Nonlinear-tolerant two-dimensional distribution matcher scheme for probabilistic shaping.

This Letter proposes a nonlinear-tolerant two-dimensional distribution matcher (2D-DM) scheme. It removes the corner points of probabilistically shaped quadrature amplitude modulation (QAM) to obtain better nonlinear tolerance. Because the remaining number of points is not a power of 2, we propose to divide constellation points into different layers and symbols. Then, the proposed 2D-DM performs matching using one-dimensional shapers, which generates the in-phase and quadrature components of QAM together. In fact, it realizes two-dimensional shapers from one-dimensional shapers. Simulation results show that two-dimensional shapers generated by the proposed 2D-DM have higher tolerance to power amplifier nonlinearity and fiber nonlinearity compared to one-dimensional shapers.

HLA-C*07:01 and HLA-DQB1*02:01 protect against white matter hyperintensities and deterioration of cognitive function: A population-based cohort study.

BACKGROUND: Neuroinflammation and aberrant immune regulation are increasingly implicated in the pathophysiology of white matter hyperintensities (WMH), an imaging marker of cerebrovascular pathologies and predictor of cognitive impairment. The role of human leukocyte antigen (HLA) genes, critical in immunoregulation and associated with susceptibility to neurodegenerative diseases, in WMH pathophysiology remains unexplored. METHODS: We performed association analyses between classical HLA alleles and WMH volume, derived from MRI scans of 38 302 participants in the UK Biobank. To identify independent functional alleles driving these associations, we conducted conditional forward stepwise regression and lasso regression. We further investigated whether these functional alleles showed consistent associations with WMH across subgroups characterized by varying levels of clinical determinants. Additionally, we validated the clinical relevance of the identified alleles by examining their association with cognitive function (n = 147 549) and dementia (n = 460 029) in a larger cohort. FINDINGS: Four HLA alleles (DQB1*02:01, DRB1*03:01, C*07:01, and B*08:01) showed an association with reduced WMH volume after Bonferroni correction for multiple comparisons. Among these alleles, DQB1*02:01 exhibited the most significant association (ß = -0.041, 95 % CI: -0.060 to -0.023, p = 1.04 × 10-5). Forward selection and lasso regression analyses indicated that DQB1*02:01 and C*07:01 primarily drove this association. The protective effect against WMH conferred by DQB1*02:01 and C*07:01 persisted in clinically relevant subgroups, with a stronger effect observed in older participants. Carrying DQB1*02:01 and C*07:01 was associated with higher cognitive function, but no association with dementia was found. INTERPRETATION: Our population-based findings support the involvement of immune-associated mechanisms, particularly both HLA class I and class II genes, in the pathogenesis of WMH and subsequent consequence of cognitive functions.

Total life expectancy and disability-free life expectancy and differences attributable to cigarettes' smoking among Chinese middle-aged and older adults.

OBJECTIVES: Middle-aged and older adults smoking for years are afflicted by smoking-related diseases and functional limitations; however, little is known about the effect of smoking on nonfatal conditions in middle and later life. This study aims to investigate the impact of smoking on both total life expectancy (TLE) and disability-free life expectancy (DFLE) and the variations in such effects by educational level in China. METHODS: Data were drawn from the China Health and Retirement Longitudinal Study (CHARLS), 2011-2018, with a total sample of 16,859 individuals aged 45 years or older involved in the final analysis. The Activities of Daily Living (ADL) scale was used to measure disability, and the population-based multistate life table method was used to estimate the differences in TLE and DFLE by smoking status and educational attainment. RESULTS: At baseline, 28.9% of participants were current smokers, 8.5% were former smokers, and 62.6% never smoked. Approximately 5.6% were identified with ADL disability. Both current smokers and former smokers experienced lower TLE and DFLE than never smokers, and such differences were particularly prominent among men. Intriguingly, former smokers manifested a lower DFLE for both sexes and a lower TLE among women, though a longer TLE among men, compared with current smokers. Similar differences in TLE and DFLE by smoking status were observed for groups with different levels of education. CONCLUSION: Never smokers live longer and healthier than current smokers and persons who quit smoking. Smoking was associated with greater reductions in TLE and DFLE among men. However, educational attainment might not moderate the adverse effect of smoking on both fatal and nonfatal conditions in the context of China. These findings have implications for disability prevention, aged care provision and informing policies of healthy aging for China and elsewhere.

