and FGD gypsum decrease N loss and increase N storage capacity through structural improvement, and lowering of Na+ concentration and alkalinity, which is crucial for improving the productivity of saline-alkali soil.
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The maintenance of hematopoietic stem cell (HSC) functional integrity is essential for effective hematopoietic regeneration when suffering from injuries. Studies have shown that the innate immune pathways play crucial roles in the stress response of HSCs, whereas how to precisely modulate these pathways is not well characterized. Here, we identify the E3 ubiquitin ligase tripartite motif-containing 47 (Trim47) as a negative regulator of the mitochondrial antiviral-signaling protein (MAVS)-mediated innate immune pathway in HSCs. We find that Trim47 is predominantly enriched in HSCs, and its deficiency impairs the function and survival of HSCs after exposure to 5-flurouracil (5-FU) and irradiation (IR). Mechanistically, Trim47 impedes the excessive activation of the innate immune signaling and inflammatory response via K48-linked ubiquitination and degradation of MAVS. Collectively, our findings demonstrate a role of Trim47 in preventing stress-induced hematopoietic failure and thus provide a promising avenue for treatment of related diseases in the clinic.
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Proteínas Adaptadoras de Transdução de Sinal , Células-Tronco Hematopoéticas , Imunidade Inata , Camundongos Endogâmicos C57BL , Transdução de Sinais , Ubiquitina-Proteína Ligases , Ubiquitinação , Animais , Células-Tronco Hematopoéticas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Camundongos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Camundongos Knockout , Humanos , Fluoruracila/farmacologia , Estresse Fisiológico , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Células HEK293RESUMO
BACKGROUND: At present, several cross-sectional studies have found that exposure to metal/metalloid elements is closely associated with male reproduction. However, the long-term effects of metal exposure on male reproduction have not been explored. METHODS: In 2013, 796 volunteers were recruited, followed by first and second follow-ups in 2014 and 2015. Urine, semen, and blood samples were collected at each stage to examine urinary metal/metalloid levels, sperm parameters, and sex hormones. Initially, the latent class trajectory model (LCTM) was utilized to analyze the trajectories of urinary metals. Subsequently, the effects of urinary metal trajectories on semen parameters and sex hormones were examined using the linear mixed model. Finally, the impact of urinary metal trajectories on the classification of semen quality (normal or abnormal) was evaluated using the generalized linear mixed model. RESULTS: Among the 18 metals/metalloids studied, trajectories were formed by 6 of them (Li, Al, Fe, Zn, As, Rb). Further analysis using the linear mixed model and the generalized linear mixed model revealed that Li was negatively correlated with semen volume, and sperm motility (P<0.05). The maximum-decreasing trajectory group had a detrimental effect on semen quality (OR=1.75, 95%CI: 1.22, 2.53) compared to the minimum-stable trajectory group. Al showed negative associations with sperm concentration, total sperm count, and normal morphology (P<0.05). Rb was positively associated with progressive motility (P<0.05). The high-stable trajectory group exhibited a protective effect on semen quality (OR=0.66, 95%CI: 0.49, 0.90) compared to the low-stable trajectory group. Additionally, Fe was observed to have a negative relationship with follicle-stimulating hormone (FSH) (P<0.05), and Rb exhibited a negative correlation with progesterone (P) (P<0.05). CONCLUSION: Our three-year cohort study provides new evidence that Li and Al have a negative impact on semen quality, whereas Rb is associated with beneficial effects. Additionally, Rb and Fe are endocrine disruptors of sex hormones.
