Acute kidney injury in China: A neglected truth and perspective

Acute kidney injury in China: A neglected truth and perspectiv

Table1_Large-scale deep reinforcement learning method for energy management of power supply units considering regulation mileage payment.XLSX

To improve automatic generation control (AGC) performance and reduce the wastage of regulation resources in interconnected grids including high-proportion renewable energy, a multi-area integrated AGC (MAI-AGC) framework is proposed to solve the coordination problem of secondary frequency regulation between different areas. In addition, a cocktail exploration multi-agent deep deterministic policy gradient (CE-MADDPG) algorithm is proposed as the framework algorithm. In this algorithm, the controller and power distributor of an area are combined into a single agent which can directly output the power generation command of different units. Moreover, the cocktail exploration strategy as well as various other techniques are introduced to improve the robustness of the framework. Through centralized training and decentralized execution, the proposed method can nonlinearly and adaptively derive the optimal coordinated control strategies for multiple agents and is verified on the two-area LFC model of southwest China and the four-area LFC model of the China Southern Grid (CSG).</p

How PEGylation Enhances the Stability and Potency of Insulin: A Molecular Dynamics Simulation

While the effectiveness of PEGylation in enhancing the stability and potency of protein pharmaceuticals has been validated for years, the underlying mechanism remains poorly understood, particularly at the molecular level. A molecular dynamics simulation was developed using an annealing procedure that allowed an all-atom level examination of the interaction between PEG polymers of different chain lengths and a conjugated protein represented by insulin. It was shown that PEG became entangled around the protein surface through hydrophobic interaction and concurrently formed hydrogen bonds with the surrounding water molecules. In addition to enhancing its structural stability, as indicated by the root-mean-square difference (rmsd) and secondary structure analyses, conjugation increased the size of the protein drug while decreasing the solvent accessible surface area of the protein. All these thus led to prolonged circulation life despite kidney filtration, proteolysis, and immunogenic side effects, as experimentally demonstrated elsewhere. Moreover, the simulation results indicated that an optimal chain length exists that would maximize drug potency underpinned by the parameters mentioned above. The simulation provided molecular insight into the interaction between PEG and the conjugated protein at the all-atom level and offered a tool that would allow for the design of PEGylated protein pharmaceuticals for given applications

MOESM1 of Green synthesis of enzyme/metal-organic framework composites with high stability in protein denaturing solvents

Additional file 1. Additional information

Realization of a coupled-mode heat engine with cavity-mediated nanoresonators

We report an experimental demonstration of a coupled-mode heat engine in a two-membrane-in-the-middle cavity optomechanical system. The normal mode of the cavity-mediated strongly coupled nanoresonators is utilized as the working medium and an Otto cycle is realized by extracting work between two phononic thermal reservoirs. The heat engine performance is characterized in both normal mode and bare mode pictures, which reveals that the correlation of two membranes plays a significant role during the thermodynamic cycle. Moreover, a straight-twin nanomechanical engine is implemented by engineering the normal modes and operating two cylinders out-of-phase. Our results demonstrate an essential class of heat engine for the first time in cavity optomechanical systems and provide a novel platform for investigating heat engines of interacting subsystems in small scales with controllability and scalability

Supramolecular Enantiodifferentiating Photocyclodimerization of 2-Anthracenecarboxylate Mediated by Capped γ-Cyclodextrins: Critical Control of Enantioselectivity by Cap Rigidity

A series of γ-cyclodextrins (CDs) modified with capping and noncapping aromatic group(s) were synthesized to mediate the enantiodifferentiating [4 + 4] photocyclodimerization of 2-anthracenecarboxylic acid (AC). The complexation behavior of these γ-CDs with AC was studied by circular dichroism, UV−vis, and NMR spectroscopy to reveal the formation of stable 1:2 host−guest complexes in all cases. The capped γ-CD with a biphenyl group bridging the A and D glucose units was shown to confine the included AC molecules most strictly among the capped and noncapped γ-CDs examined. Photocyclodimerization of AC mediated by capped γ-CDs considerably improved the yield and enantiomeric excess (ee) of the head-to-head photodimer 3. The ee and the absolute configuration of syn-head-to-tail photodimer 2 critically depended on the rigidity of capping. Thus, the flexibly capped and rim-substituted γ-CDs afforded 2 in moderate ee’s of around 40%, whereas γ-CD with a rigid biphenyl cap gave the antipodal 2 in −58% ee. Interestingly, the ee of 2 mediated by flexibly capped γ-CDs was highly sensitive to the temperature variation as a consequence of large differential entropy changes in the enantiodifferentiation process. In contrast, the entropy effect does not appear to play a significant role in the photocyclodimerization of AC with rigidly capped γ-CDs. The differential enthalpy and entropy changes obtained for the enantiodifferentiating photocyclodimerization mediated by native and most of the modified γ-CDs gave an excellent enthalpy−entropy compensation plot with an exception of the biphenyl-capped γ-CD, indicating the operation of significantly different enantiodifferentiation mechanism within the rigidly capped cyclodextrin cavity

Revisiting the seismic hazards of faults surrounding the 2022 Ms6.8 Luding earthquake, Sichuan, China

