Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator.

Objective: This study aims to address the substantive issue of lacking reliable prognostic biomarkers in hepatocellular carcinoma (HCC) by investigating the relationship between TP53-inducible glycolysis and apoptosis regulator (TIGAR) and HCC prognosis using The Cancer Genome Atlas database. Methods: (1) Integrated statistical analyses, including logistic regression, Wilcoxon signed-rank test, and Kruskal-Wallis test, were conducted to explore the association between TIGAR expression and clinical-pathological features of HCC. (2) The Kaplan-Meier method combined with univariate and multivariate Cox regression models underscored TIGAR as a prognostic factor in HCC. (3) Gene set enrichment analysis (GSEA) revealed key pathways associated with TIGAR, while single-sample gene set enrichment analysis (ssGSEA) determined its relevance to cancer immune infiltration. Results: (1) Elevated TIGAR expression was significantly correlated with decreased survival outcomes in HCC patients. (2) GSEA highlighted the significant link between TIGAR and humoral immunity. (3) ssGSEA revealed a positive correlation between TIGAR expression and infiltration of Th1 and Th2 cells and a negative correlation with Th17 cell infiltration. Conclusion: TIGAR, as a potential prognostic biomarker for HCC, holds significant value in immune infiltration. Understanding the role of TIGAR could contribute to improved prognostic predictions and personalized treatment strategies for HCC patients.

Tuning the Inter-Metal Interaction between Ni and Fe Atoms in Dual-Atom Catalysts to Boost CO2 Electroreduction.

Dual-atom catalysts (DACs) are promising for applications in electrochemical CO2 reduction due to the enhanced flexibility of the catalytic sites and the synergistic effect between dual atoms. However, precisely controlling the atomic distance and identifying the dual-atom configuration of DACs to optimize the catalytic performance remains a challenge. Here, the Ni and Fe atomic pairs were constructed on nitrogen-doped carbon support in three different configurations: NiFe-isolate, NiFe-N bridge, and NiFe bonding. It was found that the NiFe-N bridge catalyst with NiN4 and FeN4 sharing two N atoms exhibited superior CO2 reduction activity and promising stability when compared to the NiFe-isolate and NiFe-bonding catalysts. A series of characterizations and density functional theory calculations suggested that the N-bridged NiFe sites with an appropriate distance between Ni and Fe atoms can exert a more pronounced synergy. It not only regulated the suitable adsorption strength for the *COOH intermediate but also promoted the desorption of *CO, thus accelerating the CO2 electroreduction to CO. This work provides an important implication for the enhancement of catalysis by the tailoring of the coordination structure of DACs, with the identification of distance effect between neighboring dual atoms.

Yttrium doping stabilizes the structure of Ni3(NO3)2(OH)4 cathodes for application in advanced Ni-Zn batteries.

Ni3(NO3)2(OH)4 has a high theoretical specific capacitance, low cost, and environmental friendliness, making it a promising electrode material. Specifically, Ni3(NO3)2(OH)4 electrodes have a larger layer spacing (c = 6.898 Å) than Ni(OH)2 electrodes since NO3- has a much larger ionic radius than OH-. The larger layer spacing stores more electrolyte ions, significantly improving the electrochemical activity of the electrodes. Additionally, the interlayer NO3- can enhance the structural stability of Ni3(NO3)2(OH)4. However, since Ni3(NO3)2(OH)4 has a higher molar mass than Ni(OH)2, it has a lower theoretical specific capacity. Consequently, Ni3(NO3)2(OH)4 has not been used in zinc-based alkaline batteries. Studies showed that doping could enhance the electrochemical performance of electrode materials. Therefore, this study used a simple solvothermal reaction to synthesize yttrium-doped Ni3(NO3)2(OH)4 (Y-Ni3(NO3)2(OH)4), assembling a Y-Ni3(NO3)2(OH)4//Zn battery for electrochemical testing. Y-Ni3(NO3)2(OH)4 served as the cathode in the battery. The analysis of Y-Ni3(NO3)2(OH)4 showed that yttrium (Y) doping increased the specific surface area and pore size of Ni3(NO3)2(OH)4 significantly. The increased specific surface area improved the active material utilization, and the abundant mesopores facilitated OH- transport, substantially enhancing the battery's specific capacity and energy density. Ultimately, the specific discharge capacity of the advanced Y-Ni3(NO3)2(OH)4//Zn battery reached 177.97 mA h g-1 at a current density of 4 A g-1, nearly doubling the capacity of the earlier Ni3(NO3)2(OH)4//Zn battery (103.59 mA h g-1).

