Continuous-wave and SESAM mode-locked operation of a Yb:YSr3(PO4)3 laser.

We report on the continuous-wave (CW) and, for what we believe to be the first time, passively mode-locked (ML) laser operation of an Yb3+-doped YSr3(PO4)3 crystal. Utilizing a 976-nm spatially single-mode, fiber-coupled laser diode as pump source, the Yb:YSr3(PO4)3 laser delivers a maximum CW output power of 333 mW at 1045.8 nm with an optical efficiency of 55.7% and a slope efficiency of 60.9%. Employing a quartz-based Lyot filter, an impressive wavelength tuning range of 97 nm at the zero level was achieved in the CW regime, spanning from 1007 nm to 1104 nm. In the ML regime, incorporating a commercially available semiconductor saturable absorber mirror (SESAM) to initiate and maintain soliton-like pulse shaping, the Yb:YSr3(PO4)3 laser generated pulses as short as 61 fs at 1062.7 nm, with an average output power of 38 mW at a repetition rate of ∼66.7 MHz.

SESAM mode-locked Yb:GdScO3 laser.

We report on the investigation of continuous-wave (CW) and SEmiconductor Saturable Absorber Mirror (SESAM) mode-locked operation of a Yb:GdScO3 laser. Using a single-transverse-mode, fiber-coupled InGaAs laser diode at 976 nm as a pump source, the Yb:GdScO3 laser delivers 343 mW output power at 1062 nm in the CW regime, which corresponds to a slope efficiency of 52%. Continuous tuning is possible across a wavelength range of 84 nm (1027-1111 nm). Using a commercial SESAM to initiate mode-locking and stabilize soliton-type pulse shaping, the Yb:GdScO3 laser produces pulses as short as 42 fs at 1065.9 nm, with an average output power of 40 mW at 66.89 MHz. To the best of our knowledge, this is the first demonstration of passively mode-locking with Yb:GdScO3 crystal.

Growth, spectroscopy and laser operation of Tm,Ho:GdScO3 perovskite crystal.

We report on the growth, polarized spectroscopy and first laser operation of an orthorhombic (space group Pnma) Tm3+,Ho3+-codoped gadolinium orthoscandate (GdScO3) perovskite-type crystal. A single crystal of 3.76 at.% Tm, 0.35 at.% Ho:GdScO3 was grown by the Czochralski method. Its polarized absorption and fluorescence properties were studied revealing a broadband emission around 2 µm. The parameters of the Tm3+ ↔ Ho3+ energy transfer was quantified, P28 = 1.30 × 10-22 cm3µs-1, and P71 = 0.99 × 10-23 cm3µs-1, and the thermal equilibrium lifetime was measured to be 3.5 ms. The crystal-field splitting of Tm3+ and Ho3+ multiplets in Cs symmetry sites of the perovskite structure was determined by low-temperature spectroscopy and the mechanism of spectral line broadening is discussed. The continuous-wave Tm,Ho:GdScO3 laser generated 1.16 W at ∼2.1 µm with a slope efficiency of 50.5%, a laser threshold of 184 mW, a linear laser polarization (E || c) and a spatially single-mode output. The Tm,Ho:GdScO3 crystal is promising for broadly tunable and femtosecond mode-locked lasers emitting above 2 µm.

Growth, spectroscopy and SESAM mode-locking of a "mixed" Yb:Ca(Gd,Y)AlO4 disordered crystal.

We present the growth, spectroscopy, continuous-wave (CW) and passively mode-locked (ML) operation of a novel "mixed" tetragonal calcium rare-earth aluminate crystal, Yb3+:Ca(Gd,Y)AlO4. The absorption, stimulated-emission, and gain cross-sections are derived for π and σ polarizations. The laser performance of a c-cut Yb:Ca(Gd,Y)AlO4 crystal is studied using a spatially single-mode, 976-nm fiber-coupled laser diode as a pump source. A maximum output power of 347 mW is obtained in the CW regime with a slope efficiency of 48.9%. The emission wavelength is continuously tunable across 90 nm (1010 - 1100 nm) using a quartz-based Lyot filter. With a commercial SEmiconductor Saturable Absorber Mirror to initiate and maintain ML operation, soliton pulses as short as 35 fs are generated at 1059.8 nm with an average output power of 51 mW at ∼65.95 MHz. The average output power can be scaled to 105 mW for slightly longer pulses of 42 fs at 1063.5 nm.

