Liquid flow and control without solid walls.

When miniaturizing fluidic circuitry, the solid walls of the fluid channels become increasingly important1 because they limit the flow rates achievable for a given pressure drop, and they are prone to fouling2. Approaches for reducing the wall interactions include hydrophobic coatings3, liquid-infused porous surfaces4-6, nanoparticle surfactant jamming7, changes to surface electronic structure8, electrowetting9,10, surface tension pinning11,12 and use of atomically flat channels13. A better solution may be to avoid the solid walls altogether. Droplet microfluidics and sheath flow achieve this but require continuous flow of the central liquid and the surrounding liquid1,14. Here we demonstrate an approach in which aqueous liquid channels are surrounded by an immiscible magnetic liquid, both of which are stabilized by a quadrupolar magnetic field. This creates self-healing, non-clogging, anti-fouling and near-frictionless liquid-in-liquid fluidic channels. Manipulation of the field provides flow control, such as valving, splitting, merging and pumping. The latter is achieved by moving permanent magnets that have no physical contact with the liquid channel. We show that this magnetostaltic pumping method can be used to transport whole human blood with very little damage due to shear forces. Haemolysis (rupture of blood cells) is reduced by an order of magnitude compared with traditional peristaltic pumping, in which blood is mechanically squeezed through a plastic tube. Our liquid-in-liquid approach provides new ways to transport delicate liquids, particularly when scaling channels down to the micrometre scale, with no need for high pressures, and could also be used for microfluidic circuitry.

In situ optical spectroscopy of crystallization: One crystal nucleation at a time.

While crystallization is a ubiquitous and an important process, the microscopic picture of crystal nucleation is yet to be established. Recent studies suggest that the nucleation process can be more complex than the view offered by the classical nucleation theory. Here, we implement single crystal nucleation spectroscopy (SCNS) by combining Raman microspectroscopy and optical trapping induced crystallization to spectroscopically investigate one crystal nucleation at a time. Raman spectral evolution during a single glycine crystal nucleation from water, measured by SCNS and analyzed by a nonsupervised spectral decomposition technique, uncovered the Raman spectrum of prenucleation aggregates and their critical role as an intermediate species in the dynamics. The agreement between the spectral feature of prenucleation aggregates and our simulation suggests that their structural order emerges through the dynamic formation of linear hydrogen-bonded networks. The present work provides a strong impetus for accelerating the investigation of crystal nucleation by optical spectroscopy.

In situ/In vivo Optical Microspectroscopy to Probe the Emergence of Morphology.

Morphology governs function. Yet, understanding and controlling the emergence of morphology at the molecular level remains challenging. The difficulty in studying the early stage of morphology formation is due to its stochastic nature both spatially and temporally occurring at the nanoscale. This nature has been particularly detrimental for the application of optical spectroscopy. To overcome this problem, we have been developing new in situ/in vivo optical spectroscopy tools, which are label-free and non-invasive. This account highlights several examples of how optical spectroscopy can become an important tool in studying the birth of morphology.

Efficient Photoredox Cycles to Control Perylenediimide Self-Assembly.

Photoreduction of perylenediimide (PDI) derivatives has been widely studied for use in photocatalysis, hydrogen evolution, photo-responsive gels, and organic semiconductors. Upon light irradiation, the radical anion (PDI⋅- ) can readily be obtained, whereas further reduction to the dianion (PDI2- ) is rare. Here we show that full 2-electron photoreduction can be achieved using UVC light: 1) in anaerobic conditions by 'direct photoreduction' of PDI aggregates, or 2) by 'indirect photoreduction' in aerobic conditions due to acetone ketyl radicals. The latter strategy is also efficient for other dyes, such as naphthalenediimide (NDI) and methylviologen (MV2+ ). Efficient photoreduction on the minute time-scale using simple LED light in aerobic conditions is attractive for use in dissipative light-driven systems and materials.

Physical Frailty May Predict 2-Year Prognosis in Elderly Patients With Acute Myocardial Infarction　- A Report From the FLAGSHIP Study.