Bidirectional, longitudinal associations between depressive symptoms and IADL/ADL disability in older adults in China: a national cohort study.

INTRODUCTION: Based on the data from the China Health and Retirement longitudinal study (CHARLS), we aimed to investigate the bidirectional relationship between depressive symptoms and functional disability. METHODS: Data were collected across 3 waves from 2013 to 2018. The activities of daily living (ADLs) and the instrumental activities of daily living (IADLs) scales were used to measure functional disability and the CESD-10 was used to measure depressive symptoms. Cross-lagged models were performed to examine cross effect between depressive symptoms and functional disability across three waves. RESULTS: Data on 10,092(mean [SD] age, 61.98[8.44] years; 3764 females [37.30%]) and 10,180 participants (mean [SD] age, 62.01[8.46] years; 3788 females [37.21%]) in IADL sample and ADL sample were included in the analyses. For IADL disability, the cross-lagged model shows a bidirectional association across three waves; the multivariable GEE model revealed that changes in CESD-10 score across waves were associated with worse IADL disability (ß ranges: 0.08-0.10) and vice versa, worsen of IADL disability ascending developing of CESD-10 score (ß ranges: 0.09-0.10). For ADL disability, the cross-lagged model shows a bidirectional association across three waves; the multivariable GEE model revealed that changes of CESD-10 score across waves were associated with worse IADL disability (ß ranges: 0.08-0.10) and vice versa, worsen of IADL disability ascending developing of CESD-10 score (ß ranges: 0.09-0.10). DISCUSSION: Study findings underscore a significant bidirectional between depressive symptoms and functional disability in older adults. Thus, simultaneous intervention should be taken to manage the mutual development of functional disability and depression.

Post-traumatic growth in later-life cognitive function? Evidence from the 1976 Great Tangshan Earthquake.

OBJECTIVES: This study aimed to explore the long-term impacts of exposure to earthquake in adolescence on later-life cognitive function in China. METHODS: Data were from the 2015 China Health and Retirement Longitudinal Study (CHARLS). Our analytical sample comprised 4394 participants aged 49 to 78 from two birth cohorts born between 1937 and 1966: exposed cohort during adolescence (born between 1952 and 1966), and non-exposed cohort during adolescence (born between 1937 and 1951). We defined earthquake exposure as the exposure severity of the 1976 Great Tangshan Earthquake (GTE). We selected community environmental characteristics as our key moderators. A difference-in-differences (DID) method was employed to estimate the long-term impact of the GTE on later-life cognitive function. RESULTS: We found that exposure to the earthquake during adolescence resulted in higher scores of later-life cognitive function (for males: ß = 2.18; 95% CI: 0.70-3.66; for females: ß = 1.22; 95% CI: 0.11-2.33). For males, this impact was moderated by community environmental characteristics including the old-age allowance program (ß = 3.07; 95% CI: 1.94-4.19) and the condition of basic community infrastructures (ß = 1.52; 95% CI: 0.84-2.19). CONCLUSIONS: Our study supports the post-traumatic growth theory. This finding suggest that individuals with early-life traumatic exposure need to be focused on. Additionally, improving the conditions of community infrastructures and establishing a community environment with comfort and security may be pretty important for promoting cognitive function and post-traumatic growth.

The interrelationships of hearing function, allostatic load, and cognitive function: Evidence among middle-aged and older Chinese adults.

