Steady Cycle Research Articles

Late Holocene echinoderm assemblages can serve as paleoenvironmental tracers in an Antarctic fjord

High Latitude fjords can serve as sediment trap, bearing different type of proxies, from geochemical to micropaleontological ones, making them exceptional tools for paleoenvironmental reconstruction. However, some unconventional proxies can be present and can be used to depict a comprehensive and exhaustive interpretation of past changes. Here, studying a sediment core in Edisto Inlet (Ross Sea, Antarctica) we used irregular echinoid spines and ophiuroids (Ophionotus victoriae) ossicles to trace environmental changes throughout the last 3.6 kyrs BP. Irregular echinoids can serve as proxy for the organic matter content, while O. victoriae ossicles can be used as proxy for steady sea-ice cycle along with organic deposition events. O. victoriae release a high number of ossicles, making estimation about the population quite challenging; still, presence data, can be easily collected. By applying Generative Additive Models to the stratigraphical distribution of these data, we detected an environmental phase that was previously unnoticed by other traditional proxies: the Ophiuroid Optimum (2–1.5 kyrs BP). In conclusion, here we demonstrate how echinoderm presence can be used as a valuable source of information, while proving the potential of modelling binary data to detect long-term trend in Holocene stratigraphical records.

Safe Insulation from the Inside as a Solution to the Energy and Climate Crisis

Along with rapid climate changes, issues related to energy efficiency and efficient use of energy are becoming more and more relevant in the EU. One of the energy-consuming sectors is buildings, which are responsible for about 40% of the EU final energy consumption and 36% of CO2 emissions. In addition to this, the current energy crisis has acutely raised the issue of energy poverty. Therefore, one of the ways to fight with energy poverty and high energy consumption in buildings is insulation from the inside. However, warming from the inside is risky due to hygrothermal processes and mold risks. This study assesses the hygrothermal performance of masonry walls with 9 interior insulation systems exposed to different external conditions in the climate chambers. Masonry walls were tested in a steady cycle, a dynamic cycle, a dynamic cycle with rain and a steady cycle as drying. Also, an identical simulation of the hygrothermal process was carried out in the DELPHIN software to compare results of both testing methods. Both vapor-open and vaportight systems were chosen as insulation systems. Results show that the hygrothermal behavior of vapor-open and vapor-tight insulation systems are different under different test cycles regarding different vapor diffusion resistance of materials. Mathematical simulations results are different from the climate chamber simulations, because of the change in material humidity, that are changing during climate chambers simulations. From this it can be concluded that mathematical simulations do not give a complete vision of hydrothermal processes, because they are dynamic, but in modeling the properties of materials are defined. The study provides valuable data on hygrothermal processes in different wall insulation systems from the inside.

Ultrafast-Loaded Nickel Sulfide on Vertical Graphene Enabled by Joule Heating for Enhanced Lithium Metal Batteries.

The design and fabrication of a lithiophilic skeleton arehighly important for constructing advanced Li metal anodes. In this work, a new lithiophilic skeleton is reported by planting metal sulfides (e.g., Ni3S2) on vertical graphene (VG) via a facile ultrafast Joule heating (UJH) method, which facilitates the homogeneous distribution of lithiophilic sites on carbon cloth (CC) supported VG substrate with firm bonding. Ni3S2 nanoparticles are homogeneously anchored on the optimized skeleton as CC/VG@Ni3S2, which ensures high conductivity and uniform deposition of Li metal with non-dendrites. By means of systematic electrochemical characterizations, the symmetric cells coupled with CC/VG@Ni3S2 deliver a steady long-term cycle within 14mV overpotential for 1800h (900 cycles) at 1mA cm-2 and 1 mAh cm-2. Meanwhile, the designed CC/VG@Ni3S2-Li||LFP full cell shows notable electrochemical performance with a capacity retention of 92.44% at 0.5 C after 500 cycles and exceptional rate performance. This novel synthesis strategy for metal sulfides on hierarchical carbon-based materials sheds new light on the development of high-performance lithium metal batteries (LMBs).