BACKGROUND: Elderly patients with acute myocardial infarction (AMI) are a high-risk population for heart failure (HF), but the association between physical frailty and worsening prognosis, including HF development, has not been documented extensively.Methods and Results: As part of the FLAGSHIP study, we enrolled 524 patients aged ≥70 years hospitalized for AMI and capable of walking at discharge. Physical frailty was assessed using the FLAGSHIP frailty score. The primary outcome was a composite outcome of all-cause death and HF rehospitalization within 2 years after discharge. The secondary outcome was all-cause death and HF rehospitalization. After adjusting for confounders, physical frailty showed a significant association with an increased risk of the composite outcome (hazard ratio [HR]=2.09, 95% confidence interval [CI]: 1.03-4.22, P=0.040). The risk of HF rehospitalization increased with physical frailty, but the association was not statistically significant (HR=2.14, 95% CI: 0.84-5.44, P=0.110). Physical frailty was not associated with an increased risk of all-cause death (HR=1.45, 95% CI: 0.49-4.26, P=0.501). CONCLUSIONS: The findings suggest that physical frailty assessment serves as a stratifying tool to identify high-risk populations for post-discharge clinical events among ambulant elderly patients with AMI.

Unveiling the Configurational Landscape of Carbamate: Paving the Way for Designing Functional Sequence-Defined Polymers.

Carbamate is an emerging class of a polymer backbone for constructing sequence-defined, abiotic polymers. It is expected that new functional materials can be de novo designed by controlling the primary polycarbamate sequence. While amino acids have been actively studied as building blocks for protein folding and peptide self-assembly, carbamates have not been widely investigated from this perspective. Here, we combined infrared (IR), vibrational circular dichroism (VCD), and nuclear magnetic resonance (NMR) spectroscopy with density functional theory (DFT) calculations to understand the conformation of carbamate monomer units in a nonpolar, aprotic environment (chloroform). Compared with amino acid building blocks, carbamates are more rigid, presumably due to the extended delocalization of π-electrons on the backbones. Cis configurations of the amide bond can be energetically stable in carbamates, whereas peptides often assume trans configurations at low energies. This study lays an essential foundation for future developments of carbamate-based sequence-defined polymer material design.

Cognitive decline assessed using a brief screening test and cardiovascular and non-cardiovascular events in older patients with heart failure.

BACKGROUND: Although cognitive decline is recognized as a prognostic factor of heart failure (HF), the association of cognitive decline with specific clinical outcomes in patients with HF remains unclear. AIM: This study examines the relationship between cognitive decline using a brief test and cardiovascular and non-cardiovascular events in older patients with HF. METHODS: This study included 146 hospitalised patients with HF (median age, 77 years; male, 56.8%). Cognitive decline was defined as a score of ≤ 9 points on the Rapid Dementia Screening Test at the time of discharge. RESULTS: Cumulative incidence of cardiovascular events after discharge was twofold higher in patients with cognitive decline (Model 1 adjusted for basic characteristics, hazard ratio (HR) = 2.01, 95% confidence interval (CI): 0.94-4.31; Model 2 adjusted for potential confounders, HR = 2.30, 95% CI: 1.07-4.97). The association between cognitive decline and non-cardiovascular events decreased after adjusting for potential confounders. CONCLUSION: The results of this study emphasize the clinical utility of cognitive assessment for risk stratification of worsening cardiovascular conditions, including HF.

Estimation of reduced walking speed using simple measurements of physical and psychophysiological function in community-dwelling elderly people: a cross-sectional and longitudinal study.

BACKGROUND: Early detection of reduced mobility function is important in elderly people. Usual walking speed is useful to assess mobility function, but is often not feasible in a community setting. AIMS: This study aimed to explore a simple surrogate indicator of usual walking speed in elderly people. METHODS: The participants were 516 community-dwelling elderly people. As a baseline survey, the usual walking speed and candidates of surrogate indicators including physical function and psychophysiological function were measured. After 2 years, the occurrence of mobility limitation was assessed. RESULTS: In cross-sectional analysis, a linear regression model with maximum step length, age, and sex presented the most favourable adjusted R2 of 0.426 for estimating usual walking speed. Maximum step length (MSL) also showed good predictive accuracy for usual walking speed < 0.8 m/s {area under the curve [AUC] 0.908 [95% confidence interval (CI) 0.811, 1.000]} and < 1.0 m/s [AUC 0.883 (95% CI) 0.832, 0.933)] in receiver-operating characteristic (ROC) analysis. In longitudinal analysis, the predictive accuracy of MSL for mobility limitation [AUC 0.813 (95% CI 0.752, 0.874)] was similar to that of usual walking speed [AUC 0.808 (95% CI 0.747, 0.869)] in ROC analysis. CONCLUSIONS AND DISCUSSION: The results of this study suggest that MSL may serve as a simple surrogate indicator of UWS in elderly people.

