State Of Dynamic Equilibrium Research Articles

Abstract 2532: Deciphering multiple protein complexes in BCL2 family to measure apoptotic dependencies in acute myeloid leukemia

Abstract The BCL2 protein family controls apoptosis by shifting the dynamic equilibrium state of complex formation. BH3 mimetics disrupt this balance by disturbing the interaction of a specific anti-apoptotic protein, leading to the initiation of apoptosis. However, relying solely on molecular data for the specific anti-apoptotic protein can be challenging due to the functional redundancy within the BCL2 protein family and their complex interaction network. Therefore, comprehensive profiling information considering protein complexes is essential to determine apoptotic dependencies, particularly in a clinical context. In this study, we adapted a Single-molecule Protein Interaction Detection (SPID) platform that can assess levels of protein complexes in a quantitative manner. Out of the 47 metrics included in our Apoptosis Signaling 47 panel, we utilized 22 assays to measure apoptosis dependencies in acute myeloid leukemia (AML) cells obtained from 32 patients. By combining these metrics, we developed a predictive model for the ex vivo response to ABT-199 treatment, focusing on three key biomarkers: BCL2-BAX complex, BCL2-BIM binding potential, and BCLxl-BAK level. From a receiver operating curve (ROC) analysis, the model exhibited high accuracy with a value of 0.94 area under the curve (AUC). We further validated our model by comparing the predicted response to the therapeutic outcomes in 10 AML patients according to the 2017 ELN guidelines, and achieved 100% sensitivity (4 out of 4 identified correctly) and 83.3% specificity (5 out of 6 identified correctly). Overall, our platform provides an effective method to explore apoptosis dependencies in clinical samples based on the information regarding protein complexes within the BCL2 protein family. Three key molecular biomarkers can be translated into a gauge for predicting therapeutic outcomes of BH3 mimetics, suggesting an improvement of precision medicine in AML treatment. Citation Format: Hongwon Lee, Changju Chun, Byungsan Choi, Saem Hong, Yunseo Lee, Youngil Koh, Tae-Young Yoon. Deciphering multiple protein complexes in BCL2 family to measure apoptotic dependencies in acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2532.

Experimental study on mine water purification mechanism for broken coal and rock masses in the underground reservoir of ecologically vulnerable mining area.

Water-rock interaction mechanism and water purification capacity of broken coal and rock masses are very important for the efficient operation of the underground reservoir. In this paper, a water purification simulation device for an underground mine reservoir was designed. The experimental study on the dynamic interaction between broken coal and rock masses and mine water was carried out. The water purification mechanism is analyzed from the changes in rock mineral composition and mine water quality before and after the test. The results show that after the broken coal and rock mass purification, the water turbidity and the concentration of chlorides and suspended solids decreased obviously. The water purification capacities of mudstone and sandstone are stronger than that of coal samples. After 60days of reaction between the working face sewage and the broken samples (mudstone, sandstone, and coal), the turbidity, chromaticity, and residual chlorine decreased by > 90%, 90%, and 60%, respectively; and COD decreased by 35.29%, 30.59%, and 28.99%, respectively. While the TDS and the total hardness increased by about 40%, 30%, and 10% for the mudstone, sandstone, and coal, respectively. It shows that coal also has the worst degradation performance. The water purification effect of broken coal and rock masses has a significant time effect. The early stage of water-rock interaction is dominated by mineral dissolution, and the middle stage is dominated by precipitation and adsorption. The pH value of the solution has a certain influence on the ion change. In the later stage, the water-rock interaction is weak in a dynamic equilibrium state, and the change in the mine water quality index is not obvious. Considering the influence of rock lithology on water quality and the law of water-rock interaction time, the construction site selection and water storage time optimization of underground reservoirs in Jinjie Coal Mine were carried out, respectively.

