Systemic inflammatory markers in ageing, Alzheimer's disease and other dementias.

Systemic inflammation with alterations in inflammatory markers is involved in aging and Alzheimer's disease. However, few studies have investigated the longitudinal trajectories of systemic inflammatory markers during aging and Alzheimer's disease, and specific markers contributing to Alzheimer's disease remain undetermined. In this study, a longitudinal cohort (cohort 1: n = 290; controls, 136; preclinical Alzheimer's disease, 154) and a cross-sectional cohort (cohort 2: n = 351; controls, 62; Alzheimer's disease, 63; vascular dementia, 58; Parkinson's disease dementia, 56; behavioural variant frontotemporal dementia, 57; dementia with Lewy bodies, 55) were included. Plasma levels of inflammatory markers were measured every 2 years during a 10-year follow-up in the longitudinal cohort and once in the cross-sectional cohort. The study demonstrated that the inflammatory markers significantly altered during both aging and the development of Alzheimer's disease. However, only complement C3, interleukin-1ß, and interleukin-6 exhibited significant changes in participants with preclinical Alzheimer's disease, and their longitudinal changes were significantly associated with the development of Alzheimer's disease compared to controls over the 10-year follow-up. In the cross-sectional cohort, complement C3 demonstrates specificity to Alzheimer's disease, while interleukin-1ß and interleukin-6 were also altered in other dementias. The study provides a new perspective on the involvement of inflammatory markers in the aging process and the development of Alzheimer's disease, implying that regulating inflammation may have a pivotal role in promoting successful aging and in the prevention and treatment of Alzheimer's disease.

Mechanochemical reduction of alkyl and aryl halides using mesoporous zinc oxide.

In this study, we propose a mechanochemical approach that combines mesoporous ZnO (m-ZnO) as a mechanoredox catalyst and silane-mediated atom transfer chemistry to achieve efficient hydrodehalogenation of organic halides. The reaction can be conducted under mild conditions without the use of a large amount of organic solvent. Substrates ranging from activated alkyl halides to unactivated aryl halides were converted to the corresponding debrominated hydrogenation products in moderate to excellent isolated yields (50-95%). In addition, m-ZnO can be recycled and reused without appreciable loss of catalytic activity.

Delivering synaptic protein mRNAs via extracellular vesicles ameliorates cognitive impairment in a mouse model of Alzheimer's disease.

BACKGROUND: Synaptic dysfunction with reduced synaptic protein levels is a core feature of Alzheimer's disease (AD). Synaptic proteins play a central role in memory processing, learning, and AD pathogenesis. Evidence suggests that synaptic proteins in plasma neuronal-derived extracellular vesicles (EVs) are reduced in patients with AD. However, it remains unclear whether levels of synaptic proteins in EVs are associated with hippocampal atrophy of AD and whether upregulating the expression of these synaptic proteins has a beneficial effect on AD. METHODS: In this study, we included 57 patients with AD and 56 healthy controls. We evaluated their brain atrophy through magnetic resonance imaging using the medial temporal lobe atrophy score. We measured the levels of four synaptic proteins, including synaptosome-associated protein 25 (SNAP25), growth-associated protein 43 (GAP43), neurogranin, and synaptotagmin 1 in both plasma neuronal-derived EVs and cerebrospinal fluid (CSF). We further examined the association of synaptic protein levels with brain atrophy. We also evaluated the levels of these synaptic proteins in the brains of 5×FAD mice. Then, we loaded rabies virus glycoprotein-engineered EVs with messenger RNAs (mRNAs) encoding GAP43 and SNAP25 and administered these EVs to 5×FAD mice. After treatment, synaptic proteins, dendritic density, and cognitive function were evaluated. RESULTS: The results showed that GAP43, SNAP25, neurogranin, and synaptotagmin 1 were decreased in neuronal-derived EVs but increased in CSF in patients with AD, and the changes corresponded to the severity of brain atrophy. GAP43 and SNAP25 were decreased in the brains of 5×FAD mice. The engineered EVs efficiently and stably delivered these synaptic proteins to the brain, where synaptic protein levels were markedly upregulated. Upregulation of synaptic protein expression could ameliorate cognitive impairment in AD by promoting dendritic density. This marks the first successful delivery of synaptic protein mRNAs via EVs in AD mice, yielding remarkable therapeutic effects. CONCLUSIONS: Synaptic proteins are closely related to AD processes. Delivery of synaptic protein mRNAs via EVs stands as a promising effective precision treatment strategy for AD, which significantly advances the current understanding of therapeutic approaches for the disease.

