F-actin architecture determines the conversion of chemical energy into mechanical work.

Mechanical work serves as the foundation for dynamic cellular processes, ranging from cell division to migration. A fundamental driver of cellular mechanical work is the actin cytoskeleton, composed of filamentous actin (F-actin) and myosin motors, where force generation relies on adenosine triphosphate (ATP) hydrolysis. F-actin architectures, whether bundled by crosslinkers or branched via nucleators, have emerged as pivotal regulators of myosin II force generation. However, it remains unclear how distinct F-actin architectures impact the conversion of chemical energy to mechanical work. Here, we employ in vitro reconstitution of distinct F-actin architectures with purified components to investigate their influence on myosin ATP hydrolysis (consumption). We find that F-actin bundles composed of mixed polarity F-actin hinder network contraction compared to non-crosslinked network and dramatically decelerate ATP consumption rates. Conversely, linear-nucleated networks allow network contraction despite reducing ATP consumption rates. Surprisingly, branched-nucleated networks facilitate high ATP consumption without significant network contraction, suggesting that the branched network dissipates energy without performing work. This study establishes a link between F-actin architecture and myosin energy consumption, elucidating the energetic principles underlying F-actin structure formation and the performance of mechanical work.

Enhanced hydrogen uptake of dihydrogen complex via porous materials support.

This research focuses on enhancing H2 adsorption by using the [Mo(PCy3)2(CO)3] complex supported on porous materials such as silica gel and mesoporous carbon. The study reports a significant increase in hydrogen adsorption capacity, reaching up to 9.3 times that of the bulk complex. This improvement suggests that using mesoporous materials as supports for the [Mo(PCy3)2(CO)3] complex enhances the accessibility of H2 gas to its open-metal sites.

Association of decreased frequency of conversation with depression, oral function and eating alone: A cross-sectional study of older adults during the COVID-19 pandemic.

AIM: This study examined the associations between geriatric factors and decreased opportunities for conversation among older adults amid a period of self-restraint during the COVID-19 pandemic. METHODS: A cross-sectional questionnaire-based survey was carried out in October 2020. The participants were 204 residents aged ≥65 years staying at a private care home in Kyoto city, Japan. Logistic regression analysis was carried out with the reduction of conversation opportunities as the dependent variable, and geriatric factors as independent variables after adjusting for age and sex. We compared the decreased frequency of opportunities between residents in the assisted living wing and in the nursing care wing of the private care home. RESULTS: The percentages of respondents who reported a decrease in the opportunities for conversation among themselves were 43.9% for residents in the assisted living wing and 19.7% for those in the nursing care wing. After adjusting for age and sex, the opportunities for conversation was significantly associated with the basic activities of daily living (OR 1.07, 95% CI 1.01-1.12), instrumental self-maintenance (OR 1.25, 95% CI 1.08-1.46), intellectual activity (OR 1.35, 95% CI 1.09-1.66), depression (OR 1.13, 95% CI 1.04-1.23), depressive mood (OR 3.83, 95% CI 1.98-7.42), decreased motivation (OR 3.11, 95% CI 1.58-6.12), appetite loss (OR 4.32, 95% CI 1.54-12.07), swallowing function (OR 1.05, 95% CI 1.00-1.10), chewing difficulty (OR 2.50, 95% CI 1.31-4.75) and eating alone (OR 2.5, 95% CI 1.35-4.62). CONCLUSION: Decreased opportunities for conversation was more perceived among older adults with higher daily functioning, suggesting that it is associated with depressed mood, oral function and solitary eating. Geriatr Gerontol Int 2024; 24: 385-391.

Unveiling the physics underlying symmetry breaking of the actin cytoskeleton: An artificial cell-based approach.

Single-cell behaviors cover many biological functions, such as cell division during morphogenesis and tissue metastasis, and cell migration during cancer cell invasion and immune cell responses. Symmetry breaking of the positioning of organelles and the cell shape are often associated with these biological functions. One of the main players in symmetry breaking at the cellular scale is the actin cytoskeleton, comprising actin filaments and myosin motors that generate contractile forces. However, because the self-organization of the actomyosin network is regulated by the biochemical signaling in cells, how the mechanical contraction of the actin cytoskeleton induces diverse self-organized behaviors and drives the cell-scale symmetry breaking remains unclear. In recent times, to understand the physical underpinnings of the symmetry breaking exhibited in the actin cytoskeleton, artificial cell models encapsulating the cytoplasmic actomyosin networks covered with lipid monolayers have been developed. By decoupling the actomyosin mechanics from the complex biochemical signaling within living cells, this system allows one to study the self-organization of actomyosin networks confined in cell-sized spaces. We review the recent developments in the physics of confined actomyosin networks and provide future perspectives on the artificial cell-based approach. This review article is an extended version of the Japanese article, The Physical Principle of Cell Migration Under Confinement: Artificial Cell-based Bottom-up Approach, published in SEIBUTSU BUTSURI Vol. 63, p. 163-164 (2023).