OBJECTIVES: We aim to examine the interrelationships of self-reported hearing function, allostatic load (AL), and cognitive function among middle aged and older adults. METHODS: Our data were collected from two waves of the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2011 and 2015. The participants' hearing function was measured using self-rated subjective hearing function. Allostatic load (AL) was evaluated by measuring 14 biomarkers associated with physiological health, which were derived from blood samples. Cognitive function was assessed using three domains: episodic memory, mental intactness, and global cognition. To examine the relationships between hearing function, AL, and cognitive function, path analysis with structural equation modeling (SEM) methodology was employed. RESULTS: Among individuals aged 60 and above non-hearing aids users, the hearing function at Time 1 (T1) in 2011 has a significant association with the level of AL at T1 (ß = 0.02, p < 0.001), as well as on cognitive function at Time 2 (T2) in 2015 (ß = -0.1, p < 0.001). Additionally, the AL related to the hearing function at T1 associates an increased risk of AL at T2 (ß = 0.5, p < 0.001), and is significantly associated with a decrease of cognitive function scores at T2 (ß = -0.4, p < 0.001). However, no significant relationship was found among individuals aged 45 - 59 with non-hearing aids utilizers. Similar findings were in the domains of epidemic memory and mental intactness for cognitive function. CONCLUSIONS: There were interrelationships of subjective hearing function, AL, and cognitive function among aged 60 years and above, but not among those aged 45-59 years old. It may provide valuable insights for identifying subclinical thresholds in the physiological systems of individuals at risk of pathology in cognitive function.

The longitudinal association between adverse childhood experiences, childhood socioeconomic status, and lung function among middle-aged and older adults.

OBJECTIVES: This study aims to investigate the association between adverse childhood experiences (ACEs), childhood socioeconomic status (SES) with lung function among general Chinese middle-aged and older adults. METHODS: Participants at baseline were 9052 individuals aged 45 years old and above from the China Health and Retirement Longitudinal Study (CHARLS), a population-based cohort of Chinese adults. Analyses were conducted with data from three waves (2011, 2013, and 2015). The ACEs included five threat-related indicators (i.e., physical abuse, household substance abuse, domestic violence, unsafe neighborhood, and bullying) and five deprivation-related adversities (i.e., emotional neglect, household mental illness, incarcerated household member, parental separation or divorce, and parental death). The cumulative score of threat-related and deprivation-related ACEs was used for analysis. Lung function was assessed by peak expiratory flow (PEF). Two-level linear mixed growth models were used to evaluate the longitudinal association between and ACEs, childhood SES, and PEF. RESULTS: Participants with more than three deprivation-related ACEs were significantly associated with lower PEF (b = -11.45 L/min, 95%CI: -18.40, -4.49) after adjusting for multiple confounding factors. Threat-related ACEs were not associated with PFF. Father's illiterate education predicted lower lung function (b = -8.49 L/min, 95%CI: -11.68, -5.31) for all middle-aged and older adults while mother's illiterate education was only significantly associated with PEF among the men (b = -9.21 L/min, 95%CI: -18.20, -0.22), and middle-aged adults (b = -7.96 L/min, 95%CI: -14.35, -1.57). DISCUSSION: ACEs and disadvantaged childhood SES are important predictors of lower lung function during adulthood. Reducing ACEs and improving childhood SES may be beneficial for long-term health development.

Investigation of the effect of residual waviness formed by rail profile milling of reshaped surface on wheel-rail contact stresses and low cyclic fatigue.

The rail profile milling process allows considerable thickness to be removed in a single pass. However, the residual waviness formation law after milling and its subsequent effect on rail performance remains uncertain. In this paper, the wavelength and wave height of the residual waviness are identified as the key characteristics. The relationship between milling speed and residual waviness is determined, and a numerical model of the residual waviness formed on the surface after milling is established based on the commonly used three milling speeds of 300, 600, and 1000 m/h, and its accuracy is verified using the parameters of the residual waviness detected by the milling experiments. A three-dimensional finite element analysis model of wheel-rail contact was employed to analyze the contact stresses and low fatigue cycles at a wheel load of 11.5 tons with no residual waviness on the rail profile surface and with three types of residual waviness, respectively. The results show that the residual waviness changes the wheel-rail contact position and the morphology of the contact area, reduces the maximum contact stress and increases the strain fatigue cycles. The application of elevated milling speeds reduces the wheel-rail contact stresses after milling, thereby increasing the low fatigue cycles.

