Mechanical Manipulation of Quantum Interference in Single-Molecule Junctions.

Mechanosensitive molecular junctions, where conductance is sensitive to an applied stress such as force or displacement, are a class of nanoelectromechanical systems unique for their ability to exploit quantum mechanical phenomena. Most studies so far relied on reconfiguration of the molecule-electrode interface to impart mechanosensitivity, but this approach is limited and, generally, poorly reproducible. Alternatively, devices that exploit conformational flexibility of molecular wires have been recently proposed. The mechanosensitive properties of molecular wires containing the 1,1'-dinaphthyl moiety are presented here. Rotation along the chemical bond between the two naphthyl units is possible, giving rise to two conformers (transoid and cisoid) that have distinctive transport properties. When assembled as single-molecule junctions, it is possible to mechanically trigger the transoid to cisoid transition, resulting in an exquisitely sensitive mechanical switch with high switching ratio (> 102 ). Theoretical modeling shows that charge reconfiguration upon transoid to cisoid transition is responsible for the observed behavior, with generation and subsequent lifting of quantum interference features. These findings expand the experimental toolbox of molecular electronics with a novel chemical structure with outstanding electromechanical properties, further demonstrating the importance of subtle changes in charge delocalization on the transport properties of single-molecule devices.

The Effect of Sitting Duration on Peripheral Blood Pressure Responses to Prolonged Sitting, With and Without Interruption: A Systematic Review and Meta-Analysis.

BACKGROUND: A previous meta-analysis reported that: (i) an acute bout of prolonged uninterrupted sitting induces a significant increase in peripheral blood pressure (BP) and (ii) the increase in BP can be offset by interrupting the sitting bout with light aerobic activities such as walking. However, the temporal association between prolonged uninterrupted sitting and BP was not determined. A better understanding of temporality, for example, how long it takes BP to increase, will assist in prescribing sitting interruption strategies. OBJECTIVES: We aimed to determine: (1) the temporal association between the duration of uninterrupted sitting and BP and (2) whether regular sitting interruptions moderate the association between uninterrupted sitting and BP. DATA SOURCES: Electronic databases (PubMed, Web of Science, SPORTDiscus) were searched from inception to July 2022. Reference lists of eligible studies and relevant reviews were also screened. STUDY SELECTION: Inclusion criteria for objective (1) were: (i) participants aged ≥ 18 years; (ii) a prolonged sitting bout ≥ 1 h; and (iii) peripheral BP measurements (systolic BP, diastolic BP, and/or mean arterial pressure) at more than two timepoints during the sitting bout. Additional criteria for objective (2) were: (i) the sitting interruption strategy was implemented during the sitting bout (i.e., not prior to engaging in sitting) and (ii) the study included a control (uninterrupted sitting) condition or group. APPRAISAL AND SYNTHESIS METHODS: There were 1555 articles identified, of which 33 met inclusion criteria for objective (1). Of those articles, 20 met inclusion criteria for objective (2). To investigate the effect of sitting duration on the BP response, unstandardized b coefficients (mmHg/h) and 95% confidence intervals (CIs) were calculated using a three-level mixed-effect meta-regression. RESULTS: Increased sitting duration was positively associated with systolic BP (b = 0.42 mmHg/h, 95% CI 0.18-0.60), diastolic BP (b = 0.24 mmHg/h, 95% CI 0.06-0.42), and mean arterial pressure (b = 0.66 mmHg/h, 95% CI 0.36-0.90). In trials where sitting was interrupted, there was a significant decrease in systolic BP (b = - 0.24 mmHg/h, 95% CI - 0.42 to - 0.06) and diastolic BP (b = - 0.24 mmHg/h, 95% CI - 0.42 to - 0.12), and a non-significant change in mean arterial pressure (p = 0.69). CONCLUSIONS: Increased uninterrupted sitting duration results in greater increases in BP; however, regularly interrupting sitting may offset negative effects.

An Orthogonal Conductance Pathway in Spiropyrans for Well-Defined Electrosteric Switching Single-Molecule Junctions.

