Dual-Function Nanoscale Coordination Polymer Nanoparticles for Targeted Diagnosis and Therapeutic Delivery in Atherosclerosis.

Atherosclerosis is the primary cause of cardiovascular events such as heart attacks and strokes. However, current medical practice lacks non-invasive, reliable approaches for both imaging atherosclerotic plaques and delivering therapeutic agents directly therein. Here, a biocompatible and biodegradable pH-responsive nanoscale coordination polymers (NCPs) based theranostic system is reported for managing atherosclerosis. NCPs are synthesized with a pH-responsive benzoic-imine (BI) linker and Gd3+. Simvastatin (ST), a statin not used for lowering blood cholesterol but known for its anti-inflammatory and antioxidant effects in mice, is chosen as the model drug. By incorporating ST into the hydrophobic domain of a lipid bilayer shell on NCPs surfaces, ST/NCP-PEG nanoparticles are created that are designed for dual purposes: they diagnose and treat atherosclerosis. When administered intravenously, they target atherosclerotic plaques, breaking down in the mild acidic microenvironment of the plaque to release ST, which reduces inflammation and oxidative stress, and Gd-complexes for MR imaging of the plaques. ST/NCP-PEG nanoparticles show efficacy in slowing the progression of atherosclerosis in live models and allow for simultaneous in vivo monitoring without observed toxicity in major organs. This positions ST/NCP-PEG nanoparticles as a promising strategy for the spontaneous diagnosis and treatment of atherosclerosis.

NIR-II Ratiometric Lanthanide-Dye Hybrid Nanoprobes Doped Bioscaffolds for In Situ Bone Repair Monitoring.

In situ monitoring of tissue regeneration progression is of primary importance to basic medical research and clinical transformation. Despite significant progress in the field of tissue engineering and regenerative medicine, few technologies have been established to in situ inspect the regenerative process. Here, we present an integrated second near-infrared (NIR-II, 1000-1700 nm) window in vivo imaging strategy based on 3D-printed bioactive glass scaffolds doped with NIR-II ratiometric lanthanide-dye hybrid nanoprobes, allowing for in situ monitoring of the early inflammation, angiogenesis, and implant degradation during mouse skull repair. The functional bioactive glass scaffolds contribute to more effective bone regeneration because of their excellent angiogenic and osteogenic activities. The reliability of ratiometric fluorescence imaging, coupled with low autofluoresence in the NIR-II window, facilitates the accuracy of in vivo inflammation detection and high-resolution visualization of neovascularization and implant degradation in deep tissue.

Noninvasive Early Diagnosis of Allograft Rejection by a Granzyme B Protease Responsive NIR-II Bioimaging Nanosensor.

Early diagnosis of allograft rejection helps to improve the immune-related management of transplant recipients. The clinically-used core needle biopsy method is invasive and subject to sampling error. In vivo fluorescence imaging for monitoring immune-related processes has the advantages of non-invasiveness, fast feedback and high sensitivity. Herein, we report a responsive second near-infrared (NIR-II) fluorescent nanosensor (ErGZ) to detect early allograft rejection. ErGZ allows ratiometric in vivo fluorescence sensing of granzyme B, which is overexpressed in recipients' T cells during the onset of rejection. The sensor demonstrates efficacious detection of allograft rejection with high sensitivity and specificity, which accomplishes non-invasive diagnosis of rejection in skin and deep buried islets transplant mice models 2 d and 5 d earlier than biopsy, by in vivo fluorescence imaging and urinary detection, respectively, providing a valuable approach for therapeutical management.

Detoxification of Ochratoxin A by a novel Aspergillus oryzae strain and optimization of its biodegradation.

