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1.
Sci Total Environ ; 950: 175203, 2024 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-39127216

RESUMEN

Recent studies have indicated a good potential for using solar-induced chlorophyll fluorescence (SIF) to estimate photosynthetic CO2 assimilation. SIF can be emitted by both Photosystem I (PSI) and Photosystem II (PSII), but it is the SIF signals from PSII which are related to photosynthetic carbon fixation. However, since top-of-canopy SIF observations (SIFTOC) always contain contributions from both photosystems, to mechanistically estimate gross primary productivity (GPP) from SIF, it is essential to extract PSII SIF from SIFTOC. Based on the differences in the relative contribution of PSII across different wavelengths, we propose a practical approach for extracting PSII contribution to SIFTOC at the near-infrared (NIR) band (fPSII_760) using measurements of SIFTOC in the red and NIR spectral regions. A leaf-scale concurrent instrument was developed to assess the response of fPSII_760 under varying environments. For winter-wheat leaves, as light intensity increased from 0 to 400 µmol m-2 s-1, fPSII_760 rose from 0.6 to 0.8; with further increase in light intensity to 1800 µmol m-2 s-1, fPSII_760 consistently decreased to 0.65. There was a slight decreasing trend in fPSII_760 with rising temperatures, with values dropping from 0.65 at 15 °C to 0.61 at 40 °C. We found that variations in fPSII_760 are due to changes in the fluorescence yield of PSII, with the two having a positively proportional relationship. We also estimated canopy-scale fPSII_760 for a winter-wheat study site: fPSII_760 varied from 0.61 to 0.83, with a mean value of 0.78 during the peak growing season. A comparison with eddy covariance-derived GPP reveals that GPP estimated with dynamic fPSII_760 was more accurate than that calculated using fixed fPSII_760, with R2 increasing from 0.6 to 0.84. This study contributes to a deeper understanding of the link between SIF and photosynthetic CO2 assimilation, paving the way for more effective use of SIF to estimate GPP.


Asunto(s)
Clorofila , Fotosíntesis , Complejo de Proteína del Fotosistema II , Complejo de Proteína del Fotosistema II/metabolismo , Clorofila/metabolismo , Fluorescencia , Luz Solar , Hojas de la Planta/metabolismo , Triticum
2.
J Pharm Biomed Anal ; 250: 116411, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39141978

RESUMEN

Hydrogen polysulfide (H2Sn, n≥2), as a kind of active sulfur species (RSS), has become a hot topic in RSS. It can regulate the biological activity of many proteins through S-sulfhydrylation of cysteine residues (protein Cys-SSH), and has a protective effect on cells. Although there have been some studies on hydrogen polysulfide, its production, degradation pathway and regulation mechanism still need further be researched. In presented study, an original lysosome-localized fluorescent probe for determining H2Sn was developed utilizing rhodamine as the fluorogen. The probe used morpholine as the locating unit of lysosomes and chose 2-fluoro-5-nitrobenzoate as the recognizing group. Before adding H2Sn, the proposed probe displayed a spironolactone structure and emitted very weak fluorescence. After adding H2Sn, a conjugated xanthene was formed and the probe demonstrated green fluorescence. When the H2Sn concentration was varied from 6.0×10-7 mol·L-1 to 10.0×10-5 mol·L-1, the fluorescence intensity of the probe was linearly dependent on the H2Sn concentration. And the detection limit was 1.5×10-7 mol·L-1. The presented probe owned a fast response speed, good selectivity, excellent sensitivity and broad pH work scope. In addition, the probe had been well utilized to sense endogenic and exogenic H2Sn in lysosomes.


Asunto(s)
Colorantes Fluorescentes , Límite de Detección , Lisosomas , Rodaminas , Sulfuros , Colorantes Fluorescentes/química , Lisosomas/metabolismo , Rodaminas/química , Sulfuros/química , Sulfuros/análisis , Humanos , Espectrometría de Fluorescencia/métodos , Sulfuro de Hidrógeno/análisis , Sulfuro de Hidrógeno/química , Morfolinas/química , Concentración de Iones de Hidrógeno , Fluorescencia
3.
Med Decis Making ; : 272989X241264287, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39082512

