Rapid simulation of glycoprotein structures by grafting and steric exclusion of glycan conformer libraries.

Most membrane proteins are modified by covalent addition of complex sugars through N- and O-glycosylation. Unlike proteins, glycans do not typically adopt specific secondary structures and remain very mobile, shielding potentially large fractions of protein surface. High glycan conformational freedom hinders complete structural elucidation of glycoproteins. Computer simulations may be used to model glycosylated proteins but require hundreds of thousands of computing hours on supercomputers, thus limiting routine use. Here, we describe GlycoSHIELD, a reductionist method that can be implemented on personal computers to graft realistic ensembles of glycan conformers onto static protein structures in minutes. Using molecular dynamics simulation, small-angle X-ray scattering, cryoelectron microscopy, and mass spectrometry, we show that this open-access toolkit provides enhanced models of glycoprotein structures. Focusing on N-cadherin, human coronavirus spike proteins, and gamma-aminobutyric acid receptors, we show that GlycoSHIELD can shed light on the impact of glycans on the conformation and activity of complex glycoproteins.

Exploration of the Polymorphism Distribution of Bovine HMGA2 Gene in Worldwide Breeds and Its Associations with Ovarian Traits.

The high-mobility group AT-hook 2(HMGA2) gene has been widely studied in the context of cancer and animal growth. However, recently, several studies have uncovered its critical role in cell proliferation. A genome-wide association study (GWAS) further suggests that the HMGA2 gene is a candidate gene in fertility, indicating its connection not only to growth traits but also to reproduction, specifically ovarian traits. Thus, this study aimed to analyze the distribution of the HMGA2 gene in 54 bovine breeds worldwide, identify important short fragment variants (indels), and investigate the relationship between HMGA2 and ovarian development. The dataset included genotypic information from a bovine population of 634 individuals (n = 634). After genotyping and analyzing four selected loci, we found that one out of four loci, rs133750033 (P4-D22-bp), was polymorphic. Our results also reveal that this indel of HMGA2 is significantly associated with certain ovarian traits (p < 0.05). Specifically, it has connection with ovarian length (p = 0.004) and ovarian height (p = 0.026) during diestrus. Additionally, we discovered a higher expression of the HMGA2 gene in Asian cattle breeds. In summary, this study suggests that HMGA2 has the potential to serve as an animal fertility testing marker gene. Moreover, these findings contribute to a more promising outlook for the bovine industry.

Study on Viscoelastic Properties of Various Fiber-Reinforced Asphalt Binders.

This study analyzed the viscoelastic properties of asphalt binders reinforced with various fibers, such as modified asphalt binder, modified asphalt binder reinforced with lignin fibers (LFs), polyester fibers (PFs), and polypropylene fibers (PPFs), using dynamic shear rheological (DSR) testing. Then, the experiment generated data on the dynamic modulus and phase angle, which described the dynamic rheological characteristics at varying temperatures. The generalized Maxwell model was employed to select the appropriate element, and the test curve was fitted into a discrete time spectrum based on the time-temperature equivalence principle (TTSP). The master curves of the relaxation modulus and creep compliance were established to predict the relaxation and creep properties of various asphalt binders. The analysis indicated that fiber-reinforced binders offer superior resistance to high temperatures and long-term deformation, while being less sensitive to temperature and having a more significant elastic characterization. The binders reinforced with PPFs and LFs exhibited superior performance in high-temperature settings and long-term durability, respectively. On the other hand, the binder reinforced with PFs displayed exceptional high-temperature elastic properties. Additionally, based on the experimental data and corresponding discussion, it appears that the 13-element GM model is more appropriate for fitting the data.

Inhibition of HSP90AA1 induces abnormalities in bovine oocyte maturation and embryonic development.

