Amorphous curcumin-based hydrogels to reduce the incidence of post-surgical intrauterine adhesions.

The incidence of intrauterine adhesions (IUA) has increased with the rising utilization of intrauterine surgery. The postoperative physical barrier methods commonly used, such as balloons and other fillers, have limited effectiveness and may even cause further damage to the remaining endometrial tissue. Herein, we developed an injectable thermosensitive hydrogel using Pluronic F127/F68 as pharmaceutical excipients and curcumin as a natural active molecule. The hydrogel effectively addresses solubility and low bioavailability issues associated with curcumin. In vitro, drug release assays revealed that the amorphous curcumin hydrogel promotes dissolution and sustained release of curcumin. In vitro experiments reveal high biocompatibility of the hydrogel and its ability to enhance vascular formation while inhibiting the expression of fibrotic factor TGF-ß1. To assess the effectiveness of preventing IUAs, in vivo experiments were conducted using IUA rats and compared with a class III medical device, a new-crosslinked hyaluronic acid (NCHA) gel. According to the study, curcumin hydrogel is more effective than the NCHA group in improving the regeneration of the endometrium, increasing the blood supply to the endometrium and reducing the abnormal deposition of fibrin, thus preventing IUA more effectively. This study provides a promising strategy for treating and preventing IUA.

Association between Age at Diagnosis of Hyperlipidemia and Subsequent Risk of Dementia.

OBJECTIVES: The relationship between age at diagnosis of hyperlipidemia and dementia remains unclear. We examined whether younger age at diagnosis of hyperlipidemia is associated with higher risk of subsequent dementia. DESIGN: A longitudinal population-based study with a median follow-up of 12.8 years. SETTING AND PARTICIPANTS: We analyzed data on a sample of 489,642 participants in the United Kingdom. METHODS: This study was based on the UK Biobank. Information on hyperlipidemia and dementia diagnoses was collected at baseline (2006-2010) and follow-up [median = 12.8 years, interquartile range (IQR): 12.1-13.6 years]. Propensity score matching method and Cox proportional hazards models were used to assess the association between age at diagnosis of hyperlipidemia and dementia. RESULTS: Among 489,642 participants (mean age: 56.9 ± 8.1 years; female: 54.7%), 114,112 (23.3%) were diagnosed with hyperlipidemia. Younger age at diagnosis of hyperlipidemia (per 10-year decrease) was significantly associated with higher risks of all-cause dementia [hazard ratio (HR), 1.12; 95% CI, 1.07-1.18; P < .001], Alzheimer's disease (AD) (HR, 1.22; 95% CI, 1.14-1.31; P < .001), and vascular dementia (VD) (HR, 1.16; 95% CI, 1.05-1.27; P < .001). After propensity score matching, patients with hyperlipidemia diagnosed before 50 years had the highest HR for all-cause dementia (HR, 1.46; 95% CI, 1.15-1.86; P = .002), followed by patients diagnosed between 50 and 69 years (HR, 1.21; 95% CI, 1.12-1.31; P < .001) and then patients diagnosed aged 70 years and older (HR, 0.94; 95% CI, 0.84-1.06; P = .302). Similar results were observed for AD and VD. CONCLUSIONS AND IMPLICATIONS: A dose-response relationship between age at hyperlipidemia diagnosis and risk of dementia was found in the longitudinal cohort study, with younger age at diagnosis of hyperlipidemia being associated with higher subsequent risk.

Associations Between Onset Age of Orthostatic Hypotension and Incident Myocardial Infarction, Stroke, and Dementia: A Prospective Cohort Study.

