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Systemic inflammation is reported in normal-weight obesity (NWO) and metabolically healthy obesity (MHO), which may be linked to their increased cardiovascular disease (CVD) risk. Yet, drivers of this inflammation remain unclear. We characterized factors known to influence inflammatory status (i.e., intestinal permeability, adipose tissue, diet quality, microbiota) - and their relationships with measured inflammation - in NWO and MHO, healthy controls (CON) and metabolically unhealthy obesity (MUO; N=80; n=20/group). Serum indicators of intestinal permeability and inflammation were assessed using ELISA and/or multiplex. Total, visceral, and percent body fat were measured with dual-energy X-ray absorptiometry (DXA). Fecal microbiota composition was assessed via 16S rRNA sequencing (n=9-10/group). For C-reactive protein (CRP), MUO > NWO > CON ( p <0.0001). In MHO, CRP was intermediate - and similar to - both MUO and NWO. Lipopolysaccharide binding protein (LBP) and the ratio of LBP to soluble CD14 (sCD14) were higher in MHO and MUO versus CON/NWO ( p 's<0.0001). Across correlation and regression analyses, LBP consistently displayed the strongest relationships with CRP in the entire sample (r=0.78;β = 0.57; p 's<0.0001) and in MHO (r=0.74; p <0.01), but not NWO (r=0.37; p = 0.11). Shannon index was higher in CON compared to MUO ( p <0.05) and inversely correlated with CRP in the full sample (r=-0.37; p <0.05). These data are consistent with the notion that intestinal permeability is associated with low-grade inflammation in MHO, which could be implicated in this population's reported CVD risk.

Exposure-based treatments such as prolonged exposure therapy (PE) are effective for veterans with PTSD. However, dropout rates as high as 50% are common. The Department of Veterans Affairs employs peers to increase mental health treatment engagement, however peers are not routinely used to help patients complete PE homework assignments. The present study included 109 veterans who decided to drop out from exposure-based treatment after completing seven or fewer sessions and used a randomized controlled design to compare PE treatment completion rates in response to 2 forms of peer support: (1) standard weekly telephone-based peer support vs. (2) peer-assisted in vivo exposure, wherein peers accompanied veterans (virtually or in person) during a limited number of in vivo exposure assignments. There were no differences between instrumental vs general peer support conditions as randomized. However, post hoc analyses indicated that 87% of those who completed at least one peer-assisted in vivo exposure completed treatment, compared to 56% of those not completing any peer-assisted in vivo exposure. The dose effect of peer-assisted in vivo exposure increased to 93% with 2 or more peer-assisted exposures, and 97% with 3 or more peer-assisted exposures. The present study suggests that augmenting PE with instrumental peer support during in vivo exposure homework may reduce dropout if completed. Future research should test whether the impact of peer-assisted in vivo exposure is enhanced when offered at the beginning of treatment as opposed to waiting until the point of dropout.

Natural light-harvesting systems spatially organize densely packed dyes in different configurations to either transport excitons or convert them into charge photoproducts, with high efficiency. In contrast, artificial photosystems like organic solar cells and light-emitting diodes lack this fine structural control, limiting their efficiency. Thus, biomimetic multi-dye systems are needed to organize dyes with the sub-nanometer spatial control required to sculpt resulting photoproducts. Here, we synthesize 11 distinct perylene diimide (PDI) dimers integrated into DNA origami nanostructures and identify dimer architectures that offer discrete control over exciton transport versus charge separation. The large structural-space and site-tunability of origami uniquely provides controlled PDI dimer packing to form distinct excimer photoproducts, which are sensitive to interdye configurations. In the future, this platform enables large-scale programmed assembly of dyes mimicking natural systems to sculpt distinct photophysical products needed for a broad range of optoelectronic devices, including solar energy converters and quantum information processors., Competing Interests: Declaration of interests The authors declare no competing interests.

