Afterglow Electrochemiluminescence from Nitrogen-Deficient Graphitic Carbon Nitride.

Almost all current electrochemiluminescent reagents require real-time electrochemical stimulation to emit light. Here, we report a novel electrochemiluminescent reagent, nitrogen-deficient graphitic carbon nitride (CNx), that can emit afterglow electrochemiluminescence (ECL) after cessation of electric excitation. CNx obtained by post-thermal treatment of graphitic carbon nitride (CN) with KSCN has a cyanamide group and a nitrogen vacancy, which created defects to trap electrically injected electrons. The trapped electrons can slowly release and react with coreactants to emit light with longevity. The cathodic afterglow ECL lasts for 70 s after pulsing the CNx nanosheet (CNxNS-1.6)-modified glassy carbon electrode at -1.0 V for 20 s in 2.0 M PBS containing 1 mM K2S2O8. The afterglow ECL mechanism is revealed by investigation of its influencing factors and ECL wavelength. The discovery of afterglow ECL may open a new doorway for new significant applications of the ECL technique and provide a deeper understanding of the structure-property relationships of CN.

Hybridizing Carbon-Based Dot-Capped Manganese Dioxide Nanosheets and Gold Nanoparticles as a Highly Sensitive Surface-Enhanced Raman Scattering Substrate.

Surface-enhanced Raman Scattering (SERS) is a sensitive and nondestructive technique that provides fingerprint structural information of molecules. Designing and constructing sensitive and stable SERS substrates is of great significance for the application of the technique. In this study, single-layer carbon-based dots (CDs) are used as capping agents to synthesize gold nanoparticles (AuNPs/CDs) and manganese dioxide nanosheets (MnO2/CDs), which are then hybridized through a simple cocentrifugation method. After the hybridization, the monodispersive AuNPs/CDs aggregate obviously into some clusters exhibiting strong SERS activity due to the electromagnetic "hot spots" effect, and the MnO2/CDs also show outstanding SERS activity due to the charge-transfer resonance effect. The obtained nanohybrids (MnO2/CDs/AuNPs) with robust chemical stability combine well with the electromagnetic enhancement of AuNPs/CDs and chemical enhancement of MnO2/CDs, leading to an ultrahigh enhancement factor of 3.9 × 108. Based on the novel SERS substrate, a sensitive and rapid sensing system for the detection of malachite green is developed, with a low detection limit of 1 × 10-9 M. This work provides a valuable model for designing and fabricating high-performance SERS substrates.

Tune the Fluorescence and Electrochemiluminescence of Graphitic Carbon Nitride Nanosheets by Controlling the Defect States.

The effects of defect states on the fluorescence (FL) and electrochemiluminescence (ECL) properties of graphite phase carbon nitride (g-CN) are systematically investigated for the first time. The g-CN nanosheets (CNNSs) obtained at different condensation temperatures are used as the study models. It can be found that all the CNNSs have two kinds of defect states, one is originated from the edge of CNNSs (labeled as CN-defect) and the other is attributed to the partially carbonization regions (labeled as C-defect). Both two kinds of defect states substantially affect the luminescent properties of CNNSs. Both the FL and ECL signals of CNNSs contain a band gap emission and two defect emissions. For the FL of CNNSs, decreasing the density of defect states can increase efficiently the FL quantum yield, while increasing the density of defect states can make the FL spectra red shift. For the ECL of CNNSs, increasing the density of CN-defect states and decreasing the density of C-defect states are greatly important to improve the ECL activity. This work provides a deep insight into the FL and ECL mechanisms of g-CN, and is of significance in tuning the FL and ECL properties of g-CN. Also, it will greatly promote the applications of CNNSs based on the FL and ECL properties.

Heparin versus 0.9% saline solution to maintain patency of totally implanted venous access ports in cancer patients: A systematic review and meta-analysis.