While a multitude of studies have appeared touting the use of molecules as electronic components, the design of molecular switches is crucial for the next steps in molecular electronics. In this work, single-molecule devices incorporating spiropyrans, made using break junction techniques, are described. Linear spiropyrans with electrode-contacting groups linked by alkynyl spacers to both the indoline and chromenone moieties have previously provided very low conductance values, and removing the alkynyl spacer has resulted in a total loss of conductance. An orthogonal T-shaped approach to single-molecule junctions incorporating spiropyran moieties in which the conducting pathway lies orthogonal to the molecule backbone is described and characterized. This approach has provided singlemolecule conductance features with good correlation to molecular length. Additional higher conducting states are accessible using switching induced by UV light or protonation. Theoretical modeling demonstrates that upon (photo)chemical isomerization to the merocyanine, two cooperating phenomena increase conductance: release of steric hindrance allows the conductance pathway to become more planar (raising the mid-bandgap transmission) and a bound state introduces sharp interference near the Fermi level of the electrodes similarly responding to the change in state. This design step paves the way for future use of spiropyrans in single-molecule devices and electrosteric switches.

Single-Molecule Conductance Behavior of Molecular Bundles.

Controlling the orientation of complex molecules in molecular junctions is crucial to their development into functional devices. To date, this has been achieved through the use of multipodal compounds (i.e., containing more than two anchoring groups), resulting in the formation of tri/tetrapodal compounds. While such compounds have greatly improved orientation control, this comes at the cost of lower surface coverage. In this study, we examine an alternative approach for generating multimodal compounds by binding multiple independent molecular wires together through metal coordination to form a molecular bundle. This was achieved by coordinating iron(II) and cobalt(II) to 5,5'-bis(methylthio)-2,2'-bipyridine (L1) and (methylenebis(4,1-phenylene))bis(1-(5-(methylthio)pyridin-2-yl)methanimine) (L2) to give two monometallic complexes, Fe-1 and Co-1, and two bimetallic helicates, Fe-2 and Co-2. Using XPS, all of the complexes were shown to bind to a gold surface in a fac fashion through three thiomethyl groups. Using single-molecule conductance and DFT calculations, each of the ligands was shown to conduct as an independent wire with no impact from the rest of the complex. These results suggest that this is a useful approach for controlling the geometry of junction formation without altering the conductance behavior of the individual molecular wires.

Sciducio: a practical framework for guiding the development and leadership of the academic research environment.

The goal of this paper is to introduce Sciducio, a practical framework for guiding the development and leadership of an academic research environment. The principal audience for this framework is new academics, that is individuals beginning a tenure-track position in the U.S or a lecturing position elsewhere in the world. However, we also believe this framework will be of use to established academics searching for structure, academics moving to a new institution, and can serve as a training tool for doctoral and postdoctoral mentees. We briefly describe the theory supporting Sciducio, outline the framework and its individual components (blocks), then provide suggested instructions for use. We provide suggested instructions (i.e., descriptive rather than prescriptive), because there is no one-size-fits-all approach for ensuring success. Sciducio incorporates three domains (Plan, Manage, and Deliver), encompasses eight blocks, and is intended to fit on one-sheet of paper or one screen. The Plan domain includes the blocks: value, strategy, and leadership. The Manage domain includes the blocks: activities, key resources, and finances. The Deliver domain includes the blocks: solution and channels. Considering each of the framework blocks is complex, we cannot provide full justice to each component. This paper serves as a general overview and subsequent papers will be more topic specific. Additionally, we encourage others to contribute to and advance this framework.

The 24-h activity cycle and cardiovascular outcomes: establishing biological plausibility using arterial stiffness as an intermediate outcome.

