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1.
bioRxiv ; 2024 May 01.
Article En | MEDLINE | ID: mdl-38746191

The ubiquitin kinase-ligase pair PINK1-PRKN identifies and selectively marks damaged mitochondria for elimination via the autophagy-lysosome system (mitophagy). While this cytoprotective pathway has been extensively studied in vitro upon acute and complete depolarization of mitochondria, the significance of PINK1-PRKN mitophagy in vivo is less well established. Here we used a novel approach to study PINK1-PRKN signaling in different energetically demanding tissues of mice during normal aging. We demonstrate a generally increased expression of both genes and enhanced enzymatic activity with aging across tissue types. Collectively our data suggest a distinct regulation of PINK1-PRKN signaling under basal conditions with the most pronounced activation and flux of the pathway in mouse heart compared to brain or skeletal muscle. Our biochemical analyses complement existing mitophagy reporter readouts and provide an important baseline assessment in vivo, setting the stage for further investigations of the PINK1-PRKN pathway during stress and in relevant disease conditions.

2.
ACS Appl Mater Interfaces ; 16(19): 24908-24919, 2024 May 15.
Article En | MEDLINE | ID: mdl-38706177

Perovskite nanocrystal (PeNC) arrays are showing a promising future in the next generation of micro-light-emitting-diode (micro-LED) displays due to the narrow emission linewidth and adjustable peak wavelength. Electrohydrodynamic (EHD) inkjet printing, with merits of high resolution, uniformity, versatility, and cost-effectiveness, is among the competent candidates for constructing PeNC arrays. However, the fabrication of red light-emitting CsPbBrxI(3-x) nanocrystal arrays for micro-LED displays still faces challenges, such as low brightness and poor stability. This work proposes a design for a red PeNC colloidal ink that is specialized for the EHD inkjet printing of three-dimensional PeNC arrays with enhanced luminescence and stability as well as being adaptable to both rigid and flexible substrates. Made of a mixture of PeNCs, polymer polystyrene (PS), and a nonpolar xylene solvent, the PeNC colloidal ink enables precise control of array sizes and shapes, which facilitates on-demand micropillar construction. Additionally, the inclusion of PS significantly increases the brightness and environmental stability. By adopting this ink, the EHD printer successfully fabricated full-color 3D PeNC arrays with a spatial resolution over 2500 ppi. It shows the potential of the EHD inkjet printing strategy for high-resolution and robust PeNC color conversion layers for micro-LED displays.

3.
Angew Chem Int Ed Engl ; : e202403919, 2024 May 24.
Article En | MEDLINE | ID: mdl-38794786

Functional liquid-based interfaces, with their inhomogeneous regions that emphasize the functionalized liquids, have attracted much interest as a versatile platform for a broad spectrum of applications, from chemical manufacturing to practical uses. These interfaces leverage the physicochemical characteristics of liquids, alongside dynamic behaviors induced by macroscopic wettability and microscopic molecular exchange balance, to allow for tailored properties within their functional structures. In this Minireview, we provide a foundational overview of these functional interfaces, based on the structural investigations and molecular mechanisms of interaction forces that directly modulate functionalities. Then, we discuss design strategies that have been employed in recent applications, and the crucial aspects that require focus. Finally, we highlight the current challenges in functional liquid-based interfaces and provide a perspective on future research directions.