In brief: HSP90AA1 is a ubiquitous molecular chaperone that can resist cellular stress, such as oxidative stress and apoptosis, and mediate the efficacy and protein folding of normal cells during heat stress, as well as many other functions. This study further reveals the role of HSP90AA1 in bovine oocyte maturation and early embryonic development. Abstract: HSP90AA1, a highly abundant and ubiquitous molecular chaperone, plays important roles in various cellular processes including cell cycle control, cell survival, and hormone signaling pathways. In this study, we investigated the functions of HSP90AA1 in bovine oocyte and early embryo development. We found that HSP90AA1 was expressed at all stages of development, but was mainly located in the cytoplasm, with a small amount distributed in the nucleus. We then evaluated the effect of HSP90AA1 on the in vitro maturation of bovine oocytes using tanespimycin (17-AAG), a highly selective inhibitor of HSP90AA1. The results showed that inhibition of HSP90AA1 decreased nuclear and cytoplasmic maturation of oocytes, disrupted spindle assembly and chromosome distribution, significantly increased acetylation levels of α-tubulin in oocytes and affected epigenetic modifications (H3K27me3 and H3K27ac). In addition, H3K9me3 was increased at various stages during early embryo development. Finally, the impact of HSP90AA1 on early embryo development was explored. The results showed that inhibition of HSP90AA1 reduced the cleavage and blastocyst formation rates, while increasing the fragmentation rate and decreasing blastocyst quality. In conclusion, HSP90AA1 plays a crucial role in bovine oocyte maturation as well as early embryo development.

Miniaturized Lens Antenna with Enhanced Gain and Dual-Focusing for Millimeter-Wave Radar System.

This paper presents a waveguide Lens antenna at the W-band adopting dual-focusing Lens to improve the performance. The Lens antenna consisted of a waveguide slotted structure and lenses processed using NOA73 meet the demands of miniaturization for current communication systems. The antenna radome fabricated using NOA73 not only protects the antenna structure but also improves the gain of the antenna by about 9.5 dBi via electromagnetic wave dual-focusing. A prototype is fabricated using novel UV-LIGA technology. Measured results are compared with simulated values. Measured results confirmed the fabricated antenna operated in the W-band with a 10 dB fractional bandwidth (FBW) of 6.5% from 97.5 to 104 GHz and a peak gain of 22 dBi at 100 GHz in the direction perpendicular to the plane of the feed waveguide. A good agreement between simulation and measurement is obtained, demonstrating efficient radiations in the operating band.

Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial.

The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32-0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30-0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.

[Develop the rural ecology in the New Era]. / 发展新时代的乡村生态学.

Rural ecology is a comprehensive field of study that takes the rural social-ecological-economic systems as the objective object and emphasizes spatial carrier governance. The development of rural ecology in the New Era embodies and implements comprehensively the core concepts of Xi Jinping Thought on Socialism with Chinese Cha-racteristics for a New Era, including harmonious coexistence between humans and nature, rural revitalization, green development, and the comprehensive construction of a socialist modernized nation. Under the goal of Chinese-style modernization, rural ecology exhibits characteristics distinct from the past, such as the integration of research objects, the intersectionality of basic theories, the computational feature of technical methods, and the orientation of exporting outcomes. To provide disciplinary support for modernization-oriented science to meet the new demands of country's rural development, effectively narrating the story of sustainable rural development in China and providing fundamental guarantees for the safety of rural systems, a number of issues such as paradigm innovation in research, improvement of data quality, and integration of comprehensive technologies, should be fully considered.

Phase I pharmacokinetic, safety, and preliminary efficacy study of tiragolumab in combination with atezolizumab in Chinese patients with advanced solid tumors.

PURPOSE: Tiragolumab is an immunoglobulin G1 monoclonal antibody targeting the immune checkpoint T cell immunoreceptor with immunoglobulin and immunoreceptor ITIM domains. Targeting multiple immune pathways may improve anti-tumor responses. The phase I YP42514 study assessed the pharmacokinetics (PK), safety, and preliminary efficacy of tiragolumab plus atezolizumab in Chinese patients with advanced solid tumors. METHODS: Adult patients from mainland China with Eastern Cooperative Oncology Group performance score 0/1, life expectancy of ≥ 12 weeks, and adequate hematologic/end organ function were eligible. Patients received tiragolumab 600 mg and atezolizumab 1200 mg intravenous every 3 weeks. Key endpoints were PK (serum concentrations of tiragolumab and atezolizumab) and safety. Results from this study were compared with the global phase I study, GO30103 (NCT02794571). RESULTS: In this study, 20 patients received a median of five doses of tiragolumab plus atezolizumab. Median age was 57.5 years, 85.0% of patients were male and the most common tumor type was non-small cell lung cancer. Exposures in Chinese patients were comparable to the global GO30103 population: geometric mean ratio was 1.07 for Cycle 1 tiragolumab area under the concentration-time curve0-21 and 0.92 and 0.93 for Cycle 1 peak and trough atezolizumab exposure, respectively. Treatment-related adverse events were consistent across the Chinese and global populations. Two patients (10.0%) in this study achieved a partial response. CONCLUSION: In this study, tiragolumab plus atezolizumab was tolerable and demonstrated preliminary anti-tumor activity. There were no meaningful differences in the PK or safety of tiragolumab plus atezolizumab between the Chinese and global populations. CLINICAL TRIAL REGISTRATION NUMBER: China Clinical Trial Registry Identifier CTR20210219/YP42514. Date of registration 16 March 2021.

