Tethered peptide activation mechanism of the adhesion GPCRs ADGRG2 and ADGRG4.

Adhesion G protein-coupled receptors (aGPCRs) constitute an evolutionarily ancient family of receptors that often undergo autoproteolysis to produce α and ß subunits1-3. A tethered agonism mediated by the 'Stachel sequence' of the ß subunit has been proposed to have central roles in aGPCR activation4-6. Here we present three cryo-electron microscopy structures of aGPCRs coupled to the Gs heterotrimer. Two of these aGPCRs are activated by tethered Stachel sequences-the ADGRG2-ß-Gs complex and the ADGRG4-ß-Gs complex (in which ß indicates the ß subunit of the aGPCR)-and the other is the full-length ADGRG2 in complex with the exogenous ADGRG2 Stachel-sequence-derived peptide agonist IP15 (ADGRG2(FL)-IP15-Gs). The Stachel sequences of both ADGRG2-ß and ADGRG4-ß assume a U shape and insert deeply into the seven-transmembrane bundles. Constituting the FXφφφXφ motif (in which φ represents a hydrophobic residue), five residues of ADGRG2-ß or ADGRG4-ß extend like fingers to mediate binding to the seven-transmembrane domain and activation of the receptor. The structure of the ADGRG2(FL)-IP15-Gs complex reveals the structural basis for the improved binding affinity of IP15 compared with VPM-p15 and indicates that rational design of peptidic agonists could be achieved by exploiting aGPCR-ß structures. By converting the 'finger residues' to acidic residues, we develop a method to generate peptidic antagonists towards several aGPCRs. Collectively, our study provides structural and biochemical insights into the tethered activation mechanism of aGPCRs.

Structures of the glucocorticoid-bound adhesion receptor GPR97-Go complex.

Adhesion G-protein-coupled receptors (GPCRs) are a major family of GPCRs, but limited knowledge of their ligand regulation or structure is available1-3. Here we report that glucocorticoid stress hormones activate adhesion G-protein-coupled receptor G3 (ADGRG3; also known as GPR97)4-6, a prototypical adhesion GPCR. The cryo-electron microscopy structures of GPR97-Go complexes bound to the anti-inflammatory drug beclomethasone or the steroid hormone cortisol revealed that glucocorticoids bind to a pocket within the transmembrane domain. The steroidal core of glucocorticoids is packed against the 'toggle switch' residue W6.53, which senses the binding of a ligand and induces activation of the receptor. Active GPR97 uses a quaternary core and HLY motif to fasten the seven-transmembrane bundle and to mediate G protein coupling. The cytoplasmic side of GPR97 has an open cavity, where all three intracellular loops interact with the Go protein, contributing to the high basal activity of GRP97. Palmitoylation at the cytosolic tail of the Go protein was found to be essential for efficient engagement with GPR97 but is not observed in other solved GPCR complex structures. Our work provides a structural basis for ligand binding to the seven-transmembrane domain of an adhesion GPCR and subsequent G protein coupling.

Loss-free tensile ductility of dual-structure titanium composites via an interdiffusion and self-organization strategy.

The deformation-coordination ability between ductile metal and brittle dispersive ceramic particles is poor, which means that an improvement in strength will inevitably sacrifice ductility in dispersion-strengthened metallic materials. Here, we present an inspired strategy for developing dual-structure-based titanium matrix composites (TMCs) that achieve 12.0% elongation comparable to the matrix Ti6Al4V alloys and enhanced strength compared to homostructure composites. The proposed dual-structure comprises a primary structure, namely, a TiB whisker-rich region engendered fine grain Ti6Al4V matrix with a three-dimensional micropellet architecture (3D-MPA), and an overall structure consisting of evenly distributed 3D-MPA "reinforcements" and a TiBw-lean titanium matrix. The dual structure presents a spatially heterogeneous grain distribution with 5.8 µm fine grains and 42.3 µm coarse grains, which exhibits excellent hetero-deformation-induced (HDI) hardening and achieves a 5.8% ductility. Interestingly, the 3D-MPA "reinforcements" show 11.1% isotropic deformability and 66% dislocation storage, which endows the TMCs with good strength and loss-free ductility. Our enlightening method uses an interdiffusion and self-organization strategy based on powder metallurgy to enable metal matrix composites with the heterostructure of the matrix and the configuration of reinforcement to address the strength-ductility trade-off dilemma.