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Soil microbial communities are major drivers of cycling of soil nutrients that sustain plant growth and productivity. Yet, a holistic understanding of the impact of abandoned agricultural land reclamation on the soil microbe is still poorly understood, especially for the microbial community assembly mechanisms. Here, we investigated the influence of reclamation on the relative importance of stochastic and deterministic processes in shaping microbial community assembly. After reclaiming abandoned cropland for corn and soybean cultivation, the fungal community assembly was shifted to stochastic processes, while bacterial communities remained predominantly influenced by stochastic processes. Our study revealed that reclamation did not significantly affect bacterial diversity, community niche breadth, and community similarity. In contrast, fungal communities exhibited lower alpha diversity, narrower niche breadths, greater niche overlap and higher community similarity in corn and soybean cultivation treatment in response to reclamation. Moreover, soil pH and soil available phosphorus were the most important environmental factors influencing fungal richness, niche breadths, community assembly processes, and community similarity. Together, the reclamation of abandoned cropland promoted the transformation of the fungal community assembly from deterministic process to a stochastic process, leading to decreased fungal diversity and broader ecological niche width, ultimately resulting in greater similarity among fungal communities. This finding provides insight into the varied responses of microbial diversity and ecological process to abandoned cropland reclamation, offering valuable guidance for the conservation and sustainable management of abandoned cropland in future land-use practices.
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Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.
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Carcinoma de Células Renais , Neoplasias Renais , Recidiva Local de Neoplasia , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Feminino , Recidiva Local de Neoplasia/genética , Pessoa de Meia-Idade , Idoso , Prognóstico , Genômica/métodos , Adulto , Estadiamento de Neoplasias , Aprendizado Profundo , Intervalo Livre de DoençaRESUMO
The water-soluble nido-carborane was prepared by alkali treatment of o-carborane. A polymer PInd containing a polyindole structure was synthesized and employed to label the modified o-carborane. Subsequently, four polymeric nanomaterials were synthesized with the objective of encapsulating them in order to enhance its bioavailability. The experimental results showed that the fluorescent complex encapsulated by the pH-sensitive polymer A had the best UV absorption and fluorescence intensity, and thus A-PInd-C was chosen for subsequent experiments. The Transmission electron microscopy images revealed that the compounds exhibited a rounded internal morphology, with the layers exhibiting a tightly stacked arrangement. The AFM imaging revealed that the surface of the sample exhibited a relatively uniform and smooth appearance. In vitro release experiments conducted under acidic conditions demonstrated that A-PInd-C was released in a predominantly linear manner, with a maximum release rate of 80% observed within 48 h. Cellular imaging experiments showed that the compound could enter HeLa and HCT-116 cells and was mainly distributed around the nucleus, especially in the acidic environment. The results of the cell proliferation toxicity experiments demonstrated that A-PInd-C exhibited inhibitory effects on HeLa, PC-3 and L02 cells. Among these, the inhibitory effect on PC-3 cells was the most pronounced, reaching up to 70%. In conclusion, this paper solves the problem of poor bioavailability of carborane by improving the boron containing compounds and also makes the system have potential for Boron neutron capture therapy.
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We present a method for modification of silicon nitride (Si3N4) waveguide resonators using femtosecond laser annealing. The quality (Q) factor of the waveguide resonators can be improved by approximately 1.3 times after annealing. Notably, waveguides that originally had a high Q value maintained their quality after the annealing process. However, those with a lower initial Q value experienced a noticeable improvement post-annealing. To characterize the annealing effect, the surface morphologies of Si3N4 films, both pre- and post-annealing, were analyzed using atomic force microscopy. The findings suggest a potential enhancement in surface refinement. Furthermore, Raman spectroscopy confirmed that the Si3N4 film's composition remains largely consistent with its original state within the annealing power range of 0.6-1.6 W. This research underscores the potential of femtosecond laser annealing as an efficient, cost-effective, and localized technique for fabricating low-loss integrated photonics.
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Heterotrophic-sulfur autotrophic denitrification (HAD) has been proposed to be a prospective nitrogen removal process. In this work, the potential of fermentation liquid (FL) from waste-activated sludge (WAS) as the electron donor for denitrification in the HAD system was explored and compared with other conventional carbon sources. Results showed that when FL was used as a carbon source, over 99% of NO3--N was removed and its removal rate exceeded 14.00 mg N/g MLSS/h, which was significantly higher than that of methanol and propionic acid. The produced sulfate was below the limit value and the emission of N2O was low (1.38% of the NO3--N). Microbial community analysis showed that autotrophic denitrifiers were predominated in the HAD system, in which Thiobacillus (16.4%) was the dominant genus. The economic analysis showed the cost of the FL was 0.062 /m3, which was 30% lower than that in the group dosed with methanol. Our results demonstrated the FL was a promising carbon source for the HAD system, which could reduce carbon emission and cost, and offer a creative approach for waste-activated sludge resource reuse.
