Ultrasensitive Urinary Diagnosis of Organ Injuries Using Time-Resolved Luminescent Lanthanide Nano-bioprobes.

Urinary sensing of synthetic biomarkers that are released into urine after specific activation in an in vivo disease environment is an emerging diagnosis strategy to overcome the insensitivity of a previous biomarker assay. However, it remains a great challenge to achieve sensitive and a specific urinary photoluminescence (PL) diagnosis. Herein, we report a novel urinary time-resolved PL (TRPL) diagnosis strategy by exploiting europium complexes of diethylenetriaminepentaacetic acid (Eu-DTPA) as synthetic biomarkers and designing the activatable nanoprobes. Notably, TRPL of Eu-DTPA in the enhancer can eliminate the urinary background PL for ultrasensitive detection. We achieved sensitive urinary TRPL diagnosis of mice kidney and liver injuries by using simple Eu-DTPA and Eu-DTPA-integrated nanoprobes, respectively, which cannot be realized by traditional blood assays. This work demonstrates the exploration of lanthanide nanoprobes for in vivo disease-activated urinary TRPL diagnosis for the first time, which might advance the noninvasive diagnosis of diverse diseases via tailorable nanoprobe designs.

Wind Energy Harvesting with Vertically Aligned Piezoelectric Inverted Flags.

Wind-energy-harvesting generators based on inverted flag architecture are an attractive option to replace batteries in low-power wireless electronic devices and deploy-and-forget distributed sensors. This study examines two important aspects that have been overlooked in previous research: the interaction between an inverted flag and a neighboring solid boundary and the interaction among multiple contiguous inverted flags arranged in a vertical row. Systematic tests have been carried out with metal-only 'baseline' flags as well as a 'harvester' variant, i.e., the baseline metal flag covered with PVDF (polyvinylidene difluoride) piezoelectric polymer elements. In each case, dynamic response and power generation were measured and assessed. For baseline metal flags, the same qualitative trend is observed when the flag approaches an obstacle, whether this is a wall or another flag. As the gap distance reduces, the wind speed range at which flapping occurs gradually shrinks and shifts towards lower velocities. The increased damping introduced by attaching PVDF elements to the baseline metal flags led to a considerable narrowing of the flapping wind speed range, and the wall-to-flag or flag-to-flag interaction led to a power reduction of up to one order of magnitude compared to single flags. The present findings highlight the strong dependence of the power output on the flapping frequency, which decreases when the flag approaches a wall or other flags mounted onto the same pole. Minimum flag-to-flag and flag-to-wall spacing values are suggested for practical applications to avoid power reduction in multi-flag arrangements (2-3H and 1-2H respectively, where H is flag height).

A Lanthanide Upconversion Nanothermometer for Precise Temperature Mapping on Immune Cell Membrane.

Cell temperature monitoring is of great importance to uncover temperature-dependent intracellular events and regulate cellular functions. However, it remains a great challenge to precisely probe the localized temperature status in living cells. Herein, we report a strategy for in situ temperature mapping on an immune cell membrane for the first time, which was achieved by using the lanthanide-doped upconversion nanoparticles. The nanothermometer was designed to label the cell membrane by combining metabolic labeling and click chemistry and can leverage ratiometric upconversion luminescence signals to in situ sensitively monitor temperature variation (1.4% K-1). Moreover, a purpose-built upconversion hyperspectral microscope was utilized to synchronously map temperature changes on T cell membrane and visualize intracellular Ca2+ influx. This strategy was able to identify a suitable temperature status for facilitating thermally stimulated calcium influx in T cells, thus enabling high-efficiency activation of immune cells. Such findings might advance understandings on thermally dependent biological processes and their regulation methodology.

Near-Infrared II Gold Nanocluster Assemblies with Improved Luminescence and Biofate for In Vivo Ratiometric Imaging of H2S.