Research on LIBS online monitoring criteria for aircraft skin laser paint removal based on OPLS-DA.

Online monitoring technology plays a pivotal role in advancing the utilization of laser paint removal in aircraft maintenance and automation. Through the utilization of a high-frequency infrared pulse laser paint removal laser-induced breakdown spectroscopy (LIBS) online monitoring platform, this research conducted data collection encompassing 60 sets of LIBS spectra during the paint removal process. Classification and identification models were established employing principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA). These models served as the foundation for creating criteria and rules for the online LIBS monitoring of the controlled paint removal process for aircraft skin. In this research, 12 selected characteristic spectral lines were used to construct the OPLS-DA model, with a predictive root mean square error (RMSEP) of 0.2873. Both full spectrum and feature spectral line data achieved a predictive accuracy of 94.4%. The selection of feature spectral lines maintains predictive performance while significantly reducing the amount of input data. Consequently, this research offers a methodological reference for further advancements in online monitoring technology for laser paint removal in aircraft skin.

Intracardiac echocardiography-guided catheter ablation of highly symptomatic accelerated idioventricular rhythm originating from the right ventricular apical diverticulum.

Ventricular diverticula are saccule-like structures formed by the protrusion of the ventricular myocardium from the endocardial surface towards the free wall. Most diverticula are muscular structures, and patients usually have no obvious clinical symptoms. However, diverticula may contribute to arrhythmogenesis due to localized myocardial structural disturbances. Right ventricular apical diverticulum (RVAD) is very rare, and we report a case of highly symptomatic accelerated idioventricular rhythm (AIVR) originating from the RVAD that underwent intracardiac echocardiography (ICE)-guided catheter ablation with no recurrence during follow-up.

Electrolysis Synthesis of Carbides and Carbon Dioxide Capture in Molten Salts.

The application of carbides in catalysis, batteries, aerospace fields, etc. has been continuously expanded and deepened, which is attributed to the diversified physicochemical properties of carbides via a tune-up of their morphology, composition, and microstructure. The emergence of MAX phases and high entropy carbides with unparalleled application potential undoubtedly further stimulates the research upsurge of carbides. The traditional pyrometallurgical or hydrometallurgical synthesis of carbides inevitably faces the shortcomings of complex process, unacceptable energy consumption, extreme environmental pollution, and beyond. The molten salt electrolysis synthesis method with the superiorities of straightforward route, high efficiency, and environmental friendliness has demonstrated its validity in the synthesis of various carbides, which naturally initiates more research. In particular, the process can achieve CO2 capture while synthesizing carbides based on the excellent CO2 capture capability of some molten salts, which is of great significance for carbon neutralization. In this paper, the synthesis mechanism of carbide by molten salt electrolysis, the process of CO2 capture and carbides conversion, the latest research progress in the synthesis of binary, ternary, multi-component, and composite carbides are reviewed. Finally, the challenges, development perspectives, and research directions of electrolysis synthesis of carbides in molten salts are featured.

Integrating Postradiotherapy MRI-Detected Lymph Node Necrosis and Pre- and Posttreatment Epstein-Barr Virus-DNA for Risk Stratification in Nasopharyngeal Carcinoma.