RESUMEN

BACKGROUND: The expected value of sample information (EVSI) measures the expected benefits that could be obtained by collecting additional data. Estimating EVSI using the traditional nested Monte Carlo method is computationally expensive, but the recently developed Gaussian approximation (GA) approach can efficiently estimate EVSI across different sample sizes. However, the conventional GA may result in biased EVSI estimates if the decision models are highly nonlinear. This bias may lead to suboptimal study designs when GA is used to optimize the value of different studies. Therefore, we extend the conventional GA approach to improve its performance for nonlinear decision models. METHODS: Our method provides accurate EVSI estimates by approximating the conditional expectation of the benefit based on 2 steps. First, a Taylor series approximation is applied to estimate the conditional expectation of the benefit as a function of the conditional moments of the parameters of interest using a spline, which is fitted to the samples of the parameters and the corresponding benefits. Next, the conditional moments of parameters are approximated by the conventional GA and Fisher information. The proposed approach is applied to several data collection exercises involving non-Gaussian parameters and nonlinear decision models. Its performance is compared with the nested Monte Carlo method, the conventional GA approach, and the nonparametric regression-based method for EVSI calculation. RESULTS: The proposed approach provides accurate EVSI estimates across different sample sizes when the parameters of interest are non-Gaussian and the decision models are nonlinear. The computational cost of the proposed method is similar to that of other novel methods. CONCLUSIONS: The proposed approach can estimate EVSI across sample sizes accurately and efficiently, which may support researchers in determining an economically optimal study design using EVSI. HIGHLIGHTS: The Gaussian approximation method efficiently estimates the expected value of sample information (EVSI) for clinical trials with varying sample sizes, but it may introduce bias when health economic models have a nonlinear structure.We introduce the spline-based Taylor series approximation method and combine it with the original Gaussian approximation to correct the nonlinearity-induced bias in EVSI estimation.Our approach can provide more precise EVSI estimates for complex decision models without sacrificing computational efficiency, which can enhance the resource allocation strategies from the cost-effective perspective.

4.
Front Oncol ; 14: 1354940, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38854728

RESUMEN

Nasopharyngeal carcinoma (NPC) is commonly diagnosed at an advanced stage with a high incidence rate in Southeast Asia and Southeast China. However, the limited availability of NPC patient survival data in public databases has resulted in less rigorous studies examining the prediction of NPC survival through construction of Kaplan-Meier curves. These studies have primarily relied on small samples of NPC patients with progression-free survival (PFS) information or data from head and neck squamous cell carcinoma (HNSCC) studies almost without NPC patients. Thus, we coanalyzed RNA expression profiles in eleven datasets (46 normal (control) vs 160 tumor (NPC)) downloaded from the Gene Expression Omnibus (GEO) database and survival data provided by Jun Ma from Sun Yat-sen University. Then, differential analysis, gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and network analysis were performed using STRING database. After that, 2142 upregulated differentially expressed genes (DEGs) and 3857 downregulated DEGs were screened. Twenty-five of them were identified as hub genes, which were enriched in several pathways (cilium movement, extracellular matrix structural constituent, homologous recombination and cell cycle). Utilizing the comprehensive dataset we amassed from GEO database, we conducted a survival analysis of DEGs and subsequently constructed survival models. Seven DEGs (RASGRP2, MOCOS, TTC9, ARHGAP4, DPM3, CD37, and CD72) were identified and closely related to the survival prognosis of NPC. Finally, qRT-PCR, WB and IHC were performed to confirm the elevated expression of RASGRP2 and the decreased expression of TTC9, CD37, DPM3 and ARHGAP4, consistent with the DEG analysis. Conclusively, our findings provide insights into the novel prognostic biomarkers of NPC by mega-data bioinformatics analysis, which suggests that they may serve special targets in the treatment of NPC.