AIM: The use of heparin and 0.9% saline solution is always controversial for central venous catheters. However, there is no systematic review or guideline about whether saline solution can replace heparin solution in adult cancer patients with totally implantable venous access ports (TIVAPs). The purpose of this review is to evaluate whether saline solution can replace heparin saline to lock TIVAPs. METHODS: The following databases were searched: PubMed, the Cochrane Library, Web of Science, Embase, CINAHL and Ovid (January 1, 1982, and February 21, 2020). All statistical analyses of the meta-analysis were completed using the Review Manager 5.3. RESULTS: A total of 201 studies were identified from these databases after initial review, and four studies met inclusion criteria, including 2652 cases. There was little heterogeneity among the included studies (I2 < 30%), and all analyses were conducted by the fixed-effects model. The total complications, catheter occlusions, catheter-related bloodstream infections and other complication rates in the heparin solution group were higher than in the saline solution group. In the subgroup analysis of heparin concentration, total complication rates in the saline solution group were higher than with 50 U of heparin and lower than with 100 U of heparin. However, the differences in these complications were small, and no significant difference was observed (all P > 0.05). CONCLUSIONS: Based on existing clinical studies, we recommend that saline solution can replace 50 or 100 U/ml of heparin as a safe and effective flush solution for TIVAPs.

Effects of C-Related Dangling Bonds and Functional Groups on the Fluorescent and Electrochemiluminescent Properties of Carbon-Based Dots.

Single-layer carbon-based dots (SCDs) were chosen as a model to investigate the effect of the C-related dangling bonds with spin S=1/2 and functional groups on the electrochemiluminescent (ECL) and fluorescent (FL) properties of CDs. The C-related dangling bonds and functional groups of SCDs were tuned by chemical reduction with NaBH4 . There have several main findings via investigating the ECL and FL properties of SCDs before and after the chemical reduction. First, the FL and ECL of CDs are highly dependent on their concentration, and luminescent resonance energy transfer is observed in ECL studies when the concentration of CDs is high. Second, the ECL activity of CDs is greatly enhanced as the C-related dangling bonds increase, proving that the ECL of CDs originates from the C-related dangling bonds. Third, the FL of CDs is the synthesis of the inner FL originated from the contained isolated sp2 units and the defect FL from the C-related dangling bonds. The inner FL of CDs is enhanced greatly by removing the carboxyl groups, while the defect FL is increased slightly due to the increased C-related dangling bonds. We believe this study would promote our understanding in the ECL and FL mechanisms of CDs, advancing the applications of CDs based on their ECL and FL properties.

While it is not deliberate, much of today's biomedical research contains logical and technical flaws, showing a need for corrective action.

Biomedical research has advanced swiftly in recent decades, largely due to progress in biotechnology. However, this rapid spread of new, and not always-fully understood, technology has also created a lot of false or irreproducible data and artifacts, which sometimes have led to erroneous conclusions. When describing various scientific issues, scientists have developed a habit of saying "on one hand… but on the other hand…", because discrepant data and conclusions have become omnipresent. One reason for this problematic situation is that we are not always thoughtful enough in study design, and sometimes lack enough philosophical contemplation. Another major reason is that we are too rushed in introducing new technology into our research without assimilating technical details. In this essay, we provide examples in different research realms to justify our points. To help readers test their own weaknesses, we raise questions on technical details of RNA reverse transcription, polymerase chain reactions, western blotting and immunohistochemical staining, as these methods are basic and are the base for other modern biotechnologies. Hopefully, after contemplation and reflection on these questions, readers will agree that we indeed know too little about these basic techniques, especially about the artifacts they may create, and thus many conclusions drawn from the studies using those ever-more-sophisticated techniques may be even more problematic.

The well-accepted notion that gene amplification contributes to increased expression still remains, after all these years, a reasonable but unproven assumption.

"Gene amplification causes overexpression" is a longstanding and well-accepted concept in cancer genetics. However, raking the whole literature, we find only statistical analyses showing a positive correlation between gene copy number and expression level, but do not find convincing experimental corroboration for this notion, for most of the amplified oncogenes in cancers. Since an association does not need to be an actual causal relation, in our opinion, this widespread notion still remains a reasonable but unproven assumption awaiting experimental verification.

Installing logic gates in permeability controllable polyelectrolyte-carbon nitride films for detecting proteases and nucleases.