Development of a Self-Efficacy Questionnaire for Walking in Patients with Mild Ischemic Stroke.

PURPOSE: This study aimed to develop a self-efficacy questionnaire, which particularly focuses on walking in patients with mild ischemic stroke and transient ischemic attack. METHODS: We enrolled patients with acute ischemic stroke and transient ischemic attack who scored 0-2 on the modified Rankin Scale. The process of development of questionnaire on self-efficacy for walking with 7 items (SEW-7) was composed of 3 steps: (1) item generation; (2) item reduction; and (3) testing the final version. The measurement properties were assessed according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. RESULTS: A total of 168 patients (mean age 69.4 ± 10.1 years) were enrolled for testing the questionnaire on SEW-7. The total score of the SEW-7 ranged from 7 to 35 points. Internal consistency was acceptable with the Cronbach's alpha coefficient of .93. Test-retest reliability was good with intraclass correlation coefficient of .83 (95% confidence interval: .67-.91). The smallest detectable changes at individual and group levels were 8.0 and 1.5, respectively. The results of principal component analysis showed a single factor explaining 71.8% of the total variance. The SEW-7 questionnaire showed moderate to strong correlation with physical activity parameters (step counts: r = .596, P < .001; physical activity-related energy expenditure: r = .615, P < .001; low-intensity physical activity: r = .449, P < .001; moderate- to vigorous-intensity physical activity: r = .581, P < .001). CONCLUSIONS: We propose a simple self-report questionnaire for walking, with 7 items. The SEW-7 has adequate measurement properties and may serve as a time-saving tool for promoting physical activity in mild ischemic stroke patients.

A multicenter prospective cohort study to develop frailty-based prognostic criteria in heart failure patients (FLAGSHIP): rationale and design.

BACKGROUND: Heart failure (HF) and frailty often co-exist, and frailty in HF results in a poor prognosis. However, in Asian populations, prognostic criteria are needed to examine the effect of frailty on HF. Therefore, we conducted a nationwide cohort study to develop frailty-based prognostic criteria in HF patients (FLAGSHIP). FLAGSHIP mainly aims to 1) develop the frailty criteria based on HF-specific outcomes, 2) propose a hypothesis of the potential mechanisms of frailty manifestations in HF, and 3) examine the effects of outpatient cardiac rehabilitation on frailty. METHODS: In this prospective study, we consecutively enroll ambulatory patients admitted because of acute HF or exacerbation of HF and elderly patients admitted for acute myocardial infarction (age ≥ 70 years). They will be followed up for 2 years to assess frailty and hard clinical events. The primary endpoints of FLAGSHIP are cardiac events including cardiac mortality and HF-related readmission after discharge. Secondary endpoints are readmissions because of fracture or pneumonia and all-cause mortality. We used clinical data, including the items related to the frailty phenotype to develop diagnostic criteria for frailty and known prognostic factors of HF. Cognitive function, depression, and anorexia are also considered as potential components of frailty. As of March 2018, 2650 patients (85% was patients admitted for HF) have been registered from 30 collaborating hospitals nationwide in Japan. DISCUSSION: FLAGSHIP provides diagnostic criteria and fundamental information on frailty manifestations to develop the best practices for the long-term management of HF. Diagnostic criteria on frailty developed by FLAGSHIP is expected to become a novel indicator for the stratification of patients at risk to functional decline after medical or surgical treatment, and in turn to contribute to the best practices in the long-term management of HF.

Versatile and Resilient Hydrogen-Bonded Host Frameworks.