Purpose: Cardiorespiratory fitness (CRF) is critical for cardiovascular health. Normal-weight obesity (NWO) and metabolically healthy obesity (MHO) may be at increased risk for cardiovascular disease, but a comparison of CRF and submaximal exercise dynamics against rigorously defined low- and high-risk groups is lacking., Methods: Four groups (N = 40; 10/group) based on body mass index (BMI), body fat %, and metabolic syndrome (MetS) risk factors were recruited: healthy controls (CON; BMI 18.5-24.9 kg/m 2 , body fat < 25% [M] or < 35% [F], 0-1 risk factors), NWO (BMI 18.5-24.9 kg/m 2 , body fat ≥ 25% [M] or ≥ 35% [F]), MHO (BMI > 30 kg/m 2 , body fat ≥ 25% [M] or ≥ 35% [F], 0-1 risk factors), or metabolically unhealthy obesity (MUO; BMI > 30 kg/m 2 , body fat ≥ 25% [M] or ≥ 35% [F], 2 + risk factors). All participants completed a V ˙ O 2peak test on a cycle ergometer., Results: V ˙ O 2peak was similarly low in NWO (27.0 ± 4.8 mL/kg/min), MHO (25.4 ± 6.7 mL/kg/min) and MUO (24.6 ± 10.0 mL/kg/min) relative to CON (44.2 ± 11.0 mL/kg/min) when normalized to total body mass (p's < 0.01), and adjusting for fat mass or lean mass did not alter these results. This same differential V ˙ O 2 pattern was apparent beginning at 25% of the exercise test (P Group*Time  < 0.01)., Conclusions: NWO and MHO had similar peak and submaximal CRF to MUO, despite some favorable health traits. Our work adds clarity to the notion that excess adiposity hinders CRF across BMI categories., Clinicaltrials: gov registration: NCT05008952., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background & Aims: Elevated postprandial triglycerides are an independent cardiovascular disease risk factor and observed in older adults. However, differences in postprandial triglycerides across the spectrum of adulthood remain unclear., Methods and Results: We performed a secondary analysis of six studies where adults (aged 18-84 years; N = 155) completed an abbreviated fat tolerance test (9 kcal/kg; 70% fat). Differences in postprandial triglycerides were compared in those ≥50 and <50 years and by decade of life, adjusting for sex and BMI. Compared to those <50 years, participants ≥50 years had higher fasting, 4 h, and Δ triglycerides from baseline (p's < 0.05). When examining triglyceride parameters by decade, no differences were observed for fasting triglycerides, but 50 s, 60 s, and 70s-80 s displayed greater 4 h and Δ triglycerides versus 20 s (p's ≤ 0.001). The frequency of adverse postprandial triglyceride responses (i.e., ≥220 mg/dL) was higher in participants ≥50 versus <50 years (p < 0.01), and in 60 s compared to all other decades (p = 0.01)., Conclusion: Older age was generally associated with higher postprandial triglycerides, with no divergence across the spectrum of older adulthood. In our sample, postprandial triglyceride differences in older and younger adults were driven by those >50 years relative to young adults in their 20 s., Registration: N/A (secondary analysis)., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Transition metal-based charge-transfer complexes represent a broad class of inorganic compounds with diverse photochemical applications. Charge-transfer complexes based on earth-abundant elements have been of increasing interest, particularly the canonical [Fe(bpy) 3 ] 2+ . Photoexcitation into the singlet metal-ligand charge transfer ( 1 MLCT) state is followed by relaxation first to the ligand-field manifold and then to the ground state. While these dynamics have been well-studied, processes within the MLCT manifold that facilitate and/or compete with relaxation have been more elusive. We applied ultrafast two-dimensional electronic spectroscopy (2DES) to disentangle the dynamics immediately following MLCT excitation of this compound. First, dynamics ascribed to relaxation out of the initially formed 1 MLCT state was found to correlate with the inertial response time of the solvent. Second, the additional dimension of the 2D spectra revealed a peak consistent with a ∼20 fs 1 MLCT → 3 MLCT intersystem crossing process. These two observations indicate that the complex simultaneously undergoes intersystem crossing and direct conversion to ligand-field state(s). Resolution of these parallel pathways in this prototypical earth-abundant complex highlights the ability of 2DES to deconvolve the otherwise obscured excited-state dynamics of charge-transfer complexes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Excitons are the molecular-scale currency of electronic energy. Control over excitons enables energy to be directed and harnessed for light harvesting, electronics, and sensing. Excitonic circuits achieve such control by arranging electronically active molecules to prescribe desired spatiotemporal dynamics. Photosynthetic solar energy conversion is a canonical example of the power of excitonic circuits, where chromophores are positioned in a protein scaffold to perform efficient light capture, energy transport, and charge separation. Synthetic systems that aim to emulate this functionality include self-assembled aggregates, molecular crystals, and chromophore-modified proteins. While the potential of this approach is clear, these systems lack the structural precision to control excitons or even test the limits of their power. In recent years, DNA origami has emerged as a designer material that exploits biological building blocks to construct nanoscale architectures. The structural precision afforded by DNA origami has enabled the pursuit of naturally inspired organizational principles in a highly precise and scalable manner. In this Account, we describe recent developments