Observing heroic behavior and its influencing factors in immersive virtual environments.

Studying heroism in controlled settings presents challenges and ethical controversies due to its association with physical risk. Leveraging virtual reality (VR) technology, we conducted a three-study series with 397 participants from China to investigate heroic actions. Participants unexpectedly witnessed a criminal event in a simulated scenario, allowing observation of their tendency to physically intercept a thief. We examined situational factors (voluntariness, authority, and risk) and personal variables [gender, impulsivity, empathy, and social value orientation (SVO)] that may influence heroism. Also, the potential association between heroism and social conformity was explored. In terms of situational variables, voluntariness modulated participants' tendency to intercept the escaping thief, while perceived risk demonstrated its impact by interacting with gender. That is, in study 3 where the perceived risk was expected to be higher (as supported by an online study 5), males exhibited a greater inclination toward heroic behavior compared to females. Regarding other personal variables, the tendency to engage in heroic behavior decreased as empathy levels rose among males, whereas the opposite trend was observed for females. SVO influenced heroic behavior but without a gender interaction. Finally, an inverse relationship between heroism and social conformity was observed. The robustness of these findings was partly supported by the Chinese sample (but not the international sample) of an online study 4 that provided written descriptions of VR scenarios, indicating cultural variations. These results advance insights into motivational factors influencing heroism in the context of restoring order and highlight the power of VR technology in examining social psychological hypotheses beyond ethical constraints.

Esculin suppresses the PERK-eIF2α-CHOP pathway by enhancing SIRT1 expression in oxidative stress-induced rat chondrocytes, mitigating osteoarthritis progression in a rat model.

OBJECTIVE: Osteoarthritis (OA) is a degenerative disease characterized by the gradual degeneration of chondrocytes, involving endoplasmic reticulum (ER) stress. Esculin is a natural compound with antioxidant, anti-inflammatory and anti-tumor properties. However, its impact on ER stress in OA therapy has not been thoroughly investigated. We aim to determine the efficiency of Esculin in OA treatment and its underlying mechanism. METHODS: We utilized the tert-butyl hydroperoxide (TBHP) to establish OA model in chondrocytes. The expression of SIRT1, PERK/eIF2α pathway-related proteins, apoptosis-associated proteins and ER stress-related proteins were detected by Western blot and Real-time PCR. The apoptosis was evaluated by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. X-ray imaging, Hematoxylin & Eosin staining, Safranin O staining and immunohistochemistry were used to assess the pharmacological effects of Esculin in the anterior cruciate ligament transection (ACLT) rat OA model. RESULTS: Esculin downregulated the expression of PERK/eIF2α pathway-related proteins, apoptosis-associated proteins and ER stress-related proteins, while upregulated the expression of SIRT1 and Bcl2 in the TBHP-induced OA model in vitro. It was coincident with the results of TUNEL staining and flow cytometry. We further confirmed the protective effect of Esculin in the rat ACLT-related model. CONCLUSION: Our results suggest the potential therapeutic value of Esculin on osteoarthritis. It probably inhibits the PERK-eIF2α-ATF4-CHOP pathway by upregulating SIRT1, thereby mitigating endoplasmic reticulum stress and protecting chondrocytes from apoptosis.

Deep eutectic polymer/Ti3C2Tx for enhancing mechanical properties, photothermal conversion, and bacterial inactivation of cellulose textiles.

Two-dimensional (2D) transition metal carbides (Ti3C2Tx MXene) have gained significant attention for their potential in constructing diverse functional materials, However, MXene is easily oxidized and weakly bound to the cellulose matrix, which pose challenges in developing MXene-decorated non-woven fabric with strong bonding and stable thermal management properties. Herein, we successfully prepared deep eutectic supramolecular polymer (DESP) functionalized MXene to address these issues. MXene can be wrapped with DESP to be insulated from water and protected from being oxidized. Subsequently, we achieved an efficient in-situ deposition of DESP-functionalized MXene onto fibers through a combination of dip coating and photopolymerization technique. The resulting nonwoven fabric (CNs-DESP@M) exhibited excellent photothermal conversion properties along with rapid thermal response and functional stability. Interestingly, the interface bonding between MXene and the fiber surface was significantly enhanced due to the abundant pyrogallol groups in DESP, resulting in the composite textile exhibiting commendable mechanical properties (2.68 MPa). Moreover, the as-prepared textile demonstrates outstanding bactericidal efficacy against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The multifunctional textile, created through a facile and efficient approach, demonstrates remarkable potential for applications in smart textiles, catering to the diverse needs of individuals in the future.