This review proposes a biologically plausible working model for the relationship between the 24-h activity cycle (24-HAC) and cardiovascular disease. The 24-HAC encompasses moderate-to-vigorous physical activity (MVPA), light physical activity, sedentary behavior (SB), and sleep. MVPA confers the greatest relative cardioprotective effect, when considering MVPA represents just 2% of the day if physical activity guidelines (30 min/day) are met. While we have well-established guidelines for MVPA, those for the remaining activity behaviors are vague. The vague guidelines are attributable to our limited mechanistic understanding of the independent and additive effects of these behaviors on the cardiovascular system. Our proposed biological model places arterial stiffness, a measure of vascular aging, as the key intermediate outcome. Starting with prolonged exposure to SB or static standing, we propose that the reported transient increases in arterial stiffness are driven by a cascade of negative hemodynamic effects following venous pooling. The subsequent autonomic, metabolic, and hormonal changes further impair vascular function. Vascular dysfunction can be offset by using mechanistic-informed interruption strategies and by engaging in protective behaviors throughout the day. Physical activity, especially MVPA, can confer protection by chronically improving endothelial function and associated protective mechanisms. Conversely, poor sleep, especially in duration and quality, negatively affects hormonal, metabolic, autonomic, and hemodynamic variables that can confound the physiological responses to next-day activity behaviors. Our hope is that the proposed biologically plausible working model will assist in furthering our understanding of the effects of these complex, interrelated activity behaviors on the cardiovascular system.

Single-Molecule Junction Formation in Deep Eutectic Solvents with Highly Effective Gate Coupling.

The environment surrounding a molecular junction affects its charge-transport properties and, therefore, must be chosen with care. In the case of measurements in liquid media, the solvent must provide good solvation, grant junction stability, and, in the case of electrolyte gating experiments, allow efficient electrical coupling to the gate electrodes through control of the electrical double layer. We evaluated in this study the deep eutectic solvent mixture (DES) ethaline, which is a mixture of choline chloride and ethylene glycol (1:2), for single-molecule junction fabrication with break-junction techniques. In ethaline, we were able to (i) measure challenging and poorly soluble molecular wires, exploiting the improved solvation capabilities offered by DESs, and (ii) efficiently apply an electrostatic gate able to modulate the conductance of the junction by approximately an order of magnitude within a ∼1 V potential window. The electrochemical gating results on a Au-VDP-Au junction follow exceptionally well the single-level modeling with strong gate coupling (where VDP is 1,2-di(pyridine-4-yl)ethene). Ethaline is also an ideal solvent for the measurement of very short molecular junctions, as it grants a greatly reduced snapback distance of the metallic electrodes upon point-contact rupture. Our work demonstrates that DESs are viable alternatives to often relatively expensive ionic liquids, offering good versatility for single-molecule electrical measurements.

Reimagining the Value of Brachial-Ankle Pulse Wave Velocity as a Biomarker of Cardiovascular Disease Risk-A Call to Action on Behalf of VascAgeNet.

This review critiques the literature supporting clinical assessment and management of cardiovascular disease and cardiovascular disease risk stratification with brachial-ankle pulse wave velocity (baPWV). First, we outline what baPWV actually measures-arterial stiffness of both large central elastic arteries and medium-sized muscular peripheral arteries of the lower limb. Second, we argue that baPWV is not a surrogate for carotid-femoral pulse wave velocity. While both measures are dependent on the properties of the aorta, baPWV is also strongly dependent on the muscular arteries of the lower extremities. Increased lower-extremity arterial stiffness amplifies and hastens wave reflections at the level of the aorta, widens pulse pressure, increases afterload, and reduces coronary perfusion. Third, we used an established evaluation framework to identify the value of baPWV as an independent vascular biomarker. There is sufficient evidence to support (1) proof of concept; (2) prospective validation; (3) incremental value; and (4) clinical utility. However, there is limited or no evidence to support (5) clinical outcomes; (6) cost-effectiveness; (8) methodological consensus; or (9) reference values. Fourth, we address future research requirements. The majority of the evaluation criteria, (1) proof of concept, (2) prospective validation, (3) incremental value, (4) clinical utility and (9) reference values, can be supported using existing cohort datasets, whereas the (5) clinical outcomes and (6) cost-effectiveness criteria require prospective investigation. The (8) methodological consensus criteria will require an expert consensus statement. Finally, we finish this review by providing an example of a future clinical practice model.

Association between Yoga Participation and Arterial Stiffness: A Cross-Sectional Study.

