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Clozapine (CLZ) -related accidents or crimes are common in the world. Oral fluid drug detection is a convenient measure of dealing with things like that. There has not been any literature reported detailedly the representation rule of clozapine and its metabolites in oral fluid so far. The study aimed to describe the pharmacokinetics of CLZ and its metabolites N-desmethylclozapine and clozapine-N-oxide in human oral fluid after a single 12.5 mg oral dose of CLZ. Twenty-nine volunteers, including 20 males and 9 females, were recruited, and 2 mL oral fluid was collected from each participant at post-consumption time-points of prior (zero), 0.5, 1.5, 3, 5, 8, 12, 24, 36, 51, 82, and 130 h, respectively. Analytes of interest were extracted with solid-phase extraction and analyzed with liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters were calculated using the pharmacokinetic software DAS according to the non-compartment model. The maximum concentration, the time of maximum concentration, oral clearance, and the elimination half-life of clozapine were 16.57 ± 9.63 ng/mL, 4.53 ± 3.61 h, 57.65 ± 23.77 L/h and 53.58 ± 52.28 h, respectively. The maximum concentration, the time of maximum concentration, and the elimination half-life of the metabolite N-desmethylclozapine were 3.08 ± 1.19 ng/mL, 9.38 ± 9.33 h and 62.67 ± 82.57 h, respectively; of clozapine-N-oxide were 1.15 ± 0.36 ng/mL, 4.53 ± 2.19 h and 19.15 ± 23.11 h, respectively. It was the first study on the pharmacokinetics of CLZ and its metabolites in the oral fluid of Chinese healthy volunteers, and it provided a basis for the therapeutic drug monitoring and toxicological interpretation in clozapine-related cases.
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Backgrounds: In order to detect early gastric cancer (EGC), this research sought to assess the diagnostic utility of magnifying endoscopy (ME) as well as the significance of mucin phenotype and microvessel features. Methods: 402 individuals with an EGC diagnosis underwent endoscopic submucosal dissection (ESD) at the Department of ME between 2012 and 2020. After adjusting for image distortion, high-magnification endoscopic pictures were taken and examined to find microvessels in the area of interest. The microvessel density was measured as counts per square millimeter (counts/mm2) after segmentation, and the vascular bed's size was computed as a percentage of the area of interest. To identify certain properties of the microvessels, such as end-points, crossing points, branching sites, and connection points, further processing was done using skeletonized pixels. Results: According to the research, undifferentiated tumors often lacked the MS pattern and showed an oval and tubular microsurface (MS) pattern, but differentiated EGC tumors usually lacked the MS pattern and presented a corkscrew MV pattern. Submucosal invasion was shown to be more strongly associated with the destructive MS pattern in differentiated tumors as opposed to undifferentiated tumors. While lesions with a corkscrew MV pattern and an antrum or body MS pattern revealed greater MUC5AC expression, lesions with a loop MV pattern indicated higher MUC2 expression. Furthermore, CD10 expression was higher in lesions with a papillary pattern and an antrum or body MS pattern. Conclusion: These results imply that evaluating mucin phenotype and microvessel features in conjunction with magnifying endoscopy (ME) may be a useful diagnostic strategy for early gastric cancer (EGC) detection. Nevertheless, further investigation is required to confirm these findings and identify the best course of action for EGC diagnosis.