4.
J Am Chem Soc ; 146(21): 14558-14565, 2024 May 29.
Article En | MEDLINE | ID: mdl-38755097

The biological neural network is a highly efficient in-memory computing system that integrates memory and logical computing functions within synapses. Moreover, reconfiguration by environmental chemical signals endows biological neural networks with dynamic multifunctions and enhanced efficiency. Nanofluidic memristors have emerged as promising candidates for mimicking synaptic functions, owing to their similarity to synapses in the underlying mechanisms of ion signaling in ion channels. However, realizing chemical signal-modulated logic functions in nanofluidic memristors, which is the basis for brain-like computing applications, remains unachieved. Here, we report a single-pore nanofluidic logic memristor with reconfigurable logic functions. Based on the different degrees of protonation and deprotonation of functional groups on the inner surface of the single pore, the modulation of the memristors and the reconfiguration of logic functions are realized. More noteworthy, this single-pore nanofluidic memristor can not only avoid the average effects in multipore but also act as a fundamental component in constructing complex neural networks through series and parallel circuits, which lays the groundwork for future artificial nanofluidic neural networks. The implementation of dynamic synaptic functions, modulation of logic gates by chemical signals, and diverse combinations in single-pore nanofluidic memristors opens up new possibilities for their applications in brain-inspired computing.

5.
Autophagy ; : 1-16, 2024 May 27.
Article En | MEDLINE | ID: mdl-38802071

The selective removal of dysfunctional mitochondria, a process termed mitophagy, is critical for cellular health and impairments have been linked to aging, Parkinson disease, and other neurodegenerative conditions. A central mitophagy pathway is orchestrated by the ubiquitin (Ub) kinase PINK1 together with the E3 Ub ligase PRKN/Parkin. The decoration of damaged mitochondrial domains with phosphorylated Ub (p-S65-Ub) mediates their elimination though the autophagy system. As such p-S65-Ub has emerged as a highly specific and quantitative marker of mitochondrial damage with significant disease relevance. Existing p-S65-Ub antibodies have been successfully employed as research tools in a range of applications including western blot, immunocytochemistry, immunohistochemistry, and enzyme-linked immunosorbent assay. However, physiological levels of p-S65-Ub in the absence of exogenous stress are very low, therefore difficult to detect and require reliable and ultrasensitive methods. Here we generated and characterized a collection of novel recombinant, rabbit monoclonal p-S65-Ub antibodies with high specificity and affinity in certain applications that allow the field to better understand the molecular mechanisms and disease relevance of PINK1-PRKN signaling. These antibodies may also serve as novel diagnostic or prognostic tools to monitor mitochondrial damage in various clinical and pathological specimens.Abbreviations: AD: Alzheimer disease; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; ELISA: enzyme-linked immunosorbent assay; HEK293E cell: human embryonic kidney E cell; ICC: immunocytochemistry; IHC: immunohistochemistry: KO: knockout; LoB: limit of blank; LoD: limit of detection; LoQ: limit of quantification; MEF: mouse embryonic fibroblast; MSD: Meso Scale Discovery; n.s.: non-significant; nonTg: non-transgenic; PBMC: peripheral blood mononuclear cell; PD: Parkinson disease; p-S65-PRKN: phosphorylated PRKN at serine 65; p-S65-Ub: phosphorylated Ub at serine 65; Ub: ubiquitin; WT: wild-type.

6.
Acta Neuropathol ; 147(1): 54, 2024 Mar 12.
Article En | MEDLINE | ID: mdl-38472443

Rare and common GBA variants are risk factors for both Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, the degree to which GBA variants are associated with neuropathological features in Lewy body disease (LBD) is unknown. Herein, we assessed 943 LBD cases and examined associations of 15 different neuropathological outcomes with common and rare GBA variants. Neuropathological outcomes included LBD subtype, presence of a high likelihood of clinical DLB (per consensus guidelines), LB counts in five cortical regions, tyrosine hydroxylase immunoreactivity in the dorsolateral and ventromedial putamen, ventrolateral substantia nigra neuronal loss, Braak neurofibrillary tangle (NFT) stage, Thal amyloid phase, phospho-ubiquitin (pS65-Ub) level, TDP-43 pathology, and vascular disease. Sequencing of GBA exons revealed a total of 42 different variants (4 common [MAF > 0.5%], 38 rare [MAF < 0.5%]) in our series, and 165 cases (17.5%) had a copy of the minor allele for ≥ 1 variant. In analysis of common variants, p.L483P was associated with a lower Braak NFT stage (OR = 0.10, P < 0.001). In gene-burden analysis, presence of the minor allele for any GBA variant was associated with increased odds of a high likelihood of DLB (OR = 2.00, P < 0.001), a lower Braak NFT stage (OR = 0.48, P < 0.001), a lower Thal amyloid phase (OR = 0.55, P < 0.001), and a lower pS65-Ub level (ß: -0.37, P < 0.001). Subgroup analysis revealed that GBA variants were most common in LBD cases with a combination of transitional/diffuse LBD and Braak NFT stage 0-II or Thal amyloid phase 0-1, and correspondingly that the aforementioned associations of GBA gene-burden with a decreased Braak NFT stage and Thal amyloid phase were observed only in transitional or diffuse LBD cases. Our results indicate that in LBD, GBA variants occur most frequently in cases with greater LB pathology and low AD pathology, further informing disease-risk associations of GBA in PD, PD dementia, and DLB.


