Sevoflurane causes neurotoxicity and cognitive impairment by regulating Hippo signaling pathway-mediated ferroptosis via upregulating PRKCD.

BACKGROUND: Sevoflurane (SEV) has been found to induce neurotoxicity and cognitive impairment, leading to the development of degenerative diseases. Protein kinase C delta (PRKCD) is upregulated in the hippocampus of SEV-treated mice and may be related to SEV-related neurotoxicity. However, the underlying molecular mechanisms by which SEV mediates neurotoxicity via PRKCD remain unclear. METHODS: Normal mice and PRKCD knockout (KO) mice were exposed to SEV. Hippocampal neurons were isolated from mice hippocampal tissues. H&E staining was used for pathological morphology of hippocampal tissues, and NISSL staining was used to analyze the number of hippocampal neurons. The mRNA and protein levels were determined using quantitative real-time PCR, western blot, immunofluorescence staining and immunohistochemical staining. The mitochondrial microstructure was observed by transmission electron microscopy. Cell viability was detected by cell counting kit 8 assay, and ferroptosis was assessed by detecting related marker levels. The cognitive ability of mice was assessed by morris water maze test. And the protein levels of PRKCD, ferroptosis-related markers and Hippo pathway-related markers were examined by western bolt. RESULTS: SEV increased PRKCD expression and ferroptosis in hippocampal tissues of mice. Also, SEV promoted mouse hippocampal neuron injury by inducing ferroptosis via upregulating PRKCD expression. Knockout of PRKCD alleviated SEV-induced neurotoxicity and cognitive impairment in mice, and relieved SEV-induced ferroptosis in hippocampal neurons. PRKCD could inhibit the activity of Hippo pathway, and its knockdown also overturned SEV-mediated ferroptosis by activating Hippo pathway. CONCLUSION: SEV could induce neurotoxicity and cognitive impairment by promoting ferroptosis via inactivating Hippo pathway through increasing PRKCD expression.

Crown-Assisted CsCu2I3 Growth and Trap Passivation for Perovskite Light-Emitting Diodes.

Copper (Cu)-based perovskites are promising for lead-free perovskite light-emitting diodes (PeLEDs). However, it remains a significant challenge to achieve high performance devices due to the nonradiative loss caused by the disordered crystallization and lack of passivation. Crown ethers are known to form host-guest complexes by the interaction between C-O-C groups and certain cations, and 18-crown-6 (18C6) with an appropriate complementary size can interact with Cs+ and Cu+ cations. Herein, we studied the interaction between CsCu2I3 and two crowns with the same cyclic size, 18C6 and dibenzo-18-crown-6 (D18C6). Particularly, D18C6 can reduce the nonradiative recombination rate of CsCu2I3 film by passivating the defects and optimizing the film morphology effectively. The room mean square (RMS) decreased from 5.06 to 2.95 nm, and the PLQY was promoted from 4.71% to 19.9%. Besides, D18C6 can also decrease the barrier of hole injection. The PeLEDs based on D18C6-modified CsCu2I3 realized noticeable improvement with a maximum luminance and EQE of 583 cd/m2 and 0.662%, respectively.

Statins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1.

Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.

Research Progress of Mitophagy in Alzheimer's Disease.

The prevalence of Alzheimer's disease (AD) is increasing as the elderly population, which hurts elderly people's cognition and capacity for self-care. The process of mitophagy involves the selective clearance of ageing and impaired mitochondria, which is required to preserve intracellular homeostasis and energy metabolism. Currently, it has been discovered that mitophagy abnormalities are intimately linked to the beginning and progression of AD. This article discusses the mechanism of mitophagy, abnormal mitophagy, and therapeutic effects in AD. The purpose is to offer fresh perspectives on the causes and remedies of AD.

Electrocardiogram identification based on data generative network and non-fiducial data processing.