Peculiarities Formation of Welded Joints under the External Electromagnetic Influence

Controlling the movement of liquid metal by selecting the parameters of an external electromagnetic effect makes it possible to change the conditions of dynamic equilibrium of the weld pool and, as a result, the formation of a weld. Magnetic process control has advantages over mechanical control methods, since it is carried out without contact with the welding zone. The study of processes leading to a decrease in the concentration of defects in metals, recombination of dislocations, polygonization, recrystallization, defect healing, etc., is an urgent task for technologists. The purpose of the work is to study the laws of formation of phase composition, microhardness, grain, lath, subgrain, dislocation structures of low-alloy steel welds in underwater welding and the relationship of structural parameters with the properties of strength and crack resistance of these joints. Microstructure studies were carried out by light, scanning, and transmission electron microscopy. Mathematical modelling was carried out to optimize the research efficiency. The developed computer application implements the idea of sequential calculation of quantities, where the value of the welding current and the current in the inductor is selected by the researcher. The influence of structural factors at the dislocation level on local internal stresses, which determine the deformation localization zones in the structures of the upper and lower bainites in the deposited metal, is analyzed. The conditions for obtaining high-quality welded joints in the welding of low-alloy steels, which ensure their strength and crack resistance, are established.

High effective generation of hydrogen peroxide by adjusting three-phase interfaces of gas diffusion electrode during the oxygen reduction reaction

Mass transfer of oxygen is a critical issue in the two-electron oxygen reduction reaction (2e− ORR) for the generation of hydrogen peroxide (H2O2). In this study, a novel constant velocity gas diffusion electrode (CVGDE) that can control the gas flow rate through the catalyst layer was fabricated, and the effect of the gas flow rate on three-phase interfaces (TPIs) formation and the mass transfer of oxygen in gas diffusion electrode (GDE) was investigated. In CVGDE, oxygen mass transfer was significantly improved, and the yield of H2O2 reached up to 73.65 mg cm−2 h−1 at 200 mA cm−2, which was 74.3 % higher than that of conventional GDE. Furthermore, the oxygen utilization efficiency of CVGDE reached 22.4 %, and the aeration energy consumption was decreased to 5.48 Wh kg−1, which was 1000 times less than the energy consumption required for H2O2 electrosynthesis. The experiments and theoretical calculations showed that the dynamic equilibrium state of TPI was achieved by the influence of both the electric field and air flow in the catalyst layer, which leading to a substantial increase in oxygen mass transfer and H2O2 yield. Finally, CVGDE was utilized in the electro-Fenton process for the degradation of organic contaminants. This study will contribute to the understanding of the oxygen mass transfer process in GDE.

Modeling and simulation of arc dynamic behavior in Tri-Arc twin wire GMAW

The triple-arc (Tri-Arc) twin wire gas metal arc welding (GMAW) is an innovative approach to twin-wire welding. It establishes two arcs between the welding wires and the workpiece and introduces a third arc, called the “M arc” between the two wires. To theoretically analyze how various welding parameters affect this process, an equivalent circuit method is employed to establish a dynamic mathematical model for Tri-Arc twin wire gas metal arc welding. The welding process is characterized and simulated using MATLAB simulations to analyze variations in current signals and the wire stick-out. The results indicate that the main arc burns in a dynamic equilibrium state with periodic fluctuations, the current gradually decreases over time, and the arc is elongated. These simulation outcomes closely mirror real welding processes.

Time-Lapse Geophysical Measurements for Monitoring Coastal Groundwater Dynamics in an Unconfined Aquifer.

The coastal zone, which is the interface between land and sea, is hydrodynamically very active due to the complex interactions of various hydrological controls and variable-density fluids. These forces vary over time, resulting in a state of dynamic equilibrium in the system. The major hydrological processes in coastal aquifer systems are salt water intrusion and submarine groundwater discharge, which are interdependent. Monitoring these complex processes is crucial for sustainable coastal zone management but poses a significant research challenge. In this study, we demonstrate the effectiveness of non-invasive geophysical techniques, specifically the time-lapse electrical resistivity imaging method, in conjunction with groundwater monitoring, for monitoring coastal groundwater dynamics in an unconfined aquifer at varying time scales and hydrogeological settings present at formerly glaciated sites worldwide. We generated two-dimensional baseline salt water intrusion maps for the test site, located on the coast of Rhode Island, USA. The time-lapse electrical resistivity survey method enables the rapid estimation of fresh groundwater discharge. Our approach offers insight into the mechanisms and seasonably variable salt water-freshwater interactions in unconfined heterogeneous aquifers. Although the results are site-specific, their implications are broad and may stimulate other studies related to sea to land pollution (sea water intrusion) and land to sea pollution (groundwater discharge) in heterogeneous coastal aquifer settings.

