3D-Printed Shape Memory and Piezoelectric Bifunctional Thermoplastic Polyurethane/Polyvinylidene Fluoride Porous Composite Scaffold for Bone Regeneration.

Physical stimulations such as mechanical and electric stimulation can continuously work on bone defect locations to maintain and enhance cell activity, and it has become a hotspot for research in the field of bone repair. Herein, bifunctional porous composite scaffolds with shape memory and piezoelectric functions were fabricated using thermoplastic polyurethane (TPU) and poly(vinylidene fluoride) through triply periodic minimal surfaces design and selective laser sintering technology. Thereinto, the shape fixity ratio and recovery ratio of the composite scaffold reached 98.6% and 81.2%, respectively, showing excellent shape memory functions. More importantly, its piezoelectric coefficient (d33 = 2.47 pC/N) is close to the piezoelectric constant of bone tissue (d33 = 0.7-2.3 pC/N), and the voltage released during the compression process can reach 0.5 V. Furthermore, cyclic compression experiments showed that the strength of composite scaffold was up to 8.3 times compared with the TPU scaffold. Besides, the composite scaffold showed excellent cytocompatibility. In conclusion, the composite scaffold is expected to continuously generate mechanical and electric stimulation due to shape memory and piezoelectric function, respectively, which provide an effective strategy for bone repair.

Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition.

As the first identified multidrug efflux pump in Mycobacterium tuberculosis (Mtb), EfpA is an essential protein and promising drug target. However, the functional and inhibitory mechanisms of EfpA are poorly understood. Here we report cryo-EM structures of EfpA in outward-open conformation, either bound to three endogenous lipids or the inhibitor BRD-8000.3. Three lipids inside EfpA span from the inner leaflet to the outer leaflet of the membrane. BRD-8000.3 occupies one lipid site at the level of inner membrane leaflet, competitively inhibiting lipid binding. EfpA resembles the related lysophospholipid transporter MFSD2A in both overall structure and lipid binding sites and may function as a lipid flippase. Combining AlphaFold-predicted EfpA structure, which is inward-open, we propose a complete conformational transition cycle for EfpA. Together, our results provide a structural and mechanistic foundation to comprehend EfpA function and develop EfpA-targeting anti-TB drugs.

Nucleation and growth process of a softened-spark layer during microarc oxidation on a selective laser melted Ti alloy.

A two-step method for preparing composite coatings with different composition on Ti alloys using softened spark microarc oxidation technology was proposed. The nucleation and growth processes of a softened spark layer, as well as the influence of softened sparks on the deposition of anions in electrolytes, were studied. The results show that the process voltage of the softened spark discharge on the selective laser-melted Ti6Al4V alloy was lower than the breakdown voltage of its anodic oxide film. The softened sparks prioritized nucleation at the coating/substrate interface in the initial spark discharge area rather than in the microarc discharge area. On one hand, the softened spark layer grew towards the Ti6Al4V substrate, and on the other hand, the molten oxide generated by the softened sparking was transferred into the external porous layer. The softened sparks generated inside the coating promoted the rutile phase formation and linear growth in the thickness of the softened spark layer. Ca and P are mainly distributed in the external porous layer or at the interface between the softened-spark and external porous layers. Nevertheless, softened sparking had little effect on the initial micro/nanoporous structures of the coatings.

The integration of geographic methods and ecological momentary assessment in public health research: A systematic review of methods and applications.

With the widespread prevalence of mobile devices, ecological momentary assessment (EMA) can be combined with geospatial data acquired through geographic techniques like global positioning system (GPS) and geographic information system. This technique enables the consideration of individuals' health and behavior outcomes of momentary exposures in spatial contexts, mostly referred to as "geographic ecological momentary assessment" or "geographically explicit EMA" (GEMA). However, the definition, scope, methods, and applications of GEMA remain unclear and unconsolidated. To fill this research gap, we conducted a systematic review to synthesize the methodological insights, identify common research interests and applications, and furnish recommendations for future GEMA studies. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to systematically search peer-reviewed studies from six electronic databases in 2022. Screening and eligibility were conducted following inclusion criteria. The risk of bias assessment was performed, and narrative synthesis was presented for all studies. From the initial search of 957 publications, we identified 47 articles included in the review. In public health, GEMA was utilized to measure various outcomes, such as psychological health, physical and physiological health, substance use, social behavior, and physical activity. GEMA serves multiple research purposes: 1) enabling location-based EMA sampling, 2) quantifying participants' mobility patterns, 3) deriving exposure variables, 4) describing spatial patterns of outcome variables, and 5) performing data linkage or triangulation. GEMA has advanced traditional EMA sampling strategies and enabled location-based sampling by detecting location changes and specified geofences. Furthermore, advances in mobile technology have prompted considerations of additional sensor-based data in GEMA. Our results highlight the efficacy and feasibility of GEMA in public health research. Finally, we discuss sampling strategy, data privacy and confidentiality, measurement validity, mobile applications and technologies, and GPS accuracy and missing data in the context of current and future public health research that uses GEMA.