The mycotoxin Ochratoxin A (OTA) causes serious health risks and is found in food products throughout the world. The most promising method to detoxify this compound is biodegradation. In this study, Aspergillus oryzae strain M30011 was isolated and characterized based on its considerable capacity to degrade OTA. The degradation product (compound I) of A. oryzae-treated OTA was isolated, and its toxicity response was also evaluated. Furthermore, the relationships between three key cultivation condition factors affecting the OTA degradation rate were examined using the response surface methodology (RSM). Compound I was identified as ochratoxin α (C11H9O5Cl), and the toxicity response experiments indicated that A. oryzae detoxified OTA to a great extent. A maximum degradation rate of 94% was observed after 72h. This study demonstrates the potential for using A. oryzae to detoxify OTA and suggests that it could be applied in the food industry to improve food safety and quality.

A Promising NIR-II Fluorescent Sensor for Peptide-Mediated Long-Term Monitoring of Kidney Dysfunction.

Kidney disease is usually "silent" at the early stage but can lead to severe kidney failure later on. The development of bioimaging probes with rapid distribution and long-term retention in the kidney is significant for the precise diagnosis of renal diseases. Here, a strategy for the peptide-mediated delivery and long-term accumulation (>48 h) of second near-infrared window (NIR-II) fluorophores into the kidney is demonstrated. It is shown that both the hepatic-cleared organic molecules and fast renal-cleared ultrasmall nanoparticles can be retained in the kidney after conjugation to the peptide with high polarity. Moreover, a ROS-responsive activatable bilateral NIR-II sensor was designed based on the kidney targeting peptide, which enables both in vivo long-term kidney monitoring and in vitro urine analysis. The capability of the peptide-based sensor to detect early kidney injury and report on kidney dysfunctional progression is particularly crucial for chemotherapy regimen optimization and timely renoprotective intervention during medication.

High-Fidelity NIR-II Multiplexed Lifetime Bioimaging with Bright Double Interfaced Lanthanide Nanoparticles.

Fluorescence lifetime imaging provides more possibility of in vivo multiplexing in second near infrared (NIR-II) window. However, it still faces the obstacle that fluorescent probes with differentiable lifetime often exhibit quite different fluorescence intensity, especially the short lifetime usually accompanies with a weak fluorescence intensity, resulting in the difficulty for simultaneously decoding multiplexed lifetime information due to the interference of background noise. To facilitate high-fidelity lifetime multiplexed imaging, we developed a series of Er3+ doped double interface fluorescent nanoprobes (Er-DINPs): α-NaYF4 @NaErF4 : Ce@NaYbF4 @NaErF4 : Ce@NaYF4 with strong fluorescence intensity and easily distinguishable fluorescence lifetime. Both in vitro and in vivo experimental results confirmed the advantage of these probes with comparable fluorescence intensity for high-fidelity multiplexed lifetime bioimaging.

Tm3+ -Sensitized NIR-II Fluorescent Nanocrystals for In†Vivo Information Storage and Decoding.

In vivo fluorescence imaging in the second near-infrared window (NIR-II) affords deep-tissue penetration and high spatial resolution. Herein, we present a new type of Tm3+ -sensitized lanthanide nanocrystals with both excitation (1208 nm) and emission (1525 nm) located in the NIR-II window for in vivo optical information storage and decoding. Taking advantage of the tunable fluorescence lifetimes, the optical multiplexed encoding capacity is enhanced accordingly. Micro-devices with QR codes featuring the NIR-II fluorescence-lifetime multiplexed encoding were implanted into mice and were successfully decoded through time-gated fluorescence imaging technology.

Stable, Wavelength-Tunable Fluorescent Dyes in the NIR-II Region for In†Vivo High-Contrast Bioimaging and Multiplexed Biosensing.

Small-molecule organic fluorophores, spectrally active in the 900-1700 nm region, with tunable wavelength and sensing properties are sought-after for in vivo optical imaging and biosensing. A panel of fluorescent dyes (CX) has been developed to meet this challenge. CX dyes exhibit the wavelength tunability of cyanine dyes and have a rigidified polymethine chain to guarantee their stability. They are chemo- and photo-stable in an aqueous environment and have tunable optical properties with maximal absorbing/emitting wavelength at 1089/1140 nm. They show great potential in high-contrast in vivo bioimaging and multicolor detection with negligible optical cross talk. Förster resonance energy transfer (FRET) between CX dyes was demonstrated in deep tissue, providing an approach for monitoring drug-induced hepatotoxicity by detection of OONO- . This report presents a series of NIR-II dyes with promising spectroscopic properties for high-contrast bioimaging and multiplexed biosensing.

