Cell Behavior Research Articles

Degradation Behavior of Galvanostatic and Galvanodynamic Cells for Hydrogen Production from High Temperature Electrolysis of Water

High temperature electrolysis of water using solid oxide electrochemical cells (SOEC) is a promising technology for hydrogen production with high energy efficiency and may promote decarbonization when coupled with renewable energy sources and excess heat from nuclear reactors. One of the challenges facing the commercial deployment of this technology is improving the cost competitiveness of hydrogen produced by electrolysis, which, among other factors, critically depends on the long-term durability of the SOEC system under relevant duty cycles. To extend the lifetime and optimize hydrogen production costs over projected lifetimes, fundamental knowledge of degradation mechanisms and rates as a function of operating conditions is a critical gap to close. Degradation mechanisms of solid oxide electrolysis cells are often coupled with each other and may vary based on cell overpotential and current, making them difficult to isolate and investigate effectively. Pulse Width Modulation (PWM) can be used to create a low-time scale variation under operating conditions that can identify non-linear degradation mechanisms between current and voltage. The short-term perturbations caused by PWM can help relieve stressors compared to cells running under constant (e.g., galvanostatic) conditions, even if the average current that the cell experiences over time is the same. In this work, water electrolysis cells were operated under dynamic conditions and compared with galvanostatic cells with respect to overall cell lifetime and degradation behavior. Specifically, the increases in overpotential and impedance are analyzed and compared between these two different operating modes to provide insights into the differences between average and instantaneous current.

Developmental endothelial locus 1: the present and future of an endogenous factor in vessels.

Developmental Endothelial Locus-1 (DEL-1), also known as EGF-like repeat and discoidin I-like domain-3 (EDIL3), is increasingly recognized for its multifaceted roles in immunoregulation and vascular biology. DEL-1 is a protein that is mainly produced by endothelial cells. It interacts with various integrins to regulate the behavior of immune cells, such as preventing unnecessary recruitment and inflammation. DEL-1 also helps in resolving inflammation by promoting efferocytosis, which is the process of clearing apoptotic cells. Its potential as a therapeutic target in immune-mediated blood disorders, cardiovascular diseases, and cancer metastasis has been spotlighted due to its wide-ranging implications in vascular integrity and pathology. However, there are still unanswered questions about DEL-1's precise functions and mechanisms. This review provides a comprehensive examination of DEL-1's activity across different vascular contexts and explores its potential clinical applications. It underscores the need for further research to resolve existing controversies and establish the therapeutic viability of DEL-1 modulation.

Doping of Porous Transport Layers to Optimize Electrical Contact Behaviour in PEM Water Electrolysis Cells

A high overall efficiency is crucial for large-scale polymer electrolyte membrane water electrolysers. Due to the harsh environment at the anode, a titanium oxide layer with high electrical resistivity passivates porous transport layers (PTL). A common used way to overcome this problem is noble metal coating (e.g. with platinum, gold or iridium). [1] For the very first time, we present a new and inexpensive way of maintaining the high conductivity of PTLs by doping the titanium surface that faces the catalyst layer. Sun et al. [2] modelled the conductivity of doped titanium oxide for different elements. With respect to their results and Koech et al. [3] we chose tin, niobium, antimony and yttrium as dopants. The implantation was carried out at the Ion Beam Center of the HZDR in Dresden, Germany. All doped PTLs displayed a lower cell voltage than the undoped reference as visible in figure 1a). While tin improves in the range of 2-3 % at a current density of 2A/cm², the other dopants best results reach values of over 4 % with niobium achieving the best performance with 4.4 % improvement (see figure 1b) for comparison). Figure 1c) shows the high frequency resistance (HFR) originating from impedance measurements. The observable improvement of up to 11.4% at 2A/cm² proves the fact that the advantage corresponds to a better contact resistance due to a lower resistance of the doped titanium oxide layer. The improvement in percent presents figure 1d).The measurement results show that doping can have a great impact on the contact resistance of titanium PTLs. These results open a new opportunity in the manipulation of porous transport layers for enhanced contact behaviour, where no experimental publications exist yet. Especially in comparison to noble metal coatings like iridium, doping has an enormous cost advantage when using non noble metals with the potential of lowering the overall electrolyser system costs while increasing its efficiency.[1] Liu, C., Shviro, M., Gago, A. S., Zaccarine, S. F., Bender, G., Gazdzicki, P., Morawietz, T., Biswas, I., Rasinski, M., Everwand, A., Schierholz, R., Pfeilsticker, J., Müller, M., Lopes, P. P., Eichel, R.-A., Pivovar, B., Pylypenko, S., Friedrich, K. A., Lehnert, W., Carmo, M., Exploring the Interface of Skin-Layered Titanium Fibers for Electrochemical Water Splitting. Adv. Energy Mater. 2021, 11, 2002926. https://doi.org/10.1002/aenm.202002926[2] Hu Sun, Zhu-tian Xu, Di Zhang. First-principles calculations to investigate doping effects on electrical conductivity and interfacial contact resistance of TiO2, Applied Surface Science, Volume 614, 2023, 156202, ISSN 0169-4332, https://doi.org/10.1016/j.apsusc.2022.156202.[3] Koech, R.K.; Ichwani, R.; Oyewole, D.; Kigozi, M.; Amune, D.; Sanni, D.M.; Adeniji, S.; Oyewole, K.; Bello, A.; Ntsoenzok, E.; et al. Tin Oxide Modified Titanium Dioxide as Electron Transport Layer in Formamidinium-Rich Perovskite Solar Cells. Energies 2021, 14, 7870. https://doi.org/10.3390/en14237870 Figure 1