SlPHL1 positively modulates acid phosphatase in response to phosphate starvation by directly activating the genes SlPAP10b and SlPAP15 in tomato.

Increased acid phosphatase (APase) activity is a prominent feature of tomato (Solanum lycopersicum) responses to inorganic phosphate (Pi) restriction. SlPHL1, a phosphate starvation response (PHR) transcription factor, has been identified as a positive regulator of low Pi (LP)-induced APase activity in tomato. However, the molecular mechanism underlying this regulation remains to be elucidated. Here, SlPHL1 was found to positively regulate the LP-induced expression of five potential purple acid phosphatase (PAP) genes, namely SlPAP7, SlPAP10b, SlPAP12, SlPAP15, and SlPAP17b. Furthermore, we provide evidence that SlPHL1 can stimulate transcription of these five genes by binding directly to the PHR1 binding sequence (P1BS) located on their promoters. The P1BS mutation notably weakened SlPHL1 binding to the promoters of SlPAP7, SlPAP12, and SlPAP17b but almost completely abolished SlPHL1 binding to the promoters of SlPAP10b and SlPAP15. As a result, the transcriptional activation of SlPHL1 on SlPAP10b and SlPAP15 was substantially diminished. In addition, not only did transient overexpression of either SlPAP10b or SlPAP15 in tobacco leaves increase APase activity, but overexpression of SlPAP15 in Arabidopsis and tomato also increased APase activity and promoted plant growth. Subsequently, two SPX proteins, SlSPX1 and SlSPX4, were shown to physically interact with SlPHL1. Moreover, SlSPX1 inhibited the transcriptional activation of SlPHL1 on SlPAP10b and SlPAP15 and negatively regulated the activity of APase. Taken together, these results demonstrate that SlPHL1-mediated LP signaling promotes APase activity by activating the transcription of SlPAP10b and SlPAP15, which may provide valuable insights into the mechanisms of tomato response to Pi-limited stress.

Simple, sensitive, colorimetric detection of pyrophosphate via the analyte-triggered decomposition of metal-organic frameworks regulating their adaptive multi-color Tyndall effect.

This paper describes initially the application of the Tyndall effect (TE) of metal-organic framework (MOF) materials as a colorimetric signaling strategy for the sensitive detection of pyrophosphate ion (PPi). The used MOF NH2-MIL-101(Fe) was prepared with Fe3+ ions and fluorescent ligands of 2-amino terephthalic acid (NH2-BDC). The fluorescence of NH2-BDC in MOF is quenched due to the ligand-to-metal charge transfer effect, while the NH2-MIL-101(Fe) suspension shows a strong TE. In the presence of PPi analyte, the MOFs will undergo decomposition because of the competitive binding of Fe3+ by PPi over NH2-BDC, resulting in a significant decrease in the TE signal and fluorescence restoration from the released ligands. The results demonstrate that the new method only requires a laser pointer pen (for TE creation) and a smartphone (for portable quantitative readout) to detect PPi in a linear concentration range of 1.25-800 µM, with a detection limit of ~210 nM (3σ) which is ~38 times lower than that obtained from traditional fluorescence with a spectrophotometer (linear concentration range, 50-800 µM; detection limit, 8.15 µM). Moreover, the acceptable recovery of PPi in several real samples (i.e., pond water, black tea, and human serum and urine) ranges from 97.66 to 119.15%.

Single-step batch fabrication of microfluidic paper-based analytical devices with a 3D printer and their applications in nanoenzyme-enhanced visual detection of dopamine.

