Direct analysis in real time mass spectrometry (DART-MS/MS) for rapid urine opioid detection in a clinical setting.

BACKGROUND AND AIMS: Current laboratory methods for opioid detection involve an initial screening with immunoassays which offers efficient but non-specific results and a subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmation which offers accurate results but requires extensive sample preparation and turnaround time. Direct Analysis in Real Time (DART) tandem mass spectrometry is evaluated as an alternative approach for accurate opioid detection with efficient sample preparation and turnaround time. MATERIALS AND METHODS: DART-MS/MS was optimized by testing the method with varying temperatures, operation modes, extraction methods, hydrolysis times, and vortex times. The method was evaluated for 12 opioids by testing the analytical measurement range, percent carryover, precision studies, stability, and method-to-method comparison with LC-MS/MS. RESULTS: DART-MS/MS shows high sensitivity and specificity for the detection of 6-acetylmorphine, codeine, hydromorphone, oxymorphone, hydrocodone, naloxone, buprenorphine, norfentanyl, and fentanyl in urine samples. However, its performance was suboptimal for norbuprenorphine, morphine and oxycodone. CONCLUSION: In this proof-of-concept study, DART-MS/MS is evaluated for its rapid quantitative definitive testing of opioids drugs in urine. Further research is needed to expand its application to other areas of drug testing.

Bioactive Compounds and Valorization of Coffee By-Products from the Origin: A Circular Economy Model from Local Practices in Zongolica, Mexico.

The by-products of green coffee processing are rich in compounds that can be recycled for their possible use in the production of beverages, fertilizers and weed control in production areas. The objective of this work was to identify the organic and inorganic bioactive compounds of green coffee and the coffee by-products related to the production of origin, such as dried cascara (skin-pulp), parchment and silverskin (unroasted), in order to investigate the role their biomolecules may have in reuse through practices and local knowledge, not yet valued. The metabolomic profile by HPLC-ESI-HRMS of the aqueous extract of the dried cascara highlighted 93 non-volatile molecules, the highest number reported for dried cascara. They belong to groups of organic acids (12), alkaloids (5), sugars (5), fatty acids (2), diglycerides (1), amino acids (18), phospholipids (7), vitamins (5), phenolic acids (11), flavonoids (8), chlorogenic acids (17), flavones (1) and terpenes (1). For the first time, we report the use of direct analysis in real-time mass spectrometry (DART-MS) for the identification of metabolites in aqueous extracts of dried cascara, parchment, silverskin and green coffee. The DART analysis mainly showed the presence of caffeine and chlorogenic acids in all the extracts; additionally, sugar adducts and antioxidant compounds such as polyphenols were detected. The mineral content (K, Ca, P, S, Mg and Cl) by EDS spectrometry in the by-products and green coffee showed a relatively high content of K in the dried cascara and green coffee, while Ca was detected in double quantity in the silverskin. These metabolomic and mineral profile data allow enhancement of the link between the quality of green coffee and its by-products and the traditional local practices in the crop-growing area. This consolidates the community's experience in reusing by-products, thereby minimizing the impact on the environment and generating additional income for coffee growers' work, in accordance with the principles of circular economy and bioeconomy.

Molecular Insights into Gas-Particle Partitioning and Viscosity of Atmospheric Brown Carbon.

Biomass burning organic aerosol (BBOA), containing brown carbon chromophores, plays a critical role in atmospheric chemistry and climate forcing. However, the effects of evaporation on BBOA volatility and viscosity under different environmental conditions remain poorly understood. This study focuses on the molecular characterization of laboratory-generated BBOA proxies from wood pyrolysis emissions. The initial mixture, "pyrolysis oil (PO1)", was progressively evaporated to produce more concentrated mixtures (PO1.33, PO2, and PO3) with volume reduction factors of 1.33, 2, and 3, respectively. Chemical speciation and volatility were investigated using temperature-programmed desorption combined with direct analysis in real-time ionization and high-resolution mass spectrometry (TPD-DART-HRMS). This novel approach quantified saturation vapor pressures and enthalpies of individual species, enabling the construction of volatility basis set distributions and the quantification of gas-particle partitioning. Viscosity estimates, validated by poke-flow experiments, showed a significant increase with evaporation, slowing particle-phase diffusion and extending equilibration times. These findings suggest that highly viscous tar ball particles in aged biomass burning emissions form as semivolatile components evaporate. The study highlights the importance of evaporation processes in shaping BBOA properties, underscoring the need to incorporate these factors into atmospheric models for better predictions of BBOA aging and its environmental impact.