Low-density molecular host frameworks, whether equipped with persistent molecular-scale pores or virtual pores that are sustainable only when occupied by guest molecules, have emerged as a promising class of materials owing to the ability to tailor the size, geometry, and chemical character of their free space through the versatility of organic synthesis. As such, molecular frameworks are promising candidates for storage, separations of commodity and fine chemicals, heterogeneous catalysis, and optical and electronic materials. Frameworks assembled through hydrogen bonds, though generally not stable toward collapse in the absence of guests, promise significant chemical and structural diversity, with pores that can be tailored for a wide range of guest molecules. The utility of these frameworks, however, depends on the resilience of n-dimensional hydrogen-bonded motifs that serve as reliable building blocks so that the molecular constituents can be manipulated without disruption of the anticipated global solid-state architecture. Though many hydrogen-bonded frameworks have been reported, few exist that are amenable to systematic modification, thus limiting the design of functional materials. This Account reviews discoveries in our laboratory during the past decade related to a series of host frameworks based on guanidinium cations and interchangeable organosulfonate anions, in which the 3-fold symmetry and hydrogen-bonding complementarity of these ions prompt the formation of a two-dimensional (2-D) quasi-hexagonal hydrogen-bonding network that has proven to be remarkably resilient toward the introduction of a wide range of organic pendant groups attached to the sulfonate. Since an earlier report in this journal that focused primarily on organodisulfonate host frameworks with lamellar architectures, this unusually persistent network has afforded an unparalleled range of framework architectures and hundreds of new crystalline materials with predictable solid-state architectures. These range from the surprising discovery of inclusion compounds in organomonosulfonates (GMS), as well as organodisulfonates (GDS), structural isomerism reminiscent of microstructures observed in soft matter, a retrosynthetic approach to the synthesis of polar crystals, separation of molecular isomers, storage of unstable molecules, formation of a zeolite-like hydrogen-bonded framework, and postsynthetic pathways to inclusion compounds through reversible guest swapping in flexible GS frameworks. Collectively, the examples described in this Account illustrate the potential for hydrogen-bonded frameworks in the design of molecular materials, the prediction of solid-state architecture from simple empirical parameters, and the importance of design principles based on robust high dimensional networks. These and other emerging hydrogen-bonded frameworks promise new advanced materials that capitalize fully on the ability of materials chemists to manipulate solid-state structure through molecular design.

Guiding microscale swimmers using teardrop-shaped posts.

The swimming direction of biological or artificial microscale swimmers tends to be randomised over long time-scales by thermal fluctuations. Bacteria use various strategies to bias swimming behaviour and achieve directed motion against a flow, maintain alignment with gravity or travel up a chemical gradient. Herein, we explore a purely geometric means of biasing the motion of artificial nanorod swimmers. These artificial swimmers are bimetallic rods, powered by a chemical fuel, which swim on a substrate printed with teardrop-shaped posts. The artificial swimmers are hydrodynamically attracted to the posts, swimming alongside the post perimeter for long times before leaving. The rods experience a higher rate of departure from the higher curvature end of the teardrop shape, thereby introducing a bias into their motion. This bias increases with swimming speed and can be translated into a macroscopic directional motion over long times by using arrays of teardrop-shaped posts aligned along a single direction. This method provides a protocol for concentrating swimmers, sorting swimmers according to different speeds, and could enable artificial swimmers to transport cargo to desired locations.

Encapsulation of Isolated Luminophores within Supramolecular Cages.

The sequestration of luminophores within supramolecular polyhedral compartments of a crystalline zeolite-like hydrogen-bonded framework illustrates a unique approach to limiting the self-quenching ordinarily exhibited at the high concentrations achievable in this framework. A range of differently sized luminescent guests, namely coumarin 1, coumarin 4, fluorescein, [Ru(bpy)3 ]Cl2 , and rhodamine B, can be encapsulated in amounts of up to one molecule per cage, equivalent to a concentration of 0.175 m, which is significantly higher than the concentration at which aggregation-induced quenching occurs in other media. The luminescence spectra of the encapsulated guests are consistent with the presence of isolated monomers and the absence of self-quenching. The emission color of the single crystals can be tuned readily from blue to red through the choice of guest molecules. These observations promise an approach to organic solid-state lasing compounds if crystals of sufficient size and quality can be prepared.