Er3+ Sensitized 1530†nm to 1180†nm Second Near-Infrared Window Upconversion Nanocrystals for In†Vivo Biosensing.

Fluorescent bioimaging in the second near-infrared window (NIR-II) can probe deep tissue with minimum auto-fluorescence and tissue scattering. However, current NIR-II fluorophore-related biodetection in vivo is only focused on direct disease lesion or organ bioimaging, it is still a challenge to realize NIR-II real-time dynamic biosensing. A new type of Er3+ sensitized upconversion nanoparticles are presented with both excitation (1530 nm) and emission (1180 nm) located in the NIR-II window for in vivo biosensing. The microneedle patch sensor for in vivo inflammation dynamic detection is developed based on the ratiometric fluorescence by combining the effective NIR-II upconversion emission and H2 O2 sensing organic probes under the Fenton catalysis of Fe2+ . Owing to the large anti-Stokes shifting, low auto-fluorescence, and tissue scattering of the NIR-II upconversion luminescence, inflammation can be dynamically evaluated in vivo at very high resolution (200×200 µm).

The influence of perceptual and semantic chunking on the neural mechanism of remote association.

Studies on remote association tests (RATs) have mainly focused on cognitive processes involved in searching for remote associations. However, factors affecting these search processes and remote associations remain unclear. In order to address this issue, this study compared non-chunking condition (e.g., "//") with perceptual chunking (two red color characters in the three-character item "//") and semantic chunking (high-frequency word-pair in the item; e.g., "//", "," literally "philosophy") conditions in the Chinese Remote Association Test (CRAT). The behavioral results on the CRAT found that the semantic ones resulted in significantly lower successful solving rates and longer response times than the other two conditions. The event-related potential (ERP) results showed that in contrast to the perceptual-chunking and the non-chunking condition, the semantic-chunking elicited enhanced P200, which might be related to the intuitive awareness of the mental fixation. However, relative to the non-chunking condition, the two chunking conditions evoked increased N400 and late positive component (LPC), indexing the late reflection and implementation of cognitive control. Our results suggest that it is the early awareness of the semantic chunk, rather than the general cognitive control process involved in representing and solving the semantically and perceptually chunk-induced interferences, that critically determines the final solving of RATs.

Fluorescence-amplified nanocrystals in the second near-infrared window for in vivo real-time dynamic multiplexed imaging.

Optical imaging in the second near-infrared window (NIR-II, 1,000-1,700 nm) holds great promise for non-invasive in vivo detection. However, real-time dynamic multiplexed imaging remains challenging due to the lack of available fluorescence probes and multiplexing techniques in the ideal NIR-IIb (1,500-1,700 nm) 'deep-tissue-transparent' sub-window. Here we report on thulium-based cubic-phase downshifting nanoparticles (α-TmNPs) with 1,632 nm fluorescence amplification. This strategy was also validated for the fluorescence enhancement of nanoparticles doped with NIR-II Er3+ (α-ErNPs) or Ho3+ (α-HoNPs). In parallel, we developed a simultaneous dual-channel imaging system with high spatiotemporal synchronization and accuracy. The NIR-IIb α-TmNPs and α-ErNPs facilitated the non-invasive real-time dynamic multiplexed imaging of cerebrovascular vasomotion activity and the single-cell-level neutrophil behaviour in mouse subcutaneous tissue and ischaemic stroke model.

Meta-analysis reveals variations in microbial communities from diverse stony coral taxa at different geographical distances.

