Low Intake of Total Antioxidant Nutrients as a Risk Factor for Incident Dementia in Older Adults: the Shanghai Aging Study.

INTRODUCTION: Previous longitudinal studies reported the impact of antioxidant nutrients (AN) on cognitive impairment in the older population but the conclusions were inconsistent. This study aimed to verify the hypothesis that dietary intake of total AN was associated with incident dementia among older individuals. METHODS: Community residents without dementia aged ≥60 years were prospectively followed up for an average of 5.2 years in the Shanghai Aging Study. At baseline, daily intakes of total dietary AN (the sum of carotene, vitamin C, vitamin E, lutein, and flavonoids) and energy were calculated based on an interviewer-administered food frequency questionnaire measuring the dietary intake over the past 1 year for each participant. A battery of neuropsychological tests was used to evaluate cognitive function, and a consensus diagnosis of dementia was made according to the DSM-IV criteria at baseline and follow-up. RESULTS: Among 1550 dementia-free participants, 135 (8.7%) incident dementia cases were identified during the average of 5.2 years of follow-up. Participants with low AN intake (<112mg/d) had a significantly higher risk of incident dementia than those with high AN intake (≥ 112 mg/d) (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26 - 2.77) after adjusting for age, gender, education, obesity, APOE-ε4, hypertension, diabetes, depression, baseline Mini-Mental State Examination score, and total energy intake. The significant association of total AN intake with incident dementia was only found in individuals ≥70 years. CONCLUSION: Low total AN intake may be a risk factor for incident dementia among older adults. Maintaining sufficient AN intake may be beneficial against age-related cognitive decline.

Palladium-catalyzed 1,1-aminoxylation of 3-butenoic acid with 2-alkynylanilines.

Herein, a palladium-catalyzed 1,1-aminoxylation of 3-butenoic acid and 2-alkynylanilines has been developed, achieving the installation of two distinct heteroatom motifs across an olefin skeleton. The strategy features a high step and atom economy and good functional group tolerance, which outlines an efficient approach for simultaneously building up γ-butylactone and indole skeletons. Notably, an external ligand, 2,9-dimethyl-1,10-phenanthroline, has been used to succeed in this protocol to effectively suppress the production of indole byproducts.

Palladium-catalyzed syn-alkynylarylation of internal alkynes: rapid access to all-carbon tetrasubstituted alkenes.

Herein, a straightforward method for rapid access to all-carbon tertrasubstituted alkenes bearing alkyl, aryl and alkynyl groups is established via palladium-catalyzed three-component cross-coupling reaction of internal alkynes, haloalkynes and arylboronic acids. This protocol is characterized by a broad substrate scope and excellent chemo- and regioselectivities. The dual beneficial roles of silver salts in activating haloalkynes and inhibiting bromoalkynylation have been demonstrated by serving as both the Lewis acid and halide scavenger.

Pd-catalyzed Markovnikov selective oxidative amination of 4-pentenoic acid.

Pd-catalyzed regioselective amination of unactivated alkene remains a challenge and is of great interest. Herein, a palladium-catalyzed and ligand-controlled strategy for the Markovnikov selective oxidative amination of 4-pentenoic acid has been described. The protocol effectively reverses the carboxylic acid-directed anti-Markovnikov selectivity in oxidative amination of 4-pentenoic acid, successfully constructing γ-ketoamide derivatives.

Advances in the selection of functional monomers for molecularly imprinted polymers: A review.

Molecularly imprinted polymers, a type of special polymer materials, are widely used in biosensing and other fields due to their ability to specifically recognize target molecules, often called "artificial receptors.". Nowadays, researchers are constantly exploring new design and synthesis methods for molecularly imprinted materials to improve the selectivity and sensitivity of molecularly imprinted materials. Among them, the selection of functional monomers has attracted great attention. This review comprehensively analyzes and discusses the selection methods of functional monomers. The most commonly used functional monomers among different types of templates are screened based on the structural properties of the template molecules, including the selection of functional monomers among ion-imprinted polymers, protein-imprinted polymers, and bacterial imprinted polymers. The rich binding sites and functional group types of multifunctional monomers are also highlighted to advance the development of molecular imprinting technology. The article further explores the current challenges and prospects in the selection of functional monomers and emphasizes multiplex experiments and computer simulations as important directions for future research. This review provides comprehensive information and constructive guidelines for researchers in selecting functional monomers in areas such as analytical chemistry and biosensors.