BACKGROUND: The associations of age at orthostatic hypotension onset with incident myocardial infarction (MI), stroke, and dementia remain unknown. This study aimed to examine whether younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia. METHODS: Data were obtained from the UK Biobank. Information on the diagnosis of orthostatic hypotension, MI, stroke, and dementia was collected at baseline (2006-2010) and follow-ups (median = 13 years). The propensity score matching method and the Cox proportional hazard models were employed. RESULTS: A total of 448 374 adults (mean age: 56.8 ±â€…8.1 years), of whom 3 795 had orthostatic hypotension, were included. orthostatic hypotension patients exhibited higher risks of developing MI, stroke, and dementia than non-orthostatic hypotension participants. Importantly, among orthostatic hypotension patients, younger onset age (per 10-year decrement) was significantly associated with high risks of MI (HR = 3.15, 95% CI: 2.54-3.90, p < .001), stroke (HR = 1.72, 95% CI: 1.33-2.23, p < .001), and dementia (HR = 1.26, 95% CI: 1.02-1.57, p = .034). After propensity score matching, orthostatic hypotension patients had significantly higher risks of MI, stroke, and dementia than matched controls among all onset age groups, and the HRs gradually increased with descending onset age. CONCLUSIONS: Younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia, underscoring the necessity to pay additional attention to the cardiovascular health and neurocognitive status of individuals diagnosed with orthostatic hypotension at younger ages to attenuate subsequent risks of incident cardiovascular diseases and dementia.

Protocol for culturing and functionally manipulating planarian neoblasts using SiR-DNA-based flow cytometry.

Neoblasts are the only cells capable of proliferation in planarians. The traditional flow cytometry protocol using Hoechst inhibits the cell cycle. Here, we present a protocol for culturing and functionally manipulating planarian neoblasts using SiR-DNA-based flow cytometry. We describe steps for cell dissociation and staining, flow cytometry, and cell collection and culture. We then detail procedures for Nanoluciferase mRNA transfection. This protocol facilitates further investigations into the pluripotency and regeneration mechanisms within neoblasts. For complete details on the use and execution of this protocol, please refer to Lei et al.1.

Evaluating the capacity of heavy metal pollution enrichment in green vegetation in the industrial zone, Northwest China.

It focused on heavy metal pollution of green vegetation in Tuokexun County, Xinjiang Northwest China's suburban industrial area, using inductively coupled plasma emission spectrometer to analyze the samples for Mn, Ni, Zn, Cd, Hg, Pb, As, Cu, and Cr contents. The soil's heavy metal content in the study area indicated a minor level of pollution overall (P = 1.77), with the most severe contamination being Hg, which is more likely to be caused by human activities. Heavy metal elements in trees have the most stable composition in comparison to grass and shrubs, with varying concentrations across different vegetation. The concentrations of Mn, Cd and Hg were highest in the Haloxylon ammodendron, Ni in Morus alba, Pb, As and Cu in Nitraria tangutorums, and Cr in Phragmites australis. Heavy metal restoration is most effectively performed by shrubs, and there are disparities in heavy metal enrichment among various vegetation. No significant difference was found in heavy metal enrichment between the aboveground and underground parts of vegetation. Based on the average of the membership function, Tamarix exhibits the strongest ability to enrich heavy metals, while Nitraria tangutorum comes in second, and Cynanchum chinense R.Br. is the least effective among all plant species. Morus alba is recommended as the primary planting species in the area. Nitraria tangutorum and Haloxylon ammodendron have good potential for Cd and As restoration and can be used as supporting vegetation.

mTOR hypoactivity leads to trophectoderm cell failure by enhancing lysosomal activation and disrupting the cytoskeleton in preimplantation embryo.

BACKGROUND: Metabolic homeostasis is closely related to early impairment of cell fate determination and embryo development. The protein kinase mechanistic target of rapamycin (mTOR) is a key regulator of cellular metabolism in the body. Inhibition of mTOR signaling in early embryo causes postimplantation development failure, yet the mechanisms are still poorly understood. METHODS: Pregnancy mice and preimplantation mouse embryo were treated with mTOR inhibitor in vivo and in vitro respectively, and subsequently examined the blastocyst formation, implantation, and post-implantation development. We used immunofluorescence staining, RNA-Seq smart2, and genome-wide bisulfite sequencing technologies to investigate the impact of mTOR inhibitors on the quality, cell fate determination, and molecular alterations in developing embryos. RESULTS: We showed mTOR suppression during preimplantation decreases the rate of blastocyst formation and the competency of implantation, impairs the post implantation embryonic development. We discovered that blocking mTOR signaling negatively affected the transformation of 8-cell embryos into blastocysts and caused various deficiencies in blastocyst quality. These included problems with compromised trophectoderm cell differentiation, as well as disruptions in cell fate specification. mTOR suppression significantly affected the transcription and DNA methylation of embryos. Treatment with mTOR inhibitors increase lysosomal activation and disrupts the organization and dynamics of the actin cytoskeleton in blastocysts. CONCLUSIONS: These results demonstrate that mTOR plays a crucial role in 8-cell to blastocyst transition and safeguards embryo quality during early embryo development.

