Discriminating active sites for the electrochemical synthesis of H2O2 by molecular functionalisation of carbon nanotubes.

The electrochemical production of H2O2via the two-electron oxygen reduction reaction (2e- ORR) has recently attracted attention as a promising alternative to the current anthraquinone process. Identification of active sites in O-doped carbon materials, which exhibit high activities and selectivities for the 2e- ORR, is important for understanding the selective electrocatalytic process and achieving the rational design of active electrocatalysts. However, this is impeded by the heterogeneous distribution of various active sites on these catalysts. In this study, we exploited the molecular functionalisation approach to implant anthraquinone, benzoic acid, and phenol groups on carbon nanotubes and systematically compared the electrocatalytic activities and selectivities of these functional groups. Among these oxygen functional groups, the anthraquinone group showed the highest surface-area-normalised and active-site-normalised activities.

Synthesis of Sulfonated Poly(Arylene Ether Sulfone)s Containing Aliphatic Moieties for Effective Membrane Electrode Assembly Fabrication by Low-Temperature Decal Transfer Methods.

The purpose of this study was to investigate the effect of the aliphatic moiety in the sulfonated poly(arylene ether sulfone) (SPAES) backbone. A new monomer (4,4'-dihydroxy-1,6-diphenoxyhexane) was synthesized and polymerized with other monomers to obtain partially alkylated SPAESs. According to differential scanning calorimetry analysis, the glass transition temperature (Tg) of these polymers ranged from 85 to 90 °C, which is 100 °C lower than that of the fully aromatic SPAES. Due to the low Tg values obtained for the partially alkylated SPAESs, it was possible to prepare a hydrocarbon electrolyte membrane-based membrane electrode assembly (MEA) with Nafion® binder in the electrode through the use of a decal transfer method, which is the most commercially suitable system to obtain an MEA of proton exchange membrane fuel cells (PEMFCs). A single cell prepared using this partially alkylated SPAES as an electrolyte membrane exhibited a peak power density of 539 mW cm-2.

Overview of global status and challenges for end-of-life crystalline silicon photovoltaic panels: A focus on environmental impacts.

Recent developments in photovoltaic (PV) technology have enabled a reduction of fossil fuel usage and subsequent carbon dioxide (CO2) release from energy production. However, end-of-life (EoL) crystalline silicon (c-Si) PV panels have become an emerging waste issue. This overview attempts to update and forecast the global status of renewable energy capacity and c-Si PV waste generation under different scenarios and to present a summary of the recent literature on recycling technologies and life cycle assessment (LCA) of EoL c-Si PV panels with a focus on reclaimable resources. For most LCA studies in the 1980s and the 2000s, the EoL phase of PV systems has often neglected or oversimplified (e.g., disposal after low-rate recovery) the fact that various recycling procedures and reclaimable resources from each stage cannot be appropriately considered. A limited number of studies have been available since the 2010s that highlight the high-rate recovery from EoL PV panels. However, the differences in functional unit, system boundary and impact analysis methodology make it difficult to compare the results directly, and spatio-temporal uncertainties are yet to be thoroughly quantified due to the lack of workable localized data. More efforts are needed to identify complementary environmental impacts (i.e., burden and credit) from the individual recycling processes. Correspondingly impacts from transport need to be fully incorporated for the optimization of the recycling process which has been neglected in most of the previous studies.

Polystyrene-Based Hydroxide-Ion-Conducting Ionomer: Binder Characteristics and Performance in Anion-Exchange Membrane Fuel Cells.

Polystyrene-based polymers with variable molecular weights are prepared by radical polymerization of styrene. Polystyrene is grafted with bromo-alkyl chains of different lengths through Friedel-Crafts acylation and quaternized to afford a series of hydroxide-ion-conducting ionomers for the catalyst binder for the membrane electrode assembly in anion-exchange membrane fuel cells (AEMFCs). Structural analyses reveal that the molecular weight of the polystyrene backbone ranges from 10,000 to 63,000 g mol-1, while the ion exchange capacity of quaternary-ammonium-group-bearing ionomers ranges from 1.44 to 1.74 mmol g-1. The performance of AEMFCs constructed using the prepared electrode ionomers is affected by several ionomer properties, and a maximal power density of 407 mW cm-2 and a durability exceeding that of a reference cell with a commercially available ionomer are achieved under optimal conditions. Thus, the developed approach is concluded to be well suited for the fabrication of next-generation electrode ionomers for high-performance AEMFCs.