Effect of an Internet-Delivered Cognitive Behavioral Therapy-Based Sleep Improvement App for Shift Workers at High Risk of Sleep Disorder: Single-Arm, Nonrandomized Trial.

BACKGROUND: Shift workers are at high risk of developing sleep disorders such as shift worker sleep disorder or chronic insomnia. Cognitive behavioral therapy (CBT) is the first-line treatment for insomnia, and emerging evidence shows that internet-based CBT is highly effective with additional features such as continuous tracking and personalization. However, there are limited studies on internet-based CBT for shift workers with sleep disorders. OBJECTIVE: This study aimed to evaluate the impact of a 4-week, physician-assisted, internet-delivered CBT program incorporating machine learning-based well-being prediction on the sleep duration of shift workers at high risk of sleep disorders. We evaluated these outcomes using an internet-delivered CBT app and fitness trackers in the intensive care unit. METHODS: A convenience sample of 61 shift workers (mean age 32.9, SD 8.3 years) from the intensive care unit or emergency department participated in the study. Eligible participants were on a 3-shift schedule and had a Pittsburgh Sleep Quality Index score ≥5. The study comprised a 1-week baseline period, followed by a 4-week intervention period. Before the study, the participants completed questionnaires regarding the subjective evaluation of sleep, burnout syndrome, and mental health. Participants were asked to wear a commercial fitness tracker to track their daily activities, heart rate, and sleep for 5 weeks. The internet-delivered CBT program included well-being prediction, activity and sleep chart, and sleep advice. A job-based multitask and multilabel convolutional neural network-based model was used for well-being prediction. Participant-specific sleep advice was provided by sleep physicians based on daily surveys and fitness tracker data. The primary end point of this study was sleep duration. For continuous measurements (sleep duration, steps, etc), the mean baseline and week-4 intervention data were compared. The 2-tailed paired t test or Wilcoxon signed rank test was performed depending on the distribution of the data. RESULTS: In the fourth week of intervention, the mean daily sleep duration for 7 days (6.06, SD 1.30 hours) showed a statistically significant increase compared with the baseline (5.54, SD 1.36 hours; P=.02). Subjective sleep quality, as measured by the Pittsburgh Sleep Quality Index, also showed statistically significant improvement from baseline (9.10) to after the intervention (7.84; P=.001). However, no significant improvement was found in the subjective well-being scores (all P>.05). Feature importance analysis for all 45 variables in the prediction model showed that sleep duration had the highest importance. CONCLUSIONS: The physician-assisted internet-delivered CBT program targeting shift workers with a high risk of sleep disorders showed a statistically significant increase in sleep duration as measured by wearable sensors along with subjective sleep quality. This study shows that sleep improvement programs using an app and wearable sensors are feasible and may play an important role in preventing shift work-related sleep disorders. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/24799.

Differential Metabolic Stability of 4α,25- and 4ß,25-Dihydroxyvitamin D3 and Identification of Their Metabolites.

Vitamin D3 (1) is metabolized by various cytochrome P450 (CYP) enzymes, resulting in the formation of diverse metabolites. Among them, 4α,25-dihydroxyvitamin D3 (6a) and 4ß,25-dihydroxyvitamin D3 (6b) are both produced from 25-hydroxyvitamin D3 (2) by CYP3A4. However, 6b is detectable in serum, whereas 6a is not. We hypothesized that the reason for this is a difference in the susceptibility of 6a and 6b to CYP24A1-mediated metabolism. Here, we synthesized 6a and 6b, and confirmed that 6b has greater metabolic stability than 6a. We also identified 4α,24R,25- and 4ß,24R,25-trihydroxyvitamin D3 (16a and 16b) as metabolites of 6a and 6b, respectively, by HPLC comparison with synthesized authentic samples. Docking studies suggest that the ß-hydroxy group at C4 contributes to the greater metabolic stability of 6b by blocking a crucial hydrogen-bonding interaction between the C25 hydroxy group and Leu325 of CYP24A1.