Characteristics of Quasi-static and Dynamic Failure of Inconel 625 Superalloy under Simple Shear

The shear flow and failure of a superalloy Inconel 625, conceived for jet engine applications, are investigated by using a modified flat gauge shear specimen with the assistance of Digital Image Correlation (DIC). The constant strain rate shear tests were successfully performed by using a screw driven Zwick machine and a bespoke spilt Hopkinson tension bar (SHTB). Nearly all gauge section is in a uniform strain state at dynamic force equilibrium condition. The constitutive relationships and the crystallographic texture show strain rate dependence. Different from the void growth induced failure at quasi-isothermal condition, the Inconel 625 fails by adiabatic shear at high strain rates. The present shear testing provides an opportunity to study the shear flow and failure of superalloy of small structural components in turbine engine.

Repeated Cyclogenesis on Hot-Exoplanet Atmospheres with Deep Heating.

Most current models of hot-exoplanet atmospheres assume shallow heating, a strong day-night differential heating near the top of the atmosphere. Here we investigate the effects of energy deposition at differing depths in a model tidally locked gas-giant exoplanet. We perform high-resolution atmospheric flow simulations of hot-exoplanet atmospheres forced with idealized thermal heating representative of shallow and deep heating (i.e., stellar irradiation strongly deposited at ∼10^{3} Pa and ∼10^{5} Pa pressure levels, respectively). Unlike with shallow heating, the flow with deep heating exhibits a new dynamic equilibrium state, characterized by repeated generation of giant cyclonic storms that move away westward once formed. The formation is accompanied by a burst of heightened turbulence, leading to the production of small-scale flow structures and large-scale mixing of temperature on a timescale of ∼3 planetary rotations. Significantly, while effects that could be important (e.g., coupled radiative flux and convectively excited gravity waves) are not included, over a timescale of several hundred days the simulations robustly show that the emergent thermal flux depends strongly on the heating type and is distinguishable by current observations.

Turbulence intensity effect on axial-flow-induced vibration of a two-cylinder cluster

This numerical study aims to investigate the effect of inlet turbulence intensity Tu (0.05 – 5.0%) on flow-induced vibration of an elastic cylinder with fixed ends placed next to a rigid cylinder of the same diameter and length in axial flow. Turbulent flow structure and fluid-structure interaction are captured using large eddy simulation and two-way coupling calculation, respectively. It is found that Tu produces a pronounced effect on vibration characteristics of the elastic cylinder. Given a dimensionless velocity U̅ (i.e., 3.49, less than critical U̅ for onset of buckling), root-mean-square vibration amplitude Arms⁎ increases rapidly with increasing Tu from 0.7% to 5.0% for any given center-to-center cylinder spacing P⁎ (1.20 – ∞). This change in Arms* is attributed to the interactions between turbulent structures of different scales, where interactions between large-scale eddies result in the formation of small-scale eddies in the interstitial flow between the cylinders, thus enhancing greatly the flow instability and hence Arms*. Another interesting phenomenon takes place at U̅ = 7.62 (beyond the critical U̅ for onset of buckling) and P⁎ = 1.80, where the elastic cylinder buckles into a new dynamic equilibrium state. As Tu increases from 0.3% to 1.5%, the flutter instability occurs merely along the y direction that is normal to the plane of two cylinders axes and also normal to main stream direction. It has been found that the high-Tu flow triggers two vortices in this direction, giving rise to two regions of different pressures around the cylinder. The two regions reposition quasi-periodically themselves, thus producing lateral forces that account for this flutter instability in the y direction. Scaling analysis of the dependence of Arms⁎ on Tu and U̅ reveals that the relationship Arms⁎ = g1(Tu, U̅) may be reduced to Arms⁎ = g2(U̅eff); g1 and g2 are different functions and the scaling factor U̅eff = U̅ TF, where TF is the turbulence factor that accounts for the effect of Tu on Arms⁎. The scaling law is discussed in detail, along with the physical meanings of U̅eff.