Punicalagin attenuates hyperuricemia via restoring hyperuricemia-induced renal and intestinal dysfunctions.

INTRODUCTION: It is estimated that 90% of hyperuricemia cases are attributed to the inability to excrete uric acid (UA). The two main organs in charge of excreting UA are the kidney (70%) and intestine (30%). Previous studies have reported that punicalagin (PU) could protect against kidney and intestinal damages, which makes it a potential candidate for alleviating hyperuricemia. However, the effects and deeper action mechanisms of PU for managing hyperuricemia are still unknown. OBJECTIVE: To investigate the effect and action mechanisms of PU for ameliorating hyperuricemia. METHODS: The effects and action mechanisms of PU on hyperuricemia were assessed using a hyperuricemia mice model. Phenotypic parameters, metabolomics analysis, and 16S rRNA sequencing were applied to explore the effect and fundamental action mechanisms inside the kidney and intestine of PU for improving hyperuricemia. RESULTS: PU administration significantly decreased elevated serum uric acid (SUA) levels in hyperuricemia mice, and effectively alleviated the kidney and intestinal damage caused by hyperuricemia. In the kidney, PU down-regulated the expression of UA resorption protein URAT1 and GLUT9, while up-regulating the expression of UA excretion protein ABCG2 and OAT1 as mediated via the activation of MAKP/NF-κB in hyperuricemia mice. Additionally, PU attenuated renal glycometabolism disorder, which contributed to improving kidney dysfunction and inflammation. Similarly, PU increased UA excretion protein expression via inhibiting MAKP/NF-κB activation in the intestine of hyperuricemia mice. Furthermore, PU restored gut microbiota dysbiosis in hyperuricemia mice. CONCLUSION: This research revealed the ameliorating impacts of PU on hyperuricemia by restoring kidney and intestine damage in hyperuricemia mice, and to be considered for the development of nutraceuticals used as UA-lowering agent.

Status and Influencing Factors of Foot Care Behavior for Patients with Diabetic Foot Amputation: Across-Sectional Study.

This study aimed to investigate the contemporary status and influencing factors of foot self-care behavior in diabetic foot amputation patients. A total of 250 patients with diabetic foot amputation were included. The general information questionnaire, Chinese Version of the Nottingham Assessment of Function Footcare (CNAFF), Knowledge of Diabetic Foot Questionnaire, and The Third Version of the Diabetes Attitude Scale were used to investigate the status and influencing factors of foot self-care behavior in patients with diabetic foot amputation. From our sample, the Chinese version of Nottingham foot care behavior score was 68.32 ± 10.35 points, which showed that the foot self-care behavior of patients with diabetic foot amputation is at a medium level. Multiple linear regression analysis showed that education level, the knowledge of how to choose shoes and socks, the knowledge of self-care for feet, the need for special training in education, and the patient's autonomy in diabetes care were the main factors influencing foot self-care behavior of patients with diabetic foot amputation (P < 0.05). The total variation of CNAFF score was 49%. The results of this study show that the level of foot care of diabetic amputees must be improved, and medical staffs need to take targeted intervention measures to help patients improve their self-care behavior after amputation, thereby reducing the recurrence rate of diabetic feet and improving their quality of life.

Tracing the entry process of submicrometre plastics in soybean sprouts by leaf-derived fluorescent carbon dots.

As a global emerging contaminant, microplastics (MPs) in water or soil can accumulate in vegetables, making them easily ingested through the diet. With excellent and tunable optical properties, carbon dots (CDs) are highly advantageous for tracing the entry process of MPs. Originally, long-wavelength CDs were synthesized from leaf-derived extracts, and fluorescent submicrometer plastics (CDs-MPs) with clean surfaces and concentrated particle sizes were obtained by soap-free microemulsion polymerization. The concentration of CDs-MPs exhibits a significant linear relationship with long-wavelength fluorescence intensity (λEx/λEm: 415/676 nm). Soybean sprouts (SBS), as an important type of food, are susceptible to contamination of MPs due to their soft epidermis and rapidly growing biomass. The results showed that CDs-MPs could be embedded into the cortex of SBS and enter the plant with cell division and elongation, leading to an increase in pore size on the cell wall surface. After entering the root system, CDs-MPs will pass through the Casparian strip and migrate in the vessels. Then, CDs-MPs enter the leaves through vascular bundles, and the distribution and size of epicuticular wax on leaves have changed. Furthermore, SBS showed resistant growth and increased levels of oxidative response when exposed to MPs/CDs-MPs. It is the first study to demonstrate the application of leaf-derived CDs in the prevention of MPs pollution by revealing the migration behavior of submicrometre plastics in SBS.

