Advances in nanomedicine, coupled with novel methods of creating advanced materials at the nanoscale, have opened new perspectives for the development of healthcare and medical products. Special attention must be paid toward safe design approaches for nanomaterial‐based products. Recently, artificial intelligence (AI) and machine learning (ML) gifted the computational tool for enhancing and improving the simulation and modeling process for nanotoxicology and nanotherapeutics. In particular, the correlation of in vitro generated pharmacokinetics and pharmacodynamics to in vivo application scenarios is an important step toward the development of safe nanomedicinal products. This review portrays how in vitro and in vivo datasets are used in in silico models to unlock and empower nanomedicine. Physiologically based pharmacokinetic (PBPK) modeling and absorption, distribution, metabolism, and excretion (ADME)‐based in silico methods along with dosimetry models as a focus area for nanomedicine are mainly described. The computational OMICS, colloidal particle determination, and algorithms to establish dosimetry for inhalation toxicology, and quantitative structure–activity relationships at nanoscale (nano‐QSAR) are revisited. The challenges and opportunities facing the blind spots in nanotoxicology in this computationally dominated era are highlighted as the future to accelerate nanomedicine clinical translation.

The global community decided in 2015 to improve people’s lives by 2030 by setting 17 global goals for sustainable development. The second goal of this community was to end hunger. Plant seeds are an essential input in agriculture; however, during their developmental stages, seeds can be negatively affected by environmental stresses, which can adversely affect seed vigor, seedling establishment, and crop production. Seeds resistant to high salinity, droughts and climate change can result in higher crop yield. The major findings suggested in this review refer nanopriming as an emerging seed technology towards sustainable food amid growing demand with the increasing world population. This novel growing technology could influence the crop yield and ensure the quality and safety of seeds, in a sustainable way. When nanoprimed seeds are germinated, they undergo a series of synergistic events as a result of enhanced metabolism: modulating biochemical signaling pathways, trigger hormone secretion, reduce reactive oxygen species leading to improved disease resistance. In addition to providing an overview of the challenges and limitations of seed nanopriming technology, this review also describes some of the emerging nano-seed priming methods for sustainable agriculture, and other technological developments using cold plasma technology and machine learning.

The perspective of machine learning for modeling plasma treatment parameters in agriculture for the development of synergistic protocols for different types of seed priming.

The inhalation toxicology of multifaceted particulate matter from the environment, cigarette smoke, and e-cigarette liquid vapes is a major research topic concerning the adverse effect of these items on lung tissue. In vitro air−liquid interface (ALI) culture models hold more potential in an inhalation toxicity assessment. Apropos to e-cigarette toxicity, the multiflavor components of the vapes pose a complex experimental bottleneck. While an appropriate ALI setup has been one part of the focus to overcome this, parallel attention towards the development of an ideal exposure system has pushed the field forward. With the advent of microfluidic devices, lung-on-chip (LOC) technologies show enormous opportunities in in vitro smoke-related inhalation toxicity. In this review, we provide a framework, establish a paradigm about smoke-related inhalation toxicity testing in vitro, and give a brief overview of breathing LOC experimental design concepts. The capabilities with optimized bioengineering approaches and microfluidics and their fundamental pros and cons are presented with specific case studies. The LOC model can imitate the structural, functional, and mechanical properties of human alveolar-capillary interface and are more reliable than conventional in vitro models. Finally, we outline current perspective challenges as well as opportunities of future development to smoking lungs-on-chip technologies based on advances in soft robotics, machine learning, and bioengineering. ■ CONTENTS 1991 5. Case Reports, Challenges, and Opportunities of Emerging Breathing Lungs-on-Chip to Test Cigarettes, and e-Cigarettes Related Pathology 1994 5.a. In Vitro Inhalation Exposure with a Biomimetic Smoking Robot Compliant with Microfluidic Organ Chips 1994 5.b.

With the advent of Nanotechnology, the use of nanomaterials in consumer products is increasing on a daily basis, due to which a deep understanding and proper investigation regarding their safety and risk assessment should be a major priority. To date, there is no investigation regarding the microrheological properties of nanomaterials (NMs) in biological media. In our study, we utilized in silico models to select the suitable NMs based on their physicochemical properties such as solubility and lipophilicity. Then, we established a new method based on dynamic light scattering (DLS) microrheology to get the mean square displacement (MSD) and viscoelastic property of two model NMs that are dendrimers and cerium dioxide nanoparticles in Dulbecco’s Modified Eagle Medium (DMEM) complete media at three different concentrations for both NMs. Subsequently, we established the cytotoxicological profiling using water-soluble tetrazolium salt-1 (WST-1) and a reactive oxygen species (ROS) assay. To take one step forward, we further looked into the tight junction properties of the cells using immunostaining with Zonula occluden-1 (ZO-1) antibodies and found that the tight junction function or transepithelial resistance (TEER) was affected in response to the microrheology and cytotoxicity. The quantitative polymerase chain reaction (q-PCR) results in the gene expression of ZO-1 after the 24 h treatment with NPs further validates the findings of immunostaining results. This new method that we established will be a reference point for other NM studies which are used in our day-to-day consumer products.