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BACKGROUND: This study aimed to investigate the timing of and indications for the Tajima reverse U incision for correcting secondary unilateral cleft nasal deformities. METHODS: Non-syndromic patients with secondary cleft lip and nasal deformity who received Tajima reverse-U incision rhinoplasty were grouped by age (4-13 years, n=56;13-18 years, n=22; >18 years, n=18) and severity of deformity (mild deformity, n=7; moderate deformity=22; severity deformity=67) during 5-year follow-up. Face-Q assessment, a rating scale, and nasal symmetry measurements were employed in this study. RESULTS: Ninety-six patients completed the FACE-Q assessment for the nose and nostril. The results showed higher satisfaction with nostril appearance 1-week after surgery (85.95±13.01) compared with pre-operation (79.72±11.89) and maintained 5-year follow-up (82.61±14.06). Significant differences were observed in five nasal parameters (nasal height ratio, one-fourth media part of nostril height ratio, nasal sill height ratio, columellar angle, and inner nostril height-to-width ratio (cleft)) for 1-week postoperatively and the corrected outcome of the Tajima technique was maintained 5 years after surgery in aged 4-13 years group. The same statistically significant changes were found in nasal sill height ratio in mild deformity group and nostril width ratio, one-fourth media part of nostril height ratio, columellar angle, and inner nostril height-to-width ratio (cleft) in moderate deformity group. CONCLUSION: The Tajima procedure was beneficial for preadolescent children and children with mild to moderate unilateral cleft nasal deformities.
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Poly (vinyl alcohol) (PVA), as an excellent degradable plastic feedstock, is limited by its diminishing stability in wet environment, low strength, thermal instability and nonopaque properties. In response to these concerns, a PVA/demethylated lignin-based supramolecular plastic (DPVA-HA-Fe-5) was designed and produced from PVA, demethylated lignin (DL), humic acid (HA) and Fe3+ ions via a simple casting method. As compared with pure PVA plastic, the tensile strength of DPVA-HA-Fe-5 were increased by 411 % to 410.61 MPa, and the breaking strain was increased by 149 % to 239.47 %. Notably, the hydrophobicity of DPVA-HA-Fe-5 was also significantly improved. Although in highly humid environment (stored in RH = 100 % for 10 days) or in alkaline organic solvent (stored in pyridine for 3 h), DPVA-HA-Fe-5 also showed excellent mechanical strengths of 302.9 and 222.99 MPa, respectively, which are equivalent or even superior to the most of commercial petroleum-based plastics. Moreover, the prepared plastics showed an outstanding UV resistance and shading performance, and about 98.3 % protection against ultraviolet radiation B rays and 90.7 % protection against visible light were obtained. In short, the introduction of lignin to improve the performance of PVA-based plastic is a feasible method, and it could facilitate the development of high-value utilization of lignin.
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N-Acyl/sulfonyl-α-functionalized 1,2,3,4-tetrahydroisoquinolines (THIQs) are significant structural motifs in organic synthesis and drug discovery. However, the one-pot approach enabling direct difunctionalization of THIQs remains challenging. Herein we report a photomediated one-pot three-component strategy to access N-acyl/sulfonyl-α-functionalized THIQs. This method features the use of oxygen (from air) as the green oxidant, high atom and step economy, and decent structural diversity. The synthetic applicability of the method was further demonstrated via the facile construction of valuable bioactive molecules. Mechanistic studies indicated that oxidation with singlet oxygen and the acceptor-less dehydrogenation were involved in the photoredox process.
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Aim: We aimed to investigate the predictive value of the Grainyhead-like 2 (GRHL2) expression from circulating blood for recurrence, metastasis and overall death on patients with non-small-cell lung cancer (NSCLC). Materials & Methods: We collected blood samples from 122 patients who were admitted to our hospital for NSCLC. Results: Multivariable Cox proportional-hazards analysis in adjusted Model II showed that compared with GRHL2-negative expression, positive expression in patients with NSCLC was associated with increased death risk (HR = 7.0, 95% CI: 2.1-20.9, p = 0.03) and risk for composite end point (HR = 8.2, 95% CI: 4.0-27.1, p <0.01). Conclusion: This study supported that elevated circulating GRHL2 expression might be considered as a candidate prognostic biomarker for poor prognosis among these NSCLC patients.
[Box: see text].
