Dispersion-assisted high-dimensional photodetector.

Intensity, polarization and wavelength are intrinsic characteristics of light. Characterizing light with arbitrarily mixed information on polarization and spectrum is in high demand1-4. Despite the extensive efforts in the design of polarimeters5-18 and spectrometers19-27, concurrently yielding high-dimensional signatures of intensity, polarization and spectrum of the light fields is challenging and typically requires complicated integration of polarization- and/or wavelength-sensitive elements in the space or time domains. Here we demonstrate that simple thin-film interfaces with spatial and frequency dispersion can project and tailor polarization and spectrum responses in the wavevector domain. By this means, high-dimensional light information can be encoded into single-shot imaging and deciphered with the assistance of a deep residual network. To the best of our knowledge, our work not only enables full characterization of light with arbitrarily mixed full-Stokes polarization states across a broadband spectrum with a single device and a single measurement but also presents comparable, if not better, performance than state-of-the-art single-purpose miniaturized polarimeters or spectrometers. Our approach can be readily used as an alignment-free retrofit for the existing imaging platforms, opening up new paths to ultra-compact and high-dimensional photodetection and imaging.

Genomic loci influence patterns of structural covariance in the human brain.

Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data-driven, multi-scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are newly identified, and 72% were independently replicated. Key pathways influencing PSCs involve reelin signaling, apoptosis, neurogenesis, and appendage development, while pathways of breast cancer indicate potential interplays between brain metastasis and PSCs associated with neurodegeneration and dementia. Using support vector machines, multi-scale PSCs effectively derive imaging signatures of several brain diseases. Our results elucidate genetic and biological underpinnings that influence structural covariance patterns in the human brain.

Proteomic Indicators of Health Predict Alzheimer's Disease Biomarker Levels and Dementia Risk.

OBJECTIVE: Few studies have comprehensively examined how health and disease risk influence Alzheimer's disease (AD) biomarkers. The present study examined the association of 14 protein-based health indicators with plasma and neuroimaging biomarkers of AD and neurodegeneration. METHODS: In 706 cognitively normal adults, we examined whether 14 protein-based health indices (ie, SomaSignal® tests) were associated with concurrently measured plasma-based biomarkers of AD pathology (amyloid-ß [Aß]42/40 , tau phosphorylated at threonine-181 [pTau-181]), neuronal injury (neurofilament light chain [NfL]), and reactive astrogliosis (glial fibrillary acidic protein [GFAP]), brain volume, and cortical Aß and tau. In a separate cohort (n = 11,285), we examined whether protein-based health indicators associated with neurodegeneration also predict 25-year dementia risk. RESULTS: Greater protein-based risk for cardiovascular disease, heart failure mortality, and kidney disease was associated with lower Aß42/40 and higher pTau-181, NfL, and GFAP levels, even in individuals without cardiovascular or kidney disease. Proteomic indicators of body fat percentage, lean body mass, and visceral fat were associated with pTau-181, NfL, and GFAP, whereas resting energy rate was negatively associated with NfL and GFAP. Together, these health indicators predicted 12, 31, 50, and 33% of plasma Aß42/40 , pTau-181, NfL, and GFAP levels, respectively. Only protein-based measures of cardiovascular risk were associated with reduced regional brain volumes; these measures predicted 25-year dementia risk, even among those without clinically defined cardiovascular disease. INTERPRETATION: Subclinical peripheral health may influence AD and neurodegenerative disease processes and relevant biomarker levels, particularly NfL. Cardiovascular health, even in the absence of clinically defined disease, plays a central role in brain aging and dementia. ANN NEUROL 2024;95:260-273.

Deciphering adipose development: Function, differentiation and regulation.

The overdevelopment of adipose tissues, accompanied by excess lipid accumulation and energy storage, leads to adipose deposition and obesity. With the increasing incidence of obesity in recent years, obesity is becoming a major risk factor for human health, causing various relevant diseases (including hypertension, diabetes, osteoarthritis and cancers). Therefore, it is of significance to antagonize obesity to reduce the risk of obesity-related diseases. Excess lipid accumulation in adipose tissues is mediated by adipocyte hypertrophy (expansion of pre-existing adipocytes) or hyperplasia (increase of newly-formed adipocytes). It is necessary to prevent excessive accumulation of adipose tissues by controlling adipose development. Adipogenesis is exquisitely regulated by many factors in vivo and in vitro, including hormones, cytokines, gender and dietary components. The present review has concluded a comprehensive understanding of adipose development including its origin, classification, distribution, function, differentiation and molecular mechanisms underlying adipogenesis, which may provide potential therapeutic strategies for harnessing obesity without impairing adipose tissue function.