Comparative analysis of I2-KI and HNO3 leaching in a life cycle perspective: Towards sustainable recycling of end-of-life c-Si PV panel.

An iodine-iodide system was investigated as an alternative lixiviant for HNO3 for leaching precious metals from the end-of-life c-Si photovoltaic (PV) cell. A series of batch experiments were conducted for the optimization of leaching kinetics and thermodynamic equilibrium followed by a life cycle assessment (LCA) using data from the experiments. The results showed that more than 95% of Ag and Al leached out within the first 5 min. The optimum conditions for equilibrium leaching were as follows: solid to liquid ratio of 1:10 for Ag (1:9 ml for Al), and I2 concentration of 0.35 M for Ag (0.3 M for Al), with I- concentration of 0.7 M. In addition, selective leaching of Ag could also be accomplished by adjusting the reaction pH to 9.6%, and 93% of reproducibility was achieved via the rejuvenation of the exhausted leaching solution, which can benefit the subsequent recovery process. The leaching efficiency of iodine-iodide system was nearly comparable to that of HNO3, and the environmental impacts of the two cycle of continuous process with rejuvenation of the iodine leaching solution can be effectively reduced especially in the acidification & eutrophication, respiratory effect, and mineral extraction categories with subsequent exclusion of the additional neutralization process.

Cilostazol restores autophagy flux in bafilomycin A1-treated, cultured cortical astrocytes through lysosomal reacidification: roles of PKA, zinc and metallothionein 3.

Cilostazol, a phosphodiesterase 3 inhibitor, reduces the amyloid-beta (Aß) burden in mouse models of Alzheimer disease by as yet unidentified mechanisms. In the present study, we examined the possibility that cilostazol ameliorates lysosomal dysfunction. Astrocytes treated with bafilomycin A1 (BafA1) exhibited markedly reduced DND-189 and acridine orange (AO) fluorescence, indicating reduced lysosomal acidity. In both cases, BafA1-induced alkalization was reversed by addition of cilostazol, dibutyryl cAMP or forskolin. All three agents significantly increased free zinc levels in lysosomes, and addition of the zinc chelator TPEN abrogated lysosomal reacidification. These treatments did not raise free zinc levels or reverse BafA1-mediated lysosomal alkalization in metallothionein 3 (Mt3)-null astrocytes, indicating that the increases in zinc in astrocytes were derived mainly from Mt3. Lastly, in FITC-Aß-treated astrocytes, cilostazol reversed lysosomal alkalization, increased cathepsin D activity, and reduced Aß accumulation in astrocytes. Cilostazol also reduced mHtt aggregate formation in GFP-mHttQ74-expressing astrocytes. Collectively, our results present the novel finding that cAMP/PKA can overcome the v-ATPase blocking effect of BafA1 in a zinc- and Mt3-dependent manner.

Vasa Vasorum Densities in Human Carotid Atherosclerosis Is Associated with Plaque Development and Vulnerability.

OBJECTIVE: The extensive vasa vasorum network functions as a conduit for the entry of inflammatory cells or factors that promote the progression of angiogenesis and plaque formation. Therefore, we investigated the correlation between the carotid vasa vasorum activities and carotid plaque vulnerability using indocyanine green video angiography (ICG-VA) during carotid endarterectomy (CEA). METHODS: Sixty-nine patients who underwent CEA were enrolled prospectively from September 2015 to December 2017. During CEA, a bolus of ICG was injected intravenously before and after resecting the atheroma. Additionally, we performed immunohistochemistry using CD68 (a surface marker of macrophages), CD117 (a surface marker of mast cells), and CD4 and CD8 (surface markers of T-cells) antibodies to analyze the resected plaque specimens. RESULTS: The density of active vasa vasorum was observed in all patients using ICG-VA. The vasa vasorum externa (VVE) and interna (VVI) were seen in 11 (16%) and 57 patients (82.6%), respectively. Macroscopically, the VVE-type patterns were strongly associated with preoperative angiographic instability (81.8%, p=0.005) and carotid plaque vulnerability (90.9%, p=0.017). In contrast, the VVI-type patterns were weakly associated with angiographic instability (31.6%) and plaque vulnerability (49.1%). CD68-stained macrophages and CD117-stained mast cells were observed more frequently in unstable plaques than in stable plaques (p<0.0001, p=0.002, respectively). CONCLUSION: The early appearance of VVE, along with the presence of many microvessel channels that provided nutrients to the developing and expanding atheroma during ICG-VA, was strongly associated with unstable carotid plaques. The degree of infiltration of macrophages and mast cells is possibly related to the formation of unstable plaques.

