Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies.

Parkinson's disease (PD), an adult neurodegenerative disorder, has been clinically linked to the lysosomal storage disorder Gaucher disease (GD), but the mechanistic connection is not known. Here, we show that functional loss of GD-linked glucocerebrosidase (GCase) in primary cultures or human iPS neurons compromises lysosomal protein degradation, causes accumulation of α-synuclein (α-syn), and results in neurotoxicity through aggregation-dependent mechanisms. Glucosylceramide (GlcCer), the GCase substrate, directly influenced amyloid formation of purified α-syn by stabilizing soluble oligomeric intermediates. We further demonstrate that α-syn inhibits the lysosomal activity of normal GCase in neurons and idiopathic PD brain, suggesting that GCase depletion contributes to the pathogenesis of sporadic synucleinopathies. These findings suggest that the bidirectional effect of α-syn and GCase forms a positive feedback loop that may lead to a self-propagating disease. Therefore, improved targeting of GCase to lysosomes may represent a specific therapeutic approach for PD and other synucleinopathies.

Unipolar Solution Flow in Calcium-Organic Frameworks for Seawater-Evaporation-Induced Electricity Generation.

Seawater-flow- and -evaporation-induced electricity generation holds significant promise in advancing next-generation sustainable energy technologies. This method relies on the electrokinetic effect but faces substantial limitations when operating in a highly ion-concentrated environment, for example, natural seawater. We present herein a novel solution using calcium-based metal-organic frameworks (MOFs, C12H6Ca2O19·2H2O) for seawater-evaporation-induced electricity generation. Remarkably, Ca-MOFs show an open-circuit voltage of 0.4 V and a short-circuit current of 14 µA when immersed in seawater under natural conditions. Our experiments and simulations revealed that sodium (Na) ions selectively transport within sub-nanochannels of these synthetic superhydrophilic MOFs. This selective ion transport engenders a unipolar solution flow, which drives the electricity generation behavior in seawater. This work not only showcases an effective Ca-MOF for electricity generation through seawater flow/evaporation but also contributes significantly to our understanding of water-driven energy harvesting technologies and their potential applications beyond this specific context.

Lattice Strain and Charge Redistribution of Pt Cluster/Ir Metallene Heterostructure for Ethylene Glycol to Glycolic Acid Conversion Coupled with Hydrogen Production.

Upgrading overall water splitting (OWS) system and developing high-performance electrocatalysts is an attractive way to the improve efficiency and reduce the consumption of hydrogen (H2 ) production from electrolyzed water. Here, a Pt cluster/Ir metallene heterojunction structure (Pt/Ir hetero-metallene) with a unique Pt/Ir interface is reported for the conversion of ethylene glycol (EG) to glycolic acid (GA) coupled with H2 production. With the assistance of ethylene glycol oxidation (EGOR), the Pt/Ir||Pt/Ir hetero-metallene two-electrode water electrolysis system exhibits a lower cell voltage of 0.36 V at 10 mA cm-2 . Furthermore, the Faradaic efficiency of EG to GA is as high as 87%. The excellent performance of this new heterostructure arise from the charge redistribution and strain effects induced by Pt-Ir interactions between the heterogeneous interfaces, as well as the larger specific surface area and more active sites due to the metallene structure.

High-Performance Flexible Ionically Conductive Superhydrophobic Papers via Deep Eutectic Polymer-Enhanced Interfacial Interactions.

Endowing paper with highly flexible, conductive, and superhydrophobic properties will effectively expand its applications in fields such as green packaging, smart sensing, and paper-based electronics. Herein, a multifunctional superhydrophobic paper is reported in which a highly flexible transparent conductive substrate is prepared by introducing a hydrophobic deep eutectic polymer into the ethylcellulose network via a matrix swelling-polymerization strategy, and then the substrate is modified using fluorinated silica to impart superhydrophobicity. By introducing soft deep eutectic polymers, (1) the superhydrophobic paper can efficiently dissipate energy during deformation, (2) intrinsically ion-conducting deep eutectic polymers can endow the material with good electrical sensing properties, and (3) meanwhile, enhanced interfacial interactions can anchor inorganic particles, thereby improving the coating stability. The prepared superhydrophobic paper has an ultrahigh water contact angle (contact angle ≈ 162.2°) and exhibits a stable electrical response signal to external deformation/pressure, and the electrical properties are almost unaffected by external water molecules. In addition, the superhydrophobic paper was able to withstand 5000 bending-recovery cycles at a large angle of 150°, exhibiting stable electrical performance. The design concepts demonstrated here will provide insights into the development of superhydrophobic paper-based flexible electronic devices.