Alzheimer Disease , Lewy Body Disease , Parkinson Disease , Humans , Lewy Body Disease/pathology , Parkinson Disease/pathology , Alzheimer Disease/pathology , Substantia Nigra/pathology , Neurofibrillary Tangles/pathology
7.
Int J Biol Macromol ; 267(Pt 1): 131150, 2024 May.
Article En | MEDLINE | ID: mdl-38556236

Gut microbial ß-glucuronidases (gmß-GUS) played crucial roles in regulating a variety of endogenous substances and xenobiotics on the circulating level, thus had been recognized as key modulators of drug toxicity and human diseases. Inhibition or inactivation of gmß-GUS enzymes has become a promising therapeutic strategy to alleviate drug-induced intestinal toxicity. Herein, the Rhodiola crenulata extract (RCE) was found with potent and broad-spectrum inhibition on multiple gmß-GUS enzymes. Subsequently, the anti-gmß-GUS activities of the major constituents in RCE were tested and the results showed that 1,2,3,4,6-penta-O-galloyl-ß-d-glucopyranose (PGG) acted as a strong and broad-spectrum inhibitor on multiple gmß-GUS (including EcGUS, CpGUS, SaGUS, and EeGUS). Inhibition kinetic assays demonstrated that PGG effectively inhibited four gmß-GUS in a non-competitive manner, with the Ki values ranging from 0.12 µM to 1.29 µM. Docking simulations showed that PGG could tightly bound to the non-catalytic sites of various gmß-GUS, mainly via hydrogen bonding and aromatic interactions. It was also found that PGG could strongly inhibit the total gmß-GUS activity in mice feces, with the IC50 value of 1.24 µM. Collectively, our findings revealed that RCE and its constituent PGG could strongly inhibit multiple gmß-GUS enzymes, suggesting that RCE and PGG could be used for alleviating gmß-GUS associated enterotoxicity.


Enzyme Inhibitors , Gastrointestinal Microbiome , Molecular Docking Simulation , Rhodiola , Rhodiola/chemistry , Animals , Mice , Gastrointestinal Microbiome/drug effects , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Medicine, Tibetan Traditional , Kinetics , Male
8.
ACS Nano ; 18(10): 7327-7333, 2024 Mar 12.
Article En | MEDLINE | ID: mdl-38407020

Liquid-based interface behaviors at micro/nano or even smaller scales induced by biomolecules take us into a fascinating realm, fostering a deeper understanding and innovation in visual biosensing. This biosensing technology, grounded in specific liquid-based interface behaviors, redefines how diseases can be detected, monitored, and diagnosed in resource-limited settings, providing rapid, cost-effective, and self-testing solutions to the current healthcare landscape. To date, the technology has witnessed significant advancements in visual sensing, driven by diverse liquid-based materials, advanced nanomanufacturing techniques, and a profound understanding of interface-material interactions. In this Perspective, we discuss and elucidate the interface biosensing mechanisms arising from three types, including liquid-solid, liquid-liquid, and liquid-gas interfaces, and we provide insights into the challenges and future development of visual biosensing applications.