General technoeconomic analysis for electrochemical coproduction coupling carbon dioxide reduction with organic oxidation.

Electrochemical processes coupling carbon dioxide reduction reactions with organic oxidation reactions are promising techniques for producing clean chemicals and utilizing renewable energy. However, assessments of the economics of the coupling technology remain questionable due to diverse product combinations and significant process design variability. Here, we report a technoeconomic analysis of electrochemical carbon dioxide reduction reaction-organic oxidation reaction coproduction via conceptual process design and thereby propose potential economic combinations. We first develop a fully automated process synthesis framework to guide process simulations, which are then employed to predict the levelized costs of chemicals. We then identify the global sensitivity of current density, Faraday efficiency, and overpotential across 295 electrochemical coproduction processes to both understand and predict the levelized costs of chemicals at various technology levels. The analysis highlights the promise that coupling the carbon dioxide reduction reaction with the value-added organic oxidation reaction can secure significant economic feasibility.

Identifying New AMP-Activated Protein Kinase Inhibitors That Protect against Ischemic Brain Injury.

We recently reported that AMP-activated protein kinase (AMPK) contributes to zinc-induced neuronal death by inducing Bim, a pro-apoptotic Bcl-2 homology domain 3-only protein, in a liver kinase B1 (LKB1)-dependent manner. Current data suggest AMPK plays key roles in excitotoxicity and ischemic brain injury, with zinc neurotoxicity representing at least one mechanism of ischemic neuronal death. Inhibition of AMPK could be a viable therapeutic strategy to prevent ischemic brain injury following stroke. This prompted our search for novel inhibitors of AMPK activity and zinc-induced neuronal death using cultured mouse cortex and a rat model of brain injury after middle cerebral artery occlusion (MCAO). In structure-based virtual screening, 118 compounds were predicted to bind the active site of AMPK α2, and 40 showed in vitro AMPK α2 inhibitory activity comparable to compound C (a well-known, potent AMPK inhibitor). In mouse cortical neuronal cultures, 7 of 40 compound reduced zinc-induced neuronal death at levels comparable to compound C. Ultimately, only agents 2G11 and 1H10 significantly attenuated various types of neuronal death, including oxidative stress, excitotoxicity, and apoptosis. When administered as intracerebroventricular injections prior to permanent MCAO in rats, 2G11 and 1H10 reduced brain infarct volumes, whereas compound C did not. Therefore, these novel AMPK inhibitors could be drug development candidates to treat stroke.

Practical Design Considerations for Compact Array-Fed Huygens' Dielectric Lens Antennas.

This paper presents a practical design consideration for the dielectric lens based on Huygens' principle (HP) at a short distance (=λ0/2) from a feed antenna to overcome the limitation of the conventional design method. It is suggested that certain ranges of dielectric thickness values are not considered to exclude undesired resonant effects that hamper the effectiveness of Huygens' lens which relies on phase shifting elements. In the proposed HP-based design method, phase distributions are captured at the target distance away from the feed array for the two cases of 2 × 2 and 1 × 4 array antennas and based on these, the proposed lens topology is designed to compensate the phase distributions for gain enhancement. A case study shows that the proposed HP-based design approach considering the actual phase information and undesired dielectric resonant phenomenology can achieve a gain enhancement of up to 5.34 dB compared to the conventional dielectric lens, depending on the feed array arrangement that can render circular or elliptic shapes of phase distributions for radiated fields.

Contribution of Zinc-Dependent Delayed Calcium Influx via TRPC5 in Oxidative Neuronal Death and its Prevention by Novel TRPC Antagonist.