Wax printing is the most widely used method for fabricating microfluidic paper-based analytical devices (µPADs), but it still suffers from disadvantages like discontinuation of wax printers and need for additional equipment for heating treatment. To address these issues, this work initially describes a new class of wax printing approach for high-precision, batch fabrication of µPADs using a household 3D printer. It only involves a one patterning step of printing polyethylene wax into rice paper body. Under optimized parameters, a fabrication resolution, namely the minimum hydrophilic channel width, down to ~189 ± 30 µm could be achieved. In addition, the analytical applicability of such polyethylene wax-patterned µPADs was demonstrated well with enhanced colorimetric detection of dopamine as a model analyte by combining metal-organic framework (MOF) based nanoenzymes (ZIF-67) with a smartphone (for portable quantitative readout). The developed nanosensor could linearly detect dopamine over a concentration range from 10 to 1000 µM, with a detection limit of ca. 2.75 µM (3σ). The recovery results for analyzing several real samples (i.e., pig feed, chicken feed, pork and human serum) were between 91.82 and 102.79%, further validating its good detection accuracy for potential practical applications in food safety and medical diagnosis.

Spatiotemporal dynamics of functional connectivity and association with molecular architecture in schizophrenia.

Schizophrenia is a self-disorder characterized by disrupted brain dynamics and architectures of multiple molecules. This study aims to explore spatiotemporal dynamics and its association with psychiatric symptoms. Resting-state functional magnetic resonance imaging data were collected from 98 patients with schizophrenia. Brain dynamics included the temporal and spatial variations in functional connectivity density and association with symptom scores were evaluated. Moreover, the spatial association between dynamics and receptors/transporters according to prior molecular imaging in healthy subjects was examined. Patients demonstrated decreased temporal variation and increased spatial variation in perceptual and attentional systems. However, increased temporal variation and decreased spatial variation were revealed in higher order networks and subcortical networks in patients. Specifically, spatial variation in perceptual and attentional systems was associated with symptom severity. Moreover, case-control differences were associated with dopamine, serotonin and mu-opioid receptor densities, serotonin reuptake transporter density, dopamine transporter density, and dopamine synthesis capacity. Therefore, this study implicates the abnormal dynamic interactions between the perceptual system and cortical core networks; in addition, the subcortical regions play a role in the dynamic interaction among the cortical regions in schizophrenia. These convergent findings support the importance of brain dynamics and emphasize the contribution of primary information processing to the pathological mechanism underlying schizophrenia.

Diet and lifestyle behaviours simultaneously act on frailty: it is time to move the threshold of frailty prevention and control forward.

BACKGROUND: To analyse the association among the simultaneous effects of dietary intake, daily life behavioural factors, and frailty outcomes in older Chinese women, we predicted the probability of maintaining physical robustness under a combination of different variables. METHODS: The Fried frailty criterion was used to determine the three groups of "frailty", "pre-frailty", and "robust", and a national epidemiological survey was performed. The three-classification decision tree model was fitted, and the comprehensive performance of the model was evaluated to predict the probability of occurrence of different outcomes. RESULTS: Among the 1,044 participants, 15.9% were frailty and 50.29% were pre-frailty; the overall prevalence first increased and then decreased with age, reaching a peak at 70-74 years of age. Through univariate analysis, filtering, and embedded screening, eight significant variables were identified: staple food, spices, exercise (frequency, intensity, and time), work frequency, self-feeling, and family emotions. In the three-classification decision tree, the values of each evaluation index of Model 3 were relatively average; the accuracy, recall, specificity, precision, and F1 score range were between 75% and 84%, and the AUC was also greater than 0.800, indicating excellent performance and the best interpretability of the results. Model 3 takes exercise time as the root node and contains 6 variables and 10 types, suggesting the impact of the comprehensive effect of these variables on robust and non-robust populations (the predicted probability range is 6.67-93.33%). CONCLUSION: The combined effect of these factors (no exercise or less than 0.5 h of exercise per day, occasional exercise, exercise at low intensity, feeling more tired at work, and eating too many staple foods (> 450 g per day) are more detrimental to maintaining robustness.