Does college education reduce the risk of schizophrenia? Evidence from a college enrollment expansion policy in China.

BACKGROUND: Schizophrenia occurs worldwide, and the health, and economic burden is substantial. As one of the common proxies of socioeconomic status (SES), education was reported to be associated with the risk of developing schizophrenia. However, there is no causal evidence about the relationship. This paper explores the health benefits of college education for schizophrenia. METHOD: Based on exogenous variation in college enrollment across regions and cohorts induced by college enrollment expansion policy, we use instrument variable (IV) estimate strategy to estimate impacts of college education on the risk of schizophrenia with the data from Second National Sample Survey on Disability. RESULTS: We find that college education reduces the risk of developing schizophrenia by 4.2 percentage points. Some further analyses suggest the causal protective effect is only found among men, rural, and low-income individuals. CONCLUSIONS: These findings provide new evidence for the causal relationship between college education and schizophrenia, and add to the literature on the health benefits of education.

The trends of mental disorders mortality in China over a 33-year period.

OBJECTIVES: We investigated the variations in the trends of mental disorders mortality by age, period, and cohort, over a 33-year period from 1987 to 2020, to reveal the relationship between age, period, cohort, and mental disorders mortality, as well as providing guidance for resource allocation to prevent mental disorders-related deaths in vulnerable target populations. METHODS: The data of mental disorders mortality 1987-2020 were from five administrative organizations, which collected from the National Health Commission in China with national monitoring by sex and age, covering 31 provinces in China. The International Classification of Diseases (ICD), its 9th Revision (ICD-9) and its 10th Revision were used to code the mental diseases. From 1987-2002, ICD-9 was used, and ICD-10 was used from 2003 to 2020. The age standardized mortality rates (ASMRs) were calculated using the World Standard Population as the reference. We used joinpoint models to assess the trends of mental disorders mortality in China for the period 1987-2020. And the age-period-cohort models were employed to estimate the age-period-cohort effect on mental disorders mortality. RESULTS: The age-standardized overall mental disorders mortality rate (ASMR) showed a downward trend from 1987 to 2020. Further, the ASMR of individuals in urban was higher than that in rural from 1987 to 2001, but, post-2002, this urban-rural disparity in ASMR showed a less clear pattern, with urban areas occasionally surpassing rural areas and vice versa. ASMR is less prevalent among females compared to males overall. The contribution of age effects to mental disorders mortality gradually increases with advancing age, the period effects of mental disorders mortality gradually decrease over time. The cohort effect's contribution to mental disorders mortality decreases in the newly born population, while in the older birth cohorts, the cohort effect's contribution to the mortality rate of mental disorders increases. CONCLUSIONS: The ASMR exhibits a decreasing trend from 1987 to 2020, and these change trend showed urban-rural and sex differences. The primary factors contributing to this overall decline are period effects and cohort effects. Our results provide valuable information for shaping mental health policies, designing targeted interventions, and preparing for future changes in disease mortality rates. The focus on different demographic factors allows for a nuanced and tailored approach to mental health promotion and intervention strategies.

Relationship Between Physical Exercise and Cognitive Function Among Older Adults in China: Cross-Sectional Population-Based Study.