Coordination and Hydrogen Bond Chemistry in Tungsten Oxide@Polyaniline Composite toward High-Capacity Aqueous Ammonium Storage.

Aqueous ammonium ion batteries (AAIBs) have garnered significant attention due to their unique energy storage mechanism. However, their progress is hindered by the relatively low capacities of NH4 + host materials. Herein, the study proposes an electrodeposited tungsten oxide@polyaniline (WOx@PANI) composite electrode as a NH4 + host, which achieves an ultrahigh capacity of 280.3 mAh g-1 at 1 A g-1, surpassing the vast majority of previously reported NH4 + host materials. The synergistic interaction of coordination chemistry and hydrogen bond chemistry between the WOx and PANI enhances the charge storage capacity. Experimental results indicate that the strong interfacial coordination bonding (N: →W6+) effectively modulates the chemical environment of W atoms, enhances the protonation level of PANI, and thus consequently the conductivity and stability of the composites. Spectroscopy analysis further reveals a unique NH4 +/H+ co-insertion mechanism, in which the interfacial hydrogen bond network (N-H···O) accelerates proton involvement in the energy storage process and activates the Grotthuss hopping conduction of H+ between the hydrated tungsten oxide layers. This work opens a new avenue to achieving high-capacity NH4 + storage through interfacial chemistry interactions, overcoming the capacity limitations of NH4 + host materials for aqueous energy storage.

Hydrogen bonding chemistry in aqueous ammonium ion batteries.

Aqueous ammonium ion batteries (AIBs) pose the advantages of high safety, low cost, and high efficiency, capturing substantial research interest. The intrinsic chemical properties of NH4+ promote the formation of hydrogen bonds with other constituents in AIBs, critically influencing the processes of NH4+ transfer, storage, and diffusion. This review delves into the pivotal role of hydrogen bonding chemistry in AIBs. Firstly, the principles of hydrogen bond are elucidated as the dominant chemical interaction governing NH4+ dynamics in AIBs. Subsequently, a detailed analysis is conducted on the impacts of hydrogen bonds in both electrolytes and electrode materials. Furthermore, the practical applications of hydrogen bonding chemistry within the context of AIBs are assessed. Finally, strategic insights and future research directions are proposed to harness hydrogen bonding effects for optimizing AIB performance. This review aims to define the mechanisms and impacts of hydrogen bonds in AIBs, providing robust strategies to enhance electrochemical performance, deepen the understanding of energy storage mechanisms, and guide the future advancement of AIBs technology.

Mg ions intercalated with V3O7·H2O to construct ultrastable cathode materials for aqueous zinc-ion batteries.

V3O7·H2O (VO) stands out as a highly promising cathode material for aqueous zinc-ion batteries (AZIB). However, due to the instability of the VO structure and the limited ion transport rate, achieving the required specific capacity and extended cycling lifespan has been challenging. To tackle this issue, we synthesized Mg-ion intercalated VO (MgVO) using a straightforward hydrothermal method. Introducing Mg2+ as an interlayer support enhanced the flexibility of MgVO within the confined layer space, stabilized its lamellar structure, and expanded the VO layer spacing. The AZIB employing the MgVO cathode demonstrated a high specific capacity of 382.7 mA h g-1 at a current density of 0.1 A g-1 and showed excellent cycling stability. The robust structural stability of MgVO suggests promising applications for large-scale energy storage, while the Mg2+ intercalation strategy presents a novel approach for exploring other potential cathode materials.

Promoting Photon-to-Chemical Conversion through a Dielectric Antenna-Hybrid Bilayered Reactor Configuration.