Nowadays, the use of biological signals as a criterion for identity recognition has gained increasing attention from various organizations and companies. Therefore, it has become crucial to have a biometric identity recognition method that is fast and accurate. In this paper, we propose a linear electrocardiogram (ECG) data preprocessing algorithm based on Kalman filters for rapid noise data filtering (wavelet transform filtering algorithm). Additionally, we introduce a generative network model called Data Generation Strategy Network (DRCN) based on generative networks. The DRCN is employed to augment training samples for convolutional classification networks, ultimately improving the classification performance of the model. Through the final experiments, our method successfully reduced the average misidentification rate of ECG-based identity recognition to 2.5%, and achieved an average recognition rate of 98.7% for each category, significantly surpassing previous achievements. In the future, this method is expected to be widely applied in the field of ECG-based identity recognition.

Sub-Second Long Lifetime Triplet Exciton Reservoir for Highly Efficient and Stable Organic Light-Emitting Diode.

In organic light-emitting diode (OLED), achieving high efficiency requires effective triplet exciton confinement by carrier-transporting materials, which typically have higher triplet energy (ET) than the emitter, leading to poor stability. Here, an electron-transporting material (ETM), whose ET is 0.32 eV lower than that of the emitter is reported. In devices, it surprisingly exhibits strong confinement effect and generates excellent efficiency. Additionally, the device operational lifetime is 4.9 times longer than the device with a standard ETM, 1,3,5-tri(1-phenyl-1H-benzo[d]imidazol-2-yl) phenyl (whose ET 0.36 eV is higher than the emitter). This anomalous finding is ascribed to the exceptionally long triplet state lifetime (≈0.2 s) of the ETM. It is named as long-lifetime triplet exciton reservoir effect. The systematic analysis reveals that the long triplet lifetime of ETM can compensate the requirement for high ET with the help of endothermic energy transfer. Such combination of low ET and long lifetime provides equivalent exciton confinement effect and high molecular stability simultaneously. It offers a novel molecular design paradigm for breaking the dilemma between high efficiency and prolonged operational lifetime in OLEDs.

Multimodal Brain Tumor Segmentation Boosted by Monomodal Normal Brain Images.

Many deep learning based methods have been proposed for brain tumor segmentation. Most studies focus on deep network internal structure to improve the segmentation accuracy, while valuable external information, such as normal brain appearance, is often ignored. Inspired by the fact that radiologists often screen lesion regions with normal appearance as reference in mind, in this paper, we propose a novel deep framework for brain tumor segmentation, where normal brain images are adopted as reference to compare with tumor brain images in a learned feature space. In this way, features at tumor regions, i.e., tumor-related features, can be highlighted and enhanced for accurate tumor segmentation. It is known that routine tumor brain images are multimodal, while normal brain images are often monomodal. This causes the feature comparison a big issue, i.e., multimodal vs. monomodal. To this end, we present a new feature alignment module (FAM) to make the feature distribution of monomodal normal brain images consistent/inconsistent with multimodal tumor brain images at normal/tumor regions, making the feature comparison effective. Both public (BraTS2022) and in-house tumor brain image datasets are used to evaluate our framework. Experimental results demonstrate that for both datasets, our framework can effectively improve the segmentation accuracy and outperforms the state-of-the-art segmentation methods. Codes are available at https://github.com/hb-liu/Normal-Brain-Boost-Tumor-Segmentation.

Passivating A-Site and X-Site Vacancies Simultaneously via N-Heterocyclic Amines for Efficient Cs2AgBiBr6 Solar Cells.

To address the toxicity and stability issues of traditional lead halide perovskite solar cells (PSCs), the development of lead-free PSCs, such as Cs2AgBiBr6 solar cells, is of great significance. However, due to the low defect formation energy of Cs2AgBiBr6, a large number of vacancies, including A-site vacancies and X-site vacancies, form during the fabrication process of the Cs2AgBiBr6 film, which seriously damage the performance of the devices. The traditional phenylethylammonium (PEA) cation, mainly focusing on passivating A-site vacancies, is incapable of reducing X-site vacancies and so results in a limited performance improvement in Cs2AgBiBr6 solar cells. Herein, inspired by the capability of the Lewis base to coordinate with metal cations, a series of N-heterocyclic amines are introduced to serve as a dual-site passivator, reducing A-site and X-site vacancies at the same time. The highest power conversion efficiency of modified Cs2AgBiBr6 solar cells has been increased 36% from 1.10 to 1.50%. Further investigation reveals that the higher electron density of additives would lead to a stronger interaction with metal cations like Ag+ and Bi3+, thus reducing more X-site defects and improving carrier dynamics. Our work provides a strategy for passivating perovskite with various kinds of defects and reveals the connection between the coordination capability of additives and device performance enhancement, which could be instructive in improving the performance of lead-free PSCs.