Enhancing Zn2+ Storage Performance by Constructing the Interfaces Between VO2 and Co-N-C Layers.

Vanadium oxides have aroused attention as cathode materials in aqueous zinc-ion batteries (AZIBs) due to their low cost and high safety. However, low ion diffusion and vanadium dissolution often lead to capacity decay and deteriorating stability during cycling. Herein, vanadium dioxides (VO2) nanobelts are coated with a single-atom cobalt dispersed N-doped carbon (Co-N-C) layer via a facile calcination strategy to form Co-N-C layer coated VO2 nanobelts (VO2@Co-N-C NBs) for cathodes in AZIBs. Various in-/ex situ characterizations demonstrate the interfaces between VO2 layers and Co-N-C layers can protect the VO2 NBs from collapsing, increase ion diffusion, and enhance the Zn2+ storage performance. Additional density functional theory (DFT) simulations demonstrate that Co─O─V bonds between VO2 and Co-N-C layers can enhance interfacial Zn2+ storage. Moreover, the VO2@Co-N-C NBs provided an ultrahigh capacity (418.7 mAh g-1 at 1 A g-1), outstanding long-term stability (over 8000 cycles at 20 A g-1), and superior rate performance.

Plasma proteins related to inflammatory diet predict future cognitive impairment.

Dysregulation of the immune system and dietary patterns that increase inflammation can increase the risk for cognitive decline, but the mechanisms by which inflammatory nutritional habits may affect the development of cognitive impairment in aging are not well understood. To determine whether plasma proteins linked to inflammatory diet predict future cognitive impairment, we applied high-throughput proteomic assays to plasma samples from a subset (n = 1528) of Women's Health Initiative Memory Study (WHIMS) participants (mean [SD] baseline age, 71.3 [SD 3.8] years). Results provide insights into how inflammatory nutritional patterns are associated with an immune-related proteome and identify a group of proteins (CXCL10, CCL3, HGF, OPG, CDCP1, NFATC3, ITGA11) related to future cognitive impairment over a 14-year follow-up period. Several of these inflammatory diet proteins were also associated with dementia risk across two external cohorts (ARIC, ESTHER), correlated with plasma biomarkers of Alzheimer's disease (AD) pathology (Aß42/40) and/or neurodegeneration (NfL), and related to an MRI-defined index of neurodegenerative brain atrophy in a separate cohort (BLSA). In addition to evaluating their biological relevance, assessing their potential role in AD, and characterizing their immune-tissue/cell-specific expression, we leveraged published RNA-seq results to examine how the in vitro regulation of genes encoding these candidate proteins might be altered in response to an immune challenge. Our findings indicate how dietary patterns with higher inflammatory potential relate to plasma levels of immunologically relevant proteins and highlight the molecular mediators which predict subsequent risk for age-related cognitive impairment.

A multicrosslinked network composite hydrogel scaffold based on DLP photocuring printing for nasal cartilage repair.

Natural hydrogels are widely employed in tissue engineering and have excellent biodegradability and biocompatibility. Unfortunately, the utilization of such hydrogels in the field of three-dimensional (3D) printing nasal cartilage is constrained by their subpar mechanical characteristics. In this study, we provide a multicrosslinked network hybrid ink made of photocurable gelatin, hyaluronic acid, and acrylamide (AM). The ink may be processed into intricate 3D hydrogel structures with good biocompatibility and high stiffness properties using 3D printing technology based on digital light processing (DLP), including intricate shapes resembling noses. By varying the AM content, the mechanical behavior and biocompatibility of the hydrogels can be adjusted. In comparison to the gelatin methacryloyl (GelMA)/hyaluronic acid methacryloyl (HAMA) hydrogel, adding AM considerably enhances the hydrogel's mechanical properties while also enhancing printing quality. Meanwhile, the biocompatibility of the multicrosslinked network hydrogels and the development of cartilage were assessed using neonatal Sprague-Dawley (SD) rat chondrocytes (CChons). Cells sown on the hydrogels considerably multiplied after 7 days of culture and kept up the expression of particular proteins. Together, our findings point to GelMA/HAMA/polyacrylamide (PAM) hydrogel as a potential material for nasal cartilage restoration. The photocuring multicrosslinked network ink composed of appropriate proportions of GelMA/HAMA/PAM is very suitable for DLP 3D printing and will play an important role in the construction of nasal cartilage, ear cartilage, articular cartilage, and other tissues and organs in the future. Notably, previous studies have not explored the application of 3D-printed GelMA/HAMA/PAM hydrogels for nasal cartilage regeneration.

