Associations of Dynapenic Abdominal Obesity and Frailty Progression: Evidence from Two Nationwide Cohorts.

The associations of dynapenic abdominal obesity and transitions with frailty progression remain unclear among middle-aged and older adults. We included 6937 participants from the China Health and Retirement Longitudinal Study (CHARLS) and 3735 from the English Longitudinal Study of Aging (ELSA). Participants were divided into non-dynapenia and non-abdominal obesity (ND/NAO), abdominal obesity alone (AO), dynapenia alone (D), and dynapenic abdominal obesity (D/AO). Frailty status was assessed by the frailty index (FI), and a linear mixed-effect model was employed to analyze the associations of D, AO, D/AO, and transitions with frailty progression. Participants with AO, D, and D/AO had increased FI progression compared with ND/NAO in both cohorts. D/AO possessed the greatest additional annual FI increase of 0.383 (95% CI: 0.152 to 0.614), followed by D and AO in the CHARLS. Participants with D in the ELSA had the greatest magnitude of accelerated FI progression. Participants who transitioned from ND/NAO to D and from AO to D/AO presented accelerated FI progression in the CHARLS and ELSA. In conclusion, dynapenic abdominal obesity, especially for D/AO and D, presented accelerated frailty progression. Our findings highlighted the essential intervention targets of dynapenia and abdominal obesity for the prevention of frailty progression.

Therapeutic Supramolecular Polymers: Designs and Applications.

The self-assembly of low-molecular-weight building motifs into supramolecular polymers has unlocked a new realm of materials with distinct properties and tremendous potential for advancing medical practices. Leveraging the reversible and dynamic nature of non-covalent interactions, these supramolecular polymers exhibit inherent responsiveness to their microenvironment, physiological cues, and biomolecular signals, making them uniquely suited for diverse biomedical applications. In this review, we intend to explore the principles of design, synthesis methodologies, and strategic developments that underlie the creation of supramolecular polymers as carriers for therapeutics, contributing to the treatment and prevention of a spectrum of human diseases. We delve into the principles underlying monomer design, emphasizing the pivotal role of non-covalent interactions, directionality, and reversibility. Moreover, we explore the intricate balance between thermodynamics and kinetics in supramolecular polymerization, illuminating strategies for achieving controlled sizes and distributions. Categorically, we examine their exciting biomedical applications: individual polymers as discrete carriers for therapeutics, delving into their interactions with cells, and in vivo dynamics; and supramolecular polymeric hydrogels as injectable depots, with a focus on their roles in cancer immunotherapy, sustained drug release, and regenerative medicine. As the field continues to burgeon, harnessing the unique attributes of therapeutic supramolecular polymers holds the promise of transformative impacts across the biomedical landscape.

Sarcopenia Transitions and Influencing Factors Among Chinese Older Adults With Multistate Markov Model.

Background and Objectives: Little is known about the sarcopenia transition process across different stages among Chinese community-dwelling older adults. We aimed to explore dynamic transitions of sarcopenia and its influencing factors in Chinese older adults. Research Design and Methods: Data were derived from the China Health and Retirement Longitudinal Study. A total of 2856 older adults with complete data in the 2011, 2013, and 2015 waves were included in our study. Participants were categorized into 3 states: no sarcopenia, possible sarcopenia, and sarcopenia according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria. Continuous-time multistate Markov model was performed to estimate the 1-year transition probabilities and the associated factors of sarcopenia transitions. The association strength was expressed as hazard ratio and 95% confidence interval. Results: The progression and reversion rates between no sarcopenia and sarcopenia state were 6.01 and 9.20 per 100 person-years, respectively. The 1-year progression probability to possible sarcopenia was higher compared with the likelihood of moving to the sarcopenia state (0.127 vs 0.034). The reversion probability to no sarcopenia was also higher among those with possible sarcopenia (0.281 vs 0.157). Older age, rural living, worse cognition status, higher chronic disease numbers, and lower nutrition status measured by body mass index accelerated the sarcopenia progression. Cognition status and body mass index level were related to higher chances of reverting. Discussion and Implications: Possible sarcopenia might be a critical time window to promote sarcopenia reversion. Timely interventions aimed at delaying the progression and facilitating sarcopenia recovery should focus on improving cognitive function and nutrition levels.

Associations of types of grains and lifestyle with all-cause mortality among Chinese adults aged 65 years or older: a prospective cohort study.