Oxidative stress is a key mediator of neuronal death in acute brain injuries, such as epilepsy, trauma, and stroke. Although it is accompanied by diverse cellular changes, increases in levels of intracellular zinc ion (Zn2+) and calcium ion (Ca2+) may play a critical causative role in oxidative neuronal death. However, the mechanistic link between Zn2+ and Ca2+ dyshomeostasis in neurons during oxidative stress is not well-understood. Here, we show that the exposure of cortical neurons to H2O2 led to a zinc-triggered calcium influx, which resulted in neuronal death. The cyclin-dependent kinase inhibitor, NU6027, inhibited H2O2-induced Ca2+ increases and subsequent cell death in cortical neurons, without affecting the early increase in Zn2+. Therefore, we attempted to identify the zinc-regulated Ca2+ pathway that was inhibited by NU6027. The expression profile in cortical neurons identified transient receptor potential cation channel 5 (TRPC5) as a candidate that is known to involve in the generation of epileptiform burst firing and epileptic neuronal death (Phelan KD et al. 2012a; Phelan KD et al. 2013b). NU6027 inhibited basal and zinc-augmented TRPC5 currents in TRPC5-overexpressing HEK293 cells. Consistently, cortical neurons from TRPC5 knockout mice were highly resistant to H2O2-induced death. Moreover, NU6027 is neuroprotective in kainate-treated epileptic rats. Our results demonstrate that TRPC5 is a novel therapeutic target against oxidative neuronal injury in prolonged seizures and that NU6027 is a potent inhibitor of TRPC5.

Correction to: Contribution of Zinc-Dependent Delayed Calcium Influx via TRPC5 in Oxidative Neuronal Death and its Prevention by Novel TRPC Antagonist.

After the publication of this work errors were noticed in Fig. 3b and 4d.

Potential Role of Zinc Dyshomeostasis in Matrix Metalloproteinase-2 and -9 Activation and Photoreceptor Cell Death in Experimental Retinal Detachment.

Purpose: We investigated whether zinc dyshomeostasis, a known mechanism of cell death in acute brain injury, contributes to the activation of matrix metalloproteinases (MMPs) and photoreceptor cell death in experimental retinal detachment (RD). Methods: RD was induced in mice by subretinal injection of 1:1 mixture of balanced salt solution and 1% sodium hyaluronate. On days 1 and 3 post RD, eyeballs were sectioned and examined for cell death (TUNEL staining), the degree of hypoxic insult (Hypoxyprobe staining), free zinc levels (TFL-Zn staining), and MMP-2 and -9 activity (gelatin zymography). In addition, we examined whether modulating extracellular zinc concentration or MMP activation in subretinal fluid affected photoreceptor cell death in RD. These changes were further examined in primary retinal cell and photoreceptor-derived cell (661W) cultures. Results: Photoreceptor cell death peaked on day 3 post RD. Intracellular zinc markedly decreased on day 1 post RD, and subsequently accumulated on day 3. MMP-2 and -9 activity showed a concurrent increase in detached retinas. Detached retinas stained with Hypoxyprobe showed strongly positive cells, especially in the photoreceptor layer. Subretinal injection of a zinc-chelator (CaEDTA) or MMP inhibitor (GM6001, minocycline) at the time of RD significantly attenuated photoreceptor cell death in RD. Similar findings were confirmed in oxygen-glucose-deprived or zinc-exposed cell cultures. Conclusions: Upon RD, hypoxic retinal cells in deep layers underwent zinc dyshomeostasis, MMP activation, and ultimately death. These findings provide new insight into the possible mechanism of photoreceptor death in RD, and as such may prove useful in crafting protective measures for photoreceptor cells.

Preferential horizontal growth of tungsten sulfide on carbon and insight into active sulfur sites for the hydrogen evolution reaction.

Transition metal dichalcogenides (TMDs) have attracted considerable attention as active electrocatalysts for the hydrogen evolution reaction (HER). Since TMD catalysts are commonly supported on carbon to endow electrical conductivity, understanding the growth behaviour of TMDs on carbon surfaces is crucial, and yet remains to be explored. In this work, we investigated the growth behaviour of tungsten sulfide (WSx) on carbon surfaces inside the confined nanopores. Experimental and computational studies revealed the preferential bonding between the basal planes of WSx and carbon surfaces, as well as the subsequent horizontal growth of WSx. As a result, subnanometer WSx clusters were formed at a low WSx loading, and grew into monolayer WS2 nanoplates with increased WSx loadings. In contrast, a TMD analogue, MoS2, favors edge plane bonding with carbon surfaces and subsequent stacking of nanoplate layers, leading to multilayer MoS2 nanoplates with increased MoS2 loadings. A time-dependent growth of WSx further corroborated the formation of WS2 nanoplates at the expense of ultrasmall WSx nanoclusters. Interestingly, the sample prepared with a short sulfidation time, which was mainly comprised of WSx nanoclusters, showed higher HER activity compared to the sample prepared with a prolonged sulfidation time, which mostly contained WS2 nanoplates. The higher HER activity of WSx nanoclusters is attributed to the larger density of active bridging S22- sites, compared to the WS2 nanoplates. These findings may provide important insights into the growth behaviour of layered TMD materials at the nanoscale, as well as potential active species in WSx for the HER.

