The development of high-performance near-infrared organic light-emitting diodes is hindered by strong non-radiative processes as governed by the energy gap law. Here, we show that exciton ...delocalization, which serves to decouple the exciton band from highly vibrational ladders in the S0 ground state, can bring substantial enhancements in the photoluminescence quantum yield of emitters, bypassing the energy gap law. Experimental proof is provided by the design and synthesis of a series of new Pt(ii) complexes with a delocalization length of 5–9 molecules that emit at 866–960 nm with a photoluminescence quantum yield of 5–12% in solid films. The corresponding near-infrared organic light-emitting diodes emit light with a 930 nm peak wavelength and a high external quantum efficiency up to 2.14% and a radiance of 41.6 W sr−1 m−2. Both theoretical and experimental results confirm the exciton–vibration decoupling strategy, which should be broadly applicable to other well-aligned molecular solids.Pt(ii) complexes allow the fabrication of efficient near-infrared organic light-emitting diodes that operate beyond the 900 nm region.
Taking advantage of outstanding precision in target recognition and trans-cleavage ability, the recently discovered CRISPR/Cas12a system provides an alternative opportunity for designing fluorescence ...biosensors. To fully exploit the analytical potential, we introduce here some meaningful concepts. First, the collateral cleavage of CRISPR/Cas12a is efficiently activated in a functional DNA regulation manner and the bottleneck which largely applicable to nucleic acids detection is broken. After selection of a representative aptamer and DNAzyme as the transduction pathways, the sensing coverage is extended to a small organic compound (ATP) and a metal ion (Na+). The assay sensitivity is significantly improved by utilizing a bead-supported enrichment strategy wherein emerging holographic optical tweezers are used to enhance imaging stability and simultaneously achieve multiflux analysis. Last, a sandwich-structured energy-concentrating upconversion nanoparticle triggered boosting luminescent resonance energy transfer mode is comined to face with complicated biological samples by skillfully confining the emitters into a very limited inner shell. Following the above attempts, the developed CRISPR/Cas12a biosensors not only present an ultrasensitive assay behavior toward these model non-nucleic acid analytes but also can serve as a formidable toolbox for determining real samples including single cell lysates and human plasma, proving a good practical application capacity.
The further development of high-performance fluorescent biosensors to image intracellular microRNAs is beneficial to cancer medicine. By virtue of the need for enzymes and hairpin DNA probes, the ...entropy-driven reaction-assisted signal amplification strategy has shown an enormous potential to accomplish this task. Nevertheless, this good option still meets with poor biostability, low cell uptake efficiency, and unsatisfactory accuracy. On the basis of these challenges, we put forward here a battery of solving pathways. First, the straight DNA probes are anchored onto the vertexes of dual DNA tetrahedrons, and thus the enzyme resistance of the whole sensing system is observably enhanced. A metal–organic framework (ZIF-8 nanoparticle), which can be effectively dissociated into a weakly acidic environment, then is employed as an additional delivery vehicle to encapsulate such a DNA tetrahedron sustained biosensor and finally bring about a more efficient endocytosis. Last, a kind of photocleavage-linker triggered photoresponsive manner is incorporated to achieve an exceptional precise target identification, by which the biosensor can only be initiated under the irradiation of an externally mild 365 nm ultraviolet light source. In accordance with the above efforts, worthy assay performance toward microRNA-196a has given rise to this newly constructed biosensor, whose sensitivity is down to 2.7 pM and also able to distinguish single-base variation. Beyond that, the amplifier can work as a powerful imaging toolbox to accurately determine the targets in living cells, providing a promising intracellular sensing platform.