Palladium-catalyzed cascade of aza-Wacker and Povarov reactions of aryl amines and 1,6-dienes for hexahydro-cyclopenta[b]quinoline framework.

Palladium catalyzed tandem reaction represents a one-pot synthetic approach to efficiently synthesize complex functionalized molecules while reducing synthetic steps, aligning with the principles of green chemistry. However, achieving a direct cascade of the aza-Wacker and Povarov reactions in one-pot synthesis presents a challenge due to substrate compatibility issues between the two reactions. In this work, we describe an aza-Wacker/Povarov reaction employing a highly electrophilic palladium catalyst, which effectively converts anilines and 1,6-dienes into hexahydro-cyclopenta[b]quinolines. The optimized conditions yield up to 79%, with a diastereoselectivity > 20:1. Substrate range testing reveals compatibility with various sensitive functional groups, and successful late-stage modifications are performed on several natural products and drug molecules, demonstrating the versatility and practicality of the method. Additionally, a preliminary investigation into the reaction mechanism suggests an aza-Wacker process followed by a Povarov process.

Base-Promoted (5 + 2) Annulation between 2-(Alkynylaryl)acetonitriles and Arylalkynes for the Synthesis of Benzocycloheptene Derivatives.

Herein, we describe a novel approach to the synthesis of benzocycloheptene derivatives via base-promoted (5 + 2) annulation between 2-(alkynylaryl)acetonitriles and arylalkynes. In this chemistry, 2-(alkynylaryl)acetonitriles are employed as a new C5 synthon to construct various benzocycloheptene(s) derivatives by building two C-C bonds in one single step. This method features excellent regioselectivity, the use of readily available starting materials, and good functional group tolerance. The practicality of the strategy was further demonstrated by gram-scale synthesis, late-stage functionalizations, and the post-modification of natural products such as probenecid and tetrahydrofurfuryl alcohol.

High χ P2PFBEMA-b-P2VP Block Copolymers Forming 6-8 nm Domains for Semiconductor Lithography.

We leveraged the potential of high χ-low N block copolymer (BCP), namely, poly[2-(perfluorobutyl) ethyl methacrylate]-block-poly(2-vinylpyridine) (P2PFBEMA-b-P2VP), and demonstrated its utility in next-generation nanomanufacturing. By combining molecular dynamics simulations with experiments, the χ value was calculated to be as high as 0.4 (at 150 °C), surpassing similar structures. Highly ordered features suitable for application were observed, ranging in periods from 19.0 nm down to 12.1 nm, with feature sizes as small as 6 nm. Transmission electron microscopy images of the BCP solutions indicated that preformed micelles in the solution facilitated the self-assembly process of the thin film. In addition, the vertical or parallel orientation of the cylindrical structure was determined by manipulating the solvent, substrate, and annealing conditions. Finally, guided by a wide topographical template, nearly defect-free directed self-assembly (DSA) lines with a resolution of 8 nm were achieved, highlighting its potential practical application in DSA lithography technology.

Palladium-Catalyzed Annulation of Tertiary Anilines with 3-Butenoic Acid via Dual C-H Bond Activation.

Catalytic cyclization via dual C-H bond activation has evolved as a powerful strategy for building bi- and polycyclic molecules. Herein, a palladium-catalyzed annulation of tertiary anilines with 3-butenoic acid via N-α-C(sp3)-H and ortho-C(sp2)-H activation is described. The remarkable characteristics of this reaction include excellent diastereoselectivity, broad substrate scope, and good tolerance for some highly sensitive groups. In addition, the KIE experiment suggested that the C-H bond abscission is not the turnover-limiting step.