Thermal Runaway in Battery Cells: Guiding Principles for Continuum Scale Modeling

Lithium-ion batteries are sensitive to temperature. Low-temperature or high-temperature operation may lead to lithium plating and dendrites, SEI decomposition, and separator collapse. Such phenomena may cause internal short circuits, rapid heat generation and, subsequently, may trigger thermal runaway, resulting in fire or explosion [1][2]. Hence, accurate modeling and prediction of the thermal response of battery cells inside the pack is critical to preventing safety hazards as well as optimizing battery performance. Battery thermal management system (BTMS) plays a significant role in maintaining an optimal operation temperature and ensuring thermal safety for electric vehicles [3]. However, the large number of battery cells inside one module makes it challenging for BTMS algorithms to realize real-time simulations based on fully resolved physics-based models. The conventional lumped capacitance (LC) thermal model achieves reduced computation costs under the hypothesis that temperature is spatially uniform. Nevertheless, such a model works better for small Biot number conditions, usually under low C-rate operation and moderate cooling scenarios, and it lacks justification under a broad range of battery operating conditions and materials [4]. To overcome such limitations, rigorous multiscale models, based on mathematical coarse-graining theories, have been developed to predict the thermal response of batteries at the module scale [5] while not compromising on computational cost. In this work, we investigate the accuracy of the classical LC thermal model for twenty potential battery modules constructed with commercial batteries and packing materials. We show that the classical LC thermal model may be inaccurate under a broad range of design conditions. In the context of multiscale modeling, we identify which effective models should be instead used, and analyze the impact of SOC and the relative strength of heat insulation and heat dissipation on model selection and accuracy. This work provides guidance, based on first principles and rigorous multiscale theory, on best practices for model selection in practical applications involving thermal behavior and thermal runaway in battery cells at the module scale.

Comparative Investigation of Large-Scale Cells of Supercapacitors Using Low-Temperature Electrolytes