Double S-scheme Cu2-xSe/twinned-Cd0.5Zn0.5S homo-heterojunctions with surface plasmon effects for efficient photocatalytic H2 evolution.

The enhancement of charge separation and utilization efficiency in both the bulk phase and interface of semiconductor photocatalysts, as well as the expansion of light absorption range, are crucial research topics in the field of photocatalysis. To address this issue, twinned Cd0.5Zn0.5S (T-CZS) homojunctions consisting of wurtzite Cd0.5Zn0.5S (WZ-CZS) and zinc blende Cd0.5Zn0.5S (ZB-CZS) were synthesized via a hydrothermal method to facilitate the bulk-phase charge separation. Meanwhile, Cu2-xSe with localized surface plasmon resonance effect (LSPR) generated by Cu vacancies was also obtained through a hydrothermal process. Due to their opposite electronegativity, a solvent evaporation strategy was employed to combine Cu2-xSe and T-CZS by intermolecular electrostatic. After optimization, the photocatalytic hydrogen (H2) evolution rate of 5 wt% Cu2-xSe/T-CZS reached an impressive value of 60 mmol∙h-1∙g-1, which was 4.6 and 66.6 times higher than that of pure Cu2-xSe and T-CZS, respectively. Furthermore, this composites demonstrated a remarkable rate of 0.46 mmol∙h-1∙g-1 under near-infrared (NIR) wavelength (>800 nm). The enhanced performance observed in Cu2-xSe/T-CZS can be attributed to its unique and efficient double S-scheme charge transfer mechanism which effectively suppresses rapid recombination of electron-hole pairs both within the bulk phase and at the surface interfaces; this conclusion is supported by Density Functional Theory (DFT) calculations as well as electron paramagnetic resonance spectroscopy analysis. Moreover, incorporation of Cu2-xSe enables effective utilization ultraviolet visible-near infrared (UV-Vis-NIR) light by the composites while facilitating injection "hot electrons" into T-CZS for promoting photocatalytic reactions. This study provides a potential strategy for achieving efficient solar energy conversion through synergistic integration of non-stoichiometric plasmonic materials with photocatalysts with twinned-twinned structures.

Leaf Senescence Regulation Mechanism Based on Comparative Transcriptome Analysis in Foxtail Millet.

Leaf senescence, a pivotal process in plants, directly influences both crop yield and nutritional quality. Foxtail millet (Setaria italica) is a C4 model crop renowned for its exceptional nutritional value and stress tolerance characteristics. However, there is a lack of research on the identification of senescence-associated genes (SAGs) and the underlying molecular regulatory mechanisms governing this process. In this study, a dark-induced senescence (DIS) experimental system was applied to investigate the extensive physiological and transcriptomic changes in two foxtail millet varieties with different degrees of leaf senescence. The physiological and biochemical indices revealed that the light senescence (LS) variety exhibited a delayed senescence phenotype, whereas the severe senescence (SS) variety exhibited an accelerated senescence phenotype. The most evident differences in gene expression profiles between these two varieties during DIS included photosynthesis, chlorophyll, and lipid metabolism. Comparative transcriptome analysis further revealed a significant up-regulation of genes related to polysaccharide and calcium ion binding, nitrogen utilization, defense response, and malate metabolism in LS. In contrast, the expression of genes associated with redox homeostasis, carbohydrate metabolism, lipid homeostasis, and hormone signaling was significantly altered in SS. Through WGCNA and RT-qPCR analyses, we identified three SAGs that exhibit potential negative regulation towards dark-induced leaf senescence in foxtail millet. This study establishes the foundation for a further comprehensive examination of the regulatory network governing leaf senescence and provides potential genetic resources for manipulating senescence in foxtail millet.

