Simple thiol derivatives, such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), play key roles in biological processes, and the fluorescent probes to detect such thiols in vivo ...selectively with high sensitivity and fast response times are critical for understanding their numerous functions. However, the similar structures and reactivities of these thiols pose considerable challenges to the development of such probes. This review focuses on various strategies for the design of fluorescent probes for the selective detection of biothiols. We classify the fluorescent probes for discrimination among biothiols according to reaction types between the probes and thiols such as cyclization with aldehydes, conjugate addition-cyclization with acrylates, native chemical ligation, and aromatic substitution-rearrangement.
Exhaustion of cytotoxic effector natural killer (NK) and CD8
T cells have important functions in the establishment of persistent viral infections, but how exhaustion is induced during chronic ...hepatitis C virus (HCV) infection remains poorly defined. Here we show, using the humanized C/O
mice permissive for persistent HCV infection, that NK and CD8
T cells become sequentially exhausted shortly after their transient hepatic infiltration and activation in acute HCV infection. HCV infection upregulates Qa-1 expression in hepatocytes, which ligates NKG2A to induce NK cell exhaustion. Antibodies targeting NKG2A or Qa-1 prevents NK exhaustion and promotes NK-dependent HCV clearance. Moreover, reactivated NK cells provide sufficient IFN-γ that helps rejuvenate polyclonal HCV CD8
T cell response and clearance of HCV. Our data thus show that NKG2A serves as a critical checkpoint for HCV-induced NK exhaustion, and that NKG2A blockade sequentially boosts interdependent NK and CD8
T cell functions to prevent persistent HCV infection.
•Monthly runoff is divided into several subseries by variational mode decomposition.•Support vector machine models the input-output relationships of all the subseries.•Quantum-behaved particle swarm ...algorithm searches for suitable model parameters.•The hybrid method obtains satisfying results in the real-world simulations.
Accurate monthly runoff prediction plays an important role in the planning and management of water resources. However, owing to climate changes and human activities, natural runoff often contains a variety of frequency components, and existing monthly runoff estimation techniques may fail to capture potential change processes effectively. To overcome this problem, we have developed a hybrid model for monthly runoff prediction. First, observed runoff is decomposed into several subcomponents via variational mode decomposition. Second, support vector machine models based on quantum-behaved particle swarm optimization are adopted to identify the input-output relationships hidden in each subcomponent. Finally, the total output of all submodules is treated as the final forecasting result for the original runoff. Three quantitative indexes are considered to test the performance of the developed models. The monthly streamflow of two reservoirs in China’s Yangtze Valley is considered as the survey target. This area contains the world’s largest hydropower project (Three Gorges Reservoir) and the waterhead of the middle line of Asia's largest inter-basin water transfer project (Danjiangkou Reservoir). Test results indicate that the hybrid model provides better forecasting accuracy compared to several traditional methods (artificial neural networks and extreme learning machines), making it an effective tool for the scientific operation of hydropower reservoirs.
Acoustic metamaterials with artificial microstructures are attractive to realize intriguing functions, including efficient waveguiding, which requires large impedance mismatches to realize total side ...reflection with negligible transmission and absorption. While large impedance mismatch can be readily realized in an air environment, acoustic waveguiding in an underwater environment remains elusive due to insufficient impedance mismatch of state‐of‐the‐art metamaterials. Here, a superhydrophobic acoustic metasurface of microstructured poly(vinylidene fluoride) membrane, referred to as a “meta‐skin” insulator, which is able to confine acoustic waves in an all‐angle and wide spectrum range due to tremendous impedance mismatch at stable air/water interfaces, viz., the Cassie–Baxter state is demonstrated. By utilizing the meta‐skin insulator with broadband and high throughput, orbital‐angular‐momentum multiplexing at a high spectral efficiency and binary coding along large‐angle bending channels for bit‐error‐free acoustic data transmission in an underwater environment are demonstrated. Very different from optical and/or electrical cable communications, acoustic waves can be simply and effectively coupled into remote meta‐skin acoustic fibers from free space, which is technologically significant for long‐haul and anti‐interference communication. This work can enlighten many fluidic applications based on efficient waveguiding, such as in vivo ultrasound medical treatment and imaging.
Underwater acoustic wave confinement in an all‐angle and wide spectrum range can be realized in a meta‐skin insulator due to the tremendous impedance mismatch originating from the stable Cassie–Baxter state. Acoustic‐wave‐based underwater orbital‐angular‐momentum multiplexing and binary coding are implemented, which is promising for long‐haul and anti‐interference communication. This work also benefits in vivo ultrasound medical treatment and imaging.
Objectives
To determine and validate alanine aminotransferase (ALT)-adapted dual cut-offs of liver stiffness measurements (LSMs) for assessing liver fibrosis with two-dimensional shear wave ...elastography (2D-SWE) in patients with chronic hepatitis B (CHB) infection.
Methods
Patients with CHB infection who underwent liver biopsy to assess liver fibrosis were consecutively included. 2D-SWE confirmation thresholds with a positive likelihood ratio ≥10 and 2D-SWE exclusion thresholds with a negative likelihood ratio ≤0.1 were identified to rule in or rule out significant fibrosis and cirrhosis, respectively.