Phenylglycine amphiphile-metal ion chiral supramolecular nanozymes for enantioselective catalysis.

L/D-Phenylglycine amphiphiles and metal ions with peroxidase-like activity self-assembled into chiral nanoribbons, which act as efficient chiral supramolecular nanozymes for catalyzing the 3,4-dihydroxy-L/D-phenylalanine (L/D-DOPA) oxidation reactions. The catalytic efficiency and enantioselectivity are dominated by the chirality transfer and the synergistic effect between the metal ions and chiral nanoribbons.

A framework enabling LLMs into regulatory environment for transparency and trustworthiness and its application to drug labeling document.

Regulatory agencies consistently deal with extensive document reviews, ranging from product submissions to both internal and external communications. Large Language Models (LLMs) like ChatGPT can be invaluable tools for these tasks, however present several challenges, particularly the proprietary information, combining customized function with specific review needs, and transparency and explainability of the model's output. Hence, a localized and customized solution is imperative. To tackle these challenges, we formulated a framework named askFDALabel on FDA drug labeling documents that is a crucial resource in the FDA drug review process. AskFDALabel operates within a secure IT environment and comprises two key modules: a semantic search and a Q&A/text-generation module. The Module S built on word embeddings to enable comprehensive semantic queries within labeling documents. The Module T utilizes a tuned LLM to generate responses based on references from Module S. As the result, our framework enabled small LLMs to perform comparably to ChatGPT with as a computationally inexpensive solution for regulatory application. To conclude, through AskFDALabel, we have showcased a pathway that harnesses LLMs to support agency operations within a secure environment, offering tailored functions for the needs of regulatory research.

A systematic review of the relationship between natural environments and physiological and mental health during different stages of the COVID-19 pandemic.

COVID-19 has altered how individuals interact with natural environments. Numerous studies have investigated the effects of such environments on health. However, how natural environments influenced individuals' physiological and mental health during various stages of the COVID-19 pandemic remains unclear. Therefore, we conducted this study to investigate the effects of natural environments on individuals' physiological and mental health during different stages of the pandemic; we also identified factors that mediated these effects. Overall, we evaluated the importance of natural environments during challenging times. This study adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The pandemic period was divided into three stages on the basis of severity: pandemic (March 2020 - February 2022), easing (February 2022-September 2022), and post-acute COVID pandemic (September 2022 - present). An initial pool of 3018 studies was narrowed down to a final sample of 73 studies. During the pandemic stage, individuals frequenting public green spaces exhibited improved well-being, reduced stress levels, and a sense of nature deprivation. Private green spaces played crucial roles in maintaining health during the pandemic stage. Highquality window views were associated with improved well-being and reduced depression. During the easing stage, the environmental quality of public green spaces influenced individuals' perceived safety and sense of belonging. And coastal areas were the preferred natural destinations in this stage. During the post-acute COVID pandemic stage, individuals acknowledged the importance of natural environments in maintaining physiological and mental health as they gradually returned to prepandemic normalcy. In conclusion, the COVID-19 pandemic highlighted humanity's reliance on nature. Therefore, sufficient urban spaces should be dedicated to preservation of natural environments to mitigate negative emotions arising from prolonged indoor stays.

In-depth analysis of the treatment effect and synergistic mechanism of TanReQing injection on clinical multi-drug resistant Pseudomonas aeruginosa.