Icephobic Durability of Molecular Brush-Structured PDMS Soft Coatings.

The accumulation of ice can pose numerous inconveniences and potential hazards, profoundly affecting both human productivity and daily life. To combat the challenges posed by icing, extensive research efforts have been dedicated to the development of low-ice adhesion surfaces. In this study, we harness the power of molecular dynamics simulations to delve into the intricate dynamics of polymer chains and their role in determining the modulus of the material. We present a novel strategy to prepare ultralow-modulus poly(dimethylsiloxane) (PDMS) elastomers with a molecular brush configuration as icephobic materials. The process involves grafting monohydride-terminated PDMS (H-PDMS) as side chains onto backbone chain PDMS with pendant vinyl functional groups to yield a molecular brush structure. The segments of this polymer structure effectively restrict interchain entanglement, thereby rendering a lower modulus compared to traditional linear structures at an equivalent cross-linking density. The developed soft coating exhibits a remarkably ultralow ice adhesion strength of 13.1 ± 1.1 kPa. Even after enduring 50 cycles of icing and deicing, the ice adhesion strength of this coating steadfastly stayed below 16 kPa, showing no notable increase. Importantly, the molecular brush coating applied to glass demonstrated an impressive light transmittance of 92.1% within the visible light spectrum, surpassing the transmittance of bare glass, which was measured at 91.3%. This icephobic coating with exceptional light transmittance offers a wide range of applications and holds significant potential as a practical icephobic material.

Growth of millimeter-sized 2D metal iodide crystals induced by ion-specific preference at water-air interfaces.

Conventional liquid-phase methods lack precise control in synthesizing and processing materials with macroscopic sizes and atomic thicknesses. Water interfaces are ubiquitous and unique in catalyzing many chemical reactions. However, investigations on two-dimensional (2D) materials related to water interfaces remain limited. Here we report the growth of millimeter-sized 2D PbI2 single crystals at the water-air interface. The growth mechanism is based on an inherent ion-specific preference, i.e. iodine and lead ions tend to remain at the water-air interface and in bulk water, respectively. The spontaneous accumulation and in-plane arrangement within the 2D crystal of iodide ions at the water-air interface leads to the unique crystallization of PbI2 as well as other metal iodides. In particular, PbI2 crystals can be customized to specific thicknesses and further transformed into millimeter-sized mono- to few-layer perovskites. Additionally, we have developed water-based techniques, including water-soaking, spin-coating, water-etching, and water-flow-assisted transfer to recycle, thin, pattern, and position PbI2, and subsequently, perovskites. Our water-interface mediated synthesis and processing methods represents a significant advancement in achieving simple, cost-effective, and energy-efficient production of functional materials and their integrated devices.

Towards a Human-Centric Digital Twin for Human-Machine Collaboration: A Review on Enabling Technologies and Methods.

With the intent to further increase production efficiency while making human the centre of the processes, human-centric manufacturing focuses on concepts such as digital twins and human-machine collaboration. This paper presents enabling technologies and methods to facilitate the creation of human-centric applications powered by digital twins, also from the perspective of Industry 5.0. It analyses and reviews the state of relevant information resources about digital twins for human-machine applications with an emphasis on the human perspective, but also on their collaborated relationship and the possibilities of their applications. Finally, it presents the results of the review and expected future works of research in this area.

DFSNet: A 3D Point Cloud Segmentation Network toward Trees Detection in an Orchard Scene.

In order to guide orchard management robots to realize some tasks in orchard production such as autonomic navigation and precision spraying, this research proposed a deep-learning network called dynamic fusion segmentation network (DFSNet). The network contains a local feature aggregation (LFA) layer and a dynamic fusion segmentation architecture. The LFA layer uses the positional encoders for initial transforming embedding, and progressively aggregates local patterns via the multi-stage hierarchy. The fusion segmentation module (Fus-Seg) can format point tags by learning a multi-embedding space, and the generated tags can further mine the point cloud features. At the experimental stage, significant segmentation results of the DFSNet were demonstrated on the dataset of orchard fields, achieving an accuracy rate of 89.43% and an mIoU rate of 74.05%. DFSNet outperforms other semantic segmentation networks, such as PointNet, PointNet++, D-PointNet++, DGCNN, and Point-NN, with improved accuracies over them by 11.73%, 3.76%, 2.36%, and 2.74%, respectively, and improved mIoUs over the these networks by 28.19%, 9.89%, 6.33%, 9.89, and 24.69%, respectively, on the all-scale dataset (simple-scale dataset + complex-scale dataset). The proposed DFSNet can capture more information from orchard scene point clouds and provide more accurate point cloud segmentation results, which are beneficial to the management of orchards.