5.
Anal Biochem ; 692: 115552, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38718956

RESUMEN

The reactive nitrogen species (RNS) in lysosomes play a major role during the regulation of lysosomal microenvironment. Nitroxyl (HNO) belongs to active nitrogen species (RNS) and is becoming a potential diagnostic and therapeutic biomarker. However, the complex synthesis routes of HNO in biosystem always hinder the exact determination of HNO in living cells. Here, a rhodamine-based fluorescent probe used to determine nitroxyl (HNO) in lysosomes was constructed and synthesized. 2-(Diphenylphosphino)benzoate was utilized as the sensing unit for HNO and morpholine was chose as the targeting group for lysosome. Before the addition of HNO, the probe displayed a spirolactone structure and almost no fluorescence was found. After the addition of HNO, the probe existed as a conjugated xanthene form and an intense green fluorescence was observed. The fluorescent probe possessed fast response (3 min) and high selectivity for HNO. Furthermore, fluorescence intensity of the probe linearly related with the HNO concentration in the range of 6.0 × 10-8 to 6.0 × 10-5 mol L-1. The detection limit was found to be 1.87 × 10-8 mol L-1 for HNO. Moreover, the probe could selectively targeted lysosome with excellent biocompatibility and had been effectually utilized to recognize exogenous HNO in A549 cells.


Asunto(s)
Colorantes Fluorescentes , Lisosomas , Óxidos de Nitrógeno , Rodaminas , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Lisosomas/metabolismo , Óxidos de Nitrógeno/análisis , Óxidos de Nitrógeno/química , Humanos , Rodaminas/química , Rodaminas/síntesis química
6.
Adv Mater ; 36(30): e2404774, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38721927

RESUMEN

Green ammonia synthesis through electrocatalytic nitrate reduction reaction (eNO3RR) can serve as an effective alternative to the traditional energy-intensive Haber-Bosch process. However, achieving high Faradaic efficiency (FE) at industrially relevant current density in neutral medium poses significant challenges in eNO3RR. Herein, with the guidance of theoretical calculation, a metallic CoNi-terminated catalyst is successfully designed and constructed on copper foam, which achieves an ammonia FE of up to 100% under industrial-level current density and very low overpotential (-0.15 V versus reversible hydrogen electrode) in a neutral medium. Multiple characterization results have confirmed that the maintained metal atom-terminated surface through interaction with copper atoms plays a crucial role in reducing overpotential and achieving high current density. By constructing a homemade gas stripping and absorption device, the complete conversion process for high-purity ammonium nitrate products is demonstrated, displaying the potential for practical application. This work suggests a sustainable and promising process toward directly converting nitrate-containing pollutant solutions into practical nitrogen fertilizers.

7.
Int Dent J ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38688802

RESUMEN

INTRODUCTION AND AIMS: Periodontitis, a chronic inflammatory condition affecting the supporting structures of the teeth, is a substantial public health burrden whilst impacting the life quality of those affected. Elevated levels of systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) have been implicated in various inflammatory conditions. This study aimed to investigate the relationship between SII and SIRI with periodontitis. METHODS: The study examined a total of 8666 participants in the 2009 to 2014 National Health and Nutrition Examination Survey (NHANES). The study compared the weighted prevalence of periodontitis among various groups. The association between SII, SIRI levels, and periodontitis was analyzed using binary logistic regression. Additionally, we explored nonlinear relationships between SII, SIRI, and the prevalence of periodontitis using restricted cubic spline (RCS) plots. RESULTS: Among participants in the fourth quartile (Q4) of SII and SIRI, the highest prevalence of periodontitis was observed, with rates of 44.87% and 48.41%, respectively. After adjusting for all covariates, the odds ratio (OR) for periodontitis associated with SII Q4 was 1.19 (95% CI 1.02, 1.39, P = .03), while for SIRI Q4, it was 1.18 (95% CI 1.01, 1.39, P = .04). In addition, the results of sensitivity analysis revealed consistent findings, indicating that after adjusting for all covariates, the OR for periodontitis associated with SII Q4 and SIRI Q4 remained statistically significant. Specifically, the OR for periodontitis associated with SII Q4 was 1.19 (95% CI 1.02, 1.39, P = .03), while for SIRI Q4, it was 1.19 (95% CI 1.01, 1.40, P = .04). CONCLUSIONS: These results indicate that elevated SII and SIRI levels are associated with an increased prevalence of periodontitis. CLINICAL RELEVANCE: These findings suggest a potential connection between systemic inflammation and periodontitis, highlighting the importance of periodontitis patients being aware of their systemic diseases that are inflammatory in nature such as chronic cardiovascular afflictions.

8.
Front Immunol ; 15: 1392734, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38515740

RESUMEN

[This corrects the article DOI: 10.3389/fimmu.2024.1258740.].