Proteases and nucleases are enzymes heavily involved in many important biological processes, such as cancer initiation, progression, and metastasis; hence, they are indicative of potential diagnostic biomarkers. Here, we demonstrate a new label free and sensitive electrochemiluminescent (ECL) sensing strategy for protease and nuclease assays that utilize target-triggered desorption of programmable polyelectrolyte films assembled on graphite-like carbon nitride (g-C3N4) film to regulate the diffusion flux of a coreactant. Furthermore, we have built Boolean logic gates OR and AND into the polyelectrolyte films, capable of simultaneously sensing proteases and nucleases in a complicated system by breaking it into simple functions. The developed intelligent permeability controlled enzyme sensor may prove valuable in future medical diagnostics.

Gold nanoparticle-graphite-like C3N4 nanosheet nanohybrids used for electrochemiluminescent immunosensor.

Two-dimensional graphite-like carbon nitride nanosheets (g-C3N4 NSs) were hybridized with gold nanoparticles (Au NPs) to construct an electrochemiluminescence (ECL) immunosensor. The prepared Au NP-functionalized g-C3N4 NS nanohybrids (Au-g-C3N4 NHs) exhibit strong and stable cathodic ECL activity compared to g-C3N4 NSs due to the important roles of Au NPs in trapping and storing the electrons from the conduction band of g-C3N4 NSs, as well as preventing high energy electron-induced passivation of g-C3N4 NSs. On the basis of the improved ECL stability and ECL peak intensity of the Au-g-C3N4 NHs, a novel ECL immunosensor was developed to detect carcinoembryonic antigen (CEA) as a model target analyte. The ECL immunosensor has a sensitive response to CEA in a linear range of 0.02-80 ng mL(-1) with a detection limit of 6.8 pg mL(-1). Additionally, the proposed immunosensor shows high specificity, good reproducibility, and long-term stability.

Capillary electrophoresis coupled with electrochemiluminescence detection for the separation and determination of thyreostatic drugs in animal feed.

A rapid, simple, and practical method for the determination of four of the most used thyreostatic drugs (methimazole, 2-thiouracil, 6-methyl-2-thiouracil, and 6-propyl-2-thiouracil) using CE coupled to electrochemiluminescence detection has been established, based on the electrochemiluminescence enhancement of tris(2,2-bipyridyl)ruthenium(II) with these analytes. Parameters that affect separation and detection were optimized. Under the optimum experimental conditions, the four analytes could be well separated within 11 min at the separation voltage of 16 kV in a running solution containing 20 mM phosphate buffer (pH 9.0) and 1.0 × 10(-4) M Ru(bpy)(3)(2+), with a solution of 20 mM phosphate buffer (pH 12.0) containing 1.0 × 10(-4) M Ru(bpy)(3)(2+) in the electrochemiluminescence detection cell. The detection limits for methimazole, 6-methyl-2-thiouracil, 6-propyl-2-thiouracil, and 2-thiouracil were 0.1, 0.05, 0.05, and 0.01 µM, respectively. The proposed method was applied to analyze these drugs in spiked animal feed samples. The recoveries were 88.2∼99.0 and 86.4∼98.7% for the intraday and interday analyses, respectively. The RSDs were 2.7∼4.8 and 1.8∼5.0% for the intraday and interday analyses, respectively. The results demonstrate that the proposed method has promising applications in the detection of thyreostatic drugs in animal feeds.

An ionic liquid-mediated electrochemiluminescent sensor for the detection of sulfur dioxide at the ppb level.

A novel portable SO2 gas sensor based on ionic liquid (IL) mediated electrochemiluminescence (ECL) for detecting SO2 at the ppb levels has been developed. The sensing system for SO2 detection is based on the strong quenching effect of SO2 on the ECL of the tris(2,2'-bipyridine)ruthenium(ii) (Ru(bpy)3(2+))/O2 coreactant system in the IL film. Over the potential window between -1.0 and +1.3 V, O2 can act as an effective coreactant for Ru(bpy)3(2+) ECL in ILs, giving a bright ECL emission. The ECL of the Ru(bpy)3(2+)/O2 system can be strongly inhibited by SO2 through the direct quenching of the excited state of the luminophore, i.e. Ru(bpy)3(2+)*, by SO2 molecules. The inhibited ECL intensity is proportional to the concentration of SO2 in the range from 40 to 2000 ppb with a detection limit of 20 ppb. The proposed SO2 ECL sensor can be operated at room temperature and shows high selectivity, good reproducibility and long-term stability in a dry atmosphere.