First-principles study of multifunctional Mn2B3 materials with high hardness and ferromagnetism.

Transition metal boride TM2B3 is widely studied in the field of physics and materials science. However, Mn2B3 has not been found in Mn-B systems so far. Mn2B3 undergoes phase transitions from Cmcm (0-28 GPa) to C2/m (28-80 GPa) and finally to C2/c (80-200 GPa) under pressure. Among these stable phases, Cmcm- and C2/m-Mn2B3s comprise six-membered boron rings and C2/c-Mn2B3 has wavy boron chains. They all have good mechanical properties and can become potential multifunctional materials. The strong B-B covalent bonding is mainly responsible for the structural stability and hardness. Comparison of the hardness of the five TM2B3s with different bonding strengths of TM-B and B-B bonds reveals a nonlinear change in the hardness. According to the Stoner model, these structures possess ferromagnetism, and the corresponding magnetic moments are almost the same as those of GGA and GGA + U (U = 3.9 eV, J = 1 eV).

Topological corner state localized bound states in continuum in photonic crystals.

In the field of optics, bound states in the continuum (BICs) are of significant practical importance as they can trap electromagnetic waves spatially, even though their frequency lies within the continuous spectrum. Previous research, however, has shown that BICs localized in optical cavities are highly sensitive to geometric and environmental changes. This sensitivity implies that slight variations can lead to the loss of BICs, necessitating extreme precision in manufacturing, which poses a challenge for practical implementation. To overcome this issue, this study employs topological photonic crystals (PhCs) to engineer topological corner states (TCS) within PhCs. By doing so, it establishes a method for creating topological BICs that are inherently robust against disturbances, thereby enhancing their suitability for real-world applications.

Research Progress on Extracellular Matrix Involved in the Development of Preeclampsia.

Preeclampsia (PE) is a serious pregnancy complication, and its primary clinical manifestations are gestational hypertension and proteinuria. Trophoblasts are responsible for the basic functions of the placenta during placental development; recent studies have revealed that placental "shallow implantation" caused by the decreased invasiveness of placental trophoblasts plays a crucial role in PE pathogenesis. The interaction between the cells and the extracellular matrix (ECM) plays a crucial role in trophoblast proliferation, differentiation, and invasion. Abnormal ECM function can result in insufficient migration and invasion of placental trophoblasts, thus participating in PE. This article summarizes the recent studies on the involvement of ECM components, including small leucine-rich proteoglycans, syndecans, glypicans, laminins, fibronectin, collagen, and hyaluronic acid, in the development of PE. ECM plays various roles in PE development, most notably by controlling the activities of trophoblasts. The ECM is structurally stable and can serve as a biological diagnostic marker and therapeutic target for PE.

Identifying key mental health and improvement factors in hospital administrators working from home using a DEMATEL-based network analysis model.

Purpose: To identify the key mental health and improvement factors in hospital administrators working from home during COVID-19 normalization prevention and control. Methods: The survey was conducted from May to June 2023, and the practical experiences of 33 hospital administrators were collected using purposive sampling. The study examined a set of mental health factor systems. The relationship structure between the factors was constructed using the Decision-making Trial and Evaluation Laboratory (DEMATEL) method. Finally, the structure was transformed using the influence weight of each factor via the DEMATEL-based Analytic Network Process. Results: Regarding influence weight, the key mental health factors of hospital administrators are mainly "lack of coordination," "time management issues," and "work-life imbalances." The influential network relation map shows that improvements can be made by addressing "improper guidelines," "laziness due to being at home," and "job insecurity" because they are the main sources of influence. The reliability level of the results for the network structure and weight was 98.79% (i.e., the gap was 1.12% < 5%). Conclusion: The network analysis model based on DEMATEL proposed in this study can evaluate the mental health factors of hospital administrators during the pandemic period from a multidimensional and multidirectional perspective and may help improve mental health problems and provide suggestions for hospital administrators.

Light on Alzheimer's disease: from basic insights to preclinical studies.