Plasma biomarkers predict Alzheimer's disease before clinical onset in Chinese cohorts.

Plasma amyloid-ß (Aß)42, phosphorylated tau (p-tau)181, and neurofilament light chain (NfL) are promising biomarkers of Alzheimer's disease (AD). However, whether these biomarkers can predict AD in Chinese populations is yet to be fully explored. We therefore tested the performance of these plasma biomarkers in 126 participants with preclinical AD and 123 controls with 8-10 years of follow-up from the China Cognition and Aging Study. Plasma Aß42, p-tau181, and NfL were significantly correlated with cerebrospinal fluid counterparts and significantly altered in participants with preclinical AD. Combining plasma Aß42, p-tau181, and NfL successfully discriminated preclinical AD from controls. These findings were validated in a replication cohort including 51 familial AD mutation carriers and 52 non-carriers from the Chinese Familial Alzheimer's Disease Network. Here we show that plasma Aß42, p-tau181, and NfL may be useful for predicting AD 8 years before clinical onset in Chinese populations.

Enhancing Ultrasound-Assisted Iodine-Mediated Reversible-Deactivation Radical Polymerization by Piezoelectric Nanoparticles.

The development of mechanochemical tools for regulating the polymerization process has received an increasing amount of attention in recent years. Herein, we report the example of the mechanically controlled iodine-mediated reversible-deactivation radical polymerization (mechano-RDRP) using piezoelectric tetragonal BaTiO3 nanoparticles (T-BTO) as mechanoredox catalyst and alkyl iodide as the initiator. We demonstrated a more efficient mechanochemical initiation and reversible deactivation process than sonochemical activation via a mechanoredox-mediated alkyl iodide cleavage reaction. The mechanochemical activation of the C-I bond was verified by density functional theory (DFT) calculations. Theoretical calculations together with experimental results confirmed the more efficient initiation and polymerization than the traditional sonochemical approach. The influence of BaTiO3, initiator, and solvent was further examined to reveal the mechanism of the mechano-RDRP. The results showed good controllability over molecular weight and capacity for a one-pot chain extension. This work expands the scope of mechanically controlled polymerization and shows good potential in the construction of adaptive materials.

Synergistic effects of rare earth doping and carbon quantum dots on BiOF/Bi2MoO6 heterojunctions for enhanced visible-near-infrared photocatalysis.

Herein, we designed and synthesized a series of rare earth doped BiOF/Bi2MoO6 heterojunctions. The doping locations of rare earth ions were altered to determine the influence on the visible and near-infrared photocatalytic activity of heterojunctions. It is experimentally and theoretically confirmed that doping with Tm3+/Yb3+ in one semiconductor of the heterojunction produces superior photocatalytic efficiency than doping in both semiconductors. In addition, the near infrared photocatalytic efficiency strongly relied on upconversion luminescence from the Re3+ doped semiconductor in the heterojunction. By further modifying with CQDs, the CQDs/BiOF:Tm3+,Yb3+/Bi2MoO6 sample shows excellent visible and near-infrared photocatalytic performance, with 90% degradation of RhB occurring in the first 20 min under visible irradiation. This can be attributed to the large BET area, efficient photoinduced carrier separation and the upconversion process of the composite. This research will provide a systematic solution for realizing full-spectrum responsive and highly efficient photocatalysis by combination of rare earth ion doping, quantum dot modification and Z-scheme heterojunctions.

A blood mRNA panel that differentiates Alzheimer's disease from other dementia types.

BACKGROUND: Messenger RNAs (mRNAs) have been reported to be associated with Alzheimer's disease (AD). In this study, we investigated whether plasma-based mRNAs could distinguish AD from cognitively normal controls and other types of dementia, including vascular dementia (VaD), Parkinson's disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB). METHODS: Plasma mRNA expression was measured in three independent datasets. Dataset 1 (n = 40; controls, 20; AD, 20) was used to identify the differentially expressed mRNAs. Dataset 2 (n = 122; controls: 60; AD: 62) was used to develop a diagnostic AD model using an mRNA panel. Furthermore, we applied the model to Dataset 3 (n = 334; control, 57; AD, 58; VaD, 55; PDD, 54; bvFTD, 55; DLB, 55) to verify its ability to identify AD and other types of dementia. RESULTS: Dataset 1 showed 22 upregulated and 21 downregulated mRNAs. A panel of six mRNAs distinguished AD from the control group in Dataset 2. The panel was used to successfully differentiate AD from other types of dementia in Dataset 3. CONCLUSIONS: An AD-specific panel of six mRNAs was created that can be used for AD diagnosis.