Dynamic metastable polymersomes enable continuous flow manufacturing

Polymersomes are polymeric analogues of liposomes with exceptional physical and chemical properties. Despite being dubbed as next-generation vesicles since their inception nearly three decades ago, polymersomes have yet to experience translation into the clinical or industrial settings. This is due to a lack of reliable methods to upscale production without compromising control over polymersome properties. Herein we report a continuous flow methodology capable of producing near-monodisperse polymersomes at scale (≥3 g/h) with the possibility of performing downstream polymersome manipulation. Unlike conventional polymersomes, our polymersomes exhibit metastability under ambient conditions, persisting for a lifetime of ca. 7 days, during which polymersome growth occurs until a dynamic equilibrium state is reached. We demonstrate how this metastable state is key to the implementation of downstream processes to manipulate polymersome size and/or shape in the same continuous stream. The methodology operates in a plug-and-play fashion and is applicable to various block copolymers.

Сезонные изменения кумуляции углеводородов в вобле дельты Волги

The importance of the research is conditioned by the increasing activity of the fuel and energy complex in the Volga-Caspian basin and as a consequence by the emergence of threat to the biodiversity of aquatic ecosystems. The assessment of the long-term and seasonal dynamics of hydrocarbon accumulation in the Volga River delta fish was carried out using the example of a roach. IR spectrophotometry method revealed the hydrocarbon content in the muscles and internal organs of the fish. It is demonstrated that the maximum level of hydrocarbons accumulation in the organs and tissues of the roach was observed from 2007 to 2013, relative to the later period from 2014 to 2020, excluding 2016. The regularity of increasing hydrocarbons concentration in the roach from summer to autumn in the period from 2007 to 2012 is pronounced. Until 2013 (inclusive), there were a number of conditions that contribute to the pronounced hydrocarbons accumulation in the body of the roach in the period from summer to autumn (the period of its summer feeding), which is primarily due to the general level of ecosystem pollution as well as the ability of forage objects to effectively accumulate a wide variety of substances. Later the process of hydrocarbon intake and elimination processes came to a state of dynamic equilibrium which is probably due to a decrease in the overall level of environmental pollution.

Simulation study on cuttings transport of the backreaming operation for long horizontal section wells

The backreaming operation plays a significant role in safe drilling for horizontal wellbores, while it may cause severe stuck pipe accidents. To lower the risk of the stuck pipe in backreaming operations, the mechanism of cuttings transport needs to be carefully investigated. In this research, a transient cuttings transport with multiple flow patterns model is developed to predict the evolution of cuttings transported in the annulus while backreaming. The established model can provide predictions of the distribution of cuttings bed along the wellbore considering the bulldozer effect caused by large-size drilling tools (LSDTs). The sensitivity analyses of the size of LSDTs, and backreaming operating parameters are conducted in Section 4. And a new theory is proposed to explain the mechanism of cuttings transport in the backreaming operation, in which both the bit and LSDTs have the “cleaning effect” and “plugging effect”. The results demonstrate that the cuttings bed in annuli is in a state of dynamic equilibrium, but the overall trend and the distribution pattern are obvious. First, larger diameters and longer drilling tools could lead to a higher risk of the stuck pipe. Second, we find that it is not the case that the higher flow rate is always better for hole cleaning, so three flow-rate intervals are discussed separately under the given conditions. When the “dangerous flow rate” (<33 L/s in Case 4) is employed, the cuttings bed completely blocks the borehole near the step surface and causes a stuck pipe directly. If the flow rate increases to the “low flow rate” interval (33–35 L/s in Case 4), a smaller flow rate instead facilitates borehole cleaning. If the flow rate is large enough to be in the “high flow rate” interval (>35 L/s in Case 4), the higher the flow rate, the better the cleaning effect of cuttings beds. Third, an interval of tripping velocity called “dangerous velocity” is proposed, in which the cuttings bed accumulation near the LSDTs is more serious than those of other tripping velocities. As long as the applied tripping velocity is not within the “dangerous velocity” (0.4–0.5 m/s in Case 5) interval in the backreaming operation, the risk of the stuck pipe can be controlled validly. Finally, through the factors analyses of the annular geometry, particle properties, and fluid properties in Section 5, it can be found that the “low flow rate”, “high flow rate” and “dangers flow rate” tend to decrease and the “dangerous velocity” tends to increase with the conditions more favorable for hole cleaning. This study has some guiding significance for risk prediction and parameter setting of the backreaming operation.