BACKGROUND: Residual lymphadenopathy and detectable Epstein-Barr virus (EBV) DNA after radiotherapy (RT) are known negative prognostic factors for nasopharyngeal carcinoma (NPC). However, there is a need to distinguish between patients with residual disease that will metastasize and those who will not. PURPOSE: To develop a prognostic model to improve the risk stratification of NPC patients after RT. STUDY TYPE: Retrospective. POPULATION: Three hundred eighty-seven NPC patients treated with RT between January 2010 and January 2013. FIELD STRENGTH/SEQUENCE: T1-, T2-weighted and enhanced T1-weighted imaging at 1.5 or 3.0 T pretreatment and 3-4 months post-RT. ASSESSMENT: Post-RT central nodal necrosis (CNN) and other nodal characteristics on MRI were assessed by three radiologists independently. EBV DNA was measured by quantitative polymerase chain reaction. The association between these variables and the primary endpoint (5-year distant metastasis-free survival [DMFS], time from the day of diagnosis to any distant metastasis) was analyzed. Nomograms A (pre-/posttreatment EBV-DNA + N stage + post-RT retropharyngeal lymph node [RLN] CNN), B (tumor-node-metastasis [TNM] stage + pretreatment EBV-DNA), and C (TNM stage + post-RT EBV-DNA) were developed. STATISTICAL TESTS: Univariate and multivariate analyses were performed with the Cox regression model. Nomograms were developed based on the Cox regression model and two prognostic models. The concordance index (C-index) and calibration curve were used to evaluate the discriminative ability of the nomograms and TNM stage. P-values < 0.05 were considered statistically significant. RESULTS: Post-RT RLN CNN was an independent prognostic factor for 5-year DMFS (hazard ratio, 2.88 [1.48-5.62]). Nomogram A (C-index 0.728 [0.660-0.797]) demonstrated better risk discrimination than nomogram B (0.638 [0.571-0.705]), nomogram C (0.707 [0.636-0.778]), and the TNM stage (0.587 [0.515-0.659]) for 5-year DMFS in NPC. DATA CONCLUSION: Nomogram A combining pretreatment EBV-DNA and N stage with post-RT EBV-DNA and RLN CNN improved the prognostic risk stratification for DMFS in NPC. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Real-time LIBS monitoring of laser-based layered controlled paint removal from aircraft skin based on random forest.

Laser-induced breakdown spectroscopy (LIBS) is expected to be used for real-time monitoring and closed-loop control of laser-based layered controlled paint removal (LLCPR) from aircraft skin. However, the LIBS spectrum must be rapidly and accurately analyzed, and the monitoring criteria should be established based on machine learning algorithms. Hence, this study develops a self-built LIBS monitoring platform for the paint removal process utilizing a high-frequency (kilohertz-level) nanosecond infrared pulsed laser and collects the LIBS spectrum during the laser removal process of the top coating (TC), primer (PR), and aluminum substrate (AS). After subtracting the spectrum's continuous background and screening the key features, we construct a classification model of three types of spectra (TC, PR, and AS) based on a random forest algorithm, and the real-time monitoring criterion based on the classification model and multiple LIBS spectra was established and verified experimentally. The results show that the classification accuracy is 98.89%, the time-consuming classification is about 0.03 ms per spectrum, and the monitoring results of the paint removal process are consistent with the macroscopic observation and microscopic profile analysis results of the samples. Overall, this research provides core technical support for the real-time monitoring and closed-loop control of LLCPR from aircraft skin.

Hepatic Artery Infusion Chemotherapy Using Fluorouracil, Leucovorin, and Oxaliplatin versus Transarterial Chemoembolization as Initial Treatment for Locally Advanced Hepatocellular Carcinoma: A Propensity Score-Matching Analysis.

PURPOSE: To compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with a modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) regimen with that of transarterial chemoembolization as a locoregional treatment for patients with locally advanced hepatocellular carcinoma (HCC). METHODS: This retrospective study included adult patients with locally advanced HCC who received first-line treatment with either HAIC-mFOLFOX or conventional transarterial chemoembolization monotherapy from January 2015 to December 2016. The outcomes, including tumor response rates, evaluated via imaging assessment using the modified response evaluation criteria in solid tumors; overall survival; progression-free survival; and safety, were compared. The propensity score-matching methodology was used to reduce the influence of confounding factors on the outcomes. RESULTS: The study included 131 patients with locally advanced HCC who underwent transarterial chemoembolization and 101 who received HAIC-mFOLFOX as initial treatment. After propensity score matching (n = 67 in each group), patients who received HAIC-mFOLFOX had a higher objective response rate (43.3% vs 13.4%, P = .001), longer median overall survival (13.9 vs 6.0 months, P < .001), and longer median progression-free survival (6.4 vs 2.8 months, P = .001) than those who underwent transarterial chemoembolization. The survival benefit with HAIC-mFOLFOX was strengthened in patients with HCC with vascular invasion (hazard ratio: 0.379; 95% confidence interval: 0.237-0.607). HAIC-mFOLFOX was associated with lower incidences of severe adverse events (8.9% vs 22.9%) and liver toxicity than transarterial chemoembolization. CONCLUSIONS: Compared with transarterial chemoembolization, HAIC-mFOLFOX is a potentially safer and more effective locoregional therapy for patients with locally advanced HCC.