Probing the Limits to Near-Field Heat Transfer Enhancements in Phonon-Polaritonic Materials.

Near-field radiative heat transfer (NFRHT) arises between objects separated by nanoscale gaps and leads to dramatic enhancements in heat transfer rates compared to the far-field. Recent experiments have provided first insights into these enhancements, especially using silicon dioxide (SiO2) surfaces, which support surface phonon polaritons (SPhP). Yet, theoretical analysis suggests that SPhPs in SiO2 occur at frequencies far higher than optimal. Here, we first show theoretically that SPhP-mediated NFRHT, at room temperature, can be 5-fold larger than that of SiO2, for materials that support SPhPs closer to an optimal frequency of 67 meV. Next, we experimentally demonstrate that MgF2 and Al2O3 closely approach this limit. Specifically, we demonstrate that near-field thermal conductance between MgF2 plates separated by 50 nm approaches within nearly 50% of the global SPhP bound. These findings lay the foundation for exploring the limits to radiative heat transfer rates at the nanoscale.

Endogenous Hormone Levels and Transcriptomic Analysis Reveal the Mechanisms of Bulbil Initiation in Pinellia ternata.

Pinellia ternata is a medicinal plant that has important pharmacological value, and the bulbils serve as the primary reproductive organ; however, the mechanisms underlying bulbil initiation remain unclear. Here, we characterized bulbil development via histological, transcriptomic, and targeted metabolomic analyses to unearth the intricate relationship between hormones, genes, and bulbil development. The results show that the bulbils initiate growth from the leaf axillary meristem (AM). In this stage, jasmonic acid (JA), abscisic acid (ABA), isopentenyl adenosine (IPA), and salicylic acid (SA) were highly enriched, while indole-3-acetic acid (IAA), zeatin, methyl jasmonate (MeJA), and 5-dexoxystrigol (5-DS) were notably decreased. Through OPLS-DA analysis, SA has emerged as the most crucial factor in initiating and positively regulating bulbil formation. Furthermore, a strong association between IPA and SA was observed during bulbil initiation. The transcriptional changes in IPT (Isopentenyltransferase), CRE1 (Cytokinin Response 1), A-ARR (Type-A Arabidopsis Response Regulator), B-ARR (Type-B Arabidopsis Response Regulator), AUX1 (Auxin Resistant 1), ARF (Auxin Response Factor), AUX/IAA (Auxin/Indole-3-acetic acid), GH3 (Gretchen Hagen 3), SAUR (Small Auxin Up RNA), GA2ox (Gibberellin 2-oxidase), GA20ox (Gibberellin 20-oxidase), AOS (Allene oxide synthase), AOC (Allene oxide cyclase), OPR (Oxophytodienoate Reductase), JMT (JA carboxy l Methyltransferase), COI1 (Coronatine Insensitive 1), JAZ (Jasmonate ZIM-domain), MYC2 (Myelocytomatosis 2), D27 (DWARF27), SMAX (Suppressor of MAX2), PAL (Phenylalanine Ammonia-Lyase), ICS (Isochorismate Synthase), NPR1 (Non-expressor of Pathogenesis-related Genes1), TGA (TGACG Sequence-specific Binding), PR-1 (Pathogenesis-related), MCSU (Molybdenium Cofactor Sulfurase), PP2C (Protein Phosphatase 2C), and SnRK (Sucrose Non-fermenting-related Protein Kinase 2) were highly correlated with hormone concentrations, indicating that bulbil initiation is coordinately controlled by multiple phytohormones. Notably, eight TFs (transcription factors) that regulate AM initiation have been identified as pivotal regulators of bulbil formation. Among these, WUS (WUSCHEL), CLV (CLAVATA), ATH1 (Arabidopsis Thaliana Homeobox Gene 1), and RAX (Regulator of Axillary meristems) have been observed to exhibit elevated expression levels. Conversely, LEAFY demonstrated contrasting expression patterns. The intricate expression profiles of these TFs are closely associated with the upregulated expression of KNOX(KNOTTED-like homeobox), suggesting a intricate regulatory network underlying the complex process of bulbil initiation. This study offers a profound understanding of the bulbil initiation process and could potentially aid in refining molecular breeding techniques specific to P. ternata.

