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1.
Biomed Res Int ; 2021: 9247541, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959666

RESUMO

Atrioventricular block (AVB) is a leading cause of sudden cardiac death, and most of AVB cases are presented as autosomal dominant. The electrocardiogram of AVB patients presents an abnormal progressive cardiac conduction disorder between atria and ventricles. Transient receptor potential melastatin 4 (TRPM4) is a nonselective Ca2+-activated cation channel gene defined as a novel disease-causing gene of AVB. So far, 47 mutations of TRPM4 have been recorded in Human Gene Mutation Database. The aim of this study was to explore the relationship between TRPM4 mutation and pathogenesis of AVB. We investigated a Chinese family with AVB by whole-exome sequencing. An arrhythmia-related gene filtering strategy was used to analyze the disease-causing mutations. Three different bioinformatics programs were used to predict the effects of the mutation result. A novel mutation of TRPM4 was identified (c.2455C>T/p.R819C) and cosegregated in the affected family members. The three bioinformatics programs predicted that the novel mutation may lead to damage. Our study will contribute to expand the spectrum of TRPM4 mutations and supply accurate genetic testing information for further research and the clinical therapy of AVB.

3.
BMC Med Imaging ; 21(1): 75, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902469

RESUMO

BACKGROUND: Multiple guidelines for pancreatic ductal adenocarcinoma (PDAC) suggest that all stages of patients need to receive postoperative adjuvant chemotherapy. S-1 is a recently emerged oral antitumour agent recommended by the guidelines. However, which population would benefit from S-1 needs to be determined, and predictors of chemotherapy response are needed for personalized precision medicine. This pilot study aimed to initially identify whether whole-tumour evaluation with MRI and radiomics features could be used for predicting the efficacy of S-1 and to find potential predictors of the efficacy of S-1 as evidence to assist personalized precision treatment. METHODS: Forty-six patients with PDAC (31 in the primary cohort and 15 in the validation cohort) who underwent curative resection and subsequently adjuvant chemotherapy with S-1 were included. Pre-operative abdominal contrast-enhanced MRI was performed, and radiomics features of the whole PDAC were extracted from the primary cohort. After univariable analysis and radiomics features selection, a multivariable Cox regression model for survival analysis was subsequently used to select statistically significant factors associated with postoperative disease-free survival (DFS). Predictive capacities of the factors were tested on the validation cohort by using Kaplan-Meier method. RESULTS: Multivariable Cox regression analysis identified the probability of T1WI_NGTDM_Strength and tumour location as independent predictors of the efficacy of S-1 for adjuvant chemotherapy of PDAC (p = 0.005 and 0.013) in the primary cohort, with hazard ratios (HRs) of 0.289 and 0.293, respectively. Further survival analysis showed that patients in the low-T1WI_NGTDM_Strength group had shorter DFS (median = 5.1 m) than those in the high-T1WI_NGTDM_Strength group (median = 13.0 m) (p = 0.006), and patients with PDAC on the pancreatic head exhibited shorter DFS (median = 7.0 m) than patients with tumours in other locations (median = 20.0 m) (p = 0.016). In the validation cohort, the difference in DFS between patients with low-T1WI_NGTDM_Strength and high-T1WI_NGTDM_Strength and the difference between patients with PDAC on the pancreatic head and that in other locations were approved, with marginally significant (p = 0.073 and 0.050), respectively. CONCLUSIONS: Whole-tumour radiomics feature of T1WI_NGTDM_Strength and tumour location were potential predictors of the efficacy of S-1 and for the precision selection of S-1 as adjuvant chemotherapy regimen for PDAC.