Targeted therapy for intervertebral disc degeneration: inhibiting apoptosis is a promising treatment strategy.

Intervertebral disc (IVD) degeneration (IDD) is a multifactorial pathological process associated with low back pain (LBP). The pathogenesis is complicated, and the main pathological changes are IVD cell apoptosis and extracellular matrix (ECM) degradation. Apoptotic cell loss leads to ECM degradation, which plays an essential role in IDD pathogenesis. Apoptosis regulation may be a potential attractive therapeutic strategy for IDD. Previous studies have shown that IVD cell apoptosis is mainly induced by the death receptor pathway, mitochondrial pathway, and endoplasmic reticulum stress (ERS) pathway. This article mainly summarizes the factors that induce IDD and apoptosis, the relationship between the three apoptotic pathways and IDD, and potential therapeutic strategies. Preliminary animal and cell experiments show that targeting apoptotic pathway genes or drug inhibition can effectively inhibit IVD cell apoptosis and slow IDD progression. Targeted apoptotic pathway inhibition may be an effective strategy to alleviate IDD at the gene level. This manuscript provides new insights and ideas for IDD therapy.

Comparison between zero-profile and cage plate devices in the treatment of single-level cervical spondylopathy.

OBJECTIVE: To compare the new zero-profile (Zero-P) fusion cage with regular cage and plate (CP) in the treatment of anterior cervical single-level cervical degenerative diseases. METHODS: Patients operated from January 2013 to August 2018 were enrolled. They were divided into the Zero-P group (n = 74 cases) and CP groups (n = 116 cases). Follow-up assessment was at 1, 3, 12, and 24 months after surgery, including the incidence of dysphagia, visual analogue scale (VAS) score, Japanese orthopaedic association (JOA)score, C2-C7 Cobb angle, intervertebral disc height (IDH) and adjacent joint degeneration. RESULTS: The operation time and blood loss of patients in Zero-P group were less than those in the CP group, and there was no difference in hospitalization time. All 190 patients were followed up for 24 to 72 months, with an average of 35.29 months. In terms of clinical outcomes, vas and JOA scores of the two groups were significantly improved at one month and the last follow-up. The incidence of dysphagia in the Zero-P group was lower than that in the CP group. On radiological effects, Cobb angle and IDH showed significant correction in both groups, but the degeneration rate of adjacent joints in the Zero-P group was lower than the CP group. CONCLUSIONS: In ACDF, the clinical and radiological results of Zero-P and CP devices are satisfactory, but Zero-P cage may be superior in operation time, blood loss, the incidence of dysphagia and adjacent joint degeneration.

Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin in Hepatocellular Cancer with Extrahepatic Spread.

PURPOSE: To compare treatment with hepatic arterial infusion of chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC) with both extrahepatic spread (EHS) and intrahepatic tumor and patients with intrahepatic tumor only. MATERIALS AND METHODS: This single-center retrospective study comprised 116 patients with advanced HCC with both intrahepatic tumor and EHS (EHS group; n = 50) or with intrahepatic tumor only (non-EHS group; n = 66) treated with HAIC including oxaliplatin, fluorouracil, and leucovorin between June 2014 and July 2016. Overall survival (OS) and radiologic responses to treatment were determined and compared between the 2 groups. RESULTS: Both the objective response rate and the clinical benefit rate were higher in the non-EHS group than in the EHS group (37.9% vs 16% objective response rate, P = .010; 81.8% vs 62% clinical benefit rate, P = .017). Median OS was not statistically different between the 2 groups (14.8 months vs 9.8 months, P = .068). Subgroup analysis of OS found that patients with lung metastases survived for a shorter time (OS 7 months) than patients with other metastatic sites (P = .003) and patients free of metastases (P = .001). CONCLUSIONS: HAIC is a potential treatment option for advanced HCC with limited extrahepatic metastases in a population with hepatitis B virus infection.

Survival benefits of computed tomography-guided thermal ablation for adrenal metastases from hepatocellular carcinoma.