Bimetallic metal-organic frameworks -derived lithiophilic and conductive MnO/Co/C enabled intermittent deposition model for high-performance lithium metal anode

The design of lithiophilic three-dimensional (3D) skeletons has proven to be effective in inhibiting dendrite growth and improving the Coulombic efficiency of lithium metal anodes (LMAs). However, for the 3D skeletons with homogenous lithiophilicity, Li would preferentially deposit on the top of 3D collectors, what's more, the intrinsic low electrical conductivity of metal-organic frameworks (MOFs)-derived oxides which are often employed as the lithiophilic materials on 3D skeletons affects their electrochemical kinetics. We firstly prepare MnO/Co/C derived from MnCo-MOFs on carbon cloths (CC) by a simple method and a composite anode (Li-CC@MnO/Co/C) is obtained. The synergistic effect of the electrical conductivity of Co and lithiophilicity of MnO facilitates their electrochemical kinetics. The Li-CC@MnO/Co/C composite anode exhibites long cycle life and low hysteretic voltage in the symmetrical cell with a high areal capacity and current density (5 mA h cm−2, 5 mA cm−2) and a steady cycle performance of 80 mA h g−1 at 10 C for nearly 300 cycles in easter-based electrolyte. This work might propose a rational design for a high-performance LMA, particularly suitable for practical applications.

Polyethylene oxide-Based solid electrolytes with fast Li-ion transport channels constructed from 2D montmorillonite for solid-state lithium-metal batteries

Polyethylene oxide (PEO)-based solid-state electrolytes (SSEs) typically struggle with poor ionic conductivity, low lithium (Li)-ion transference number, and narrow electrochemical window. For overcoming these drawbacks, we designed a promising composite SSE (CSSE), i.e., a Li-containing ionic liquid (LiIL) was inserted into the Li-montmorillonite (LiMNT) layered structure to form an active filler (LiIL@LiMNT), involving two-dimensional (2D) fast transport channels of Li-ion inside PEO electrolyte. Benefitting from an enhancement of the 2D Li-ion transport channels, the obtained CSSE exhibited an excellent ion conductivity of 1.38 × 10−4 S cm−1 at 30 °C as well as a satisfactory Li-ion transference number (0.38). A Li symmetric battery with the CSSE exhibited a steady cycle for 3000 h with 0.2 mA cm−2 at 60 °C. Under the rate of 0.5C at 60 °C, the solid-state Li-metal batteries (SSLMBs) assembled with LiFePO4 and LiNi0.33Co0.33Mn0.33O2 cathodes maintained a considerable reversible capacity after 400 and 100 cycles, respectively. The assembled SSLMB also achieved a satisfactory performance at 40 °C. The 2D active filler prepared in this work forms efficient 2D Li-ion transport channels inside the CSSE while maintaining a tight interfacial contact with electrodes, which is crucial to achieve a superior performance for CSSEs. This strategy of constructing 2D ion transport channels in polymer electrolytes also provides another way for the design of other CSSEs.

Performance analysis and multi-objective optimization of an irreversible isothermal heating modified air standard Brayton cycle

In this paper, a new five-branch Brayton cycle, i.e., isothermal heating modified air standard Brayton cycle, is proposed based on the isothermal heating modified steady flow Brayton cycle models established in previous literatures. The finite time thermodynamics theory is used to build the irreversible isothermal heating modified air standard Brayton cycle model. The impacts of the cycle maximum temperature ratio (τ), pre-expansion ratio (ρ) and various losses on the properties of power (P) versus compression ratio (γ), efficiency (η) versus γ, power density (Pd) versus γ, ecological function (E) versus γ, P versus η, Pd versus η and E versus η are examined. The multi-objective genetic algorithm is used to optimize different objective (η, E, P and Pd) combinations when γ is taken as the optimization variables. The deviation indexes (Ds) of the Shannon Entropy, TOPSIS and LINMAP are calculated to determine the optimal solution set. The findings demonstrate that raising ρ and τ, and lowering various losses can clearly improve cycle performance. For the optimization of P−E, the decision-making schemes of TOPSIS is better and corresponding D is 0.1342. The performance of the modified BC is better than that of the classical BC.