Results
The first 515 patients (index cohort) and the next 421 patients (validation cohort) were included in the final analysis. The low and high cut-offs to rule out and rule in patients with significant fibrosis (≥ F2) were 5.4 kPa and 9.0 kPa, respectively, in patients with ALT levels ≤ 2 × the upper limit of normal (ULN) and 7.1 kPa and 11.2 kPa in patients with ALT levels > 2 × ULN. For cirrhosis (F4), the corresponding values were 8.1 kPa and 12.3 kPa in patients with ALT levels ≤ 2 × ULN and 11.9 kPa and 24.7 kPa in patients with ALT levels > 2 × ULN. The dual cut-off values showed an overall accuracy of more than 90% for diagnosis of the presence or absence of significant fibrosis and cirrhosis in the index and validation cohorts. There were no significant differences in the accuracy values between the cohorts (all
p
>0.05).
Conclusion
The ALT-adapted dual cut-offs of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis in patients with CHB infection.
Key Points
• The ALT-adapted dual cut-off values of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis.
• ALT levels did not influence the overall diagnostic accuracy for predicting significant fibrosis and cirrhosis.
• The ALT-adapted dual cut-offs in patients with ALT levels > 2 × ULN were markedly higher than those in patients with ALT levels
≤
2 × ULN.
•ELM suffers from local convergence in hydrological prediction problems.•CSA is used to search for good model parameters of ELM for the first time.•Proposed method yields satisfying results in ...multiple time-scale runoff series.
Reliable and stable hydrological prediction plays a vitally crucial role in the scientific operation of water resources system. As a famous artificial intelligence method for hydrological forecasting, extreme learning machine (ELM) has the virtues of fast training efficiency and strong generalization performance but is easily trapped into local optima because the preset computation parameters often remain unchanged in the learning process. In order to overcome this shortcoming, a practical evolutionary artificial intelligence model is developed for multiple scales nonstationary hydrological time series prediction. In the proposed method, an emerging evolutionary method called cooperation search algorithm (CSA) is used to search for the optimal input-hidden weights and hidden biases of the ELM model for the first time. The proposed method is used to forecast the runoff time series of three real-world hydrological stations in China. The experimental results show that the CSA approach can effectively determine satisfying network parameters of the ELM model, while our method can produce better results than the traditional ELM method in terms of all the performance evaluation indexes. Taking 1-step-ahead runoff forecasting at station B as an example, our method betters the ELM method with 15.76% and 42.35% improvements in both root mean squared error and mean absolute percentage error at the testing phase. Thus, a novel multiscale nonstationary hydrological prediction tool is developed to support the decision-making of water resource system.
We reported a BODIPY-based fluorescent probe for the simultaneous detection of GSH and Cys/Hcy. The nitrothiophenol moiety of the probe serves not only as a leaving group for the thiol-substitution ...reaction, but also a fluorescence quencher to provide a low emission background. The electron-withdrawing imidazolium group drastically increases reactivity of the Cys/Hcy-induced substitution–rearrangement reaction. The imidazolium group can further be replaced by GSH and resulted in a bithioether-product ( λ abs = 568 nm, λ em = 588 nm), which showed distinct photophysical properties from the amino-product ( λ abs = 443 nm, λ em = 530 nm) in the case of Cys/Hcy. It is noted that they exhibited great differences in absorption spectra of more than 120 nm. Thus, the simultaneous detection of GSH and Cys/Hcy can be achieved at different excitation wavelengths. The probe can quantitatively determinate the amount of Cys, Hcy and GSH in certain concentration ranges. We also found that the probe could detect GSH and Cys in living cells from different emission channels.
Four β-cyclodextrin (β-CD)/benzene derivatives gels were developed as temporary plugging agent for different formation temperature ranges. The gel was composed of β-CD as the host, benzene ...derivatives as the guest and 1,2-propylene glycol as solvent. The systems undergo a "sol-gel" phase transition when the temperature rises. By adding different benzene derivatives (toluene/phenol/benzoic acid) in the system, the gel temperature could be controlled between 70 and 130 ℃. And the gel turns into a solution again upon further heating. Further, FT-IR, X-ray diffractometer (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) were used to analyze the micromorphology and phase transformation mechanism of the gel. The results confirmed that the gelling process of the four systems mainly depends on non-covalent bond action. Furthermore, the degradation rate and the plugging and permeability recovery rate were tested. The results showed that the degradation rate of the four systems were finally greater than 98%, the plugging rate was greater than 85%, and permeability recovery value was more than 98%, which can meet the requirements of fracturing temporary plugging with the formation temperature of 70 ∼ 130 ℃.
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•The binding ability of benzene derivatives to β-cyclodextrin affects the gelation temperature.•As the temperature increases, the system is self-assembly into a three-dimensional network structure.•The “sol-gel” phase transformation mainly depends on supramolecular force rather than chemical change.•Supramolecular gel based on cyclodextrin has good temporary plugging and self-degradation effect in tight oil reservoirs.
Biological thiols, including cysteine (Cys), homocystein (Hcy) and glutathione (GSH), play crucial roles in maintaining the appropriate redox status of biological systems. An abnormal level of ...biothiols is associated with different diseases, therefore, the discrimination between them is of great importance. Herein, we present two fluorescent sensors for selective detection of biothiols based on our recently reported intramolecular displacement mechanism. We expanded this mechanism to commercially available chromophores, 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) and heptamethine cyanine dye IR-780. The sensors operate by undergoing displacement of chloride by thiolate. The amino groups of Cys/Hcy further replace the thiolate to form amino-substituted products, which exhibit dramatically different photophysical properties compared to sulfur-substituted products from the reaction with GSH. NBD-Cl is highly selective towards Cys/Hcy and exhibits significant fluorescence enhancement. IR-780 showed a variation in its fluorescence ratio towards Cys over other thiols. Both of the sensors can be used for live-cell imaging of Cys. The wide applicability of the mechanism may provide a powerful tool for developing novel fluorescent sensors for selective detection of biothiols.
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