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Electrochemical water splitting is one of the most sustainable approaches for generating hydrogen. Because of the inherent constraints associated with the architecture and materials, the conventional alkaline water electrolyzer and the emerging proton exchange membrane electrolyzer are suffering from low efficiency and high materials/operation costs, respectively. Herein, we design a membrane-free flow electrolyzer, featuring a sandwich-like architecture and a cyclic operation mode, for decoupled overall water splitting. Comprised of two physically-separated compartments with flowing H 2 -rich catholyte and O 2 -rich anolyte, the cell delivers H 2 with a purity >99.1%. Its low internal ohmic resistance, highly active yet affordable bifunctional catalysts and efficient mass transport enable the water splitting at current density of 750 mA cm −2 biased at 2.1 V. The eletrolyzer works equally well both in deionized water and in regular tap water. This work demonstrates the opportunity of combining the advantages of different electrolyzer concepts for water splitting via cell architecture and materials design, opening pathways for sustainable hydrogen generation. Seawater electrolysis is promising for grid-scale H 2 production without freshwater reliance, but high energy costs and detrimental Cl chemistry reduce its practical potential. Here, authors developed an energy-saving hybrid seawater electrolyzer for chlorine-free H 2 production and N 2 H 4 degradation.

With the advancement of technology, drug delivery systems and molecules with more complex architecture are developed. As a result, the drug absorption and disposition processes after administration of these drug delivery systems and engineered molecules become exceedingly complex. As the pharmacokinetic and pharmacodynamic (PK-PD) modeling allows for the separation of the drug-, carrier- and pharmacological system-specific parameters, it has been widely used to improve understanding of the in vivo behavior of these complex delivery systems and help their development. In this review, we summarized the basic PK-PD modeling theory in drug delivery and demonstrated how it had been applied to help the development of new delivery systems and modified large molecules. The linkage between PK and PD was highlighted. In particular, we exemplified the application of PK-PD modeling in the development of extended-release formulations, liposomal drugs, modified proteins, and antibody-drug conjugates. Furthermore, the model-based simulation using primary PD models for direct and indirect PD responses was conducted to explain the assertion of hypothetical minimal effective concentration or threshold in the exposure-response relationship of many drugs and its misconception. The limitations and challenges of the mechanism-based PK-PD model were also discussed.

To date, there are no studies regarding the lactylation profile and its role in critically ill patients. Thus, we aimed to examine expression of histone H3 lysine 18 (H3K18) lactylation and its role in patients with septic shock. Thirteen healthy volunteers and 35 critically ill patients from the Department of Surgical Intensive Care Medicine, Beijing Hospital were enrolled in our study. Baseline information and clinical outcomes were obtained prospectively. Lactylation levels of all proteins and H3K18 from peripheral blood mononuclear (PBMC) were determined by western blotting and serum levels of inflammatory cytokines by flow cytometry. Arginase-1 ( ) and Krüppel-like factor-4 ( ) mRNA expression was evaluated by quantitative real-time PCR (qRT-PCR). Lactylation was found to be an all-protein post-translational modification and was detected in PBMCs from both healthy volunteers and critically ill patients, with a significantly higher relative density in shock patients ( =2.172, =0.045). H3K18la was expressed in all subjects, including healthy volunteers, with the highest level in septic shock patients (compared with non-septic shock patients, critically ill without shock patients and healthy volunteers =0.033, 0.000 and 0.000, respectively). Furthermore, H3K18la protein expression correlated positively with APACHE II scores, SOFA scores on day 1, ICU stay, mechanical ventilation time and serum lactate ( =0.42, 0.63, 0.39, 0.51 and 0.48, respectively, =0.012, 0.000, 0.019, 0.003 and 0.003, respectively). When we matched patients with septic shock and with non-septic shock according to severity, we found higher H3K18la levels in the former group ( =-2.208, =0.040). Moreover, H3K18la exhibited a close correlation with procalcitonin levels ( =0.71, =0.010). Patients with high H3K18la expression showed higher IL-2, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-α levels ( =0.33, 0.37, 0.62, 0.55, 0.65, 0.49 and 0.374 respectively, =0.024, 0.011, 0.000, 0.000, 0.000 and 0.000 respectively). H3K18la expression also displayed a positive correlation with the level of mRNA ( =0.561, =0.005). Lactylation is an all-protein post-translational modification occurring in both healthy subjects and critically ill patients. H3K18la may reflect the severity of critical illness and the presence of infection. H3K18la might mediate inflammatory cytokine expression and overexpression and stimulate the anti-inflammatory function of macrophages in sepsis.

