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Background and objectivesAmyloid pathology, vascular disease pathology, and pathologies affecting the medial temporal lobe are associated with cognitive trajectories in older adults. However, only limited evidence exists on how these pathologies influence cognition in the oldest old. We evaluated whether amyloid burden, white matter hyperintensity (WMH) volume, and hippocampal volume (HV) are associated with cognitive level and decline in the oldest old.MethodsThis was a longitudinal, observational community-based cohort study. We included participants with 18F-florbetapir PET and MRI data from the 90+ Study. Amyloid load was measured using the standardized uptake value ratio in the precuneus/posterior cingulate with eroded white matter mask as reference. WMH volume was log-transformed. All imaging measures were standardized using sample means and SDs. HV and log-WMH volume were normalized by total intracranial volume using the residual approach. Global cognitive performance was measured by the Mini-Mental State Examination (MMSE) and modified MMSE (3MS) tests, repeated every 6 months. We used linear mixed-effects models with random intercepts; random slopes; and interaction between time, time squared, and imaging variables to estimate the associations of imaging variables with cognitive level and cognitive decline. Models were adjusted for demographics, APOE genotype, and health behaviors.ResultsThe sample included 192 participants. The mean age was 92.9 years, 125 (65.1%) were female, 71 (37.0%) achieved a degree beyond college, and the median follow-up time was 3.0 years. A higher amyloid load was associated with a lower cognitive level (βMMSE = -0.82, 95% CI -1.17 to -0.46; β3MS = -2.77, 95% CI -3.69 to -1.84). A 1-SD decrease in HV was associated with a 0.70-point decrease in the MMSE score (95% CI -1.14 to -0.27) and a 2.27-point decrease in the 3MS score (95% CI -3.40 to -1.14). Clear nonlinear cognitive trajectories were detected. A higher amyloid burden and smaller HV were associated with faster cognitive decline. WMH volume was not significantly associated with cognitive level or decline.DiscussionAmyloid burden and hippocampal atrophy are associated with both cognitive level and cognitive decline in the oldest old. Our findings shed light on how different pathologies contributed to driving cognitive function in the oldest old.

Most neuroimaging studies linking regional brain volumes with cognition correct for total intracranial volume (ICV), but methods used for this correction differ across studies. It is unknown whether different ICV correction methods yield consistent results. Using a brain-wide association approach in the MRI substudy of UK Biobank (N = 41,964; mean age = 64.5 years), we used regression models to estimate the associations of 58 regional brain volumetric measures with eight cognitive outcomes, comparing no correction and four ICV correction approaches. Approaches evaluated included: no correction; dividing regional volumes by ICV (proportional approach); including ICV as a covariate in the regression (adjustment approach); and regressing the regional volumes against ICV in different normative samples and using calculated residuals to determine associations (residual approach). We used Spearman-rank correlations and two consistency measures to quantify the extent to which associations were inconsistent across ICV correction approaches for each possible brain region and cognitive outcome pair across 2320 regression models. When the association between brain volume and cognitive performance was close to null, all approaches produced similar estimates close to the null. When associations between a regional volume and cognitive test were not null, the adjustment and residual approaches typically produced similar estimates, but these estimates were inconsistent with results from the crude and proportional approaches. For example, when using the crude approach, an increase of 0.114 (95% confidence interval [CI]: 0.103-0.125) in fluid intelligence was associated with each unit increase in hippocampal volume. However, when using the adjustment approach, the increase was 0.055 (95% CI: 0.043-0.068), while the proportional approach showed a decrease of -0.025 (95% CI: -0.035 to -0.014). Different commonly used methods to correct for ICV yielded inconsistent results. The proportional method diverges notably from other methods and results were sometimes biologically implausible. A simple regression adjustment for ICV produced biologically plausible associations.

