Biological Systems Research Articles

Synthesis and Development of Inverse-Type Nucleoside Diarylethene Photoswitches.

Nucleosidic diarylethenes (DAEs) have evolved from an emerging class of photochromes into a well-established option for integrating photochromic functionalities into biological systems. However, a comprehensive understanding of how chemical structure influences their photochromic properties remains essential. While structural features, such as an inverse connection between the aryl residues and the ethene bridge, are well-documented for classical DAEs, their application to nucleosidic DAEs has been underexplored. In this study, we address this gap by developing three distinct types of inverse nucleosidic DAEs - semi-inverse thiophenes, semi-inverse uridines and inverse uridines. We successfully synthesized these compounds and conducted comprehensive analyses of their photostationary states, thermal stability, reversibility, and reaction quantum yields. Additionally, we conducted an in-depth comparison of their photochromic properties with those of their normal-type counterparts. Among the synthesized compounds, seven semi-inverse thiophenes exhibited the most promising characteristics. Notably, these compounds demonstrated excellent fatigue resistance, with up to 96% retention of photochromic activity over 40 switching cycles, surpassing the performance of all comparable nucleosidic DAEs reported to date. These findings hold significant promise for future applications in various fields.

The disordering effect of SARMs on a biomembrane model.

From medicine to sport, selective androgen receptor modulators (SARMs) have represented promising applications. The ability of SARMs to selectively interact with the androgen receptor (AR) indicates that this kind of molecule can interfere with numerous physiological and pathological processes controlled by the AR regulatory mechanism. However, critical concerns in relation to safety and potential side effects of SARMs remain under discussion and investigation. SARMs, being hydrophobic/organic compounds, can be subjected to hydrophobic interactions. In this perspective, we hypothesize that SARMs interact with lipid membranes, producing significant physical and chemical changes that could be associated with several effects that SARMs represent in biological systems. In this context, the effect of SARMs on lipid membranes mediated by non-specific interactions is little explored. Here, we report significant information related to the changes that ostarine, ligandrol, andarine, and cardarine produce in the thermodynamic properties of a lipid biomembrane model. Physical changes and chemical interactions of the systems were investigated by differential scanning calorimetry (DSC), dynamic light scattering (DLS), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and theoretical calculations implementing density functional theory (DFT). We demonstrate that ostarine, ligandrol, andarine, and cardarine can strongly interact with a lipid biomembrane model composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and accordingly, these molecules can be incorporated into the polar/hydrophobic regions of the lipid bilayer. By employing theoretical calculations, we gained insights into the possible electrostatic interactions between SARMs and phospholipid molecules, enhancing our understanding of the driving forces behind the interactions of SARMs with lipid membranes. Overall, this investigation provides relevant knowledge related to the biophysical-chemical effects that SARMs produce in biomembrane models and could be of practical reference for promising applications of SARMs in medicine and sport.

Cytotoxicity and antibacterial susceptibility assessment of a newly developed pectin–chitosan polyelectrolyte composite for dental implants

Biopolymers such as chitosan and pectin are currently attracting significant attention because of their unique properties, which are valuable in the food industry and pharmaceutical applications. These properties include non-toxicity, compatibility with biological systems, natural decomposition ability, and structural adaptability. The objective of this study was to assess the performance of two different ratios of pectin–chitosan polyelectrolyte composite (PCPC) after applying them as a coating to commercially pure titanium (CpTi) substrates using electrospraying. The PCPC was studied in ratios of 1:2 and 1:3, while the control group consisted of CpTi substrates without any coating. The pull-off adhesion strength, cytotoxicity, and antibacterial susceptibility tests were utilized to evaluate the PCPC coatings. In order to determine whether the composite coating was the result of physical blending or chemical bonding, the topographic surface parameters were studied using Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). PCPC (1:3) had the highest average cell viability of 93.42, 89.88, and 86.85% after 24, 48, and 72 h, respectively, as determined by the cytotoxicity assay, when compared to the other groups. According to the Kirby–Bauer disk diffusion method for testing antibacterial susceptibility, PCPC (1:3) showed the highest average diameter of the zone of inhibition, measuring 14.88, 14.43, and 11.03 mm after 24, 48, and 72 h of incubation, respectively. This difference was highly significant compared to Group 3 at all three time periods. PCPC (1:3) exhibited a significantly higher mean pull-off adhesion strength (521.6 psi) compared to PCPC (1:2), which revealed 419.5 psi. PCPC (1:3) coated substrates exhibited better surface roughness parameters compared to other groups based on the findings of the AFM. The FTIR measurement indicated that both PCPC groups exhibited a purely physical blending in the composite coating. Based on the extent of these successful in vitro experiments, PCPC (1:3) demonstrates its potential as an effective coating layer. Therefore, the findings of this study pave the way for using newly developed PCPC after electrospraying coating on CpTi for dental implants.