9.
Front Neurosci ; 18: 1272786, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38327848

RESUMEN

Sensorineural hearing loss (SNHL), a highly prevalent sensory impairment, results from a multifaceted interaction of genetic and environmental factors. As we continually gain insights into the molecular basis of auditory development and the growing compendium of deafness genes identified, research on gene therapy for SNHL has significantly deepened. Adeno-associated virus (AAV), considered a relatively secure vector for gene therapy in clinical trials, can deliver various transgenes based on gene therapy strategies such as gene replacement, gene silencing, gene editing, or gene addition to alleviate diverse types of SNHL. This review delved into the preclinical advances in AAV-based gene therapy for SNHL, spanning hereditary and acquired types. Particular focus is placed on the dual-AAV construction method and its application, the vector delivery route of mouse inner ear models (local, systemic, fetal, and cerebrospinal fluid administration), and the significant considerations in transforming from AAV-based animal model inner ear gene therapy to clinical implementation.

10.
Front Immunol ; 15: 1258740, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38322269

RESUMEN

Ubiquitin-specific proteases (USPs), as one of the deubiquitinating enzymes (DUBs) families, regulate the fate of proteins and signaling pathway transduction by removing ubiquitin chains from the target proteins. USPs are essential for the modulation of a variety of physiological processes, such as DNA repair, cell metabolism and differentiation, epigenetic modulations as well as protein stability. Recently, extensive research has demonstrated that USPs exert a significant impact on innate and adaptive immune reactions, metabolic syndromes, inflammatory disorders, and infection via post-translational modification processes. This review summarizes the important roles of the USPs in the onset and progression of inflammatory diseases, including periodontitis, pneumonia, atherosclerosis, inflammatory bowel disease, sepsis, hepatitis, diabetes, and obesity. Moreover, we highlight a comprehensive overview of the pathogenesis of USPs in these inflammatory diseases as well as post-translational modifications in the inflammatory responses and pave the way for future prospect of targeted therapies in these inflammatory diseases.


Asunto(s)
Proteasas Ubiquitina-Específicas , Ubiquitina , Humanos , Ubiquitina/metabolismo , Procesamiento Proteico-Postraduccional , Diferenciación Celular , Reparación del ADN
11.
J Med Genet ; 61(5): 459-468, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38296632

RESUMEN

BACKGROUND: Townes-Brocks syndrome (TBS) is a rare genetic disorder characterised by multiple malformations. Due to its phenotypic heterogeneity and rarity, diagnosis and recognition of TBS can be challenging and there has been a lack of investigation of patients with atypical TBS in large cohorts and delineation of their phenotypic characteristics. METHODS: We screened SALL1 and DACT1 variants using next-generation sequencing in the China Deafness Genetics Consortium (CDGC) cohort enrolling 20 666 unrelated hearing loss (HL) cases. Comprehensive clinical evaluations were conducted on seven members from a three-generation TBS family. Combining data from previously reported cases, we also provided a landscape of phenotypes and genotypes of patients with TBS. RESULTS: We identified five novel and two reported pathogenic/likely pathogenic (P/LP) SALL1 variants from seven families. Audiological features in patients differed in severity and binaural asymmetry. Moreover, previously undocumented malformations in the middle and inner ear were detected in one patient. By comprehensive clinical evaluations, we further provide evidence for the causal relationship between SALL1 variation and certain endocrine abnormalities. Penetrance analysis within familial contexts revealed incomplete penetrance among first-generation patients with TBS and a higher disease burden among their affected offspring. CONCLUSION: This study presents the first insight of genetic screening for patients with TBS in a large HL cohort. We broadened the phenotypic-genotypic spectrum of TBS and our results supported an underestimated prevalence of TBS. Due to the rarity and phenotypic heterogeneity of rare diseases, broader spectrum molecular tests, especially whole genome sequencing, can improve the situation of underdiagnosis and provide effective recommendations for clinical management.