Antibiotic resistance is a recognized and concerning public health issue. Gram-negative bacilli, such as Pseudomonas aeruginosa (P. aeruginosa), are notorious for their rapid development of drug resistance, leading to treatment failures. TanReQing injection (TRQ) was chosen to explore its pharmacological mechanisms against clinical multidrug-resistant P. aeruginosa (MDR-PA), given its antibacterial and anti-inflammatory properties. We revealed the expression of proteins and genes in P. aeruginosa after co-culture with TRQ. This study developed an assessment method to evaluate clinical resistance of P. aeruginosa using MALDI-TOF MS identification and Biotyper database searching techniques. Additionally, it combined MIC determination to investigate changes in MDR-PA treated by TRQ. TRQ effectively reduced the MICs of ceftazidime and cefoperazone and enhanced the confidence scores of MDR-PA as identified by mass spectrometry. Using this evaluation method, the fingerprints of standard P. aeruginosa and MDR-PA were compared, and the characteristic peptide sequence (Seq-PA No. 1) associated with flagellum was found. The phenotypic experiments were conducted to confirm the effect of TRQ on the motility and adhesion of P. aeruginosa. A combination of co-immunoprecipitation and proteome analysis was employed, and 16 proteins were significantly differentially expressed and identified as potential candidates for investigating the mechanism of inhibiting resistance in P. aeruginosa treated by TRQ. The candidates were verified by quantitative real-time PCR analysis, and TRQ may affect these core proteins (MexA, MexB, OprM, OprF, OTCase, IDH, and ASL) that influence resistance of P. aeruginosa. The combination of multiple methods helps elucidate the synergistic mechanism of TRQ in overcoming resistance of P. aeruginosa.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen closely associated with various life-threatening acute and chronic infections. The presence of antimicrobial resistance and multidrug resistance in P. aeruginosa infections significantly complicates antibiotic treatment. The expression of ß-lactamase, efflux systems such as MexAB-OprM, and outer membrane permeability are considered to have the greatest impact on the sensitivity of P. aeruginosa. The study used a method to assess the clinical resistance of P. aeruginosa using matrix-assisted laser desorption ionization time of flight mass spectrometry identification and Biotyper database search techniques. TanReQing injection (TRQ) effectively reduced the MICs of ceftazidime and cefoperazone in multidrug-resistant P. aeruginosa (MDR-PA) and improved the confidence scores for co-cultured MDR-PA. The study found a characteristic peptide sequence for distinguishing whether P. aeruginosa is resistant. Through co-immunoprecipitation and proteome analysis, we explored the mechanism of TRQ overcoming resistance of P. aeruginosa.

Exploring the association between campus environment of higher education and student health: A systematic review of findings and measures.

Numerous studies have investigated the relationship between the neighborhood environments and residents' health. However, other important settings, such as university campuses, have received little attention. This paper conducted a systematic review and synthesized existing empirical works examining the association between the university/college campuses built and natural environments and students' health. Following the PRISMA guidelines, we searched nine databases using keywords related to higher-education campuses and health-related outcomes. A total of 19 articles were identified, including fifteen cross-sectional studies, three experimental studies, and one longitudinal study. The majority of the studies were conducted in Asian countries and published in the past five years. The findings indicate that active transportation infrastructure, such as increased road intersections and better walkability, were found to be positively associated with students' physical activity. The natural environments, including perceived naturalness, blue space, and greenness was shown to support student's mental health and quality of life. Specifically, blue space was found to be the most preferred place for mental restoration, and scattered trees demonstrated a supportive effect in reducing depression symptoms. Even just viewing virtual trees had a restorative effect and feel less anxiety. Additionally, during the summer, tree shadows were identified as the most important factors for enhancing thermal comfort. This review emphasizes the crucial role of campus environments in promoting college students' health. Future longitudinal studies and investigations using multiple campuses would provide a more comprehensive understanding of this relationship. Such endeavors can contribute to the development of evidence-based strategies for designing and planning healthy campus environments that optimize students' well-being.

The spatial relationship between long-term vacant housing and non-communicable diseases in U.S. shrinking and growing metropolitan areas.

The rising prevalence of non-communicable diseases (NCDs) has led to increased attention on understanding how built environments affect NCD risks. However, there's a significant gap in the literature regarding the relationship between housing vacancy duration and NCDs in metropolitan areas with varying development rates. Our research addresses this gap by examining the association between housing vacancy duration and NCDs across all U.S. metropolitan areas, considering growing, shrinking, and fluctuating counties. We used a Multiscale Geographically Weighted Regression (MGWR) model to analyze this relationship, finding that longer-term vacant housing (over 3 years) is more positively associated with NCDs compared to short-term vacancies. We also discovered that this association is non-uniform across metropolitan counties, except for cancer and stroke outcomes. Shrinking counties in the Northeast are particularly affected, emphasizing the need for targeted public health interventions in these areas. This study underscores the importance of revitalizing vacant homes, especially those vacant for over 3 years, in both shrinking and growing regions to improve public health. Policymakers should adopt tailored strategies, engage public health experts, and invest in healthcare infrastructure to effectively address the health risks linked to vacant housing.