Boron-intercalation-triggered crystalline transition of Pd nanosheet assemblies for an enhanced oxygen reduction reaction.

The development of effective and stable cathode electrocatalysts is highly desired for fuel cells. Controlling the composition and morphology of Pd-based materials can provide a great opportunity to improve their oxygen reduction reaction (ORR) performance. Here, we report the synthesis of hexagonal close-packed (hcp) Pd2B nanosheet assemblies (Pd2B NAs) via the boronation reaction between as-synthesized Pd NAs and N,N-dimethylformamide. The hcp Pd2B NAs with uniform pore distribution can provide sufficient active sites for ORRs. The insertion of B atoms can induce the phase transition from face-centered cubic structure to hcp structure, as the most thermodynamically stable phase in the Pd-B alloy, which is beneficial for enhancing the ORR stability and toxicity resistance. Therefore, the hcp Pd2B NAs exhibit superior mass activity, specific activity and excellent stability for ORR. The present strategy of boron-intercalation-triggered crystalline transition of Pd-based nanomaterials is valuable for the design of metal-nonmetal catalysts with enhanced performance.

Amorphous/crystalline RhFeP metallene for hydrazine-assisted water splitting.

Replacing the slow oxygen evolution reaction with favorable hydrazine oxidation reaction (HzOR) is a green and efficient way to produce hydrogen. In this work, we synthesize amorphous/crystalline RhFeP metallene via phase engineering and heteroatom doping. RhFeP metallene has good catalytic activity and stability for HER and HzOR, and only an ultralow voltage of 18 mV is required to achieve 10 mA cm-2in a two-electrode hydrazine-assisted water splitting system. The superior result is mainly ascribed to the co-doping of Fe and P and the formation of amorphous/crystalline RhFeP metallene with abundant phase boundaries, thereby adjusting electronic structure and increasing active sites.

Smart Galactosidase-Responsive Antimicrobial Dendron: Towards More Biocompatible Membrane-Disruptive Agents.

Antimicrobial resistance is a global healthcare challenge that urgently needs the development of new therapeutic agents. Antimicrobial peptides and mimics thereof are promising candidates but mostly suffer from inherent toxicity issues due to the non-selective binding of cationic groups with mammalian cells. To overcome this toxicity issue, this work herein reports the synthesis of a smart antimicrobial dendron with masked cationic groups (Gal-Dendron) that could be uncaged in the presence of ß-galactosidase enzyme to form the activated Enz-Dendron and confer antimicrobial activity. Enz-Dendron show bacteriostatic activity toward Gram-negative (P. aeruginosa and E. coli) and Gram-positive (S. aureus) bacteria with minimum inhibitory concentration values of 96 µm and exerted its antimicrobial mechanism via a membrane disruption pathway, as indicated by inner and outer membrane permeabilization assays. Crucially, toxicity studies confirmed that the masked prodrug Gal-Dendron exhibited low hemolysis and is at least 2.4 times less toxic than the uncaged cationic Enz-Dendron, thus demonstrating the advantage of masking the cationic groups with responsive immolative linkers to overcome toxicity and selectivity issues. Overall, this study highlights the potential of designing new membrane-disruptive antimicrobial agents that are more biocompatible via the amine uncaging strategy.

Doxepin is more effective than zolpidem in improving executive function in patients with insomnia disorder.