Coral-associated microbial communities play a vital role in underpinning the health and resilience of reef ecosystems. Previous studies have demonstrated that the microbial communities of corals are affected by multiple factors, mainly focusing on host species and geolocation. However, up-to-date, insight into how the coral microbiota is structured by vast geographic distance with rich taxa is deficient. In the present study, the coral microbiota in six stony coral species collected from the coastal area of three countries, including United States of America (USA), Australia and Fiji, was used for analysis. It was found that the geographic influence on the coral microbiota was stronger than the coral host influence, even though both were significant. Interestingly, the contribution of the deterministic process to bacterial community composition increased as geographical distance grew. A total of 65 differentially abundant features of functions in coral microbial communities were identified to be associated with three geolocations. While in the same coastal area of USA, the similar relationship of coral microbiota was consistent with the phylogenetic relationship of coral hosts. In contrast to the phylum Proteobacteria, which was most abundant in other coral species in USA, Cyanobacteria was the most abundant phylum in Orbicella faveolata. The above findings may help to better understand the multiple natural driving forces shaping the coral microbial community to contribute to defining the healthy baseline of the coral microbiome.

Site-selective superassembly of biomimetic nanorobots enabling deep penetration into tumor with stiff stroma.

Chemotherapy remains as the first-choice treatment option for triple-negative breast cancer (TNBC). However, the limited tumor penetration and low cellular internalization efficiency of current nanocarrier-based systems impede the access of anticancer drugs to TNBC with dense stroma and thereby greatly restricts clinical therapeutic efficacy, especially for TNBC bone metastasis. In this work, biomimetic head/hollow tail nanorobots were designed through a site-selective superassembly strategy. We show that nanorobots enable efficient remodeling of the dense tumor stromal microenvironments (TSM) for deep tumor penetration. Furthermore, the self-movement ability and spiky head markedly promote interfacial cellular uptake efficacy, transvascular extravasation, and intratumoral penetration. These nanorobots, which integrate deep tumor penetration, active cellular internalization, near-infrared (NIR) light-responsive release, and photothermal therapy capacities into a single nanodevice efficiently suppress tumor growth in a bone metastasis female mouse model of TNBC and also demonstrate potent antitumor efficacy in three different subcutaneous tumor models.

Sensitization to Per a 2 of the American cockroach correlates with more clinical severity among airway allergic patients in Taiwan.

BACKGROUND: In Taiwan, 57.5% of asthmatic patients are allergic to cockroaches, which are a major indoor allergen for immunoglobulin E (IgE)-mediated respiratory diseases. OBJECTIVE: To determine whether sensitization to different cockroach allergenic components correlates with different clinical manifestations and severities. METHODS: The complementary DNAs (cDNAs) encoding for Per a 1 through 7 and Per a 9 were generated by reverse transcription polymerase chain reaction and cloned into the Escherichia coli expression system. Sixty-four subjects were divided into 3 groups based on the clinical severity of their allergic reaction: those with persistent asthma and rhinitis (AS), those with allergic rhinitis only (AR), and the nonallergic controls (NA). Serum levels of interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), chemokine (C-C motif) ligand 20 (CCL-20), and granulocyte macrophage colony-stimulating factor (GM-CSF) were measured, and the binding frequencies to each recombinant allergen were examined. RESULTS: Serum levels of IL-8, MCP-1, and CCL-20 were significantly higher in the AS group than in the AR and NA groups. The numbers of IgE-binding allergens did not correlate with the clinical severity of airway allergy to cockroaches. However, 81% in the AS group had IgE-binding activity to Per a 2, which was significantly higher than that of the AR group (45%, P < .05). In contrast, 80% of AR patients had IgE-binding activity to Per a 9 compared with only 28.5% of AS patients (P < .01). CONCLUSION: Allergens from American cockroaches do not have equal importance in terms of pathogenicity. Sensitization to Per a 2 correlates with more severe airway allergy and elevated proinflammatory chemokines. This may help in selecting target allergens for component resolved diagnosis and immunotherapeutic agents.

[Structural Characteristics of Micro-nano Particle Size Biochar and Its Adsorption Mechanism for Cd2].