Apart from gene editing capacity, the newly discovered CRISPR/Cas systems offer an exciting option for biosensing field because of their excellent target recognition accuracy. However, the currently ...constructed sensors are not only limited to nucleic acid analysis but also suffer from poor adaptability in complex samples and unsatisfying sensitivity. We herein introduce some advanced concepts to break through these bottlenecks. First, the sensing targets are extended by skillfully designing a functional DNA such as aptamer (for protein) and DNAzyme (for metal ion) to regulate the transduction of non-nucleic acid species and further activate the trans cleavage of CRISPR/Cas12a. Second, a boosting upconversion luminescent resonance energy is triggered by using a peculiar energy-confining notion, whereby the luminescence domain is intensively restricted in a very narrow space (~2.44 nm) and up to 92.9% of the green emission can be quenched by the approaching BHQ-1 modified reporters. Third, a bio-inspired periodic arrangement biomimetic chip (photonic crystal) is employed to selectively reflect the upconversion luminescence to achieve noteworthy signal enhancement (~35-fold). By utilizing very simple detection devices (a 980 nm portable laser and a smartphone), the CRISPR/Cas12a biosensor shows commendable sensitivity and specificity toward model targets (ATP and Na+, limits of detection are ~ 18 nM and ~0.37 μM, respectively). More importantly, the analysis of real complex samples demonstrate that the as-proposed platform can work as a powerful toolbox for monitoring the ATP fluctuation in single cell and point-of-care testing Na+ in human plasma, enabling a broad application prospect.
•A functional DNA regulated transduction is introduced into CRISPR/Cas12a biosensor.•An energy-confining boosted upconversion LRET is constructed to face with complex samples.•A biomimetric chip is employed to simplify sensing devices and perform signal amplification.•Favorable assay performance toward model non-nucleic acid targets (ATP and Na+) are obtained.•Good sensing abilities toward single cell and human plasma are presented.
Exploring new electrochemiluminescence (ECL) luminophores with strong ECL emission is highly desirable for developing ultrasensitive ECL sensors. Herein, a pyrene-based hydrogen-bonded organic ...framework (Py-HOF) featuring prominent ECL performance was prepared by utilizing 1,3,6,8-tetrakis(p-benzoic acid) pyrene (H4TBAPy) with an aggregation-induced enhanced emission (AIEE) property as a building block, exhibiting a stronger ECL emission than those of H4TBAPy monomers, H4TBAPy aggregates, the low-porosity Py-HOF-210 °C and Py-HOF-180 °C. We have coined the term “the porosity- and aggregation-induced enhanced ECL (PAIE-ECL)” for this intriguing phenomenon. The Py-HOF displayed superb and stable ECL intensity, not only because the luminophore H4TBAPy was assembled into the Py-HOF via four pairs of O–H···O hydrogen bonds, which constrained the intramolecular movements to reduce nonradiative transition, but also because the H4TBAPy in Py-HOF was stacked in a slipped face-to-face mode to form J-aggregates that benefited the ECL enhancement. Furthermore, the high porosity of Py-HOF allowed the enrichment of coreactants and facilitated the migration of ions, electrons, and coreactants, which made it possible for the inner and outer H4TBAPy to be electrochemically excited. Considering the remarkable ECL performance, Py-HOF was first employed as an ECL probe combined with a 3D DNA nanomachine amplification strategy to assemble a hypersensitive “on–off” ECL sensor for the microRNA-141 assay, presenting a satisfactory linear range (100 aM to 1 nM) with a detection limit of 14.4 aM. The PAIE-ECL manifested by Py-HOF provided a bright avenue for the design and synthesis of outstanding HOF-based ECL materials and offered new opportunities for the development of ECL biosensors with excellent sensitivity.
