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.

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 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.

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 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.

The Role of Smoking, Obesity, and Physical Inactivity in Cognitive Performance and Decline: A Multicohort Study.

BACKGROUND: Unhealthy lifestyles are recognized contributors to cognitive decline, yet limited evidence focuses on their roles in cognitive decline rate. This study examined the role of smoking, obesity, and physical inactivity in cognitive performance and rate of cognitive decline by birth cohort on a global scale. METHODS: Utilizing data from 4 prospective cohort studies (China Health and Retirement Longitudinal Study, English Longitudinal Study on Ageing, Health and Retirement Study, and Survey of Health, Ageing and Retirement in Europe) across 14 countries, a multicohort study was performed. Eligible participants were aged 50 years and older. Linear mixed models were employed to detect the role of smoking, obesity, and physical inactivity in cognitive function domains (epidemic memory, working memory, and time orientation). RESULTS: Higher scores of cognitive functions were found in participants who engaged in more vigorous physical activity, were noncurrent smokers, and maintained underweight (eg, for episodic memory scores in females at 60 years, vigorous physical activity: 0.47, 95% CI: 0.46, 0.49). In addition, a slower rate of cognitive decline was also found in individuals who engaged in moderate or vigorous physical activity, were noncurrent smokers, and maintained not being underweight (eg, for episodic memory scores changing from 50 to 70 years old in females, vigorous physical activity: from 0.54 (95% CI: 0.51, 0.57) to 0.40 (95% CI: 0.37, 0.44) and in males from 0.33 (95% CI: 0.30, 0.36) to 0.11 (95% CI: 0.08, 0.14). CONCLUSIONS: We confirmed the beneficial impact of healthy lifestyles in preventing cognitive decline and promoting healthy aging. Urgent measures are needed to identify and encourage healthy lifestyles, such as strengthening tobacco control, developing policy on physical activity promotion, and preventing underweight, to minimize worldwide levels of cognitive decline.

The "spillover effect" of long-term care insurance in China on spouses' health and well-being.

This study examined the spillover effect of long-term care insurance (LTCI) on the health outcomes and well-being of spouses for Chinese middle and old-aged adults with expected LTC demand or actual care burdens. Using panel data from the China Health and Retirement Longitudinal Study between 2011 and 2018, we investigated the impact of the introduction of LTCI pilots across several cities on old individuals by using the difference-in-differences (DID) approach. We found a spillover effect of LTCI on the health and well-being outcomes of spouses of middle and old-aged individuals with functional limitations. It might due to the fact that LTCI could relieve economic burden by reducing out-of-pocket medical expenditures, which further affects health and well-being of spouses. The spillover effect on health and well-being was found to be stronger for male spouses and low-educated spouses. Spouses of the individuals aged below 80 years old and those live without adult children were more likely to benefit from the introduction of LTCI. Moreover, providing combination benefits seems to make spouses better off than offering direct services. Therefore, the results implied that the expansion of LTCI not only helped the care recipients themselves but could also improve the health and well-being of the spouses of functionally impaired older adults.

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.

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.

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.

A Link between Prenatal Stage of Life during the Great Chinese Famine and Subsequent Depressive Symptoms among Middle-Aged and Older Adults.

Prenatal malnutrition may increase the risk of depressive symptoms in adulthood. This study investigated the association between prenatal exposure to malnutrition with risk of depressive symptoms in middle-aged and older adults using the Chinese Great Famine of 1959-1961 as a natural experiment. Data were obtained from the China Health and Retirement Longitudinal Study baseline survey (2011). A total of 5391 individuals born from 1956 to 1965 were included in the study. Depressive symptoms were ascertained via the Center for Epidemiological Studies Depression Scale short form. Famine severity was measured using the cohort size shrinkage index. Difference-in-differences models were used to explore the association between prenatal famine exposure and later-life depressive symptoms. Compared with the post-famine cohort (1963-1965), famine cohorts (1959-1962) were 4.74 times (95% CI = 1.28-8.20) as likely to develop depressive symptoms. The stratified analysis found that prenatal exposure to famine was associated with depressive symptoms in rural residents but not those living in urban areas. In rural females, prenatal malnutrition was associated with a higher risk of depressive symptoms. However, there was no significant association between prenatal malnutrition and depressive symptoms in rural males. Our results indicated that prenatal malnutrition may contribute to a higher risk for depressive symptoms in later life among female rural residents.