Nickel-Based Bifunctional Cocatalyst to Enhance CdS Photocatalytic Hydrogen Production.

The design of nanocomposites as a light-capturing system applied in photocatalytic water splitting is an emerging area of research. In our study, a simple in situ photodeposition method was proposed for the synthesis of CdS nanoflowers modified by nickel-based bifunctional, i.e., Ni/Ni(OH)2, cocatalysts. The introduction of cocatalysts has demonstrated a notable enhancement in the photocatalytic hydrogen evolution efficiency of CdS. The quantity of cocatalysts supported on CdS played an important role in governing the light absorption capability and photocatalytic efficacy. Ni-CdS-10 showed the best photocatalytic activity of 30.51 mmol g-1 h-1, which was 1.8 times and 2.6 times higher activity than Pt-CdS-1 wt % and pure CdS, respectively. Mechanism studies with UV-vis DRS, photoluminescence, and Mott-Schottky plots revealed the intrinsic electric field created at the p-n Ni(OH)2/CdS junctions, which can effectively implement the transport and separation of photoinduced carriers. From linear sweep voltammetry, electrochemical impedance spectroscopy, and DFT calculation, both Ni(OH)2 and Ni can effectively decrease the Gibbs free energies of hydrogen adsorption and reduce the overpotential of hydrogen evolution. As a result, the efficiency of generating H2 through photocatalysis experienced significant improvement, and the participation of bifunctional cocatalysts further reduced the photocorrosion of CdS, enhanced stability, improved low price, and efficient photocatalyst production.

Age at Diagnosis of Atrial Fibrillation and Incident Dementia.

Importance: Epidemiological evidence regarding the association between atrial fibrillation (AF) onset age and risk of incident dementia remains unexplored. Objective: To examine whether age at AF diagnosis is associated with risk of incident dementia and its subtypes. Design, Setting, and Participants: This prospective, population-based cohort study used data from UK Biobank, a public, open-access database in the UK with baseline information collected from 2006 to 2010. A total of 433 746 participants were included in the main analysis after excluding participants with a diagnosis of dementia or AF at baseline, missing data on covariates, or having dementia before AF onset during a median follow-up of 12.6 years. Data were analyzed from October to December 2022. Exposures: AF diagnosis and age at AF diagnosis according to age groups (<65 years, 65-74 years, or ≥75 years). Main Outcomes and Measures: Incident dementia, ascertained through linkage from multiple databases until December 31, 2021. Cox proportional hazards models and the propensity score matching method were adopted to estimate the association between AF onset age and incident dementia. Results: Of 433 746 included participants, 236 253 (54.5%) were female, the mean (SD) age was 56.9 (8.1) years, and 409 990 (94.5%) were White. Compared with individuals without AF, 30 601 individuals with AF had a higher risk of developing all-cause dementia (adjusted hazard ratio [HR], 1.42; 95% CI, 1.32-1.52) and vascular dementia (VD; adjusted HR, 2.06; 95% CI, 1.80-2.36), but not Alzheimer disease (AD; adjusted HR, 1.08; 95% CI, 0.96-1.21). Among participants with AF, younger age at AF onset was associated with higher risks of developing all-cause dementia (adjusted HR per 10-year decrease, 1.23; 95% CI, 1.16-1.32), AD (adjusted HR per 10-year decrease, 1.27; 95% CI, 1.13-1.42), and VD (adjusted HR per 10-year decrease, 1.35; 95% CI, 1.20-1.51). After propensity score matching, individuals with AF diagnosed before age 65 years had the highest HR of developing all-cause dementia (adjusted HR, 1.82; 95% CI, 1.54-2.15), followed by AF diagnosed at age 65 to 74 years (adjusted HR, 1.47; 95% CI, 1.31-1.65) and diagnosed at age 75 years or older (adjusted HR, 1.11; 95% CI, 0.96-1.28). Similar results can be seen in AD and VD. Conclusions and Relevance: In this prospective cohort study, earlier onset of AF was associated with an elevated risk of subsequent all-cause dementia, AD, and VD, highlighting the importance of monitoring cognitive function among patients with AF, especially those younger than 65 years at diagnosis.