Integrated in silico analysis of transcriptomic alterations in nanoparticle toxicity across human and mouse models

Nanoparticles, due to their exceptional physicochemical properties are used in our day-to-day environment. They are currently not regulated which might lead to increased levels in the biological systems causing adverse effects. However, the overall mechanism behind nanotoxicity remains elusive. Previously, we analysed the transcriptome datasets of copper oxide nanoparticles using in silico tools and identified IL-17, chemokine signaling pathway, and cytokine-cytokine receptor interaction as the key pathways altered. Based on the findings, we hypothesized a common pathway involved in transition metal oxide nanoparticles toxicity irrespective of the variables. Further, there could be unique transcriptome changes between metal oxide nanoparticles and other nanoparticles. To accomplish this, the overall transcriptome datasets of nanoparticles consisting of microarray and RNA-Seq were obtained. >90 studies for 17 different nanoparticles, performed in humans, rats, and mice were assessed. After initial screening, 24 mouse studies (with 196 datasets) and 34 human studies (with 200 datasets) were used for further analyses. The common genes that are dysregulated upon NPs exposure were identified for human and mouse datasets separately. Further, an overrepresentation functional enrichment analysis was performed. The common genes, their gene ontology, gene-gene, and protein-protein interactions were assessed. The overall results suggest that IL-17 and its related pathways might be commonly altered in nanoparticle exposure with lung as one of the major organs affected.

Droplet Electrophoresis with Internal Free Ions: Effect of Permittivity Changes in the Electric Double Layer.

Droplet electrophoresis (EP) is of interest in biological systems, microfluidics, and separation techniques. We investigate EP of an oil droplet that contains free ions and is stabilized in an electrolyte solution through an amphoteric surfactant. The presence of mobile ions within the droplet leads to the creation of a distinct nonzero space charge density inside the droplet and consequently, formation of an inner EDL inside the droplet in addition to the traditionally considered outside EDL. While we assume the permittivity inside the inner EDL to remain constant, we consider both the case of constant and variable permittivity in the outer EDL. Our findings demonstrate a change in the droplet direction of motion in the electric field when transitioning from acidic to alkaline pH, regardless of permittivity and ionic strength in both oil and electrolyte. We further find a significant reduction in the magnitude of droplet velocity in the case of a variable permittivity due to reduction of the local space charge density within the EDL surrounding the droplet. When decreasing the viscosity ratio of the oil to the electrolyte, in all cases we find a reduction in droplet velocity. This decline is attributed mostly to the formation and strength of a vortex around the droplet. We finally demonstrate that with constant permittivity in the outer EDL, the variation in κaouter has a more significant effect on the droplet's EP velocity than altering κainner. However, in cases where the body forces inside of the droplet dominate, minor changes in the outer electrolyte concentration have no influence on the droplet motion, which is relevant for biological colloids that can contain significant free internal charges. Our results are important for the manipulation of biological colloids, water and waste treatment such as lubricant removal from processing streams.

Analysis of nanomaterial biocoronas in biological and environmental surroundings.

A biomolecular coating, or biocorona, forms on the surface of engineered nanomaterials (ENMs) immediately as they enter biological or environmental systems, defining their biological and environmental identity and influencing their fate and performance. This biomolecular layer includes proteins (the protein corona) and other biomolecules, such as nucleic acids and metabolites. To ensure a meaningful and reproducible analysis of the ENMs-associated biocorona, it is essential to streamline procedures for its preparation, separation, identification and characterization, so that studies in different labs can be easily compared, and the information collected can be used to predict the composition, dynamics and properties of biocoronas acquired by other ENMs. Most studies focus on the protein corona as proteins are easier to monitor and characterize than other biomolecules and play crucial roles in receptor engagement and signaling; however, metabolites play equally critical roles in signaling. Here we describe how to reproducibly prepare and characterize biomolecule-coated ENMs, noting especially the steps that need optimization for different types of ENMs. The structure and composition of the biocoronas are characterized using general methods (transmission electron microscopy, dynamic light scattering, capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry) as well as advanced techniques, such as transmission electron cryomicroscopy, synchrotron-based X-ray absorption near edge structure and circular dichroism. We also discuss how to use molecular dynamic simulation to study and predict the interaction between ENMs and biomolecules and the resulting biocorona composition. The application of this protocol can provide mechanistic insights into the formation, composition and evolution of the ENM biocorona, ultimately facilitating the biomedical and agricultural application of ENMs and a better understanding of their impact in the environment.