BACKGROUND: The existing literature reveals several significant knowledge gaps that hinder health care providers in formulating exercise prescriptions for cognitive health. OBJECTIVE: This study endeavors to elucidate the relationship between the level of physical activity and cognitive function in older adults in China. Moreover, it seeks to explore the associations between distinct exercise behaviors-such as exercise types, the purpose motivating engagement in exercise, the accessibility of exercise fields, and the inclination toward exercise-and cognitive function. METHODS: Using data from the China Longitudinal Aging Social Survey (CLASS conducted in 2016, cognitive function was meticulously assessed through the modified Chinese version of the Mini-Mental State Examination, encompassing measures of orientation, memory, and calculation. Using self-report structured questionnaires, a myriad of information about physical activity during leisure time, exercise engagement, exercise intensity, primary exercise types, reasons for exercise participation, availability of sports facilities, and exercise willingness was diligently gathered. Robust ordinary least squares regression models were then used to compute coefficients along with 95% CIs. RESULTS: A discernible inverted U-shaped trend in cognitive scores emerged as the level of physical activity surpassed the threshold of 500 metabolic equivalents of task (MET) minutes per week. Notably, individuals with a physical activity level between 500 and 999 MET minutes per week exhibited a coefficient of 0.31 (95% CI 0.09 to 0.54), those with a physical activity level between 1000 and 1499 MET minutes per week displayed a coefficient of 0.75 (95% CI 0.52 to 0.97), and those with a physical activity level above 1500 MET minutes per week demonstrated a coefficient of 0.45 (95% CI 0.23 to 0.68). Older individuals engaging in exercise at specific MET levels showcased superior cognitive function compared to their inactive counterparts. Furthermore, individuals driven by exercise motivations aimed at enhancing physical fitness and health, as well as those using sports facilities or public spaces for exercise, exhibited notably higher cognitive function scores. CONCLUSIONS: The findings underscore the potential of exercise as a targeted intervention for the prevention and treatment of dementia or cognitive decline associated with aging in older individuals. Leveraging these insights to formulate informed exercise recommendations holds promise in addressing a significant public health challenge linked to aging populations.

Age, Sex, and Disease-Specific Mortality Contributions to Life Expectancy in Urban and Rural China, 1987-2021.

What is already known about this topic?: Over the past several decades, China has experienced substantial improvements in life expectancy (LE), signifying major advancements in public health outcomes. What is added by this report?: This study offers an in-depth analysis of the contributions made by various diseases and age demographics to the growth of LE in China over the past 35 years, highlighting crucial factors that influence population health. What are the implications for public health practice?: The results highlight the need for interventions tailored to various disease types and age groups in order to enhance LE and improve public health outcomes. Public health strategies should prioritize disease prevention, control initiatives, and enhancements in healthcare services that are specifically designed to meet the needs of distinct population demographics.

Multimorbidity, lifestyle, and cognitive function: A cross-cultural study on the role of diabetes, cardiovascular disease, cancer, and chronic respiratory diseases.

BACKGROUND: The effect of lifestyle factors on cognitive function related to four major noncommunicable diseases (NCDs) including diabetes, cardiovascular disease, cancer, and chronic respiratory diseases, and the relationship between these NCDs and cognitive function have not been fully studied. We aimed to investigate the longitudinal associations between these NCDs and cognitive function in middle-aged and older people, and the combined effects of lifestyle factors. METHODS: By employing the data from three large-scale cohort studies from the U.S. Health and Retirement Study (2010-2019), English Longitudinal Study of Aging (2014-2019), and China Health and Retirement Longitudinal Study (2011-2019), this study carried out a multi-cohort analysis to 77, 210 participants. Fixed-effects regression models were used to examine associations between NCD status and cognitive function. Margin plots were used to illustrate the effect of lifestyle factors. RESULTS: Our findings revealed the dose-dependent association between mounting these NCDs and declining cognitive performance, ranging from one NCD (ß = -0.05, 95 % CI: -0.08 to -0.02) to four NCDs (ß = -0.51, 95 % CI: -0.75 to -0.28). Decline in cognitive function associated with NCDs was exacerbated with physical inactivity, current smoking status, and an increase in unhealthy lifestyle behaviors. LIMITATIONS: The observational study design precludes causal interrogation of lifestyles and four NCDs on cognitive function. CONCLUSIONS: An increasing number of these NCDs were dose-dependently associated with the decline in cognitive function score. Unhealthy lifestyle factors expedite decline in cognitive function linked to these NCDs.