The aim of this study was to investigate the structural characteristics of biochar with different micro/nano particle sizes and its effect on the adsorption performance of Cd2+. Corn stalk biochar with different particle sizes (180-250 µm, 50-75 µm, and ≤ 20 µm, denoted as BC-1, BC-2, and BC-3, respectively) were prepared using the sieving and ball milling method. The structural properties of different particle sizes of biochar were analyzed via elemental analysis, laser particle size analysis, SEM, BET, FTIR, and XPS. Additionally, the adsorption mechanisms of Cd2+ by three particle sizes of biochar under initial Cd2+ concentrations, adsorption times, and pH conditions were comparatively studied using static adsorption experiments. The results showed that with the decrease in particle size, the pH and zeta potential of biochar were reduced; the aromaticity and polarity decreased; the specific surface area and pore volume increased; and the intensity of the characteristic peaks containing OH, C[FY=,1]C/C[FY=,1]O, and C-O groups increased. The adsorption kinetics of Cd2+ with different particle diameters of biochar were in accordance with the pseudo-secondary kinetic model, with chemisorption dominating. The equilibrium times were in the decreasing order of BC-1 (540 min)>BC-2 (360 min)>BC-3 (80 min). The Langmuir model could better fit the adsorption isotherm process of Cd2+ on biochar of different particle sizes (R2>0.97), and the maximum adsorption capacity of Cd2+ increased with the decrease in particle size, which was expressed as BC-3 (74.43 mg·g-1)>BC-2 (45.71 mg·g-1)>BC-1 (44.59 mg·g-1). The main mechanisms of Cd2+adsorption by biochar were electrostatic attraction, surface complexation, and cation-π interaction.

Macroporous Vanadium Oxide Ion Storage Films Enable Fast Switching Speed and High Cycling Stability of Electrochromic Devices.

Compared to the significant effort dedicated toward developing efficient electrochromic materials for the working electrodes of electrochromic (EC) devices, the attention paid to developing ion storage counter electrode materials for EC devices has been trivial. Herein, we report that a macroporous crystalline V2O5 film as an ion storage layer paired with a WO3 working electrode results in an EC device with high performance. The macroporous vanadium oxide films are prepared by a simple template-free photodeposition method that allows us to tune the thickness and crystallinity of the film, thus giving access to a full EC device with optimal EC performance: short response time of about 2 s, high electrochromic cycling stability up to 10,000 times, long memory effect over 24 h, and an exceedingly high coloration efficiency of 189 cm2/C that are superior to the state-of-the-art performance of solution-processed vanadium oxide based EC devices. The extraordinary EC performance can be attributed to the macroporous structure, high crystallinity, and optimized thickness of the vanadium oxide films that boost the charge-balancing capability of the films. The easy and controllable preparation and the efficient charge-balancing capability of the macroporous vanadium oxide film make it a promising ion storage material for developing high-performance EC devices.

Characterizing the long-term occurrence of polycyclic aromatic hydrocarbons and their driving forces in surface waters.

As carcinogenic and ubiquitous pollutants, an in-depth understanding of the long-term environmental behaviors of polycyclic aromatic hydrocarbons (PAHs) and their driving forces is crucial for reducing human health risks. Based on long-term monitoring data from 2001 to 2016, this study systematically investigated the temporal and seasonal trends, periodic oscillation, source apportionment, and human health risks of PAHs in eight rivers in the Free State of Saxony, Germany. The results showed that the annual average ∑16PAHs (sum of 16 PAH concentrations) ranged from 28.2 ng L-1 to 202 ng L-1. Using the Mann-Kendall test, a trend of decreasing PAH concentrations was determined (slope range: -0.103 to -0.0159). Wavelet analysis indicated that the most significant periodic oscillation of PAHs was 10-30 months, with more pollution in winter. Source apportionment analysis suggested that vehicular emissions and coal combustion contributed the most to PAH concentrations (20.6-40.3% and 21.7-41.4%, respectively) and related health risks (54.1-80.1% and 5.61-37.9%, respectively). Furthermore, the risks (oral lifetime: 4.24×10-7-1.34×10-6; dermal lifetime: 2.86×10-5-9.05×10-5) were determined to be low. The data revealed that the substitution of petroleum and coal with cleaner energy would facilitate the mitigation of PAHs.