Recent advances in unveiling active sites in molybdenum sulfide-based electrocatalysts for the hydrogen evolution reaction.

Hydrogen has received significant attention as a promising future energy carrier due to its high energy density and environmentally friendly nature. In particular, the electrocatalytic generation of hydrogen fuel is highly desirable to replace current fossil fuel-dependent hydrogen production methods. However, to achieve widespread implementation of electrocatalytic hydrogen production technology, the development of highly active and durable electrocatalysts based on Earth-abundant elements is of prime importance. In this context, nanostructured molybdenum sulfides (MoS x ) have received a great deal of attention as promising alternatives to precious metal-based catalysts. In this focus review, we summarize recent efforts towards identification of the active sites in MoS x -based electrocatalysts for the hydrogen evolution reaction (HER). We also discuss recent synthetic strategies for the engineering of catalyst structures to achieve high active site densities. Finally, we suggest ongoing and future research challenges in the design of advanced MoS x -based HER electrocatalysts.

Cactus-Like Hollow Cu2-x S@Ru Nanoplates as Excellent and Robust Electrocatalysts for the Alkaline Hydrogen Evolution Reaction.

The development of Pt-free electrocatalysts for the hydrogen evolution reaction (HER) recently is a focus of great interest. While several strategies are developed to control the structural properties of non-Pt catalysts and boost their electrocatalytic activities for the HER, the generation of highly reactive defects or interfaces by combining a metal with other metals, or with metal oxides/sulfides, can lead to notably enhanced catalytic performance. Herein, the preparation of cactus-like hollow Cu2-x S@Ru nanoplates (NPs) that contain metal/metal sulfide heterojunctions and show excellent catalytic activity and durability for the HER in alkaline media is reported. The initial formation of Ru islands on presynthesized Cu1.94 S NPs, via cation exchange between three Cu+ ions and one Ru3+ , induces the growth of the Ru phase, which is concomitant with the dissolution of the Cu1.94 S nanotemplate, culminating in the formation of a hollow nanostructure with numerous thin Ru pillars. Hollow Cu2-x S@Ru NPs exhibit a small overpotential of 82 mV at a current density of -10 mA cm-2 and a low Tafel slope of 48 mV dec-1 under alkaline conditions; this catalyst is among state-of-the-art HER electrocatalysts in alkaline media. The excellent performance of hollow Cu2-x S@Ru NPs originates from the facile dissociation of water in the Volmer step.

Metallothionein-3 modulates the amyloid ß endocytosis of astrocytes through its effects on actin polymerization.

BACKGROUND: Astrocytes may play important roles in the pathogenesis of Alzheimer's disease (AD) by clearing extracellular amyloid beta (Aß) through endocytosis and degradation. We recently showed that metallothionein 3 (Mt3), a zinc-binding metallothionein that is enriched in the central nervous system, contributes to actin polymerization in astrocytes. Because actin is likely involved in the endocytosis of Aß, we investigated the possible role of Mt3 in Aß endocytosis by cortical astrocytes in this study. RESULTS: To assess the route of Aß uptake, we exposed cultured astrocytes to fluorescently labeled Aß1-40 or Aß1-42 together with chloropromazine (CP) or methyl-beta-cyclodextrin (MßCD), inhibitors of clathrin- and caveolin-dependent endocytosis, respectively. CP treatment almost completely blocked Aß1-40 and Aß1-42 endocytosis, whereas exposure to MßCD had no significant effect. Actin disruption with cytochalasin D (CytD) or latrunculin B also completely blocked Aß1-40 and Aß1-42 endocytosis. Because the absence of Mt3 also results in actin disruption, we examined Aß1-40 and Aß1-42 uptake and expression in Mt3 (-/-) astrocytes. Compared with wild-type (WT) cells, Mt3 (-/-) cells exhibited markedly reduced Aß1-40 and Aß1-42 endocytosis and expression of Aß1-42 monomers and oligomers. A similar reduction was observed in CytD-treated WT cells. Finally, actin disruption and Mt3 knockout each increased the overall levels of clathrin and the associated protein phosphatidylinositol-binding clathrin assembly protein (PICALM) in astrocytes. CONCLUSIONS: Our results suggest that the absence of Mt3 reduces Aß uptake in astrocytes through an abnormality in actin polymerization. In light of evidence that Mt3 is downregulated in AD, our findings indicate that this mechanism may contribute to the extracellular accumulation of Aß in this disease.