Doctor interaction behavior, patient participation in value co-creation and patient satisfaction: cross-sectional survey in a tertiary-level hospital from Guangzhou, China.

Value co-creation can be defined as the joint benefit that is created by patients and medical service providers through the integration of their respective resources. Participation and interaction between doctors and patients can generate an outcome that benefits both sides. Relevant studies of value co-creation in the healthcare field are limited. This study established hypotheses to explore the association between doctor interaction behavior, patient participation in value co-creation, and patient satisfaction. A cross-sectional survey was conducted with 637 patients (outpatients and inpatients) at a tertiary-level hospital in Guangzhou, China. The analysis result indicated that doctor interaction behavior could stimulate patient participation in value co-creation then increase patient satisfaction. The standardized total effect, direct effect, and indirect effect were 0.641 (95%CI: 0.055 ~ 0.067), 0.546 (95%CI: 0.044 ~ 0.059), and 0.095 (95%CI: 0.032 ~ 0.166), respectively. Patient participation in value co-creation mediated the relationship between doctor interaction behavior and patient satisfaction. Among the different dimensions of doctor interaction behavior, access, risk assessment and transparency dimensions were associated with positive patient participation in value co-creation. During the treatment process, doctor interaction and patient participation can get satisfying results.

Determining the optimal challenge point for learning motor skills in children with attention deficit/hyperactivity disorder.

The purpose of this study was to investigate the optimal challenge point for learning motor skills in children with and without attention deficit/hyperactivity disorder (ADHD). Ninety-six 9- to 10-year-old children, including 48 children with ADHD and 48 neurotypical children, were randomly assigned to one of four practice groups with varying levels of nominal and functional task difficulty. They performed 63 trials of a dart throwing task in the acquisition phase and 18 trials in the retention and transfer tests a day later. The results showed that neurotypical children outperformed children with ADHD in all phases of the study. Both groups improved in the acquisition phase and performed better in the retention and transfer tests. Interestingly, low nominal task difficulty was associated with better learning for both groups, despite lower average performance for children with ADHD. Thus, despite their performance differences, we did not find a difference in the effective challenge point between children with ADHD and their neurotypical peers.

The genome sequence of the Heart and Dart moth, Agrotis exclamationis (Linnaeus, 1758).

We present a genome assembly from an individual female Heart and Dart moth, Agrotis exclamationis (Arthropoda; Insecta; Lepidoptera; Noctuidae). The genome sequence has a total length of 725.10 megabases. Most of the assembly is scaffolded into 32 chromosomal pseudomolecules, including the W and Z sex chromosomes. The mitochondrial genome has also been assembled and is 15.39 kilobases in length. Gene annotation of this assembly on Ensembl identified 20,008 protein-coding genes.

Genetic diversity, population structure, and a genome-wide association study of sorghum lines assembled for breeding in Uganda.

Sorghum is an important source of food and feed worldwide. Developing sorghum core germplasm collections improves our understanding of the evolution and exploitation of genetic diversity in breeding programs. Despite its significance, the characterization of the genetic diversity of local germplasm pools and the identification of genomic loci underlying the variation of critical agronomic traits in sorghum remains limited in most African countries, including Uganda. In this study, we evaluated a collection of 543 sorghum accessions actively used in Ugandan breeding program across two cropping seasons at NaSARRI, Uganda, under natural field conditions. Phenotypic data analysis revealed significant (p<0.01) variation among accessions for days to 50% flowering, plant height, panicle exsertion, and grain yield, with broad-sense heritability (H²) estimates of 0.54, 0.9, 0.81, and 0.48, respectively, indicating a high genetic variability for these traits. We used a newly developed genomic resource of 7,156 single nucleotide polymorphism (SNP) markers to characterize the genetic diversity and population structure of this collection. On average, the SNP markers exhibited moderately high polymorphic information content (PIC = 0.3) and gene diversity (He = 0.3), while observed heterozygosity (Ho = 0.07) was low, typical for self-pollinating crops like sorghum. Admixture-based models, PCA, and cluster analysis all grouped the accessions into two subpopulations with relatively low genetic differentiation. Genome-wide association study (GWAS) identified candidate genes linked to key agronomic traits using a breeding diversity panel from Uganda. GWAS analysis using three different mixed models identified 12 genomic regions associated with days to flowering, plant height, panicle exsertion, grain yield, and glume coverage. Five core candidate genes were co-localized with these significant SNPs. The SNP markers and candidate genes discovered provide valuable insights into the genetic regulation of key agronomic traits and, upon validation, hold promise for genomics-driven breeding strategies in Uganda.