INTRODUCTION: We estimated the ages when associations between Alzheimers disease (AD) genes and brain volumes begin among middle-aged and older adults. METHODS: Among 45,616 dementia-free participants aged 45-80, linear regressions tested whether genetic risk score for AD (AD-GRS) had age-dependent associations with 38 regional brain magnetic resonance imaging volumes. Models were adjusted for sex, assessment center, genetic ancestry, and intracranial volume. RESULTS: AD-GRS modified the estimated effect of age (per decade) on the amygdala (-0.41 mm3 [-0.42, -0.40]); hippocampus (-0.45 mm3 [-0.45, -0.44]), nucleus accumbens (-0.55 mm3 [-0.56, -0.54]), thalamus (-0.38 mm3 [-0.39, -0.37]), and medial orbitofrontal cortex (-0.23 mm3 [-0.24, -0.22]). Trends began by age 45 for the nucleus accumbens and thalamus, 48 for the hippocampus, 51 for the amygdala, and 53 for the medial orbitofrontal cortex. An AD-GRS excluding apolipoprotein E (APOE) was additionally associated with entorhinal and middle temporal cortices. DISCUSSION: APOE and other genes that increase AD risk predict lower hippocampal and other brain volumes by middle age.

IntroductionThe prevalence of poor sleep quality and sleep apnea differs by race and ethnicity and may contribute to racial disparities in cognitive aging. We investigated whether sleep quality and sleep apnea risk were associated with cognitive function and decline and whether the associations differed by race/ethnicity.MethodsParticipants from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE; N = 1690; mean age: 75.7 years) study, a cohort of Asian, Black, Latino, and White participants, completed a modified Pittsburgh Sleep Quality Index assessing subjective sleep quality, latency, duration, disturbances, sleep medication use, and daytime dysfunction. Sleep apnea risk was measured by questions about snoring, tiredness, and whether apnea was observed. Executive function and verbal episodic memory were assessed at three time points over an average of 2.7 years with the Spanish and English Neuropsychological Assessment Scale. We fit linear mixed-effect models and stratified analyses by race/ethnicity.ResultsHigher sleep apnea risk was associated with faster declines in verbal episodic memory (β^ sleep apnea = -0.02, 95% confidence interval [CI], -0.04, -0.001) but not in executive function. Poorer sleep quality was associated with lower levels of and faster decline in executive function but not in verbal episodic memory. Race/ethnicity modified these associations: compared to estimated effects among White participants, poorer global sleep quality (β^ sleep*time = -0.02, 95% CI, -0.02, -0.01) was associated with larger effects on decline in executive function among Black participants. Estimated effects of some individual sleep quality components were also modified by race/ethnicity; for example, sleep medication use was associated with faster declines in executive function (β^ sleep*time = -0.05, 95% CI, -0.07, -0.03) and verbal episodic memory β^ sleep*time = -0.04, 95% CI, -0.07, -0.02) among Black participants compared to White participants.DiscussionObservational evidence indicates sleep quality is a promising target for addressing racial/ethnic disparities in cognitive aging, especially among Black older adults.HighlightsSleep apnea risk was associated with faster declines in verbal episodic memory but not executive function among all participants.Global sleep quality was associated with lower levels of and faster decline in executive function but not verbal episodic memory among all participants.Black older adults were particularly susceptible to the estimated adverse cognitive impacts of global sleep quality, particularly the use of sleep medication.

The Domain of Unknown Function 506 (DUF506) belongs to the PD-(D/E) XK nuclease superfamily and has been reported to play critical roles in growth and development as well as responses to abiotic stresses. However, the function of DUF506 genes in Brassica rapa (B. rapa) remains unclear. In this study, a total of 18 BrDUF506 genes were identified and randomly distributed across eight chromosomes, categorized into four subfamilies. Analyzing their promoter sequences has uncovered various stress-responsive elements, such as those for drought, methyl jasmonate (MeJA), and abscisic acid (ABA). Bra000098 and Bra017099 exhibit significantly enhanced expression in response to heat and drought stress. Protein interaction predictions indicate that Bra000098 homolog, At2g38820, is interacting with ERF012 and PUB48 and is involved in abiotic stress regulation. Furthermore, gene expression profiling has identified Bra026262 with a high expression level in flowers and significantly decreased in female sterile mutants. Protein interaction prediction further revealed that its homolog, At4g32480, interacts with MYB and AGL proteins, suggesting the potential roles in female gametophyte development. The current study enhances our understanding of the functional roles of BrDUF506s, providing significant insights that are valuable in investigating sexual reproduction and abiotic stress responses in B. rapa. [ABSTRACT FROM AUTHOR]