Electrochemical carbon dioxide reduction reaction using sustainable energy is a promising approach of synthesizing chemicals and fuels, yet is highly energy intensive. The oxygen evolution reaction is particularly problematic, which is kinetically sluggish and causes anodic carbon loss. In this context, we couple CO 2 electrolysis with hydrogen oxidation reaction in a single electrochemical cell. A Ni(OH) 2 /NiOOH mediator is used to fully suppress the anodic carbon loss and hydrogen oxidation catalyst poisoning by migrated reaction products. This cell is highly flexible in producing either gaseous (CO) or soluble (formate) products with high selectivity (up to 95.3%) and stability (>100 h) at voltages below 0.9 V (50 mA cm −2 ). Importantly, thanks to the “transferred” oxygen evolution reaction to a water electrolyzer with thermodynamically and kinetically favored reaction conditions, the total polarization loss and energy consumption of our H 2 -integrated CO 2 reduction reaction, including those for hydrogen generation, are reduced up to 22% and 42%, respectively. This work demonstrates the opportunity of combining CO 2 electrolysis with the hydrogen economy, paving the way to the possible integration of various emerging energy conversion and storage approaches for improved energy/cost effectiveness. Electrochemical CO2 reduction is a promising method of producing sustainable chemicals and fuels, yet is highly energy intensive. Here, the authors couple CO2 electrolysis with hydrogen oxidation using a Ni(OH) 2 /NiOOH auxiliary electrode to enhance energy efficiency.

Alkaline water electrolysis (AWE) is among the most developed technologies for green hydrogen generation. Despite the tremendous achievements in boosting the catalytic activity of the electrode, the operating current density of modern water electrolyzers is yet much lower than the emerging approaches such as the proton‐exchange membrane water electrolysis (PEMWE). One of the dominant hindering factors is the high overpotentials induced by the gas bubbles. Herein, the bubble dynamics via creating the superaerophobic electrode assembly is optimized. The patterned Co‐Ni phosphide/spinel oxide heterostructure shows complete wetting of water droplet with fast spreading time (≈300 ms) whereas complete underwater bubble repelling with 180° contact angle is achieved. Besides, the current collector/electrode interface is also modified by coating with aerophobic hydroxide on Ti current collector. Thus, in the zero‐gap water electrolyzer test, a current density of 3.5 A cm−2 is obtained at 2.25 V and 85 °C in 6 m KOH, which is comparable with the state‐of‐the‐art PEMWE using Pt‐group metal catalyst. No major performance degradation or materials deterioration is observed after 330 h test. This approach reveals the importance of bubble management in modern AWE, offering a promising solution toward high‐rate water electrolysis. The superaerophobic electrode assembly enables the optimization of bubble dynamics in the alkaline electrolyzer, significantly decreasing the ohmic loss during water splitting at high current densities. The resulting zero‐gap water electrolyzer delivers a current density of 3.5 A cm−2 at 2.25 V and 85 °C in 6 m KOH.

Inductive power transfer (IPT) technology is used in various applications owing to its safety features, robust environmental adaptability, and convenience. In some special applications, the charging pads are required to be as compact as possible to accommodate practical spatial requirements, and even size requirements dictate that the diameter of the charging pad matches the air gap. However, such requirements bring about a decrease in the transmission efficiency, power, and tolerance to misalignment of the system. In this paper, by comparing a double-sided inductor–capacitor–capacitor (LCC), double-sided inductor–capacitor–inductor (LCL), series–series (SS), and inductor–capacitor–capacitor–series (LCC-S) compensation topologies in IPT systems, we identified a double-sided LCC compensation topology that is suitable for weak coupling coefficients. Furthermore, this study modeled and simulated the typical parameters of coreless coils in circular power pads, such as the number of coil layers, turns, wire diameter, and wire spacing, to enhance the mutual inductance of the magnetic coupler during misalignment and long-distance transmission. A wireless charging system with 640 W output power was built, and the experimental results show that a maximum dc-dc efficiency of over 86% is achieved across a 200 mm air gap when the circular power pad with a diameter of 200 mm is well aligned. The experimental results show that using a suitable compensation topology and optimizing the charging pad parameters enables efficient IPT system operation when the coupling coefficient is 0.02.