Pulmonary fibrosis (PF) progression may be involved with arginine (Arg) metabolism and immune balance. The present study aimed to explore the effects of L-Arginine (L-Arg) and L-Norvaline (L-Nor) on ...bleomycin (BLM)-induced PF in mice, meanwhile, and observe dynamic changes of Arg metabolism, immune balance and crosstalk between them in PF progression. Followed intratracheal instillation of BLM or saline, Kunming mice were treated orally with saline, L-Arg, L-Nor and L-Arg + L-Nor three times a day. And the mice were sacrificed on Day 3, 14 and 28 after treatment. Changes of body weight, lung index, lung hydroxyproline and histopathology were analyzed to evaluate the PF degree. Peripheral blood Arg, Citrulline (Cit), Ornithine (Orn) and Proline (Pro), lung NO, NOS and arginase were analyzed to evaluate the Arg metabolism. Peripheral blood Tregs, Th17 and γδT cells were analyzed to evaluate the immune balance. Our data showed that combination of L-Arg and L-Nor dynamically reversed the weight loss, decreased lung index and hydroxyproline, and improved lung histopathological damages induced by BLM. The combination dynamically and significantly rectified Tregs, Th17, γδT and Tregs/Th17 abnormal changes. Meanwhile, these disorders of peripheral blood Arg, Cit, Orn, Pro, Orn/Cit and Pro/Orn, and lung NO, iNOS and TNOS were also improved accordingly. These results demonstrated that combination of L-Arg and L-Nor had inhibitory effects on BLM-induced PF progression, possibly due to their corrective action on immune imbalance, Arg metabolism disorder and crosstalk abnormality in the progression of PF.
Although the recently found CRISPR/Cas12a system is a promising choice to significantly enhance the analytical accuracy and the construction flexibility of fluorescent biosensors, the traditional ...“one-to-one” mediation type and the short of effective target transduction routes can lead to a difficulty in improving sensitivity and detecting non-DNA analytes, respectively. In response to these challenging problems, we present here an exceptional and universal DNA walker amplified “one-to-many” CRISPR/Cas12a-mediated fluorescent biosensor. For this design, a nicking endonuclease is selected as the energy supply to drive an efficient walking process on the surface of a small size magnetic nanosphere. With the release of abundant activators, many CRISPR/Cas12a systems will be activated and finally trans-cleave a large number of reporters to actualize signal amplification. To extend the sensing species, a strand displacement and an aptamer competition triggered target transduction strategies are conceptually proposed. After using a photonic crystal coated biochip to further amplify the fluorescence emission, the newly-raised assay method can be successfully employed to severally determine a liver injury associated biomarker (microRNA-122) and a broad-spectrum tumor biomarker (carcinoembryonic antigen) by just a simple smartphone assisted imaging in an ultrasensitive and highly-specific manner. Moreover, our approach is capable of precisely measuring these targets in clinical human plasmas and also offer useful diagnostic information for drug-induced liver injury and lung cancer, greatly boosting the practical application ability of CRISPR based biosensors.
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•An exceptional DNA walker amplified “one-to-many” CRISPR/Cas12a-mediated fluorescent biosensor is proposed.•A strand displacement and an aptamer competition triggered target transduction strategies are designed to non-DNA biomarkers.•The conceptual biosensors own ultra-sensitivity by further using a photonic crystal coated biochip.•This assay method can precisely measure the targets in clinical human plasmas for disease diagnosis.
Background
We aimed to analyze the differences in the peripheral blood cells and tumor biomarkers between the patients with endometriosis and healthy people, and establish a more efficient combined ...diagnostic model.
Methods
We retrospectively analyzed the differences in the peripheral blood cells and tumor biomarkers between the patients with endometriosis and healthy people. Binary logistic regression analysis was used to establish a combined diagnostic model. We plotted the receiver operator characteristic (ROC) curve to analyze the diagnostic efficiency of different diagnostic indexes.
Results
Compared with patients in the control group, patients in the endometriosis group had significantly lower eosinophil% (p = 0.045), neutrophil (p = 0.001), lymphocyte (p < 0.001), red blood cells (RBCs) (p < 0.001), and hemoglobin (HGB) (p < 0.001), and had significantly higher monocyte% (p = 0.008), monocyte‐to‐lymphocyte ratio (MLR) (p = 0.001), platelet‐to‐lymphocyte ratio (PLR) (p < 0.001), carbohydrate antigen (CA)‐199 (p < 0.001), CA125 (p < 0.001), human epididymis protein (HE)‐4 (p < 0.001), and the risk of ovarian malignancy algorithm (ROMA) (p < 0.001). The combined diagnostic model of HGB, CA199, CA125, and HE4 was established by binary logistic regression analysis. The ROC curve showed that the combined diagnostic model reached a sensitivity of 85.4%, a specificity of 78.83%, and an area under the curve of 0.900, which was significantly higher than that of the individual index in endometriosis diagnosis.