BACKGROUND : Insomnia disorder is associated with an impairment in cognitive performance. Doxepin and zolpidem have been found to be effective in improving sleep. In this study, we aimed to compare the effects of doxepin and zolpidem on sleep structure and executive function in patients with insomnia disorder. METHODS: Patients with primary insomnia were randomly assigned to receive doxepin 6 mg/day orally or zolpidem 5-10 mg/day orally. Polysomnography (PSG) and the Pittsburgh Sleep Quality Index (PSQI) were used at baseline and after the 8-week treatment to compare clinical efficacy in the two groups. Safety was assessed using the Treatment Emergent Symptom Scale (TESS). Executive function was evaluated using the Wisconsin sorting card test (WSCT). RESULTS: Of 120 patients enrolled in the study, 60 participants were assigned to each group. A total of 109 participants (53 in the doxepin group and 56 in the zolpidem group) completed the study. After treatment, the wake after sleep onset (WASO) and total sleep time (TST) values in the doxepin group were 80.3 ± 21.4 min and 378.9 ± 21.9 min, respectively, which were significantly better than those in the zolpidem group (132.9 ± 26.5 min and 333.2 ± 24.2 min, respectively; (P < 0.05)). The sleep onset latency (SOL) value in the zolpidem group (20.3 ± 4.7 min) was significantly better than that in the doxepin group (28.2 ± 5.6 min; P < 0.05). The sleep efficiency (SE) in the doxepin group was 77.8 ± 4.2%, which was significantly better than that in the zolpidem group (68.6 ± 5.0%; P < 0.05). The PSQI score of the doxepin group was 6.1 ± 1.1, which was significantly lower than that in the zolpidem group (7.9 ± 1.9; P < 0.05). The treatment adverse events in the doxepin group was 23.3%, which was significantly higher than that in the zolpidem group (13.3%; P < 0.05). The WSCT showed a significant improvement in persistent errors (PE), random errors (RE), and categories in the two groups after 8-week treatment, and the improvement in RE and the categories was more obvious in the doxepin group (P < 0.05). CONCLUSIONS: Both doxepin and zolpidem were found to be effective in improving sleep quality, but the effects exhibited different patterns. Doxepin improved executive function more effectively than zolpidem in patients with insomnia disorder.

Glutamate Receptor-like (GLR) Family in Brassica napus: Genome-Wide Identification and Functional Analysis in Resistance to Sclerotinia sclerotiorum.

Plant glutamate receptor-like channels (GLRs) are homologs of animal ionotropic glutamate receptors. GLRs are critical in various plant biological functions, yet their genomic features and functions in disease resistance remain largely unknown in many crop species. Here, we report the results on a thorough genome-wide study of the GLR family in oilseed rape (Brassica napus) and their role in resistance to the fungal pathogen Sclerotinia sclerotiorum. A total of 61 GLRs were identified in oilseed rape. They comprised three groups, as in Arabidopsis thaliana. Detailed computational analyses, including prediction of domain and motifs, cellular localization, cis-acting elements, PTM sites, and amino acid ligands and their binding pockets in BnGLR proteins, unveiled a set of group-specific characteristics of the BnGLR family, which included chromosomal distribution, motif composition, intron number and size, and methylation sites. Functional dissection employing virus-induced gene silencing of BnGLRs in oilseed rape and Arabidopsis mutants of BnGLR homologs demonstrated that BnGLR35/AtGLR2.5 positively, while BnGLR12/AtGLR1.2 and BnGLR53/AtGLR3.2 negatively, regulated plant resistance to S. sclerotiorum, indicating that GLR genes were differentially involved in this resistance. Our findings reveal the complex involvement of GLRs in B. napus resistance to S. sclerotiorum and provide clues for further functional characterization of BnGLRs.

Visualizing Cardiolipin In Situ with HKCL-1M, a Highly Selective and Sensitive Fluorescent Probe.