The implementation of the concept of sustainable development for humanity, the advancement of alternative energy, hybrid and electric transport, and backup power supply systems, necessitate the creation of efficient energy storage devices. Such systems include lithium-ion, nickel-metal hydride, and redox flow batteries, where Faraday processes play a crucial role in energy storage mechanisms. One notable advantage of double-layer supercapacitors (SCs) as energy storage devices is the absence of Faraday processes during charge and discharge [1,2]. Moreover, the absence of Faraday processes, the rate of which sharply decreases with decreasing temperature, makes SC cells practically the only devices where power and energy features can potentially be maintained at a sufficient level at extremely low temperatures, down to minus 70-80°C [3]. The demand for developing energy storage systems capable of operating at extreme temperatures without extensive thermal control, such as space avionics systems, electric aircraft, uncrewed aerial vehicles, and electric and hybrid electric vehicles, is growing.Various methods have been adopted today to improve the performance of supercapacitors at low temperatures [4,5]. The central aspect in this direction is electrolytes, which have the most critical impact on the supercapacitor performance at these temperatures. While many investigations have been conducted on laboratory cells, a comparative analysis of the electrochemical characteristics of cells based on the developed electrolytes (non-aqueous electrolytes) was carried out to understand the correlation between laboratory and large-scale manufactured SC cells.The electrolyte mixture was prepared using organic substances: acetonitrile (AN), ethyl acetate (EA), toluene (TL), diethyl ether (DE), and vinylene carbonate (VC). A 1.2 M solution of salt TEMA TFB was used to prepare the electrolyte. Test electrolyte mixtures were prepared by adding the test additive in the amount of 5, 10, 15, and 20 vol% for DE and TL and 0.1, 1, 3, and 5 vol% for VC to the AN: EA (3:1 by volume %) mixture. These co-solvents were chosen due to their low melting point, relatively low viscosity, and moderate dielectric constant values.A comprehensive investigation of the physical-chemical and electrochemical properties demonstrates that additives to the electrolyte mixture can extend the lower boundary of the operating temperature range down to −68°C, providing good electrochemical characteristics of the cells: capacitance and stability during long-term cycling [6].To understand the behavior of developed electrolytes in large-scale SC cells, manufactured large-scale SC cells (LSC) with a standard initial capacitance of 1500F were used. Figure 1a shows the capacitance change of large-scale SC cells based on electrolyte mixture AN: EA (3:1), AN: EA (3:1) +3%VC, AN: EA (3:1) +10%DE, and AN: EA (3:1) +10%TL at +25°C. It is evident that the capacitance of LSC-based SC is nearly maintained for more than 1000 charge-discharge cycles at a temperature of +25°C, demonstrating better performance than laboratory cells. Equivalent measurements were also carried out on the self-discharge of LSC-based SC cells (Fig. 1d), showing only a slight voltage drop for just over 2 days.This behaviour indicates high resistance to various electrochemical processes, such as electrochemical decomposition of the activated electrode material and electrolyte compound,corrosion of the current-collector material,undesirable Faraday redox processes. Notably, the leakage current for large-scale cells is lower than for small (laboratory) cells, enhancing the capacitance retention ability for large-scale cells. Figure 1. Cycle-life stability (a, b, c) and self-discharge behavior (d) of the LSC cells based on electrolyte mixtures at temperatures of 25 °C (a, d), -60 (b) and -65 (c).For all samples, an increase in capacitance is observed as the number of charge-discharge cycles increases (Fig.1). This is likely due to the high current value (50A) used for large-scale cells, causing Joule heating in the cell structures, and increasing the temperature of the electrolyte mixture by several degrees.Tests of the developed electrolytes as part of laboratory SC cells and large-scale industrially produced SC cells confirmed their high resource stability during 10,000 cycles of continuous charge-discharge at a current density of 1.5 A/g, including at a temperature corresponding to the upper limit of the operating temperature range. Additionally, the resistance of SCs with these electrolytes to self-discharge was demonstrated, showcasing the possibility of a "cold start" of SC elements at a temperature of –60 °C.

Electrochemical Performance of Lithium-Ion Cells with Lithium- and Manganese- Rich Oxide Cathodes

State-of the-art (SOA) lithium-ion batteries (LIBs) being developed for transportation applications contain a transition metal (TM) oxide cathode and a graphite anode; both serve as host-matrices to house lithium ions during battery operation. The cathodes typically contains Li1+xNiaCobAlcO2 (NCA) or Li1+xNiaMnbCocO2 (NMC) oxides: both oxide chemistries contain Co, which is known to preserve the layered structure during lithium extraction/insertion reactions. However, the possibility of a global Co shortage and soaring costs has galvanized the LIB community to explore sustainable cathode chemistries, while maintaining cell performance (energy/power densities), safety and cycle/calendar life. In this context the U.S. Department of Energy (DOE) initiated the Earth-Abundant Cathode Active Material (EaCAM) Program for the development of sustainable cathode chemistries, based on earth-abundant elements.Materials of particular interest to the EaCAM program are the x Li2MnO3 ● (1-x) LiMnaNibZcO2 composites; here Z refers to various elements that could be included in the oxide structure. These lithium- and manganese- rich materials are considered attractive candidates because of their high specific capacities, zero cobalt content, and lower costs compared to the SOA oxides. We have been examining the electrochemical behavior of cells with these oxides, with a particular focus on the 0.3 Li2MnO3 ● 0.7 LiMn0.5Ni0.5O2 (LMR) compound.During this presentation, we will show results from battery cells, containing LMR cathodes and either graphite or lithium-titanate anodes. In particular, the use of a microprobe reference electrode to monitor the cathode and anode potentials will be discussed. The effect of activation on cell performance and the performance loss characteristics during cycling will be highlighted. We will show how cell impedance is affected by voltage hysteresis and the voltage fade that results from cycling. Our ultimate goal is to identify constituents and mechanisms responsible for the cell performance loss and develop solutions to mitigate this degradation.Acknowledgement: This document has been created by UChicago Argonne, LLC, Operator of Argonne National Laboratory (“Argonne”). Argonne, a U.S. Department of Energy Office of Science laboratory, is operated under Contract No. DE-AC02-06CH11357.