Understanding pedestrian route choice behavior in the continuous space: Diversity and equilibrium

Exploring general rules from diverse motion choices in the real world is a pivotal area of study that deepens our understanding of pedestrian behavior. In this research, we conduct pedestrian circle antipode experiments, from which we extract pedestrians' trajectories from repeated trials. We focus on the symmetric features identified from these experiments and employ the K-Medoids trajectory clustering method alongside several behavioral indicators, namely route length, travel time, and comfort level, to distinguish and compare different trajectory route choice patterns. In doing so, we delve into the heterogeneous behaviors exhibited by pedestrians within a single experiment and the stochastic behaviors seen across different experiments for a single pedestrian. Additionally, we establish a linear model to scrutinize the equilibrium relationship among these behavioral indicators, and further deploy the Gaussian process to shed light on the equilibrium characteristics inherent in pedestrian route choice behavior. Our findings suggest that despite the inherent heterogeneity and stochastic nature of individual behaviors, pedestrian route choice overall operates in a dynamic equilibrium state. These insights offer valuable implications for the design of facilities in transport hubs and crowd management strategies in social activities, potentially leading to more effective and organized public spaces.

Determine the Correlation between Different Forms of Sulphur in Surface Soil of Ashoknagar District of MP

Sulphur is one of the essential elements for plant growth. It is an important constituent of man,y enzymes and amino acids. Photosynthesis and nitrogen fixation are attributed to the type of sulphur linkage present. Sulphur has been found to help the synthesis of amino acids and hence increase the protein content of plants, boosting the oil content. Today, the Sulfur (S) research has extended to various soils, crops cropping systems and different sources of sulphur. Several soil factors influence the availability of sulphur and hence the status of different forms of sulphur in soil varies widely with soil types. Keeping in view, One hundred twenty-five GPS-based surface soil samples (0-15 cm) were collected from five blocks (Mungaoli, Chanderi, Ishagarh, Ashoknagar and Sadora) of Ashoknagar district from April to May 2017. Soils were studied for their physical and chemical characteristics and status of different forms of sulphur and their relationship with different soil properties.The different forms of sulphur, that is water soluble, available, organic and total-S were observed in the range of 1.23 – 7.67, 4.36 – 40.25, 89.08 – 194.53 and 167.45 – 422.20 mg kg-1 under different villages of the investigated area with the average value of 4.09, 14.68, 124.21 and 309.17 mg kg-1, respectively. Out of 125 surface samples, 36 samples (28.8%) were found under deficient, 72 (57.6%) under medium and 17 (13.6%) samples were found in sufficient category. The availability of sulphur increased with an increase in organic carbon and clay content in the soil. The correlation study revealed that organic carbon had a greater impact on different forms of sulphur followed by soil texture. It suggested that organic matter was the main contributing factor affecting the sulphur availability in soil. Total S maintained a significant positive association with all the forms of sulphur. Such a relationship suggests that sulphur exists in a state of dynamic equilibrium in these soils.