The application of scattered light via an antenna-reactor configuration is promising for converting thermocatalysts into photocatalysts. However, the efficiency of dielectric antennas in photon-to-chemical conversion remains suboptimal. Herein, we present an effective approach to promote light utilization efficiency by designing dielectric antenna-hybrid bilayered reactors. Experimental studies and finite-difference time-domain simulations demonstrate that the engineered SiO2-carbon/metal dielectric antenna-hybrid bilayered reactors exhibit a synergy of absorption superposition and electric field confinement between carbon and metals, leading to the improved absorption of scattered light, upgraded charge carriers density, and ultimately promoted photoactivity in hydrogenating chlorobenzene with an average benzene formation rate of 18 258 µmol g-1 h-1, outperforming the reported results. Notably, the carbon interlayer proves to be more effective than the commonly explored dielectric TiO2 interlayer in boosting the benzene formation rate by over 3 times. This research paves the way for promoting near-field scattered photon-to-chemical conversion through a dielectric antenna-hybrid reactor configuration.

The Function and Mechanism of Long Noncoding RNAs in Adipogenic Differentiation.

Adipocytes are crucial for maintaining energy balance. Adipocyte differentiation involves distinct stages, including the orientation stage, clone amplification stage, clone amplification termination stage, and terminal differentiation stage. Understanding the regulatory mechanisms governing adipogenic differentiation is essential for comprehending the physiological processes and identifying potential biomarkers and therapeutic targets for metabolic diseases, ultimately improving glucose and fat metabolism. Adipogenic differentiation is influenced not only by key factors such as hormones, the peroxisome proliferator-activated receptor (PPAR) family, and the CCATT enhancer-binding protein (C/EBP) family but also by noncoding RNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA). Among these, lncRNA has been identified as a significant regulator in adipogenic differentiation. Research has demonstrated various ways in which lncRNAs contribute to the molecular mechanisms of adipogenic differentiation. Throughout the adipogenesis process, lncRNAs modulate adipocyte differentiation and development by influencing relevant signaling pathways and transcription factors. This review provides a brief overview of the function and mechanism of lncRNAs in adipogenic differentiation.

Lipoprotein (a)-Related Inflammatory Imbalance: A Novel Horizon for the Development of Atherosclerosis.

PURPOSE OF REVIEW: The primary objective of this review is to explore the pathophysiological roles and clinical implications of lipoprotein(a) [Lp(a)] in the context of atherosclerotic cardiovascular disease (ASCVD). We seek to understand how Lp(a) contributes to inflammation and arteriosclerosis, aiming to provide new insights into the mechanisms of ASCVD progression. RECENT FINDINGS: Recent research highlights Lp(a) as an independent risk factor for ASCVD. Studies show that Lp(a) not only promotes the inflammatory processes but also interacts with various cellular components, leading to endothelial dysfunction and smooth muscle cell proliferation. The dual role of Lp(a) in both instigating and, under certain conditions, mitigating inflammation is particularly noteworthy. This review finds that Lp(a) plays a complex role in the development of ASCVD through its involvement in inflammatory pathways. The interplay between Lp(a) levels and inflammatory responses highlights its potential as a target for therapeutic intervention. These insights could pave the way for novel approaches in managing and preventing ASCVD, urging further investigation into Lp(a) as a therapeutic target.

Atomic Confinement Empowered CoZn Dual-Single-Atom Nanotubes for H2O2 Production in Sequential Dual-Cathode Electro-Fenton Process.

Single-atom catalysts (SACs) are flourishing in various fields because of their 100% atomic utilization. However, their uncontrollable selectivity, poor stability and vulnerable inactivation remain critical challenges. According to theoretical predictions and experiments, a heteronuclear CoZn dual-single-atom confined in N/O-doped hollow carbon nanotube reactors (CoZnSA@CNTs) is synthesized via spatial confinement growth. CoZnSA@CNTs exhibit superior performance for H2O2 electrosynthesis over the entire pH range due to dual-confinement of atomic sites and O2 molecule. CoZnSA@CNTs is favorable for H2O2 production mainly because the synergy of adjacent atomic sites, defect-rich feature and nanotube reactor promoted O2 enrichment and enhanced H2O2 reactivity/selectivity. The H2O2 selectivity reaches ∼100% in a range of 0.2-0.65 V versus RHE and the yield achieves 7.50 M gcat -1 with CoZnSA@CNTs/carbon fiber felt, exceeding most of the reported SACs in H-type cells. The obtained H2O2 is converted directly to sodium percarbonate and sodium perborate in a safe way for H2O2 storage/transportation. The sequential dual-cathode electron-Fenton process promotes the formation of reactive oxygen species (•OH, 1O2 and •O2 -) by activating the generated H2O2, enabling accelerated degradation of various pollutants and Cr(VI) detoxification in actual wastewater. This work proposes a promising confinement strategy for catalyst design and selectivity regulation of complex reactions.