Ultrasmall gold nanoclusters (AuNCs) are emerging as promising luminescent nanoprobes for bioimaging due to their fantastic photoluminescence (PL) and renal-clearable ability. However, it remains a great challenge to design them for in vivo sensitive molecular imaging in desired tissues. Herein, we have developed a strategy to tailor the PL and biofate of near-infrared II (NIR-II)-emitting AuNCs via ligand anchoring for improved bioimaging. By optimizing the ligand types in AuNCs and using Er3+-doped lanthanide (Ln) nanoparticles as models, core-satellite Ln@AuNCs assemblies were rationally constructed, which enabled 2.5-fold PL enhancement of AuNCs at 1100 nm and prolonged blood circulation compared to AuNCs. Significantly, Ln@AuNCs with dual intense NIR-II PL (from AuNCs and Er3+) can effectively accumulate in the liver for ratiometric NIR-II imaging of H2S, facilitated by H2S-mediated selective PL quenching of AuNCs. We have then demonstrated the real-time imaging evaluation of liver delivery efficacy and dynamics of two H2S prodrugs. This shows a paradigm to visualize liver H2S delivery and its prodrug screening in vivo. Note that Ln@AuNCs are body-clearable via the hepatobiliary excretion pathway, thus reducing potential long-term toxicity. Such findings may propel the engineering of AuNC nanoprobes for advancing in vivo bioimaging analysis.

An improved genetic algorithm for solving the helicopter routing problem with time window in post-disaster rescue.

The vehicle routing problem (VRP) is a highly significant and extensively studied issue in post-disaster rescue. In recent years, there has been widespread utilization of helicopters for post-disaster rescue. However, efficiently dispatching helicopters to reach rescue sites in post-disaster rescue is a challenge. To address this issue, this study models the issue of dispatching helicopters as a specific variant of the VRP with time window (VRPTW). Considering that the VRPTW is an NP-hard problem, the genetic algorithm (GA) as one of the prominent evolutionary algorithms with robust optimization capabilities, is a good candidate to deal with this issue. In this study, an improved GA with a local search strategy and global search strategy is proposed. To begin, a cooperative initialization strategy is proposed to generate an initial population with high quality and diversity. Subsequently, a local search strategy is presented to improve the exploitation ability. Additionally, a global search strategy is embedded to enhance the global search performance. Finally, 56 instances extended from Solomon instances are utilized for conducting simulation tests. The simulation results indicate that the average relative percentage increase (RPI) of the distance travelled by helicopters as obtained by the proposed algorithm is 0.178, 0.027, 0.075 and 0.041 times smaller than the average RPIs obtained by the tabu search algorithm, ant colony optimization algorithm, hybrid GA and simulated annealing algorithm, respectively. Simulation results reveal that the proposed algorithm is more efficient and effective for solving the VRPTW to reduce the driving distance of the helicopters in post-disaster rescue.

Interleukin-17A knockout or self-recovery alleviated autoimmune reaction induced by fluoride in mouse testis.

Fluoride (F) is usually treated as a hazardous material, and F-caused public health problem has attracted global attention. Previous studies demonstrate that interleukin-17A (IL-17A) plays a crucial role in F-elicited autoimmune orchitis and self-recovery reverses F-induced testicular toxicity to some extent, but these basic mechanisms remain unclear. Thus, we established a 180 d F exposure model of wild type (WT) mice and IL-17A knockout mice (C57BL/6 J background), and 60 d & 120 d self-recovery model based on F exposure model of WT mice, and used various techniques like qRT-PCR, western blot, immunohistochemistry and ELISA to further explore the mechanism of F-induced autoimmune reaction, the role of IL-17A in it and the reversibility of F-caused toxicity in testis. The results indicated that F exposure for 180 d caused the decreased sperm quality, the damaged testis histopathology, the enhanced mRNA and protein expression levels of inflammatory cytokines, the changes of autoantibody such as the appearance and increased content of anti-testicular autoantibodies in sera and the autoantibody deposition in testis, the alterations of autoimmune related genes containing the decreased mRNA and protein expressions of AIRE and FOXP3 with an increase of MHCII, and the reduced protein expressions of CTLA4, and the activation of IL-17A signaling cascade like the elevated mRNA and protein expressions of IL-17A, Act1, NF-κB, AP-1 and CEBPß, and the increased protein expressions of IL-17RC, with a decrease of IκBα. After IL-17A knockout, 29 of 35 F-induced changes were alleviated. In two self-recovery models, all F-caused differences except fluorine concentration in femur were gradually restored in a time-dependent manner. This study concluded that IL-17A knockout or self-recovery attenuated F-induced testicular injury and decrease of sperm quality through alleviating autoimmune reaction which was involved with the activation of IL-17A pathway, the damage of self-tolerance and the enhancement of antigen presentation.