Targeting tumor-infiltrating tregs for improved antitumor responses.

Immunotherapies have revolutionized the landscape of cancer treatment. Regulatory T cells (Tregs), as crucial components of the tumor immune environment, has great therapeutic potential. However, nonspecific inhibition of Tregs in therapies may not lead to enhanced antitumor responses, but could also trigger autoimmune reactions in patients, resulting in intolerable treatment side effects. Hence, the precision targeting and inhibition of tumor-infiltrating Tregs is of paramount importance. In this overview, we summarize the characteristics and subpopulations of Tregs within tumor microenvironment and their inhibitory mechanisms in antitumor responses. Furthermore, we discuss the current major strategies targeting regulatory T cells, weighing their advantages and limitations, and summarize representative clinical trials targeting Tregs in cancer treatment. We believe that developing therapies that specifically target and suppress tumor-infiltrating Tregs holds great promise for advancing immune-based therapies.

M-Ni-Co MOF (M=Zn, Fe, Mn) for high-performance supercapacitors by adjusting its morphology.

Metal-organic frameworks (MOF) have been wildly synthesised and studied as electrode materials for supercapacitors, and bimetallic MOF of Ni and Co has been broadly studied to enhance both specific capacitance and stability of supercapacitors. Herein, a best performance (about 320 F/g) of Ni-Co bimetallic MOF was found in a uniform preparation condition by adjusting the ratio of Ni to Co. Then tiny third metal ion was introduced, and we found that the morphology of material has a significant change on the original basis. Furthermore, certain ions (Zn, Fe, Mn) introduced make a huge improvement in capacitance based on Ni-Co MOF of 320 F/g. The result shows that Zn-Ni-Co MOF, Fe-Ni-Co MOF and Mn-Ni-Co MOF perform specific capacitance of 1135 F/g, 870 F/g and 760F/g at 1 A/g, respectively. Meanwhile, the asymmetric supercapacitor (ASC) was constructed by Zn-Ni-Co MOF as positive electrode and active carbon (AC) as negative electrode. The Zn-Ni-Co MOF//AC ASC possesses a energy density of 58 Wh/kg at a power density of 775 W/kg. This research provides a new methods to regulate the morphology of MOF and a novel viewpoint for assembling high-performance, low-price, and eco-friendly green energy storage devices.

Chlorothalonil exposure compromised mouse oocyte in vitro maturation through inducing oxidative stress and activating MAPK pathway.

Chlorothalonil (CTL) is widely used in agricultural production and antifoulant additive globally due to its broad spectrum and non-systemic properties, resulting in its widespread existence in foods, soil and water. Extensive evidence demonstrated that exposure to CTL induced adverse effects on organisms and in particular its reproductive toxicity has been attracted public concern. However, the influences of CTL on oocyte maturation is mysterious so far. In this study, we documented the toxic effects of CTL on oocyte in vitro maturation and the related underlying mechanisms. Exposure to CTL caused continuous activation of spindle assembly checkpoints (SAC) which in turn compromised meiotic maturation in mouse oocyte, featured by the attenuation of polar body extrusion (PBE). Detection of cytoskeletal dynamics demonstrated that CTL exposure weakened the acetylation level of α-tubulin and impaired meiotic spindle apparatus, which was responsible for the aberrant state of SAC. Meanwhile, exposure to CTL damaged the function of mitochondria, inducing the decline of ATP content and the elevation of reactive oxygen species (ROS), which thereby induced early apoptosis and DNA damage in mouse oocytes. In addition, exposure to CTL caused the alteration of the level of histone H3 methylation, indicative of the harmful effects of CTL on epigenetic modifications in oocytes. Further, the CTL-induced oxidative stress activated mitogen-activated protein kinase (MAPK) pathway and injured the maturation of oocytes. In summary, exposure to CTL damaged mouse oocyte in vitro maturation via destroying spindle assembly, inducing oxidative stress and triggering MAPK pathway activation.