4.
J Clin Gastroenterol ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33852447

RESUMO

BACKGROUND AND AIMS: High prevalence of minimal change lesion (MCL) in nonerosive reflux esophagitis (NERD) patients is commonly recognized by many endoscopists. However, it is difficult to detect MCL with conventional white-light imaging (WLI) endoscopy. Linked color imaging (LCI), a novel image-enhanced endoscopy technology with strong, unique color enhancement, is used for easy recognition of early gastric cancer and detection of Helicobacter pylori infection. The aim of the study was to compare the efficacy of LCI and WLI endoscopy in evaluating MCL in patients with NER. MATERIALS AND METHODS: Forty-one patients with NERD and 38 subjects with nongastroesophageal reflux disease (non-GERD) were recruited in this study between August 2017 and July 2018. During upper gastrointestinal endoscopy, the distal 5 cm of the esophageal mucosal morphology at the squamocolumnar junction was visualized using WLI followed by LCI. MCL was defined as areas of erythema, blurring of the Z-line, friability, decreased vascularity, white turbid discoloration, and edema or accentuation of the mucosal folds. Three experienced endoscopists evaluated the color patterns for MCL on WLI images and on WLI combined with LCI images in both groups. A biopsy was taken 2 cm above the esophagogastric junction. Histologic slides were scored by a pathologist in a blinded manner. RESULTS: The proportion of MCL was higher in the patients with NERD (70.7%, 29/41) than in patients with non-GERD (39.5%, 15/38) using WLI combined with LCI. In 12 patients with NERD, both WLI and LCI showed normal mucosa. The MCL detection rate was significantly higher when using WLI combined with LCI than when using WLI (70.7% vs. 51.2%, P=0.039) in patients with NERD. The histopathologic score of MCL (+) was significantly higher than that of MCL (-) patients in both the NERD group (4.59±0.32 vs. 2.36±0.34, P<0.01) and the non-GERD group (3.47±0.50 vs. 2.00±0.28, P<0.01). The intraobserver reproducibility levels and interobserver agreement were better with LCI than with WLI alone. CONCLUSIONS: Frequency of MCL was higher in patients with NERD than in those with non-GERD. MCL can be identified by using WLI combined with LCI in patients with NERD. By enhancing endoscopic images, LCI is more sensitive in detecting MCL compared with WLI.

5.
Hemoglobin ; : 1-3, 2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33843396

RESUMO

We report a novel mutation on the ß-globin gene, Hb Hezhou [ß64(E8)Gly→Ser; HBB: c.193G>A] that was detected in two unrelated Chinese individuals. Patient 1 also carried an α+-thalassemia (α+-thal) -α4.2 (leftward) deletion, but hematological analyses showed no clinical consequences. Patient 2 was heterozygous for Hb Hezhou. Hemoglobin (Hb) analysis was performed using capillary electrophoresis (CE) and high performance liquid chromatography (HPLC). The Hb variant remained undetected using HPLC, while an additional peak was detected by CE. The finding of Hb Hezhou indicates that the possibilities of rare Hb variants should be alerted in the thalassemia screening program and precisely diagnosed depending on the Hb separation technique used.

7.
Clin Respir J ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825329

RESUMO

OBJECTIVES: No large sample studies have been designed to evaluate the efficacy of glucagon-like peptide-1 receptor agonists (GLP1RAs) in the primary and secondary prevention of respiratory disorders. We aimed at evaluating the relationship between use of GLP1RAs and occurrence of 12 kinds of respiratory disorders. METHODS: Large randomized placebo-controlled trials of GLP1RAs were included. We conducted meta-analysis using random effects model and measured heterogeneity using I2 . Treatment effect was presented as risk ratio (RR) and 95% confidence interval (CI). RESULTS: Seven trials including 55 922 participants were included in meta-analysis. The occurrence rates of various respiratory disorders were low, with the minimum of 0.02% (pulmonary fibrosis) and the maximum of 2.31% (pneumonia). Although not reaching statistical significance, GLP1RAs versus placebo showed the reduced trends in the risks of nine kinds of respiratory disorders including pneumonia (RR 0.89, 95% CI 0.78-1.01), squamous cell carcinoma of lung (SCCL; RR 0.55, 95% CI 0.25-1.21), asthma (RR 0.82, 95% CI 0.51-1.32), and chronic obstructive pulmonary disease (COPD; RR 0.89, 95% CI 0.73-1.10), but the increased trend in interstitial lung disease (ILD; RR 1.89, 95% CI 0.87-4.08). GLP1RAs had neutral effects on two other respiratory disorders. Heterogeneity in any meta-analysis was absent or low. CONCLUSION: GLP1RAs show the reduced trends in the risks of nine kinds of respiratory disorders (eg, pneumonia, SCCL, asthma, and COPD), but the increased trend in the risk of ILD. However, these findings need to be validated by further studies due to the low incidence rates of all the respiratory disorders.