New genes driven by segmental duplications share a testis-specific expression pattern in the chromosome-level genome assembly of tree sparrow.

Based on a chromosome-level genome assembly, a burst of new genes with different structures but a similar testis-specific expression pattern was detected in tree sparrow.

Association Between Onset Age of Coronary Heart Disease and Incident Dementia: A Prospective Cohort Study.

BACKGROUND: The association of age at coronary heart disease (CHD) onset with incident dementia remains unexplored. This study aimed to examine whether younger onset age of CHD is associated with a higher risk of incident dementia. METHODS AND RESULTS: Data were obtained from the UK Biobank. Information on the diagnosis of CHD and dementia was collected at baseline and follow-ups. Propensity score matching method and Cox proportional hazards models were used to evaluate the association between different ages at CHD onset and incident dementia. A total of 432 667 adults (mean±SD age, 56.9±8.1 years) were included, of whom 11.7% had CHD. Compared with participants without CHD, participants with CHD exhibited higher risks of developing all-cause dementia, Alzheimer's disease, and vascular dementia. More importantly, younger age at CHD onset (per 10-year decrease) was significantly associated with elevated risks of all-cause dementia (hazard ratio [HR], 1.25 [95% CI, 1.20-1.30]; P<0.001), Alzheimer's disease (HR, 1.29 [95% CI, 1.20-1.38]; P<0.001), and vascular dementia (HR, 1.22 [95% CI, 1.13-1.31]; P<0.001). After propensity score matching, patients with CHD had significantly higher risks of all-cause dementia, Alzheimer's disease, and vascular dementia than matched controls among all onset age groups, and the HRs gradually elevated with decreasing age at CHD onset. CONCLUSIONS: Younger onset age of CHD is associated with higher risks of incident all-cause dementia, Alzheimer's disease, and vascular dementia, underscoring the necessity to pay attention to the neurocognitive status of individuals diagnosed with CHD at younger age to conduct timely interventions to attenuate subsequent risk of incident dementia.

Heavy metal pollution alters reproductive performance and mate choice in an anuran, Strauchbufo raddei.

Understanding the effects of pollution on reproductive performance and sexual selection is crucial for the conservation of biodiversity in an increasingly polluted world. The present study focused on the effect of environmental heavy metal pollution on sexually selected traits, including morphological characteristics and acoustic parameters, as well as mate choice in Strauchbufo raddei, an anuran species widely distributed in Northern China. The results showed that male courtship signals, including forelimb length, forelimb force, and advertisement calls, have evolved under the pressure of heavy metal pollution in young S. raddei. In addition, the breeding age was lower in the polluted areas, and younger individuals had more mating opportunities. However, males with heightened reproductive performance did not show the expected higher individual quality. The current study suggests that exposure to heavy metal pollution can induce stress in males, altering reproductive performance and further disrupting mate choice.

Age at Onset of Heart Failure and Subsequent Risk of Dementia: A Longitudinal Cohort Study.