Analysis of the Efficacy of Psychological Intervention in 85 patients with New Coronavirus Pneumonia.

Objective: To investigate the effectiveness of strengthen psychological intervention in 85 clients who had pneumonia caused by a novel coronavirus. Methods: As the study's subjects, 162 new coronavirus pneumonia clients admitted to our hospital between January 2020 and September 2020 had their clinical records retrospectively examined. According to different nursing methods, 162 patients with new coronavirus pneumonia were separated into a control team (n=77) and an experimental team (n=85). The test group received the intense psychological intervention, whereas the controlling team only received standard nursing care. The two groups' treatment compliance and nursing satisfaction were observed, the self-rating symptom scale (SCL-90) scores and coping style (MCMQ) grades of the two teams prior to and after the interference was contrasted, and the nursing quality of the two teams was contrasted. Results: In terms of compliance, the overall treatment compliance rate of patients in the experimental group increased significantly. In terms of the psychological state of the experimental group, significant improvements were observed in all psychological dimensions of the patients in the experimental group, including a reduction in negative emotions and an increase in nursing satisfaction. In terms of self-coping, patients in the experimental group showed significant improvement in various dimensions. And the quality of nursing care in the experimental group has been significantly improved. Conclusion: This study highlights the importance of intensive psychological intervention in the overall care of COVID-19 patients and its role in improving patient treatment compliance, negative emotions, self-coping styles and patient health.

A Safe Technique for Excising the Perpendicular Plate of the Ethmoid Bone in Patients with Crooked Nose: A Finite Element Analysis.

BACKGROUND: Correction of the crooked nose, especially the perpendicular plate of the ethmoid bone, has the potential to cause skull base injury. At present, the safe and effective method for perpendicular plate resection has not been clearly defined through biomechanics. METHOD: CT scan data of 48 patients with crooked nose and deviated nasal septum were divided into C-type, angular deformity-type, and S-type based on the morphology of the 3D model. Different types of finite element models of the nasal bony septum and skull base were established. The osteotomy depth, angle, and force mode of the PPE resection were simulated by assembling different working conditions for the models. The von Mises stress of the anterior cranial fossa was observed. RESULTS: When the osteotomy line length was 0.5 cm, the angle was at 30° to the Frankfurt plane, and 50 N·mm torque was applied, the von Mises stress of the skull base was minimal in the four models, showing 0.049 MPa (C-type), 0.082 MPa (S-type), 0.128 MPa (angular deformity-type), and 0.021 MPa (control model). The maximum von Mises stress values were found at the skull base when the osteotomy line was 1.5 cm, the angle was 50°, and the force was 10 N along the X-axis, showing 0.349 MPa (C-type), 0.698 MPa (S-type), 0.451 MPa (angular deformity-type), and 0.149 MPa (control model). CONCLUSION: The use of smaller resection angle with the Frankfurt plane, conservative resection depth, and torsion force can better reduce the stress value at the skull base and reduce the risk of basicranial fracture. It is a safe and effective technique for perpendicular plate resection of the ethmoid bone in the correction of crooked nose. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Three-Dimensional Morphological Study on the Effectiveness of Expanded Polytetrafluoroethylene Prosthesis in the Paranasal Augmentation.