9.
JAMA Oncol ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792623

RESUMO

Importance: This study demonstrates that tislelizumab in combination with chemotherapy is associated with improved progression-free survival (PFS) in patients with advanced squamous non-small-cell lung cancer (sq-NSCLC). Objective: To assess the efficacy and safety/tolerability of tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment for patients with advanced sq-NSCLC. Design, Setting, and Participants: This open-label, randomized phase 3 clinical trial was conducted at 46 sites in China between July 2018 and June 2019 and included patients with treatment-naive, histologically confirmed stage IIIB/IV sq-NSCLC. The data cutoff for these analyses was December 6, 2019; data extraction occurred on January 7, 2020. Interventions: Patients were randomized (1:1:1) to receive 1 of the following regimens intravenously on a 21-day cycle: tislelizumab (200 mg, day 1) plus paclitaxel (175 mg/m2, day 1) and carboplatin (area under the concentration of 5, day 1) (arm A); tislelizumab plus nab-paclitaxel (100 mg/m2, days 1, 8, and 15) and carboplatin (arm B); and paclitaxel and carboplatin (arm C). Patients were stratified by disease stage and tumor programmed cell death 1 ligand 1 (PD-L1) expression (<1% vs 1%-49% vs ≥50%). Main Outcomes and Measures: The primary end point was progression-free survival (PFS) assessed by an independent review committee (IRC). Secondary end points included overall survival, investigator-assessed (INV) PFS, IRC-assessed objective response rate (ORR), and IRC-assessed duration of response, as well as the incidence and severity of adverse events (AEs). Results: Overall, 355 patients (median [range] age, 62 [34-74] years; 330 men [91.7%]) with sq-NSCLC received treatment. After a median study follow-up of 8.6 months (95% CI, 8.1-9.0 months), IRC-assessed PFS was significantly improved with tislelizumab plus chemotherapy (arm A, 7.6 months; arm B, 7.6 months) vs chemotherapy alone (arm C, 5.5 months; hazard ratios were 0.524 (95% CI, 0.370-0.742; P < .001 [A vs C]) and 0.478 (95% CI, 0.336-0.679; P < .001 [B vs C]). Higher IRC-assessed ORR and longer IRC-assessed duration of response were observed in arms A (72.5%; 8.2 months) and B (74.8%; 8.6 months) vs C (49.6%; 4.2 months). No association was observed between PD-L1 expression and IRC-assessed PFS or ORR. Discontinuation of any treatment because of AEs was reported in 15 (12.5%; arm A), 35 (29.7%; arm B), and 18 (15.4%; arm C) patients. In each arm, the most common grade of 3 or greater AE was decreased neutrophil levels, which aligned with known chemotherapy toxic effects. Six treatment-related AEs leading to death occurred; however, no deaths were solely attributed to tislelizumab. Conclusions and Relevance: In this phase 3 randomized clinical trial, adding tislelizumab to chemotherapy was associated with significantly prolonged IRC-assessed PFS, higher IRC-assessed ORRs, and a manageable safety/tolerability profile in patients with advanced sq-NSCLC, regardless of PD-L1 expression. Trial Registration: ClinicalTrials.gov Identifier: NCT03594747.

10.
J Am Chem Soc ; 143(17): 6401-6406, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33904721

RESUMO

Chiral propargylsilanes and chiral allenylsilanes have emerged as versatile building blocks for organic synthesis. However, efficient methods for preparing these organosilicon compounds are lacking. We herein report a highly enantioselective method for synthesis of chiral propargylsilanes and chiral allenylsilanes from readily available alkynyl sulfonylhydrazones. Specifically, chiral spiro phosphate dirhodium complexes were used to catalyze asymmetric insertion of alkynyl carbenes into the Si-H bonds of silanes to afford a variety of chiral propargylsilanes with excellent enantioselectivity. Subsequently, a platinum catalyst was used for stereospecific isomerization of the chiral propargylsilanes to the corresponding chiral allenylsilanes.