Reliable probing of cardiolipin (CL) content in dynamic cellular milieux presents significant challenges and great opportunities for understanding mitochondria-related diseases, including cancer, neurodegeneration, and diabetes mellitus. In intact respiring cells, selectivity and sensitivity for CL detection are technically demanding due to structural similarities among phospholipids and compartmental secludedness of the inner mitochondrial membrane. Here, we report a novel "turn-on" fluorescent probe HKCL-1M for detecting CL in situ. HKCL-1M displays outstanding sensitivity and selectivity toward CL through specific noncovalent interactions. In live-cell imaging, its hydrolyzed product HKCL-1 efficiently retained itself in intact cells independent of mitochondrial membrane potential (Δψm). The probe robustly co-localizes with mitochondria and outperforms 10-N-nonyl acridine orange (NAO) and Δψm-dependent dyes with superior photostability and negligible phototoxicity. Our work thus opens up new opportunities for studying mitochondrial biology through efficient and reliable visualization of CL in situ.

Interface Engineering and Boron Modification of Pd-B/Pd Hetero-Metallene Synergistically Accelerate Oxygen Reduction Catalysis.

2D metallene possess high surface area and excellent electron transport capability, thus enabling efficient application in oxygen reduction reaction (ORR). However, the interface regulation and electronic structure optimization of metallene are still great challenges. Herein, Pd-B/Pd hetero-metallene is constructed by interface engineering and B modification strategies for efficient electrocatalytic ORR. The 2D configuration of Pd-B/Pd hetero-metallene exposes a large number of surface atoms and unsaturated defect sites, thus providing abundant catalytic active sites and exhibiting high electron mobility. More importantly, interface engineering and B modification synergistically optimizing the electronic configuration of the metallene system. This work not only provides an effective strategy for the rational regulation of the electronic configuration of metallene, but also offers a reference for the construction of efficient ORR catalysts.

A General Synthesis of Crystal Phase Controllable Aerogels for Efficient Hydrogen Evolution.

Amorphous/crystalline (a/c) hetero-phase structures are considered as a class of efficient electrocatalysts for hydrogen evolution reaction (HER), but it remains a substantial challenge to obtain the specific phase by phase-selective synthesis. In this work, a general route for the preparation of various heterogeneous aerogels (RuB, PtB, PdB, and RhB) consisting of amorphous and crystalline phases is presented through a controlled NaBH4 reduction method. The prepared a/c-RuB aerogel exhibits better HER performance due to their desirable compositional and structural advantages such as more exposed active sites, optimized electronic structure, and interfacial synergistic effects. It requires only a low overpotential of 39 mV to reach a density of 10 mA cm-2 and also exhibits excellent stability. This work provides a new phase-selective synthesis strategy for the design and development of advanced hetero-phase electrocatalysts.

Defect-Rich PdIr Bimetallene Nanoribbons with Interatomic Charge Localization for Isopropanol-Assisted Seawater Splitting.

Metallene with outstanding physicochemical properties is an efficient two-dimensional electrocatalysts for sustainable hydrogen (H2 ) production applications. However, the controllable fabrication of extended atomically thin metallene nanoribbons remains a formidable challenge. Herein, this work proposes a controllable preparation strategy for atomically thin defect-rich PdIr bimetallene nanoribbons (PdIr BNRs) with a thickness of only 1.5 nm for the efficient and stable isopropanol-assisted seawater electrolytic H2 production. When using PdIr BNRs as catalyst to build an isopropanol-assisted seawater electrolysis system, a voltage of only 0.38 V is required at @10 mA cm-2 to achieve energy-saving H2 production, while producing high value-added acetone at the anode. The aberration-corrected high-resolution transmission electron microscopy (HRTEM) clearly reveals that the PdIr BNRs possess abundant structural defects, which can additionally serve as highly catalytically active sites. Density functional theory (DFT) calculations combined with X-ray absorption spectroscopy studies reveal that the introduction of Ir atoms can induce the formation of a localized charge region and shift the d-band center of Pd down, thereby reducing the adsorption energy on the catalyst in favor of the rapid desorption of H2 . This work opens the way for the controllable design and construction of defect-rich atomically thin metallene nanoribbons for efficient electrocatalytic applications.

Sulfur-Induced Low Crystallization of Ultrathin Pd Nanosheet Arrays for Sulfur Ion Degradation-Assisted Energy-Efficient H2 Production.