BACKGROUND: The paranasal depression is a common facial feature of Oriental populations. One of the most wildly used method to improve it was paranasal augmentation using expanded polytetrafluoroethylene (ePTFE). The effectiveness of it should be tested by three-dimensional morphological measurements. METHODS: Patients who underwent paranasal augmentation using ePTFE between January 2017 and December 2022 were recruited in the study. The preoperative and postoperative clinical variables and three-dimensional measurement of patients were also collected. The satisfaction outcome were assessed. RESULTS: By establishing a coordinate system based on the Frankfurt plane, 16 landmarks including nasal alar crest, subnasal point, upper lip, pogonion, glabella, sub-cheek, orbitale, tragion in left and right side of faces were marked. Five segments, 4 ratios, and 3 angles were measured based on it. The significant increase of segments, ratios, and angles indicated that paranasal augmentation could increase the protrusion of paranasal area, both in absolute value and relative proportion. The significant decrease of other data indicated that the protrusion difference between paranasal base and upper lip, forehead, and chin, respectively, were shortened after surgery. The average size of implant was 6.54 ± 1.02 mm, and the average increase of paranasal height was 4.38 ± 1.04 mm postoperatively. This indicates that two-thirds of its height will ultimately be reflected effectively in the sagittal elevation of the paranasal base. CONCLUSIONS: Paranasal augmentation using ePTFE could effectively increase paranasal height and improve subunits relationships, and the ePTFE prosthesis should be designed and carve considering the 1/3 loss of height after implantation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Double Reinforcing Strategy with Perpendicular Plate of Ethmoid in Asian Secondary Unilateral Cleft Rhinoplasty: A Finite Element Analysis.

BACKGROUND: Deviation and asymmetry relapse after secondary unilateral cleft rhinoplasty with septal extension graft is a common yet serious problem especially among Asian patients. Therefore, finding an effective approach to reduce deformity relapse remains a great challenge to plastic surgeons. METHODS: In this study, authors established finite element models to simulate different nasal cartilage-corrected options and different reinforcing strategies in secondary unilateral cleft rhinoplasty. A load of 0.01N was given to the nasal tip to simulate the soft tissue pressure, while two loads of 0.5N were separately given to the anterior and posterior part of the septal extension graft to simulate the rhinoplasty condition. Maximum deformations were evaluated to make stability judgments. RESULTS: The maximum deformation of different cartilage correction models in ascending order was: UCL deformity with septum correction, normal nasal cartilage, UCL nasal deformity, and UCL nasal deformity with lower lateral cartilage correction. When applied L-strut reinforcement graft was harvested from the perpendicular plate of the ethmoid bone, the maximum deformation of the models decreased significantly, and strong fixation of the septum could further enhance this decreasing effect. CONCLUSIONS: Correcting the septum and lower lateral cartilage together could improve the structural stability and symmetry in secondary unilateral cleft rhinoplasty. To keep the corrected septum stable and thus reduce deformity relapse, reinforcing the L-strut with perpendicular plate of ethmoid graft while strongly anchoring the septal cartilage to the anterior nasal spine was proved to be effective in both finite element analysis and clinical observation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Discovery of Natural Potent HMG-CoA Reductase Degraders for Lowering Cholesterol.

Exploitation of key protected wild plant resources makes great sense, but their limited populations become the major barrier. A particular strategy for breaking this barrier was inspired by the exploration of a resource-saving fungal endophyte Penicillium sp. DG23, which inhabits the key protected wild plant Schisandra macrocarpa. Chemical studies on the cultures of this strain afforded eight novel indole diterpenoids, schipenindolenes A-H (1-8), belonging to six diverse skeleton types. Importantly, semisyntheses suggested some key nonenzymatic reactions constructing these molecules and provided targeted compounds, in particular schipenindolene A (Spid A, 1) with low natural abundance. Remarkably, Spid A was the most potent HMG-CoA reductase (HMGCR) degrader among the indole diterpenoid family. It degraded statin-induced accumulation of HMGCR protein, decreased cholesterol levels and acted synergistically with statin to further lower cholesterol. Mechanistically, transcriptomic and proteomic profiling suggested that Spid A potentially activated the endoplasmic reticulum-associated degradation (ERAD) pathway to enhance the degradation of HMGCR, while simultaneously inhibiting the statin-activated expression of many key enzymes in the cholesterol and fatty acid synthesis pathways, thereby strengthening the efficacy of statins and potentially reducing the side effects of statins. Collectively, this study suggests the potential of Spid A for treating cardiovascular disease.

Mechanisms regulating wound healing: Functional changes in biology mediated by lactate and histone lactylation.