Conclusion
The combined diagnostic model of HGB, CA199, CA125, and HE4 may provide a new approach for the early non‐invasive diagnosis of endometriosis.
This study retrospectively analyzed the differences in the peripheral blood cells and their derivative parameters and tumor biomarkers between the patients with endometriosis and healthy people, and established a more efficient combined diagnostic model based on HGB, CA199, CA125, and HE4. The combined diagnostic model reached a sensitivity of 85.4%, a specificity of 78.83%, and an area under the curve of 0.900, which may provide a novel approach for the early non‐invasive diagnosis of endometriosis.
miR-34a is an important tumor suppressor gene in various cancer types. But little is known about the dysregulation of miR-34a in tongue squamous cell carcinoma (TSCC). In this study, we investigate ...the expression and potential role of miR-34a in TSCC.
We evaluated miR-34a expression and its relationship with clinicopathological characters in 75 pairs of TSCC samples, and confirmed the role of miR-34a for predicting lymph node metastases from a further 15 pairs of paraffin-embedded TSCC specimens with stringent clinicopathological recruitment criteria using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effects of miR-34a on cell proliferation, migration and invasion were examined in TSCC cell lines using Cell Counting Kit-8 assay, wound healing assay and transwell assay, respectively. The effects of miR-34a on the expression of matrix metalloproteinase (MMP) 9 and 14 were detected by luciferase reporter assays and Western blot analysis. The expression of miR-34a, MMP9 and MMP14 were also confirmed in TSCC samples by in situ hybridization and immunohistochemistry.
miR-34a expression in tumor tissues from TSCC patients with positive lymph node metastases was significantly lower than that with negative lymph node metastases. Overexpression of miR-34a significantly suppressed migration and invasion in TSCC cells and simultaneously inhibited the expression of MMP9 and MMP14 through targeting the coding region and the 3'untranslated region, respectively. Moreover, miR-34a expression in TSCC was inversely correlated with protein expression of MMP9 and MMP14 in the TSCC samples.
miR-34a plays an important role in lymph node metastases of TSCC through targeting MMP9 and MMP14 and may have potential applications in prognosis prediction and gene therapy for lymph node metastases of TSCC patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Polycyclic aromatic hydrocarbons (PAHs) are classic electrochemiluminescence (ECL) materials. However, the ECL performance of PAHs aggregates in water phase is limited owing to the ...aggregation-induced quenching (ACQ) effect of PAHs. To surmount this shortcoming, we proposed an innovative strategy for enhancing the ECL performance by assembling PAH derivative ligands into metal-organic framework nanosheets (MONs), which can separate ACQphores to eliminate the ACQ effect. Gratifyingly, the ECL intensity of Hf-DEADB MON (DEADB = 4,4′-(diethylanthracene-9,10-diyl)dibenzoate) prepared according to the strategy was 5.71-fold higher than that of H2DEADB aggregates. This improvement occurred not only because the distance between the ACQphores in the Hf-DEADB MON was enlarged to surmount the ACQ effect but also because the ultrathin porous Hf-DEADB MON could shorten the diffusion pathways of ion/electron and co-reactant, which boosted electrochemical activation of DEADB luminophores. Given the prominent ECL performance of Hf-DEADB MON, it was used to fabricate a hypersensitive biosensor for detecting microRNA-21, displaying a broad response range (100 aM–10 nM) with an ultralow detection limit (24 aM). Overall, our work developed a promising strategy to eradicate the ACQ effect of PAHs for ECL enhancement, thus pointing out a new direction to design high-efficient ECL materials for constructing ultrasensitive ECL sensors.
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•This work proposed a new strategy to conquer the ACQ effect of PAHs.•A high-performing MON-based ECL material was constructed.•This work provided an effective strategy to design high-efficient ECL materials.•The designed ECL sensor achieved ultrasensitive detection of miRNA-21.
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