Alzheimer's disease (AD), referring to a gradual deterioration in cognitive function, including memory loss and impaired thinking skills, has emerged as a substantial worldwide challenge with profound social and economic implications. As the prevalence of AD continues to rise and the population ages, there is an imperative demand for innovative imaging techniques to help improve our understanding of these complex conditions. Photoacoustic (PA) imaging forms a hybrid imaging modality by integrating the high-contrast of optical imaging and deep-penetration of ultrasound imaging. PA imaging enables the visualization and characterization of tissue structures and multifunctional information at high resolution and, has demonstrated promising preliminary results in the study and diagnosis of AD. This review endeavors to offer a thorough overview of the current applications and potential of PA imaging on AD diagnosis and treatment. Firstly, the structural, functional, molecular parameter changes associated with AD-related brain imaging captured by PA imaging will be summarized, shaping the diagnostic standpoint of this review. Then, the therapeutic methods aimed at AD is discussed further. Lastly, the potential solutions and clinical applications to expand the extent of PA imaging into deeper AD scenarios is proposed. While certain aspects might not be fully covered, this mini-review provides valuable insights into AD diagnosis and treatment through the utilization of innovative tissue photothermal effects. We hope that it will spark further exploration in this field, fostering improved and earlier theranostics for AD.

TMC7 functions as a suppressor of Piezo2 in primary sensory neurons blunting peripheral mechanotransduction.

The transmembrane channel-like (TMC) protein family comprises eight members, with TMC1 and TMC2 being extensively studied. This study demonstrates substantial co-expression of TMC7 with the mechanosensitive channel Piezo2 in somatosensory neurons. Genetic deletion of TMC7 in primary sensory ganglia neurons in vivo enhances sensitivity in both physiological and pathological mechanosensory transduction. This deletion leads to an increase in proportion of rapidly adapting (RA) currents conducted by Piezo2 in dorsal root ganglion (DRG) neurons and accelerates RA deactivation kinetics. In HEK293 cells expressing both proteins, TMC7 significantly suppresses the current amplitudes of co-expressed Piezo2. Our findings reveal that TMC7 and Piezo2 exhibit physical interactions, and both proteins also physically interact with cytoskeletal ß-actin. We hypothesize that TMC7 functions as an inhibitory modulator of Piezo2 in DRG neurons, either through direct inhibition or by disrupting the transmission of mechanical forces from the cytoskeleton to the channel.

Genome analysis of a newly isolated Bacillus velezensis-YW01 for biodegrading acetaldehyde.

Acetaldehyde (AL), a primary carcinogen, not only pollutes the environment, but also endangers human health after drinking alcohol. Here a promising bacterial strain was successfully isolated from a white wine cellar pool in the province of Shandong, China, and identified as Bacillus velezensis-YW01 with 16 S rDNA sequence. Using AL as sole carbon source, initial AL of 1 g/L could be completely biodegraded by YW01 within 84 h and the cell-free extracts of YW01 has also been detected to biodegrade the AL, which indicate that YW01 is a high-potential strain for the biodegradation of AL. The optimal culture conditions and the biodegradation of AL of YW01 are at pH 7.0 and 38 °C, respectively. To further analyze the biodegradation mechanism of AL, the whole genome of YW01 was sequenced. Genes ORF1040, ORF1814 and ORF0127 were revealed in KEGG, which encode for acetaldehyde dehydrogenase. Furthermore, ORF0881 and ORF052 encode for ethanol dehydrogenase. This work provides valuable information for exploring metabolic pathway of converting ethanol to AL and subsequently converting AL to carboxylic acid compounds, which opened up potential pathways for the development of microbial catalyst against AL.

Covariate modeling in pharmacometrics: General points for consideration.

Modeling the relationships between covariates and pharmacometric model parameters is a central feature of pharmacometric analyses. The information obtained from covariate modeling may be used for dose selection, dose individualization, or the planning of clinical studies in different population subgroups. The pharmacometric literature has amassed a diverse, complex, and evolving collection of methodologies and interpretive guidance related to covariate modeling. With the number and complexity of technologies increasing, a need for an overview of the state of the art has emerged. In this article the International Society of Pharmacometrics (ISoP) Standards and Best Practices Committee presents perspectives on best practices for planning, executing, reporting, and interpreting covariate analyses to guide pharmacometrics decision making in academic, industry, and regulatory settings.