The zinc ionophore clioquinol reverses autophagy arrest in chloroquine-treated ARPE-19 cells and in APP/mutant presenilin-1-transfected Chinese hamster ovary cells.

Arrested autophagy may contribute to the pathogenesis of Alzheimer's disease. Because we found that chloroquine (CQ) causes arrested autophagy but clioquinol (ClioQ), a zinc ionophore, activates autophagic flux, in the present study, we examined whether ClioQ can overcome arrested autophagy induced by CQ or mutant presenilin-1 (mPS1). CQ induced vacuole formation and cell death in adult retinal pigment epithelial (ARPE-19) cells, but co-treatment with ClioQ attenuated CQ-associated toxicity in a zinc-dependent manner. Increases in lysosome dilation and blockage of autophagic flux by CQ were also markedly attenuated by ClioQ treatment. Interestingly, CQ increased lysosomal pH in amyloid precursor protein (APP)/mPS1-expressing Chinese hamster ovary 7WΔE9 (CHO-7WΔE9) cell line, and ClioQ partially re-acidified lysosomes. Furthermore, accumulation of amyloid-ß (Aß) oligomers in CHO-7WΔE9 cells was markedly attenuated by ClioQ. Moreover, intracellular accumulation of exogenously applied fluorescein isothiocyanate-conjugated Aß(1-42) was also increased by CQ but was returned to control levels by ClioQ. These results suggest that modulation of lysosomal functions by manipulating lysosomal zinc levels may be a useful strategy for clearing intracellular Aß oligomers.

Impact of a conductive oxide core in tungsten sulfide-based nanostructures on the hydrogen evolution reaction.

Tungsten oxide/tungsten sulfide (W18O49@WS2) core-shell nanorods prepared via a controlled sulfidization reaction of W18O49 nanowhiskers showed hydrogen evolution reaction (HER) activity superior to WS2 nanotubes, indicating the critical role of a highly conductive oxide core in enhancing HER activity.

Monolayer-precision synthesis of molybdenum sulfide nanoparticles and their nanoscale size effects in the hydrogen evolution reaction.

Metal sulfide-based nanostructured materials have emerged as promising catalysts for hydrogen evolution reaction (HER), and significant progress has been achieved in enhancing their activity and durability for the HER. The understanding of nanoscale size-dependent catalytic activities can suggest critical information regarding catalytic reactivity, providing the scientific basis for the design of advanced catalysts. However, nanoscale size effects in metal sulfide-based HER catalysts have not yet been established fully, due to the synthetic difficulty in precisely size-controlled metal sulfide nanoparticles. Here we report the preparation of molybdenum sulfide (MoS2) nanoparticles with monolayer precision from one to four layers with the nearly constant basal plane size of 5 nm, and their size-dependent catalytic activity in the HER. Using density functional theory (DFT) calculations, we identified the most favorable single-, double-, and triple-layer MoS2 model structures for the HER, and calculated elementary step energetics of the HER over these three model structures. Combining HER activity measurements and the DFT calculation results, we establish that the turnover frequency of MoS2 nanoparticles in the HER increases in a quasi-linear manner with decreased layer numbers. Cobalt-promoted MoS2 nanoparticles also exhibited similar HER activity trend. We attribute the higher HER activity of smaller metal sulfide nanoparticles to the higher degree of oxidation, higher Mo-S coordination number, formation of the 1T phase, and lower activation energy required to overcome transition state. This insight into the nanoscale size-dependent HER activity trend will facilitate the design of advanced HER catalysts as well as other hydrotreating catalysts.