Dimensional Reduction of Metal-Organic Frameworks for Photocatalytic Synthesis of Fused Tetracyclic Heterocycles.

Heterogeneous palladium catalysts with high efficiency, high Pd atom utilization, simplified separation, and recycle have attracted considerable attention in the field of synthetic chemistry. Herein, we reported a zirconium-based two-dimensional metal-organic framework (2D-MOF)-based Pd(II) photocatalyst (Zr-Ir-Pd) by merging the Ir photosensitizers and Pd(II) species into the skeletons of the 2D-MOF for the Pd(II)-catalyzed oxidation reaction. Morphological and structural characterization identified that Zr-Ir-Pd with a specific nanoflower-like structure consists of ultrathin 2D-MOF nanosheets (3.85 nm). Due to its excellent visible-light response and absorption capability, faster transfer and separation of photogenerated carriers, more accessible Pd active sites, and low mass transfer resistance, Zr-Ir-Pd exhibited boosted photocatalytic activity in catalyzing sterically hindered isocyanide insertion of diarylalkynes for the construction of fused tetracyclic heterocycles, with up to 12 times the Pd catalyst turnover number than the existing catalytic systems. In addition, Zr-Ir-Pd inhibited the competitive agglomeration of Pd(0) species and could be reused at least five times, owing to the stabilization of 2D-MOF on the single-site Pd and Ir sites. Finally, a possible mechanism of the photocatalytic synthesis of fused tetracyclic heterocycles catalyzed by Zr-Ir-Pd was proposed.

Synthesis of Dienamides via Palladium-catalyzed Oxidative N-α,ß-Dehydrogenation of Amides.

Enamides and their derivatives are prominent bioactive pharmacophores found in various bioactive molecules. Herein we report a palladium-catalyzed oxidative N-α,ß-dehydrogenation of amides to produce a range of enamides with high yields and excellent tolerance toward different functional groups. Mechanistic studies indicate that the reaction involves allylic C(sp3)-H activation followed by ß-H elimination. The effectiveness of this approach is demonstrated through late-stage functionalization of bioactive molecules and the synthesis of valuable compounds through product elaboration.

Identification and validation of anti-protein arginine methyltransferase 5 (PRMT5) antibody as a novel biomarker for systemic sclerosis (SSc).

OBJECTIVES: In the complex panorama of autoimmune diseases, the characterisation of pivotal contributing autoantibodies that are involved in disease progression remains challenging. This study aimed to employ a global antibody profiling strategy to identify novel antibodies and investigate their association with systemic sclerosis (SSc). METHODS: We implemented this strategy by conducting immunoprecipitation (IP) following on-bead digestion with the sera of patients with SSc or healthy donors, using antigen pools derived from cell lysates. The enriched antigen-antibody complex was proceeded with mass spectrometry (MS)-based quantitative proteomics and over-represented by bioinformatics analysis. The candidate antibodies were then orthogonally validated in two independent groups of patients with SSc. Mice were immunised with the target antigen, which was subsequently evaluated by histological examination and RNA sequencing. RESULTS: The IP-MS analysis, followed by validation in patients with SSc, revealed a significant elevation in anti-PRMT5 antibodies among patients with SSc. These antibodies exhibited robust diagnostic accuracy in distinguishing SSc from healthy controls and other autoimmune conditions, including systemic lupus erythematosus and Sjögren's syndrome, with an area under the curve ranging from 0.900 to 0.988. The elevation of anti-PRMT5 antibodies was verified in a subsequent independent group with SSc using an additional method, microarray. Notably, 31.11% of patients with SSc exhibited seropositivity for anti-PRMT5 antibodies. Furthermore, the titres of anti-PRMT5 antibodies demonstrated a correlation with the progression or regression trajectory in SSc. PRMT5 immunisation displayed significant inflammation and fibrosis in both the skin and lungs of mice. This was concomitant with the upregulation of multiple proinflammatory and profibrotic pathways, thereby underscoring a potentially pivotal role of anti-PRMT5 antibodies in SSc. CONCLUSIONS: This study has identified anti-PRMT5 antibodies as a novel biomarker for SSc.