9.
ACS Appl Mater Interfaces ; 16(2): 2231-2239, 2024 Jan 17.
Article En | MEDLINE | ID: mdl-38165218

Flexible ferroelectric films with high polarization hold great promise for energy storage and electrocaloric (EC) refrigeration. Herein, we fabricate a lead-free Mn-modified 0.75 Bi(Mg0.5Ti0.5)O3-0.25 BaTiO3 (BMT-BTO) thin film based on a flexible mica substrate. Excellent EC performance with maximum adiabatic temperature change (ΔT ∼23.5 K) and isothermal entropy change (ΔS ∼33.1 J K-1 kg-1) is achieved in the flexible BMT-BTO film, which is attributed to the local structural transition and lattice disorder near 90 °C. Meanwhile, a good energy storage density of ∼70.6 J cm-3 and a quite high efficiency of ∼82% are realized in the same ferroelectric film, accompanied by excellent stability of frequency and electric fatigue (500-10 kHz and 108 cycles). Furthermore, there is no apparent variation in performance under different bending strains. These prominent properties indicate that the multifunctional BMT-BTO ferroelectric film is a promising candidate for applications of flexible energy storage and EC refrigeration.

10.
bioRxiv ; 2024 Jan 16.
Article En | MEDLINE | ID: mdl-38293125

The selective removal of dysfunctional mitochondria, a process termed mitophagy, is critical for cellular health and impairments have been linked to aging, Parkinson disease, and other neurodegenerative conditions. A central mitophagy pathway is orchestrated by the ubiquitin (Ub) kinase PINK1 together with the E3 Ub ligase PRKN/Parkin. The decoration of damaged mitochondrial domains with phosphorylated Ub (p-S65-Ub) mediates their elimination though the autophagy system. As such p-S65-Ub has emerged as a highly specific and quantitative marker of mitochondrial damage with significant disease relevance. Existing p-S65-Ub antibodies have been successfully employed as research tools in a range of applications including western blot, immunocytochemistry, immunohistochemistry, and ELISA. However, physiological levels of p-S65-Ub in the absence of exogenous stress are very low, therefore difficult to detect and require reliable and ultrasensitive methods. Here we generated and characterized a collection of novel recombinant, rabbit monoclonal p-S65-Ub antibodies with high specificity and affinity in certain applications that allow the field to better understand the molecular mechanisms and disease relevance of PINK1-PRKN signaling. These antibodies may also serve as novel diagnostic or prognostic tools to monitor mitochondrial damage in various clinical and pathological specimens.

11.
Chemistry ; 30(18): e202303742, 2024 Mar 25.
Article En | MEDLINE | ID: mdl-38214487

Excess fluoride ions in groundwater accumulate through the roots of crops, affecting photosynthesis and inhibiting their growth. Long-term bioaccumulation also threatens human health because it is poorly degradable and toxic. Currently, one of the biggest challenges is developing a unique material that can efficiently remove fluoride ions from the environment. The excellent properties of functionalized pillar[5]arene polymer-filled nanochannel membranes were explored to address this challenge. Constructing a multistage porous nanochannel membrane, consisting of microscale etched nanochannels and nanoscale pillar[5]arene cross-linked polymer voids. A fluoride removal rate of 0.0088 mmol ⋅ L-1 ⋅ min-1 was achieved. Notably, this rate surpassed the rates observed with other control ions by a factor of 6 to 8.8. Our research provides a new direction for developing water fluoride ion removal materials.