High mechanical strength Si anode synthesis with interlayer bonded expanded graphite structure for lithium-ion batteries

Despite advancements in silicon-based anodes for high-capacity lithium-ion batteries, their widespread commercial adoption is still hindered by significant volume expansion during cycling, especially at high active mass loadings crucial for practical use. The root of these challenges lies in the mechanical instability of the material, which subsequently leads to the structural failure of the electrode. Here, we present a novel synthesis of a composite combining expanded graphite and silicon nanoparticles. This composite features a unique interlayer-bonded graphite structure, achieved through the application of a modified spark plasma sintering method. Notably, this innovative structure not only facilitates efficient ion and electron transport but also provides exceptional mechanical strength (Vickers hardness: up to 658 MPa, Young’s modulus: 11.6 GPa). This strength effectively accommodates silicon expansion, resulting in an impressive areal capacity of 2.9 mA h cm−2 (736 mA h g−1) and a steady cycle life (93% after 100 cycles). Such outstanding performance is paired with features appropriate for large-scale industrial production of silicon batteries, such as active mass loading of at least 3.9 mg cm−2, a high-tap density electrode material of 1.68 g cm−3 (secondary clusters: 1.12 g cm−3), and a production yield of up to 1 kg per day.

The Safe Insulation from the Inside as a Solution to the Energy and Climate Crisis

Abstract During the time when the European Union is facing an energy crisis, it is essential to understand ways to overcome it more easily. As one of the consuming sectors, buildings play a crucial role in improving energy efficiency. Therefore, one of the ways to fight with energy crisis and high energy consumption in buildings is insulation from the inside. This study assesses the hygrothermal performance of masonry walls with 9 interior insulation systems (mineral wool with vapor barrier, XPS, PIR, cork, expanded cork, aerogel blanket, wood fibre plates, perlite board) exposed to different external conditions in the climate chambers. Masonry walls were tested in a steady cycle with cold box temperature 18 °C and 40 % RH), a dynamic cycle that follows daily fluctuations, a dynamic cycle with rain. Also, an identical simulation of the hygrothermal process was carried out in the DELPHIN software to compare results of both testing methods. The temperature between the thermal insulation layer and the brick wall in all thermal insulation systems is approximately 7-8 hours behind the temperature of the outdoor climatic chamber. A dynamic cycle with rain simulation has a significant impact on the hygrothermal behaviour of thermal insulation systems. The study provides valuable data on hygrothermal processes in different wall insulation systems from the inside.

The influence of particle oxidation catalyst (POC) mode on emissions reduction of a turbo-charging non-road diesel under wide operating conditions

In the present study, the influence of particle oxidation catalyst (POC) on emissions reduction of a non-road diesel engine is experimentally investigated under wide operating conditions. First, the diesel engine with four POC-aftertreatments (other reactors are kept unchanged) is tested under eight operating conditions non-road steady cycle (NRSC). Then, the diesel engine emissions with best POC-aftertreatment combination and without aftertreatment are comparatively tested under universal conditions. The experiments show that under NRSC, POC-3 which has Pt catalysts with Al2O3 support, asymmetrical channels layout and closed outlet form structure has the best overall exhaust purification, especially for nitrogen oxides (NOx) and particulate matter (PM). The PM conversions efficiency of POC-1, POC-2, POC-3 and POC-4 is 15.3%, 51.7%, 60.9% and 58.8%, respectively under NRSC. The contribution rates of emissions analysis results under NRSC indicated that a single POC mode cannot cover the whole engine operating range. Under universal characteristic test, the brake specific fuel consumption (BSFC) of original engine is a little lower than that of POC-3 in the whole engine operating conditions due to higher exhaust back pressure of POC-3. The engine with POC-3 has very good exhaust conversion efficiencies, the average conversion efficiency of NOx, PM, carbon monoxide (CO), and hydrocarbons (HC) is 96.1%, 51.9%, 77.8%, and 95.6%, respectively. The PM capture efficiency of POC-3 at low load of whole speed range and all load of medium speed are more than 50% compared to other operating conditions. There is little effect on carbon dioxide (CO2) emissions by POC.