A New Multi-Atlas Based Deep Learning Segmentation Framework With Differentiable Atlas Feature Warping.

Deep learning based multi-atlas segmentation (DL-MA) has achieved the state-of-the-art performance in many medical image segmentation tasks, e.g., brain parcellation. In DL-MA methods, atlas-target correspondence is the key for accurate segmentation. In most existing DL-MA methods, such correspondence is usually established using traditional or deep learning based registration methods at image level with no further feature level adaption. This could cause possible atlas-target feature inconsistency. As a result, the information from atlases often has limited positive and even counteractive impact on the final segmentation results. To tackle this issue, in this paper, we propose a new DL-MA framework, where a novel differentiable atlas feature warping module with a new smooth regularization term is presented to establish feature level atlas-target correspondence. Comparing with the existing DL-MA methods, in our framework, atlas features containing anatomical prior knowledge are more relevant to the target image feature, leading the final segmentation results to a high accuracy level. We evaluate our framework in the context of brain parcellation using two public MR brain image datasets: LPBA40 and NIREP-NA0. The experimental results demonstrate that our framework outperforms both traditional multi-atlas segmentation (MAS) and state-of-the-art DL-MA methods with statistical significance. Further ablation studies confirm the effectiveness of the proposed differentiable atlas feature warping module.

Reversible splenial lesion syndrome in children: a retrospective study of 130 cases.

Background: Reversible splenial lesion syndrome (RESLES) is a new clinico-radiological syndrome. We retrospectively analyzed the clinical features of 130 children with RESLES in China, which is the largest case series available in the literature. Methods: The clinical data of children diagnosed as RESLES in Jiangxi Provincial Children's Hospital between 2017 and 2023 were retrospectively analyzed. The 130 cases were divided into two groups: ≤ 3 years old group (group A) (n = 83) and > 3 years old group (group B) (n = 47). The chi-squared test or Fisher's test was used to evaluate the data. Results: The vast majority of patients (127/130 cases, 97.7%) had prodromal symptoms of infection. Preceding infections of the gastrointestinal tract were statistically more significant in group A (60/83, 72.3%) than in group B (11/47, 23.4%) (P < 0.05). Preceding infections of the respiratory tract were statistically more significant in group B (33/47, 70.2%) than in group A (17/83, 20.5%) (P < 0.05). Seizures were statistically more significant in group A (82/83, 98.8%) than in group B (24/47,51.1%) (P < 0.05). The disturbance of consciousness and headache/dizziness were statistically more significant in group B (27/47, 57.4%; 37/47, 78.7%) than in group A (3/83, 3.6%; 1/83, 1.2%), respectively (P < 0.05). Convulsions with mild gastroenteritis (CwG) were statistically more significant in group A (50/83, 60.2%) than in group B (8/47, 17.0%) (P < 0.05). However, encephalitis/encephalopathy was statistically more significant in group B (20/47, 42.6%) than in group A (10/83, 12.0%) (P < 0.05). MRI showed cytotoxic edema in typical locations (RESLES type-1 limited to the splenium of the corpus callosum and RESLES type-2 spread to the entire corpus callosum, adjacent white matter, or both). There was full recovery of the lesions of MRI in all cases from 3 days to 50 days after the initial examinations. All the children showed normal neurodevelopment. Conclusion: Infection was the most common cause of RESLES. Infections of the gastrointestinal tract are common in ≤ 3 years old children, while infections of the respiratory tract are common in >3 years old children. Younger patients are more likely to develop convulsions, and older children were more likely to have symptoms with disturbance of consciousness and headache/dizziness. RESLES has characteristic MRI manifestations and a good prognosis.