Human liver cancer organoids: Biological applications, current challenges, and prospects in hepatoma therapy.

Liver cancer and disease are among the most socially challenging global health concerns. Although organ transplantation, surgical resection and anticancer drugs are the main methods for the treatment of liver cancer, there are still no proven cures owing to the lack of donor livers and tumor heterogeneity. Recently, advances in tumor organoid technology have attracted considerable attention as they can simulate the spatial constructs and pathophysiological characteristics of tumorigenesis and metastasis in a more realistic manner. Organoids may further contribute to the development of tailored therapies. Combining organoids with other emerging techniques, such as CRISPR-HOT, organ-on-a-chip, and 3D bioprinting, may further develop organoids and address their bottlenecks to create more practical models that generalize different tissue or organ interactions in tumor progression. In this review, we summarize the various methods in which liver organoids may be generated and describe their biological and clinical applications, present challenges, and prospects for their integration with emerging technologies. These rapidly developing liver organoids may become the focus of in vitro clinical model development and therapeutic research for liver diseases in the near future.

Ultrasensitive gaseous NH3 sensor based on ionic liquid-mediated signal-on electrochemiluminescence.

This work reports that ammonia (NH(3)) can be used as an efficient co-reactant for tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)(3)(2+)) electrochemiluminescence (ECL) in ionic liquids (ILs), on the basis of which a signal-on ECL sensor for directly detecting gaseous NH(3) has been developed. The NH(3) ECL sensor has a very high sensitivity, with a detection limit of 10 ppt NH(3) (at signal-to-noise ratio of 3) without any preconcentration. The high sensitivity is mainly due to the zero ECL background of Ru(bpy)(3)(2+) in the ILs, strong co-reactant ECL activity of NH(3), and high solubility of NH(3) in imidazolium-based ILs. Additionally, the ECL sensor shows an excellent selectivity against common interfering gases and a wide linear response range from 10 ppt to 10 ppm.

Tumor Cell-Specific and Lipase-Responsive Delivery of Hydrogen Sulfide for Sensitizing Chemotherapy of Pancreatic Cancer.

The inability of small molecule drugs to diffuse into tumor interstitium is responsible for the relatively low effectiveness of chemotherapy. Herein, a hydrogen sulfide (H2S) gas-involved chemosensitization strategy is proposed for pancreatic cancer treatment by developing a tumor-specific lipase-responsive nanomedicine based on aptamer-conjugated DATS/Dox co-loaded PCL-b-PEO micelle (DA/D@Ms-A). After receptor-mediated endocytosis and subsequent digestion of PCL blocks by intracellular lipase, the nanomedicine releases Dox and DATS, which then react with intracellular glutathione to produce H2S. The cytotoxicity result indicates that H2S can enhance Dox chemotherapy efficiency owing to the synergetic therapeutic effect of Dox and H2S. Moreover, the nanomedicine is featured with well tumor penetration capability benefitting from the targeting ability of aptamers and high in vivo biocompatibility due to the high density of PEO and biodegradable PCL. The nanomedicine capable of synergetic gas-chemotherapy holds great potential for pancreatic cancer treatment.

DDX56 transcriptionally activates MIST1 to facilitate tumorigenesis of HCC through PTEN-AKT signaling.