Asunto(s)
Anomalías Múltiples , Ano Imperforado , Pérdida Auditiva Sensorineural , Pulgar/anomalías , Factores de Transcripción , Humanos , Mutación , Factores de Transcripción/genética , Síndrome , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/genética , Fenotipo , Proteínas Nucleares/genética , Proteínas Adaptadoras Transductoras de Señales/genética
12.
ACS Appl Mater Interfaces ; 15(41): 48800-48809, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37788171

RESUMEN

Capacitive deionization (CDI) is a promising desalination technology, and metal-organic framework (MOF)-derived carbon as an electrode material has received more and more attention due to its designable structure. However, MOF-derived carbon materials with single-pore structures have been difficult to meet the technical needs of related fields. In this work, the ordered hierarchical porous carbon framework (OMCF) was prepared by the template method using zeolitic imidazolate frameworks-8 (ZIF-8) as a precursor. The pore structures, surface properties, electrochemical properties, and CDI performances of the OMCF were investigated and compared with the microporous carbon framework (MCF), also derived from ZIF-8. The results show that the hierarchical porous carbon OMCF possessed a higher specific surface area, better hydrophilic surface (with a contact angle of 13.45°), and higher specific capacitance and ion diffusion rate than those of the MCF, which made the OMCF exhibit excellent CDI performances. The adsorption capacity and salt adsorption rate of the OMCF in a 500 mg·L-1 NaCl solution at 1.2 V and a 20 mL·min-1 flow rate were 12.17 mg·g-1 and 3.34 mg·g-1·min-1, respectively, higher than those of the MCF. The deionization processes of the OMCF and MCF closely follow the pseudo-first-order kinetics, indicating the double-layer capacitance control. This work serves as a valuable reference for the CDI application of N-doped hierarchical porous carbon derived from MOFs.

13.
Inorg Chem ; 62(35): 14385-14392, 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37607345

RESUMEN

A one-dimensional Cd(II) chain coordination polymer constructed by an electron-deficient viologen-anchored carboxylate ligand was successfully synthesized. Owing to the favorable stimuli-chromic properties of viologen, the title compound shows reversible photochromism, thermochromism, electrochromism, and naked-eye-detectable differentiable vapochromic response to different volatile amines. The chromic behaviors of it are ascribed to the formation of viologen radicals triggered by external stimuli. And the differentiated response to volatile amines is attributed to the size effect of the amines as well as the steric hindrance effect of forming α/ß Cv-H···Namines interactions of the viologen unit to further affect the occurrence of electron transfer. Such an all-in-one crystalline material might have more practical applications in photoelectric, erasable inkless printing, light printing, and volatile amine detection fields.

14.
Anal Chem ; 95(24): 9173-9181, 2023 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-37279018

RESUMEN

As an important metabolic intermediate of sulfur-containing amino acids in human body, homocysteine (Hcy) is regarded as an independent risk factor for atherosclerotic cardiovascular disease. Therefore, real-time monitoring of the fluctuation of Hcy level is of great importance for the early diagnosis as well as the treatment of atherosclerosis. Herein, a new two-photon (TP) fluorescent probe (RH-2) was developed via a hydrogen bond-assisted strategy, which had a high specificity for detecting Hcy over cysteine (Cys) and glutathione (GSH) in solution, cells, and tissue. Probe RH-2 was applied to the quantitative determination of Hcy in human serum successfully. Moreover, the two-photon fluorescence (TPF) imaging of abnormal expression of Hcy in aortic vessels and liver of atherosclerotic model mice were fulfilled by RH-2. Therefore, probe RH-2 can be served as a potential tool to understand the function of Hcy in atherosclerosis, supplying a clinical promise for the early diagnosis of atherosclerosis (AS).


Asunto(s)
Aterosclerosis , Colorantes Fluorescentes , Humanos , Animales , Ratones , Colorantes Fluorescentes/química , Cisteína/metabolismo , Células HeLa , Microscopía Fluorescente/métodos , Glutatión , Espectrometría de Fluorescencia , Aterosclerosis/diagnóstico por imagen , Homocisteína
15.
Methods ; 215: 38-45, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37268033