Highly Efficient Light-Emitting Diodes Based on Self-Assembled Colloidal Quantum Wells.

Nanocrystal-based light-emitting diodes (Nc-LEDs) have immense potential for next-generation high-definition displays and lighting applications. They offer numerous advantages, such as low cost, high luminous efficiency, narrow emission, and long lifetime. However, the external quantum efficiency (EQE) of Nc-LEDs, typically employing isotropic nanocrystals, is limited by the out-coupling factor. Here efficient, bright, and long lifetime red Nc-LEDs based on anisotropic nanocrystals of colloidal quantum wells (CQWs) are demonstrated. Through modification of the substrate's surface properties and control of the interactions among CQWs, a self-assembled layer with an exceptionally high distribution of in-plane transitions dipole moment of 95%, resulting in an out-coupling factor of 37% is successfully spin-coated. The devices exhibit a remarkable peak EQE of 26.9%, accompanied by a maximum brightness of 55 754 cd m-2 and a long operational lifetime (T95 @100 cd m-2 ) over 15 000 h. These achievements represent a significant advancement compared to previous studies on Nc-LEDs incorporating anisotropic nanocrystals. The work is expected to provide a general self-assembly strategy for enhancing the light extraction efficiency of Nc-LEDs based on anisotropic nanocrystals.

Acupuncture Improves Synaptic Plasticity of SAMP8 Mice through the RhoA/ROCK Pathway.

BACKGROUND: Studies have found synaptic plasticity damage to be an early marker of Alzheimer's disease (AD). RhoA/ROCK pathway is involved in the regulation of synaptic plasticity. Acupuncture can significantly improve the cognitive state of AD. OBJECTIVE: We aimed to use modern biological technology to detect the changes in synaptic plasticity and RhoA/ROCK pathway in SAMP8 mice, as well as the intervention effect of acupuncture. METHODS: Morris water maze and electrophysiological techniques were used in vivo to detect the changes in spatial memory and LTP of mice. Golgi Cox staining and CASEVIEWER2.1 software were used to quantitatively analyze the changes in the morphology and number of dendritic spines in the hippocampus of mice. The activity of RhoA and ROCK2 in the hippocampus of mice was detected, respectively, by pull-down technique and ELISA. WB technique was used to detect the protein expression of ROCK2 and phosphorylation level of MLC2, LIMK2, and CRMP2 in the hippocampus of mice. RESULTS: The neurobehavior and synaptic plasticity of 8-month-old SAMP8 mice were found to be significantly impaired. Acupuncture could improve the spatial learning and memory ability of SAMP8 mice, and partially prevent the reduction in the number of spines on the secondary branches of the apical dendrites in the hippocampus and the attenuation of LTP. The RhoA/ROCK pathway was significantly activated in the hippocampus of 8-month-old SAMP8 mice, and acupuncture had an inhibitory effect on it. CONCLUSION: Acupuncture can improve synaptic plasticity by inhibiting the abnormal activation of the RhoA/ROCK pathway, and improve the spatial learning and memory ability of AD, so as to achieve the purpose of treating AD.

Superstable CsxSnBrx+2@CsBr Nanocrystals with Over 1200 h of Half-Value PLQY in Air.

Tin-based perovskites comprise one of the preferred nontoxic alternatives to Pb-based perovskites due to their desirable optoelectronic properties. However, there remains a crucial stability problem due to the property of Sn2+ oxidation. In this study, we reported stable tin-based perovskite nanocrystals (NCs) using stannous acetate as the Sn2+ source because of its stronger Sn-O bonding. To prevent the oxidation of Sn2+, a thin layer of CsBr coverage was formed in situ; tin-based perovskite NCs, CsxSnBrx+2@CsBr (1 < x < 4), show a high photoluminescence quantum yield (PLQY) of 78.2% and high stability. The measured lifetime of PLQY decrease to half of the initial value is ∼1287 h under ambient conditions and ∼2200 h under a nitrogen atmosphere, respectively. Furthermore, the as-fabricated light-emitting diodes based on CsxSnBrx+2@CsBr NCs as the emitting layer exhibit a maximum luminescence of 16 cd/m2 and an external quantum efficiency of 0.035% with peaks at 451 and 615 nm, corresponding to the emissions of CsBr and CsxSnBrx+2, respectively. This work provided a new way to obtain stable Sn-based perovskite NCs and exhibited their potential for application in white light-emitting diodes (LEDs).