Development of DNA Markers for Acute Hepatopancreatic Necrosis Disease Tolerance in Litopenaeus vannamei through a Genome-Wide Association Study.

Shrimp aquaculture is facing a serious disease, acute hepatopancreatic necrosis disease (AHPND), caused by Vibrio paraheamolyticus (VpAPHND). For sustainable shrimp aquaculture, massive losses of shrimp infected with VpAPHND must be prevented. Research and selection of shrimp tolerant to VpAPHND infection is a sustainable approach to reducing the risk of AHPND. This study focused on the identification and development of potential DNA markers associated with AHPND using DArT sequencing (DArTSeq) and a genome-wide association study. Three populations of post-larval Litopenaeus vannamei were immersed in VpAPHND to collect susceptible (D) and tolerant (S) samples. The 45 D and 48 S shrimp had their genotypes analyzed using DArTSeq. A total of 108,983 SNPs and 17,212 InDels were obtained from the DArTseq data, while the biallelic 516 SNPs and 2293 InDels were finally filtered with PIC < 0.1, MAF < 0.05, and a call rate ≥ 80%. The filtered variants were analyzed for their association with AHPND tolerance. Although there were no significantly associated SNPs and InDels above the Bonferroni correction threshold, candidate variants, four SNPs and 17 InDels corresponding to p < 0.01, were provided for further validation of the AHPND tolerance trait. The candidate SNPs are located on an exon of the zinc finger protein 239-like gene, an intron of an uncharacterized gene, and in intergenic regions. Most of the candidate InDels are in the intergenic regions, with fewer in the intronic and exonic regions. This study provides information on SNPs and InDels for white shrimp. These markers will support the variant database of shrimp and be useful in shrimp aquaculture for breeding selection.

Direct analysis in real time mass spectrometry (DART-MS) for rapid screening of Carpaine in Carica papaya leaf products.

Carpaine, a major alkaloid present in Carica papaya leaves, has been shown to increase platelet counts in patients suffering from thrombocytopenia. Numerous commercial papaya leaf products are available, but few provide proper bioactive ingredient information. We present herein a technique for rapid screening of carpaine in these products using DART-MS. The results indicate that carpaine was detected in various forms (powder, solution) of papaya leaves. Its presence was confirmed by examining the mass pattern when conducted on a standard solution at both low and high voltages (+10 V and +90 V), using MS1 and MS2 data obtained from LC-QTOF-MS/MS. The protonated molecule was identified at m/z = 479.38, with a fragment ion at m/z = 240.20. LOD for identifying carpaine in powder and solution matrices were 5.0 × 10-5 %w/w and 0.05 µg/mL, respectively. The proposed method has been successfully validated with the AOAC International standards and can be used to identify carpaine in papaya leaf products.

Rapid Assessment of Metabolomic Fingerprinting of Recycled Sunflower By-Products via DART-HRMS.

To comply with a more circular and environmentally friendly European common agricultural policy, while also valorising sunflower by-products, an ultrasound assisted extraction (UAE) was tested to optimise ethanol-wash solutes (EWS). Furthermore, the capabilities of DART-HRMS as a rapid and cost-effective tool for determining the biochemical changes after valorisation of these defatted sunflower EWS were investigated. Three batches of EWS were doubly processed into optimised EWS (OEWS) samples, which were analysed via DART-HRMS. Then, the metabolic profiles were submitted to a univariate analysis followed by a partial least square discriminant analysis (PLS-DA) allowing the identification of the 15 most informative ions. The assessment of the metabolomic fingerprinting characterising EWS and OEWS resulted in an accurate and well-defined spatial clusterization based on the retrieved pool of informative ions. The outcomes highlighted a significantly higher relative abundance of phenolipid hydroxycinnamoyl-glyceric acid and a lower incidence of free fatty acids and diglycerides due to the ultrasound treatment. These resulting biochemical changes might turn OEWS into a natural antioxidant supplement useful for controlling lipid oxidation and to prolong the shelf-life of foods and feeds. A standardised processing leading to a selective concentration of the desirable bioactive compounds is also advisable.