12.
ChemSusChem ; 17(4): e202301269, 2024 Feb 22.
Article En | MEDLINE | ID: mdl-37848390

Rechargeable magnesium batteries could provide future energy storage systems with high energy density. One remaining challenge is the development of electrolytes compatible with the negative Mg electrode, enabling uniform plating and stripping with high Coulombic efficiencies. Often improvements are hindered by a lack of fundamental understanding of processes occurring during cycling, as well as the existence and structure of a formed interphase layer at the electrode/electrolyte interface. Here, a magnesium model electrolyte based on magnesium bis(trifluoromethanesulfonyl)imide (Mg(TFSI)2 ) and MgCl2 with a borohydride as additive, dissolved in dimethoxyethane (DME), was used to investigate the initial galvanostatic plating and stripping cycles operando using electrochemical quartz crystal microbalance with dissipation monitoring (EQCM-D). We show that side reactions lead to the formation of an interphase of irreversibly deposited Mg during the initial cycles. EQCM-D based hydrodynamic spectroscopy reveals the growth of a porous layer during Mg stripping. After the first cycles, the interphase layer is in a dynamic equilibrium between the formation of the layer and its dissolution, resulting in a stable thickness upon further cycling. This study provides operando information of the interphase formation, its changes during cycling and the dynamic behavior, helping to rationally develop future electrolytes and electrode/electrolyte interfaces and interphases.

13.
Small ; 20(23): e2308577, 2024 Jun.
Article En | MEDLINE | ID: mdl-38145960

Aqueous lithium-ion batteries (ALIBs) are promising for large-scale energy storage systems because of the cost-effective, intrinsically safe, and environmentally friendly properties of aqueous electrolytes. Practical application is however impeded by interfacial side-reactions and the narrow electrochemical stability window (ESW) of aqueous electrolytes. Even though higher electrolyte salt concentrations (e.g., water-in-salt electrolyte) enhance performance by widening the ESW, the nature and extent of side-reaction processes are debated and more fundamental understanding thereof is needed. Herein, the interfacial chemistry of one of the most popular electrode materials, V2O5, for aqueous batteries is systematically explored by a unique set of operando analytical techniques. By monitoring electrode/electrolyte interphase deposition, electrolyte pH, and gas evolution, the highly dynamic formation/dissolution of V2O5/V2O4, Li2CO3 and LiF during dis-/charge is demonstrated and shown to be coupled with electrolyte decomposition and conductive carbon oxidation, regardless of electrolyte salt concentration. The study provides deeper understanding of interfacial chemistry of active materials under variable proton activity in aqueous electrolytes, hence guiding the design of more effective electrode/electrolyte interfaces for ALIBs and beyond.

14.
Autophagy ; : 1-12, 2023 Dec 02.
Article En | MEDLINE | ID: mdl-38041584

The ubiquitin kinase-ligase pair PINK1-PRKN recognizes and transiently labels damaged mitochondria with ubiquitin phosphorylated at Ser65 (p-S65-Ub) to mediate their selective degradation (mitophagy). Complete loss of PINK1 or PRKN function unequivocally leads to early-onset Parkinson disease, but it is debated whether impairments in mitophagy contribute to disease later in life. While the pathway has been extensively studied in cell culture upon acute and massive mitochondrial stress, basal levels of activation under endogenous conditions and especially in vivo in the brain remain undetermined. Using rodent samples, patient-derived cells, and isogenic neurons, we here identified age-dependent, brain region-, and cell type-specific effects and determined expression levels and extent of basal and maximal activation of PINK1 and PRKN. Our work highlights the importance of defining critical risk and therapeutically relevant levels of PINK1-PRKN signaling which will further improve diagnosis and prognosis and will lead to better stratification of patients for future clinical trials.

15.
Phys Chem Chem Phys ; 25(48): 33104-33111, 2023 Dec 13.
Article En | MEDLINE | ID: mdl-38044721

Plastic waste is causing serious environment pollution and its efficient disposal is attracting more and more attention. The use of catalysts not only reduced the degradation temperature of plastic wastes but also facilitated the production of valuable chemicals. Herein, mesopores were introduced into HZSM-5 zeolites by alkali and acid treatment, which was expected to eliminate the diffusion resistance caused by bulky polymer molecules and improve the catalytic activity. It was found that HZSM-5 zeolites enhanced PE, PP and PS degradation, and an increase of mesopore volume further improved the catalytic activity and reduced the activation energy. For example, the use of HZSM-5 in PP degradation decreased the activation energy from 146.9 kJ mol-1 to 93.1 kJ mol-1, and mesopore-rich HZSM-5 further decreased the activation energy to 84.0 kJ mol-1. The molecular diameter of the PP fragment was obtained by theoretical calculations, and it was close to 1.6 nm, which was significantly higher than the micropore diameter of HZSM-5 zeolites (0.5-0.6 nm) while lower than the mesopore diameter. It was concluded that the presence of mesopores provided the place and space for plastics degradation.