Sensory impairment, loneliness, and the discordance between subjective and objective cognitive function among older adults: A multi-cohort study.

OBJECTIVES: This study aimed to examine the association between sensory impairment and the discordance between subjective/objective cognitive function among older adults and test the mediating effect of loneliness. METHODS: We used data from four cohort studies conducted in 16 countries (N = 19,119). Sensory impairment and subjective cognitive impairment were self-reported. Objective cognitive impairment was measured in three dimensions. Generalized estimating equations were conducted to examine the association between sensory impairment and discordance in subjective/objective cognitive function. Cross-lagged panel model and a bootstrap method with 2,000 samples were employed to verify the mediating effect. RESULTS: Sensory impairment was related to an increased risk of subjective cognitive impairment (OR = 4.70, 95 % CI 4.33-5.10), objective impairment (OR = 1.51, 95 %CI 1.31-1.74), as well as the discordance in subjective/objective cognitive function (OR = 1.35, 95 %CI 1.06-1.71 for older adults with normal subjective cognitive function). In contrast, sensory impairment was associated with a decreased risk of discordant subjective/objective cognitive function among those with subjective cognitive impairment (OR = 0.79, 95 %CI 0.66-0.94). Moreover, loneliness mediated the association between sensory impairment and subjective cognitive impairment (standardized indirect effect = 0.002, 95 %CI 0.001-0.004), objective cognitive impairment (standardized indirect effect = 0.005, 95 %CI 0.003-0.007) as well as the discordance in subjective/objective cognitive function (standardized indirect effect = 0.001, 95 %CI 0.001-0.003 for older adults with normal subjective cognitive function). CONCLUSIONS: Significant association between sensory impairment and discordance in subjective/objective cognitive function and the mediating role of loneliness were revealed, varying by subjective cognitive function. Early screening on sensory impairment and targeted interventions on loneliness should be considered in future policies on cognitive impairment.

Trends and Distribution of Infertility - Asia Pacific Region, 1990-2021.

What is already known about this topic?: Infertility represents a significant global public health concern, impacting approximately 15% of couples of reproductive age worldwide. Despite this, data on infertility prevalence in the demographically diverse Asia-Pacific region remains sparse. What is added by this report?: This study examines the trends and distribution of infertility in the Asia-Pacific region from 1990 to 2021, revealing a significant increase in female infertility. The growth rate of secondary infertility has exceeded that of primary infertility. Additionally, an increase in the prevalence of polycystic ovary syndrome (PCOS) may be a significant contributor. The research also highlights geographical variations in the prevalence and trends of infertility across different countries. What are the implications for public health practice?: The findings emphasize the significance of sexual and reproductive health services and rights in safeguarding fertility.

The economic burden of autism spectrum disorder with and without intellectual disability in China: A nationwide cost-of-illness study.

OBJECTIVE: The economic burden of autism spectrum disorder (ASD) on individuals, their families and society as a whole is poorly understood. Accurate figures are crucial for economic estimates and service planning. METHODS: The total lifetime individual costs and annual societal costs of ASD in China were estimated with a prevalence-based, gross cost of illness approach and data from multiple sources. The direct medical costs in outpatient and inpatient settings from the electronic health records (EHRs) of hospitals, and direct nonmedical costs from a national survey were included. The indirect costs were from both the national survey and the estimation using human capital methods. Age-specific lifetime incremental societal costs were measured. Comorbidity-related and unrelated costs were analyzed separately. RESULTS: The discounted lifetime cost for an individual with ASD in China was $2.65 million (at 2020 prices, $) for those without intellectual disability (ID) and $4.61 million (at 2020 prices, $) for those with ID. The total cost of ASD amounted to $41.8 billion in 2020. Productivity loss were major cost drivers for ASD individuals without ID. Direct nonmedical costs (rehabilitation or adult care costs etc.) were major drivers for ASD individuals with ID. In a lifetime course, the total annual costs for middle aged and elderly (>42 years) were highest, followed by transitional adults (18-29 years) and preschoolers, both for individuals with or without ID. The distribution of costs over the lifespan varied by the cost category. CONCLUSIONS: ASD imposes a substantial economic burden on families and health care systems. Sectors and services coordination should be given policy considerations.