Improvement of Ionic Conductivity in Li7La3Zr2O12 (LLZO) Solid Electrolyte By Doping with Aluminum/Tungsten

Recently, there has been increasing interest in solid electrolytes, which are the most important materials in all-solid-state lithium-ion batteries. Among all solid electrolytes, garnet-type Li7La3Zr2O12 (LLZO) has been proven to be one of the most promising electrolytes due to its high Li+ conductivity, wide potential window, and electrochemical stability towards metallic lithium anode. In particular, cubic garnet-type LLZO solid electrolytes have received a lot of attention for the development of high-performance all-solid-state batteries with safety, energy density, and long cycle life. In this study, we synthesized LLZO solid electrolyte powders with garnet structure and determined the optimal composition and sintering temperature by adding Al/W to form a stable cubic phase.In this study, Al or W-doped LLZO were prepared by a post-doping method. In this process, LLZO powder was first prepared, and then mixed with Al2O3 or WO3 powders to produce doped LLZO ceramic electrolytes, respectively. During this process, the doped ions entered the LLZO lattice, increasing the lithium ion transport channels and promoting lithium ion conductivity. The sintering time, crucible, and sintering temperature were adjusted to investigate the optimal process conditions of the post-doping method. As a result, the doped solid electrolyte exhibited high lithium ion conductivity and low activation energy. Using the high lithium ion conductivity and broad electrochemical stability window of the Al or W doped LLZO SSE, the (NCM622)/(Al or W doped-LLZO) cell delivered a steady cycle for 100 cycles at 0.1C. The Al or W doped-LLZO prepared in this study showed advantages of high conductivity, simple preparation process, high reproducibility, and low cost, which provides technical support and reference for further application of garnet-type SSEs in solid-state batteries with high energy density.

Prediction of the transient emission characteristics from diesel engine using temporal convolutional networks

In order to predict the transient emission characteristics from diesel engine accurately and quickly, a novel prediction model, based on temporal convolutional networks (TCN) that incorporates the dilated convolutions and residual connections, was presented in the paper. Firstly, 1800 samples from the World Harmonized Transient Cycle (WHTC) were employed to train and validate the model. A Random Forest algorithm was used to select six top important variables as inputs to reduce the data dimensionality. Then the effect of model hyperparameters on the prediction performance was discussed and the optimal hyperparameter combination was obtained by a particle swarm optimization (PSO) algorithm. The optimized TCN model showed a coefficient of determination value (R2) above 0.972 for training dataset and 0.941 for validation dataset, respectively. The root mean squared error (RMSE) and the mean absolute error (MAE) were relatively low. Finally, the measured data from World Harmonized Steady Cycle (WHSC) was used to test model, and the average R2 value of 0.936 demonstrated that TCN model has excellent robustness and generalization. Moreover, a comparative investigation between TCN model and other advanced algorithms, including BP, GBRT, XGBoost, RNN, LSTM and Transformer, was also conducted. The result showed that TCN model has not only higher accuracy, but also has less computing time. This demonstrates that it is a promising method to predict the emission characteristics of diesel engine.

An optimizing hybrid interface architecture for unleashing the potential of sulfide-based all-solid-state battery

Sulfide-based all-solid-state lithium metal batteries are received tremendous focus due to the potential to deliver high energy density. Nevertheless, extremely unstable lithium/sulfide interface reaction and growth of unfavorable Li dendrites upon cycling remain challenging aspects and not yet fully settled. In this work, a lithophilic and high interfacial-energy hybrid interphase rich in chloride and Li-Ga alloy was in-situ constructed at Li/Li7P3S11 interface to tackle the vexing issue. Benefiting from the high interfacial energy and electronic insulation of LiCl in the hybrid interphase, lithium dendrites were effectively inhibited. In addition, the Li-Ga alloy-rich layer possesses excellent lithiophilicity and low diffusion energy, which can provide a uniform electric field distribution and induce rapid conduction of Li-ions. Consequently, the densification of Li/Li7P3S11 interface is achieved, which contributes to the decrease of interfacial impedance, uniform Li-ion flux and inhibition of continuous side reactions. Exalting, the Li symmetric cells with the Li-Ga alloy/LiCl (LGC) interlayer display high critical current density of 1.5 mA cm−2 and steady cycle for 1000 h at 0.3 mA cm−2 (0.3 mAh cm−2) at room temperature. Furthermore, the modified all-solid-state lithium battery also demonstrates an ultra-stable cycling. This work provides a reasonable design approach for the selection of interface layers in the all-solid-state lithium metal batteries (ASSLMBs) based on theoretical calculations, with the objective of attaining a stable Li/sulfide solid electrolyte interface.