Enhanced LRP8 expression induced by Helicobacter pylori drives gastric cancer progression by facilitating ß-Catenin nuclear translocation.

INTRODUCTION: Helicobacter pylori (H. pylori) infection has been associated with gastric carcinogenesis. However, the precise involvement of LRP8, the low-density lipoprotein receptor-related protein 8, in H. pylori pathogenesis and gastric cancer (GC) remains poorly understood. OBJECTIVES: To investigate the potential role of LRP8 in H. pylori infection and gastric carcinogenesis. METHODS: Three-dimensional human-derived gastric organoids (hGO) and gastric cancer organoids (hGCO) were synthesized from the tissues obtained from human donors. In this work, multi-omics combined with in vivo and in vitro studies were conducted to investigate the potential involvement of LRP8 in H. pylori-induced GC. RESULTS: We found that H. pylori infection significantly upregulated the expression of LRP8 in human GC tissues, cells, organoids, and mouse gastric mucous. In particular, LRP8 exhibited a distinct enrichment in cancer stem cells (CSC). Functionally, silencing of LRP8 affected the formation and proliferation of tumor spheroids, while increased expression of LRP8 was associated with increased proliferation and stemness of GC cells and organoids. Mechanistically, LRP8 promotes the binding of E-cadherin to ß-catenin, thereby promoting nuclear translocation and transcriptional activity of ß-catenin. Furthermore, LRP8 interacts with the cytotoxin-associated gene A (CagA) to form the CagA/LRP8/ß-catenin complex. This complex further amplifies H. pylori-induced ß-catenin nuclear translocation, leading to increased transcription of inflammatory factors and CSC markers. Clinical analysis demonstrated that abnormal overexpression of LRP8 is correlated with a poor prognosis and resistance to 5-Fluorouracil in patients with GC. CONCLUSION: Our findings provide valuable information on the molecular intricacies of H. pylori-induced gastric carcinogenesis, offering potential therapeutic targets and prognostic markers for GC.

Palladium-Catalyzed Carbohalogenation of Olefins with Alkynyl Oxime Ethers: Rapid Access to Chlorine-Containing Isoxazoles.

A palladium-catalyzed carbohalogenation of olefins with alkynyl oxime ethers has been described, which provides efficient and practical access to various chlorine-containing isoxazoles. This method exhibits excellent regioselectivity, good functional group compatibility, and mild reaction conditions. The mechanistic studies suggest that the reaction proceeds via a stabilized π-benzyl palladium intermediate, which is essential for the formation of C(sp3)-Cl bonds.

Palladium-Catalyzed 1,2-Alkynylarylation of Vinyl Arenes with Haloalkynes and Arylboronic Acids.

We herein disclose a novel palladium-catalyzed 1,2-alkynylarylation of vinyl arenes using haloalkynes and arylboronic acids as coupling partners. This reaction is characterized by broad substrate scope, controllable reaction sequence, and excellent chemo- and regioselectivities. Mechanistic investigations suggest that the reaction is initiated by regioselective insertion of vinyl arenes into the alkynyl-Pd(II) species, and the silver salt is crucial for this transformation, serving as both the Lewis acid and halide scavenger. This protocol provides efficient access to new carbon skeletons, which are embedded in the key biologically active motifs.

The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study.

BACKGROUND: The blood-based biomarkers are approaching the clinical practice of Alzheimer's disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers. METHODS: Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted. RESULTS: The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = - 0.19, 95% CI - 0.224 to - 0.156, P < 0.001; B = - 0.009, 95% CI - 0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = - 0.010, 95% CI - 0.133 to - 0.068, P < 0.001), but not with P-tau181 (B = - 0.003, 95% CI - 0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = - 0.790, 95% CI - 1.026 to - 0,554, P < 0.001). CONCLUSIONS: Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.

Palladium-catalyzed ligand-regulated divergent synthesis of pyrrole[2,3-b]indoles and ureas from 2-ethynylanilines and isocyanides.