A Group of Long Non-coding RNAs in Blood Acts as a Specific Biomarker of Alzheimer's Disease.

Long non-coding RNAs (lncRNAs) have been identified to be involved in the pathogenesis of Alzheimer's disease (AD). In this study, we evaluated whether lncRNAs can be used to discriminate AD patients from controls and patients with other dementias, such as vascular, Parkinson's disease, behavioral variant frontotemporal, and dementia with Lewy body. In this study, we used three datasets to measure the blood lncRNA levels. A pilot study (dataset 1, n = 40; controls, 20; AD, 20) was used to screen for differentially expressed lncRNAs. Dataset 2 (n = 174; controls, 86; AD, 88) was used to identify a lncRNA panel for the diagnostic model. Dataset 3 (n = 333; control, 60; AD, 54; vascular dementia, 53; Parkinson's disease dementia, 55; behavioral variant frontotemporal dementia, 56; and dementia with Lewy body, 55) was used to validate the diagnostic model. In dataset 1, 12 upregulated and 15 downregulated lncRNAs were identified. In dataset 2, a panel of seven lncRNAs was found to have the ability to differentiate AD patients from controls. Finally, this panel was applied to dataset 3 to successfully distinguish AD from other dementias. This study proposes a panel of seven lncRNAs as specific and promising biomarker for AD diagnosis.

A circular RNA blood panel that differentiates Alzheimer's disease from other dementia types.

BACKGROUND: Circular RNAs (circRNAs) have been demonstrated to be associated with Alzheimer's disease (AD). Here, we conducted a study to explore whether circRNAs have the ability to differentiate AD from cognitively normal controls and other types of dementia, such as vascular dementia (VaD), Parkinson's disease dementia (PDD), behavioral variant frontotemporal dementia (bvFTD), and dementia with Lewy body (DLB). METHODS: Three datasets were included in this study to measure blood circRNAs. The pilot study (Dataset 1, n = 40; controls, 20; AD, 20) was used to screen differentially expressed circRNAs. Dataset 2 (n = 124; controls, 61; AD, 63) was recruited for the establishment of the diagnostic model using a circRNA panel. Further, the Dataset 3 (n = 321; control, 58; AD, 60; VaD, 50; PDD, 51; bvFTD, 52; DLB, 50) was used to verify the diagnostic model. RESULTS: In Dataset 1, 22 upregulated and 19 downregulated circRNAs were revealed. In Dataset 2, a six-circRNA panel was found to be able to distinguish patients with AD from controls. Then this panel was applied to Dataset 3 and successfully differentiated AD from other types of dementia. CONCLUSION: This study suggested that a six-circRNA panel is AD-specific and a promising biomarker of AD.

Highly Efficient Amide Michael Addition and Its Use in the Preparation of Tunable Multicolor Photoluminescent Polymers.

The amide bond is one of the most pivotal functional groups in chemistry and biology. It is also the key component of proteins and widely present in synthetic materials. The majority of studies have focused on the formation of the amide group, but its postmodification has scarcely been investigated. Herein, we successfully develop the Michael additions of amide to acrylate, acrylamide, or propiolate in the presence of phosphazene base at room temperature. This amide Michael addition is much more efficient when the secondary amide instead of the primary amide is used under the same conditions. This reaction was applied to postfunctionalize poly(methyl acrylate-co-acrylamide), P(MA-co-Am), and it is shown that the amide groups of P(MA-co-Am) could be completely modified by N,N-dimethylacrylamide (DMA). Interestingly, the resulting copolymer exhibited tailorable fluorescence with emission wavelength ranging from 380 to 613 nm, which is a desired property for luminescent materials. Moreover, the emissions of the copolymer increased with increasing concentration in solution for all excitation wavelengths from 320 to 580 nm. Therefore, this work not only develops an efficient t-BuP4-catalyzed amide Michael addition but also offers a facile method for tunable multicolor photoluminescent polymers, which is expected to find a wide range of applications in many fields, such as in anticounterfeiting technology.