16.
Health Sci Rep ; 6(12): e1762, 2023 Dec.
Article En | MEDLINE | ID: mdl-38116174

Background and Aims: Percutaneous transcatheter left atrial appendage (LAA) closure (LAAC) is an effective approach for preventing ischemic stroke in nonvalvular atrial fibrillation patients. Intracardiac echocardiography (ICE), a new imaging modality, is a promising strategy for guiding LAAC. This review highlights the various strategies for ICE-guided-LAAC as an option for clinical policy. Methods: A comprehensive literature search was conducted of PubMed, ScienceDirect, Ovid Web of Science, SpringerLink, and other notable databases to identify recent peer-reviewed clinical trials, reviews, and research articles related to ICE and its application in the guidance of LAAC. Results: Various methods are used to evaluate the spatial structure and dimensions of the LAA. The main techniques for guiding LAAC are transesophageal echocardiography (TEE), cardiac computed tomography (CTA), and ICE. Among these techniques, the advantages of ICE typically include (1) multiangle and real-time assessment of intracardiac structure, (2) a reduction in procedural fluoroscopy, (3) reduced operation time and improved workflow in the catheterization laboratory, and (4) the avoidance of general anesthesia and the early detection of complications. Conclusion: ICE is a promising strategy for the guidance of LAAC. Among the most advanced and recent technological innovations in cardiovascular imaging in general and volume imaging in particular, ICE offers greater efficacy and safety.

17.
Heliyon ; 9(11): e21906, 2023 Nov.
Article En | MEDLINE | ID: mdl-38028013

Background: In this study, we aimed to investigate the performance of GALAD, GALAD-C, and GAAP models in Chinese population in comparison to our newly build statistical model. Methods: In this study, we built the AALP model based on age, α-fetoprotein (AFP), AFP-L3, and prothrombin induced by vitamin K absence-II (PIVKA II) to differentiate between patients with HCC and patients with CLD. We then compared the serum levels of AFP-L3 and PIVKA II in patients with HCC who were defined as remission or progression and showed the prognostic value of combined biomarkers. Results: The AUC value of the AALP model for HCC detection was 0.939 and AALP model exhibited a sensitivity of 81 % and a high specificity of 95 %. AALP model also exhibited good performance in the subgroups of patients with CLD. Furthermore, we demonstrated the consistency between imaging results and serum levels of AFP-L3 and PIVKA II. Conclusions: The AALP model achieved a good diagnostic performance and a high sensitivity for predicting HCC patients. Our research also showed that AFP-L3 and PIVKA II are complementary to each other but irreplaceable in the clinical detection and monitoring of HCC.

18.
Nano Lett ; 23(20): 9383-9391, 2023 Oct 25.
Article En | MEDLINE | ID: mdl-37792754

Vertically aligned carbon nanotubes array offers unique properties for various applications. Detaching them from the growth substrate, while preserving their vertical structure, is essential. Quartz, a cost-effective alternative to silicon wafers and metal-based substrates, can serve as both a reaction chamber and a growth substrate. However, the strong adhesive interaction with the quartz substrate remains an obstacle for further applications. Herein, we presented a simple and well-controlled exfoliation strategy assisted by the introduction of heteroatoms at root ends of a carbon nanotubes array. This strategy forms lower surface polarity of the carbon fragment to significantly reduce adhesion to the quartz substrate, which contributes to the effortless exfoliation. Furthermore, this scalable approach enables potential mass production on recyclable quartz substrates, enhancing the cost-effectiveness and efficiency. This work can establish a solid foundation for cost-competitive carbon nanotube-based technologies, offering a promising avenue for their widespread applications.