The occurrence of the Ms6.8 Luding earthquake on 5 September 2022 filled the seismic gap in the southeastern segment of the Xianshuihe fault zone and transferred stress to the surrounding faults, which attracted much more attention to the seismic hazard. In this study, we calculate the coseismic Coulomb stress changes caused by the Ms6.8 Luding earthquake and analyze its relationship with the relocated aftershocks, and further explore the stress evolution before the Luding earthquake and seismic hazards on the surrounding faults after it. The results show significant coseismic Coulomb stress increases in the northern Anninghe fault zone and the coseismic unruptured section of the southeastern Xianshuihe fault zone. Aftershocks are highly correlated with the positive coseismic Coulomb stress change, wherein eight out of eleven aftershocks of M ≥ 3.0 occurred in areas with significant stress increases ranging from 0.03 MPa to 0.44 MPa, indicating the triggering effect. The Moxi fault experiences co- and post-seismic Coulomb stress changes due to historical M ≥ 7.0 strong earthquakes since 1515, which help understand the seismogenic mechanism of the Luding earthquake. Moreover, the Luding earthquake advanced the potential earthquakes in the northern section of the Anninghe fault zone by approximately 60 years, further highlighting the potential seismic hazards.</p

Real-Time Study of Interactions between Cytosine–Cytosine Pairs in DNA Oligonucleotides and Silver Ions Using Dual Polarization Interferometry

The real-time conformational changes of cytosine (C)-rich ssDNA oligonucleotides upon binding with silver ions (Ag⁺) were studied using dual polarization interferometry (DPI). Upon the addition of Ag⁺, Ag⁺ selectively bound to cytosine–cytosine mismatches and formed C–Ag⁺–C complexes, inducing change of the structure of the C-rich ssDNA from random coil conformation to duplex conformation, whereas the control ssDNA without cytosine–cytosine mismatches had no such signal, which was consistent with circular dichroism (CD) characterization. The conformational change of DNA was reflected on the changes of the mass, thickness, and density values resolved by DPI. The calibration curves showed that as the concentration of Ag⁺ increased from 10 nM to 8 μM, the thickness and mass values increased linearly while the density values decreased linearly. Other metal ions such as K⁺, Ca²⁺, Na⁺, Mg²⁺, Zn²⁺, Mn²⁺, Ni²⁺, and Pb²⁺ did not interfere with the interaction between Ag⁺ and C-rich ssDNA, indicating that this method had a good selectivity. The practical application of this biosensor was also investigated in real samples such as drinking water. Besides, cysteine could specifically capture Ag⁺ from C–Ag⁺–C complexes and transformed the structure of the C-rich DNA back from rigid double-stranded conformation to random coil conformation, which allowed cysteine to be detected selectively as well. It is expected that this biosensing strategy may be utilized to study the interaction of DNA with other molecules

Nanothorn Filter-Facilitated Online Cell Lysis for Rapid and Deep Intracellular Profiling by Single-Cell Mass Spectrometry

Mass spectrometry combined with flow cytometry is emerging for high-throughput single-cell metabolite analysis but still has problems with limited intracellular information coverage. Here, we show a simple and efficient all-in-one system integrating cell injection, cell extraction, online cell lysis, analyte ionization, and mass spectrometric detection for rapid single-HeLa-cell screening with in-depth profiling of cellular metabolites and drugs. Zinc oxide nanothorn-decorated filters with three bore sizes (5.22, 8.36, and 16.75 μm) were fabricated for efficient online lysis of the cell membrane (even nuclear membrane) to facilitate intracellular analyte release and demonstrated to have a size effect for potential subcellular discrimination. The two smaller-bore filters gave 2–11-fold improvements in signal response for representative intracellular metabolites, such as adenosine, glutamine, and leucine/isoleucine. Especially, the smallest-bore filter enabled successful detection of the metabolites in the nucleus, including tetrahydrobiopterin and cyclic guanosine monophosphate. The developed all-in-one system was explored to monitor the uptake of four anticancer drugs, including 5-fluorouracil, doxorubicin, gambogic acid, and paclitaxel in single cells, and further to investigate the drug uptake trends at the subcellular level. The all-in-one system integrates the merits of high-throughput single-cell screening and in-depth intracellular information profiling and is promising for high-coverage single-cell metabolome analysis to serve cell biology research and cancer research

Organic Mass Cytometry Discriminating Cycle Stages of Single Cells with Small Molecular Indicators

Cell cycle is a significant factor toward cellular heterogeneity, so cell cycle discrimination is a precise measurement on the top of single-cell analysis. Single-cell analysis based on organic mass spectrometry has received great attention for its unique ability to profile single-cell metabolome, but the influence of cell cycle on cellular metabolome heterogeneity has been overlooked until now due to the lack of a compatible cell cycle discrimination method. Here, we report a robust protocol based on the combination of three small molecular indicators, consisting of two small molecular labels (Hoechst and docetaxel) and one cellular endogenous compound [phosphocholine (34:1)], to discriminate single cells at different cycle stages in real time by organic mass cytometry. More than 6000 HeLa cells were acquired by an improved organic mass cytometry system to build a cell cycle differentiation model. The model successfully discriminated single HeLa cells, SCC7, and Hep G2 cells, at G0/G1, S, and G2/M stages with larger than 85% sensitivity and larger than 89% specificity. Along with cell cycle discrimination, obvious heterogeneity of amino acids, nucleotides, energy metabolic intermediates, and phospholipids was observed among single cells at different cycle stages by this protocol, further demonstrating the necessity of cell cycle discrimination for cellular metabolome heterogeneity research and the potential of more endogenous small molecular compounds for cell cycle discrimination