Structures of the essential efflux pump EfpA from Mycobacterium tuberculosis reveal the mechanisms of substrate transport and small-molecule inhibition.

As the first identified multidrug efflux pump in Mycobacterium tuberculosis (Mtb), EfpA is an essential protein and promising drug target. However, the functional and inhibitory mechanisms of EfpA are poorly understood. Herein we report cryo-EM structures of EfpA in outward-open conformation, either bound to three endogenous lipids or the inhibitor BRD-8000.3. Three lipids inside EfpA span from the inner leaflet to the outer leaflet of the membrane. BRD-8000.3 occupies one lipid site at the level of inner membrane leaflet, competitively inhibiting lipid binding. EfpA resembles the related lysophospholipid transporter MFSD2A in both overall structure and lipid binding sites, and may function as a lipid flippase. Combining AlphaFold-predicted EfpA structure, which is inward-open, we propose a complete conformational transition cycle for EfpA. Together, our results provide a structural and mechanistic foundation to comprehend EfpA function and develop EfpA-targeting anti-TB drugs.

Theoretical Insights on the Charge State and Bifunctional OER/ORR Electrocatalyst Activity in 4d-Transition-Metal-Doped g-C3N4 Monolayers.

Exploring efficient and stable electrocatalysts for the bifunctional oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) is vital to developing renewable energy technologies. However, due to the substantial and intricate design space associated with these bifunctional OER/ORR electrocatalysts, their development presents a formidable challenge, resulting in their cost-prohibitive nature in both experimental and computational studies. Herein, using the defect physics method, we systematically investigate the formation energies and bifunctional overpotential (ηBi) of 4d-transition-metal (4d-TM, 4d-TM = Zr, Nb, Mo, Ru, Rh, Pd, and Ag)-doped monolayer supercell g-C3N4 (4d-TM@C54N72) based on the density functional theory (DFT) calculations. Under N-rich and C-rich conditions, we find that the formation energies of RhN@C54N71 (Rh occupation N) and PdN@C54N71 (Pd occupation N) are smaller than that of other 4d-TMN@C54N71 (4d-TM occupation N site); for the 4d-TMint@C54N72 (4d-TM interstitial site occupation), the lowest-formation energy defects are Pdint@C54N72. These results indicate that they have better stabilities. Interestingly, for these formation energy lower systems, Pd0int@C54N72 (ηBi = 1.00 V) and Rh1+N@C54N71 (ηBi = 0.73 V) have ultralow overpotential and can be great candidates for bifunctional OER/ORR electrocatalysts. We find the reason is that adjusting the charge states of 4d-TM@C54N72 can tune the interaction strength between the oxygenated intermediates and the 4d-TM@C54N72, which plays a crucial role in the activity of reactions. Additionally, the data obtained through machine learning (ML) application suggest that the electronegativity (Nm) and bond length of 4d-TM and coordination atoms (dTM-OOH) are primary descriptors characterizing the OER and ORR activities, respectively. The charged defect tuning of the bifunctional OER/ORR activity for 4d-TM@C54N72 would enable electrocatalytic performance optimization and the development of potential electrocatalysts for renewable energy applications.

Ligand Control of Copper-Mediated Cycloadditions of Acetylene to Azides: Chemo- and Regio-Selective Formation of Deutero- and Iodo-Substituted 1,2,3-Triazoles.

The participation of σ-monocopper and σ-bis-copper acetylide in mechanistic pathways for copper-catalyzed cycloaddition (CuAAC) reactions of acetylene with azides was probed by analysis of deuterium distributions in the 1,2,3-triazole product formed by deuterolysis of initially formed mono- and bis-copper triazoles. The results show that, when Cu(Phen)(PPh3)2NO3 is used as the catalyst for reactions of acetylene with azides in DMF/D2O, 1-substituted-5-deutero-1,2,3-triazoles are generated selectively. This finding demonstrates that the Cu(Phen)(PPh3)2NO3-catalyzed cycloadditions utilize monocopper acetylide as the substrate and produce 5-copper-1,2,3-triazoles initially. Conversely, when DBU or Et3N is the copper ligand, the process takes place through initial formation and cycloaddition of bis-copper acetylide to produce 4,5-bis-copper-triazole, which reacts with D2O to form the corresponding 4,5-bis-deutero-triazole. Moreover, when C2D2 is used as the substrate, Cu(Phen)(PPh3)2NO3 as the Cu ligand, and H2O/DMF as the solvent, mono-C4-deutreo 1,2,3-triazoles are generated in high yields and excellent levels of regioselectivity. Lastly, CuAAC reactions of acetylene with azides, promoted by CuCl2·2H2O and NaI, yield 4,5-diiodo-1,2,3-triazoles with moderate to high efficiencies.