BACKGROUND: Yoga may help adults of all fitness levels increase their physical activity and decrease their cardiovascular disease risk. AIM: To determine if arterial stiffness is lower (beneficial) in yoga versus non-yoga participants. METHOD: This cross-sectional study included 202 yoga (48.4 + 14.1 years, 81% female) and 181 (42.8 + 14.1 years, 44% female) non-yoga participants. The primary outcome was carotid-femoral pulse wave velocity (cfPWV). The two groups were compared using analysis of covariance with adjustments for demographic (age and sex), hemodynamic (mean arterial pressure and heart rate), lifestyle (physical activity levels, sedentary behaviour, smoking status and perceived stress score) and cardiometabolic (waist-to-hip ratio, total cholesterol and fasting glucose) factors. RESULTS: Following adjustments, cfPWV was significantly lower in yoga compared to non-yoga participants with a mean difference: -0.28 m.s-1, (95% CI = -0.55 to 0.08). CONCLUSION: At a population level, yoga participation may assist with decreasing the risk of cardiovascular disease in adults.

Not So Innocent After All: Interfacial Chemistry Determines Charge-Transport Efficiency in Single-Molecule Junctions.

Most studies in molecular electronics focus on altering the molecular wire backbone to tune the electrical properties of the whole junction. However, it is often overlooked that the chemical structure of the groups anchoring the molecule to the metallic electrodes influences the electronic structure of the whole system and, therefore, its conductance. We synthesised electron-accepting dithienophosphole oxide derivatives and fabricated their single-molecule junctions. We found that the anchor group has a dramatic effect on charge-transport efficiency: in our case, electron-deficient 4-pyridyl contacts suppress conductance, while electron-rich 4-thioanisole termini promote efficient transport. Our calculations show that this is due to minute changes in charge distribution, probed at the electrode interface. Our findings provide a framework for efficient molecular junction design, especially valuable for compounds with strong electron withdrawing/donating backbones.

A Cross-Sectional Investigation of Preadolescent Cardiometabolic Health: Associations with Fitness, Physical Activity, Sedentary Behavior, Nutrition, and Sleep.

BACKGROUND: Cardiometabolic disease (CMD) risk often begins early in life. Healthy lifestyle behaviors can mitigate risk, but the optimal combination of behaviors has not been determined. This cross-sectional study simultaneously examined the associations between lifestyle factors (fitness, activity behaviors, and dietary patterns) and CMD risk in preadolescent children. METHODS: 1480 New Zealand children aged 8-10 years were recruited. Participants included 316 preadolescents (50% female, age: 9.5 ± 1.1 years, BMI: 17.9 ± 3.3 kg/m2). Fitness (cardiorespiratory fitness [CRF], muscular fitness), activity behaviors (physical activity, sedentary, sleep), and dietary patterns were measured. Factor analysis was used to derive a CMD risk score from 13 variables (adiposity, peripheral and central hemodynamics, glycemic control, and blood lipids). RESULTS: Only CRF (ß = -0.45, p < 0.001) and sedentary time (ß = 0.12, p = 0.019) were associated with the CMD risk score in the adjusted multivariable analysis. CRF was found to be nonlinear (VO2 max ≤ ≈42 mL/kg/min associated with higher CMD risk score), and thus a CRF polynomial term was added, which was also associated (ß = 0.19, p < 0.001) with the CMD risk score. Significant associations were not found with sleep or dietary variables. CONCLUSION: The findings indicate that increasing CRF and decreasing sedentary behavior may be important public health targets in preadolescent children.

Acute sedentary behavior and cardiovascular disease research: standardizing the methodological posture.

Sedentary behavior has been identified as an independent predictor of future cardiovascular disease risk and all-cause mortality. To explain this association, a growing body of literature has sought to investigate the physiological underpinnings of this association with the goal of developing a biologically plausible model. In time, this biologically plausible model can be tested, and effective, translatable public health guidelines can be developed. However, to ensure that evidence across studies can be effectively synthesized, it is necessary to ensure their congruency and comparability. Although there are several key factors that should be considered and controlled across prolonged sitting studies, one pertinent issue is that of participant posture. There is currently a discourse within the literature regarding the posture that cardiovascular assessments are performed in and rest periods between posture transitions and subsequent measures. This perspectives piece makes the case for standardizing approaches across the research area and offers practical recommendations for future work.