Rationale: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver that is the leading cause of cancer-related mortality worldwide. However, genetic alterations and mechanisms underlying HCC development remain unclear. Methods: Tissue specimens were used to evaluate the expression of DEAD-Box 56 (DDX56) to determine its prognostic value. Colony formation, CCK8, and EdU-labelling assays were performed to assess the effects of DDX56 on HCC proliferation. The in vivo role of DDX56 was evaluated using mouse orthotopic liver xenograft and subcutaneous xenograft tumor models. Dual-luciferase reporter, chromatin immunoprecipitation, and electrophoretic mobility shift assays were performed to examine the effect of DDX56 on the MIST1 promoter. Results: DDX56 expression in HCC tissues was elevated and this increase was strongly correlated with poor prognoses for HCC patients. Functionally, DDX56 promoted HCC cell proliferation both in vitro and in vivo, while mechanistically interacting with MECOM to promote HCC proliferation by mono-methylating H3K9 (H3K9me1) on the MIST1 promoter, leading to enhanced MIST1 transcription and subsequent regulation of the PTEN/AKT signaling pathway, which promotes HCC proliferation. More importantly, the PTEN agonist, Oroxin B (OB), blocked the DDX56-mediated PTEN-AKT signaling pathway, suggesting that treating HCC patients with OB may be beneficial as a therapeutic intervention. Furthermore, we observed that ZEB1 bound to DDX56 and transcriptionally activated DDX56, leading to HCC tumorigenesis. Conclusions: Our results indicated that the ZEB1-DDX56-MIST1 axis played a vital role in sustaining the malignant progression of HCC and identified DDX56 as a potential therapeutic target in HCC tumorigenesis.

Carbon dioxide gas sensor based on ionic liquid-induced electrochemiluminescence.

Electrochemiluminescence of the luminol-O(2) system in an electrolyte-free N,N-dimethylformamide (DMF)-dipropylamine (DPA) cosolution is induced by the formation of a carbamate ionic liquid (IL) from the reaction between CO(2) and DPA, on the basis of which a facile ECL sensor for measuring atmospheric CO(2) has been developed. This ECL sensing method shows several advantages in the detection of CO(2), such as high safety, high selectivity, wide linear response range, and good sensitivity. The gas sensor was found to have a linear response range from 100 ppm to 100 v/v% and a detection limit of 80 ppm (at signal-to-noise ratio of 3). This is the first reported IL-induced ECL sensor for a gas, thus the principle of this type of sensor and the IL-induced ECL mechanism have been demonstrated in detail.

Nano-sized platinum as a mimic of uricase catalyzing the oxidative degradation of uric acid.

Uric acid (UA) deposition in human body is very harmful, since it may induce gout. Therefore, it would be of great significance to catalyze the degradation of UA in human body. Herein, platinum nanoparticles (PtNPs) were found to be an effective mimic of uricase in the oxidation of UA. PtNPs could lower the activation energy of UA oxidation (i.e., from 139.49 kJ mol(-1) to 61.73 kJ mol(-1)), and thus increase the reaction rate constant dramatically (e.g., by the catalysis of 2.63 mg L(-1) PtNPs, the reaction rate constant of UA degradation at 37 °C was 5.85 × 10(-4) s(-1), which was almost 29000 times higher than that of without PtNPs (2.02 × 10(-8) s(-1))). Effects of degradation conditions, such as the concentration and size of PtNPs, concentration of dissolved oxygen and pH value of the solution on the catalytic degradation of UA have been studied. Furthermore, products of UA degradation were analyzed by GC-MS spectroscopy and FT-IR spectrometry. On this basis, a detailed mechanism was finally proposed for the PtNPs-catalyzed UA degradation.

Prolonging the flush-lock interval of totally implantable venous access ports in patients with cancer: A systematic review and meta-analysis.