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Carbono , Desnitrificação , Fermentação , Nitrogênio , Esgotos , Carbono/metabolismo , Nitrogênio/metabolismo , Eliminação de Resíduos Líquidos/métodosRESUMO
Podocyte injury or dysfunction can lead to proteinuria and glomerulosclerosis. Zonula occludens 1 (ZO-1) is a tight junction protein which connects slit diaphragm (SD) proteins to the actin cytoskeleton. Previous studies have shown that the expression of ZO-1 is decreased in chronic kidney disease (CKD). Thus, elucidation of the regulation mechanism of ZO-1 has considerable clinical importance. Triptolide (TP) has been reported to exert a strong antiproteinuric effect by inhibiting podocyte epithelial mesenchymal transition (EMT) and inflammatory response. However, the underlying mechanisms are still unclear. We found that TP upregulates ZO-1 expression and increases the fluorescence intensity of ZO-1 in a puromycin aminonucleoside (PAN)-induced podocyte injury model. Permeablity assay showed TP decreases podocyte permeability in PAN-treated podocyte. TP also upregulates the DNA demethylase TET2. Our results showed that treatment with the DNA methyltransferase inhibitors 5-azacytidine (5-AzaC) and RG108 significantly increased ZO-1 expression in PAN-treated podocytes. Methylated DNA immunoprecipitation (MeDIP) and hydroxymethylated DNA immunoprecipitation (hMeDIP) results showed that TP regulates the methylation status of the ZO-1 promoter. Knockdown of TET2 decreased ZO-1 expression and increased methylation of its promoter, resulting in the increase of podocyte permeability. Altogether, these results indicate that TP upregulates the expression of ZO-1 and decreases podocyte permeability through TET2-mediated 5 mC demethylation. These findings suggest that TP may alleviate podocyte permeability through TET2-mediated hydroxymethylation of ZO-1.
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Dioxigenases , Diterpenos , Compostos de Epóxi , Fenantrenos , Podócitos , Proteína da Zônula de Oclusão-1 , Podócitos/metabolismo , Podócitos/efeitos dos fármacos , Podócitos/patologia , Proteína da Zônula de Oclusão-1/metabolismo , Fenantrenos/farmacologia , Diterpenos/farmacologia , Compostos de Epóxi/farmacologia , Dioxigenases/metabolismo , Animais , Proteínas de Ligação a DNA/metabolismo , Camundongos , Proteínas Proto-Oncogênicas/metabolismo , Permeabilidade/efeitos dos fármacos , Humanos , Metilação de DNA/efeitos dos fármacosRESUMO
Background: Esophageal gastrointestinal stromal tumors (E-GISTs) are highly uncommon and have not been thoroughly examined. Objectives: The objective of this multi-center study was to assess the viability of endoscopic resection (ER) in the treatment of E-GISTs and to explore its clinical implications. Design: This was a multi-center retrospective study. Consecutive patients referred to the four participating centers. Methods: E-GISTs among the consecutive subepithelial tumors (SETs) treated by ER methods were enrolled from April 2019 to August 2022. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. Results: A total of 23 patients with E-GISTs were included for analysis, accounting for 1.9% of all the esophageal SETs (1243 patients). The average size of the tumor lesions was 2.3 cm (range 1.0-4.0 cm). We observed that tumors larger than 2.0 cm were more likely to grow deeper, with a statistically significant difference (p < 0.001). End bloc resection was achieved in all 23 patients. The mean operation time was 53.6 min (range 25-111 min). One patient experienced significant intraoperative bleeding, which was promptly managed endoscopically without necessitating surgery. The average hospital stay was 4.5 days (range 3-8 days). The overall median follow-up period was 31 months (range 13-47 months). No tumor recurrence, residual tumor, distal metastasis, or death was observed during the follow-up period. Conclusion: Based on our limited data, our study indicates that ER may be a feasible and effective option for treating esophageal GISTs measuring 4 cm or less. We suggest submucosal tunnel endoscopic resection as the preferred approach, as all E-GISTs in our study were situated in the muscularis propria layer. Additionally, tumors larger than 2 cm were more prone to deeper growth or extraluminal extension.