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OBJECTIVES: RNA sequencing (RNA-seq) and bioinformatic analysis were combined and used to explore the anti-inflammatory effects and mechanisms of naringenin (Nar) in lipopolysaccharide (LPS)-stimulated human periodontal ligament stem cells (hPDLSCs). METHODS: Cell counting kit-8, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA) were adopted to detect the effects of Nar on the proliferation and expression of inflammatory factors in LPS-stimulated hPDLSCs, screening for the optimal anti-inflammatory concentration of Nar. Differentially expressed genes (DEGs) were screened using |log2FC|≥1 and P≤0.05 as criteria. Volcano plot analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the String database, and the MCODE module of Cytoscape were utilized to select core genes and enriched pathways. The effects on the nuclear factor κB (NF-κB) signaling pathway were verified using ELISA, qRT-PCR, and Western blot. RESULTS: Appropriate concentrations of Nar could alleviate the expression of inflammatory factors and promote the proliferation of hPDLSCs stimulated by LPS. The best anti-inflammatory effect was achieved with 20 µmol/L Nar. RNA-seq showed significant enrichment of inflammation-related signaling pathways. The anti-inflammatory effect of Nar was mediated by inhibiting the NF-κB signaling pathway, similar to the effect of the NF-κB inhibitor BAY 11-7802. CONCLUSIONS: Nar could exert its anti-inflammatory effects by inhibiting the NF-κB signaling pathway, making it a potential therapeutic option for the adjuvant treatment of periodontitis.
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Anti-Inflamatórios , Flavanonas , Lipopolissacarídeos , NF-kappa B , Ligamento Periodontal , Análise de Sequência de RNA , Transdução de Sinais , Células-Tronco , Humanos , Lipopolissacarídeos/farmacologia , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos dos fármacos , Ligamento Periodontal/metabolismo , Flavanonas/farmacologia , Anti-Inflamatórios/farmacologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , NF-kappa B/metabolismo , Proliferação de Células/efeitos dos fármacos , Nitrilas/farmacologia , SulfonasRESUMO
Electrochemical urea oxidation offers a sustainable avenue for H2 production and wastewater denitrification within the water-energy nexus; however, its wide application is limited by detrimental cyanate or nitrite production instead of innocuous N2. Herein we demonstrate that atomically isolated asymmetric Ni-O-Ti sites on Ti foam anode achieve a N2 selectivity of 99%, surpassing the connected symmetric Ni-O-Ni counterparts in documented Ni-based electrocatalysts with N2 selectivity below 55%, and also deliver a H2 evolution rate of 22.0 mL h-1 when coupled to a Pt counter cathode under 213 mA cm-2 at 1.40 VRHE. These asymmetric sites, featuring oxygenophilic Ti adjacent to Ni, favor interaction with the carbonyl over amino groups in urea, thus preventing premature resonant CâN bond breakage before intramolecular N-N coupling towards N2 evolution. A prototype device powered by a commercial Si photovoltaic cell is further developed for solar-powered on-site urine processing and decentralized H2 production.
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Microplastic (MP) contamination in soil severely impairs plant growth. However, mechanisms underlying the effects of MPs on plant nutrient uptake remain largely unknown. In this study, we revealed that NO3- content was significantly decreased in shoots and roots of wheat plants exposed to high concentrations (50-100 mg L-1) of MPs (1 µm and 0.1 µm; type: polystyrene) in the hydroponic solution. Isotope labeling experiments demonstrated that MP exposure led to a significant inhibition of NO3- uptake in wheat roots. Further analysis indicated that the presence of MPs markedly inhibited root growth and caused oxidative damage to the roots. Additionally, superoxide dismutase and peroxidase activities in wheat roots decreased under all MP treatments, whereas catalase and ascorbate peroxidase activities significantly increased under the 100 mg L-1 MP treatment. The transcription levels of most nitrate transporters (NRTs) in roots were significantly downregulated by MP exposure. Furthermore, exposure to MPs distinctly suppressed the activity of nitrate reductase (NR) and nitrite reductase (NiR), as well as the expression levels of their coding genes in wheat shoots. These findings indicate that a decline in root uptake area and root vitality, as well as in the expression of NRTs, NR, and NiR genes caused by MP exposure may have adverse effects on NO3- uptake and assimilation, consequently impairing normal growth of plants.