in DNA-based platforms that spatially organize chromophores to construct tunable excitonic systems. The high fidelity of DNA base pairing enables the formation of programmable nanoscale architectures, and sequence-specific placement allows for the precise positioning of chromophores within the DNA structure. The integration of a wide range of chromophores across the visible spectrum introduces spectral tunability. These excitonic DNA-chromophore assemblies not only serve as model systems for light harvesting, solar conversion, and sensing but also lay the groundwork for the integration of coupled chromophores into larger-scale nucleic acid architectures.We have used this approach to generate DNA-chromophore assemblies of strongly coupled delocalized excited states through both sequence-specific self-assembly and the covalent attachment of chromophores. These strategies have been leveraged to independently control excitonic coupling and system-bath interaction, which together control energy transfer. We then extended this framework to identify how scaffold configurations can steer the formation of symmetry-breaking charge transfer states, paving the way toward the design of dual light-harvesting and charge separation DNA machinery. In an orthogonal application, we used the programmability of DNA chromophore assemblies to change the optical emission properties of strongly coupled dimers, generating a series of fluorophore-modified constructs with separable emission properties for fluorescence assays. Upcoming advances in the chemical modification of nucleotides, design of large-scale DNA origami, and predictive computational methods will aid in constructing excitonic assemblies for optical and computing applications. Collectively, the development of DNA-chromophore assemblies as a platform for excitonic circuitry offers a pathway to identifying and applying design principles for light harvesting and molecular electronics.

In photosynthesis, absorbed light energy transfers through a network of antenna proteins with near-unity quantum efficiency to reach the reaction center, which initiates the downstream biochemical reactions. While the energy transfer dynamics within individual antenna proteins have been extensively studied over the past decades, the dynamics between the proteins are poorly understood due to the heterogeneous organization of the network. Previously reported timescales averaged over such heterogeneity, obscuring individual interprotein energy transfer steps. Here, we isolated and interrogated interprotein energy transfer by embedding two variants of the primary antenna protein from purple bacteria, light-harvesting complex 2 (LH2), together into a near-native membrane disc, known as a nanodisc. We integrated ultrafast transient absorption spectroscopy, quantum dynamics simulations, and cryogenic electron microscopy to determine interprotein energy transfer timescales. By varying the diameter of the nanodiscs, we replicated a range of distances between the proteins. The closest distance possible between neighboring LH2, which is the most common in native membranes, is 25 Å and resulted in a timescale of 5.7 ps. Larger distances of 28 to 31 Å resulted in timescales of 10 to 14 ps. Corresponding simulations showed that the fast energy transfer steps between closely spaced LH2 increase transport distances by ∼15%. Overall, our results introduce a framework for well-controlled studies of interprotein energy transfer dynamics and suggest that protein pairs serve as the primary pathway for the efficient transport of solar energy.

Background: Normal-weight obesity (NWO) describes individuals with a normal body mass index (BMI), but high body fat percent. NWO are at-risk for cardiometabolic diseases, but little is known about their bone health., Methods: Adults (N = 24) were classified as NWO (n = 12; 5M/7F) or low body fat percent controls (Con; n = 12; 6M/6F). Body composition and whole-body bone mineral density (BMD) were assessed using DXA. A serum bioplex assay was performed to examine markers related to bone formation and resorption., Results: In addition to higher body fat percent and visceral fat, NWO had lower whole-body BMD relative to Con ( p 's < 0.05). Circulating leptin was higher in NWO than Con ( p  < 0.05). Two biomarkers generally associated with lower bone mass - sclerostin and parathyroid hormone - were higher in NWO compared to Con ( p 's < 0.05)., Conclusion: In this preliminary study, adults with NWO displayed lower whole-body BMD alongside evidence of bone resorption. Impaired bone health may be another subclinical risk factor present in NWO., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Strongly-coupled multichromophoric assemblies orchestrate the absorption, transport, and conversion of photonic energy in natural and synthetic systems. Programming these functionalities involves the production of materials in which chromophore placement is precisely controlled. DNA nanomaterials have emerged as a programmable scaffold that introduces the control necessary to select desired excitonic properties. While the ability to control photophysical processes, such as energy transport, has been established, similar control over photochemical processes, such as interchromophore charge transfer, has not been demonstrated in DNA. In particular, charge transfer requires the presence of close-range interchromophoric interactions, which have a particularly steep distance dependence, but are required for eventual energy conversion. Here, we report a DNA-chromophore platform in which long-range excitonic couplings and short-range charge-transfer couplings