19.
medRxiv ; 2023 Oct 16.
Article En | MEDLINE | ID: mdl-37905059

The PINK1-PRKN pathway mediates a critical quality control to maintain mitochondrial health and function. Together the kinase-ligase pair identifies and decorate damaged mitochondria with phosphorylated ubiquitin (p-S65-Ub). This selective label serves as the mitophagy tag and facilitates their degradation via autophagy-lysosome system. While complete loss of PINK1 or PRKN function causes early-onset Parkinson disease, much broader mitophagy impairments are emerging across neurodegenerative disorders. We previously found age- and disease-dependent accumulation of p-S65-Ub signal in the hippocampus of autopsy brains with Lewy body disease (LBD). However, the contribution of genetic variation to mitochondrial damage and p-S65-Ub levels remains unknown in LBD cases. To identify novel regulators of PINK1-PRKN mitophagy in LBD, we performed an unbiased genome-wide association study of hippocampal p-S65-Ub level with 1,012 autopsy confirmed LBD samples. Using an established, mostly automated workflow, hippocampal sections were immunostained for p-S65-Ub, scanned, and quantified with unbiased algorithms. Functional validation of the significant hit was performed in animal model and human induced pluripotent stem cells (hiPSCs). We identified a strong association with p-S65-Ub for APOE4 (rs429358; ß : 0.50, 95% CI: 0.41 to 0.69; p =8.67x10 -25 ) and a genome-wide significant association for ZMIZ1 (rs6480922; ß : -0.33, 95% CI: -0.45 to -0.22; p =1.42x10 -8 ). The increased p-S65-Ub levels in APOE4 -carrier may be mediated by both co-pathology-dependent and -independent mechanisms, which was confirmed in Apoe-targeted replacement mice and hiPSC-derived astrocytes. Intriguingly, ZMIZ1 rs6480922 also significantly associated with increased brain weight and reduced neuropathological burden indicating a potential role as a resilience factor. Our findings nominate novel mitophagy regulators in LBD brain ( ZMIZ1 locus) and highlight a strong association of APOE4 with mitophagy alteration. With APOE4 being the strongest known risk factor for clinical Alzheimer's disease and dementia with Lewy bodies, our findings suggest a common mechanistic link underscoring the importance of mitochondrial quality control.

20.
ACS Appl Mater Interfaces ; 15(37): 43845-43858, 2023 Sep 20.
Article En | MEDLINE | ID: mdl-37690049

Cobalt is an alternative catalyst for furfural hydrogenation but suffers from the strong binding of H and furan ring on the surface, resulting in low catalytic activity and chemoselectivity. Herein, by constructing a Pd-Co interface in cobalt oxide-supported Pd catalysts to tailor the d-band center of Co, the concerted effort of Pd and Co boosts the catalytic performance for the hydroconversion of furfural to cyclopentanone and cyclopentanol. The increased dispersion of Pd on acid etching Co3O4 promotes the reduction of Co3+ to Co0 by enhancing hydrogen spillover, favoring the creation of the Pd-Co interface. Both experimental and theoretical calculations demonstrate that the electron transfer from Pd to Co at the interface results in the downshift of the d-band center of Co atoms, accompanied by the destabilization of H and furan ring adsorption on the Co surface, respectively. The former improves the furfural hydrogenation with TOF on Co elevating from 0.20 to 0.62 s-1, and the latter facilitates the desorption of formed furfuryl alcohol from the Co surface for subsequently hydrogenative rearrangement of the furan ring to cyclopentanone on acid sites. The resultant Pd/Co3O4-6 catalyst delivers superior activity with a 99% furfural conversion and 85% overall selectivity toward cyclopentanone/cyclopentanol. We anticipate that such a concept of tailoring the d-band center of Co via interface engineering provides novel insight and feasible approach for the design of highly efficient catalysts for furfural hydroconversion and beyond.

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