Synergistic material–microbe interface toward deeper anaerobic defluorination

Per- and polyfluoroalkyl substances (PFAS), particularly the perfluorinated ones, are recalcitrant to biodegradation. By integrating an enrichment culture of reductive defluorination with biocompatible electrodes for the electrochemical process, a deeper defluorination of a C6-perfluorinated unsaturated PFAS was achieved compared to the biological or electrochemical system alone. Two synergies in the bioelectrochemical system were identified: i) The in-series microbial-electrochemical defluorination and ii) the electrochemically enabled microbial defluorination of intermediates. These synergies at the material-microbe interfaces surpassed the limitation of microbial defluorination and further turned the biotransformation end products into less fluorinated products, which could be less toxic and more biodegradable in the environment. This material-microbe hybrid system brings opportunities in the bioremediation of PFAS driven by renewable electricity and warrants future research on mechanistic understanding of defluorinating and electroactive microorganisms at the material-microbe interface for system optimizations.

Unified understanding of the impact of semiflexibility, concentration, and molecular weight on macromolecular-scale ring diffusion

Conformationally fluctuating, globally compact macromolecules such as polymeric rings, single-chain nanoparticles, microgels, and many-arm stars display complex dynamic behaviors due to their rich topological structure and intermolecular organization. Synthetic rings are hybrid objects with conformations that display both ideal random walk and compact globular features, which can serve as models of genomic DNA. To date, emphasis has been placed on the effect of ring molecular weight on their unusual behaviors. Here, we combine simulations and a microscopic force-level theory to build a unified understanding for how key aspects of ring dynamics depend on different tunable molecular properties including backbone rigidity, monomer concentration, degree of traditional entanglement, and molecular weight. Our large-scale molecular dynamics simulations of ring melts with very different backbone stiffnesses reveal unanticipated behaviors which agree well with our generalized theory. This includes a universal master curve for center-of-mass diffusion constants as a function of molecular weight scaled by a chemistry and thermodynamic state-dependent critical molecular weight that generalizes the concept of an entanglement cross-over for linear chains. The key physics is how backbone rigidity and monomer concentration induced changes of the entanglement length, interring packing, degree of interpenetration, and liquid compressibility slow down space-time dynamic-force correlations on macromolecular scales. A power law decay of the center-of-mass diffusion constant with inverse molecular weight squared is the first consequence, followed by an ultraslow activated hopping transport regime. Our results set the stage to address slow dynamics and kinetic arrest in different families of compact synthetic and biological polymeric systems.

Pink noise promotes sooner state transitions during bimanual coordination

The seemingly straightforward task of tying one's shoes requires a sophisticated interplay of joints, muscles, and neural pathways, posing a formidable challenge for researchers studying the intricacies of coordination. A widely accepted framework for measuring coordinated behavior is the Haken-Kelso-Bunz (HKB) model. However, a significant limitation of this model is its lack of accounting for the diverse variability structures inherent in the coordinated systems it frequently models. Variability is a pervasive phenomenon across various biological and physical systems, and it changes in healthy adults, older adults, and pathological populations. Here, we show, both empirically and with simulations, that manipulating the variability in coordinated movements significantly impacts the ability to change coordination patterns-a fundamental feature of the HKB model. Our results demonstrate that synchronized bimanual coordination, mirroring a state of healthy variability, instigates earlier transitions of coordinated movements compared to other variability conditions. This suggests a heightened adaptability when movements possess a healthy variability. We anticipate our study to show the necessity of adapting the HKB model to encompass variability, particularly in predictive applications such as neuroimaging, cognition, skill development, biomechanics, and beyond.

Light-Driven Multidirectional Bending in Artificial Muscles.