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To investigate the association between COVID-19 and Parkinson's disease (PD) via a single-center study and a Mendelian randomization (MR) study. A questionnaire-based survey was conducted among PD patients at a single center from December 7, 2022, to March 10, 2023. Logistic regression analysis was performed to identify the infection-related risk factors. Subsequently, bidirectional two-sample Mendelian randomization was employed to explore the association between COVID-19 and PD. In the cross-sectional analysis, it was found that the prevalence of COVID-19 infection in PD patients was 65.7%. Forty-eight (35.3%) PD patients experienced exacerbation of motor symptoms following COVID-19 infection. Long PD disease duration (≥ 10 years) (OR: 3.327, P = 0.045) and long time since last vaccination (> 12 m) (OR: 4.916, P = 0.035) were identified as significant risk factors related to infection. The MR analysis results supported that PD increases the COVID-19 susceptibility (ß = 0.081, OR = 1.084, P = 0.006). However, the MR analysis showed that PD did not increases the COVID-19 severity and hospitalization, and no significant association of COVID-19 on PD was observed. The findings from this cross-sectional study suggest that individuals with PD may experience worsened motor symptoms following COVID-19 infection. Long disease duration (≥10 years) and long time since last vaccination (> 12 m) are identified as important risk factors for infection in these patients. Furthermore, our MR study provides evidence supporting an association between PD and COVID-19 susceptibility.
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COVID-19 , Análise da Randomização Mendeliana , Doença de Parkinson , SARS-CoV-2 , Humanos , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Doença de Parkinson/complicações , COVID-19/epidemiologia , COVID-19/complicações , COVID-19/virologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Transversais , Fatores de Risco , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/genética , PrevalênciaRESUMO
Long-term exposure to hyperglycemic conditions leads to ß-cell dysfunction, particularly mitochondrial dysfunction, and inflammatory and oxidative stress responses, which are considered the primary causes of ß-cell death and the hallmarks of diabetes. Plant-active ingredients may play a key role in glycemic control. Epigallocatechin gallate (EGCG) is a characteristic catechin derived from tea that possesses anti-diabetic properties. Nonetheless, its underlying mechanisms remain elusive. Herein, the protective role of EGCG on high glucose (33 mM)-induced pancreatic beta cell dysfunction and its possible molecular mechanisms were investigated. Briefly, MIN6 cells were treated with glucose and EGCG (10 µM, 20 µM, and 40 µM) for 48 h. Our results revealed that EGCG dose-dependently restored mitochondrial membrane potential and concomitantly alleviated cell apoptosis. Mechanistically, the expression level of apoptotic protein BAX and Dynamic related protein 1 (DRP1) was significantly downregulated following EGCG treatment, whereas that of the anti-apoptotic protein BCL-2 was significantly upregulated. Taken together, EGCG alleviated high glucose-induced pancreatic beta cell dysfunction by targeting the DRP1-related mitochondrial apoptosis pathway and thus can serve as a nutritional intervention for the preservation of beta cell dysfunction in patients with type 2 diabetes mellitus.
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Apoptose , Catequina , Dinaminas , Glucose , Células Secretoras de Insulina , Mitocôndrias , Catequina/análogos & derivados , Catequina/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Apoptose/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Glucose/metabolismo , Dinaminas/metabolismo , Dinaminas/genética , Animais , Camundongos , Linhagem Celular , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
OBJECTIVES: Comprehensive data using Next-Generation Sequence (NGS) and fluorescence in situ hybridization (FISH) for detecting MET amplification is limited in Chinese patients, we evaluating NGS performance both in tissue and plasma samples using FISH as reference. We also sought to find optimal thresholds value for NGS in detecting MET amplification via bioinformatics methods. METHOD: Patients progressed after 1st-, 2nd-, or 3rd-generation (G) EGFR-TKIs were enrolled. Tissue biopsy samples were performed for MET amplification detection via both NGS and FISH. Paired plasma samples were collected for MET amplification detection by NGS. The sensitivity, specificity and agreement were analyzed between NGS and FISH. RESULTS: 116 eligible patients were analyzed. 44 patients were male. 82 patients were after 3rd generation EGFR-TKI. MET amplification was detected in 43 (37.1 %) patients by FISH, including 19 (16.4 %) polysomy and 24 (20.7 %) focal amplification. The positive rate of MET amplification in post 3rd generation EGFR-TKI and post 1st/2ndgeneration EGFR-TKI resistant patients was 42.7 % (35/82), and 23.5 % (8/34). The sensitivity, specificity and agreement of detecting MET amplification by NGS in tissue were 39.5 % (17/43), 98.6 % (72/73) and 76.7 % (89/116), respectively, 66.7 % (16/24), 98.6 % (72/73) and 90.7 % (88/97) for focal MET amplification in tissue and 29.2 % (7/24), 94.5 % (69/73), 78.4 % (76/97) for focal amplification in plasma. Results were shown in the table below. CONCLUSION: NGS is an alternative method for MET focal amplification detection in tissue. While the sensitivity of NGS testing in plasma needs further improvement to maximize identification of patients with potential benefit from dual-targeted therapy.