11.
Org Lett ; 23(9): 3777-3781, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33891421

RESUMO

In this work, the NHC-catalyzed Michael/Mannich/lactamization cascade reaction of enals with either indole-2-carboxaldehyde-derived aldimines or indole-7-carboxaldehyde-derived aldimines is described. This protocol enables the rapid assembly of optically active pyrroloindolones and pyrroloquinolinones derivatives under mild conditions with high yields, excellent enantioselectivities, and a broad substrate scope.

14.
Diab Vasc Dis Res ; 18(2): 14791641211011016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33887983

RESUMO

There are no relevant meta-analyses that have assessed the safety of the sodium-glucose transporter 2 (SGLT2) inhibitors in different chronic diseases. We aimed at evaluating the safety of four SGLT2 inhibitors in three chronic diseases by meta-analysis of the large randomized trials of SGLT2 inhibitors. We performed random-effects meta-analysis and carried out subgroup analysis according to type of underlying diseases and type of SGLT2 inhibitors. SGLT2 inhibitors versus placebo significantly reduced the risk of acute kidney injury (RR 0.75, 95% CI 0.66-0.85), and showed the reduced trend in the risk of severe hypoglycemia (RR 0.86, 95% CI 0.71-1.03). SGLT2 inhibitors significantly increased the risks of diabetic ketoacidosis (RR 2.57), genital infection (RR 3.75), and volume depletion (RR 1.14); and showed the increased trends in the risks of fracture (RR 1.07), amputation (RR 1.21), and urinary tract infection (RR 1.07). These effects exhibited by SGLT2 inhibitors were consistent across three chronic diseases (i.e. type 2 diabetes, chronic heart failure, and chronic kidney disease) and four SGLT2 inhibitors (i.e. dapagliflozin, empagliflozin, ertugliflozin, and canagliflozin) (all Psubgroup > 0.05). These findings will guide that specific adverse events are monitored when SGLT2 inhibitors are used in clinical practice.

15.
Ann Med ; 53(1): 639-646, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33855907

RESUMO

OBJECTIVE: Little is known about the therapeutic relationship between coblation discoplasty and cervicogenic dizziness (CGD). CGD can be caused by abnormal proprioceptive inputs from compressed nerve roots, intradiscal mechanoreceptors and nociceptors to the vestibulospinal nucleus in the degenerative cervical disc. The aim was to analyze the efficacy of coblation discoplasty in CGD through intradiscal nerve ablation and disc decompression in a 12-month follow-up retrospective study. METHODS: From 2015 to 2019, 42 CGD patients who received coblation discolplasty were recruited as the surgery group, and 22 CGD patients who rejected surgery were recruited as the conservative group. Using intent-to-treat (ITT) analysis, we retrospectively analyzed the CGD visual analogue scale (VAS), neck pain VAS, CGD frequency score, and the CGD alleviation rating throughout a 12-month follow-up period. RESULTS: Compared with conservative intervention, coblation discoplasty revealed a better recovery trend with effect sizes of 1.76, 2.15, 0.92, 0.78 and 0.81 in CGD VAS, and effect sizes of 1.32, 1.54, 0.93, 0.86 and 0.76in neck pain VAS at post-operative 1 week, and 1, 3, 6, 12 months, respectively. The lower CGD frequency score indicated fewer attacks of dizziness until postoperative 3 months (p < 0.01). At post-operative 12 months, the coblation procedure showed increased satisfactory outcomes of CGD alleviation rating (p < .001, -1.00 of effect size). CONCLUSIONS: Coblation discoplasty significantly improves the severity and frequency of CGD, which is important inbridging unresponsive conservative intervention and open surgery.Key messagesThere is a correlation between the degenerative cervical disc and cervicogenic dizziness (CGD).CGD can be caused by abnormal proprioceptive inputs from a compressed nerve root and intradiscal mechanoreceptors and nociceptors to the vestibulospinal nucleus in the degenerative cervical disc.Cervical coblation discoplasty can alleviate CGD through ablating intradiscal nerve endings and decompressing the nerve root.