Neoadjuvant Chemotherapy Is Effective in Those Infected With SARS-CoV-2: The Real-World Experience of a Large Chinese Breast Cancer Center.

PURPOSE: During the major shift in China's policies on coronavirus disease 2019 (COVID-19), many residents will be infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over a short period, including a few patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). Moreover, it is unknown whether this comorbidity affects the efficacy of NAC for breast cancer and the patient's psychological state and quality of life (QOL). This study aims to answer these questions. METHODS: The clinical data of 2,793 patients with breast cancer who received NAC at The Affiliated Hospital of Qingdao University were retrospectively collected. The infected and non-infected groups were divided according to whether they were infected with COVID-19 during NAC. Propensity score matching was used to reduce patient selection bias. The effectiveness, psychological well-being, and QOL of the two groups were compared. RESULTS: No discernible differences were observed in the pathological complete response rates (p = 0.307) and major histological responses rate (p = 0.398) between the infected and non-infected groups. Following the full course of NAC, the Functional Assessment of Cancer Treatment General (p < 0.001) and Functional Assessment of Cancer Therapy for Breast Cancer (p < 0.001) were lower in the infected group than the non-infected group, the Hospital Anxiety and Depression Scale (HADS) anxiety scale (p < 0.001) and HADS depression scale (p < 0.001) were considerably higher in the infected group than the non-infected group. CONCLUSION: With timely treatment and effective medical management, SARS-CoV-2 does not appear to affect the efficacy of NAC; however, it can significantly affect the QOL of patients and increase their psychological distress. Therefore, in addition to a timely assessment of the efficacy of NAC, it is necessary to dynamically understand the patient's psychological state and QOL.

BMSC derived EVs inhibit colorectal Cancer progression by transporting MAGI2-AS3 or something similar.

In this study, we investigated the molecular mechanisms underlying the impact of extracellular vesicles (EVs) derived from bone marrow stromal cells (BMSCs) on colorectal cancer (CRC) development. The focus was on the role of MAGI2-AS3, delivered by BMSC-EVs, in regulating USP6NL DNA methylation-mediated MYC protein translation modification to promote CDK2 downregulation. Utilizing bioinformatics analysis, we identified significant enrichment of MAGI2-AS3 related to copper-induced cell death in CRC. In vitro experiments demonstrated the downregulation of MAGI2-AS3 in CRC cells, and BMSC-EVs were found to deliver MAGI2-AS3 to inhibit CRC cell proliferation, migration, and invasion. Further exploration revealed that MAGI2-AS3 suppressed MYC protein translation modification by regulating USP6NL DNA methylation, leading to CDK2 downregulation and prevention of colorectal cancer. Overexpression of MYC reversed the functional effects of BMSC-EVs-MAGI2-AS3. In vivo experiments validated the inhibitory impact of BMSC-EVs-MAGI2-AS3 on CRC tumorigenicity by promoting CDK2 downregulation through USP6NL DNA methylation-mediated MYC protein translation modification. Overall, BMSC-EVs-MAGI2-AS3 may serve as a potential intervention to prevent CRC occurrence by modulating key molecular pathways.

Potential of FGF21 in type 2 diabetes mellitus treatment based on untargeted metabolomics.

Fibroblast growth factor 21 (FGF21) has promise for treating diabetes and its associated comorbidities. It has been found to reduce blood glucose in mice and humans; however, its underlying mechanism is not known. Here, the metabolic function of FGF21 in diabetes was investigated. Diabetic db/db mice received intraperitoneal injections of FGF21 for 28 days, the serum of each mouse was collected, and their metabolites were analyzed by untargeted metabolomics using UHPLC-MS/MS. It was found that FGF21 reduced blood glucose and oral glucose tolerance without causing hypoglycemia. Moreover, administration of FGF21 reduced the levels of TG and LDL levels while increasing those of HDL and adiponectin. Importantly, the levels of 45 metabolites, including amino acids and lipids, were significantly altered, suggesting their potential as biomarkers. We speculated that FGF21 may treat T2DM through the regulation of fatty acid biosynthesis, the TCA cycle, and vitamin digestion and absorption. These findings provide insight into the mechanism of FGF21 in diabetes and suggest its potential for treating diabetes.

