Energy Transfer between Size-Controlled CsPbI3 Quantum Dots for Light-Emitting Diode Application.

Perovskite quantum dots (PQDs) are applicable in light-emitting diodes (LEDs) owing to their color tunability, high color purity, and excellent photoluminescence quantum yield (PLQY) in the solution state. However, a PQD film obtained through nonradiative recombination by concentration quenching and the formation of surface defects exhibited a low PLQY. In this study, we focused on the energy transfer between PQDs with different energy gaps (Eg) to reduce nonradiative recombination in the film state and consequently achieve high device performance. We prepared size-controlled PQDs measuring 10.7 nm (large-size QD; LQD) and 7.9 nm (small-size QD; SQD) with different Eg values and observed a spectral overlap between SQD emission and LQD absorption. To investigate the Förster resonance energy transfer (FRET) from SQDs to LQDs, we prepared SQD-LQD mixed QDs (MQDs). The MQD film enhanced LQD emission and exhibited a higher PLQY (52%) with a longer PL decay time (7.4 ns) than those exhibited by the neat LQD film (38% and 6.2 ns). This energy transfer was determined to be FRET by photoluminescence excitation and PL decay times. Moreover, the external quantum efficiency of an MQD-based LED increased to 15%, indicating that the FRET process can enhance the PLQY of the film and LED efficiency.

Gel permeation chromatography process for highly oriented Cs3Cu2I5 nanocrystal film.

The emergence of green materials has attracted considerable attention in the field of optoelectronics. Copper-based lead-free metal halide (with a near-unity quantum yield) obtained from Cs3Cu2I5 nanocrystals (NCs) can exhibit blue emission with a wavelength of 440 nm and provide outstanding stability for various applications. However, in practical applications, colloidal dispersion purity and film quality are inadequate toward a high-performance device. In this study, antisolvent-free gel permeation chromatography is used to purify Cs3Cu2I5 NCs. The purified Cs3Cu2I5 NCs exhibit a high photoluminescent quantum yield and provide a highly oriented single-crystal film. Density functional theory calculation results indicate that the iodide-rich surface in the NCs makes them highly stable. In addition, it has been demonstrated for the first time that the mixture of polymethyl methacrylate (PMMA) and Cs3Cu2I5 NCs has waterproofing capabilities. The composite film consisting of Cs3Cu2I5 NCs and PMMA can survive in water for several days. This result opens up more possibilities for the application of these green material.

Combining MALDI-MS with machine learning for metabolomic characterization of lung cancer patient sera.

An increasing amount of evidence has proven that serum metabolites can instantly reflect disease states. Therefore, sensitive and reproducible detection of serum metabolites in a high-throughput manner is urgently needed for clinical diagnosis. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a high-throughput platform for metabolite detection, but it is hindered by significant signal fluctuations because of the "sweet spot" effect of organic matrices. Here, by screening two transformation methods and four normalization techniques to reduce the significant signal fluctuations of the DHB matrix, an integrated MALDI-MS data processing approach combined with machine learning methods was established to reveal metabolic biomarkers of lung cancer. In our study, 13 distinctive features with statistically significant differences (p < 0.001) between 34 lung cancer patients and 26 healthy controls were selected as significant potential biomarkers of lung cancer. 6 out of the 13 distinctive features were identified as intact metabolites. Our results demonstrate the potential for clinical application of MALDI-MS in serum metabolomics for biomarker screening in lung cancer.

Two-Step Crystallization for Low-Oxidation Tin-Based Perovskite Light-Emitting Diodes.