16.
Pediatr Surg Int ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33821327

RESUMO

OBJECTIVES: The purpose of this retrospective study was to evaluate the efficacy of anatomic thoracoscopic pulmonary segmentectomy performed based on three-dimensional computed tomography bronchography and angiography (3D-CTBA) in children and infants. METHODS: Totally, 22 patients received thoracoscopic segmentectomy from October 2019 to February 2020. The procedures were performed virtual segmentectomy based on 3D-CTBA. The preoperative planning depended on the 3D-CTBA result. RESULTS: All of the 22 cases ( 1 left S1, 1 right S3, 1 left S1 + 2, 1 left S1 + 2 + 3, 1 left S4 + 5, 1 right S6, 1 right S10, 1 left S10, 2 right S9 + 10, 3 left S9 + 10, 1 right S7 + 8 + 9 + 10, 8 left S7 + 8 + 9 + 10) were received thoracoscopic segmentectomy successfully. The mean procedure length was 76.6 ± 17.2 min, and the intraoperative blood loss was 16.5 ± 2.8 ml. The mean duration of chest tube insertion was 3.2 ± 0.7 days, and the mean hospital stay was 8.2 ± 2.8 days. Postoperative complications included infection (n = 1), atelectasis (n = 1), hydropneumothorax (n = 1) and pneumothorax (n = 1). No recurrence or mortality was observed during the short-term follow-up period of 3 months. CONCLUSIONS: Based on the 3D-CTBA technique, the specific pulmonary segments invaded by the lesions and the relationship between the corresponding pulmonary vessels and bronchi can be acknowledged before the operation, which is of positive significance for the resection of complex pulmonary segments and good preoperative surgical planning. It's worth popularizing in the pediatric population.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33847460

RESUMO

Tenon's capsule fibroblasts are the main cellular components of filtration tract scar that limit the success rate of glaucoma filtration surgery. Scar formation results from infiltration and proliferation of fibroblasts into damaged areas, meanwhile synthesis of extracellular matrix glycoproteins. Integrins are cell surface receptors for extracellular molecules that mediate cell adhesion, spreading, migration, and invasion. They bind their ligands often through recognition of short amino-acid sequences-arginine-glycine-aspartic acid (RGD). Peptides that contain RGD sequence can compete with RGD containing insoluble matrix proteins for binding to the integrin receptor and thus prevent the downstream signaling pathway. Increasing evidence supports that ß1-integrin/focal adhesion kinase (FAK)/Akt signal pathway plays an important role in fibrogenesis and scar formation in different tissues. In consideration of advantages of peptide hydrogel, that is well biocompatibility, gel state, degradability, good drug loading, we designed and fabricated an RGD peptide hydrogel, and hypothesized that it could inhibit the expression of ß1-integrin, FAK, and Akt in Tenon's capsule fibroblasts. Rheology results showed that 1% wt Fmoc-FFGGRGD peptide solution could self-assemble into hydrogel. Western blot analysis revealed that there were statistical differences between control group and 1% wt group in ß1-integrin/ß-actin, FAK/ß-actin, Akt/ß-actin respectively (*p < .05). The relative mRNA expression of ß1-integrin, FAK, Akt in control group and 1% wt group were also statistically different respectively (*p < .05). We proved that 1% wt Fmoc-FFGGRGD self-assembly peptide hydrogel could inhibit the expression of ß1-integrin, FAK and Akt in Tenon's capsule fibroblasts. It is a promising way to solve scar formation of glaucoma filter channel.