Previous studies have shown that a high prevalence of depression and anxiety is a key factor leading to a decrease in student satisfaction with university life. Therefore, this study used two waves of longitudinal data to investigate the longitudinal relationships among depression, anxiety, and student satisfaction with university life among college students. We employed correlation analysis and cross-lagged models to analyze the correlation and cross-lagged relationships among depression, anxiety, and student satisfaction with university life. The results indicate a significant negative correlation between depression and student satisfaction with university life. The cross-lagged models indicate that depression (Time 1) negatively predicts student satisfaction with university life (Time 2). Anxiety (Time 1) does not have a significant predictive effect on student satisfaction with university life (Time 2). Moreover, student satisfaction with university life negatively predicts both depression (Time 2) and anxiety (Time 2). Improving student satisfaction with university life has a significant impact on reducing levels of depression and anxiety among college students. The research results can provide valuable information for mental health professionals, school administrators, and policymakers, enabling them to take more targeted measures to reduce depression and anxiety symptoms among university students and enhance student satisfaction with university life. [ABSTRACT FROM AUTHOR]

PFAS (per- and polyfluoroalkyl substances) have been extensively used across numerous industries and consumer goods. Due to their high persistence and mobility, they are ubiquitous in the environment. Exposure to PFAS occurs in people via multiple pathways such as dermal contact, water supply, air inhalation, and dietary intake. Even if some PFAS are being phased out because of their persistent presence in the environment and harmful impacts on human health, mixes of replacement and legacy PFAS will continue to pollute the ecosystem. Numerous toxicological investigations have revealed harmful effects of PFAS exposure on female reproductive health, e.g., polycystic ovaries syndrome, premature ovarian failure, endometriosis, reproductive system tumors, pregnancy complications, and adverse pregnancy outcomes. Despite extensive epidemiological studies on the reproductive toxicity of PFAS, research findings remain inconsistent, and the underlying mechanisms are not well understood. In this review, we give an in-depth description of the sources and pathways of PFAS, and then review the reproductive toxicity of PFAS and its possible mechanisms. [ABSTRACT FROM AUTHOR]

Berberine hydrochloride (BH) is a versatile bioactive compound derived from the plants of the Berberis genus, known for its various pharmacological effects. However, its oral bioavailability is low due to its high hydrophilicity and limited permeability. To enhance its clinical efficacy and oral bioavailability, this study designed and prepared a BH-loaded self-microemulsifying drug delivery system (BH-SMEDDS), and characterized its in vitro and in vivo properties. Firstly, the optimal formulation of BH-SMEDDS was selected using solubility evaluations, pseudo-ternary phase diagrams, and particle size analysis. The formulation containing 55% Capmul MCM, 22.5% Kolliphor RH 40, and 22.5% 1,2-propanediol was developed. BH-SMEDDS exhibited stable physicochemical properties, with an average particle size of 47.2 ± 0.10 nm and a self-emulsification time of 26.02 ± 0.24 s. Moreover, in vitro dissolution studies showed significant improvements in BH release in simulated intestinal fluid, achieving 93.1 ± 2.3% release within 300 min. Meanwhile, BH-SMEDDS did not exhibit cytotoxic effects on the Caco-2 cells. Additionally, BH-SMEDDS achieved a 1.63-fold increase in oral bioavailability compared to commercial BH tablets. Therefore, SMEDDS presents a promising strategy for delivering BH with enhanced oral bioavailability, demonstrating significant potential for clinical application. [ABSTRACT FROM AUTHOR]