BACKGROUND: Recently, some studies have shown that prolonging flush interval is safe and feasible for patients who complete chemotherapy. However, there is no consensus about the optimal flush interval for those patients. OBJECTIVE: The purpose of this review was to evaluate whether the flush interval could be prolonged based on monthly interval for regular maintenance and to explore the optimal flush interval. DATA SOURCES: We searched the following databases for articles published between 1 January 1982 and 21 February 2020: PubMed, Cochrane Library, Web of Science, EMBASE, CINAHL, and Ovid. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials, retrospective and prospective cohort studies of flush interval less than 4 weeks versus longer than 4 weeks for patients who completed chemotherapy, were included. RESULTS: Two reviewers extracted information and assessed the quality of the articles independently. In total, 389 articles were retrieved, and 4 studies including 862 cases fulfilled the inclusion criteria. There was no statistical heterogeneity (I2 = 0, p > 0.05) among the included studies. Hence, the fixed-effects model was used for the meta-analysis. The meta-analysis showed that the total complication rate associated with longer than 4-week interval was higher than that associated with less than 4-week interval. Nevertheless, there was no significant difference between the two groups (7.2% vs 7.6%, p = 0.83). Moreover, the meta-analysis showed that the total complication and catheter occlusion rates associated with the 4-week interval were higher than those associated with the 8-week interval. However, there was no significant difference between the two groups (total complications: 11.4% vs 9.5%, p = 0.68; catheter occlusions: 4.9% vs 4.1%, p = 0.89). LIMITATIONS: Only four non-randomized controlled studies were included, and the outcomes of the included studies were reported incompletely. CONCLUSION: Extending the flush interval to longer than 4 weeks is safe and feasible. Based on previous studies, extending the flush interval to 8 weeks might not increase the incidence of total complications and catheter occlusions. However, there is no conclusion on whether the flush interval could be extended to 3 months or longer.

Efficacy of Auricular Acupressure in Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting in Patients with Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: More than 40% of patients with cancer have reported that chemotherapy-induced nausea and vomiting (CINV) remained the most debilitating side effects of treatment even in the era of new antiemetics. OBJECTIVE: The purpose of this review was to systematically evaluate the clinical effect of auricular acupressure (AA) in prevention and treatment of chemotherapy-induced nausea and vomiting. METHODS: The following databases were searched: PubMed, Cochrane Library, EMBASE, the Web of Science, Chinese Biological Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang, and VIP (from database inception to April 2020). Eligible randomized controlled trials of auricular acupressure in treating CINV were collected, including crossover randomized design study. The meta-analysis was carried out by RevMan software (5.3). RESULTS: Totally 19 RCTs with 1449 patients met the inclusion criteria. Compared with control groups, the relief efficiency of overall CINV was enhanced by AA combined with antiemetics (RR = 1.31, CI 1.22 to 1.41, p ≤ 0.001). Although the therapeutic effect on acute nausea and vomiting was not obvious, AA still played an important role in reducing delayed nausea and vomiting (delayed nausea frequency: RR = 0.68, CI -1.01 to -1.35, p ≤ 0.001; delayed vomiting frequency: RR = 0.91, CI -1.22 to -0.61, p ≤ 0.001). The likelihood of adverse reactions related to antiemetics was reduced by AA combined with antiemetics (RR = 0.62, CI 0.53 to 0.74, p ≤ 0.001). Statistically significant association was found between AA and incidence of constipation, diarrhea, and tiredness, while there was no statistically significant association between AA and abdominal distension or headache. CONCLUSION: Auricular acupressure supplementation benefited delayed chemotherapy-induced nausea and vomiting as well as constipation, diarrhea, and tiredness. AA alone or AA supplementation has little effect on acute nausea and acute vomiting. There is no conclusion on whether AA alone is superior to antiemetics in the management of delayed CINV. Further studies are needed to confirm the efficacy of auricular acupressure alone in delayed CINV and anticipatory CINV. The results of this review provided the basis for further research with more rigorous study designs, adequate sample sizes, and standardized implementation to confirm the efficacy of auricular acupressure.

Heated indium tin oxide cell for studying ionic liquid-mediated electrochemiluminescence.

A heated indium tin oxide (ITO) electrochemiluminescent (ECL) cell containing an ITO counter electrode, an ITO reference electrode, and a heated ITO working electrode has been fabricated to promote ionic liquid (IL)-mediated ECL reactions and hence improve sensitivities of IL-based ECL sensors. Heating the ITO working electrode was carried out by applying high-frequency ac voltages, and the temperature of the heated ITO working electrode was calibrated by the redox currents of ferrocenemethanol (FcMeOH) in 1-butyl-3-methylimidazolium hexafluorophosphate (BMIPF(6)) IL. A significant increase (26 times) in ECL intensity of the luminol-O(2)-BMIPF(6) system was observed when heating the ITO working electrode from room temperature to 54 degrees C. The use of the developed heated ITO ECL cell has been demonstrated to be an important way to improve IL-mediated ECL sensitivity and envisioned to enlarge applications of IL-based ECL sensors.