Multi-function screening of probiotics to improve oral health and evaluating their efficacy in a rat periodontitis model.

The oral cavity is the second most microbially rich region of the human body, and many studies have shown that there is a strong association between microorganisms and oral health. Some pathogenic bacteria produce biofilms and harmful metabolites in the mouth that may cause oral problems such as oral malodor, periodontitis, and dental caries. Altering the oral microbiota by using probiotics may alleviate oral health problems. Thus, using multi-function screening, we aimed to identify probiotics that can significantly improve oral health. The main parameters were the inhibition of pathogenic bacteria growth, inhibition of biofilm formation, reduction in the production of indole, H2S, and NH3 metabolites that cause halitosis, increase in the production of H2O2 to combat harmful bacteria, and co-aggregation with pathogens to prevent their adhesion and colonization in the oral cavity. Tolerance to cholic acid and choline was also assessed. Bifidobacterium animalis ZK-77, Lactobacillus salivarius ZK-88, and Streptococcus salivarius ZK-102 had antibacterial activity and inhibited biofilm production to prevent caries. They also improved the oral malodor parameter, H2S, NH3, and indole production. The selected probiotics (especially L. salivarius ZK-88) alleviated the inflammation in the oral cavity of rats with periodontitis. The analysis of the gingival crevicular fluid microbiome after probiotic intervention showed that B. animalis ZK-77 likely helped to restore the oral microbiota and maintain the oral microecology. Next, we determined the best prebiotics for each candidate probiotic in order to obtain a formulation with improved effects. We then verified that a probiotics/prebiotic combination (B. animalis ZK-77, L. salivarius ZK-88, and fructooligosaccharides) significantly improved halitosis and teeth color in cats. Using whole-genome sequencing and acute toxicity mouse experiments involving the two probiotics, we found that neither probiotic had virulence genes and they had no significant effects on the growth or development of mice, indicating their safety. Taking the results together, B. animalis ZK-77 and L. salivarius ZK-88 can improve oral health, as verified by in vivo and in vitro experiments. This study provides a reference for clinical research and also provides new evidence for the oral health benefits of probiotics.

Visualization of microRNA therapy in cancers delivered by small extracellular vesicles.

MicroRNA (miRNA) delivery by extracellular vesicles (EVs) has recently inspired tremendous developments in cancer treatments. However, hybridization between miRNA and its target mRNA is still difficult to be imaged in vivo to assess the therapeutic effects in time. Herein we design a nano-scale fluorescent "off-on" complex encapsulated by small extracellular vesicles (sEVs) for real-time visualization and evaluation of gene therapy efficiency in human gastric cancer cells and murine xenograft tumor models. The complex is formed by π-π stacking between graphene quantum dots (GQDs) and tumor suppressor miR-193a-3p conjugated fluorescent tag whose signals remain off when binding to GQDs. Loaded into sEVs using tunable sonication techniques, the GQDs/Cy5-miR particles enter the tumor cells and promote miR-193a-3p escape from endosomes. The miR-193a-3p in GQDs/Cy5-miR is unleashed to pair the specific target oncogene cyclin D1 (CCND1), therefore turning on the fluorescence of miRNA tags. We find out that GQDs/Cy5-miR@sEVs can activate the "turn-on" fluorescent signal and exhibit the longest retention time in vivo, which suggests a minimized degradation of miR-193a-3p in dynamic processes of miRNA-mRNA binding. More importantly, GQDs/Cy5-miR@sEVs significantly promote cancer apoptosis in vitro and in vivo via the enhanced cellular uptake. Our study demonstrates that GQDs/Cy5-miR@sEVs represent an efficient and refined theranostic platform for gene therapy in cancers.