BACKGROUND: The average age at onset of heart failure (HF) shows a progressive decrease in recent years; however, the association between age at onset of HF and risk of subsequent dementia remains undetermined. OBJECTIVES: The study sought to examine whether younger onset age of HF is associated with a higher risk of incident dementia. METHODS: Individual-level data from the UK Biobank cohort study were analyzed in the present study. Cox regression models and the propensity score matching method were used to analyze the associations of HF and its onset age with subsequent all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD). RESULTS: Compared with 442,791 participants without HF, those with HF had a higher risk of all-cause dementia (HR: 1.14). Among 14,413 participants with HF, multivariable-adjusted HRs for all-cause dementia, AD, and VD were 1.18, 1.64, and 1.27, respectively, per 10-year decrease in age at HF onset. The propensity score matching analyses found that the strength of association between HF and all-cause dementia increased with decreasing onset age of HF (≥75 years, HR: 1.05; 65-74 years, HR: 1.10; <65 years, HR: 1.67) after multivariable adjustment. Similarly, participants with onset age of HF <65 years had the greatest HRs for incident AD and VD, compared with their matched control subjects. CONCLUSIONS: Younger age at HF onset was associated with increased risk of dementia. Individuals with an onset age of HF before 65 years of age may represent a particularly vulnerable population for dementia irrespective of subtypes and need careful monitoring and timely intervention to attenuate subsequent risk of incident dementia.

Melatonin ameliorates simulated-microgravity-induced mitochondrial dysfunction and lipid metabolism dysregulation in hepatocytes.

The liver is an essential multifunctional organ, which constantly communicates with nearly all tissues. It has raised the concern that microgravity exposure can lead to liver dysfunction and metabolic syndromes. However, molecular mechanisms and intervention measures of the adverse effects of microgravity on hepatocytes are limited. In this study, we utilized the random positioning machine culture system to investigate the adverse effects on hepatocytes under simulated microgravity (SMG). Our results showed that SMG impaired hepatocyte viability, causing cell cycle arrest and apoptosis. Compared to normal gravity, it also triggered lipid accumulation, elevated triglyceride (TG) and ROS levels, and impaired mitochondria function in hepatocytes. Furthermore, RNA sequencing results showed that SMG upregulated genes implicated in lipid metabolisms, including PPARγ, PLIN2, CD36, FABPs, etc. Importantly, all these defects can be suppressed by melatonin, a potent antioxidant secreted by the pineal gland, suggesting its potential use of therapeutic intervention.

Stem Cells and Exosome Applications for Cutaneous Wound Healing: From Ground to Microgravity Environment.

The increasing number of astronauts entering microgravity environments for long-term space missions has resulted in serious health problems, including accidental injury and trauma. Skin, as the largest organ and outermost layer of the human body, has the ability to self-renew and withstand a variety of harmful biological and environmental influences. Recent spaceflight experiments and simulated studies have begun to concern the effects of microgravity on the growth of skin cells and the process of cutaneous wound healing. However, the mechanisms of the adverse effects of microgravity on skin cells and potential intervention measures are still limited. Stem cells and their exosomes provide unique opportunities for the cutaneous wound healing as they have been used to improve skin repair. This review discusses the effects of microgravity on wound healing, from cell morphological changes to molecular level alterations. Furthermore, the current research on wound healing treatment utilizing stem cells and their exosomes on the ground is summarized. Finally, this review proposes promising therapeutic strategies using stem cells or exosomes for wound healing in the microgravity environment. Graphical Abstract.

Dietary diversity and possible sarcopenia among older people in China: a nationwide population-based study.