A numerical study on heat transfer performances of horizontal ground heat exchangers in ground-source heat pumps.

Horizontal ground heat exchangers (HGHEs) have advantages such as convenient construction and low cost; however, their application and popularization are restricted owing to traditional linear HGHEs occupying large space and presenting low total heat transfer capacity. Spiral-coil and slinky-coil HGHEs have been proposed, but currently a comprehensive comparison and evaluation for these types of HGHEs are still needed. In this study, a three-dimensional heat transfer model of the three types of HGHEs for ground source heat pumps (GSHPs) was established. Based on the simulation results, the long-term heat transfer performances were investigated, including the temperature field of surrounding energy-storage soils, outlet working fluid temperature, coefficient of performance (COP) of units, and surplus temperature of the energy-storage soils. A new concept named heat transfer capacity per heat-affected area was proposed in this paper. It is found that the spiral-coil HGHEs have the best performances in terms of working-fluid outlet temperature, unit COP, total heat transfer capacity, heat transfer rate heat-affected area. The linear HGHEs shows the best performances in terms of mitigating heat imbalance risk and heat transfer rate per length. The results provide a reliable basis for selection of HGHE types in engineering practice and improvement guide in the future.

Impacts of hydrogeological characters of fractured rock on thermodynamic performance of ground-coupled heat pump.

Ground-coupled heat pump (GCHP) is used to recovery shallow geothermal energy, a widely distributed green energy source. Due to the imbalance between heat rejection and extraction, heat buildup underground is commonly associated with the long-term operation of GCHPs, which undermine system performance. Heat buildup intrinsically results the irreversibilities (entropy production) in subsurface heat sink, in which thermodynamic and transport properties are largely influenced by hydrogeologic properties, especially the existence of fractures and groundwater. This study investigates the influence of water flow in fractures on the thermodynamic performance of a single borehole heat exchanger (BHX) and heat buildup in the underground heat exchange zone (UHXZ). Potential influence factors were screened out, and new terms were proposed to quantify the scale of fractures and available heat and cold in the heat sink. Governing equations were established to calculate the impacts of vertical and horizontal fractures on the heat exchange rate in BHX as well as on the heat flow across the UHXZ. The analysis results show that water flow in fractures can significantly enhance heat transfer, reduce required number of boreholes, mitigate heat buildup and reduce irreversibilities underground. The results also suggest that the role of fracture scales and water velocity in GCHP operation should be carefully evaluated. Therefore, detailed hydrogeological survey is necessary. The study results provide a guide on more accurately evaluating the risk of heat buildup and how to take advantage of hydrogeological characters to improve the performance of GCHPs.

X-ray-activated persistent luminescence nanomaterials for NIR-II imaging.

Persistent luminescence is not affected by background autofluorescence, and thus holds the promise of high-contrast bioimaging. However, at present, persistent luminescent materials for in vivo imaging are mainly bulk crystals characterized by a non-uniform size and morphology, inaccessible core-shell structures and short emission wavelengths. Here we report a series of X-ray-activated, lanthanide-doped nanoparticles with an extended emission lifetime in the second near-infrared window (NIR-II, 1,000-1,700 nm). Core-shell engineering enables a tunable NIR-II persistent luminescence, which outperforms NIR-II fluorescence in signal-to-noise ratios and the accuracy of in vivo multiplexed encoding and multilevel encryption, as well as in resolving mouse abdominal vessels, tumours and ureters in deep tissue (~2-4 mm), with up to fourfold higher signal-to-noise ratios and a threefold greater sharpness. These rationally designed nanoparticles also allow the high-contrast multiplexed imaging of viscera and multimodal NIR-II persistent luminescence-magnetic resonance-positron emission tomography imaging of murine tumours.