RESUMEN

As an important member of reactive oxygen species, hydrogen peroxide (H2O2) plays a key role in oxidative stress and cell signaling. Abnormal levels of H2O2 in lysosomes can induce damage or even loss of lysosomal function, leading to certain diseases. Therefore, real-time monitoring of H2O2 in lysosomes is very important. In this work, we designed and synthesized a novel lysosome-targeted fluorescent probe for H2O2-specific detection based on a benzothiazole derivative. A morpholine group was used as a lysosome-targeted unit and a boric acid ester was chosen as the reaction site. In the absence of H2O2, the probe exhibited very weak fluorescence. In the presence of H2O2, the probe showed an increased fluorescence emission. The fluorescence intensity of the probe for H2O2 displayed a good linear relationship in the concentration range of H2O2 from 8.0 × 10-7 to 2.0 × 10-4 mol·L-1. The detection limit was estimated to be 4.6 × 10-7 mol·L-1 for H2O2. The probe possessed high selectivity, good sensitivity and short response time for the detection of H2O2. Moreover, the probe had almost no cytotoxicity and had been successfully applied to confocal imaging of H2O2 in lysosomes of A549 cells. These results illustrated that the developed fluorescent probe in this study could provide a good tool for the determination of H2O2 in lysosomes.


Asunto(s)
Colorantes Fluorescentes , Peróxido de Hidrógeno , Humanos , Fluorescencia , Benzotiazoles , Lisosomas , Células HeLa
16.
NPJ Regen Med ; 8(1): 20, 2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37024481

RESUMEN

When the proliferation of residual hepatocytes is prohibited, biliary epithelial cells (BECs) transdifferentiate into nascent hepatocytes to accomplish liver regeneration. Despite significant interest in transdifferentiation, little is known about the maintenance of nascent hepatocytes in post-injured environments. Here, we perform an N-ethyl-N-nitrosourea (ENU) forward genetic screen and identify a mutant containing a nonsense mutation in the gene nibrin (nbn), which encodes a component of the Mre11-Rad50-Nbn (MRN) complex that activates DNA damage response (DDR). The regenerated hepatocytes cannot be maintained and exhibit apoptosis in the mutant. Mechanistically, the nbn mutation results in the abrogation of ATR-Chk1 signaling and accumulations of DNA damage in nascent hepatocytes, which eventually induces p53-mediated apoptosis. Furthermore, loss of rad50 or mre11a shows similar phenotypes. This study reveals that the activation of DDR by the MRN complex is essential for the survival of BEC-derived hepatocytes, addressing how to maintain nascent hepatocytes in the post-injured environments.

17.
Hepatology ; 78(1): 167-178, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-36724876

RESUMEN

In cases of end-stage liver diseases, the proliferation of existing hepatocytes is compromised, a feature of human chronic liver disease, in which most hepatocytes are dysfunctional. So far, liver transplantation represents the only curative therapeutic solution for advanced liver diseases, and the shortage of donor organs leads to high morbidity and mortality worldwide. The promising treatment is to prompt the biliary epithelial cells (BECs) transdifferentiation. However, the critical factors governing the initiation of BEC-derived liver regeneration are largely unknown. The zebrafish has advantages in large-scale genetic screens to identify the critical factors involved in liver regeneration. Here, we combined N-ethyl-N-nitrosourea screen, positional cloning, transgenic lines, antibody staining, and in situ hybridization methods and identified a liver regeneration defect mutant ( lrd ) using the zebrafish extensive liver injury model. Through positional cloning and genomic sequencing, we mapped the mutation site to rngtt . Loss of rngtt leads to the defects of BEC dedifferentiation, bipotential progenitor cell activation, and cell proliferation in the initiation stage of liver regeneration. The transdifferentiation from BECs to hepatocytes did not occur even at the late stage of liver regeneration. Mechanically, Rngtt transcriptionally regulates the attachment of mRNA cap to mTOR complex 1 (mTORC1) components and dnmt1 to maintain the activation of mTORC1 and DNA methylation in BECs after severe liver injury and prompt BEC to hepatocyte conversion. Furthermore, rptor and dnmt1 mutants displayed the same liver regeneration defects as rngtt mutation. In conclusion, our results suggest Rngtt is a new factor that initiates BEC-derived liver regeneration.