Kerr-lens mode-locking of an Yb:CLNGG laser.

We report on a Kerr-lens mode-locked laser based on an Yb3+-doped disordered calcium lithium niobium gallium garnet (Yb:CLNGG) crystal. Pumping by a spatially single-mode Yb fiber laser at 976 nm, the Yb:CLNGG laser delivers soliton pulses as short as 31 fs at 1056.8 nm with an average output power of 66 mW and a pulse repetition rate of ∼77.6 MHz via soft-aperture Kerr-lens mode-locking. The maximum output power of the Kerr-lens mode-locked laser amounted to 203 mW for slightly longer pulses of 37 fs at an absorbed pump power of 0.74 W, which corresponds to a peak power of 62.2 kW and an optical efficiency of 20.3%.

Diode-pumped mode-locked Yb:Sc2SiO5 laser generating 38 fs pulses.

We report on sub-40 fs pulse generation from a Yb:Sc2SiO5 laser pumped by a spatially single-mode fiber-coupled laser diode at 976 nm. A maximum output power of 545 mW was obtained at 1062.6 nm in the continuous-wave regime, corresponding to a slope efficiency of 64% and a laser threshold of 143 mW. A continuous wavelength tuning across 80 nm (1030 -1110 nm) was also achieved. Implementing a SESAM for starting and stabilizing the mode-locked operation, the Yb:Sc2SiO5 laser delivered soliton pulses as short as 38 fs at 1069.5 nm with an average output power of 76 mW at a pulse repetition rate of ∼79.8 MHz. The maximum output power was scaled to 216 mW for slightly longer pulses of 42 fs, which corresponded to a peak power of 56.6 kW and an optical efficiency of 22.7%. To the best of our knowledge, these results represent the shortest pulses ever achieved with any Yb3+-doped rare-earth oxyorthosilicate crystal.

56-fs diode-pumped SESAM mode-locked Yb:YAl3(BO3)4 laser.

We report on the first sub-60 fs pulse generated from a diode-pumped SESAM mode-locked Yb-laser based on a non-centrosymmetric Yb:YAl3(BO3)4 crystal as a gain medium. In the continuous-wave regime, pumping with a spatially single-mode, fiber-coupled 976 nm InGaAs laser diode, the Yb:YAl3(BO3)4 laser generated 391 mW at 1041.7 nm with a slope efficiency as high as 65.1%, and a wavelength tuning across 59 nm (1019 to 1078 nm) was achieved. By implementing a commercial SESAM to initiate and sustain the soliton type mode-locking, and using only a 1 mm-thick laser crystal, the Yb:YAl3(BO3)4 laser delivered pulses as short as 56 fs at a central wavelength of 1044.6 nm with an average output power of 76 mW at a pulse repetition rate of ∼67.55 MHz. To the best of our knowledge, this result represents the shortest pulses ever achieved from Yb:YAB crystal.

Sub-50 fs diode-pumped SESAM mode-locked Yb:SrF2 laser.

We report on sub-50 fs pulse generation from a passively mode-locked Yb:SrF2 laser pumped with a spatially single-mode, fiber-coupled laser diode at 976 nm. In the continuous-wave regime, the Yb:SrF2 laser generated a maximum output power of 704 mW at 1048 nm with a threshold of 64 mW and a slope efficiency of 77.2%. A continuous wavelength tuning across 89 nm (1006 - 1095 nm) was achieved with a Lyot filter. By implementing a SEmiconductor Saturable Absorber Mirror (SESAM) for initiating and sustaining the mode-locked operation, soliton pulses as short as 49 fs were generated at 1057 nm with an average output power of 117 mW at a pulse repetition rate of ∼75.9 MHz. The maximum average output power of the mode-locked Yb:SrF2 laser was scaled up to 313 mW for slightly longer pulses of 70 fs at 1049.4 nm, corresponding to a peak power of 51.9 kW and an optical efficiency of 34.7%.