Degradation strategies for structural characterization of insoluble synthetic polymers by mass spectrometry.

With the advent of soft ionization techniques such as electrospray (ESI) and matrix-assisted laser desorption/ionization (MALDI) to produce intact gas-phase ions from nonvolatile macromolecules, mass spectrometry has become an essential technique in the field of polymeric materials. However, (co)polymers of very high molecular weight or with reticulated architectures still escape ESI or MALDI, mainly due to solubility issues. Strategies developed to tackle such an analytical challenge all rely on sample degradation to produce low-mass species amenable to existing ionization methods. Yet, chain degradation needs to be partial and controlled to generate sufficiently large species that still contain topological or architectural information. The present article reviews the different analytical degradation strategies implemented to perform mass spectrometry of these challenging synthetic polymers, covering thermal degradation approaches in sources developed in the 2000s, off-line sample pre-treatments for controlled chemical degradation of polymeric substrates, and most recent achievements employing reactive ionization modes to perform chemolysis on-line with MS.

Digital age: The path choice of government-citizen value co-creation.

This study explores the relationship between government and citizen in the digital age and proposes a specific path to realize the value co-creation of government and citizen in the digital age. Quantitative analysis of 40 policy texts on "digital government construction" of 30 provincial and municipal governments in China before November 2022 was conducted using NVivo12. The case of Minsheng Cloud revealed that provincial and municipal government departments have not paid sufficient attention to citizen participation. Furthermore, citizens' participation ability and enthusiasm are not high. The study found that in the process of strengthening the construction of digital government, "government optimisation", "citizen participation", "governance guarantee", "data governance" and "government digitization" are the key elements. We discuss the feasibility, necessity and coupling of the value co-creation theory to establish the benign interaction between government and citizens and realize co-creation. We find that the "DART" model can be co-created based on value, and that the continuous Improving the four aspects of "dialogue", "access", "transparency" and "risk assessment" will undoubtedly help realize the value co-creation of government and citizens in the digital era, and form a governance pattern of co-construction and sharing. It is therefore of great significance to promote the government's digital construction and digital governance capability to accelerate the construction of digital China and promote the modernisation of the national governance system and governance capability.

A finite volume approach to dosimetric calculations in diffusing alpha-emitters radiation therapy.

Objective.In diffusing alpha-emitters radiation therapy ('Alpha DaRT'), the diffusion-leakage (DL) model is used to determine the spatial distributions of the emitters and the corresponding alpha dose, critical for a successful treatment. This work first introduces a finite volume (FV) approach to develop numerical schemes to simulate the DL model in one, two and three dimensions then presents how variations over realistic ranges of the DL model parameters related to desorption, diffusion and leakage processes affect the alpha dose distribution and the position of the clinically significant alpha particle10Gy isodose. This work also presents the effects of three modeling approximations: two source geometry approximations (solid cylinder instead of hollow, pixelized cross section instead of circular), and one dosimetric approximation (single-source dose superposition instead of multiple-sources direct dose calculation).Approach.The introduced FV approach was used to obtain spatial distributions of the emitters, from which the corresponding alpha dose distributions were calculated under the assumption of a local deposition of the alpha particles' energies. Variation ranges of the DL model parameters were based on previously published data. For each modeling approximation studied, the error and relative error on the alpha dose distribution were calculated and the displacement of the10Gy isodose was evaluated.Main results.Over realistic ranges, the desorption probabilities, diffusion lengths, and leakage probabilities affect the position of the alpha particle10Gy isodose by∼0.1mm,∼1.5mm and∼0.5mm, respectively. The three modeling approximations studied have a negligible effect on the alpha particle10Gy isodose position, with displacements⩽0.01mm.Significance.This work quantitatively evaluates the relative importance of different parameters and approximations in Alpha-DaRT alpha dose calculations based on their impact not only on the dose variation at a given distance from the source but also on the displacement of clinically significant isodoses.

Absence of developmental and reproductive toxicity in rats, rabbits, and zebrafish embryos exposed to antimalarial drug cabamiquine.