Metal halide perovskites attract significant attention because of their excellent optoelectronic and semiconducting properties. However, there are environmental concerns related to the toxicity of the lead metal that is mainly used in these perovskites. PEA2SnI4 perovskite is a potential candidate for lead-free perovskites because of its pure red emission. Although, undesired Sn4+ oxidation results in the deterioration of PEA2SnI4 perovskite. We demonstrate the two-step crystallization of PEA2SnI4 through the (i) reprecipitation and (ii) recrystallization processes. A film prepared using this method exhibits narrowed emission, with a full width at half-maximum from 30.0 to 26.1 nm, because of its homogeneous emission. Moreover, the Sn4+ content of two-step-crystallized PEA2SnI4 films is five times lower than that of a control film. Diffusion-ordered spectroscopy analysis indicates that the two-step precursor exhibits a smaller hydrodynamic radius crystal seed, which enhances crystallization during spin coating. The resulting two-step crystallized PEA2SnI4-based light-emitting diode (LED) exhibits a maximum external quantum efficiency (EQE) of 0.4% with an average of 0.2%, which is two times greater than that of the control device. This two-step approach may be generalized to synthesize other lead-free materials.

Comparison of IOL-Master 700 and IOL-Master 500 biometers in ocular biological parameters of adolescents.

AIM: To compare the differences and consistency of IOL-Master 700 biometers applying swept optical coherence tomography with the conventional IOL-Master 500 applying partial coherence interference in terms of the ocular biological parameters in adolescents with ametropia. METHODS: A total of 110 adolescents (110 eyes) with ametropia were collected, including 55 males and 55 females; age 10.69±2.81y. Ocular biological measurements were taken by IOL-Master 700 and IOL-Master 500 respectively to obtain biological parameters including axial length (AL), mean corneal anterior surface keratometry (Km), anterior chamber depth (ACD), and horizontal corneal diameter (WTW). Paired t-test was used to compare the differences between the two instruments. The intra-group correlation coefficient (ICC) and the Bland-Altman analysis were used to evaluate the consistency of parameter measurements between the two instruments for the four biological parameters. RESULTS: Statistical analysis showed that there was no significant difference in the Km value measured by IOL-Master 700 and IOL-Master 500 (t=-1.644, P=0.116). The average differences of the AL, ACD, and WTW distances between the two instruments are 0.028, 0.101 and 0.064 mm respectively, and the differences are statistically significant (t=2.644, 12.505, 3.911, P<0.001). The consistency study results indicated high correlation in the measurement of AL, Km, ACD and WTW between the two instruments (ICC=0.994, 0.873, 0.927, 0.912). CONCLUSION: The novel biometric instrument IOL-Master 700 makes no difference with IOL-Master 500 in the measurement of Km. There are some differences in the values of AL, ACD, and WTW. However, the two instruments show good consistency in these four biological measurements. The measured values of Km are interchangeable between the instruments. These two types of biometrics can be used as mutual reference in consideration of that the differences in AL, ACD, and WTW measurements are not sufficient to produce clinically meaningful differences.

Harvesting More Energetic Photoexcited Electrons from Closely Packed Gold Nanoparticles.

The characterization of photoexcited electrons on the surface of nanomaterial remains challenging. Herein, laser excitation mass spectrometry combined with a chemical thermometer and electron acceptor has been developed to characterize the energetics and population density of photoexcited electrons transferred from gold nanoparticles (AuNPs). In contrast to laser fluence and bias voltage, the hot spots of closely packed AuNPs play a more significant role in enhancing the average energetics of photoexcited electrons, which can be harvested effectively by the electron acceptor. By harvesting more energetic photoexcited electrons for the desorption and ionization process, it is anticipated that the sensitive detection of biomarkers can be achieved, which is beneficial to metabolomic studies and early disease diagnosis.

Enzyme-free electrochemical biosensor based on amplification of proximity-dependent surface hybridization chain reaction for ultrasensitive mRNA detection.