BACKGROUND: Little is known on the association of types of grains with mortality and the moderating effect of lifestyle on this association. This study aims to evaluate the single or joint associations of types of grains and lifestyle with all-cause mortality among Chinese older adults. METHODS: Data were derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2018. Subjects aged ≥ 65 years were eligible. The types of grains included wheat, total rice, and coarse cereals. Lifestyle was derived using smoking, alcohol consumption, physical activity, and dietary pattern. All-cause mortality was the primary outcome. RESULTS: This study included 30275 participants with a mean age 87 ± 11 years and documented 19261 deaths during a mean follow-up of 4.8 years. Compared to wheat, in those with healthy and intermediate lifestyle, total rice was associated with a 13% (HR: 0.87, 95% CI 0.80, 0.93) and 6% (HR: 0.94, 95% CI 0.90, 1.00) lower risk of mortality, respectively, and coarse cereals were associated with a 14% (HR: 0.86, 95% CI 0.74, 1.00) and 12% (HR: 0.88, 95% CI 0.79, 0.97) lower risk of mortality, respectively. Meanwhile, an increase per SD in intakes of wheat and coarse cereals was associated with a 10% (HR: 1.10, 95% CI 1.03, 1.18) and 25% (HR: 1.25, 95% CI 1.08, 1.44) higher mortality rate in those with healthy lifestyle, and a 13% (HR: 1.13, 95% CI 1.08, 1.19) and 29% (HR: 1.29, 95% CI 1.17, 1.44) higher mortality in females but not males. In addition, a U-shaped association of intake of total grains with all- cause mortality was observed (P for non-linearity = 0.002), and a J-shaped association of intake of total rice with all- cause mortality was observed (P for non-linearity = 0.003). CONCLUSIONS: Specific types of grains and lifestyle were separately or jointly associated with all-cause mortality. Compared to wheat, total rice and coarse cereals were advanced grains for participants with a relatively healthy lifestyle. Intake of total rice was related to all-cause mortality in a dose-response manner. Therefore, a combination of intermediate intake of total rice and healthy lifestyle should be encouraged in older adults.

Associations of follicle-stimulating hormone and luteinizing hormone with metabolic syndrome during the menopausal transition from the National Health and Nutrition Examination Survey.

Background: The increased risk of metabolic syndrome (MetS) during the menopausal transition might partly attribute to the changes in follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, few studies were conducted to examine the associations of FSH and LH concentrations with MetS at the full range of reproductive aging, especially in the US population. The aim of this study is to examine the associations of FSH, LH, and LH/FSH ratio with the risk of MetS and severity score in the US women. Methods: Data were derived from the National Health and Nutrition Examination Survey. Women aged from 35 to 60 years were eligible. MetS was defined as having at least 3 of the following: a waist circumference ≥ 88 cm, a triglycerides level ≥ 150 mg/dL, a high density lipoprotein < 50 mg/dL, a systolic blood pressure ≥ 130 mm Hg or a diastolic blood pressure ≥ 85 mm Hg or taking hypertension medications, or a fasting plasma glucose level ≥100 mg/dL or taking diabetes medications. The MetS severity score was calculated according to race/ethnicity- specific equation. Results: There were 3,831 women included in this study. Increases in serum FSH and LH levels per 1 SD were separately linked to a 22.6% (OR: 0.774; 95% CI: 0.646, 0.929; and P= 0.006) and 18.5% (OR: 0.815; 95% CI: 0.690, 0.962; and P= 0.006) lower risk of MetS only in postmenopausal women. Meanwhile, increases in serum FSH and LH levels per 1SD were associated with a decrease of -0.157 (95% CI :-2.967, -2.034) and -0.078 (95% CI: -2.688, -1.806) MetS severity score in perimenopausal women and -0.195 (95% CI: -2.192, -1.023) and -0.098 (95% CI:-1.884, -0.733) in postmenopausal women. However, LH/FSH ratio had no connections with the risk of MetS and MetS severity score across the menopausal transition. Conclusions: Elevated serum FSH and LH levels, but not LH/FSH ratio, were associated with a lower risk of MetS and MetS severity score, especially in postmenopausal women. Therefore, serum FSH and LH levels might be efficient predictors for screening and identifying women at risk of MetS across the menopausal transition.

Supramolecular filaments for concurrent ACE2 docking and enzymatic activity silencing enable coronavirus capture and infection prevention.

Coronaviruses have historically precipitated global pandemics of severe acute respiratory syndrome (SARS) into devastating public health crises. Despite the virus's rapid rate of mutation, all SARS coronavirus 2 (SARS-CoV-2) variants are known to gain entry into host cells primarily through complexation with angiotensin-converting enzyme 2 (ACE2). Although ACE2 has potential as a druggable decoy to block viral entry, its clinical use is complicated by its essential biological role as a carboxypeptidase and hindered by its structural and chemical instability. Here we designed supramolecular filaments, called fACE2, that can silence ACE2's enzymatic activity and immobilize ACE2 to their surface through enzyme-substrate complexation. This docking strategy enables ACE2 to be effectively delivered in inhalable aerosols and improves its structural stability and functional preservation. fACE2 exhibits enhanced and prolonged inhibition of viral entry compared with ACE2 alone while mitigating lung injury in vivo.

Combined probiotics attenuate chronic unpredictable mild stress-induced depressive-like and anxiety-like behaviors in rats.