Separating Crystal Growth from Nucleation Enables the In Situ Controllable Synthesis of Nanocrystals for Efficient Perovskite Light-Emitting Diodes.

Colloidal perovskite nanocrystals (PNCs) display bright luminescence for light-emitting diode (LED) applications; however, they require post-synthesis ligand exchange that may cause surface degradation and defect formation. In situ-formed PNCs achieve improved surface passivation using a straightforward synthetic approach, but their LED performance at the green wavelength is not yet comparable with that of colloidal PNC devices. Here, it is found that the limitations of in situ-formed PNCs stem from uncontrolled formation kinetics: conventional surface ligands confine perovskite nuclei but fail to delay crystal growth. A bifunctional carboxylic-acid-containing ammonium hydrobromide ligand that separates crystal growth from nucleation is introduced, leading to the formation of quantum-confined PNC solids exhibiting a narrow size distribution. Controlled crystallization is further coupled with defect passivation using deprotonated phosphinates, enabling improvements in photoluminescence quantum yield to near unity. Green LEDs are fabricated with a maximum current efficiency of 109 cd A-1 and an average external quantum efficiency of 22.5% across 25 devices, exceeding the performance of their colloidal PNC-based counterparts. A 45.6 h operating half-time is further documented for an unencapsulated device in N2 with an initial brightness of 100 cd m-2 .

Structural credit risk model driven by Lévy process under knight uncertainty.

As per the projections of conventional credit risk structured model, the risky asset values tend to adhere to the geometric Brownian motion. On the contrary, the risky asset values remain a non-continuous and dynamic ones and jump based on the conditions. Is not possible to measure the real Knight Uncertainty risks in financial markets with the help of a single probability measure. In this background, the current research work analyzes a structural credit risk model that belongs to Levy market under Knight Uncertainty. With the help of Lévy-Laplace exponent, the authors developed a dynamic pricing model in this study and acquired the price intervals for default probability, stock value and the bond value of enterprise. To be specific, the study intended to establish explicit solutions for three value processes, discussed earlier, with an assumption that the jump process follows a log-normal distribution. At the end, the study also conducted numerical analysis to understand the crucial role played by Knight Uncertainty upon the pricing of default probability and the stock value of the enterprise.

Boosting the Performance of Perovskite Solar Cells through Systematic Investigation of the Annealing Effect of E-Beam Evaporated TiO2.

Electron transport layer (ETL) plays an undeniable role in improving the performance of n-i-p planar perovskite solar cells (PSCs). Titanium dioxide (TiO2) is known as a promising ETL material for perovskite solar cell. In this work, the effect of annealing temperature on optical, electrical, and surface morphology of the electron-beam (EB)-evaporated TiO2 ETL, and consequently on the performance of perovskite solar cell, was investigated. It was found that annealing treatment at an optimized temperature of 480 °C considerably improved the surface smoothness, density of grain boundaries, and carrier mobility of TiO2 film, which resulted in nearly 10-fold improvement in power conversion efficiency (11.16%) in comparison with the unannealed device (1.08%). The improvement in performance of the optimized PSC is attributed to the acceleration of charge carrier extraction, as well as suppression of the recombination at the ETL/Perovskite interface.