The utilization of thermodynamically favorable sulfur oxidation reaction (SOR) as an alternative to sluggish oxygen evolution reaction is a promising technology for low-energy H2 production while degrading the sulfur source from wastewater. Herein, amorphous/crystalline S-doped Pd nanosheet arrays on nickel foam (a/c S-Pd NSA/NF) is prepared by S-doping crystalline Pd NSA/NF.  Owing to the ultrathin amorphous nanosheet structure and the incorporation of S atoms, the a/c S-Pd NSA/NF provides a large number of active sitesand the optimized electronic structure, while exhibiting outstanding electrocatalytic activity in hydrogen evolution reaction (HER) and SOR. Therefore, the coupling system consisting of SOR-assisted HER can reach a current density of 100 mA cm-2 at 0.642 V lower than conventional electrolytic water by 1.257 V, greatly reducing energy consumption. In addition, a/c S-Pd NSA/NF can generate H2 over a long period of time while degrading S2- in water to the value-added sulfur powder, thus further reducing the cost of H2 production. This work proposes an attractive strategy for the construction of an advanced electrocatalyst for H2 production and utilization of toxic sulfide wastewater by combining S-doping induced partial amorphization and ultrathin metal nanosheet arrays.

Engineering Under-Coordinated Active Sites with Tailored Chemical Microenvironments over Mosaic Bismuth Nanosheets for Selective CO2 Electroreduction to Formate.

Selective electrochemical reduction of CO2 into fuels or chemical feedstocks is a promising avenue to achieve carbon-neutral goal, but its development is severely limited by the lack of highly efficient electrocatalysts. Herein, cation-exchange strategy is combined with electrochemical self-reconstruction strategy to successfully develop diethylenetriamine-functionalized mosaic Bi nanosheets (mBi-DETA NSs) for selective electrocatalytic CO2 reduction to formate, delivering a superior formate Faradaic efficiency of 96.87% at a low potential of -0.8 VRHE . Mosaic nanosheet morphology of Bi can sufficiently expose the under-coordinated Bi active sites and promote the activation of CO2 molecules to form the OCHO- * intermediate. Moreover, in situ attenuated total reflectance infrared spectra further corroborate that surface chemical microenvironment modulation of mosaic Bi nanosheets via DETA functionalization can improve CO2 adsorption on the catalyst surface and stabilize the key intermediate (OCHO- *) due to the presence of amine groups, thus facilitate the CO2 -to-HCOO- reaction kinetics and promote formate formation.

Selective CO2 Electroreduction to Formate on Polypyrrole-Modified Oxygen Vacancy-Rich Bi2 O3 Nanosheet Precatalysts by Local Microenvironment Modulation.

Challenges remain in the development of highly efficient catalysts for selective electrochemical transformation of carbon dioxide (CO2 ) to high-valued hydrocarbons. In this study, oxygen vacancy-rich Bi2 O3 nanosheets coated with polypyrrole (Bi2 O3 @PPy NSs) are designed and synthesized, as precatalysts for selective electrocatalytic CO2 reduction to formate. Systematic material characterization demonstrated that Bi2 O3 @PPy precatalyst can evolve intoBi2 O2 CO3 @PPy nanosheets with rich oxygen vacancies (Bi2 O2 CO3 @PPy NSs) via electrolyte-mediated conversion and function as the real active catalyst for CO2 reduction reaction electrocatalysis. Coating catalyst with a PPy shell can modulate the interfacial microenvironment of active sites, which work in coordination with rich oxygen vacancies in Bi2 O2 CO3 and efficiently mediate directional selective CO2 reduction toward formate formation. With the fine-tuning of interfacial microenvironment, the optimized Bi2 O3 @PPy-2 NSs derived Bi2 O2 CO3 @PPy-2 NSs exhibit a maximum Faradaic efficiency of 95.8% at -0.8 V (versus. reversible hydrogen electrode) for formate production. This work might shed some light on designing advanced catalysts toward selective electrocatalytic CO2 reduction through local microenvironment engineering.

Polyethylenimine-Ethylenediamine-Induced Pd Metallene toward Alkaline Oxygen Reduction.