Trends in Mortality and Prevalence of Reported HIV/AIDS Cases - China, 2002-2021.

What is already known about this topic?: Annually, only the incidence and mortality for Acquired Immune Deficiency Syndrome (AIDS) patients are officially disclosed. What is added by this report?: For the first time, information detailing the reported rate, mortality rate, and prevalence rate trends of HIV, AIDS, and HIV/AIDS in China's entire population over the past two decades has been provided. What are the implications for public health practice?: Our research overcomes the longstanding limitation of HIV/AIDS analysis as the sole denominator. Rather, it incorporates a comprehensive examination of the overall population, utilizing indicators and analytic methods from chronic disease analyses.

Long-term Trends in Healthy and Unhealthy Life Expectancy Among Adults Aged 60 - A Global Perspective, 1990-2019.

What is already known about this topic?: Traditionally, life expectancy has served as a pivotal measure for assessing population health. However, there is an increasing focus on distinguishing healthy years of life from those characterized by illness, particularly among the elderly population. What is added by this report?: This study conducts an exhaustive global analysis of the trends in healthy and unhealthy life expectancy among adults aged 60 and over from 1990 to 2019. These trends are further correlated with socio-demographic indicators and health services metrics. What are the implications for public health practice?: Comprehending the dynamics between healthy and unhealthy life years can equip policymakers with the necessary insights to prioritize interventions. These interventions can thereby secure both quality and longevity of life for the increasingly aging population.

Adverse childhood experiences from family and society contribute to increased risk of depressive symptoms and cognitive impairment: a cross-sectional study.

Background: Family environments can shape children's personalities and social networks, rendering distinguishing adverse childhood experiences (ACEs) from family and society essential, but related evidence remains limited. Aims: This cross-sectional study aimed to investigate the correlations between intrafamilial and social ACEs, their associations with depressive symptoms and cognitive impairment and the (education-moderated) mediating role of social ACEs. Methods: Data for this cross-sectional study were from the China Health and Retirement Longitudinal Study. Nine intrafamilial (0, 1, 2, 3, and 4 or more) and three social (0, 1, and 2 or more) ACEs were identified. Depressive symptoms were assessed using the 10-item Center for Epidemiological Studies Depression Scale. Global cognition, including episodic memory and mental intactness, was calculated as z scores. Binary and ordered logistic regressions, generalised linear models with Gaussian family and identity link, and mediation analysis were used. Results: 13 435 participants aged 59.0 (51.0-66.0) were included. Compared with participants with no intrafamilial ACEs, those with 1, 2, 3, and 4 or more intrafamilial ACEs tended to develop more social ACEs, with odds ratios (ORs) of 1.55 (95% confidence interval (CI): 1.36 to 1.76), 2.36 (95% CI: 2.08 to 2.68), 3.46 (95% CI: 3.02 to 3.96) and 6.10 (95% CI: 5.30 to 7.02), respectively. Both intrafamilial and social ACEs were associated with depressive symptoms (OR >3 for four or more intrafamilial ACEs and two or more social ACEs) and global cognition (ß=-0.26 for four or more intrafamilial ACEs and ß=-0.29 for two or more social ACEs). Social ACEs mediated the associations of intrafamilial ACEs with depressive symptoms and global cognition by 12.3% and 13.1%, respectively. Furthermore, as education levels increased, the impact of intrafamilial ACEs on depressive symptoms was increasingly mediated through social ACEs, while the mediating role of social ACEs between intrafamilial ACEs and cognitive impairment gradually diminished. Conclusions: Improving children's social environments and elevating general education can prevent later-life depressive symptoms and cognitive impairment attributed to ACEs in China.