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Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Amplificação de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Hibridização in Situ Fluorescente , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-met , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Feminino , Proteínas Proto-Oncogênicas c-met/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Receptores ErbB/genética , Inibidores de Proteínas Quinases/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Pessoa de Meia-Idade , Idoso , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Estudos Prospectivos , China/epidemiologia , Adulto , Idoso de 80 Anos ou maisRESUMO
To explore the therapeutic effects along with the molecular mechanisms of epigallocatechin gallate (EGCG) in non-alcoholic fatty liver disease (NAFLD) treatment using network pharmacology as well as animal experiments. Firstly, the Traditional Chinese Medicine (TCM) Systems Pharmacology Database was searched to identify the potential targets of EGCG. The DisGeNET Database was used to screen the potential targets of NAFLD. The GeneCards Database was searched to identify related genes involved in pyroptosis. Subsequently, the intersecting genes of EGCG targeting pyroptosis to regulate NAFLD were obtained using a Venn diagram. Simultaneously, the aforementioned intersecting genes were used to construct a drug-disease target protein-protein interaction (PPI) network. The DAVID database was adopted for Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The main pathway-target network was determined. Next, the potential mechanism of EGCG targeting pyroptosis to regulate NAFLD was investigated and validated through in vivo experiments. 626 potential targets of EGCG, 447 target genes of NAFLD, and 568 potential targets of pyroptosis were identified. The number of common targets between EGCG, NAFLD, and pyroptosis was 266. GO biological process items and 92 KEGG pathways were determined based on the analysis results. Animal experiments demonstrated that EGCG could ameliorate body weight, glucolipid metabolism, steatosis, and liver injury, enhance insulin sensitivity, and improve glucose tolerance in NAFLD mice through the classical pathway of pyroptosis. EGCG could effectively treat NAFLD through multiple targets and pathways. It was concluded that EGCG ameliorates hepatocyte steatosis, pyroptosis, dyslipidemia, and inflammation in NAFLD mice fed a high-fat diet (HFD), and the protective mechanism could be associated with the NLRP3-Caspase-1-GSDMD classical pyroptosis pathway.
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BACKGROUND: At present, liver transplantation (LT) is one of the best treatments for hepatocellular carcinoma (HCC). Accurately predicting the survival status after LT can significantly improve the survival rate after LT, and ensure the best way to make rational use of liver organs. AIM: To develop a model for predicting prognosis after LT in patients with HCC. METHODS: Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated. The expression levels of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, Golgi protein 73, cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer. The best cutoff value of biomarkers was determined using the Youden index. Cox regression analysis was used to identify the independent risk factors. A forest model was constructed using the random forest method. We evaluated the accuracy of the nomogram using the area under the curve, using the calibration curve to assess consistency. A decision curve analysis (DCA) was used to evaluate the clinical utility of the nomograms. RESULTS: The total tumor diameter (TTD), vascular invasion (VI), AFP, and cytokeratin-18 epitopes M30 (CK18-M30) were identified as important risk factors for outcome after LT. The nomogram had a higher predictive accuracy than the Milan, University of California, San Francisco, and Hangzhou criteria. The calibration curve analyses indicated a good fit. The survival and recurrence-free survival (RFS) of high-risk groups were significantly lower than those of low- and middle-risk groups (P < 0.001). The DCA shows that the model has better clinical practicability. CONCLUSION: The study developed a predictive nomogram based on TTD, VI, AFP, and CK18-M30 that could accurately predict overall survival and RFS after LT. It can screen for patients with better postoperative prognosis, and improve long-term survival for LT patients.