The ability to recognize mRNA with high efficiency in cells would greatly facilitate the elucidation of mRNA-mediated cellular cascades and their disease associations. However, most traditional electrochemical strategies targeting nucleotides are always confronted with cumbersome interface operation and washing procedures, as well as the high cost of labeling and the strict reaction conditions of tool enzymes, limiting their potential applications. To address these issues, herein we reported, for the first time, a simple label-free, isothermal, non-enzymatic, and ultrasensitive homogeneous electrochemical biosensor based on autonomous proximity-dependent surface hybridization chain reaction (HCR), for sensitive signal amplification and highly specific detection of target survivin mRNA with a detection limit of 3 fM. The target triggers hybridization chain reaction and mRNA-fueled surface hybridization of ferrocene-tagged metastable DNA hairpin probes on proximity-dependent surface hybridization, resulting in the formation of multiple long-range duplex DNA chains which are immobilized onto the gold electrodes with a substantially stable ferrocene-mediated redox current. Thus, a significant electrochemical signal increase is observed dependent on the concentration of the target RNA, with a very low detection limit. Mo-reover, this molecular biosensor also exhibits excellent specificity to distinguish even single base mismatched, with strong reliability. The developed biosensor provides a novel promising tool for ultra-sensitive and selective detection, and it has great potential to be applied in mRNA-related biochemical research and clinical cancer diagnostics in more detail.

Parafoveal retinal massage combined with autologous blood cover in the management of giant, persistent or recurrent macular holes.

AIM: To assess the efficacy and safety of parafoveal retinal massage combined with autologous whole blood cover in the treatment of refractory macular holes (MHs) and present the surgical procedure. METHODS: Patients with giant (minimum diameter ≥800 µm), recurrent or persistent MHs who underwent PPV combined with parafoveal retinal massage and autologous whole blood cover using C3F8 as tamponade agent from February 2018 to May 2019 were enrolled in this retrospective study. After surgery, all patients were informed to maintain a prone position for at least 7d. Preoperative and postoperative best-corrected visual acuities (BCVAs) were compared and MH closure rate was measured as the main outcome. RESULTS: A total of 13 MH patients consisted of 6 giant MHs, 4 persistent holes and 3 recurrent holes (5 men and 8 women; average age was 56.40±11.72y) were enrolled in this study. MH closure was achieved in 11 eyes by this modified surgical technique while 2 eyes failed. Revitrectomy with autologous neurosensory retinal patch transplantations was applied for those 2 patients and then both holes were closed. No intraoperative complications were observed. BCVA improved from 1.73 logMAR to 0.74 logMAR at 6mo postoperation. There was significant difference in BCVA before versus after the surgery (P<0.05). There were no adverse events occurred during the follow-up period. CONCLUSION: With easier surgical procedure, parafoveal retinal massage combined with autologous whole blood cover is an effective addition to the surgical options for the management of refractory MHs.

Vitrectomy with air tamponade for surgical repair of rhegmatogenous retinal detachment by eye position guided fluid-air exchange.

AIM: To observe the efficacy and safety of pars plana vitrectomy (PPV) with eye position guided fluid-air exchange (FAX) and air tamponade in the treatment of rhegmatogenous retinal detachment (RRD). METHODS: RRD patients without severe proliferative vitreoretinopathy (PVR) C1 or more were enrolled. All patients underwent PPV combining with air tamponade. During operation, the primary retinal break(s) were placed at lower site and subretinal fluid was aspirated through the break(s) at the same time when eye position guided FAX was proceeding. Sufficient laser spots were made to seal the retinal break(s) after FAX, and filtered air was left in vitreous cavity as tamponade agent finally. The main outcomes were primary and final success rates, best corrected visual acuity (BCVA), and the secondary outcomes were rate of postoperative cataract surgery and high intraocular pressure. RESULTS: A total of 37 eyes (20 males and 17 females) with a follow-up time of ≥6mo were included. The range of RRD was 5.6±1.8h, and the number of retinal breaks was 1.9±1.2. The breaks located at inferior quadrants (between 3:00 and 9:00) in 5 cases (13.5%), and both superior and inferior breaks were found in 3 cases (8.1%). A total of 25 cases (67.6%) with macular detached involvement, 9 cases (24.3%) with intraocular lens, and 8 patients (21.6%) were treated with phacoemulsification and intraocular lens implantation together. The success rate of primary retinal reattachment was 100% (37/37). At 6mo postoperatively, BCVA (logMAR) was increased from 1.13±1.07 to 0.23±0.15 (P<0.001). Phacoemulsification combined with intraocular lens implantation was performed in 2 patients (5.4%), and one of them underwent macular epiretinal membrane peeling in addition (2.7%). Furthermore, high intraocular pressure was found in 4 cases (10.8%). CONCLUSION: PPV with air tamponade by eye position guided FAX can achieve a high reattachment success rate in the management of patients with RRD, and it has the advantages of short postoperative prone time and fewer operative complications.