The high incidence, low healing rate and huge economic burden of wounds (especially chronic wounds) worldwide remain a great challenge for clinical staff and patients. The various stages of wound healing are regulated by paracrine or autocrine cytokines and growth factors, and the study of their intrinsic mechanisms is a prerequisite for better wound treatment. Lactate, the end product of glycolysis, plays a role in all stages of wound healing, and recent studies have identified lactate as an epigenetic regulator that regulates gene expression through histone lysine lactylation and stimulates posttranslational modifications to regulate related gene expression, thereby causing a series of biological functional changes. This article reviews the progress of research on lactate and lactylation during wound healing or in related diseases, including its involvement in immune regulation, inflammation control, and proliferative remodeling, and finally describes the prospects for lactate therapy regarding wound healing.

Associations of baseline and longitudinal change in cerebellum volume with age-related changes in verbal learning and memory.

The cerebellum is involved in higher-order cognitive functions, e.g., learning and memory, and is susceptible to age-related atrophy. Yet, the cerebellum's role in age-related cognitive decline remains largely unknown. We investigated cross-sectional and longitudinal associations between cerebellar volume and verbal learning and memory. Linear mixed effects models and partial correlations were used to examine the relationship between changes in cerebellum volumes (total cerebellum, cerebellum white matter [WM], cerebellum hemisphere gray matter [GM], and cerebellum vermis subregions) and changes in verbal learning and memory performance among 549 Baltimore Longitudinal Study of Aging participants (2,292 visits). All models were adjusted by baseline demographic characteristics (age, sex, race, education), and APOE e4 carrier status. In examining associations between change with change, we tested an additional model that included either hippocampal (HC), cuneus, or postcentral gyrus (PoCG) volumes to assess whether cerebellar volumes were uniquely associated with verbal learning and memory. Cross-sectionally, the association of baseline cerebellum GM and WM with baseline verbal learning and memory was age-dependent, with the oldest individuals showing the strongest association between volume and performance. Baseline volume was not significantly associated with change in learning and memory. However, analysis of associations between change in volumes and changes in verbal learning and memory showed that greater declines in verbal memory were associated with greater volume loss in cerebellum white matter, and preserved GM volume in cerebellum vermis lobules VI-VII. The association between decline in verbal memory and decline in cerebellar WM volume remained after adjustment for HC, cuneus, and PoCG volume. Our findings highlight that associations between cerebellum volume and verbal learning and memory are age-dependent and regionally specific.

Integrative roles of human amygdala subdivisions: Insight from direct intracerebral stimulations via stereotactic EEG.

Substantial studies of human amygdala function have revealed its importance in processing emotional experience, autonomic regulation, and sensory information; however, the neural substrates and circuitry subserving functions have not been directly mapped at the level of the subnuclei in humans. We provide a useful overview of amygdala functional characterization by using direct electrical stimulation to various amygdala regions in 48 patients with drug-resistant epilepsy undergoing stereoelectroencephalography recordings. This stimulation extends beyond the anticipated emotional, neurovegetative, olfactory, and somatosensory responses to include visual, auditory, and vestibular sensations, which may be explained by the functional connectivity with cortical and subcortical regions due to evoked amygdala-cortical potentials. Among the physiological symptom categories for each subnucleus, the most frequently evoked neurovegetative symptoms were distributed in almost every subnucleus. Laterobasal subnuclei are mainly associated with emotional responses, somatosensory responses, and vestibular sensations. Superficial subnuclei are mainly associated with emotional responses and olfactory and visual hallucinations. Our findings contribute to a better understanding of the functional architecture of the human amygdala at the subnuclei level and as a mechanistic basis for the clinical practice of amygdala stimulation in treating patients with neuropsychiatric disorders.

Loss of TDP-43 splicing repression occurs early in the aging population and is associated with Alzheimer's disease neuropathologic changes and cognitive decline.