The emergence of low-cost 3D printing (particularly with 3D pens) in the home and school environment is a matter of concern since there is a lack of data confirming its safe application. The filament washed with water and the particle emission during printing (captured in water) were analyzed. In this report, we provide important insights about toxicity, intracellular mitochondrial stress, and cellular metabolic alterations as a mechanistic response after exposure of emissions released during 3D pen printing with polylactic acid (PLA) and PLA filaments with additives (carbon nanotubes (CNTs), copper, or steel). We adopted the design and exposure of a realistic inhalation procedure of aerosols via introducing mist-containing particles released during 3D pen printing processes of filaments with/without additive (CNTs, steel, copper) to A549 cells in a cloud chamber. The filaments with or without additives appear benign except for copper, which causes higher changes in stress, cell death, and metabolic perturbations. Albeit live/dead cell assay fluorescence-activated cell sorting analysis revealed little or no toxicity, time-of-flight secondary ion mass spectrometry bimolecular imaging and chemical mapping show insightful changes in cell membrane lipid compositions. Biochemical profiles obtained based on ion m/z signature peaks exhibit membrane and lipoprotein metabolism alterations which are similar to those adopted by A549 cells while developing drug resistance and their activation of the expression of their efflux pump. The results sought in this report suggest the cautious use of 3D pen printers for filaments embedded with redox active metals as additives in a home environment.

The severity of global pandemic due to severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2) has engaged the researchers and clinicians to find the key features triggering the viral infection to lung cells. By utilizing such crucial information, researchers and scientists try to combat the spread of the virus. Here, in this work, we performed in silico analysis of the protein–protein interactions between the receptor-binding domain (RBD) of the viral spike protein and the human angiotensin-converting enzyme 2 (hACE2) receptor to highlight the key alteration that happened from SARS-CoV to SARS-CoV-2. We analyzed and compared the molecular differences between spike proteins of the two viruses using various computational approaches such as binding affinity calculations, computational alanine, and molecular dynamics simulations. The binding affinity calculations showed that SARS-CoV-2 binds a little more firmly to the hACE2 receptor than SARS-CoV. The major finding obtained from molecular dynamics simulations was that the RBD–ACE2 interface is populated with water molecules and interacts strongly with both RBD and ACE2 interfacial residues during the simulation periods. The water-mediated hydrogen bond by the bridge water molecules is crucial for stabilizing the RBD and ACE2 domains. Near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) confirmed the presence of vapor and molecular water phases in the protein–protein interfacial domain, further validating the computationally predicted interfacial water molecules. In addition, we examined the role of interfacial water molecules in virus uptake by lung cell A549 by binding and maintaining the RBD/hACE2 complex at varying temperatures using nanourchins coated with spike proteins as pseudoviruses and fluorescence-activated cell sorting (FACS) as a quantitative approach. The structural and dynamical features presented here may serve as a guide for developing new drug molecules, vaccines, or antibodies to combat the COVID-19 pandemic.

Increasing data on the infection indicate that maternal infections are severe. Under the realms of vaccine development, virus‐like particles (VLP)/nanoparticles (NPs) hold the promise of targeted control of therapeutics transfer across the placental barrier with the potential to trigger innate immune responses. Though the placenta is known to act as a barrier against exogenous materials, viruses exploit the transport systems and overcome the barrier properties. VLPs can be strategically designed to obtain the necessary mechanisms for navigation across the placenta and immune response. However, several knowledge gaps on the chemical, viral transmission strategies and the host defense response exist owing to the highly dynamic etiology of the placental barrier. This further complicates the toxicological analysis of the developed therapeutics. Herein, placental physiology and functions are discussed in significance with chemical toxicology, viral infections, and the host defense. Further, the promising applications of VLPs and perspective on their design to overcome the placental gatekeeper to gain the necessary immune response or therapy are provided. Finally, a holistic approach to various bioengineering models for studying chemical toxicants, viral infections, and effects of VLPs is provided to facilitate better translation of these VLPs to clinical applications.