Asunto(s)
Regeneración Hepática , Pez Cebra , Animales , Humanos , ADN (Citosina-5-)-Metiltransferasa 1 , Células Epiteliales , Hepatocitos/fisiología , Hígado , Regeneración Hepática/genética , Diana Mecanicista del Complejo 1 de la Rapamicina , Proteínas de Pez Cebra/genética
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 286: 121986, 2023 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-36265303

RESUMEN

The Golgi apparatus (GA) is a vital organelle in biological systems and excess reactive oxygen species (ROS) is produced during stress in the Golgi apparatus. Hypochlorous acid (HOCl) is a significant reactive oxygen species and has strong oxidative and antibacterial activity, but excessive secretion of hypochlorous acid can affect Golgi structure or function abnormally, it will lead to a series of diseases including Alzheimer's disease, neurodegenerative diseases, autoimmune diseases, and Parkinson's disease. In present work, a novel fluorescent probe for Golgi localization utilizing naphthalimide derivatives was constructed to detect hypochlorous acid. The fluorescent probe used a derivatived 1,8-naphthalimide as the emitting fluorescence group, phenylsulfonamide as the localization group and dimethylthiocarbamate as the sensing unit. When HOCl was absent, the intramolecular charge transfer (ICT) process of the developed probe was hindered and the probe exhibited a weak fluorescence. When HOCl was present, the ICT process occurred and the probe showed strong green fluorescence. When the HOCl concentration was altered from 5.0 × 10-7 to 1.0 × 10-5 mol·L-1, the fluorescence intensity of the probe well linearly correlated with the HOCl concentration. The detection limit of 5.7 × 10-8 mol·L-1 was obtained for HOCl. The HOCl fluorescent probe possessed a rapid reaction time, a high selectivity and a broad working pH scope. In addition, the probe possessed good biocompatibility and had been magnificently employed to image Golgi HOCl in Hela cells. These characteristics of the probe demonstrated its ability to be used for sensing endogenous and exogenous hypochlorous acids within the Golgi apparatus of living cells.


Asunto(s)
Ácido Hipocloroso , Naftalimidas , Humanos , Ácido Hipocloroso/química , Naftalimidas/química , Colorantes Fluorescentes/química , Fluorescencia , Células HeLa , Aparato de Golgi
19.
Stem Cells Int ; 2022: 5015856, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36187229

RESUMEN

Dental mesenchymal stem cells (DMSCs) are crucial in tooth development and periodontal health, and their multipotential differentiation and self-renewal ability play a critical role in tissue engineering and regenerative medicine. Methylation modifications could promote the appropriate biological behavior by postsynthetic modification of DNA or protein and make the organism adapt to developmental and environmental prompts by regulating gene expression without changing the DNA sequence. Methylation modifications involved in DMSC fate include DNA methylation, RNA methylation, and histone modifications, which have been proven to exert a significant effect on the regulation of the fate of DMSCs, such as proliferation, self-renewal, and differentiation potential. Understanding the regulation of methylation modifications on the behavior and the immunoinflammatory responses involved in DMSCs contributes to further study of the mechanism of methylation on tissue regeneration and inflammation. In this review, we briefly summarize the key functions of histone methylation, RNA methylation, and DNA methylation in the differentiation potential and self-renewal of DMSCs as well as the opportunities and challenges for their application in tissue regeneration and disease therapy.

20.
ACS Omega ; 7(33): 29236-29245, 2022 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-36033650

RESUMEN

The determination of mercuric ions (Hg2+) in environmental and biological samples has attracted the attention of researchers lately. In the present work, a novel turn-on Hg2+ fluorescent probe utilizing a rhodamine derivative had been constructed and prepared. The probe could highly sensitively and selectively sense Hg2+. In the presence of excessive Hg2+, the probe displayed about 52-fold fluorescence enhancement in 50% H2O/CH3CH2OH (pH, 7.24). In the meantime, the colorless solution of the probe turned pink upon adding Hg2+. Upon adding mercuric ions, the probe interacted with Hg2+ and formed a 1:1 coordination complex, which had been the basis for recognizing Hg2+. The probe displayed reversible dual colorimetric and fluorescence sensing of Hg2+ because rhodamine's spirolactam ring opened upon adding Hg2+. The analytical performances of the probe for sensing Hg2+ were also studied. When the Hg2+ concentration was altered in the range of 8.0 × 10-8 to 1.0 × 10-5 mol L-1, the fluorescence intensity showed an excellent linear correlation with Hg2+ concentration. A detection limit of 3.0 × 10-8 mol L-1 had been achieved. Moreover, Hg2+ in the water environment and A549 cells could be successfully sensed by the proposed probe.

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