Using light to drive polymer actuators can enable spatially selective complex motions, offering a wealth of opportunities for wireless control of soft robotics and active textiles. Here, the integration of photothermal components is reported into shape memory polymer actuators. The fabricated twist-coiled artificial muscles show on-command multidirectional bending, which can be controlled by both the illumination intensity, as well as the chirality, of the prepared artificial muscles. Importantly, the direction in which these artificial muscles bend does not depend on intrinsic material characteristics. Instead, this directionality is achieved by localized untwisting of the actuator, driven by selective irradiation. The reaction times of this bending system are significantly - at least two orders of magnitude - faster than heliotropic biological systems, with a response time up to one second. The programmability of the artificial muscles is further demonstrated for selective, reversible, and sustained actuation when integrated in butterfly-shaped textiles, along with the capacity to autonomously orient toward a light source. This functionality is maintained even on a rotating platform, with angular velocities of 6°/s, independent of the rotation direction. These attributes collectively represent a breakthrough in the field of artificial muscles, intended to adaptive shape-changing soft systems and biomimetic technologies.

Topological structures and adsorption properties of the [Fe4S4] clusters

The [Fe4S4] compositions are ubiquitous in biological systems as integral parts of the complex catalytic mechanisms as in hydrogenases and nitrogenases. The current reports about [Fe4S4] species are based on the cube-like structure framework. Here, the topological structures, stability and electronic properties of gas phase [Fe4S4]+, [Fe4S4]0 and [Fe4S4]− are analyzed. It is found that ground state structures of these three clusters have similar cubic cages but different symmetries and spin multiplicities. The molecular dynamics simulations demonstrate that the cubic cage remains thermodynamically stable at 700 K. The density of states show that the charge state is the key to affect electronic behaviors of them even under the same structural framework. The molecular orbitals show that the LUMO orbitals are distributed throughout whole structures, showing great delocalized characteristics, especially for the anionic [Fe4S4]−, while the HOMO orbits are mainly localized in Fe-S bonds, which are also confirmed by the electron localization function analyses. After one CO molecule is adsorbed on these clusters, it prefers to locate at the Fe atoms. Moreover, the C–O bond length and vibration frequency of the [Fe4S4]−-CO undergone a significant red shift. Our work shows that the [Fe4S4]− may act as a potential catalyst for activating the C–O bond.

Low-Coordinate Iron Hydride Chemistry at an N,N,C-Heteroscorpionate Platform.

Locally high-spin iron hydrides are proposed to play a critical role as intermediates in iron-molybdenum cofactor (FeMoco)-catalyzed N2 fixation. Inspired by these biological systems, we report herein our initial investigations into low-coordinate iron hydride chemistry supported by our N,N,C-heteroscorpionate ligands. Those ligands with smaller steric profiles are unable to completely suppress the formation of a binuclear [Fe(μ2-H)]2 complex; however, the incorporation of more substantial steric bulk allows for the isolation of a rare example of a terminal, high-spin (S = 2) Fe2+ hydride. Fourier transform infrared spectroscopy suggests an unusually weak Fe-H bond in the latter molecule. Mössbauer spectroscopies, coupled with density functional theory calculations, highlights the substantial influence of the terminal hydride ligand on 57Fe isomer shift.

Safe(r) landing by older people: A matter of complexity.

Maintaining balance is a complex motor problem that requires coordinated contributions from multiple biological systems. Aging inevitably lessens the fidelity of biological systems, which can result in an increased risk of falling, and associated injuries. It is advantageous to land safely, but falls manifest in diverse ways, so different motor solutions are required to land safely. However, without considerable practice, it is difficult to recall the appropriate motor solution for a fall and then apply it effectively in the brief duration before hitting the ground. A complex systems perspective provides a lens through which to view the problem of safe-landing. It may be possible to use motor analogies to promote degeneracy within the perceptual-motor system so that, regardless of the direction in which an older person falls, their body self-organizes to land with less likelihood of injury.

GaSI: A Wide-Gap Non-centrosymmetric Helical Crystal.