High-Entropy Prussian Blue Analogues Enable Lattice Respiration for Ultrastable Aqueous Aluminum-Ion Batteries.

Aqueous aluminum ion batteries (AAIBs) hold significant potential for grid-scale energy storage owing to their intrinsic safety, high theoretical capacity, and abundance of aluminum. However, the strong electrostatic interactions and delayed charge compensation between high-charge-density aluminum ions and the fixed lattice in conventional cathodes impede the development of high-performance AAIBs. To address this issue, this work introduces, for the first time, high-entropy Prussian blue analogs (HEPBAs) as cathodes in AAIBs with unique lattice tolerance and efficient multipath electron transfer. Benefiting from the intrinsic long-range disorder and robust lattice strain field, HEPBAs enable the manifestation of the lattice respiration effect and minimize lattice volume changes, thereby achieving one of the best long-term stabilities (91.2% capacity retention after 10 000 cycles at 5.0 A g-1) in AAIBs. Additionally, the interaction between the diverse metal atoms generates a broadened d-band and reduced degeneracy compared with conventional Prussian blue and its analogs (PBAs), which enhances the electron transfer efficiency with one of the best rate performance (79.2 mAh g-1 at 5.0 A g-1) in AAIBs. Furthermore, exceptional element selectivity in HEPBAs with unique cocktail effect can facile tune electrochemical behavior. Overall, the newly developed HEPBAs with a high-entropy effect exhibit promising solutions for advancing AAIBs and multivalent-ion batteries.

Long-term expandable mouse and human-induced nephron progenitor cells enable kidney organoid maturation and modeling of plasticity and disease.

Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here, manipulation of p38 and YAP activity allowed for long-term clonal expansion of primary mouse and human NPCs and induced NPCs (iNPCs) from human pluripotent stem cells (hPSCs). Molecular analyses demonstrated that cultured iNPCs closely resemble primary human NPCs. iNPCs generated nephron organoids with minimal off-target cell types and enhanced maturation of podocytes relative to published human kidney organoid protocols. Surprisingly, the NPC culture medium uncovered plasticity in human podocyte programs, enabling podocyte reprogramming to an NPC-like state. Scalability and ease of genome editing facilitated genome-wide CRISPR screening in NPC culture, uncovering genes associated with kidney development and disease. Further, NPC-directed modeling of autosomal-dominant polycystic kidney disease (ADPKD) identified a small-molecule inhibitor of cystogenesis. These findings highlight a broad application for the reported iNPC platform in the study of kidney development, disease, plasticity, and regeneration.

High-valent metal-oxo species transformation and regulation by co-existing chloride: Reaction pathways and impacts on the generation of chlorinated by-products.

High-valent metal-oxo species (HMOS) have been extensively recognized in advanced oxidation processes (AOPs) owing to their high selectivity and high chemical utilization efficiency. However, the interactions between HMOS and halide ions in sewage wastewater are complicated, leading to ongoing debates on the intrinsic reactive species and impacts on remediation. Herein, we prepared three typical HMOS, including Fe(IV), Mn(V)-nitrilotriacetic acid complex (Mn(V)NTA) and Co(IV) through peroxymonosulfate (PMS) activation and comparatively studied their interactions with Cl- to reveal different reactive chlorine species (RCS) and the effects of HMOS types on RCS generation pathways. Our results show that the presence of Cl- alters the cleavage behavior of the peroxide OO bond in PMS and prohibits the generation of Fe(IV), spontaneously promoting SO4•- production and its subsequent transformation to secondary radicals like Cl• and Cl2•-. The generation and oxidation capacity of Mn(V)NTA was scarcely influenced by Cl-, while Cl- would substantially consume Co(IV) and promote HOCl generation through an oxygen-transfer reaction, evidenced by density functional theory (DFT) and deuterium oxide solvent exchange experiment. The two-electron-transfer standard redox potentials of Fe(IV), Mn(V)NTA and Co(IV) were calculated as 2.43, 2.55 and 2.85 V, respectively. Due to the different reactive species and pathways in the presence of Cl-, the amounts of chlorinated by-products followed the order of Co(II)/PMS > Fe(II)/PMS > Mn(II)NTA/PMS. Thus, this work renovates the knowledge of halide chemistry in HMOS-based systems and sheds light on the impact on the treatment of salinity-containing wastewater.