Rare-earth doped oxysulfides have gained considerable attention as a luminescence host material owing to its good chemical stability and high efficiency. In this study, Er3+-sensitized La2O2S nanoparticles are prepared by the high-temperature co-precipitation method. La2O2S:2%Er3+ is selected to construct La2O2S:Er3+@La2O2S core/shell structures through epitaxial growth, and the luminescence properties are studied. The surface defects of La2O2S:Er3+ are repaired by the inert protective shell, and the luminescence intensity of the core/shell nanocrystals is increased by 9.6 times. Finally, MAPbI3 is spin-coated over the La2O2S:Er3+@La2O2S film to construct narrow band near-infrared photodetectors. Under 1550 nm excitation, the response rate is 23 mA W−1, detection rate is 2.57 × 108 Jones, and response time is 220 ms. [ABSTRACT FROM AUTHOR]

Microvesicles (MVs) containing proteins, nucleic acid or organelles are shed from the plasma membrane. Although the mechanisms of MV budding are well elucidated, the connection between endosomal trafficking and MV formation remains poorly understood. In this report, RAB22A is revealed to be crucial for EGFR‐containing MVs formation by the RAB GTPase family screening. RAB22A recruits TBC1D2B, a GTPase‐activating protein (GAP) of RAB7A, to inactivate RAB7A, thus preventing EGFR from being transported to late endosomes and lysosomes. RAB22A also engages SH3BP5L, a guanine‐nucleotide exchange factor (GEF) of RAB11A, to activate RAB11A on early endosomes. Consequently, EGFR is recycled to the cell surface and packaged into MVs. Furthermore, EGFR can phosphorylate RAB22A at Tyr136, which in turn promotes EGFR‐containing MVs formation. Our findings illustrate that RAB22A acts as a sorter on early endosomes to sort EGFR to recycling endosomes for MV shedding by both activating RAB11A and inactivating RAB7A. Summary: This report reveals that RAB22A acts as a sorter: to sort EGFR from early endosomes to recycling endosomes. RAB22A promotes EGFR‐containing MVs formation via recruiting TBC1D2B to inactivate RAB7A and engaging SH3BP5L to activate RAB11A. In the meantime, EGFR can phosphorylate Tyr136 of RAB22A to enhance the release of EGFR‐containing MVs. [ABSTRACT FROM AUTHOR]

Although numerous studies have emphasized the male predominance in autism spectrum disorder (ASD), how sex differences are related to the topological organization of functional networks remains unclear. This study utilized imaging data from 86 ASD (43 females, aged 7–18 years) and 86 typically developing controls (TCs) (43 females, aged 7–18 years) obtained from Autism Brain Imaging Data Exchange databases, constructed individual whole‐brain functional networks, used a graph theory analysis to compute topological metrics, and assessed sex‐related differences in topological metrics using a 2 × 2 factorial design. At the global level, females with ASD exhibited significantly higher cluster coefficient and local efficiency than female TCs, while no significant difference was observed between males with ASD and male TCs. Meanwhile, the neurotypical sex differences in cluster coefficient and local efficiency observed in TCs were not present in ASD. At the nodal level, ASD exhibited abnormal nodal centrality in the left middle temporal gyrus. Lay Summary: In this study, we focused on sex‐related alterations in the topological organization of functional networks in ASD and found greater differences between ASD and TCs in females than in males, consistent with the female protective effect hypothesis. Furthermore, the lack of neurotypical sex differences in ASD suggested that the processes of typical neural sex differentiation might be disturbed in ASD. These findings offer a fresh perspective on the sex differences of ASD at the large‐scale network level. [ABSTRACT FROM AUTHOR]