Risk prediction models for postoperative delirium in elderly patients with hip fracture: a systematic review.

Objectives: To systematically evaluate the risk prediction models for postoperative delirium in older adult hip fracture patients. Methods: Risk prediction models for postoperative delirium in older adult hip fracture patients were collected from the Cochrane Library, PubMed, Web of Science, and Ovid via the internet, covering studies from the establishment of the databases to March 15, 2023. Two researchers independently screened the literature, extracted data, and used Stata 13.0 for meta-analysis of predictive factors and the Prediction Model Risk of Bias Assessment Tool (PROBAST) to evaluate the risk prediction models for postoperative delirium in older adult hip fracture patients, evaluated the predictive performance. Results: This analysis included eight studies. Six studies used internal validation to assess the predictive models, while one combined both internal and external validation. The Area Under Curve (AUC) for the models ranged from 0.67 to 0.79. The most common predictors were preoperative dementia or dementia history (OR = 3.123, 95% CI 2.108-4.626, p < 0.001), American Society of Anesthesiologists (ASA) classification (OR = 2.343, 95% CI 1.146-4.789, p < 0.05), and age (OR = 1.615, 95% CI 1.387-1.880, p < 0.001). This meta-analysis shows that these were independent risk factors for postoperative delirium in older adult patients with hip fracture. Conclusion: Research on the risk prediction models for postoperative delirium in older adult hip fracture patients is still in the developmental stage. The predictive performance of some of the established models achieve expectation and the applicable risk of all models is low, but there are also problems such as high risk of bias and lack of external validation. Medical professionals should select existing models and validate and optimize them with large samples from multiple centers according to their actual situation. It is more recommended to carry out a large sample of prospective studies to build prediction models. Systematic review registration: The protocol for this systematic review was published in the International Prospective Register of Systematic Reviews (PROSPERO) under the registered number CRD42022365258.

Tetracalcium phosphate/polycaprolactone composite scaffold: Mechanical reinforcement, biodegradability regulation and bioactivity induction.

Polycaprolactone (PCL) is considered a potential biomaterial due to its good biocompatibility, but its slow degradability and insufficient mechanical properties limit its wide application in bone tissue engineering. Tetracalcium phosphate's (TTCP) good degradability and inherent high stiffness are expected to compensate for the aforementioned defects of PCL and endow it with good biological activity. This goal of this study was to obtain bioactive PCL composite scaffolds with tuneable degradation properties and good mechanical strength via selective laser sintering technology (SLS). Composite porous scaffolds with TTCP contents of 0%, 5%, 10%, 15%, 20%, and 25% were prepared, and the experimental results showed that the addition of TTCP significantly improved the mechanical properties of the scaffold. Notably, the tensile strength of the composite scaffold with 20% TTCP content reached 15.2 MPa, which was 2.9 times that of pure PCL, and the best flexural strength was found in the scaffold with 15% TTCP content (4.7 MPa). More importantly, the introduced TTCP not only achieved the effective pH regulation of the soaking solution and the promotion of biodegradation, but also provided the scaffold with good bioactivity and biocompatibility.

DICTrank: The largest reference list of 1318 human drugs ranked by risk of drug-induced cardiotoxicity using FDA labeling.

Drug-induced cardiotoxicity (DICT) is a leading cause of drug trial failure and discontinuation. Current drug annotations for cardiotoxicity largely focus on individual outcomes or mechanisms. Considering the broad spectrum of adverse cardiac events, we developed Drug-Induced Cardiotoxicity Rank (DICTrank) using FDA labeling and comprehensively classified 1318 human drugs into four categories: Most-DICT-Concern (n = 341), Less-DICT-Concern (n = 528), No-DICT-Concern (n = 343), and Ambiguous-DICT-Concern (n = 106). Notably, DICTrank covers diverse therapeutic categories, of which several were enriched with Most-DICT-Concern drugs, such as antineoplastic agents, sex hormones, anti-inflammatory drugs, beta-blockers, and cardiac therapy. DICTrank currently presents the largest drug list of DICT annotation, and it could contribute to the development of new approach methods, including AI models for early identification of DICT risk during drug development and beyond.