Increasing evidence indicated that probiotics can be effective in improving behaviors similar to depression and anxiety disorders. However, the underlying mechanisms remain unclear, as is the effects of single vs. combined probiotics on depression and anxiety. This study aimed to determine whether combined probiotics could attenuate depressive-like and anxiety-like behavior induced by chronic unpredictable mild stress (CUMS) and its potential mechanisms. Rats underwent CUMS treatment and then administered Lactobacillus rhamnosus HN001 (HN001) or Bifidobacterium animalis subsp. lactis HN019 (HN019), alone or in combination. Levels of neurotransmitters, inflammatory factors, and the gut microbiota were measured. HN001 and (or) HN019 treatment improved depressive-like and anxiety-like behavior in rats, including increased moving distance and exploratory behavior (p < 0.05). In addition, altered gut microbiota structure induced by CUMS was amended by HN001 and/or HN019 (p < 0.05). HN001 and/or HN019 intervention also remarkably normalized levels of 5-HT, DA, NE, HVA, DOPAC, HIAA, TNF-α, IL-6, IL-18 and IL-1ß in CUMS rats (p < 0.05). Furthermore, the effects of combined probiotics on decreasing inflammation and improved gut microbiota (Chao1 index and ACE index, p < 0.05) were superior to the single probiotics. Moreover, spearman analysis showed a certain correlation between the different microbiota, such as Firmicutes, Bacteroidetes, Verrucomicrobias, Proteobacterias and Actinobacterias, and inflammation and neurotransmitters. These findings suggested that CUMS induced depressive and anxiety-like behaviors can be alleviated by the combination of probiotics, which was possibly associated with the alterations in the gut microbiota composition and increased neurotransmitters and decreased inflammatory factors.

The Relationship of Malnutrition With Cognitive Function in the Older Chinese Population: Evidence From the Chinese Longitudinal Healthy Longevity Survey Study.

Background and Objective: Few studies have explored the relationship between malnutrition measured by the Geriatric Nutritional Risk Index (GNRI) and cognitive performance. This study aimed to investigate the association of malnutrition with cognitive function in the Chinese population. Methods: It was a prospective longitudinal study and used three waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) data in 2011-2012, 2014, and 2017-2018. Participants aged 60 years or older without mental illness and cerebrovascular diseases were eligible. The GNRI was used to assess nutritional status as follows: normal nutrition (a GNRI > 98), mild malnutrition (92 ≤ a GNRI ≤ 98), and moderate-to-severe malnutrition (a GNRI < 92). Cognitive performance was evaluated by the Mini-Mental State Examination (MMSE) scores. The relationship between the GNRI and cognitive function was analyzed using a linear mixed-effects model. Results: A total of 1,632 subjects were analyzed, including 741 males and 891 females. Of these, 65.0, 19.4, and 15.6% of subjects were at normal nutritional status, mild, and moderate-to-severe malnutrition, respectively. After adjusting for potential confounders, participants under mild and moderate-to-severe malnutrition status have a lower MMSE score [ß (95% CI): -0.95 (-1.60, -0.25) and -1.39 (-2.21, -0.57), respectively], compared with those having normal nutrition. Also, there was a linear trend in the association of malnutrition risk with cognitive function in the total population [ß (95% CI): -0.74 (-1.13, -0.35)]. However, a significant association of malnutrition with cognitive function was observed only among illiterate females aged above 90 years. Conclusion: This study suggested that there was a significant relationship between the GNRI and cognitive function in the Chinese elderly. Furthermore, subjects with more serious malnutrition have a worse cognitive function, especially in the oldest illiterate females. Clinicians should put more emphasis on assessing the nutritional and cognitive status of the elderly to timely intervene and prevent cognitive impairment.

Charge Transport in Sequence-Defined Conjugated Oligomers.

A major challenge in synthetic polymers lies in understanding how primary monomer sequence affects materials properties. In this work, we show that charge transport in single molecule junctions of conjugated oligomers critically depends on the primary sequence of monomers. A series of sequence-defined oligomers ranging from two to seven units was synthesized by an iterative approach based on the van Leusen reaction, providing conjugated oligomers with backbones consisting of para-linked phenylenes connected to oxazole, imidazole, or nitro-substituted pyrrole. The charge transport properties of these materials were characterized using a scanning tunneling microscope-break junction (STM-BJ) technique, thereby enabling direct measurement of molecular conductance for sequence-defined dimers, trimers, pentamers, and a heptamer. Our results show that oligomers with specific monomer sequences exhibit unexpected and distinct charge transport pathways that enhance molecular conductance more than 10-fold. A systematic analysis using monomer substitution patterns established that sequence-defined pentamers containing imidazole or pyrrole groups in specific locations provide molecular attachment points on the backbone to the gold electrodes, thereby giving rise to multiple conductance pathways. These findings reveal the subtle but important role of molecular structure including steric hindrance and directionality of heterocycles in determining charge transport in these molecular junctions. This work brings new understanding for designing molecular electronic components.