Arsenic-induced autophagy regulates apoptosis in AML-12 cells.

Arsenic (As), a potent toxicant, is known to be a hepatotoxicant. Although As induced liver apoptosis and autophagy, the relationship between apoptosis and autophagy of hepatocytes caused by As remains largely unknown. 3-methyladenine (3-MA) and rapamycin can inhibit and promote autophagy of AML-12 cells, respectively. Hence, in this study, AML-12 cells were treated with different concentrations (0, 2, 4, 6, 8, 10 and 12 µmol/L) of As2O3, and 5 mmol/L 3-MA or 100 nmol/L rapamycin were applied to distinguish the effect of autophagy on apoptosis in AML-12. Results showed that exposure to As induced cell apoptosis and autophagy, which were mediated by the significantly altered expression levels of autophagy markers (mTOR, LC3, PI3K and P62), and apoptosis markers (Bcl-2 and caspase-3). Further analysis indicated that a certain dosage of 3-MA and rapamycin decreased apoptosis and the caspase-3 expression, which suggested that As-induced autophagy regulated AML-12 cells apoptosis through the expressions of PI3K, mTOR, P62 and Bcl-2.

Effect of arsenic and/or fluoride gestational exposure on renal autophagy in offspring mice.

Both arsenic (As) and fluorine (F) are toxic substances widely found in the environment, which threaten to various organs of both human and animals, especially the kidney. In this study, to investigate the individual and combined effects of arsenic (15 mg/L As2O3(III)) and fluoride (100 mg/L NaF), arsenic (15 mg/L As2O3(III)) and fluoride-arsenic (15 mg/L As2O3(III)+100 mg/L NaF) on the renal autophagy during early life, a mouse model of gestationally exposed to As and/or F was established. The results showed that the mRNA expression levels of LC3, LC3I, LC3II, Beclin-1, ULK1, Atg13 and Atg14 were significantly increased with a concomitant decrease in mTOR and Bcl-2 up on individual exposure to As and F rather than in combined (As + F) exposure. In addition, the protein expression levels of LC3-II/LC3-I, Beclin-1, and LAMP1 were significantly increased with a concomitant decrease in mTOR and Bcl-2 in the mice subjected to individual exposure than the combined exposure. Based on the results, it was observed that renal tissue of mice was highly sensitive to F than As. Moreover, the toxicity of the combined (As + F) exposure was significantly lower than that of the individual exposure, which could be attributed due to the antagonism between As and F.

Effect of fluoride exposure on anxiety- and depression-like behavior in mouse.

We established the mouse model of fluoride (68 mg F ion/L deionized water) exposure for 90 days, 120 days and 150 days, and applied diverse methods as behavioral models of anxiety and depression, and analyzed the levels of the anxiety- and depression-like related genes like BDNF1, BDNF4, 5-HT1A, VGLUT, GAD67, and VGAT in the mouse hippocampus. In the mice exposed to NaF for 120 days, compared to the control group, chalky opacity was observed on the enamel of teeth; the results of anxiety-like behavior, like elevated zero maze, light/dark exploration test, novel object recognition test and emergence test were significantly altered, however in the mice exposed for 150 days, only the elevated zero maze and emergence test were significantly altered. Also, the results of depression-like behavior were significantly altered in the 120 days treated mice. Exposure to NaF for 120 days significantly decreased the mRNA expression levels of the BDNF4 with a concomitant increase in the 5-HT1A compared to the control mice. Especially the mRNA expression levels of GAD67 and VGAT were significantly decreased in all the three NaF treated groups. However, no significant changes were observed in the mRNA expression levels of the VGLUT compared to the control mice. In summary, we speculated that fluoride exposure had adverse effects on nervous system, inducing an imbalance between excitation and inhibition, which resulted in abnormal behavior and depression.