Protocol for a study on Sitting with Interruption and Whole-Body Cardiovascular Health (SWITCH) in middle-aged adults.

BACKGROUND: Sedentary behavior (SB) is a biologically distinct yet understudied cardiovascular disease risk (CVD) factor. However, specific public health policy regarding the optimal strategy for SB interruption is unavailable. This paper outlines the protocol for part I of the Sitting with Interruption and Whole-Body Cardiovascular Health (SWITCH) study, including the rationale, objectives, methodology, and next steps. We additionally detail practical considerations that went into the development of the NIH R01 grant supporting this research. METHODS: Healthy men and women (n = 56, aged 36-55) who are inactive (<90 min/wk. of moderate-to-vigorous intensity physical activities for past 3 months) and sedentary (sitting for >8 h/day), will be recruited for this randomized crossover trial. Specifically, participants will complete the following 4-h conditions: (i) SB with once/h 5 min walk break; (ii) SB with once/h 15 min stand break; (iii) SB with twice/h breaks (alternating 5 min walk and 15 min stand); and (iv) SB with no breaks (i.e., control). Focus group discussions will refine our socioecological SB reduction model. RESULTS: The primary outcome will be change in aortic arterial stiffness (i.e., pulse wave velocity; PWV, m/s) for each substitution strategy relative to the control (SB with no breaks) condition. CONCLUSIONS: The outcomes from this study will facilitate the design of a subsequent randomized controlled trial to test a mechanism-informed, feasible SB-reduction intervention and support the development of SB policy.

Connectivity-Dependent Conductance of 2,2'-Bipyridine-Based Metal Complexes.

The present work provides an insight into the effect of connectivity isomerization of metal-2,2'-bipyridine complexes. For that purpose, two new 2,2'-bipyridine (bpy) ligand systems, 4,4'-bis(4-(methylthio)phenyl)-2,2'-bipyridine (Lmeta) and 5,5'-bis(3,3-dimethyl-2,3-dihydrobenzothiophen-5-yl)-2,2'-bipyridine (Lpara) were synthesized and coordinated to rhenium and manganese to obtain the corresponding complexes MnLmeta(CO)3Br, ReLmeta(CO)3Br, MnLpara(CO)3Br, MoLpara(CO)4 and ReLpara(CO)3Br. The experimental and theoretical results revealed that coordination to the para system, i.e., the metal ion peripheral to the conductance path, gave a slightly increased conductance compared to the free ligand attributed to the reduced highest occupied molecular orbital (HOMO)-least unoccupied molecular orbital (LUMO) gap. The meta-based system formed a destructive quantum interference feature that reduced the conductance of a S···S contacted junction to below 10-5.5Go, reinforcing the importance of contact group connectivity for molecular wire conductance.

Adiposity in preadolescent children: Associations with cardiorespiratory fitness.

Lifestyle factors contribute to childhood obesity risk, however it is unclear which lifestyle factors are most strongly associated with childhood obesity. The purpose of this cross-sectional study was to simultaneously investigate the associations among dietary patterns, activity behaviors, and physical fitness with adiposity (body fat %, fat mass, body mass index [BMI], and waist to hip ratio) in preadolescent children. Preadolescent children (N = 392, 50% female, age: 9.5 ± 1.1year, BMI: 17.9 ± 3.3 kg/m2) were recruited. Body fat (%) and fat mass (kg) were measured with bioelectrical impedance analysis. Cardiorespiratory fitness (VO2 max), muscular strength (hand-grip strength), activity, sleep, and dietary pattern was assessed. Multivariable analysis revealed that cardiorespiratory fitness associated most strongly with all four indicators of adiposity (body fat (%) (ß = -0.2; p < .001), fat mass (ß = -0.2; p < .001), BMI (ß = -0.1; p < .001) and waist to hip ratio (ß = -0.2; p < .001). Additionally, fruit and vegetable consumption patterns were associated with body fat percentage, but the association was negligible (ß = 0.1; p = 0.015). Therefore, future interventions should aim to promote the use of cardiorespiratory fitness as a means of reducing the obesity epidemic in children.

Sedentary behavior and cardiovascular disease risk: An evolutionary perspective.