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Bisphenol A (BPA) is widely exposed in populations worldwide and has negative effects on spermatogenesis both in animals and humans. The homeostasis of the actin cytoskeleton in the spermatogenic epithelium is crucial for spermatogenesis. Actin cytoskeleton destruction in the seminiferous epithelium is one of the important reasons for BPA-induced spermatogenesis disorder. However, the underlying molecular mechanisms remain largely unexplored. Herein, we explored the role and mechanism of Rsad2, an interferon-stimulated gene in BPA-induced actin cytoskeleton disorder in mouse GC-2 spermatocyte cell lines. After BPA exposure, the actin cytoskeleton was dramatically disrupted and the cell morphology was markedly altered accompanied by a significant increase in Rsad2 expression both in mRNA and protein levels in GC-2 cells. Furthermore, the phalloidin intensities and cell morphology were restored obviously when interfering with the expression of Rsad2 in BPA-treated GC-2 cells. In addition, we observed a significant decrease in intracellular ATP levels after BPA treatment, while the ATP level was obviously upregulated when knocking down the expression of Rsad2 in BPA-treated cells compared to cells treated with BPA alone. Moreover, Rsad2 relocated to mitochondria after BPA exposure in GC-2 cells. BPA promoted Rsad2 expression by activating type I IFN-signaling in GC-2 cells. In summary, Rsad2 mediated BPA-induced actin cytoskeletal disruption in GC-2 cells, which provided data to reveal the mechanism of BPA-induced male reproductive toxicity.
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Background: Gastrointestinal stromal tumors (GISTs) represent the most prevalent type of subepithelial lesions (SELs) with malignant potential. Current imaging tools struggle to differentiate GISTs from leiomyomas. This study aimed to create and assess a real-time artificial intelligence (AI) system using endoscopic ultrasonography (EUS) images to differentiate between GISTs and leiomyomas. Methods: The AI system underwent development and evaluation using EUS images from 5 endoscopic centers in China between January 2020 and August 2023. EUS images of 1101 participants with SELs were retrospectively collected for AI system development. A cohort of 241 participants with SELs was recruited for external AI system evaluation. Another cohort of 59 participants with SELs was prospectively enrolled to assess the real-time clinical application of the AI system. The AI system's performance was compared to that of endoscopists. This study is registered with Chictr.org.cn, Number ChiCT2000035787. Findings: The AI system displayed an area under the curve (AUC) of 0.948 (95% CI: 0.921-0.969) for discriminating GISTs and leiomyomas. The AI system's accuracy (ACC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) reached 91.7% (95% CI 87.5%-94.6%), 90.3% (95% CI 83.4%-94.5%), 93.0% (95% CI 87.2%-96.3%), 91.9% (95% CI 85.3%-95.7%), and 91.5% (95% CI 85.5%-95.2%), respectively. Moreover, the AI system exhibited excellent performance in diagnosing ≤20 mm SELs (ACC 93.5%, 95% CI 0.900-0.969). In a prospective real-time clinical application trial, the AI system achieved an AUC of 0.865 (95% CI 0.764-0.966) and 0.864 (95% CI 0.762-0.966) for GISTs and leiomyomas diagnosis, respectively, markedly surpassing endoscopists [AUC 0.698 (95% CI 0.562-0.834) for GISTs and AUC 0.695 (95% CI 0.546-0.825) for leiomyomas]. Interpretation: We successfully developed a real-time AI-assisted EUS diagnostic system. The incorporation of the real-time AI system during EUS examinations can assist endoscopists in rapidly and accurately differentiating various types of SELs in clinical practice, facilitating improved diagnostic and therapeutic decision-making. Funding: Science and Technology Commission Foundation of Shanghai Municipality, Science and Technology Commission Foundation of the Xuhui District, the Interdisciplinary Program of Shanghai Jiao Tong University and the Research Funds of Shanghai Sixth people's Hospital.