Analysis of Green Closed-Loop Supply Chain Efficiency under Generalized Stochastic Petri Nets

In this paper, we aim to explore the operational performance of a green closed-loop supply chain under random events. A green closed-loop supply chain model based on generalized stochastic Petri nets (GSPN) is built using the Petri nets theory. According to the isomorphic relationship between GSPN and continuous-time Markov chains, the relevant Markov model is converted from GSPN, and the steady-state probability of the model is then calculated. Finally, the model is analyzed from the aspects of time performance and operation efficiency of each link. Compared to previous studies, this paper finds that: when the whole green closed-loop supply chain system reaches a dynamic equilibrium state, the product has a steady-state probability at all stages, and thus the overall operational performance of the system can be obtained; compared with the recycling of waste products, the green product takes a longer time in the production and distribution stages; since marketing, packaging processing, market feedback, and market demand formulation account for a high level of utilization throughout the life cycle of green products, decision makers need to focus on the supervision and management of these links. Managers of green closed-loop supply chain systems need to adjust their decision-making strategies in a timely manner according to the performance level of the system in the steady state to realize the efficient operation of the system. This paper not only provides theoretical support for the improvement of the operational efficiency of green closed-loop supply chain system, but also provides new ideas for the research of green closed-loop supply chain operation mode.

Macrophage Polarization and the Regulation of Bone Immunity in Bone Homeostasis.

Bone homeostasis is a dynamic equilibrium state of bone formation and absorption, ensuring skeletal development and repair. Bone immunity encompasses all aspects of the intersection between the skeletal and immune systems, including various signaling pathways, cytokines, and the crosstalk between immune cells and bone cells under both homeostatic and pathological conditions. Therefore, as key cell types in bone immunity, macrophages can polarize into classical pro-inflammatory M1 macrophages and alternative anti-inflammatory M2 macrophages under the influence of the body environment, participating in the regulation of bone metabolism and playing various roles in bone homeostasis. M1 macrophages can not only act as precursors of osteoclasts (OCs), differentiate into mature OCs, but also secrete pro-inflammatory cytokines to promote bone resorption; while M2 macrophages secrete osteogenic factors, stimulating the differentiation and mineralization of osteoblast precursors and mesenchymal stem cells (MSCs), and subsequently increase bone formation. Once the polarization of macrophages is imbalanced, the resulting immune dysregulation will cause inflammatory stimulation, and release a large amount of inflammatory factors affecting bone metabolism, leading to pathological conditions such as osteoporosis (OP), rheumatoid arthritis (RA), and steroid-induced femoral head necrosis (SANFH). In this review, we introduce the signaling pathways and related factors of macrophage polarization, as well as their relationships with immune factors, OB, OC, and MSC. We also discuss the roles of macrophage polarization and bone immunity in various diseases of bone homeostasis imbalance, as well as the factors regulating them, which may help to develop new methods for treating bone metabolic disorders.

The impact of water table fluctuation and salinity on LNAPL distribution and geochemical properties in the smear zone under completely anaerobic conditions

Climate and groundwater are always in a state of dynamic equilibrium. Subsurface systems contaminated by light non-aqueous phase liquid (LNAPL) present a challenge to understand the overall impact of water table dynamics, due to various interacting mechanisms, including volatilization, and LNAPL mobilization/dissolution along the groundwater flow direction and oscillating redox conditions. We investigated the impact of water table fluctuations on LNAPL natural attenuation and soil geochemical characteristics in semi-arid coastal areas under saline conditions. Four soil columns operated for 151 days under anoxic conditions where a layer of benzene and toluene were subjected to a stable and fluctuating water table associated with low and high salinity conditions. The bottom of stable and fluctuating columns reached an anaerobic state after 40 days, while the middle of stable column took 60 days. pH values of the fluctuating columns covered a wide range, and at the end shifted towards alkaline conditions, unlike the stable columns. In fluctuating columns, pore water sulfate decreased in the middle, but in stable columns, it decreased in the first 40 days, which suggested that sulfate was the primary electron donor and sulfate-reducing bacteria were present. At the source zone, benzene and toluene reached their maximum concentration after 30 and 10 days for the stable and the fluctuating columns, respectively. Significant decrease in benzene and toluene concentrations occurred under the fluctuating water table. Salinity did not affect benzene and toluene concentrations in the aqueous phase, although water table fluctuations have the most effect. Soil solid-phase analysis shows fluctuating columns have less toluene than stable columns. Solid-phase analysis showed the fluctuating columns have less benzene and toluene concentrations as compared to the stable columns.