Surface optimization of gold nanoparticle mass tags for the sensitive detection of protein biomarkers via immuno-capture LI-MS.

HPV-induced cervical cancer is one of the most lethal cancers. Therefore, the development of a reliable and accurate method for the early diagnosis of HPV infections is highly important. Here, gold nanoparticles (AuNPs) were utilized as mass tags in an immuno-capture LI-MS assay for the detection of HPV marker proteins. Through the optimization of the amount of antibodies and surface charges on AuNPs, high antigen detection efficiency with minimal non-specific binding was achieved. With optimized antibody-conjugated AuNPs, low attomole amount of HPV proteins in HeLa cell lysate was quantified.

Sensitive Detection of Separated Charges in Nanohybrids by Laser Excitation Mass Spectrometry with Tetrabutylammonium Cationic Probe.

Charge separation lays the foundation for photocatalysis and photovoltaics, in which the catalytic/voltaic efficiency is primarily related to the amount of separated charges generated. Yet, direct experimental approaches for the quantification of separated charges are very limited, especially for nanostructures in small quantities. Here, by laser excitation mass spectrometry with tetrabutylammonium as a sensitive probe, the separated charges in gold-metal sulfide core-shell nanostructures are determined and correlated with the bandgap of the semiconductor shell. Moreover, the separated charges formed can already be detected unambiguously in only an attomole-level of nanoparticles (i.e., 1 × 108 NPs).

Zwitterionic Polymer Conjugated Glucagon-like Peptide-1 for Prolonged Glycemic Control.

Glucagon-like peptide-1 (GLP-1) is of particular interest for treating type 2 diabetes mellitus (T2DM), as it induces insulin secretion in a glucose-dependent fashion and has the potential to facilitate weight control. However, native GLP-1 is a short incretin peptide that is susceptible to fast proteolytic inactivation and rapid clearance from the circulation. Various GLP-1 analogs and bioconjugation of GLP-1 analogs have been developed to counter these issues, but these modifications are frequently accompanied by the sacrifice of potency and the induction of immunogenicity. Here, we demonstrated that with the conjugation of a zwitterionic polymer, poly(carboxybetaine) (pCB), the pharmacokinetic properties of native GLP-1 were greatly enhanced without serious negative effects on its potency and secondary structure. The pCB conjugated GLP-1 further provided glycemic control for up to 6 days in a mouse study. These results illustrate that the conjugation of pCB could realize the potential of using native GLP-1 for prolonged glycemic control in treating T2DM.

DNA-Programmed plasmonic ELISA for the ultrasensitive detection of protein biomarkers.

We report a novel DNA-programmed plasmonic enzyme-linked immunosorbent assay (ELISA) for the ultrasensitive detection of protein biomarkers with the naked eye. The DNA-programmed plasmonic assay was based on two enzyme-free and isothermal nucleic acid amplification methods: hybridization chain reaction (HCR) and catalyzed hairpin assembly (CHA). In this study, a biotin-labeled DNA probe was utilized insteand of an enzyme-label probe in well-developed ELISA method. The biotin-labeled DNA probe was able to trigger the HCR and CHA processes, and the products could hybridize with DNA-modified gold nanoparticles (AuNPs) to induce the aggregation of the AuNPs and a color change in the solution. The developed method was able to detect as low as 1 pg mL-1 PSA target with the naked eye. Clinical serum samples demonstrated satisfactory results, indicating that the method is useful for early diagnostics and monitoring curative effects after a medical treatment. The developed method presents a simple and portable platform for ultrasensitive protein detection and has potential for point-of-care (POC) diagnostics in less developed areas.