Association between bilirubin levels and risk of stroke: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the association between bilirubin levels and stroke risk. DESIGN: Systematic review and meta-analysis, reported in accordance with Meta-analysis Of Observational Studies in Epidemiology guidelines. DATA SOURCES: The PubMed, Embase, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure Databases were searched from inception up to 27 February 2022. ELIGIBILITY CRITERIA: Cohort studies assessing the dose-response relationship between bilirubin levels and risk of stroke were eligible for inclusion. There were no language restrictions. DATA EXTRACTION AND SYNTHESIS: All data from eligible studies were collected and assessed by two independent investigators. We generated pooled relative risks (RRs) with 95% CIs. We used a restricted cubic spline model for the dose-response analyses. Subsequent subgroup analyses were conducted according to stroke outcomes, follow-up duration, geographical area and size of the cohort. RESULTS: Nine articles including results from 11 cohort studies with 7835 cases of stroke and 263 596 participants met the inclusion criteria. The summarised RR of stroke comparing the highest and lowest bilirubin level was 0.85 (95% CI 0.72 to 0.99). The dose-response analysis indicated that a 15 µmol/L increment of bilirubin level was associated with an 18% lower risk of stroke (RR=0.82, 95% CI 0.67 to 0.99). For ischaemic stroke, the RR was 0.76 (95% CI 0.58 to 0.99). Significant publication bias was not detected. CONCLUSIONS: Elevated bilirubin levels were associated with a decreased risk of stroke among adults. PROSPERO REGISTRATION NUMBER: CRD42017071497.

Effect of Interventional Therapy Unexplained Dizziness and Relationship Between Dizziness Handicap Inventory and Right-to-Left Shunt Grading.

Objective: Unexplained dizziness remains a clinical challenge. Our previous studies have shown that unexplained dizziness may be related to patent foramen ovale (PFO). This study aims to explore whether the degree of shunt is correlated with the degree of unexplained dizziness and looking for the possible clinical intervention for patients with unexplained dizziness. Methods: This study was a large single-center, prospective, controlled study. From March 2019 to March 2022, patients with unexplained dizziness and explained dizziness and healthy controls were recruited. Contrast-enhanced transcranial Doppler sonography (c-TCD) was performed to detect the existence of right-to-left shunt (RLS) and shunt grading. The dizziness handicap inventory (DHI) was completed to evaluate the dizziness. Unexplained dizziness patients with large amount of PFO were volunteered to receive medication treatment and transcatheter PFO closure and followed up six months. Results: A total of 387 patients (132 unexplained, 123 explained and 132 controls) were enrolled. There was a statistical difference in the RLS grading with three groups (p < 0.001). The Spearman correlation coefficient of RLS grading and DHI scores in unexplained dizziness patients (r=0.122, p=0.163) and explained dizziness patients (r=0.067, p=0.460). In the unexplained group, there were 49 cases with massive grading RLS. Of which 25 patients received percutaneous PFO closure treatment and 24 cases received medication treatment. Followed up six months after treatment, the amount of DHI scores change in patients who received the percutaneous PFO closure was significantly higher than that in the medication treatment group (p < 0.001). Conclusion: RLS may play an important role in unexplained dizziness. For unexplained dizziness patients, PFO closure may contribute to better outcomes. In the future, large-scale randomized controlled studies are still needed.

Association between loneliness and dementia risk: A systematic review and meta-analysis of cohort studies.

Loneliness has been reported to be associated with an increased risk of dementia; however, the extent of this relationship remains controversial. This study aimed to assess the strength of the relationship between loneliness and dementia using a meta-analysis approach. PubMed, EMBASE, and China National Knowledge Internet databases were systematically searched for potentially included studies from inception up to 17 February 2022. A meta-analysis was performed using a random-effects model to assess pooled relative risks (RRs) and 95% confidence intervals (CIs). A literature search identified 16 cohort studies (published in 15 articles), among which 4,625 dementia cases and 62,345 individuals were selected for further meta-analysis. Loneliness was associated with an increased risk of Alzheimer's disease (AD) (RR: 1.72, 95% CI: 1.32-2.23; P < 0.001) and dementia (RR: 1.23, 95% CI: 1.16-1.31; P < 0.00001). However, no significant association between loneliness and risk of mild cognitive impairment (MCI) (RR: 1.34, 95% CI: 0.97-1.87; P = 0.080) or vascular dementia (VaD) (RR: 1.01, 95% CI: 0.51-1.99; P = 0.973) was observed. Results revealed that loneliness might increase the risk of Alzheimer's disease and dementia. Early interventions that limit loneliness may reduce risk of dementia and Alzheimer's disease.