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The gut microbiota and neurological development of neonatal mice are susceptible to environmental factors that may lead to altered behavior into adulthood. However, the role that changed gut microbiota and neurodevelopment early in life play in this needs to be clarified. In this study, by modeling early-life environmental changes by cross-fostering BALB/c mice, we revealed the effects of the environment during the critical period of postnatal development on adult social behavior and their relationship with the gut microbiota and the nervous system. The neural projections exist between the ascending colon and oxytocin neurons in the paraventricular nuclei (PVN), peripheral oxytocin levels and PVN neuron numbers decreased after cross-fostering, and sex-specific alteration in gut microbiota and its metabolites may be involved in social impairments and immune imbalances brought by cross-fostering via the gut-brain axis. Our findings also suggest that social cognitive impairment may result from a combination of PVN oxytocinergic neurons, gut microbiota, and metabolites.
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Eixo Encéfalo-Intestino , Microbioma Gastrointestinal , Camundongos Endogâmicos BALB C , Neurônios , Ocitocina , Núcleo Hipotalâmico Paraventricular , Comportamento Social , Animais , Microbioma Gastrointestinal/fisiologia , Camundongos , Ocitocina/metabolismo , Masculino , Feminino , Núcleo Hipotalâmico Paraventricular/metabolismo , Eixo Encéfalo-Intestino/fisiologia , Neurônios/metabolismo , Encéfalo/metabolismo , Comportamento Animal/fisiologia , Colo/metabolismo , Colo/microbiologia , Animais Recém-NascidosRESUMO
Safety problems caused by organophosphorus pesticide (OP) residues are constantly occurring, so the development of new methods for the degradation and detection of OPs is of great scientific significance. In the present study, ß-sheet peptides and ß-hairpin peptides for catalyzing the hydrolysis of OPs were designed and synthesized. The peptide sequences with the highest hydrolytic activity (EHSGGVTVDPPLTVEHSAG) were screened by investigating the effect of the location of the active sites of the peptide and the peptide's structure on the degradation of OPs. In addition, the relationship between the peptides' conformation and hydrolytic activity was further analyzed based on density functional theory calculations. The noncovalent interactions of the peptides with the OPs and the electrostatic potential on the molecular surface and molecular docking properties were also investigated. It was found that peptides with approximate active amino acids consisting of the catalytic triad and with the hairpin structure had enhanced hydrolytic activity toward the hydrolysis of OPs. To develop an electrochemical sensor technique to detect OPs, the conductive MXene (Ti3C2) material was first immobilized with a caffeic acid monolayer via enediol-metal complex chemistry and then bound with the ß-hairpin peptide (EHSGGVTVDPPLTVEHSAG) via carboxy-amine condensation chemistry between the -COOH of caffeic acid and the -NH2 of the peptide to prepare a MXene-peptide composite. Then, the prepared composite was modified on the surface of a glassy carbon electrode to construct an electrochemical sensor for the detection of OPs. The developed technique could be used to monitor OPs within 15 min with a two orders of linear working range and with a detection limit of 0.15 µM. Meanwhile, the sensor showed good reliability for the detection of OPs in real vegetables.