Research on the Collaborative Optimization of the Power Distribution Network and Traffic Network Based on Dynamic Traffic Allocation

With the increasing penetration rate of electric vehicles, the spatiotemporal coupling relationship between the power distribution network and traffic network is stronger than ever before. Under the dynamic wireless charging mode, traffic jam charging is introduced and the dynamic loading process of traffic flow is described using a cellular transmission model. The charging load is related to traffic flow and serves as a bond between the power distribution network and traffic network. The traffic flow achieves balanced allocation under dynamic user equilibrium conditions, and cooperatively optimizes the power flow of the power distribution network in conjunction with charging loads. Numerical analysis shows that this model can accurately depict the congestion situation during peak travel periods, and alleviate traffic congestion and distribution network voltage out of range.

Copper homeostasis dysregulation promoting cell damage and the association with liver diseases.

Copper plays an important role in many metabolic activities in the human body. Copper level in the human body is in a state of dynamic equilibrium. Recent research on copper metabolism has revealed that copper dyshomeostasis can cause cell damage and induce or aggravate some diseases by affecting oxidative stress, proteasome, cuprotosis, and angiogenesis. The liver plays a central role in copper metabolism in the human body. Research conducted in recent years has unraveled the relationship between copper homeostasis and liver diseases. In this paper, we review the available evidence of the mechanism by which copper dyshomeostasis promotes cell damage and the development of liver diseases, and identify the future research priorities.

Drainage network rearrangement during the formation and segmentation of a Paleogene intraplate half-graben: Insights from fluvial captures records and longitudinal profiles

Rivers play an important role in modifying landscapes through denudation processes, which can be influenced by changes in tectonics, climate and eustasy, causing erosive pulses and river capture events that alter the geometry and topology of the drainage network. Therefore, drainage networks are not static features over time and are modified and rearranged by shifts in their boundary conditions until a state of dynamic equilibrium is reached in the landscape. The region of the Paraíba do Sul Middle Valley (PSMV), in Southeastern Brazil, has important records of captures and recent drainage rearrangements, which show a state of transition in the landscape and, consequently, the reorganization of drainage networks. This region is in the central segment of the Continental Rift of Southeastern Brazil (CRSB), a prominent tectonic feature that can be described as an intraplate half-graben. While fluvial profiles and fluvial gradient indices are valuable tools for studying the landscape evolution, their application to investigate the erosive power of rivers and how the topography of a half-graben affects the rearrangement of the drainage network over geological time is still limited. Specifically, there is a need to explore how the topography of the active border of a half-graben differs from that of the flexural border in terms of river network organization and fluvial erosion patterns. This study aims to characterize the different stages of rearrangements of the drainage network and their relation with the events of formation and segmentation of a half-graben. A total of 21 basins were analyzed in both Fault and Flexural Border sectors, extracting geomorphic parameters, such as slope, drainage area, concavity, χ and ksn. A more specific study was carried out in areas where river captures were recognized as been related to the half-graben formation and segmentation events. The ksn calculated for the main rivers demonstrates that the formation of the rift and its consequent configuration in half-graben granted a greater erosive power for the basins that drained the active fault of the rift, represented by the basins of the Fault Border Sector of the study area. The tectonic events registers in the fluvial system were analyzed using the χ method and the main migration tendency of the dividers was extracted from the difference in the values of this parameter in areas close to the interfluves. With this, it becomes evident that the geometric configuration imposed in the half-graben establishes, from the beginning of the rift phase, an important control on the erosion potential of the rivers located in the active and flexural borders. This control resulted in ancient river captures, currently exposed as inflections in the main river channels towards the local depocenters, thus demonstrating that this type of tectonic event can generate disturbances in the river system that can be observed even today, tens of millions of years after it happened.