Crosslinking of a polycaprolactone/tourmaline scaffold by sodium stearate with improved mechanical strength and bioactivity.

Although polycaprolactone (PCL) matrix composites have been extensively studied, the weak interface with nanofillers limits their further applications in bone tissue engineering. Herein, this study has designed a porous bone scaffold model using the triply periodic minimal surfaces (TPMS), and the optimal porosity was determined by comparing the mechanical properties. A sodium stearate-modified PCL/tourmaline (PCL/TM) composite scaffold with a strong interfacial effect was prepared by selective laser sintering technology. Wherein, sodium stearate acts as a bridge to improve the interaction between TM and PCL interface, while promoting its uniform dispersion. The results showed that the PCL/3% modified TM specimens exhibit the optimum mechanical properties, and their ultimate tensile and compressive strength increases by 21.8% and 32.1%, respectively, compared with pure PCL. The factors of mechanical enhancement of composite scaffolds can be elaborated from the construction of interface bridges. On the one hand, the carboxyl group at one end of sodium stearate will interact with the hydroxyl group on the surface of TM to enhance interfacial adsorption by forming ionic bonds and hydrogen bonds. On the other hand, the hydrophobic long chain at the other end of sodium stearate is universally compatible with hydrophobic PCL, thereby improving the dispersion of TM. These characteristics make the PCL/TM composite scaffold a valuable reference for its application in bone tissue engineering.

Applying genomics in regulatory toxicology: a report of the ECETOC workshop on omics threshold on non-adversity.

In a joint effort involving scientists from academia, industry and regulatory agencies, ECETOC's activities in Omics have led to conceptual proposals for: (1) A framework that assures data quality for reporting and inclusion of Omics data in regulatory assessments; and (2) an approach to robustly quantify these data, prior to interpretation for regulatory use. In continuation of these activities this workshop explored and identified areas of need to facilitate robust interpretation of such data in the context of deriving points of departure (POD) for risk assessment and determining an adverse change from normal variation. ECETOC was amongst the first to systematically explore the application of Omics methods, now incorporated into the group of methods known as New Approach Methodologies (NAMs), to regulatory toxicology. This support has been in the form of both projects (primarily with CEFIC/LRI) and workshops. Outputs have led to projects included in the workplan of the Extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST) group of the Organisation for Economic Co-operation and Development (OECD) and to the drafting of OECD Guidance Documents for Omics data reporting, with potentially more to follow on data transformation and interpretation. The current workshop was the last in a series of technical methods development workshops, with a sub-focus on the derivation of a POD from Omics data. Workshop presentations demonstrated that Omics data developed within robust frameworks for both scientific data generation and analysis can be used to derive a POD. The issue of noise in the data was discussed as an important consideration for identifying robust Omics changes and deriving a POD. Such variability or "noise" can comprise technical or biological variation within a dataset and should clearly be distinguished from homeostatic responses. Adverse outcome pathways (AOPs) were considered a useful framework on which to assemble Omics methods, and a number of case examples were presented in illustration of this point. What is apparent is that high dimension data will always be subject to varying processing pipelines and hence interpretation, depending on the context they are used in. Yet, they can provide valuable input for regulatory toxicology, with the pre-condition being robust methods for the collection and processing of data together with a comprehensive description how the data were interpreted, and conclusions reached.

Dynamic evaluation of pathological changes in a mouse acne model by optical imaging technology.

Acne vulgaris is a disorder of the pilosebaceous unit that is primarily caused by hyperseborrhoea, colonization with Propionibacterium acnes, hyperkeratosis and an inflammatory response. Existing pharmacodynamic assessment methods primarily focus on a single causative factor at a certain time point, making it difficult to assess multiple factors simultaneously in real time. Therefore, it is crucial to establish a dynamic and nondestructive method for the assessment of acne in vivo. This study utilized four-dimensional optical imaging techniques to assess the pathogenic factors and pathological progression of acne. LSCI was employed to measure blood flow; TPEF was used to observe inflammatory changes (NAD(P)H) in epidermal granular layer cells and structural changes in collagen fibres in the dermal layer. Additionally, the dermatoscope was used to investigate the micro-characterization of the lesions. We observed that the epidermis in the lesion area was thickened, hair follicles were keratinized, and there was obvious inflammation and blood flow aggregation by optical imaging technology. Based on these findings, the pathological progression of this acne model could be divided into the inflammation phase, accompanied by bacterial colonization, and the reparative phase. These results provide a new perspective for the assessment of acne and offer an experimental basis for the selection of precise drugs for clinical use.