Designing two-dimensional (2D) materials functionalized with organic molecules is an effective tactic to enhance catalytic performances for the oxygen reduction reaction (ORR). Herein, we synthesize Pd metallene with in situ modification of polyethylenimine-ethylenediamine (Pd@PEI-EDA metallene), in which PEI-EDA serves as both the structure-directing agent and modifier. Pd@PEI-EDA metallene has ample active sites and tuneable electronic structures due to ultrathin nanosheets with abundant wrinkles and interfacial structure. In contrast with commercial Pd/C and Pt/C, Pd@PEI-EDA metallene displays preferable catalytic ORR performance under alkaline conditions. This work offers an in situ interface engineering tactic for the preparation of 2D polymer-metal electrocatalysts to boost the ORR performance.

B-Doping-Induced Lattice Expansion of Pd Metallene Nanoribbons for Oxygen Reduction Reaction.

Pd-based metallene is regarded as an efficient catalyst in the field of oxygen reduction reaction (ORR) because of its fantastic physicochemical features. The morphological structure control, lattice strain engineering, and electronic structure modulation of Pd-based metallene are effective tactics to enhance its electrocatalytic performance. In this work, we fabricate atomically thin B-doped Pd metallene nanoribbons (B-Pd MNRs) for efficient alkaline ORR. The atomically thin nanoribbon structure of B-Pd MNRs can expose many surface atoms as catalytically active sites. Moreover, the incorporation of boron effectively induces the lattice expansion and modulates the electronic structure of Pd, which can synergistically weaken the adsorption of intermediate species on B-Pd MNRs. Therefore, the B-Pd MNRs display excellent activity and durability for ORR. This work opens an avenue to the synthesis of atomically thin heteroatom-doped metallene nanoribbons for energy electrocatalytic applications.

Electron Regulation of Heterostructured Pt/Rh Metallene Boosts Ethylene Glycol Electrooxidation and Hydrogen Evolution.

The research on high-efficiency two-dimensional (2D) catalytic materials for the small-molecule oxidation-assisted hydrogen evolution reaction (HER) is prospective for efficient hydrogen production. Herein, we report heterostructured Pt/Rh metallene with Pt nanoparticles (NPs) uniformly anchored on Rh metallene for the HER and ethylene glycol oxidation reaction (EGOR). The ultrathin sheet structure of the Pt/Rh metallene offers high surface areas and sufficient active sites. More importantly, the Pt/Rh heterostructure can optimize catalytic active centers and adjust electronic structure. Thus, Pt/Rh metallene exhibits superior electrocatalytic HER activity with a low overpotential of 28 mV in 1 M KOH at 10 mA cm-2 and EGOR activity with a specific activity of 8.39 mA cm-2 in 1 M KOH with 3 M EG, along with outstanding CO tolerance. In a two-electrode system, Pt/Rh metallene requires a low potential of 0.51 V for stable and efficient hydrogen production at 10 mA cm-2 in 1 M KOH + 3 M EG, with the simultaneous production of high-value-added products. The job proposes an attractive strategy for the synthesis of 0D/2D metallene toward simultaneous energy-saving hydrogen production and chemical update.

Electrochemical Postmodification-Induced Surface Atom Rearrangement over Cu Nanodendrites for Enhanced Electrosynthesis of Ammonia from Nitrate.

Utilizing nitrate from wastewater as a N-source for ammonia synthesis via electrocatalysis is of significance for both environmental protection and ecological nitrogen cycle balance, which requires high-performance electrocatalysts to drive selective nitrate-to-ammonia transformation. In this work, an electrochemical postmodification strategy was developed to regulate the surface structure of presynthesized Cu nanodendrites at the atomic level. A combination of physicochemical characterization and electrochemical study demonstrates that such a treatment could induce surface Cu atom rearrangement and result in increased electrochemically active surface area and high density of surface-active sites, disclosing a high electrocatalytic nitrate-to-ammonia capability, with an optimal NH3 yield rate of 0.2238 mmol h-1 cm-2 and a corresponding Faradaic efficiency of 94.43%. This study may provide a guiding design avenue for atomic arrangement engineering of metallic nanocrystals via electrochemical postmodification for nitrate reduction reaction and other energy conversion electrocatalysis.