What impact does hearing impairment have on cognitive health in older married couples in China?

Hearing impairment is a common geriatric health problem and chronic stressor, and it is associated with poor cognitive outcomes. However, little is known about the impact of hearing impairment in married couples, particularly its potential spillover effects on the cognitive health among spouses of individuals with impairment. Drawing on a stress-proliferation perspective, we used actor-partner interdependence models to examine (1) whether an individual's hearing impairment influences their spouse's cognitive function; and (2) whether AL, symptoms of depression, and social participation serve as mediators for such an association. We utilized data from the 2015 (baseline) and 2018 (3-year follow-up) waves of the China Health and Retirement Longitudinal Study. 4434 couples were included at baseline, and 2190 couples remained after the 3-year follow-up. Hearing impairment among married women was associated with negative impacts on their spouses' cognitive function. Symptoms of depression and social participation may have served as potential mediators in this relationship. For married men, there was no statistically significant association between hearing impairment and spouses' cognitive function. Our findings suggest that hearing impairment among one spouse can lead to negative impacts on the other, but that this effect may depend on gender. Early diagnosis and couple-based interventions for hearing impairment are important for the cognitive health of both hearing-impaired individuals and their spouses.

Insights into Dietary Different Co-Forms of Lysine and Glutamate on Growth Performance, Muscle Development, Antioxidation and Related Gene Expressions in Juvenile Grass Carp (Ctenopharyngodon idellus).

The study aimed to compare the effects of crystalline L-lysine and L-glutamate (CAA), Lys-Glu dipeptide (KE) on the growth and muscle development of grass carp (Ctenopharyngodon idellus), and related molecular mechanisms. Five experimental diets (CR, 0.5% CAA, 1.5% CAA, 0.5% KE, 1.5% KE) containing Lys and Glu as free (Lys and Glu, CAA) dipeptide (Lys-Glu, KE) forms were prepared, respectively. A total of 450 juvenile grass carp with an initial weight of 10.69 ± 0.07 g were randomly assigned to 15 cages, and 5 treatments with 3 replicates of 30 fish each for 61 days of feeding. The results showed that the group of 0.5% KE exhibited the best growth performances according to the indicator's weight gain rate (WGR) and specific growth rate (SGR), although no statistically significant occurred among all groups; diet supplemented with 0.5% CAA significantly elevated the condition factor (CF) and viscerasomatic index (VSI) of juvenile grass carp. Diet supplemented with different Lys and Glu co-forms at different levels promoted the muscle amino acid content compared with those of CR group. Comparing with the CR group and other groups, the hardness of 0.5% CAA group significantly increased, and the springiness of 0.5% KE group excelled. Both the muscle fiber diameter and density of 0.5% KE group showed significant difference with those of the CR group, and a negative correlation between them was also observed. To uncover the related molecular mechanism of the differences caused by the different co-forms of Lys and Glu, the effect of different diets on the expressions of protein absorption, muscle quality, and antioxidation-related genes was analyzed. The results suggested that comparing with those of CR group, the dipeptide KE inhibited the expressions of genes associated with protein metabolism, such as AKT, S6K1, and FoxO1a but promoted PCNA expression, while the free style of CAA would improve the FoxO1a expression. Additionally, the muscle development-related genes (MyoD, MyOG, and Myf5) were significantly boosted in CAA co-form groups, and the expressions of fMYHCs were blocked but fMYHCs30 significantly promoted in 0.5% KE group. Finally, the effect of different co-forms of Lys and Glu on muscle antioxidant was examined. The 0.5% CAA diet was verified to increase GPX1a but obstruct Keap1 and GSTP1 expressions, resulting in enhanced SOD activity and reduced MDA levels in plasma. Collectively, the different co-forms of Lys and Glu influenced the growth of juvenile grass carp, and also the muscle development and quality through their different regulation on the protein metabolism, muscle development- and antioxidative-related genes.