The Hidden Heroes: Holes in Charge-Driven Desorption Mass Spectrometry.

Photoexcited hot carriers have high impacts on various fields. However, in contrast to the attention attracted by the hot-electrons, the contributions of holes are seldom recognized. Yet, by simply removing the hot-electrons but retaining the holes on the surface of photoexcited plasmonic gold nanoparticles, a 60-fold ion intensity amplification could be achieved in laser desorption ionization mass spectrometry. A new desorption mechanism termed "charge-driven desorption" has been derived to rationalize the significant improvement.

Plasmonic gold nanoparticles as multifaceted probe for tissue imaging.

The localized surface plasmon resonance property of gold nanoparticles enables their application as a versatile and sensitive imaging probe, with intense colour, enhanced fluorescence and strong MS ion intensity for biological tissue imaging.

Plasmonic metal nanoparticles as efficient mass tags for ion signal amplification and ultrasensitive detection of protein markers.

The development of sensitive and specific analytical methods is critical for the discovery of molecular biomarkers, which assists disease diagnosis and understanding biological processes. Herein, a highly sensitive method is developed using antibody-conjugated plasmonic metal nanoparticles for the detection of targeted biomarkers down to low attomole level via coupling of immunoassay techniques with laser ionization mass spectrometry (LI-MS). The conjugated antibodies target specific antigens, while the metal nanoparticles act as mass tags and ion reservoirs for the signal amplification. With the characteristic localized surface plasmon resonance (LSPR) properties, gold (AuNPs) and silver nanoparticles (AgNPs) undergo explosive ionization upon laser irradiation to generate abundant characteristic mass reporter ions for strong MS signal amplification. With the antibody-conjugated NPs, detection of trace proteins in various biological samples with complex matrix environment, including urine, cell lysates, and animal tissues was demonstrated.

Exploring the effects of methylene blue on amyloid fibrillogenesis of lysozyme.

The 129-residue lysozyme has been shown to form amyloid fibrils in vitro. While methylene blue (MB), a compound in the phenothiazinium family, has been shown to dissemble tau fibril formation, its anti-fibrillogenic effect has not been thoroughly characterized in other proteins/peptides. This study examines the effects of MB on the in vitro fibrillogenesis of lysozyme at pH 2.0 and 55 °C. Our results demonstrated that, upon 7-day incubation, the plateau ThT fluorescence of the sample was found to be ~8.69% or ~2.98% of the control when the molar ratio of lysozyme to MB was at 1:1.11 or 1:3.33, respectively, indicating that the inhibitory potency of MB against lysozyme fibrillogenesis is positively correlated with its concentration. We also found that MB is able to destabilize the preformed lysozyme fibrils. Moreover, molecular docking and molecular dynamics simulations results revealed that MB's mechanism of fibril formation inhibition may be triggered by binding with lysozyme's aggregation-prone region. Results reported here provide solid support for MB's effect on amyloid fibrillogenesis. We believe the additional insights gained herein may pave way to the discovery of other small molecules that may have similar action toward amyloid fibril formation and its associated diseases.

Fenugreek Compound (N55) Lowers Plasma Glucose through the Enhancement of Response of Physiological Glucagon-like peptide-1.

Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) analogues are approved for treating type 2 diabetes, but are known to activate GLP-1R signaling globally and constitutively. Active compound N55, previously isolated from fenugreek, enhances the potency of GLP-1 without activating GLP-1R. Here we investigated if N55 lowers plasma glucose base on physiological levels of GLP-1. N55 was found to dose-dependently lower plasma glucose in non-fasted mice but not in the fasted mice, with the effect attenuated by GLP-1R antagonist exendin-(9-39) (Ex-9). On the other hand, when co-administered with dipeptidyl peptidase-IV (DPP4) -resistant [Aib8]-GLP-1(7-36) amide (GLP-1'), hypoglycemic response to N55 was observed in the fasted mice. This enhancement was also found to display dose dependency. N55 enhancement of the hypoglycemic and insulinotropic action of GLP-1' was eliminated upon Ex-9 treatment. Both exendin-4 (Ex-4) and DPP4-resistant GLP-1 mutant peptide ([Aib8, E22, E30]-GLP-1(7-36) amide) activated GLP-1R and improved glucose tolerance but the enhancement effect of N55 was not observed in vivo or in vitro. In conclusions, N55 lowers plasma glucose according to prandial status by enhancing the response of physiological levels of GLP-1 and is much less likely to disrupt tight regulation of GLP-1R signaling as compare to GLP-1 analogues.