Single-Crystal Structures of Benzenehexathiol and Its Disulfide Forms.

Oligothiols are useful as building blocks in the construction of disulfide-based macrocycles and polymers or as ligands for coordination polymers. Above all, benzenehexathiol (BHT) is a particularly important molecule, as it is used to construct conductive two-dimensional MOFs. Despite the desire to clarify its structure and isolate it to high purity, the chemical instability of BHT has hampered single-crystal X-ray structure analysis of intact BHT. In addition, the synthesis of discrete disulfide molecules of BHT has not been reported. Here, we succeed in obtaining the single crystals of intact BHT, which is analyzed by single crystal X-ray structure analysis. Furthermore, the structures of a group of molecules with intermolecular disulfide bonds (BHT·4im and BHT2·2TBA, im = imidazole, TBA = tetrabutylammonium cation) obtained by processing BHT in the presence of bases are determined.

Quinoid-Based Three-Dimensional Metal-Organic Framework Fe2(dhbq)3: Porosity, Electrical Conductivity, and Solid-State Redox Properties.

We report the synthesis, characterization, and electronic properties of the quinoid-based three-dimensional metal-organic framework [Fe2(dhbq)3]. The MOF was synthesized without using cations as a template, unlike other reported X2dhbq3-based coordination polymers, and the crystal structure was determined by using single-crystal X-ray diffraction. The crystal structure was entirely different from the other reported [Fe2(X2dhbq3)]2-; three independent 3D polymers were interpenetrated to give the overall structure. The absence of cations led to a microporous structure, investigated by N2 adsorption isotherms. Temperature dependence of electrical conductivity data revealed that it exhibited a relatively high electrical conductivity of 1.2 × 10-2 S cm-1 (Ea = 212 meV) due to extended d-π conjugation in a three-dimensional network. Thermoelectromotive force measurement revealed that it is an n-type semiconductor with electrons as the majority of charge carriers. Structural characterization and spectroscopic analyses, including SXRD, Mössbauer, UV-vis-NIR, IR, and XANES measurements, evidenced the occurrence of no mixed valency based on the metal and the ligand. [Fe2(dhbq)3] upon incorporating as a cathode material for lithium-ion batteries engendered an initial discharge capacity of 322 mAh/g.

Membrane tension induces F-actin reorganization and flow in a biomimetic model cortex.

The accumulation and transmission of mechanical stresses in the cell cortex and membrane determines the mechanics of cell shape and coordinates essential physical behaviors, from cell polarization to cell migration. However, the extent that the membrane and cytoskeleton each contribute to the transmission of mechanical stresses to coordinate diverse behaviors is unclear. Here, we reconstitute a minimal model of the actomyosin cortex within liposomes that adheres, spreads and ultimately ruptures on a surface. During spreading, accumulated adhesion-induced (passive) stresses within the membrane drive changes in the spatial assembly of actin. By contrast, during rupture, accumulated myosin-induced (active) stresses within the cortex determine the rate of pore opening. Thus, in the same system, devoid of biochemical regulation, the membrane and cortex can each play a passive or active role in the generation and transmission of mechanical stress, and their relative roles drive diverse biomimetic physical behaviors.

Association between glucose tolerance and mortality among Japanese community-dwelling older adults aged over 75 years: 12-year observation of the Tosa Longitudinal Aging Study.

AIM: Although the relationship between impaired glucose tolerance (IGT) and mortality has been investigated in diverse populations, few studies have focused on older populations. This study aimed to investigate the relationship between glucose tolerance and overall mortality among populations aged ≥75 years. METHODS: Data were obtained from the Tosa Longitudinal Aging Study, a community-based cohort survey conducted in Kochi, Japan. According to the results of a 75-g oral glucose tolerance test conducted in 2006, the participants were classified into four categories: normal glucose tolerance (NGT), impaired fasting glucose (IFG)/IGT, newly diagnosed diabetes mellitus (NDM), and known diabetes mellitus (KDM). The primary endpoint was overall mortality. Differences in overall mortality among the four categories were evaluated using the Cox proportional hazards model. RESULTS: During a median of 11.5 years of observation, 125 deaths of the 260 enrolled participants were recorded. The cumulative overall survival rate was 0.52, and the survival rates of NGT, IFG/IGT, NDM, and KDM were 0.48, 0.49, 0.49, and 0.25, respectively (log-rank test, P = 0.139). Adjusted hazard ratios (HRs) for mortality in the IFG/IGT and NDM groups compared with the NGT group were 1.02 (95% confidence interval [CI], 0.66-1.58) and 1.11 (95% CI, 0.56-2.22), while mortality in the KDM group was significantly higher than that in the NGT group (HR, 2.43; 95% CI, 1.35-4.37). CONCLUSION: Mortality did not differ significantly between the IFG/IGT, NDM, and NGT groups, but was higher in the KDM group than in the NGT group. Geriatr Gerontol Int 2023; 23: 341-347.