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Biomarcadores Tumorais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Nomogramas , alfa-Fetoproteínas , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/sangue , Masculino , Transplante de Fígado/efeitos adversos , Pessoa de Meia-Idade , Feminino , Fatores de Risco , alfa-Fetoproteínas/análise , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/análise , Prognóstico , Adulto , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Queratina-18/sangue , Queratina-18/análise , Técnicas de Apoio para a DecisãoRESUMO
OBJECTIVE: The aim of this study was to cephalometrically evaluate the pharyngeal morphology in adults with unoperated Submucous Cleft Palate (SMCP), adults with unoperated Overt Cleft Palate (OCP), and adults without clefts. DESIGN: This study employed a retrospective cross-sectional design. Lateral cephalometric radiography was performed on three groups of adults: 1) 29 with unrepaired SMCP; 2) 41 with unrepaired OCP; and 3) 39 without clefts, who served as controls. One-way ANOVA and rank-sum tests were used for intergroup comparisons. P value was set at .05. RESULTS: The soft palate length and the ratio of soft palate length to pharyngeal depth were significantly lower in subjects with unoperated SMCP and OCP than in non-cleft controls. Significant differences were also observed in pharyngeal depth, nasopharyngeal depth, and posterior pharyngeal wall thickness between subjects with unoperated OCP and non-cleft controls. CONCLUSIONS: Pharyngeal morphology differs significantly between individuals with and without clefts, particularly in soft palate length and the ratio of soft palate length to pharyngeal depth.
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Naringenin (NAR) is a prominent flavanone that has been recognized for its capacity to promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). The present study aimed to explore how NAR promotes the osteogenic differentiation of hPDLSCs and to assess its efficacy in repairing alveolar bone defects. For this purpose, a proteinprotein interaction network of NAR action was established by mRNA sequencing and network pharmacological analysis. Gene and protein expression levels were evaluated by reverse transcriptionquantitative and western blotting. Alizarin red and alkaline phosphatase staining were also employed to observe the osteogenic capacity of hPDLSCs, and immunofluorescence was used to examine the colocalization of NAR molecular probes and AKT in cells. The repair of mandibular defects was assessed by microcomputed tomography (microCT), Masson staining and immunofluorescence. Additionally, computer simulation docking software was utilized to determine the binding affinity of NAR to the target protein, AKT. The results demonstrated that activation of the nitric oxide (NO)cyclic guanosine monophosphate (cGMP)protein kinase G (PKG) signaling pathway could promote the osteogenic differentiation of hPDLSCs. Inhibition of AKT, endothelial nitric oxide synthase and soluble guanylate cyclase individually attenuated the ability of NAR to promote the osteogenic differentiation of hPDLSCs. MicroCT and Masson staining revealed that the NAR gavage group exhibited more new bone formation at the defect site. Immunofluorescence assays confirmed the upregulated expression of Runtrelated transcription factor 2 and osteopontin in the NAR gavage group. In conclusion, the results of the present study suggested that NAR promotes the osteogenic differentiation of hPDLSCs by activating the NOcGMPPKG signaling pathway through its binding to AKT.