The complex non-centrosymmetric and chiral nature of helical structures endow materials that possess such motifs with unusual properties. However, despite their ubiquity in biological and organic systems, there is a severe lack of inorganic crystals that display helicity in extended lattices, where these unusual properties are expected to be most pronounced. Here, we report a new inorganic helical structure, gallium sulfur iodide (GaSI), within the exfoliable class of III-VI-VII (1:1:1) one-dimensional (1D) van der Waals (vdW) crystals. Through detailed structural analyses, including single-crystal X-ray diffraction, electron microscopy, and density functional theory (DFT), we elucidate the apparent noncrystallographic screw axis and the first example of an atomic scale helical structure bearing a "squircular" cross-section in GaSI. Crystallizing in the non-centrosymmetric P4̅ space group, we found that GaSI crystals exhibit pronounced second-harmonic generation. From diffuse reflectance spectroscopy, GaSI displays a sizeable bandgap of 3.69 eV, owing tostrong covalent interactions arising from the smaller sulfur atoms within the helix core. These results position GaSI as a promising exfoliable nonlinear optical material across a broad optical window.

Semi–biological photosystem: Harnessing carbon dots and Geobacter sulfurreducens for solar–driven hydrogenation

Abstract Semi–biological photosynthesis utilises the unique ability of microbial catalysts together with synthetic photosensitisers (semiconductors) to produce high–value chemicals from sustainable feedstocks. In this work, we devise a semi–biological hybrid system consisting of sustainable photosensitisers, carbon dots in the size range of 5 nm − 35 nm (CDs) interfaced with bacteria, Geobacter sulfurreducens (G. sulfurreducens) to reduce fumarate to succinate as a model hydrogenation reaction. After seven days of solar irradiation, using quantitative proton nuclear magnetic resonance spectroscopy (qNMR), the CD–G. sulfurreducens photosystem produced approximately 18 mM of succinate without the need for a redox mediator. Moreover, in reusing the CDs approximately 70% of the succinate (compared to the previous cycle) was recovered. The proposed photobiohybrid system paves a new avenue for sustainable solar–to–chemical conversion in high–value chemical production.

Distributions, interactions, and dynamics of prokaryotes and phages in a hybrid biological wastewater treatment system

BackgroundUnderstanding the interactions and dynamics of microbiotas within biological wastewater treatment systems is essential for ensuring their stability and long-term sustainability. In this study, we developed a systematic framework employing multi-omics and Hi-C sequencing to extensively investigate prokaryotic and phage communities within a hybrid biofilm and activated sludge system.ResultsWe uncovered distinct distribution patterns, metabolic capabilities, and activities of functional prokaryotes through the analysis of 454 reconstructed prokaryotic genomes. Additionally, we reconstructed a phage catalog comprising 18,645 viral operational taxonomic units (vOTUs) with high length and contiguity using hybrid assembly, and a distinct distribution of phages was depicted between activated sludge (AS) and biofilm. Importantly, 1340 host-phage pairs were established using Hi-C and conventional in silico methods, unveiling the host-determined phage prevalence. The majority of predicted hosts were found to be involved in various crucial metabolic processes, highlighting the potential vital roles of phages in influencing substance metabolism within this system. Moreover, auxiliary metabolic genes (AMGs) related to various categories (e.g., carbohydrate degradation, sulfur metabolism, transporter) were predicted. Subsequent activity analysis emphasized their potential ability to mediate host metabolism during infection. We also profiled the temporal dynamics of phages and their associated hosts using 13-month time-series metagenomic data, further demonstrating their tight interactions. Notably, we observed lineage-specific infection patterns, such as potentially host abundance- or phage/host ratio-driven phage population changes.ConclusionsThe insights gained from this research contribute to the growing body of knowledge surrounding interactions and dynamics of host-phage and pave the way for further exploration and potential applications in the field of microbial ecology.7mTZubWt51_LqpKWPutADaVideo

Crossing the Halfway Point: Aptamer-Based, Highly Multiplexed Assay for the Assessment of the Proteome.

Measuring responses in the proteome to various perturbations improves our understanding of biological systems. The value of information gained from such studies is directly proportional to the number of proteins measured. To overcome technical challenges associated with highly multiplexed measurements, we developed an affinity reagent-based method that uses aptamers with protein-like side chains along with an assay that takes advantage of their unique properties. As hybrid affinity reagents, modified aptamers are fully comparable to antibodies in terms of binding characteristics toward proteins, including epitope size, shape complementarity, affinity and specificity. Our assay combines these intrinsic binding properties with serial kinetic proofreading steps to allow highly effective partitioning of stable specific complexes from unstable nonspecific complexes. The use of these orthogonal methods to enhance specificity effectively overcomes the severe limitation to multiplexing inherent to the use of sandwich-based methods. Our assay currently measures half of the unique proteins encoded in the human genome with femtomolar sensitivity, broad dynamic range and exceptionally high reproducibility. Using machine learning to identify patterns of change, we have developed tests based on measurement of multiple proteins predictive of current health states and future disease risk to guide a holistic approach to precision medicine.