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Compostos Organofosforados , Praguicidas , Praguicidas/análise , Praguicidas/química , Compostos Organofosforados/química , Compostos Organofosforados/análise , Hidrólise , Simulação de Acoplamento Molecular , Peptídeos/química , Limite de Detecção , Técnicas Eletroquímicas/métodos , Sequência de Aminoácidos , Ácidos CafeicosRESUMO
A novel curcumin (CUR) delivery system was developed using soybean whey protein (SWP)-based emulsions, enhanced by pH-adjustment and gum arabic (GA) modification. Modulating electrostatic interactions between SWP and GA at oil/water interface, pH provides favorable charging conditions for stable distribution between droplets. GA facilitated the SWP form a stable interfacial layer that significantly enhanced the emulsifying properties and CUR encapsulation efficiency of the system at pH 6.0, which were 90.15 ± 0.67%, 870.53 ± 3.22 m2/g and 2157.62 ± 115.31%, respectively. Duncan's test revealed significant improvements in thermal, UV, oxidative, and storage stabilities of CUR (P < 0.05). At pH 6.0, GA effectively protected CUR by inhibiting SWP degradation during gastric digestion and promoting the release of CUR by decreasing steric hindrance with oil droplets during intestinal digestion, achieving the highest CUR bioaccessibility (69.12% ± 0.28%) based on Duncan's test. The SWP-GA-CUR emulsion delivery system would be a novel carrier for nutrients.
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Curcumina , Digestão , Sistemas de Liberação de Medicamentos , Emulsões , Glycine max , Goma Arábica , Proteínas do Soro do Leite , Emulsões/química , Proteínas do Soro do Leite/química , Concentração de Íons de Hidrogênio , Goma Arábica/química , Curcumina/química , Curcumina/metabolismo , Glycine max/química , Estabilidade de Medicamentos , Tamanho da Partícula , Humanos , Portadores de Fármacos/químicaRESUMO
Licorice (Glycyrrhiza glabra) is a plant of the genus Glycyrrhiza in the family Fabaceae/Leguminosae and is a renowned natural herb with a long history of medicinal use dating back to ancient times. Glycyrrhizin (GLY), the main active component of licorice, serves as a widely utilized therapeutic agent in clinical practice. GLY exhibits diverse medicinal properties, including anti-inflammatory, antibacterial, antiviral, antitumor, immunomodulatory, intestinal environment maintenance, and liver protection effects. However, current research primarily emphasizes GLY's antiviral activity, while providing limited insight into its antibacterial properties. GLY demonstrates a broad spectrum of antibacterial activity via inhibiting the growth of bacteria by targeting bacterial enzymes, impacting cell membrane formation, and altering membrane permeability. Moreover, GLY can also bolster host immunity by activating pertinent immune pathways, thereby enhancing pathogen clearance. This paper reviews GLY's inhibitory mechanisms against various pathogenic bacteria-induced pathological changes, its role as a high-mobility group box 1 inhibitor in immune regulation, and its efficacy in combating diseases caused by pathogenic bacteria. Furthermore, combining GLY with other antibiotics reduces the minimum inhibitory concentration, potentially aiding in the clinical development of combination therapies against drug-resistant bacteria. Sources of information were searched using PubMed, Web of Science, Science Direct, and GreenMedical for the keywords "licorice", "Glycyrrhizin", "antibacterial", "anti-inflammatory", "HMGB1", and combinations thereof, mainly from articles published from 1979 to 2024, with no language restrictions. Screening was carried out by one author and supplemented by others. Papers with experimental flaws in their experimental design and papers that did not meet expectations (antifungal papers, etc.) were excluded.
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BACKGROUND: Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated. METHODS: Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing. RESULTS: CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor. CONCLUSION: A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients.