Innovation in Digital Health Interventions for Frailty and Sarcopenia.

Today, the challenges of an aging society are primarily seen in frailty, sarcopenia, and impaired functionality [...].

A 1,3-boron shift reaction of homoallenylboronates to synthesise 2-boryl-1,3-dienes.

We describe a 1,3-boron shift-type reaction of homoallenylboronates at the center (sp) carbon in allenes to afford 2-boryl-1,3-dienes with a variety of substituents. Notably, this reaction occurs in situ with allenylboronates in the presence of carbamate and a small excess of sec-BuLi, and it is not necessary to isolate the unstable homoallenylboronates.

Observation of slow magnetic relaxation phenomena in spatially isolated π-radical ions.

The use of molecular spins as quantum bits is fascinating because it offers a wide range of strategies through chemical modifications. In this regard, it is very interesting to search for organic radical ions that have small spin-orbit coupling values. On the other hand, the feature of the magnetic relaxation of π-organic radical ions is rarely exploited due to the difficulty of spin dilution, and π-stacking interaction. In this study, we focus on N,N',N''-tris(2,6-dimethylphenyl)benzenetriimide (BTI-xy), where three xylene moieties connected to the imide groups cover the π-plane of the BTI core. As a result, BTI-xy radical anions without π-stacking interaction were obtained. This led to the slow magnetization relaxation, which is reported for the first time in organic radicals. Furthermore, the relaxation times in a solution state revealed the importance of spin interaction.

Periodontal status is associated with oral function in community-dwelling older adults, independent of dentition status.

OBJECTIVE: To determine whether periodontal status is associated with oral function, including masticatory performance and occlusal force, among community-dwelling older adults. BACKGROUND: Although a potential association between periodontal status and oral function has been reported, variations in the root surface area (RSA) of each tooth have not been considered. METHODS: We used data from a population-based study involving community-dwelling older adults. The RSA with periodontal ligament (RSA-PL), which quantifies the RSA attached to the periodontal ligament and alveolar bone, was calculated based on full-mouth periodontal examination. Masticatory performance was assessed using spectrophotometric measurement of the color (a* value) of color-changing chewing gum. The bilateral maximal occlusal force (MOF) was measured using a pressure-sensitive sheet and dedicated software. The associations of the RSA-PL, a quantitative marker of periodontal tissue support, with the a* value and MOF were assessed using linear regression models. RESULTS: The analyses included data from 250 adults [60.8% women; age, mean (standard deviation) 82.5 (5.0) years]. On average, the study participants had an RSA-PL of 26.3 cm2 , a* value of 25.0, and an MOF value of 555.1 N. After adjustments for potential confounders, including dentition status, age, sex, dental visit regularity, smoking status, physical activity level, depressive symptoms, a history of stroke or diabetes mellitus, and body mass index, the RSA-PL was found to be associated with the a* value [coefficient (per 1 cm2 increase): 0.16, 95% confidence interval (CI) 0.10-0.22)] and MOF (coefficient: 9.2, 95% CI 5.3-13.1). CONCLUSION: This study demonstrated that greater amounts of remaining tooth-supporting structures, indicated by higher RSA-PL values, were associated with better masticatory performance and a higher occlusal force among community-dwelling older adults.

Social and behavioral factors related to blood pressure measurement: A cross-sectional study in Bhutan.