Experiences Shape Hippocampal Neuron Morphology and the Local Levels of CRHR1 and OTR.

The dorsal hippocampus is involved in behavioral avoidance regulation. It is unclear how experiences such as the neonatal stress of maternal deprivation (MD) and post-weaning environmental enrichment (EE) affect avoidance behavior and the dorsal hippocampal parameters, including neuronal morphology, corticotrophin-releasing hormone (CRH) signaling, and oxytocin receptor (OTR) level. In male BALB/c mice, we found that MD impaired avoidance behavior in the step-on test compared to non-MD and EE rearing conditions could alleviate that partially. MD increased neuronal branches in the CA1 but decreased synaptic connection levels in the CA2, CA3, and DG. Meanwhile, MD increased the CA1's OTR levels, which negatively correlated with nucleus densities. MD also increased the CA1's and CA2's CRH levels, which positively correlated with CRHR1 levels. However, MD statistically elevated the CA3's CRH receptor 1 (CRHR1) levels, which negatively correlated with nucleus densities and, probably, synaptic connection levels in the CA3. The additive effects of MD and EE maintained similar CRH levels and CRHR1 levels as well as OTR levels in the hippocampal areas as the additive of non-MD and non-EE. However, the presence of MD and EE still decreased the CA1's neuronal branches and the CA2's and DG's synaptic connection levels. The study illustrates how MD and EE affect avoidance behaviors, hippocampal neuron morphology, and CRH and OTR levels. The results indicate that the late-life environmental improvement partially restores the alterations in dorsal hippocampal areas induced by early life stress.

Big data on the prevalence of injury deaths among 187 488 elderly Chinese in the past 20 years (2000-2020): a systematic review and meta-analysis.

BACKGROUND: This study systematically reviewed injury death and causes in the elderly population in China from 2000 to 2020, to prevent or reduce the occurrence of injuries and death. METHODS: The CNKI, VIP, Wan Fang, MEDLINE, Embase, SinoMed, and Web of Science databases were searched to collect epidemiological characteristics of injury death among elderly over 60 years old in China from January 2000 to December 2020. Random effects meta-analysis was performed to pool injury mortality rate and identify publication bias, with study quality assessed using the AHRQ risk of bias tool. RESULTS: (1) A total of 41 studies with 187 488 subjects were included, covering 125 million elderly. The pooled injury mortality rate was 135.58/105 [95%CI: (113.36 to 162.14)/105], ranking second in the total death cause of the elderly. (2)Subgroup analysis showed that male injury death (146.00/105) was significantly higher than that of females (127.90/105), and overall injury mortality increased exponentially with age (R2 = 0.957), especially in those over 80 years old; the spatial distribution shows that the injury death rate in the central region is higher than that in the east and west and that in the countryside is higher than that in the city; the distribution of death time shows that after entering an aging society (2000-2020) is significantly higher than before (1990-2000). (3) There are more than 12 types of injury death, and the top three are falling, traffic accidents, and suicide. CONCLUSIONS: China's elderly injury death rate is at a high level in the world, with more males than females, especially after the age of 80. There are regional differences. The main types of injury death are falling, traffic, and suicide. During the 14th Five-Year Plan period, for accidental injuries and death, a rectification list for aging and barrier-free environments was issued. PROSPERO REGISTRATION: The systematic review was registered in PROSPERO under protocol number CRD42022359992.

Isolation of Structurally Heterogeneous TCR-CD3 Extracellular Vesicle Subpopulations Using Caliper Strategy.