Purpose: To evaluate the safety, efficacy, and survival outcomes of computed tomography (CT)-guided thermal ablation for adrenal metastases from hepatocellular carcinoma (HCC). Methods: This long-term retrospective study included 27 male patients (median age, 50 years; range, 34-77 years) with 29 adrenal metastatic tumors associated with HCC who underwent ablation between January 2004 and December 2015. The technical success rate, effectiveness rate, complications, and survival were recorded. Complications were assessed according to the Common Terminology Criteria for Adverse Events. Survival curves were estimated using the Kaplan-Meier method. A Cox regression model was used for the evaluation of factors predicting survival. Results: A total of 33 ablation sessions were performed for the 29 tumors. No ablation-related death was observed, and the incidence of complications was 87.9%. Grade 1-2 complications occurred in 23 of the 33 sessions (69.7%), and grade 3 hypertension was the only major complication, occurring in eight sessions (24.2%). The technical success and effectiveness rates were 93.1% (27 of 29 tumors) and 92.6% (25 of 27 patients), respectively. The median progression-free survival and overall survival (OS) durations for the 27 patients were 6.9 months and 16.8 months, respectively. The median OS duration was longer for patients with adrenal oligometastases (21.8 months) than for those with (12.8 months) multiple metastases (p = .037). Adrenal oligometastases were the only significant predictor of OS (p = .043). Conclusions: CT-guided ablation is a feasible and safe procedure for adrenal metastases from HCC, and it may be more beneficial for patients with adrenal oligometastases.

Mechanism and prognostic value of indoleamine 2,3-dioxygenase 1 expressed in hepatocellular carcinoma.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan-metabolizing enzyme that is widely distributed in normal or malignant tissues and contributes to immunologic tolerance and immune escape. However, in hepatocellular carcinoma (HCC), the characteristics and mechanism of IDO1 expression have not been well defined. In this study, IDO1 expression in tumor cells (T-IDO1) was frequently detected (109/112) by immunohistochemistry in formalin-fixed paraffin-embedded specimens from HCC patients, and the expression patterns were mostly focal (102/109). Expression of T-IDO1 was significantly associated with the infiltration of CD8+ T cells (P = .043), as well as younger age (<50 years old, P = .02). It was also found that IDO1 had diffuse expression in inflammatory cells in all specimens, which were defined as antigen-presenting cells. Significant correlations among IDO1, IFNG, and CD8A transcriptional levels were observed in freshly resected HCC specimens; moreover, no constitutive IDO1 expression was detected in HCC cell lines until stimulated by interferon-γ through the JAK2-STAT1 signaling pathway, but not type I interferon. Survival analyses showed that increased T-IDO1 and CD8+ T cell infiltration were significantly associated with superior overall survival (OS) (T-IDO1, P = .003; CD8+ T cells, P = .004), and T-IDO1 expression is an independent prognosis factor in both OS and disease-free survival (OS, P = .007; disease-free survival, P = .044). These findings indicated that T-IDO1 expression in HCC is common and is dominantly driven by the host antitumor immune response, which is a favorable prognostic factor in HCC.

Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma.

BACKGROUND & AIMS: To compare the overall survival (OS) and disease progression free survival (PFS) in patients with advanced hepatocellular carcinoma (Ad-HCC) who are undergoing hepatic arterial infusion (HAI) of oxaliplatin, fluorouracil/leucovorin (FOLFOX) treatment vs. sorafenib. METHODS: This retrospective study was approved by the ethical review committee, and informed consent was obtained from all patients before treatment. HAI of FOLFOX (HAIF) was recommended as an alternative treatment option for patients who refused sorafenib. Of the 412 patients with Ad-HCC (376 men and 36 women) between Jan 2012 to Dec 2015, 232 patients were treated with sorafenib; 180 patients were given HAIF therapy. The median age was 51 years (range, 16-82 years). Propensity-score matched estimates were used to reduce bias when evaluating survival. Survival curves were calculated by performing the Kaplan-Meier method and compared by using the log-rank test and Cox regression models. RESULTS: The median PFS and OS in the HAIF group were significantly longer than those in the sorafenib group (PFS 7.1 vs. 3.3 months [RECIST]/7.4 vs. 3.6 months [mRECIST], respectively; OS 14.5 vs. 7.0 months; p <0.001 for each). In the propensity-score matched cohorts (147 pairs), both PFS and OS in the HAIF group were longer than those in the sorafenib group (p <0.001). At multivariate analysis, HAIF treatment was an independent factor for PFS (hazard ratio [HR] 0.389 [RECIST]/0.402 [mRECIST]; p <0.001 for each) and OS (HR 0.129; p <0.001). CONCLUSION: HAIF therapy may improve survival compared to sorafenib in patients with Ad-HCC. A prospective randomized trial is ongoing to confirm this finding. LAY SUMMARY: We compared the hepatic arterial infusion of FOLFOX (a combination chemotherapy) with sorafenib (a tyrosine kinase inhibitor) in patients with advanced hepatocellular carcinoma, retrospectively. It was found that hepatic arterial infusion of FOLFOX therapy may improve both progression free and overall survival in patients with advanced hepatocellular carcinoma.