A tilapia skin-derived gelatin hydrogel combined with the adipose-derived stromal vascular fraction for full-thickness wound healing.

Biomaterials are widely used in regenerative medicine to repair full-thickness skin defect wounds. The adipose-derived stromal vascular fraction (SVF) shows pro-regenerative properties, however, the ex vivo biological activity of SVF is suppressed due to the lack of an external scaffold. Tilapia skin, as a sustained and recyclable biomaterial with low immunogenicity, was applied in the preparation of a hydrogel. The mixture of tilapia skin-derived gelatin and methacrylic anhydride as a scaffold facilitated the paracrine function of SVF and exerted a synergistic effect with SVF to promote wound healing. In this study, 30% (w/v) SVF was added to methacrylate-functionalized tilapia skin gelatin and subsequently exposed to UV irradiation to form a three-dimensional nano-scaffolding composite hydrogel (FG-SVF-3). The effects of paracrine growth factors, neovascularization, and collagen production on wound healing were extensively discussed. FG-SVF-3 displayed a pronounced wound healing ability via in vivo wound models. The FG-SVF-3 hydrogel enhanced the biocompatibility and the expression of EGF, bFGF, and VEGF. FG-SVF-3, as a promising wound dressing, exhibited superior ability to accelerate wound healing, skin regeneration, and wound closure.

Effect of home-based and remotely supervised combined exercise and cognitive intervention on older adults with mild cognitive impairment (COGITO): study protocol for a randomised controlled trial.

INTRODUCTION: Mild cognitive impairment (MCI) is an intermediate phase between normal cognitive ageing and dementia and poses a serious threat to public health worldwide; however, it might be reversible, representing the best opportunity for secondary prevention against serious cognitive impairment. As a non-pharmacological intervention for those patients, interventions that combine physical exercise and cognitive training, whether delivered simultaneously or sequentially, may have superior effects on various cognitive domains, including global cognition, memory, executive function and attention. The supportive evidence remains incomplete. This study aims to assess the effectiveness of a combined exercise and cognitive intervention in Chinese older adults with mild cognitive impairment (COGITO), empowered by digital therapy and guided by the Health Action Process Model and the Theory of Planned Behaviour (HAPA-TPB theory) in a home-based setting. METHODS AND ANALYSIS: This study is a randomised controlled, assessor-blinded multi-centre study. Four parallel groups will include a total of 160 patients, receiving either a combined exercise and cognitive intervention, an isolated exercise intervention, an isolated cognitive intervention or only health education. These interventions will be conducted at least twice a week for 50 min each session, over 3 months. All interventions will be delivered at home and remotely monitored through RehabApp and Mini-programme, along with an arm-worn heart rate telemetry device. Specifically, supervisors will receive participants' real-time training diaries, heart rates or other online monitoring data and then provide weekly telephone calls and monthly home visits to encourage participants to complete their tasks and address any difficulties based on their training information. Eligible participants are community-dwelling patients with no regular exercise habit and diagnosed with MCI. The primary outcome is cognitive function assessed by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) and Community Screening Instrument for Dementia (CSI-D), with baseline and three follow-up assessments. Secondary outcomes include quality of life, physical fitness, sleep quality, intrinsic capacity, frailty, social support, adherence, cost-effectiveness and cost-benefit. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Board of Peking University. Research findings will be presented to stakeholders and published in peer-reviewed journals and at provincial, national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073900.