Cardiovascular disease is a leading cause of death in the Kingdom of Bhutan, and early detection of hypertension is critical for preventing cardiovascular disease. However, health-seeking behavior, including blood pressure measurement, is infrequently investigated in Bhutan. Therefore, this study investigated factors related to blood pressure measurement in Bhutan. We performed a secondary data analysis of a target population of 1,962 individuals using data from the "2014 Bhutan STEPS survey data"as a cross-sectional study. Approximately 26% of those with hypertension who were detected during the STEPS survey had never had their blood pressure measured. Previous blood pressure measurement was significantly associated with age and working status in men (self-employed [odds ratio (OR): 0.219, 95% CI: 0.133-0.361], non-working [OR: 0.114, 95% CI: 0.050-0.263], employee [OR: 1.000]). Previous blood pressure measurement was significantly associated with higher income in women (Quartile-2 [OR: 1.984, 95% CI: 1.209-3.255], Quartile-1 [OR: 2.161, 95% CI: 1.415-3.299], Quartile-4 [OR: 1.000]). A family history of hypertension (OR: 2.019, 95% CI: 1.549-2.243) increased the likelihood of having experienced a blood pressure measurement in both men and women. Multivariate logistic regression showed that people with unhealthy lifestyles (high salt intake [adjusted odds ratio (AOR): 0.247, 95% confidence interval (CI): 0.068-0.893], tobacco use [AOR: 0.538, 95% CI: 0.380-0.761]) had a decreased likelihood of previous blood pressure measurement. To promote the early detection of hypertension in Bhutan, we suggest that more attention be paid to low-income women, non-working, self-employed, and low-income men, and a reduction of barriers to blood pressure measurement. Before the STEPS survey, a substantial number of hypertensive people had never had their blood pressure measured or were unconcerned about their health. As a result, we propose that early blood pressure monitoring and treatment for people with hypertension or at higher risk of hypertension be given increased emphasis.

Geometric trade-off between contractile force and viscous drag determines the actomyosin-based motility of a cell-sized droplet.

Cell migration in confined environments is fundamental for diverse biological processes from cancer invasion to leukocyte trafficking. The cell body is propelled by the contractile force of actomyosin networks transmitted from the cell membrane to the external substrates. However, physical determinants of actomyosin-based migration capacity in confined environments are not fully understood. Here, we develop an in vitro migratory cell model, where cytoplasmic actomyosin networks are encapsulated into droplets surrounded by a lipid monolayer membrane. We find that the droplet can move when the actomyosin networks are bound to the membrane, in which the physical interaction between the contracting actomyosin networks and the membrane generates a propulsive force. The droplet moves faster when it has a larger contact area with the substrates, while narrower confinement reduces the migration speed. By combining experimental observations and active gel theory, we propose a mechanism where the balance between sliding friction force, which is a reaction force of the contractile force, and viscous drag determines the migration speed, providing a physical basis of actomyosin-based motility in confined environments.

Older adults' preferences for and actual situations of artificial hydration and nutrition in end-of-life care: An 11-year follow-up study in a care home.

AIM: To clarify older adults' preferences for and actual situations of artificial hydration and nutrition (AHN) in end-of-life care in a care home. METHODS: Participants were residents of a care home who had completed advance directives regarding preferred methods of AHN from 2009 to 2018. Advance directives alone were available from April 2009 to June 2016 (Wave 1), and advance care planning for AHN including advance directives was introduced in July 2016 (Wave 2). AHN preferences included (i) intensive methods (percutaneous endoscopic gastrostomy, nasogastric tube feeding and total parenteral nutrition), (ii) drip infusion, and (iii) oral intake only. Participants were followed until the end of 2020, and we checked whether decisions about AHN were based on older adults' preferences. RESULTS: In total, 272 participants had completed advance directives. Most participants preferred "oral intake only" (59.5%), followed by drip infusion (32.0%) and intensive methods (8.5%) in advance directives. Ninety of the 272 participants completed advance directives twice; 83.3% did not change their AHN preferences from Wave 1 to Wave 2. By the end of 2020, 93 of the 272 participants died in the care home. AHN was provided according to older adults' preferences in 48.9% (oral intake only), in 51.4% (drip infusion) and in 55.6% (intensive methods) of cases respectively. CONCLUSIONS: Most participants preferred oral intake only, and their preferences were reflected in decisions about actual situations of AHN in end-of-life care. To prepare for advanced dementia and senility, early advance care planning for AHN should be promoted. Geriatr Gerontol Int 2022; 22: 581-587.

Stereodivergent Synthesis of 1,3-Dienes via Protodeboronation of Homoallenylboronic Esters.

Vinylboronic esters and allylboronic esters are well known to afford olefins by protodeboronation, and therefore homoallenylboronic esters should be similarly available as precursors for 1,3-dienes, but this strategy has not been well explored due to the limited availability of homoallenylboronic esters. Here, we describe a versatile synthesis of homoallenylboronic esters via lithiation-borylation and subsequent 1,2-rearrangement. The resulting homoallenylboronic esters were successfully converted into Z- and E-1,3-dienes by protodeboronation using Bu4NF and B(C6F5)3/PhOH, respectively.