Technical Performance Comparison of Horizontal and Vertical Ground-Source Heat Pump Systems

The configurations of ground heat exchangers (GHEs) play a significant role in the efficiency and sustainability of ground-source heat pump (GSHP) systems. However, there is a knowledge gap in understanding the performance differences between the horizontal and vertical GSHP systems in the same project under various heating and cooling demands. In this study, a technical performance comparison between GSHP systems coupled with horizontal ground loops and vertical boreholes under three scenarios of heating-to-cooling ratios (6 : 1, 2.4 : 1, and 1 : 1) was conducted. The simulations were based on a coupled thermal–hydraulic model for unsaturated soils that takes into account realistic ground surface boundary, GHE boundary, and the dynamics of heat pump efficiency. The GHEs were designed based on an experimental site located on the campus of a UK university. Results showed significant differences in the development of fluid temperatures and coefficient of performance (COP) of heat pumps between the horizontal and vertical GSHP systems due to the differences in the soil profiles and temperature boundaries. Both the fluid temperatures and heat pump COPs in the horizontal GSHP system reached a steady annual cycle after 2 years regardless of the heating-to-cooling ratios. For the vertical system, a general downward trend in the fluid temperatures and the COP of the heat pump in the heating mode can be found when a heating-to-cooling ratio was 6 : 1 or 2.4 : 1, while an overall upward trend in the fluid temperatures and the COP of the heat pump in the heating mode can be noted in the case of 1 : 1 heating-to-cooling ratio. Additionally, the heat pump operating in the cooling mode was off most of the time when a heating-to-cooling ratio was 6 : 1 or 2.4 : 1, while a declining trend in the COP of the heat pump in the cooling mode was exhibited in the case of a heating-to-cooling ratio of 1 : 1. The technical comparison reveals that the heating-to-cooling ratios would significantly affect the efficiency and sustainability of both GSHP systems.

Limited recharge of the southern highlands aquifer on early Mars

To determine plausible groundwater recharge fluxes on early Mars, we developed analytic and numerical solutions for an unconfined steady-state aquifer beneath the southern highlands. We showed that the aquifer’s mean hydraulic conductivity, K, is the primary constraint on the plausible magnitude of the mean steady recharge, r. By using geologic constraints, a mean hydraulic conductivity of K∼10−7m/s, and varying shoreline elevations and recharge distributions, the mean recharge must be of the order of 10−2 mm/yr. Recharge for other values of K can be estimated as r∼10−5K. Our recharge value is near the low end of previous estimates and significantly below published precipitation estimates. This suggests that, in a steady hydrologic cycle, most precipitation forms runoff as opposed to infiltrating into the subsurface. Alternatively, high rates of runoff production combined with a sufficiently slow transient aquifer response to recharge may limit major groundwater upwelling prior to the cessation of climatic excursions causing precipitation.

A new transient NOx prediction model for diesel engine based on neural network model with Pelican Optimization Algorithm

The World Harmonized Steady Cycle (WHSC) and the World Harmonized Transient Cycle (WHTC) are used to simulate the real driving conditions of a vehicle, which provides an opportunity for researchers to predict engine emissions through the use of models and thus investigate engine emission technologies or technology optimization to meet regulations. In this study, a Back-Propagation neural network (BPNN) is used to build an engine NOx prediction model, determine the number of nodes in the hidden layer, and optimize its weights and thresholds using the Pelican Optimization Algorithm (POA). NOx emissions from diesel engines are predicted by using the WHTC. The results show that the proposed model has a high R coefficient value of 0.9641. The results of the cold WHTC cycle NOx emission prediction shows that the mean absolute error (MAE) for the three cycles is about 32–35 ppm. The MAE was approximately 2.8% of the maximum NOx emissions in all cycles. These results indicate that the model has high accuracy in predicting transient NOx emissions.

Synergistic "Anchor-Capture" Enabled by Amino and Carboxyl for Constructing Robust Interface of Zn Anode.