A Reduced-Order Model of the Coupled Venting-Thermal-Electrochemical Behavior to Predict First Venting Under External Short Circuit Conditions

Modeling abusive battery operation before thermal runaway (TR) can reduce the testing requirements and facilitate the development of effective and reliable early failure detection and fast discharge strategies [1] which require multiple types of sensor signals, including current, voltage, temperature, and pressure. We present a multi-physics model that can predict the rapidly evolving discharge behavior of cells undergoing an external short circuit, including hazards like first venting. First venting models account for gas generation due to SEI decomposition and electrolyte vaporization at high temperatures to calculate the build-up of internal cell pressure under constant-displacement conditions [2]. Modeling gas generation requires accurate temperature prediction, which subsequently requires accurate Joule heating calculated from current and voltage predictions. From the cascading chain of model input dependencies, the first challenge is managing error propagation through the submodels with appropriate parameterization. Previous modeling work parameterized a venting model for a cell undergoing an external short circuit (ESC) but did not include a thermal or electrical model [2]. The second challenge is modeling the diffusion-limited discharge behavior with currents approaching 50-80 C with a fast and accurate model that is feasible for detection and control applications. Diffusion-limited behavior occurs when the local Li concentration saturates, suddenly causing large concentration overpotentials that are observable in the terminal voltage and current (see Fig. 1) as well as numerical instability when solving the Butler-Volmer (BV) equation. Previous ESC modeling works either used the Doyle-Fuller-Newman (DFN) model with a limiting current density in the BV equation [3] or an equivalent circuit model (Eq-CM) [1]. However, solving the DFN is computationally intensive for a control application, while Eq-CMs cannot predict the diffusion-limited electrical behavior beyond the data they were parameterized on, requiring apriori experiments to be accurate. To balance the trade-offs, we instead look towards reduced-order modeling.In this work, we present a control-oriented, reduced-order, multi-physics model that captures the electrochemical, thermal, and venting behavior of four 4.6 Ah NMC pouch cells undergoing an external short circuit with different initial state-of-charge (SOC). The multi-physics model couples a first venting model with a lumped thermal model driven by Joule heating calculated through the overpotentials from the Single-Particle Model with electrolyte (SPMe). The combined model was parameterized through four experiments by fitting five key parameters in the submodels related to the SEI decomposition rate, cell thermal behavior, and solid electrode diffusion to capture the first venting timing, peak temperature, and diffusion-limited current-voltage drops. Additionally, two resistances were tuned to match the initial current and voltage with all other parameters were taken from the literature. Applying the same parameter set consisting of the average of the fitted values on all four cells, the combined multi-physics model correctly predicted that the fully-charged cells would vent and conservatively predicted the cell venting timing up to about 40 s before it occurred in the experiment. For high initial SOC cells, the SPMe also accurately predicted the current and voltage drops associated with diffusion limitations and SOC up until the cell vented. This is the first work that systematically parameterizes and couples a reduced-order, physics-based model to capture the electrical, thermal, and venting behavior under battery abuse conditions. Future work will explore applications for the model in early detection and response to critical safety events.REFERENCES[1] Tran, Vivian, Jason Siegel, and Anna Stefanopoulou. "Emergency Li-ion Battery Discharge using Nonlinear Model Predictive Control with Temperature and Venting Pressure Constraints." 2023 American Control Conference (ACC). IEEE, 2023.[2] Cai, Ting, et al. "Modeling li-ion battery first venting events before thermal runaway." IFAC-PapersOnLine 54.20 (2021): 528-533.[3] Rheinfeld, Alexander, et al. "Quasi-isothermal external short circuit tests applied to lithium-ion cells: Part ii. modeling and simulation." Journal of The Electrochemical Society 166.2 (2019): A151. Fig. 1: 15-min simulation of an external short circuit for cells at different initial SOC. Model results and experimental measurements are shown for four cells that were externally shorted. The measured current, voltage, temperature, and expansion force were measured at 10 Hz and plotted versus log time to highlight the dynamic current-voltage behavior in the first few minutes. The diffusion-limited current and voltage behavior are captured by the model. The two cells at 100% SOC, experienced venting and higher peak temperatures, which are well captured by the model. The cell venting timing was predicted to be 43 s and 7 s early for Cell 100A and 100B, respectively. The cells that were shorted at lower SOC did not vent. Figure 1

Hydrogel crosslinking modulates macrophages, fibroblasts, and their communication, during wound healing