LATE-NC, the neuropathologic changes of limbic-predominant age-related TAR DNA-binding protein 43 kDa (TDP-43) encephalopathy are frequently associated with Alzheimer's disease (AD) and cognitive impairment in older adults. The association of TDP-43 proteinopathy with AD neuropathologic changes (ADNC) and its impact on specific cognitive domains are not fully understood and whether loss of TDP-43 function occurs early in the aging brain remains unknown. Here, using a large set of autopsies from the Baltimore Longitudinal Study of Aging (BLSA) and another younger cohort, we were able to study brains from subjects 21-109 years of age. Examination of these brains show that loss of TDP-43 splicing repression, as judged by TDP-43 nuclear clearance and expression of a cryptic exon in HDGFL2, first occurs during the 6th decade, preceding by a decade the appearance of TDP-43+ neuronal cytoplasmic inclusions (NCIs). We corroborated this observation using a monoclonal antibody to demonstrate a cryptic exon-encoded neoepitope within HDGFL2 in neurons exhibiting nuclear clearance of TDP-43. TDP-43 nuclear clearance is associated with increased burden of tau pathology. Age at death, female sex, high CERAD neuritic plaque score, and high Braak neurofibrillary stage significantly increase the odds of LATE-NC. Faster rates of cognitive decline on verbal memory (California Verbal Learning Test immediate recall), visuospatial ability (Card Rotations Test), mental status (MMSE) and semantic fluency (Category Fluency Test) were associated with LATE-NC. Notably, the effects of LATE-NC on verbal memory and visuospatial ability are independent of ADNC. However, the effects of TDP-43 nuclear clearance in absence of NCI on the longitudinal trajectories and levels of cognitive measures are not significant. These results establish that loss of TDP-43 splicing repression is an early event occurring in the aging population during the development of TDP-43 proteinopathy and is associated with increased tau pathology. Furthermore, LATE-NC correlates with high levels of ADNC but also has an impact on specific memory and visuospatial functions in aging that is independent of AD.

Circ_0059662 exerts a positive role in oxygen-glucose deprivation/reoxygenation-induced SK-N-SH cell injury.

Circular RNA (circRNA) is identified as a potential regulator of ischemic stroke (IS) progression. Through GEO database screening, it was found that circ_0059662 was highly expressed in acute IS patients. However, whether circ_0059662 participated in the IS process has not been studied. Oxygen-glucose deprivation/reoxygenation (OGD/R)-induced SK-N-SH cells were established to mimic IS cell models. The expression of circ_0059662, miR-579-3p, and ETS proto-oncogene 1 (ETS1) was measured via quantitative real-time PCR. Cell counting kit 8 assay, EdU assay and flow cytometry were utilized to detect cell proliferation and apoptosis. Western blot was employed to measure protein expression. ELISA was used to detect the levels of inflammation factors, and oxidative stress was determined by assessing SOD activity and MDA level. The relationship between miR-579-3p and circ_0059662 or ETS1 was examined via dual-luciferase reporter assay, RNA pull-down assay and RIP assay. Circ_0059662 was a circular RNA with highly expression in OGD/R-induced SK-N-SH cells. In OGD/R-induced cell injury, circ_0059662 knockdown promoted cell proliferation, and inhibited cell apoptosis, inflammation and oxidative stress. Circ_0059662 served as miR-579-3p sponge to positively regulate ETS1 expression. MiR-579-3p inhibitor and ETS1 overexpression could reverse the inhibition effect of circ_0059662 knockdown on OGD/R-induced cell injury. Besides, MiR-579-3p also could relieve OGD/R-induced SK-N-SH cell apoptosis, inflammation and oxidative stress by targeting ETS1. Our findings indicated that circ_0059662 knockdown alleviated OGD/R-induced SK-N-SH cell injury by sponging miR-579-3p to regulate ETS1 expression.

Multi-method investigation of factors influencing amyloid onset and impairment in three cohorts.