The rapid development of intelligent networked vehicles (ICVs) has brought many positive effects. Unfortunately, connecting to the outside exposes ICVs to security threats. Using secure protocols is an important approach to protect ICVs from hacker attacks and has become a hot research area for vehicle security. However, most of the previous studies were carried out on V2X networks, while those on in-vehicle networks (IVNs) did not involve Ethernet. To this end, oriented to the new IVNs based on Ethernet, we designed an efficient secure scheme, including an authentication scheme using the Scalable Service-Oriented Middleware over IP (SOME/IP) protocol and a secure communication scheme modifying the payload field of the original SOME/IP data frame. The security analysis shows that the designed authentication scheme can provide mutual identity authentication for communicating parties and ensure the confidentiality of the issued temporary session key; the designed authentication and secure communication scheme can resist the common malicious attacks conjointly. The performance experiments based on embedded devices show that the additional overhead introduced by the secure scheme is very limited. The secure scheme proposed in this article can promote the popularization of the SOME/IP protocol in IVNs and contribute to the secure communication of IVNs.

This study focuses on the development of electric vehicles (EV) in the private passenger vehicle fleet in Beijing (China), analyzes how EVs will penetrate in the market, and estimates the resulting impacts on energy consumption and CO2 emissions up to 2030. A discrete choice model is adopted with consideration of variables including vehicle technical characteristics, fuel prices, charging conditions and support policies. Results show that by 2030, without technological breakthrough and support policies, the market share of EV will be less than 7%, with gasoline dominating the energy structure. With fast technological progress, charging facility establishment, subsidies and tax breaks, EVs will account for 70% of annual new vehicle sales and nearly half of the vehicle stock by 2030, resulting in the substitution of nearly 1 million tons of gasoline with 3.2 billion kWh electricity in 2030 and the reduction of 0.6 million tons of CO2 emission in 2030. Technological progress, charging conditions and fuel prices are the top three drivers. Subsidies play an important role in the early stage, while tax and supply-side policies can be good options as long-term incentives.

Purpose Willingness-to-pay (WTP) and willingness-to-accept (WTA) are widely used measures of individual preferences in valuing healthcare services; however, a persistent disparity between them, often with WTA exceeding WTP, raises concerns. This study aims to review empirical research evidence to achieve a comprehensive understanding of the disparity between WTA and WTP for health outcomes or healthcare goods and services. Methods A search was conducted in PubMed, Embase, Web of Science, and Scopus from inception to November 15, 2023, for empirical research articles reporting both WTA and WTP in the healthcare field. Data extracted from the included studies encompassed WTA and WTP values, participation response rates, and other study characteristics. Descriptive analyses were conducted to compare WTA/WTP ratios across studies, and chi-square tests were applied to examine differences in response rates where applicable. Results A total of 779 records were identified through database searches. After removing duplicates, 405 records remained for title and abstract screening. Of these, 70 articles were retrieved for full-text review, and 28 articles met the eligibility criteria for inclusion in the final qualitative analysis, encompassing 35 distinct studies or subgroups. The reported WTA/WTP ratios ranged from 0.14 to 29.19, with a median value of 1.61, indicating that individuals often demand higher compensation to give up healthcare benefits than they are willing to pay to obtain them. Among the empirical studies analyzed, 29 studies (82.86%) from 24 articles reported WTA values that exceeded WTP values, while 6 studies (17.14%) from the remaining 4 articles indicated WTA values lower than WTP values. Among the 14 studies reporting both WTA and WTP response rates, six studies indicated a significantly lower WTA response rate compared to the WTP response rate, whereas two studies found the WTA response rate to be significantly higher ( P  < 0.05). The WTP response rate was observed to range from 0.89 to 20.23 times that of the WTA response rate. Conclusions The results of this study suggest that losses in health outcomes or healthcare goods and services are valued differently than gains. The disparities between WTA and WTP are influenced by various factors, including the income effect and personal preferences. Individual preferences shape perceptions of WTA and WTP questions, resulting in varied response rates. Considering these disparities in the medical and healthcare fields can assist policymakers in making more informed decisions regarding the allocation of medical and health resources.

One of the most striking hallmarks shared by various neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis, is microglia-mediated and astrocyte-mediated neuroinflammation. Although inhibitions of both harmful proteins and aggregation are major treatments for neurodegenerative diseases, whether the phenomenon of non-normal protein or peptide aggregation is causally related to neuronal loss and synaptic damage is still controversial. Currently, excessive production of reactive oxygen species (ROS), which induces mitochondrial dysfunction in neurons that may play a key role in the regulation of immune cells, is proposed as a regulator in neurological disorders. In this review, we propose that mitochondrial DNA (mtDNA) release due to ROS may act on microglia and astrocytes adjacent to neurons to induce inflammation through activation of innate immune responses (such as cGAS/STING). Elucidating the relationship between mtDNA and the formation of a pro-inflammatory microenvironment could contribute to a better understanding of the mechanism of crosstalk between neuronal and peripheral immune cells and lead to the development of novel therapeutic approaches to neurodegenerative diseases.