Biomaterial wound dressings, such as hydrogels, interact with host cells to regulate tissue repair. This study investigates how crosslinking of gelatin-based hydrogels influences immune and stromal cell behavior and wound healing in female mice. We observe that softer, lightly crosslinked hydrogels promote greater cellular infiltration and result in smaller scars compared to stiffer, heavily crosslinked hydrogels. Using single-cell RNA sequencing, we further show that heavily crosslinked hydrogels increase inflammation and lead to the formation of a distinct macrophage subpopulation exhibiting signs of oxidative activity and cell fusion. Conversely, lightly crosslinked hydrogels are more readily taken up by macrophages and integrated within the tissue. The physical properties differentially affect macrophage and fibroblast interactions, with heavily crosslinked hydrogels promoting pro-fibrotic fibroblast activity that drives macrophage fusion through RANKL signaling. These findings suggest that tuning the physical properties of hydrogels can guide cellular responses and improve healing, offering insights for designing better biomaterials for wound treatment.

Structure of a model lipid membrane oxidized by human 15-lipoxygenase-2

Enzyme-mediated lipid oxidation is an important regulatory event in cell signaling, with oxidized lipids being potent signaling molecules that can illicit dramatic changes in cell behavior. For example, peroxidation of an arachidonoyl poly-unsaturated fatty acid by the human enzyme 15-lipoxygenase-2 (15-LOX-2) has been associated with formation of atherosclerotic plaques. Previous work on synthetically oxidized membranes has shown that oxidized lipid tails will change their conformation to facilitate interactions between the peroxide group and the lipid headgroups. However, this phenomenon has not been directly observed for a lipid membrane that has undergone enzyme-catalyzed oxidation. In this study, we report on the structure of a model lipid membrane before and after oxidation by 15-LOX-2. A model lipid membrane monolayer at the air-liquid interface was constructed from 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (SAPC) in a Langmuir trough, and X-ray reflectivity measurements were conducted to determine the electron density profile of the system. Exposure to 15-LOX-2 caused a dramatic change in the SAPC structure, namely a blurred distinction between the lipid tail/head layers and shortening of the average lipid tail length by ∼3 Å. The electron density profile of the oxidized SAPC monolayer is similar to that of a synthetically oxidized substrate mimic. Overall, this reported observation of an enzymatically-oxidized membrane structure in situ is helping to bridge a gap in the literature between structural studies on synthetically oxidized membranes and cellular studies aiming to understand physiological responses.

Lenvatinib acts on platelet‑derived growth factor receptor β to suppress the malignant behaviors of gastric cancer cells.

Given the limited treatment options and high mortality rates associated with gastric cancer, there is a need to explore novel therapeutic options. The present study aimed to investigate the efficacy of lenvatinib, a multi-target tyrosine kinase inhibitor, in mitigating the progress of gastric cancer in vitro. Comprehensive analyses were conducted to assess the impact of lenvatinib on gastric cancer cells, focusing on the inhibition of viability, suppression of proliferation, induction of apoptosis and reduction of metastatic potential. The effects of lenvatinib on these activities were determined using 5-ethynyl-2'-deoxyuridine staining, colony formation assay, flow cytometry, western blotting, scratch assay and Transwell assay. In addition, bioinformatics analyses were employed to identify key regulatory targets of lenvatinib, with particular attention given to platelet-derived growth factor receptor β (PDGFRB). In addition, the effects of PDGFRB overexpression on the regulation of lenvatinib were explored. Lenvatinib demonstrated significant inhibitory effects on the viability, proliferation and metastatic capabilities of MKN45 and HGC27 gastric cancer cell lines. Bioinformatics analyses identified PDGFRB as a crucial target of lenvatinib, with its downregulation showing promise in enhancing overall survival rates of patients with gastric cancer. By contrast, PDGFRB overexpression reversed the effects of lenvatinib on cells. The present findings underscore the potential of lenvatinib as a promising therapeutic option in the treatment of gastric cancer. By elucidating its mechanism of action and identifying PDGFRB as a primary target, the present study may aid further clinical advancements.

Influence of inflammation on the expression of microRNA-140 in extracellular vesicles from 2D and 3D culture models of synovial-membrane-derived stem cells.