A ubiquitous aspect of contemporary societies is sedentary behavior (SB), defined as low intensity activities in a seated, reclined, or supine posture. Leading public health agencies, including the World Health Organization, have recognized the strong association between SB and poor health outcomes, particularly cardiovascular disease. However, while public health agencies have begun to advocate for "reductions" in SB, the current US guidelines are typically vague and non-specific. There is good reasoning behind this non-committal advocacy-there is limited mechanistic and clinical evidence to support policy development. To guide SB policy development, it is important to first consider the origins and evolution of SB, including the following: 1) is SB really a novel/contemporary behavior? i.e., how has this behavior evolved? 2) how did our ancestors sit and in what contexts? 3) how does SB interact with 24-hour activity behaviors, including physical activity and sleep? 4) what other historical and contemporary facets of life interact with SB? and 5) in what context do these behaviors occur and how might they provide different evolutionarily novel stressors? This perspective article will synthesize the available evidence that addresses these questions and stimulate discussion pertaining to the lessons that we can learn from an historical and evolutionary perspective. Last, it will outline the gaps in current SB interruption literature that are hindering development of feasible SB reduction policy.

2,7- and 4,9-Dialkynyldihydropyrene Molecular Switches: Syntheses, Properties, and Charge Transport in Single-Molecule Junctions.

This paper describes the syntheses of several functionalized dihydropyrene (DHP) molecular switches with different substitution patterns. Regioselective nucleophilic alkylation of a 5-substituted dimethyl isophthalate allowed the development of a workable synthetic protocol for the preparation of 2,7-alkyne-functionalized DHPs. Synthesis of DHPs with surface-anchoring groups in the 2,7- and 4,9-positions is described. The molecular structures of several intermediates and DHPs were elucidated by X-ray single-crystal diffraction. Molecular properties and switching capabilities of both types of DHPs were assessed by light irradiation experiments, spectroelectrochemistry, and cyclic voltammetry. Spectroelectrochemistry, in combination with density functional theory (DFT) calculations, shows reversible electrochemical switching from the DHP forms to the cyclophanediene (CPD) forms. Charge-transport behavior was assessed in single-molecule scanning tunneling microscope (STM) break junctions, combined with density functional theory-based quantum transport calculations. All DHPs with surface-contacting groups form stable molecular junctions. Experiments show that the molecular conductance depends on the substitution pattern of the DHP motif. The conductance was found to decrease with increasing applied bias.

Protocol for a Longitudinal Study of the Determinants of Metabolic Syndrome Risk in Young Adults.

Context: As many as 76.7% of U.S. young adults have at least one metabolic syndrome risk factor. Often undetected, metabolic syndrome risk factors cluster with other risk factors increasing risk of future cardiometabolic disease. The prevention of metabolic syndrome risk accrual through early behavioral interventions is crucial for at-risk populations. Objectives: This paper outlines the protocol for the Health E Start study, including the objectives, methodology, ethics, and dissemination. Additionally, we discuss the goals of the National Institutes of Health Research Enhancement Award (R15) that funded this project and how this funding will facilitate the comprehensive training of undergraduate researchers. The long-term goal of the study is to develop a theoretically driven intervention for the prevention of metabolic syndrome risk development in college students. To facilitate this goal, the aims are to identify 1) behavioral targets for the prevention of metabolic syndrome risk development and 2) the motivations behind such behaviors to develop a theoretical framework for use in intervention design. Design: Longitudinal observational design. Setting: Transition from living at home to independent living at colleges across the U.S. Participants: High school seniors (n = 150) who will be transitioning to college within 3 months of graduating. Main Outcome Measure: For aim 1, metabolic syndrome risk will be quantified into a risk score using a principal components analysis of traditional risk factors. Associations between changes in lifestyle behaviors and changes in the risk score will identify population-specific behavioral targets. For aim 2, changes in psychological, social, and environmental antecedents of observed behaviors will be identified. Conclusions: Identifying the relationship between behavior change and metabolic syndrome risk, and the psychosocial and environmental predictors of observed behavior changes will facilitate the design of targeted interventions for the prevention of metabolic syndrome risk progression in the early college years.