Dynamic self-assembly of microscale rotors and swimmers.

Biological systems often involve the self-assembly of basic components into complex and functioning structures. Artificial systems that mimic such processes can provide a well-controlled setting to explore the principles involved and also synthesize useful micromachines. Our experiments show that immotile, but active, components self-assemble into two types of structure that exhibit the fundamental forms of motility: translation and rotation. Specifically, micron-scale metallic rods are designed to induce extensile surface flows in the presence of a chemical fuel; these rods interact with each other and pair up to form either a swimmer or a rotor. Such pairs can transition reversibly between these two configurations, leading to kinetics reminiscent of bacterial run-and-tumble motion.

Unraveling the chromophoric disorder of poly(3-hexylthiophene).

The spectral breadth of conjugated polymers gives these materials a clear advantage over other molecular compounds for organic photovoltaic applications and is a key factor in recent efficiencies topping 10%. However, why do excitonic transitions, which are inherently narrow, lead to absorption over such a broad range of wavelengths in the first place? Using single-molecule spectroscopy, we address this fundamental question in a model material, poly(3-hexylthiophene). Narrow zero-phonon lines from single chromophores are found to scatter over 200 nm, an unprecedented inhomogeneous broadening that maps the ensemble. The giant red shift between solution and bulk films arises from energy transfer to the lowest-energy chromophores in collapsed polymer chains that adopt a highly ordered morphology. We propose that the extreme energetic disorder of chromophores is structural in origin. This structural disorder on the single-chromophore level may actually enable the high degree of polymer chain ordering found in bulk films: both structural order and disorder are crucial to materials physics in devices.

Excitonic energy migration in conjugated polymers: the critical role of interchain morphology.

Excitonic energy migration was studied using single molecule spectroscopy of individual conjugated polymer (CP) chains and aggregates. To probe the effect of interchain morphology on energy migration in CP, tailored interchain morphologies were achieved using solvent vapor annealing to construct polymer aggregates, which were then studied with single aggregate spectroscopy. We report that highly ordered interchain packing in regioregular poly(3-hexylthiophene) (rr-P3HT) enables long-range interchain energy migration, while disordered packing in regiorandom poly(3-hexylthiophene) (rra-P3HT), even in aggregates of just a few chains, can dramatically impede the interchain mechanism. In contrast to rr-P3HT, interchain energy migration in poly(3-(2'-methoxy-5'-octylphenyl)thiophene) (POMeOPT), a polythiophene derivative with bulky side chains, can be completely inhibited. We use simulated structures to show that the reduction in interchain coupling is not due simply to increased packing distance between backbones of different chains, but reflects inhibition of stacking due to side-chain-induced twisting of the contours of individual chains. A competition from intrachain coupling has also been demonstrated by comparing POMeOPT aggregates with different polymer chain sizes.

Association of Nutritional Risk With Gait Function and Activities of Daily Living in Older Adult Patients With Hip Fractures.

OBJECTIVE: To investigate the association of nutritional risk with gait function and activities of daily living (ADLs) in older adult patients with hip fractures. METHODS: The retrospective data of older adult patients diagnosed with hip fractures who visited the recovery-phase rehabilitation ward between January 2019 and December 2022 were reviewed. Nutritional risk was evaluated using the Geriatric Nutritional Risk Index; gait function and ADLs were assessed using the modified Harris Hip Score subitem and Functional Independence Measure, respectively. Multivariate linear regression and path analysis with structural equation modeling were used to examine the factors associated with ADLs and the associations among the study variables. RESULTS: This study included 206 participants (172 females and 34 males; mean age, 85.0±7.3 years). In the multivariate analysis, gait function (ß=0.488, p<0.001), cognitive function (ß=0.430, p<0.001), and surgery (ß=-0.143, p<0.001) were identified as independent factors. Pathway analysis revealed that nutritional risk was not directly correlated with ADLs but was directly associated with gait and cognitive functions. Gait and cognitive functions, in turn, were directly related to ADLs. CONCLUSION: Nutritional risk was found to be associated with ADLs through an intermediary of gait and cognitive functions.