In osteoarthritis (OA), articular homeostasis is regulated by microRNA-140 that inhibits ADAMTS-5, an enzyme that cleaves aggrecan and stimulates the synthesis of other inflammatory mediators. This study aims to evaluate the expression of microRNA-140 in extracellular vesicles (EVs) derived from equine synovial-membrane-derived mesenchymal stem cells (eqSMMSCs) cultured in monolayer (2D) and three-dimensional (3D) culture models under an in vitro inflammatory environment. Four experimental groups of eqSMMSC cultures were defined for isolation of the EVs. The 2D and 3D control groups were cultured in a conventional cell culture medium, while the 2D-OA and 3D-OA treatment groups were exposed to an OA-like medium containing IL-1β and TNFα. The culture media samples were collected at 24h, 72h, and 120h time points for EV isolation and characterization using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Reverse transcription quantitative polymerase chain reaction was employed to assess the expressions of microRNA-140 in both the cells and EVs. All statistical analyses were conducted at the 5% significance level. Encapsulation of the eqSMMSCs protected the cells from the inflammatory media compared to the monolayer cultures. EVs were found in higher concentrations in the 3D-OA cultures. Additionally, higher expressions of microRNA-140 were observed in the cells of the 3D-OA group at 24 and 72h, whereas microRNA-140 expressions in the EVs were higher in the 3D group at 72h and in the 2D-OA group at 120h (p < 0.001). However, the 3D-OA culture showed higher expression of the mRNA Adamts5 in the EVs at 120h. The responses of the eqSMMSCs to inflammatory stimuli involve intracellular expression of microRNA-140 and its subsequent transportation via the EVs, with quicker responses observed in the 3D than 2D cultures. This study sheds light on the behaviors of stem cells in restoring homeostasis in osteoarthritic joints.

An actomyosin network organizes niche morphology and responds to feedback from recruited stem cells.

Stem cells often rely on signals from a niche, which in many tissues adopts a precise morphology. What remains elusive is how niches are formed, and how morphology impacts function. To address this, we leverage the Drosophila gonadal niche, which affords genetic tractability and live-imaging. We have previously shown mechanisms dictating niche cell migration to their appropriate position within the gonad, and the resultant consequences on niche function. Here, we show that once positioned, niche cells robustly polarize filamentous actin (F-actin) and Non-muscle Myosin II (MyoII) towards neighboring germ cells. Actomyosin tension along the niche periphery generates a highly reproducible smoothened contour. Without contractility, niches are misshapen and exhibit defects in their ability to regulate germline stem cell behavior. We additionally show that germ cells aid in polarizing MyoII within niche cells, and that extrinsic input is required for niche morphogenesis and function. Our work reveals a feedback mechanism where stem cells shape the niche that guides their behavior.

Patterned PVA Hydrogels with 3D Petri Dish® Micro-Molds of Varying Topography for Spheroid Formation of HeLa Cancer Cells: In Vitro Assessment.

Cell spheroids are an important three-dimensional (3D) model for in vitro testing and are gaining interest for their use in clinical applications. More natural 3D cell culture environments that support cell-cell interactions have been created for cancer drug discovery and therapy applications, such as the scaffold-free 3D Petri Dish® technology. This technology uses reusable and autoclavable silicone micro-molds with different topographies, and it conventionally uses gelled agarose for hydrogel formation to preserve the topography of the selected micro-mold. The present study investigated the feasibility of using a patterned Poly(vinyl alcohol) hydrogel using the circular topography 12-81 (9 × 9 wells) micro-mold to form HeLa cancer cell spheroids and compare them with the formed spheroids using agarose hydrogels. PVA hydrogels showed a slightly softer, springier, and stickier texture than agarose hydrogels. After preparation, Fourier transform infrared (FTIR) spectra showed chemical interactions through hydrogen bonding in the PVA and agarose hydrogels. Both types of hydrogels favor the formation of large HeLa spheroids with an average diameter of around 700-800 µm after 72 h. However, the PVA spheroids are more compact than those from agarose, suggesting a potential influence of micro-mold surface chemistry on cell behavior and spheroid formation. This was additionally confirmed by evaluating the spheroid size, morphology, integrity, as well as E-cadherin and Ki67 expression. The results suggest that PVA promotes stronger cell-to-cell interactions in the spheroids. Even the integrity of PVA spheroids was maintained after exposure to the drug cisplatin. In conclusion, the patterned PVA hydrogels were successfully prepared using the 3D Petri Dish® micro-molds, and they could be used as suitable platforms for studying cell-cell interactions in cancer drug therapy.

PTEN in kidney diseases: a potential therapeutic target in preventing AKI-to-CKD transition.