Alzheimer's disease biomarkers are becoming increasingly important for characterizing the longitudinal course of disease, predicting the timing of clinical and cognitive symptoms, and for recruitment and treatment monitoring in clinical trials. In this work, we develop and evaluate three methods for modelling the longitudinal course of amyloid accumulation in three cohorts using amyloid PET imaging. We then use these novel approaches to investigate factors that influence the timing of amyloid onset and the timing from amyloid onset to impairment onset in the Alzheimer's disease continuum. Data were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Baltimore Longitudinal Study of Aging (BLSA) and the Wisconsin Registry for Alzheimer's Prevention (WRAP). Amyloid PET was used to assess global amyloid burden. Three methods were evaluated for modelling amyloid accumulation using 10-fold cross-validation and holdout validation where applicable. Estimated amyloid onset age was compared across all three modelling methods and cohorts. Cox regression and accelerated failure time models were used to investigate whether sex, apolipoprotein E genotype and e4 carriage were associated with amyloid onset age in all cohorts. Cox regression was used to investigate whether apolipoprotein E (e4 carriage and e3e3, e3e4, e4e4 genotypes), sex or age of amyloid onset were associated with the time from amyloid onset to impairment onset (global clinical dementia rating ≥1) in a subset of 595 ADNI participants that were not impaired before amyloid onset. Model prediction and estimated amyloid onset age were similar across all three amyloid modelling methods. Sex and apolipoprotein E e4 carriage were not associated with PET-measured amyloid accumulation rates. Apolipoprotein E genotype and e4 carriage, but not sex, were associated with amyloid onset age such that e4 carriers became amyloid positive at an earlier age compared to non-carriers, and greater e4 dosage was associated with an earlier amyloid onset age. In the ADNI, e4 carriage, being female and a later amyloid onset age were all associated with a shorter time from amyloid onset to impairment onset. The risk of impairment onset due to age of amyloid onset was non-linear and accelerated for amyloid onset age >65. These findings demonstrate the feasibility of modelling longitudinal amyloid accumulation to enable individualized estimates of amyloid onset age from amyloid PET imaging. These estimates provide a more direct way to investigate the role of amyloid and other factors that influence the timing of clinical impairment in Alzheimer's disease.

Geometrical and magnetic properties of small titanium and chromium clusters on monolayer hexagonal boron nitride.

Magnetic clusters on an insulating substrate are potential candidates for spin-based quantum devices. Here we investigate the geometric, electronic, and magnetic structures of small Ti and Cr clusters, from dimers to pentamers, adsorbed on a single-layer hexagonal boron nitride (h-BN) sheet within the framework of density functional theory. The stable adsorption configurations of the Ti clusters and Cr clusters composed of the same number of atoms are found to be totally different from each other. The difference in their bonding mechanisms has been revealed by the density of states and the charge density difference of the corresponding adsorption systems. While chemical bonds are formed between the Ti atoms and the supporting sheet, the Cr clusters are found in the physisorption state on the substrate. In addition, it is shown that the h-BN sheet is energetically favorable for building three-dimensional Ti clusters. These findings support the use of h-BN as a suitable decoupling substrate for manipulation of quantum spin states in small transition metal (TM) clusters and fabrication of devices based on them.

Optimisation of warfarin-dosing algorithms for Han Chinese patients with CYP2C9*13 variants.

BACKGROUND: Existing pharmacogenetic algorithms cannot fully explain warfarin dose variability in all patients. CYP2C9*13 is an important allelic variant in the Han Chinese population. However, adjustment of warfarin dosing in CYP2C9*13 variant carriers remains unclear. To the best of our knowledge, this study is the first to assess the effects of adjusting warfarin dosages in Han Chinese patients harbouring CYP2C9*13 variants. METHODS: In total, 971 warfarin-treated Han Chinese patients with atrial fibrillation were enrolled in this study. Clinical data were collected, and CYP2C9*2, *3, *13 and VKORC1-1639 G > A variants were genotyped. We quantitatively analysed the effect of CYP2C9*13 on warfarin maintenance dose and provided multiplicative adjustments for CYP2C9*13 using validated pharmacogenetic algorithms. RESULTS: Approximately 0.6% of the Han Chinese population carried CYP2C9*13 variant, and the genotype frequency was between those of CYP2C9*2 and CYP2C9*3. The warfarin maintenance doses were significantly reduced in CYP2C9*13 carriers. When CYP2C9*13 variants were not considered, the pharmacogenetic algorithms overestimated warfarin maintenance doses by 1.03-1.16 mg/d on average. The actual warfarin dose in CYP2C9*13 variant carriers was approximately 40% lower than the algorithm-predicted dose. Adjusting the warfarin-dosing algorithm according to the CYP2C9*13 allele could reduce the dose prediction error. CONCLUSION: Our study showed that the algorithm-predicted doses should be lowered for CYP2C9*13 carriers. Inclusion of the CYP2C9*13 variant in the warfarin-dosing algorithm tends to predict the warfarin maintenance dose more accurately and improves the efficacy and safety of warfarin administration in Han Chinese patients.