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Diferenciação Celular , Flavanonas , Osteogênese , Transdução de Sinais , Animais , Humanos , Masculino , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , GMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Flavanonas/farmacologia , Óxido Nítrico/metabolismo , Osteogênese/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/metabolismo , Células-Tronco/efeitos dos fármacos , Células-Tronco/citologiaRESUMO
Dunaliella salina is an innovative expression system due to its distinct advantages such as high salt tolerance, low susceptibility to contamination, and the absence of the cell wall. While nuclear transformation has been extensively studied, research on D. salina chloroplast transformation remains in the preliminary stages. In this study, we established an efficient chloroplast expression system for D. salina using Golden Gate assembly. We developed a D. salina toolkit comprising essential components such as chloroplast-specific promoters, terminators, homologous fragments, and various vectors. We confirmed its functionality by expressing the EGFP protein. Moreover, we detailed the methodology of the entire construction process. This expression system enables the specific targeting of foreign genes through simple homologous recombination, resulting in stable expression in chloroplasts. The toolkit achieved a relatively high transformation efficiency within a shorter experimental cycle. Consequently, the construction and utilization of this toolkit have the potential to enhance the efficiency of transgenic engineering in D. salina and advance the development of microalgal biofactories.
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Cloroplastos , Vetores Genéticos , Proteínas de Fluorescência Verde , Transformação Genética , Cloroplastos/genética , Cloroplastos/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Vetores Genéticos/metabolismo , Regiões Promotoras Genéticas , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Engenharia Genética/métodos , Microalgas/genética , Microalgas/metabolismo , Clorofíceas/genética , Clorofíceas/metabolismo , Clorófitas/genética , Clorófitas/metabolismo , Recombinação Homóloga , Expressão GênicaRESUMO
OBJECTIVES: Lung cancer is one of the most common malignant tumors threatening human life and health. At present, low-dose computed tomography (LDCT) screening for the high-risk population to achieve early diagnosis and treatment of lung cancer has become the first choice recommended by many authoritative international medical organizations. To further optimize the lung cancer screening method, we conducted a real-world study of LDCT lung cancer screening in a large sample of a healthy physical examination population, comparing differences in lung nodules and lung cancer detection between thin and thick-slice LDCT scanning. METHODS: A total of 29 296 subjects who underwent low-dose thick-slice CT scanning (5 mm thickness) from January 2015 to December 2015 and 28 058 subjects who underwent low-dose thin-slice CT scanning (1 mm thickness) from January 2018 to December 2018 in West China Hospital were included. The positive detection rate, detection rate of lung cancer, pathological stage of lung cancer, and mortality rate of lung cancer were analyzed and compared between the two groups. RESULTS: The positive rate of LDCT screening in the thin-slice scanning group was significantly higher than that in the thick-slice scanning group (20.1% vs. 14.4%, p < 0.001). In addition, the lung cancer detection rate in the thin-slice LDCT screening positive group was significantly higher than that in the thick-slice scanning group (78.0% vs. 52.9%, p < 0.001). CONCLUSIONS: The screening positive rate of low-dose thin-slice CT scanning is higher and more early-stage lung cancer (IA1 stage) can be detected in the screen-positive group.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Feminino , Tomografia Computadorizada por Raios X/métodos , China/epidemiologia , Pessoa de Meia-Idade , Detecção Precoce de Câncer/métodos , Idoso , Doses de Radiação , Adulto , Programas de Rastreamento/métodosRESUMO
Sulfonated lignin-based dye dispersants have intensively attracted attention due to their low cost, renewability and abundant sources. However, their utilization is limited by the low content of sulfonic groups and high content of hydroxyl groups in their complex lignin structure, which results in various problems such as high reducing rate of dye, severe staining of the fibers and uneven dyeing. Here, the multi-site sulfonated lignin-based dispersants were prepared with high sulfonic group content (2.20 mmol/g) and low hydroxyl content (2.43 mmol/g). When using it as the dispersant, the dye uptake rate was improved from 69.23 % to 98.55 %, the reducing rate was decreased from 20.82 % to 2.03 %, the K/S value was reduced from 0.69 to 0.02, and the particle sizes in dye system before and after high temperature treatment were stabilized below 0.5 µm. Besides, the dispersion effect was significantly improved because no obvious separation between dye and water was observed even if without the assistance of grinding process. In short, the multi-site sulfonation method proposed in this work could remarkably improve the performances of the lignin-based dye dispersants, which would facilitate the development of the dye dispersion and the high value utilization of lignin.