BACKGROUND: When developing new antimalarial drugs, considering their potential use during pregnancy as preventive or curative therapy is crucial. This prevents the parasite from affecting embryonic development and reduces maternal and fetal death risks. Consequently, understanding the exposure and safety of antimalarial drugs during pregnancy is crucial, with well-designed animal studies playing a key role in this assessment. METHODS: As part of the drug development program for cabamiquine, a series of developmental and reproductive toxicity studies were conducted in rats and rabbits. Additionally, the zebrafish embryo model was used to further improve embryo exposure, minimize confounding factors related to maternal toxicity, and assess developmental risks of cabamiquine. RESULTS: In these studies, although maternal toxicity was observed, there were no cabamiquine-related adverse effects on fertility, embryonic, or fetal development at maternal exposures representing significant multiples (up to five and 10 times higher in rabbit and rats, respectively) than the exposure at the anticipated efficacious human dose. Similarly, no adverse effects were observed on ZF embryonic development, even though cabamiquine concentrations in the embryos were 10-fold higher than nominal concentrations. CONCLUSIONS: The results obtained in a full set of reproductive toxicity studies did not provide evidence of detrimental effects on the conceptuses and progeny at maternally nontoxic doses and exposures, still representing a multiple of the anticipated systemic exposures in women of childbearing potential (WOCBP). Cabamiquine can therefore be considered a suitable therapeutic option for WOCBP and pregnant women living in malaria-endemic regions by significantly reducing maternal and infant malaria death rates.

Interlaboratory and cross-platform accessibility of time-of-flight wood identification database.

The mass spectral database of tree species built by US Fish and Wildlife Service has thousands of entries and has been a valuable resource to combat illegal logging and international trade. The database was and continues to be constructed using a particular ambient ionization time-of-flight mass spectrometry (TOF-MS) platform in the agency branch in Ashland, OR, with which queries of unknown wood samples are investigated exclusively. Laboratories that operate different MS instruments also have an interest in using the database if they can produce valid matches to known samples compatible with the database. Four species were selected for inter-laboratory comparison using Orbitrap MS instruments and the equivalent TOF-MS platform with direct analysis in real time ionization of institution-sourced wood samples. Identities of the known samples were confirmed by examination of their microscopic wood anatomy. Orbitrap analysis was able to identify each species as confidently as the TOF instruments, often with less variation in spectra but not necessarily greater mass accuracy or better-matched signal abundance to the control database. The Orbitrap program also had to be doubled to two scanned mass ranges appended for greater peak intensity, before spectra could be correctly matched to the database, but the program was successful.

T-cell specific in vivo gene delivery with DART-AAVs targeted to CD8.

One of the biggest challenges for in vivo gene therapy are vectors mediating highly selective gene transfer into a defined population of therapy-relevant cells. Here we present DARPin-targeted AAVs (DART-AAVs) displaying DARPins specific for human and murine CD8. Insertion of DARPins into the GH2/GH3 loop of the capsid protein 1 (VP1) of AAV2 and AAV6 resulted in high selectivity for CD8-positive T cells with unimpaired gene delivery activity. Remarkably, the capsid core structure was unaltered with protruding DARPins detectable. In complex primary cell mixtures, including donor blood or systemic injections into mice, the CD8-targeted AAVs were by far superior to unmodified AAV2 and AAV6 in terms of selectivity, target cell viability, and gene transfer rates. In vivo, up to 80% of activated CD8+ T cells were hit upon a single vector injection into conditioned humanized or immunocompetent mice. While gene transfer rates decreased significantly under non-activated conditions, genomic modification selectively in CD8+ T cells was still detectable upon Cre delivery into indicator mice. In both mouse models, selectivity for CD8+ T cells was close to absolute with exceptional detargeting from liver. The CD8-AAVs described here expand strategies for immunological research and in vivo gene therapy options.

Haplotypes of ATP-Binding Cassette CaABCC6 in Chickpea from Kazakhstan Are Associated with Salinity Tolerance and Leaf Necrosis via Oxidative Stress.