Background: Sarcopenia is a common geriatric disease. Many dietary factors may contribute to the development of sarcopenia. Few studies have been conducted on dietary diversity and sarcopenia in Chinese older adults. Among a nationwide sample, the objective of this study is to assess the association between the dietary diversity score (DDS) and the prevalence of possible sarcopenia. We considered the different patterns of dietary diversity in relation to possible sarcopenia. Methods: We conducted this analysis utilizing the cross-sectional data from the 2012, 2014, and 2018 waves of the Chinese longitudinal healthy longevity survey (CLHLS). A standard developed by the Asian Working Group for Sarcopenia 2019 (AWGS2019) was used to assess the possibility of sarcopenia. On the basis of the DDS generated by previous studies, we have constructed four new indicators as follows: total diet, animal-based diet, plant-based diet, and plant-based diet without the consumption of legume products and nuts. We used the generalized estimation equation (GEE) model to evaluate the associations between the DDS of the total diet, animal-based diet, plant-based diet, and plant-based diet without the intake of legume products and nuts and possible sarcopenia. These associations were statistically adjusted for a variety of potential confounders. Sensitivity analysis was performed by excluding some participants who were long-term bedridden, had Alzheimer's disease, or were terminally ill. Results: The analysis included 6,624 participants (mean age 83.4 years at baseline). In our study, we found that participants with a higher DDS of the total diet (OR = 0.62; 95% CI: 0.51-0.77), animal-based diet (OR = 0.62; 95% CI: 0.49-0.79), and plant-based diet (OR = 0.64;95% CI: 0.51-0.80) were at a lower risk of developing sarcopenia. In sensitivity analyses, the associations remained unchanged. Conclusion: Taking a diversified diet, including animal foods, may reduce the risk of developing sarcopenia. According to the findings of this study, adopting a diversified diet might reduce the risk of sarcopenia for older adults.

Parenting styles and psychological resilience: The mediating role of error monitoring.

Parenting styles are associated with children's psychological resilience. However, the underlying mechanisms of this have not been investigated. Parenting styles influence how individuals respond to self-inflicted errors, and error monitoring is related to psychological resilience. Therefore, this study proposed that error monitoring might be a bridging factor between parenting styles and psychological resilience. Seventy-two young healthy adults were recruited for this study. Parenting styles were assessed using the Parental Bonding Instrument, and psychological resilience was measured using the Connor-Davidson Resilience Scale. Error monitoring was investigated in the Flanker task using event-related potentials (ERPs), and two error-related components of ERPs were measured: error-related negativity (ERN) and error positivity. Mediation analyses showed that the ERN partially mediated the relationship between parenting styles and psychological resilience. Specifically, a higher level of self-reported parental overprotection was related to larger ERN amplitude, which in turn was associated with lower psychological resilience. Additionally, a higher level of self-reported parental allowance of autonomy was related to lower ERN amplitude, which in turn was linked to higher psychological resilience. These results suggest that shaping children's sensitivity in early automatic error detection is one possible mechanism through which parental styles influence their psychological resilience.

To validate the integral conceptual model of frailty among community-dwelling older adults in China: a cross-sectional study.

PURPOSE: The integral conceptual model of frailty (ICFM) integrates physical, psychological, social aspects of individuals and stresses that frailty is a dynamic state evolving over time. This study aimed to validate the ICMF among community-dwelling older adults in China. METHODS: The study recruited 341 older community-dwelling adults by convenient sampling method between June 1 and August 30, 2019 in Hubei province, China. The data was collected by questionnaire-based survey. Frailty was assessed by the Chinese version of the Tilburg Frailty Index. Participants were assessed for life-course determinants, disease and adverse health outcomes. Hierarchical regression analyses, Bootstrap method and the structural equation model were conducted in data analysis. RESULTS: Both linear and logistic hierarchical regression models were statistically significant. Life-course determinants, disease, and three domains of frailty together explained 35.6% to 50.6% of the variance of disability and all domains of quality of life. The mediation effect of frailty between disease and all adverse outcomes was significant, excluding hospitalization. The structural equation model guided by the ICMF fits the data well. CONCLUSIONS: The ICMF is valid among community-dwelling older adults in China. Therefore, the multidimensional concept of frailty should be widely used in Chinese communities.

The single-atom catalytic activity of the hydrogen evolution reaction of the experimentally synthesized boridene 2D material: a density functional theory study.