Cells in different states can release diverse types of extracellular vesicles (EVs) that participate in intracellular communication or pathological processes. The identification and isolation of EV subpopulations are significant to explore their physiological functions and clinical value. In this study, structurally heterogeneous T-cell receptor (TCR)-CD3 EVs were proposed and verified for the first time using a caliper strategy. Two CD3-targeting aptamers were designed in the shape of a caliper with an optimized probe distance and were assembled on gold nanoparticles (Au-Caliper) to distinguish TCR-CD3 monomeric and dimeric EVs (m/dCD3 EVs) in skin-transplanted mouse plasma. Phenotyping and sequencing analysis revealed clear heterogeneity in the isolated m/dCD3 EVs, providing the potential for mCD3 EVs as a candidate biomarker of acute cellular rejection (ACR) and holding great prospects for distinguishing EV subpopulations based on protein oligomerization states.

Highly Efficient Isolation and Sensitive Detection of Small Extracellular Vesicles Using a Paper-Based Device.

Small extracellular vesicles (sEVs) play important roles in mediating intercellular communication and regulating biological processes. Facile sEV isolation is the essential and preliminary issue for their function investigation and downstream biomedical applications, while the traditional methods are challenged by tedious procedures, low purity, low yield, and potential damage. In this work, we developed an sEV isolation paper-based device (sEV-IsoPD) based on a three-dimensional (3D) paper chip, which is composed of a porous membrane for size exclusion and a metal-organic framework (MOF)/antibody-modified paper for immunoaffinity capture. In combination with a peristaltic pump-driven flow system, the sEV-IsoPD can efficiently isolate EV from cell culture medium and serum. Compared with the ultracentrifugation method, sEV-IsoPD exhibited a 5.1 times higher yield (1.7 × 109 mL-1), 1.6 times higher purity (1.6 × 1011 mg-1), and 7.5 times higher recovery (77.3%) with only 8.3% of the time (30 min) and 1.0% of the instrument cost ($710). Moreover, sEV concentration can be visually detected in a quantitative manner with this paper-based device with a linear range from 3.0 × 106 to 3.0 × 1010 mL-1 and a detection limit of 2.2 × 106 mL-1. The sEV-IsoPD provides an efficient and practical approach for the rapid isolation and visible detection of sEVs, which are promising for the preparation of sEVs and diagnosis of disease.

Dual-Locked DNAzyme Platform for In Vitro and In Vivo Discrimination of Cancer Cells.

Imaging of tumor-associated microRNAs (miRNAs) can provide abundant information for cancer diagnosis, whereas the occurrence of trace amounts of miRNAs in normal cells inevitably causes an undesired false-positive signal in the discrimination of cancer cells during miRNA imaging. In this study, we propose a dual-locked (D-locked) platform consisting of the enzyme/miRNA-D-locked DNAzyme sensor and the honeycomb MnO2 nanosponge (hMNS) nanocarrier for highly specific cancer cell imaging. For a proof-of-concept demonstration, apurinic/apyrimidinic endonuclease 1 (APE1) and miR-21 were chosen as key models. The hMNS nanocarrier can efficiently release the D-locked DNAzyme sensor in living cells due to the decomposition of hMNS by glutathione, which can also supply Mn2+ for DNAzyme cleavage. Ascribing to the smart design of the D-locked DNAzyme sensor, the fluorescence signal can only be generated by the synergistic response of APE1 and miR-21 that are overexpressed in cancer cells. Compared with the miRNA single-locked DNAzyme sensor and the small-molecule (ATP)/miRNA D-locked DNAzyme sensor, the proposed enzyme (APE1)/miRNA D-locked DNAzyme sensor exhibited 2.6-fold and 2.4-fold higher discrimination ratio (Fcancer/Fnormal) for cancer cell discrimination, respectively. Owing to the superior performance, the D-locked strategy can selectively generate a fluorescence signal in cancer cells, facilitating accurate discrimination of cancer both in vitro and in vivo. Furthermore, this D-locked platform is easily adaptable toward other target molecules by redesigning the DNA sequences. The outstanding performance and expansibility of this D-locked platform holds promising prospects for cancer diagnosis and related biomedical applications.