While the rechargeable aqueous zinc-ion batteries (AZIBs) have been recognized as one of the most viable batteries for scale-up application, the instability on Zn anode-electrolyte interface bottleneck the further development dramatically. Herein, we utilize the amino acid glycine (Gly) as an electrolyte additive to stabilize the Zn anode-electrolyte interface. The unique interfacial chemistry is facilitated by the synergistic "anchor-capture" effect of polar groups in Gly molecule, manifested by simultaneously coupling the amino to anchor on the surface of Zn anode and the carboxyl to capture Zn2+ in the local region. As such, this robust anode-electrolyte interface inhibits the disordered migration of Zn2+, and effectively suppresses both side reactions and dendrite growth. The reversibility of Zn anode achieves a significant improvement with an average Coulombic efficiency of 99.22% at 1mAcm-2 and 0.5mAhcm-2 over 500 cycles. Even at a high Zn utilization rate (depth of discharge, DODZn) of 68%, a steady cycle life up to 200h is obtained for ultrathin Zn foils (20μm). The superior rate capability and long-term cycle stability of Zn-MnO2 full cells further prove the effectiveness of Gly in stabilizing Zn anode. This work sheds light on additive designing from the specific roles of polar groups for AZIBs.

Effects of integrated aftertreatment system on regulated and unregulated emission characteristics of non-road methanol/diesel dual-fuel engine

In order to ensure that output power, fuel economy and harmful emissions of non-road diesel engines meet the limit requirements, and reduce the dependence on fossil fuels, methanol/diesel dual-fuel combustion mode was conducted on an agricultural four-cylinder common-rail engine, and the effects of DOC + DPF + SCR aftertreatment system on overall performance and emission characteristics of dual-fuel mode were systematically investigated. Results show that dual-fuel mode can reduce both nitrogen oxide (NOx) and soot emissions, but increase nitrogen dioxide (NO2), methanol and formaldehyde (HCHO) emissions. With the increase of load, the conversion efficiency of diesel oxidation catalyst (DOC) to carbon hydrogen (HC), carbon monoxide (CO), methanol and HCHO emissions is continuously improved. DOC can increase NO2/NOx ratio for diesel mode, but reduce NO2/NOx ratio for dual-fuel mode. At full load, the average soot capture efficiency of diesel particulate filter (DPF) for dual-fuel engine is 98.84%, basically realizing zero soot emission, while the conversion efficiency of selective catalytic reduction (SCR) for NOx is 95.22%. The increase of methanol ratio can reduce NOx emissions and nitrous oxide (N2O) generation in SCR for dual-fuel mode. Under non-road steady cycle (NRSC), the maximum brake thermal efficiency (BTE) of diesel mode and dual-fuel mode are 39.4% and 41.0%, respectively. The regulation emissions of dual-fuel engine coupling with integrated DOC + DPF + SCR aftertreatment system can meet non-road Euro-V and US-Tier 4 emission standards.

Quantifying the probability of rupture arrest at restraining and releasing bends using earthquake sequence simulations

Fault bends are known to act as barriers to rupture propagation in many earthquakes. A recent compilation of the surface rupture traces of paleo earthquakes quantifies the probability of rupture termination as a function of the bend angle. To understand the physical basis of these unique statistics, we carry out 2D quasi-dynamic earthquake sequence simulations on a fault with either a restraining or releasing (double-) bend. The fault is loaded by steady sliding from an adjacent creeping region, rather than with backslip, together with a stress relaxation method to avoid unphysical stress buildup due to the curvature of faults. This relaxation is a proxy for unmodeled off-fault secondary faulting. This ensures the existence of a long-term steady earthquake cycle and stress field, the latter of which is determined by the balance between the slip-induced stress changes and relaxation terms. We quantify the influence of the bend on rupture propagation by computing passing ratio (i.e., the fraction of ruptures that propagate through the bend). Our simulations approximately reproduce the Biasi-Wesnousky empirical law for a wide range of parameters (e.g., bend width, stress relaxation time, background stress). Also, we reproduce geologic observations that the long-term slip rate of a fault has local minima at restraining bends, without assuming spatially varying loading rates using the backslip approach. Additionally, we find that restraining and releasing bends have different earthquake cycles. For restraining bends, many ruptures are arrested before reaching the center of the bend, and the passing ratio decreases with increasing the bend angle. For releasing bends, ruptures stop after passing the center of the bend, and the passing ratio abruptly drops from near unity to zero at around 20∘. This difference can be qualitatively explained by an energy balance approach. Our model has a potential to understand the seismogenesis of nonplanar faults and we can readily extend our model into 3D specific fault systems for hazard assessment.