Percutaneous CT-guided radiofrequency ablation for patients with extrahepatic oligometastases of hepatocellular carcinoma: long-term results.

BACKGROUND: The aim of this study was to evaluate the therapeutic outcome of percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) for extrahepatic oligometastases of hepatocellular carcinoma (HCC). METHODS: Institutional review board approval was obtained for this retrospective study, and all patients provided written informed consent. Between April 2004 and December 2015, 116 oligometastases (diameter, 5-50 mm; 20.3 ± 10.4) in 79 consecutive HCC patients (73 men and 6 women; average age, 50.3 years ±13.0) were treated with RFA. We focussed on patients with 1-3 extrahepatic metastases (EHM) confined to 1-2 organs (including the lung, adrenal gland, bone, lymph node and pleura/peritoneum) who were treated naïve with curative intent. Survival, technical success and safety were evaluated. The log-rank test and Cox proportional hazards regression models were used to analyse the survival data. RESULTS: No immediate technical failure occurred, and at 1 month, the technique effectiveness rate was determined to be 95.8%. After a median follow-up time of 28.0 months (range, 6-108 months), the 1-, 2- and 3-year overall survival (OS) rates were 91, 70 and 48%, respectively, with a median survival time of 33.5 months. Time to unoligometastatic progression (TTUP) of less than 6 months (p < 0.001) and a Child-Pugh score of more than 5 (p = 0.001) were significant indicators of shorter OS. The 1-, 2- and 3-year disease free survival (DFS) rates were 34, 21 and 8%, respectively, with a median DFS time of 6.8 months. DFS was better for those with lung metastases (p = 0.006). Major complication occurred in nine (9.5%, 9/95) RFA sessions without treatment-related mortality. CONCLUSIONS: CT-guided RFA for oligometastatic HCC may provide favourable efficacy and technical success with a minimally invasive approach.

Oxygen-Bridged Cobalt-Chromium Atomic Pair in MOF-Derived Cobalt Phosphide Networks as Efficient Active Sites Enabling Synergistic Electrocatalytic Water Splitting in Alkaline Media.

Electrochemical water splitting offers a most promising pathway for "green hydrogen" generation. Even so, it remains a struggle to improve the electrocatalytic performance of non-noble metal catalysts, especially bifunctional electrocatalysts. Herein, aiming to accelerate the hydrogen and oxygen evolution reactions, an oxygen-bridged cobalt-chromium (Co-O-Cr) dual-sites catalyst anchored on cobalt phosphide synthesized through MOF-mediation are proposed. By utilizing the filling characteristics of 3d orbitals and modulated local electronic structure of the catalytic active site, the well-designed catalyst requires only an external voltage of 1.53 V to deliver the current density of 20 mA cm-2 during the process of water splitting apart from the superb HER and OER activity with a low overpotential of 87 and 203 mV at a current density of 10 mA cm-2 , respectively. Moreover, density functional theory (DFT) calculations are utilized to unravel mechanistic investigations, including the accelerated adsorption and dissociation process of H2 O on the Co-O-Cr moiety surface, the down-shifted d-band center, a lowered energy barrier for the OER and so on. This work offers a design direction for optimizing catalytic activity toward energy conversion.