Herein, a palladium-catalyzed and ligand-controlled protocol for the divergent synthesis of pyrrole[2,3-b]indole and urea derivatives has been described. Pyrrole[2,3-b]indoles ("cyclization on" products) via tandem cyclization of o-alkynylanilines with isocyanides in the absence of a ligand and ureas ("cyclization off" products) via oxidative amination of anilines with isocyanides in the presence of a ligand were obtained both in moderate to good yields with high selectivity. In this chemistry, cyclic and acyclic products were easily accessed with the same starting materials under the regulation of the ligand.

TDA/rGO@WS with Joule heat and photothermal synergistic effect: A promising adsorption material for all-weather recovery of viscous oil spills at sea.

Oil spills are a global environmental protection challenge, and traditional adsorption materials have poor effect on low temperature and high viscosity marine oil spills. This article reports composite adsorption materials TDA/rGO@WS for viscous oil spills: loaded with rGO/TDA coating on a commercial biomass wood pulp sponge (WS), achieving Joule heating, photothermal effect and hydrophobic modification. The results showed that the TDA/rGO@WS has good photothermal conversion ability and Joule heating ability, and the temperature increased to 83.7 °C and 148 °C, respectively, under simulated solar irradiation and additional voltage at room temperature. The efficiency of adsorption at a low temperature of 5 °C increased by 22.41% at 1 sun and by 51.53% at 10 V. Temperature effectively reduced the viscosity of the offshore oil spill and ensures the efficient adsorption of oil spills at low temperatures promoted. The TDA/rGO@WS also showed good hydrophobicity (WCA=129°), excellent efficiency of water-oil separation (99.53%) and good adsorption capacity (9.4-13.68 g/g) for marine fuel oils. TDA/rGO@WS effectively solves the problem of cleaning up high-viscosity oil spills from ships in winter and polar waters, and proposes a new strategy for all-weather efficient treatment of oil spills at sea.

Wavelet transform and deep learning-based obstructive sleep apnea detection from single-lead ECG signals.

Sleep apnea is a common sleep disorder. Traditional testing and diagnosis heavily rely on the expertise of physicians, as well as analysis and statistical interpretation of extensive sleep testing data, resulting in time-consuming and labor-intensive processes. To address the problems of complex feature extraction, data imbalance, and low model capacity, we proposed an automatic sleep apnea classification model (CA-EfficientNet) based on the wavelet transform, a lightweight neural network, and a coordinated attention mechanism. The signal is converted into a time-frequency image by wavelet transform and put into the proposed model for classification. The effects of input time window, wavelet transform type and data balancing on the classification performance are considered, and a cost-sensitive algorithm is introduced to more accurately distinguish between normal and abnormal breathing events. PhysioNet apnea ECG database was used for training and evaluation. The 3-min Frequency B-Spline wavelets transform of ECG signal was carried out, and Dice Loss was used to train the classification model of sleep breathing. The classification accuracy was 93.44%, sensitivity was 88.9%, specificity was 96.2% and most indexes were better than other related work.

Constructing bodily emotion maps based on high-density body surface potentials for psychophysiological computing.

Emotion is a complex physiological and psychological activity, accompanied by subjective physiological sensations and objective physiological changes. The body sensation map describes the changes in body sensation associated with emotion in a topographic manner, but it relies on subjective evaluations from participants. Physiological signals are a more reliable measure of emotion, but most research focuses on the central nervous system, neglecting the importance of the peripheral nervous system. In this study, a body surface potential mapping (BSPM) system was constructed, and an experiment was designed to induce emotions and obtain high-density body surface potential information under negative and non-negative emotions. Then, by constructing and analyzing the functional connectivity network of BSPs, the high-density electrophysiological characteristics are obtained and visualized as bodily emotion maps. The results showed that the functional connectivity network of BSPs under negative emotions had denser connections, and emotion maps based on local clustering coefficient (LCC) are consistent with BSMs under negative emotions. in addition, our features can classify negative and non-negative emotions with the highest classification accuracy of 80.77%. In conclusion, this study constructs an emotion map based on high-density BSPs, which offers a novel approach to psychophysiological computing.