CONTEXT: Previous theoretical studies have suggested that two-dimensional (2D) MBene materials might display adequate monatomic catalytic activity for the hydrogen evolution reaction (HER). Recently, a study reported the experimental synthesis of a 2D MBene (Mo4/3B2), re-defined as boridene, albeit no effort has been devoted to explore the single-atom catalytic activity for HER of this experimentally synthesized 2D material. Therefore, we herein investigate the single-atom HER performance of the boridene. Interestingly, with Mo defects mixed with single Au and Zn atoms shows excellent hydrogen evolution performance, and the change in the Gibbs free energy ([Formula: see text]) value is close to 0 eV, which can even match the performance of Pt-based materials. Through analysis of the charge density difference and density of states, the mechanism affecting the HER performance is explained at the electronic level. This work provides a new direction for the use of the Mo4/3B2 monolayer two-dimensional materials in the field of single-atom catalysis for HER. METHODS: This study used the DFT calculations in Vienna ab initio simulation package. The GGA-Perdew-Burke-Ernzerhof functional with DFT-D2 correction is used to describe the exchange-correlation interactions. The projection augmented wave is used with the plane wave cutoff of 500 eV. The convergences of energy and force are 10-5 eV and 0.01 eV/Å, respectively. A vacuum layer with a height of 20 Å is set in the Z direction. For geometry optimization, self-consistent, and DOS calculations, the k-point grids sampled in Brillouin zones are 3 × 3 × 1, 9 × 9 × 1, and 9 × 9 × 1, respectively. The AIMD simulation is performed in the canonical ensemble (NVT), and the temperature was maintained at 300 K by Nosé-Hoover thermostats with a time step of 2.0 fs.

Pluripotency retention and exogenous mRNA introduction in planarian stem cells in culture.

Planarians possess naturally occurring pluripotent adult somatic stem cells (neoblasts) required for homeostasis and whole-body regeneration. However, no reliable neoblast culture methods are currently available, hindering mechanistic studies of pluripotency and the development of transgenic tools. We report robust methods for neoblast culture and delivery of exogenous mRNAs. We identify optimal culture media for the short-term maintenance of neoblasts in vitro and show via transplantation that cultured stem cells retain pluripotency for two days. We developed a procedure that significantly improves neoblast yield and purity by modifying standard flow cytometry methods. These methods enable the introduction and expression of exogenous mRNAs in neoblasts, overcoming a key hurdle impeding the application of transgenics in planarians. The advances in cell culture reported here create new opportunities for mechanistic studies of planarian adult stem cell pluripotency, and provide a systematic framework to develop cell culture techniques in other emerging research organisms.

Onset age of diabetes and incident dementia: A prospective cohort study.

BACKGROUND: Relationship between age at diagnosis of diabetes and dementia is lacking. The aim of the study was to investigate whether diabetes onset at a younger age was associated with a higher incidence of dementia. METHODS: 466,207 participants free of dementia in the UK biobank (UKB) were included in the analysis. Propensity score matching (PSM) was adopted to match diabetic and non-diabetic participants in different onset age of diabetes groups to evaluate onset age of diabetes and incident dementia. RESULTS: Compared with non-diabetic participants, diabetes participants had an adjusted hazard ratio (HR) of 1.87 (95 % confidence interval [CI]: 1.73-2.03) for all-cause dementia, 1.85 (95 % CI: 1.60-2.04) for Alzheimer's disease (AD), and 2.86 (95 % CI: 2.47-3.32) for vascular dementia (VD). Among diabetic participants who reported onset age, the adjusted HRs for incident all-cause dementia, AD, and VD were 1.20 (95 % CI: 1.14-1.25), 1.19 (95 % CI: 1.10-1.29), and 1.19 (95 % CI: 1.10-1.28), respectively, per 10 years decrease in age at diabetes onset. After PSM, strength of association between diabetes and all-cause dementia increased with decreasing onset age of diabetes (≥60 years: HR = 1.47, 95 % CI: 1.25-1.74; 45-59 years: HR = 1.66, 95 % CI: 1.40-1.96; <45 years: HR = 2.92, 95 % CI: 2.13-4.01) after multivariable adjustment. Similarly, diabetic participants with onset age <45 years had greatest HRs for incident AD and VD, compared with their matched controls. LIMITATIONS: Our results only reflect the characteristics of UKB participants. CONCLUSIONS: Younger age at diabetes onset was significantly associated with a higher risk of dementia in this longitudinal cohort study.