Renal fibrosis, a critical factor in the development of chronic kidney disease (CKD), is predominantly initiated by acute kidney injury (AKI) and subsequent maladaptive repair resulting from pharmacological or pathological stimuli. Phosphatase and tensin homolog (PTEN), also known as phosphatase and tensin-associated phosphatase, plays a pivotal role in regulating the physiological behavior of renal tubular epithelial cells, glomeruli, and renal interstitial cells, thereby preserving the homeostasis of renal structure and function. It significantly impacts cell proliferation, apoptosis, fibrosis, and mitochondrial energy metabolism during AKI-to-CKD transition. Despite gradual elucidation of PTEN's involvement in various kidney injuries, its specific role in AKI and maladaptive repair after injury remains unclear. This review endeavors to delineate the multifaceted role of PTEN in renal pathology during AKI and CKD progression along with its underlying mechanisms, emphasizing its influence on oxidative stress, autophagy, non-coding RNA-mediated recruitment and activation of immune cells as well as renal fibrosis. Furthermore, we summarize prospective therapeutic targeting strategies for AKI and CKD-treatment related diseases through modulation of PTEN.

Effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki-67 in patients with locally advanced breast cancer

Background: Neoadjuvant chemotherapy (NACT) affects the tumor protein marker’s expression and status. Changes in the expression of biomarkers during NACT may influence the clinical decision of adjuvant molecular and hormonal therapy. Hence, re-evaluation of receptor status has to be done after NACT to give a specific adjuvant therapy for patient benefit. Aims and Objectives: The aim of this study was to study the status of hormone receptors (HRs) – estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (Her-2/Neu), and Ki-67 in patients with locally advanced breast cancer (LABC) in both core needle biopsies and post-mastectomy specimens after administering neoadjuvant chemotherapy. Materials and Methods: The present study was conducted in the Department of Pathology in collaboration with the Department of Surgery, Pt B D Sharma PGIMS, Rohtak, for a period of 1 year. The study comprised 52 patients with LABC who received neoadjuvant chemotherapy and 20 control cases who did not receive neoadjuvant chemotherapy. Each case comprised two specimens: Trucut biopsy and a mastectomy specimen. Results: ER changed from positive to negative in 15.4% of the cases and from negative to positive in 1.9% of the cases. The overall change in ER was statistically significant (P=0.020). For PR, 9.6% of the cases changed from positive to negative while none of the cases showed change from negative to positive. The overall change in PR was statistically significant (P=0.025). For HER2/Neu, 19.2% of the cases changed from positive to negative, and 11.5% of the cases changed from negative to positive. The overall change in HER2/Neu was not statistically significant (P=0.317). For Ki-67, 30% of patients changed from positive to negative while 11.5% of patients changed from negative to positive. The overall change in Ki-67 was statistically significant (P=0.024). Conclusion: There was discordance in the HR status and proliferation marker after NACT in patients with breast cancer. The administration of NACT might be the main reason for the change in receptor status thus understanding the chemotherapy-induced biological conversion in the tumor cell behavior is strategically important in planning adjuvant endocrine therapy and for disease follow-up.

Testing of NMC and LFP Li-ION cells for surface temperature at various conditions

Battery electric vehicles (BEVs) are being considered as a replacement technology for diesel vehicles in underground mining of mineral resources. However, many issues related to BEVs in industrial applications still require more detailed research. One significant topic is the heat load—BEVs' heat emission into the working environment during regular operation. This paper provides an overview of the thermal behavior of NMC and LFP Li-ion cells tested under various conditions, which is an important step in determining the overall heat load of BEVs. The surface temperature of three NMC and one LFP 18650 Li-ion cells was monitored during charging and discharging at four different rates, at constant ambient temperatures of 30 °C and 40 °C. The main results pertain to the cell's thermal behavior during charging and discharging, highlighting the distinctive temperature profiles of NMC and LFP cells.

Dynamic thermal runaway evolution of Li-ion battery during nail penetration

The nail penetration test is widely adopted to evaluate the safety of lithium-ion batteries by triggering the internal short circuit. This work compares the phenomena, temperature rise rate, surface temperature, and mass loss under the penetration test for different nail materials, nail diameters, and cell SOCs. The thermal runaway behaviour and characteristics of these test cells are studied in depth. The results show that the maximum temperature and temperature rise rate of the cell increase with the increase of SOC. The maximum temperature and the temperature rise rate of the cell decrease with the increase of the nail diameter. Under high SOC conditions (greater than 75 % SOC), the more conductive nail increases the release of Joule heat generation inside the battery, which leads to a more intense thermal runaway behaviour. At low SOC (less than 50 % SOC), the more conductive nail promote cooling, which reduces the intensity of thermal runaway. However, non-conductive nails show the exact opposite effect. This dual effect of different nail materials was elucidated by a simplified heat transfer analysis. By calculating the heat production and heat dissipation during the thermal runaway process, the effects of the nail material and the cell SOCs on the thermal runaway behaviour of the battery can be summarized. This work deepens the understanding of the safety of batteries under external shocks and provides new scientific insights into battery design and its safety testing.