Mechanics limits ecological diversity and promotes heterogeneity in confined bacterial communities.

Multispecies bacterial populations often inhabit confined and densely packed environments where spatial competition determines the ecological diversity of the community. However, the role of mechanical interactions in shaping the ecology is still poorly understood. Here, we study a model system consisting of two populations of nonmotile Escherichia coli bacteria competing within open, monolayer microchannels. The competitive dynamics is observed to be biphasic: After seeding, either one strain rapidly fixates or both strains orient into spatially stratified, stable communities. We find that mechanical interactions with other cells and local spatial constraints influence the resulting community ecology in unexpected ways, severely limiting the overall diversity of the communities while simultaneously allowing for the establishment of stable, heterogeneous populations of bacteria displaying disparate growth rates. Surprisingly, the populations have a high probability of coexisting even when one strain has a significant growth advantage. A more coccus morphology is shown to provide a selective advantage, but agent-based simulations indicate this is due to hydrodynamic and adhesion effects within the microchannel and not from breaking of the nematic ordering. Our observations are qualitatively reproduced by a simple Pólya urn model, which suggests the generality of our findings for confined population dynamics and highlights the importance of early colonization conditions on the resulting diversity and ecology of bacterial communities. These results provide fundamental insights into the determinants of community diversity in dense confined ecosystems where spatial exclusion is central to competition as in organized biofilms or intestinal crypts.

Hierarchical Porous Carbon Based on Waste Quinoa Straw for High-Performance Supercapacitors.

This work presents a novel porous activated carbon electrode based on quinoa straw (QSC), which is derived from the Qinghai-Tibet Plateau. The QSC is prepared through simple precarbonization and potassium carbonate (K2CO3) activation processes and is intended for use in supercapacitors. The QSC-3 exhibits a high specific capacitance of 469.5 F g-1 at a current density of 0.5 A g-1, as well as a high specific surface area of 1802 m2 g-1. Additionally, symmetrical supercapacitors assembled using QSC-3 samples demonstrate a superior energy power density. In a 3 M KOH electrolyte, the energy density can reach 15.0 Wh kg-1 at a power density of 689.7 W kg-1. In a 1 M Na2SO4 electrolyte, the power density reaches 999.00 W kg-1, and the energy density is 39.68 Wh kg-1. Furthermore, the device shows excellent cycle life in both 3 M KOH and 1 M Na2SO4 electrolytes, with capacitance retentions of 97.55% and 96.20% after 10 000 cycles, respectively. This study provides an excellent example of utilizing waste quinoa straw to achieve low-cost, high-performance supercapacitor electrode material for sustainable electrochemical energy storage systems.

Work Function-Guided Electrocatalyst Design.

The development of high-performance electrocatalysts for energy conversion reactions is crucial for advancing global energy sustainability. The design of catalysts based on their electronic properties (e.g., work function) has gained significant attention recently. Although numerous reviews on electrocatalysis have been provided, no such reports on work function-guided electrocatalyst design are available. Herein, a comprehensive summary of the latest advancements in work function-guided electrocatalyst design for diverse electrochemical energy applications is provided. This includes the development of work function-based catalytic activity descriptors, and the design of both monolithic and heterostructural catalysts. The measurement of work function is first discussed and the applications of work function-based catalytic activity descriptors for various reactions are fully analyzed. Subsequently, the work function-regulated material-electrolyte interfacial electron transfer (IET) is employed for monolithic catalyst design, and methods for regulating the work function and optimizing the catalytic performance of catalysts are discussed. In addition, key strategies for tuning the work function-governed material-material IET in heterostructural catalyst design are examined. Finally, perspectives on work function determination, work function-based activity descriptors, and catalyst design are put forward to guide future research. This work paves the way to the work function-guided rational design of efficient electrocatalysts for sustainable energy applications.