can be tailored. Using combinatorial screening, we discovered chromophore geometries that enhance or suppress photochemistry. We combined spectroscopic and computational results to establish the presence of symmetry-breaking charge transfer in DNA-scaffolded squaraines, which had not been previously achieved in these chromophores. Our results demonstrate that the geometric control introduced through the DNA can access otherwise inaccessible processes and program the evolution of excitonic states of molecular chromophores, opening up opportunities for designer photoactive materials for light harvesting and computation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Problem: Normal-weight obesity (NWO) is associated with increased cardiovascular disease (CVD) risk. However, NWO's clinical presentation is often unremarkable based on common risk factors. We examined whether CVD risk factors not routinely measured clinically including postprandial triglycerides, flow-mediated dilation (FMD), and inflammatory cytokines would be abnormal in NWO, consistent with their future risk., Methods: Individuals were recruited into 3 groups (n = 10/ group): controls (Con), NWO, and metabolic syndrome (MetS). Con was defined as a normal body mass index (BMI), < 25% (M) or < 35% (F) body fat, and < 1 International Diabetes Federation (IDF) criteria. NWO were above this body fat cutoff while maintaining a normal BMI and MetS was defined per the IDF. Participants underwent an abbreviated fat tolerance test (i.e., difference in fasting and 4 h triglycerides following a high-fat meal [9 kcal/kg; 73% fat)] and fasting and postprandial lipid and glucose metrics, as well as FMD were measured. A T cell cytokine bioplex was also performed using fasting serum., Results: NWO and MetS had similar body fat% and both were higher than Con (p < 0.0001). Despite having similar fasting triglycerides to Con, NWO had 4-hour triglycerides 66% greater than Con, but 46% lower than MetS (p < 0.01). FMD decreased in all groups after the high-fat meal (p < 0.0001). MetS displayed lower fasting FMD than Con, and NWO was similar to both groups (p < 0.05). No group differences were observed with postprandial FMD and the majority of fasting cytokines assessed. However, MetS exhibited higher fasting TNF-α than Con (p < 0.05), and NWO was similar to both groups., Conclusions: Overall, NWO was associated with higher postprandial triglycerides than Con, but displayed little evidence of impaired vascular health or inflammation., Competing Interests: Declaration of interest The authors declare there are no conflicts of interest to disclose., (Copyright © 2022 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Molecular materials for light harvesting, computing, and fluorescence imaging require nanoscale integration of electronically active subunits. Variation in the optical absorption and emission properties of the subunits has primarily been achieved through modifications to the chemical structure, which is often synthetically challenging. Here, we introduce a facile method for varying optical absorption and emission properties by changing the geometry of a strongly coupled Cy3 dimer on a double-crossover (DX) DNA tile. Leveraging the versatility and programmability of DNA, we tune the length of the complementary strand so that it "pushes" or "pulls" the dimer, inducing dramatic changes in the photophysics including lifetime differences observable at the ensemble and single-molecule level. The separable lifetimes, along with environmental sensitivity also observed in the photophysics, suggest that the Cy3-DX tile constructs could serve as fluorescence probes for multiplexed imaging. More generally, these constructs establish a framework for easily controllable photophysics via geometric changes to coupled chromophores, which could be applied in light-harvesting devices and molecular electronics.

Post-meal triglycerides are an independent cardiovascular disease (CVD) risk factor, but the ideal high-fat meal formulation has yet to be standardized and is one challenge prohibiting widespread clinical adoption of postprandial triglyceride assessment. Two general approaches often used are giving individuals a high-fat meal scaled to body weight or a standardized high-fat meal containing a set fat bolus. A recent expert panel statement has endorsed the latter, specifying 75 g of fat as an appropriate fat dosage. Despite this recommendation, no study to date has tested whether there is a difference in postprandial triglycerides or if risk classification is affected based on these different approaches. We recruited 16 generally healthy individuals with roughly equal distribution among body mass index (BMI)class ( n = 5-6/per BMI category) and sex ( n = 2-3 M/F) within each BMI class. Each participant underwent two abbreviated fat tolerance tests separated by ~1 week: one with a scaled to body weight high-fat meal (9 kcal/kg; 70% fat) and a standardized meal containing 75 g of fat (70% fat). Fasting, 4 h, and absolute change in triglycerides across the entire sample and within each BMI category were similar regardless of high-fat meal. Only one participant with obesity had discordant postprandial responses between the fat tolerance tests (i.e., different CVD risk classification). These findings suggest that, within a certain range of fat intake, generally healthy individuals will have a similar postprandial triglyceride response. Considering the greater convenience of utilizing standardized high-fat meals, our data suggest that a standardized high-fat meal may be acceptable for large-scale studies and clinical implementation.