Experimental investigation of thermal runaway behavior and propagation inhibition of lithium-ion battery by immersion cooling

Understanding the impact of immersion cooling on thermal runaway (TR) behavior and its inhibitory effect on thermal runaway propagation (TRP) is crucial for its practical application. This study explores immersion cooling for individual cells and battery modules, examines the TR behavior of 18,650 single cells at various immersion depths and states of charge (SOC) using filament heating, and investigates TRP between cells. Immersion cooling with a depth of 70 mm significantly extends the interval between the rupture of the battery safety valve and the TR trigger from 70 s (at a 20 mm depth) to 312 s, while reducing the peak TR temperature to 306 °C. Additionally, cells with 100 %, 75 %, and 50 % SOC show that higher battery capacity increases the risk of TR and thermal hazards. TRP experiments demonstrate that immersion cooling can inhibit TRP between cells, though safety valves of adjacent cells in 100 %, 75 %, and 50 % SOC battery modules still ruptured, with peak temperatures reaching 118.2 °C, 121.4 °C, and 111.5 °C respectively, posing a potential TR risk. This study highlights the TR behavior of single cells at different immersion depths and confirms that immersion cooling can inhibit TRP, providing valuable insights for the future application of immersion cooling in lithium battery thermal management systems.

A dual crosslinking strategy to tailor rheological properties of gelatin methacryloyl

3D bioprinting is an emerging technology that enables the fabrication of three-dimensional organised cellular constructs. One of the major challenges in 3D bioprinting is to develop a material to meet the harsh requirements (cell-compatibility, printability, structural stability post-printing and bio-functionality to regulate cell behaviours) suitable for printing. Gelatin methacryloyl (GelMA) has recently emerged as an attractive biomaterial in tissue engineering because it satisfies the requirements of bio-functionality and mechanical tunability. However, poor rheological property such as low viscosity at body temperature inhibits its application in 3D bioprinting. In this work, an enzymatic crosslinking method triggered by Ca2+-independent microbial transglutaminase (MTGase) was introduced to catalyse isopeptide bonds formation between chains of GelMA, which could improve its rheological behaviours, specifically its viscosity. By combining enzymatic crosslinking and photo crosslinking, it is possible to tune the solution viscosity and quickly stabilize the gelatin macromolecules at the same time. The results showed that the enzymatic crosslinking can increase the solution viscosity. Subsequent photo crosslinking could aid in fast stabilization of the structure and make handling easy.

MSI2 regulates NLK-mediated EMT and PI3K/AKT/mTOR pathway to promote pancreatic cancer progression

BackgroundThe incidence of pancreatic cancer is increasing by years, and the 5-year survival rate is very low. Our team have revealed that Musashi2 (MSI2) could promote aggressive behaviors in pancreatic cancer by downregulating Numb and p53. MSI2 also facilitates EMT in pancreatic cancer induced by EGF through the ZEB1-ERK/MAPK signaling pathway. This study aims to further explore the molecular mechanisms of MSI2-regulated downstream pathways in pancreatic cancer.MethodsIn vitro and in vivo experiments were conducted to investigate the role and mechanism of MSI2 in promoting malignant behaviors of pancreatic cancer through regulation of NLK.ResultsGenes closely related to MSI2 were screened from the GEPIA and TCGA databases. We found that NLK showed the most significant changes in mRNA levels with consistent changes following MSI2 interference and overexpression. The high correlation between MSI2 and NLK was also observed at the protein level. Multivariate analysis revealed that both MSI2 and NLK were independent adverse indicators of survival in pancreatic cancer patients, as well as join together. In vitro, silencing or overexpressing NLK altered cell invasion and migration, by regulating EMT and the PI3K-AKT-mTOR pathway. Silencing MSI2 reduced protein expression in the EMT and PI3K-AKT-mTOR pathways, leading to decreased cell invasion and migration abilities, while these effects could be reversed by overexpression of NLK. In vivo, MSI2 silencing inhibited liver metastasis, which could be reversed by overexpressing NLK. Mechanistically, MSI2 directly binds to the translation regulatory region of NLK mRNA at positions 79–87 nt, enhancing its transcriptional activity and exerting post-transcriptional regulatory roles. The analysis of molecular docking showed the close relationship between MSI2 and NLK in pancreatic cancer patients.ConclusionsOur findings elucidate the regulatory mechanisms of the MSI2-NLK axis in modulating aggressive behaviors of pancreatic cancer cells, which providing new evidence for therapeutic strategies in pancreatic cancer.