It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles of bortezomib, lenalidomide, and dexamethasone (daratumumab was recommended for frail patients), with treatment intensity adjusted according to longitudinal changes in the frailty category (IMWG-FI) at each cycle. Of 90 patients, 33 (37%), 16 (18%), and 41 (45%) were fit, intermediate fit, and frail at baseline, respectively. Of 75 patients who had geriatric assessment at least twice, 28 (37%) experienced frailty category changes at least once. At analysis, 15/26 (58%) frail patients improved (27% became fit and 31% became intermediate fit), 4/15 (27%) intermediate fit patients either improved or deteriorated (two for each), and 6/30 (20%) fit patients deteriorated. During induction, 34/90 (38%) patients discontinued treatment, including 10/33 (30%) fit, 4/16 (25%) intermediate fit, and 20/41 (49%) frail; 14/40 (35%) frail patients discontinued treatment within the first two cycles, mainly because of non-hematologic toxicity (mostly infections). For fit, intermediate-fit, and frail patients, the overall response rate was 100%, 93%, and 73%, respectively; one-year overall survival was 90%, 75%, and 54%, respectively. Therefore, the individualized DynaFiT is feasible and promising for heterogeneous elderly patients. [ABSTRACT FROM AUTHOR]

In this article, we present a transient temperature detection device for silicon carbide (SiC) Schottky barrier diodes (SBDs) based on thermal reflection theory. We constructed a thermal reflection temperature measurement device based on a 530-nm green laser. This device is more suitable for transient temperature measurement of SiC SBDs than previous thermal reflection equipment. The accuracy of temperature measurement by our device was confirmed by comparison with the results of infrared thermal imaging. The high temporal resolution characteristics of the thermal reflection technology allowed the detection of millisecond-level transient temperature changes in SiC SBDs. In addition, we investigated the complementarity of transient temperature change curves during heating and cooling processes, as well as the reasons for the differences between these curves. Finally, we used the structural function method combined with the Bayesian deconvolution algorithm to obtain the thermal resistance along the heat flow path of the device and validated the results using an established thermal resistance testing method. [ABSTRACT FROM AUTHOR]

The story of Futijinhu 浮提金壺 ("Golden Pot of Futi") in Shiyiji 拾遺記 (Record of Gleanings), whose authorship is traditionally attributed to Wang Jia (王嘉) from the Eastern Jin Dynasty, appears to be a Daoist rendition at first glance, reimagining the legend of Laozi's Daodejing. However, upon closer examination of the depiction of "Golden Pot of Futi", the characters with "Shentong Shanshu" (神通善書, supranormal cognition and exceptional writing ability) and the narrative of writing and its outcomes, it becomes evident that this tale harbors a multifaceted Buddhist essence. In the tale, one can observe the changes and diversity in the early methods of translating Buddhist scriptures into Chinese, the references and adaptations of Buddhist imagery and narratives by Daoists, the understanding and imagination of materials used for writing Buddhist scriptures and early iconographic forms, and even the author's insights and responses to the evolving religious landscape of their era. When placed in a broader historical context, exploring the Buddhist elements in this tale further aids in understanding the dynamic interactions between Buddhism and Daoism during the Wei and Jin periods. [ABSTRACT FROM AUTHOR]

Deep models may have disappointing performance in real applications due to the domain shifts in data distributions between the source and target domain. Although a few unsupervised domain adaptation methods have been proposed to make the pre-train models effective on target domain datasets, constraints like data privacy, security, and transmission limits restrict access to VHR remote sensing images, making existing unsupervised domain adaptation methods almost ineffective in specific change detection areas. Therefore, we propose a source-free unsupervised domain adaptation change detection structure to complete specific change detection tasks, using only the pre-trained source model and unlabelled target data. The GAN-based source generation component is designed to generate synthetic source data, which, to some extent, reflects the distribution of the source domain. Moreover, these data can be utilised in model knowledge transfer. The model adaptation component facilitates knowledge transfer between models by minimising the differences between deep features, using AAM (Attention Adaptation Module) to extract the difference between high-level features, meanwhile we proposed ISM (Intra-domain Self-supervised Module) to train target model in a self-supervised strategy in order to improve the knowledge adaptation. Our SFDA-CD framework demonstrates superior accuracy over existing unsupervised domain adaptation change detection methods, which has 0.6% cIoU and 1.5% F1 score up in cross-regional tasks and 1.4% cIoU and 1.9% F1 score up in cross-scenario tasks, proving that it can effectively reduce the domain shift between the source and target domains even without access to source data. Additionally, it can facilitate knowledge transfer from the source model to the target model. [ABSTRACT FROM AUTHOR]