18.
Ann Palliat Med ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33832314

RESUMO

BACKGROUND: To evaluate the prognostic value of pretreatment prognostic nutritional index (PNI), lactated dehydrogenase (LDH) and their combination (PNI-LDH) in patients with locally advanced NPC receiving induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT). METHODS: A total of 213 patients diagnosed with locally advanced (III-IVA) NPC between January 2013 and December 2017 were retrospectively reviewed. The optimal PNI and LDH cutoff values were determined by the quartiles. The association between PNI and LDH and the clinicopathological characteristics of the patients was examined. Survival curves were analyzed using the Kaplan-Meier method and compared by the log-rank test between the different PNI and LDH subgroups. Univariate and multivariate analyses were performed by the Cox proportional hazards regression model to evaluate the prognostic impact on overall survival (OS), progression-free survival (PFS), locoregional recurrence free survival (LRFS) and distant metastasis-free survival (DMFS). Furthermore, the prognostic values of the PNI, LDH, and PNI-LDH were evaluated by comparing the AUC area. RESULTS: The optimal cut-off values of PNI and LDH were 52 and 177, respectively. Multivariate analyses revealed that patients with a higher PNI had inferior OS (P=0.027), PFS (P=0.040), LRFS (P=0.015) and DMFS (P=0.040), and patients with a higher LDH level had poorer OS (P=0.040), PFS (P=0.001), LRFS (P=0.001) and DMFS (P=0.001). Furthermore, EBV DNA positive, stage IVA were independent prognostic factors for survival outcomes in the multivariate analyses. Moreover, we further demonstrated that low PNIhigh LDH in locally advanced NPC patients was significantly related to poor OS (P=0.012), PFS (P=0.001), LRFS (P=0.001) and DMFS (P=0.001). The AUC of the PNI, LDH and PNI-LDH were 0.653 (P=0.021), 0.647 (P=0.028) and 0.751 (P=0.001), respectively, indicating that PNI-LDH is superior to either score alone. CONCLUSIONS: Pretreatment PNI and LDH could be considered as valuable predictors for survival outcomes in locally advanced NPC patients. The combination of them, superior to either score alone, can be used as a supplement to the traditional TNM staging system.

19.
Ecol Appl ; : e2323, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33655567

RESUMO

Tracking phenological change in a regionally explicit context is a key to understanding ecosystem status and change. The current study investigated long-term trends of satellite-observed land surface phenology (LSP) in the 17 National Ecological Observatory Network (NEON) domains across the conterminous United States (CONUS). Characterization of LSP trends was based on a high temporal resolution (3-day) time series of the two-band enhanced vegetation index (EVI2) derived from a long-term data record (LTDR) of the Advanced Very High Resolution Radiometer (AVHRR) and the Moderate Resolution Imaging Spectroradiometer (MODIS). We identified significant trend patterns in LSP and their seasonal climate and land use / land cover drivers for each NEON domain. Key findings include: (1) the start of season (SOS) predominantly shifted later in 13 out of 17 domains (24.3% of CONUS by area) due potentially to both a lack of spring warming in the eastern U.S. and changes in agronomic practices over agricultural lands; (2) the end of season (EOS) became predominantly later in 9 domains dominated by natural vegetation (14.1% of CONUS by area) in response to widespread warming in autumn; (3) the EOS predominantly shifted earlier in 3 domains (10.6% of CONUS by area) over primarily agricultural lands as potentially affected by changes in crop growth cycles; and (4) earlier shift in the SOS was mostly found in the Northwest (3.6% of CONUS by area) and was predominant only in the moist Pacific Northwest (27.7% of the domain by area) in response to more pronounced spring warming in the region. The overall patterns of SOS and EOS trends across CONUS appeared constrained by continental-scale temperature trends as characterized by a west-east dipole and the distribution of the nation's agricultural lands. In addition, seasonal trend analysis revealed that most NEON domains (15/17) became predominantly greener in part of or throughout the growing season, potentially contributed by both climate change induced growth increase and improved agricultural productivity. The domain-wide LSP trends with their underlying drivers identified here provide important contextual information for NEON science as well as for investigations within CONUS using other distributed observatories (e.g., LTER, LTAR, FLUXNET, USA-NPN, etc.).

20.
Spectrochim Acta A Mol Biomol Spectrosc ; 255: 119693, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33784596

RESUMO

A new morpholine functionalized coumarin-based fluorescent probe 1 was easily synthesized. The probe realized the sequentially detecting of Cu2+ and H2S in the HEPES buffer solution (20 mM, pH = 5.0). It made a turn-off fluorescence response to Cu2+ by using a complex formation with a 2:1 binding mode, and the resulting complex was able to detect H2S according to the displacement approach with a turn-on fluorescence response. The detecting limits of probe 1 for Cu2+ and 1-Cu2+ system for H2S were calculated to be 26 nM and 88.5 nM, respectively. This "on-off-on" recognition process was demonstrated by ultraviolet-visible spectroscopy, fluorescence spectroscopy, using proton nuclear magnetic resonance studies, electrospray ionization mass spectroscopy, single crystal X-ray diffraction, and using density functional theory calculations. In addition, both cell imaging and co-staining experiments showed that the probe could be utilized to visually detect Cu2+ and H2S in lysosomes.

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