Assessing therapeutic window and dose selection of ADG126 (a masked anti-CTLA-4 SAFEbody): Integrating nonclinical and clinical data using mathematical modeling.

e14518 Background: New developments have rejuvenated anti-CTLA-4 therapies, yet dose-dependent adverse events remain a core challenge, leaving dose-dependent clinical efficacy on the table. ADG126 is an anti-CTLA-4 fully human IgG1 SAFEbody with a masking peptide blocking the antigen binding site, designed to be preferentially activated in the tumor microenvironment (TME). Activated ADG126 binds to a unique and conserved epitope of CTLA-4, allowing for cross-species demonstration of improved therapeutic window and prolonged exposure to active drug in the TME through preclinical imaging/pharmacokinetic (PK) studies. Activated ADG126 potentiates T cell activation and depletes immunosuppressive Tregs through strong antibody-dependent cellular cytotoxicity specifically in the TME. Clinical data are obtained from ongoing Phase 1b/2 studies of ADG126 mono or combination therapy with toripalimab (NCT04645069) and Phase 1 monotherapy study in China (CTR20220571), to inform on its therapeutic window and dose selection. Methods: ADG126 in intact and total (i.e. intact + cleaved) forms in plasma were measured. Physiologically based PK modelling was conducted, leveraging clinical PK and tumor tissue PK from tumor-bearing mice. Clinical data of its parental antibody (Ab) was integrated. Results: The cleaved ADG126 plasma PK showed ~3-fold observed mean accumulation at steady state (SS) versus cycle 1 with Q3W dosing or <2-fold simulated accumulation with Q6W dosing. Modeling demonstrated that SS is reached between TME and plasma after releasing cleaved ADG126 into circulation, and when the production of the cleaved ADG126 reaches equilibrium with its elimination. Simulated maximum SS cleaved ADG126 exposure (Cmax,ss) at 10mpk Q3W or Q6W dosing is less than Cmax,ss of its parental Ab dosed at 3mpk Q3W (e.g., with manageable safety when combined with anti-PD-1 mAbs). This is consistent with reduced circulating PD biomarkers, reflective of reduced whole-body immune activation and superior clinical safety profiles for ADG126 as mono or combination therapies. At 10mpk, model-predicted SS tumor cleaved ADG126 exposure is greater than its in vitro binding and functional EC90s, and is higher than the predicted tumor exposure of its parental Ab at 10mpk, consistent with 10mpk Q3W or Q6W as emerging efficacious dose/regimens of ADG126. Conclusions: The SAFEbody technology enables ADG126 to be dosed at 10mpk, >3-fold higher dose levels than its parental Ab at 3mpk in a combination setting with anti-PD-1. It was demonstrated through modeling that ADG126 has higher and sustained TME active drug exposure, and therefore greater target engagement than what tolerable doses of non-masked anti-CTLA-4 molecules can achieve. The increased therapeutic window and efficacious dose selection of ADG126 is informed by quantitative integration of available data. Clinical trial information: NCT04645069 .

The Restrained Li/Gel Polymer Electrolyte Interface Deterioration Enabled by the Synergetic Effect of Ultra‐Lithiophilic Interphase and Interfacial Coupling Skeleton

AbstractQuasi‐solid‐state lithium metal batteries are deemed as one of the most promising next‐generation energy storage devices due to their enhanced safety and high energy density. However, the Li/Gel polymer Electrolyte (GPE) interface deterioration induced by the side reactions, dendrite growth during Li plating, and contact loss during Li stripping will inevitably lead to the failure of the battery. Herein, a Li/Li23Sr6–Li3N/Sr2N anode structure (LSN) prepared by hot‐rolling process is designed, where Sr2N serves as an inert skeleton to retain the interfacial coupling and to avoid contact loss. At the same time, the Li3N–Li23Sr6 interphase with high Li adsorption energy and fast Li+ transfer kinetics regulate the Li plating behavior. Benefitting from the design, when coupled with the carbonate‐based GPE, the lifespan of the symmetric battery with the LSN is extended to 1300 h at 0.2 mA cm−2/0.2 mAh cm−2. Furthermore, the LSN||LiFePO4 (LFP) full cell exhibits a steady cycle with extremely low voltage polarization at 0.5 C after 200 cycles. This study provides a practical strategy to stabilize the Li/GPE interface and deepens the understanding of Li+ plating/stripping behaviors through the interphase.