Uncovering the binding nature of thiocyanate in contact ion pairs with lithium ions.

Ion pair formation is a fundamental molecular process that occurs in a wide variety of systems, including electrolytes, biological systems, and materials. In solution, the thiocyanate (SCN-) anion interacts with cations to form contact ion pairs (CIPs). Due to its ambidentate nature, thiocyanate can bind through either its sulfur or nitrogen atoms, depending on the solvent. This study focuses on the binding nature of thiocyanate with lithium ions as a function of the solvents using FTIR, 2D infrared spectroscopy (2DIR) spectroscopies, and theoretical calculations. The study reveals that the SCN- binding mode (S or N end) in CIPs can be identified through 2DIR spectroscopy but not by linear IR spectroscopy. Linear IR spectroscopy shows that the CN stretch frequencies are too close to one another to separate N- and S-bound CIPs. Moreover, the IR spectrum shows that the S-C stretch presents different frequencies for the salt in different solvents, but it is related to the anion speciation rather than to its binding mode. A similar trend is observed for the anion bend. 2DIR spectra show different dynamics for N-bound and S-bound thiocyanate. In particular, the frequency-frequency correlation function (FFCF) dynamics extracted from the 2DIR spectra have a single picosecond exponential decay for N-bound thiocyanate and a biexponential decay for S-bound thiocyanate, consistent with the binding mode of the anion. Finally, it is also observed that the binding mode also affects the line shape parameters, probably due to the different molecular mechanisms of the FFCF for N- and S-bound CIPs.

Exploring Nanohydrogels: Crafting Innovations for Biomedical Advancements

AbstractHere in, we discuss different types of nanohydrogels in the field of biomedicine, highlighting their unique properties such as size, biocompatibility, and tuneable drug release capabilities. Nanohydrogels are considered versatile tools for applications in tissue engineering, drug delivery, and diagnostics, with the ability to target specific sites and release therapeutic agents in a controlled manner. The controlled‐release characteristics of nanohydrogels are particularly emphasized for targeted drug delivery, potentially transforming therapies for conditions like cancer by maximizing treatment efficacy while minimizing damage to healthy tissues. Several research articles published on nanohydrogels has been steadily increasing over the years, indicating growing interest and research activity in this field. This review provides an overview of contemporary methodologies employed in nanohydrogel design, their utilization in biomedical contexts, and their pivotal role in shaping advanced therapeutics. Recent investigations on nanohydrogels are scrutinized for their extensive utility in devising strategies conducive to finely tuned biological applications. Challenges and obstacles associated with the nanohydrogel technology in biomedicine also has been discussed. Cautious handling of the interaction of nanohydrogels with complex biological systems is also emphasized for the successful integration of this technology into medical applications.

Structural characterization of wax esters using ultraviolet photodissociation mass spectrometry.

Wax esters play critical roles in biological systems, serving functions from energy storage to chemical signaling. Their diversity is attributed to variations in alcohol and acyl chains, including their length, branching, and the stereochemistry of double bonds. Traditional analysis by mass spectrometry with collisional activations (CID, HCD) offers insights into acyl chain lengths and unsaturation level. Still, it falls short in pinpointing more nuanced structural features like the position of double bonds. As a solution, this study explores the application of 213-nm ultraviolet photodissociation (UVPD) for the detailed structural analysis of wax esters. It is shown that lithium adducts provide unique fragments as a result of Norrish and Norrish-Yang reactions at the ester moieties and photoinduced cleavages of double bonds. The product ions are useful for determining chain lengths and localizing double bonds. UVPD spectra of various wax esters are presented systematically, and the effect of activation time is discussed. The applicability of tandem mass spectrometry with UVPD is demonstrated for wax esters from natural sources. The UHPLC analysis of jojoba oil proves the compatibility of MS2 UVPD with the chromatography time scale, and a direct infusion is used to analyze wax esters from vernix caseosa. Data shows the potential of UVPD and its combination with CID or HCD in advancing our understanding of wax ester structures.