Silver-gold alloy nanoparticles as tunable substrates for systematic control of ion-desorption efficiency and heat transfer in surface-assisted laser desorption/ionization.

Systematically controlling heat transfer in the surface-assisted laser desorption/ionization (SALDI) process and thus enhancing the analytical performance of SALDI-MS remains a challenging task. In the current study, by tuning the metal contents of Ag-Au alloy nanoparticle substrates (AgNPs, Ag55Au45NPs, Ag15Au85NPs and AuNPs, ∅: ∼2.0 nm), it was found that both SALDI ion-desorption efficiency and heat transfer can be controlled in a wide range of laser fluence (21.3 mJ cm-2 to 125.9 mJ cm-2). It was discovered that ion detection sensitivity can be enhanced at any laser fluence by tuning up the Ag content of the alloy nanoparticle, whereas the extent of ion fragmentation can be reduced by tuning up the Au content. The enhancement effect of Ag content on ion desorption was found to be attributable to the increase in laser absorption efficiency (at 355 nm) with Ag content. Tuning the laser absorption efficiency by changing the metal composition was also effective in controlling the heat transfer from the NPs to the analytes. The laser-induced heating of Ag-rich alloy NPs could be balanced or even overridden by increasing the Au content of NPs, resulting in the reduction of the fragmentation of analytes. In the correlation of experimental measurement with molecular dynamics simulation, the effect of metal composition on the dynamics of the ion desorption process was also elucidated. Upon increasing the Ag content, it was also found that phase transition temperatures, such as melting, vaporization and phase explosion temperature, of NPs could be reduced. This further enhanced the desorption of analyte ions via phase-transition-driven desorption processes. The significant cooling effect on the analyte ions observed at high laser fluence was also determined to be originated from the phase explosion of the NPs. This study revealed that the development of alloy nanoparticles as SALDI substrates can constitute an effective means for the systematic control of ion-desorption efficiency and the extent of heat transfer, which could potentially enhance the analytical performance of SALDI-MS.

Nrf2 mediates the protective effects of homocysteine by increasing the levels of GSH content in HepG2 cells.

Homocysteine (Hcy) and glutathione (GSH) are crucial reduction­oxidation mediators. The underlying mechanisms governing the effects of Hcy on GSH generation in the progression of alcoholic liver disease has so far received little attention. The present study hypothesized that the antioxidant transcriptional factor nuclear factor (erythroid­derived 2)­like 2 (Nrf2) may participate in Hcy­mediated regulation of GSH production in HepG2 human liver cancer cells. MTT assay was used to study the cytotoxicity of homocysteine, western blot analysis and immunofluorescence staining were used to determine the effect of Hcy on Nrf2 expression. Our data demonstrated that HepG2 cells exposed to exogenous levels of Hcy (0­100 µM) exhibited elevated GSH levels in a concentration­dependent manner. Furthermore, 4­hydroxynonenal (4­HNE)­induced cell injury was attenuated by Hcy; however, this protective effect was blocked by the GSH­production inhibitor buthionine sulfoximine. Hcy treatment was able to induce Nrf2 protein expression in HepG2 cells. Treatment with the Nrf2 activator tert­butylhydroquinone (0­100 µM) increased GSH expression in a concentration­dependent manner; however, Nrf2­siRNA abolished the Hcy­induced increase in GSH expression and cellular protection in 4­HNE­stressed HepG2 cells. In conclusion, the antioxidant transcriptional factor Nrf2 was demonstrated to mediate the Hcy­induced increase in GSH expression levels and cellular protection in HepG2 cells.