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Carcinoma de Células Renais , Proliferação de Células , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais , MicroRNAs , RNA Circular , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Pessoa de Meia-Idade , Masculino , Carcinogênese/genética , Carcinogênese/patologia , Movimento Celular/genética , Fator de Transcrição PAX5/metabolismo , Fator de Transcrição PAX5/genética , Oncogenes/genética , Sequência de Bases , Progressão da Doença , Invasividade Neoplásica , Reprodutibilidade dos TestesRESUMO
Benign prostatic hyperplasia (BPH) is a multifactorial disease in which abnormal growth factor activation and embryonic reawakening are considered important factors. Here we demonstrated that the aberrant activation of transforming growth factor ß (TGF-ß)/Rho kinase 1 (ROCK1) increased the stemness of BPH tissue by recruiting mesenchymal stem cells (MSCs), indicating the important role of embryonic reawakening in BPH. When TGF-ß/ROCK1 is abnormally activated, MSCs are recruited and differentiate into fibroblasts/myofibroblasts, leading to prostate stromal hyperplasia. Further research showed that inhibition of ROCK1 activation suppressed MSC migration and their potential for stromal differentiation. Collectively, our findings suggest that abnormal activation of TGF-ß/ROCK1 regulates stem cell lineage specificity, and the small molecule inhibitor GSK269962A could target ROCK1 and may be a potential treatment for BPH.
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Células-Tronco Mesenquimais , Hiperplasia Prostática , Fator de Crescimento Transformador beta , Quinases Associadas a rho , Quinases Associadas a rho/metabolismo , Masculino , Hiperplasia Prostática/patologia , Hiperplasia Prostática/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Diferenciação Celular , Próstata/patologia , Próstata/metabolismo , Movimento Celular , Camundongos , Células Estromais/metabolismo , Células Estromais/patologiaRESUMO
The introduction of transition metal (TM) ions into polyoxometalates (POMs) cannot only bring about interesting structural diversities but also enable changes in properties. However, TM-containing Silverton-type polyoxomolybdates are still lacking in terms of structural diversity and application development. Herein, two Zn(II)-containing Silverton-type {UMo12O42}-based polyoxomolybdates, H1.89Na4.11(H2O)9Zn[UMo12O42]·4.5H2O (Zn-1) and H1.8Na4.2(H2O)12Zn[UMo12O42] (Zn-2) were hydrothermally synthesized, demonstrating a practical strategy to assembly of TM-containing Silverton-type POMs. Zn-1 is proven to be an excellent and recyclable heterogeneous catalyst in cross-dehydrogenation coupling of 1,4-naphthoquinones with amines reactions, and a series of 2-amino-1,4-naphthoquinones with potential medicinal value have been constructed.
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BACKGROUND: LncRNA PCED1B-AS1 is abnormally expressed in multiple cancers and has been confirmed as an oncogene. Our study aimed to investigate the regulatory mechanism of lncRNA PCED1B-AS1 in gastric cancer. METHODS: TCGA database was used to analyze the abnormal expression of lncRNA PCED1B-AS1 in gastric cancer. By database prediction and mass spectrometric analysis, miR-3681-3p and MAP2K7 are potential downstream target molecules of lncRNA PCED1B-AS1 and verified by dual-luciferase report assay. RT-qPCR analysis and western blot were performed to detect the expressions of PCED1B-AS1 and MAP2K7 in gastric cancer cell lines and tissues. CCK-8 kit was applied to measure the cell viability. Wound healing and Transwell experiment were used to detect the migration and invasion. Western blot and immunohistochemical staining were performed to detect the expressions of EMT-related proteins in tissues. The changes of tumor proliferation were detected by xenograft experiment in nude mice. RESULTS: PCED1B-AS1 expression was higher but miR-3681-3 expression was lower in gastric cancer cell lines or tissues, compared to normal group. Function analysis verified PCED1B-AS1 promoted cell proliferation and inhibited cell apoptosis in gastric cancer cells in vitro and in vivo. LncRNA PCED1B-AS1 could bind directly to miR-3681-3p, and MAP2K7 was found to be a downstream target of miR-3681-3p. MiR-3681-3p mimics or si-MAP2K7 could partly reverse the effect of PCED1B-AS1 on gastric cancer cells. CONCLUSION: PCED1B-AS1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-3681-3p to upregulate MAP2K7 expression in gastric cancer, which indicated PCED1B-AS1/miR-3681-3p/MAP2K7 axis may serve as a potential therapeutic target for gastric cancer.