Salinity tolerance was studied in chickpea accessions from a germplasm collection and in cultivars from Kazakhstan. After NaCl treatment, significant differences were found between genotypes, which could be arranged into three groups. Those that performed poorest were found in group 1, comprising five ICC accessions with the lowest chlorophyll content, the highest leaf necrosis (LN), Na+ accumulation, malondialdehyde (MDA) content, and a low glutathione ratio GSH/GSSG. Two cultivars, Privo-1 and Tassay, representing group 2, were moderate in these traits, while the best performance was for group 3, containing two other cultivars, Krasnokutsky-123 and Looch, which were found to have mostly green plants and an exact opposite pattern of traits. Marker-trait association (MTA) between 6K DArT markers and four traits (LN, Na+, MDA, and GSH/GSSG) revealed the presence of four possible candidate genes in the chickpea genome that may be associated with the three groups. One gene, ATP-binding cassette, CaABCC6, was selected, and three haplotypes, A, D1, and D2, were identified in plants from the three groups. Two of the most salt-tolerant cultivars from group 3 were found to have haplotype D2 with a novel identified SNP. RT-qPCR analysis confirmed that this gene was strongly expressed after NaCl treatment in the parental- and breeding-line plants of haplotype D2. Mass spectrometry of seed proteins showed a higher accumulation of glutathione reductase and S-transferase, but not peroxidase, in the D2 haplotype. In conclusion, the CaABCC6 gene was hypothesized to be associated with a better response to oxidative stress via glutathione metabolism, while other candidate genes are likely involved in the control of chlorophyll content and Na+ accumulation.

Continuance intention and digital health resources from the perspective of elaboration likelihood model and DART model: a structural equation modeling analysis.

Background: Internet hospitals, online health communities, and other digital health APPs have brought many changes to people's lives. However, digital health resources are experiencing low continuance intention due to many factors, including information security, service quality, and personal characteristics of users. Methods: We used cross-sectional surveys and structural equation modeling analysis to explore factors influencing user willingness to continue using digital health resources. Results: Information quality (ß = 0.31, p < 0.05), service quality (ß = 0.19, p < 0.05), platform reputation (ß = 0.34, p < 0.05), and emotional support (ß = 0.23, p < 0.05) have significant positive effects on user value co-creation behavior. Additionally, user trust and perceived usefulness could mediate the association between user value co-creation behavior and continuance intention, with mediation effects of 0.143 and 0.125, respectively. User involvement can positively moderate the association between user value co-creation behavior and user trust (ß = 0.151, t = 2.480, p < 0.001). Also, user involvement can positively moderate the association between value co-creation behavior and perceived usefulness (ß = 0.103, t = 3.377, p < 0.001). Conclusion: The keys to solving the problem of low continuance intention are improving the quality and service level of digital health resources, and promoting users' value co-creation behavior. Meanwhile, enterprises should build a good reputation, create a positive communication atmosphere in the community, and enhance user participation and sense of belonging.

Extended Follow-Up Outcomes from Pooled Prospective Studies Evaluating Efficacy of Interstitial Alpha Radionuclide Treatment for Skin and Head and Neck Cancers.

The initial favorable efficacy and safety profile for Alpha DaRT have been demonstrated (NCT04377360); however, the longer-term safety and durability of the treatment are unknown. This pooled analysis of four prospective trials evaluated the long-term safety and efficacy of Alpha DaRT for the treatment of head and neck or skin tumors. A total of 81 lesions in 71 patients were treated across six international institutions, with a median follow-up of 14.1 months (range: 2-51 months). Alpha DaRT sources were delivered via a percutaneous interstitial technique and placed to irradiate the tumor volume with the margin. The sources were removed two to three weeks following implantation. A complete response was observed in 89% of treated lesions (n = 72) and a partial response in 10% (n = 8). The two-year actuarial local recurrence-free survival was 77% [95% CI 63-87]. Variables, including recurrent versus non-recurrent lesions, baseline tumor size, or histology, did not impact long-term outcomes. Twenty-seven percent of patients developed related acute grade 2 or higher toxicities, which resolved with conservative measures. No grade 2 or higher late toxicities were observed. These data support the favorable safety profile of Alpha DaRT, which is currently being explored in a pivotal US trial.

Modeling the human placenta: in vitro applications in developmental and reproductive toxicology.

During its temporary tenure, the placenta has extensive and specialized functions that are critical for pre- and post-natal development. The consequences of chemical exposure in utero can have profound effects on the structure and function of pregnancy-associated tissues and the life-long health of the birthing person and their offspring. However, the toxicological importance and critical functions of the placenta to embryonic and fetal development and maturation have been understudied. This narrative will review early placental development in humans and highlight some in vitro models currently in use that are or can be applied to better understand placental processes underlying developmental toxicity due to in utero environmental exposures.