MNK: A Novel Promising Target for Cancer Immunotherapy.

Cancer immunotherapy has demonstrated remarkable success in the treatment of multiple advanced malignancies, especially approaches to target the immune checkpoint. Nonetheless, the limited response rate remains a barrier to broader application. Identifying other ways to extend the beneficiaries to a large extent is needed. Emerging evidence has shown that mitogen-activated protein kinase-interacting kinases (MNKs) could be regarded as a novel, attractive target for cancer immunotherapy that is closely correlated with cancer biology and therapies. A comprehensive understanding of the role and mechanism of MNKs in cancer will shed light on the discovery of novel therapeutic strategies for cancer treatment. In this review, we outlined the structure of MNKs, their function and expression, and how MNKs affect tumor progression and elucidated the evidence supporting MNKs as a new promising treatment modality in human cancers.

First-line treatment of driver gene-negative metastatic lung adenocarcinoma with malignant pleural effusion: Should chemotherapy be combined with an immune checkpoint inhibitor or bevacizumab?

Patients with metastatic lung adenocarcinoma (MLA) and malignant pleural effusion (MPE) without driver gene mutations have a poor prognosis. None of the standard treatment strategies is recommended for such patients. We retrospectively analyzed the efficacy of the first-line treatment for this specific population: standard platinum-based doublet chemotherapy (CT), CT plus an immune checkpoint inhibitor (CT plus ICI), and CT plus bevacizumab (CT plus Bev). A total of 323 eligible patients were enrolled: CT alone (n = 166), CT plus Bev (n = 72), and CT plus ICI (n = 85). Treatment efficacy assessments were performed every two cycles according to the RECIST guidelines. The endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan-Meier (K‒M) curves and the log-rank test were used to compare OS and PFS. p < 0.05 was the threshold of significance (statistical software: SPSS). The median follow-up was 11.4 months (range, 2.1-49.6 months). PFS and OS in the CT plus ICI/CT plus Bev cohort were significantly longer than those in the CT group (PFS: 7.8/6.4/3.9 months, p < 0.0001; OS: 16.4/15.6/9.6 months, p < 0.0001, respectively). CT plus Bev had better PFS and OS than CT plus ICI/CT in PD-L1 < 1% patients (PFS: 8.4/5.0/3.8 months, p < 0.0001; OS: 15.6/12.9/9.3 months, p < 0.0001). Among patients with PD-L1 1-49%, CT plus ICI led to a longer PFS and OS (PFS: 8.9/5.8/4.2 months, p = 0.009; OS: 24.2/18.8/11.5 months, p = 0.03). In the cohort with PD-L1 ≥ 50%, CT plus ICI was still the best first-line treatment (PFS: 19.7/13.8/9.6 months, p = 0.033; OS: 27.2/19.6/14.9 months, p = 0.047). In driver gene-negative MLA with MPE, CT plus Bev or ICI better controlled MPE and significantly prolonged survival compared to CT alone. PD-L1 expression (negative/positive) may be a key factor influencing the choice of CT plus Bev or ICI.

The effect of L-carnitine supplementation during in vitro maturation on oocyte maturation and somatic cloned embryo development.

The quality of the recipient cytoplasm was reported as a crucial factor in maintaining the vitality of SCNT embryos and SCNT efficiency for dairy cows. Compared with oocytes matured in vivo, oocytes matured in vitro showed abnormal accumulation and metabolism of cytoplasmic lipids. L-carnitine treatment was found to control fatty acid transport into the mitochondrial ß-oxidation pathway, which improved the process of lipid metabolism. The results of this study show that 0.5 mg/ml L-carnitine significantly reduced the cytoplasmic lipid content relative to control. No significant difference was observed in the rate of oocyte nuclear maturation, but the in vitro developmental competence of SCNT embryos was improved in terms of increased blastocyst production and lower apoptotic index in the L-carnitine treatment group. In addition, the pregnancy rate with SCNT embryos in the treatment group was significantly higher than in the control group. In conclusion, the present study demonstrated that adding L-carnitine to the maturation culture medium could improve the developmental competence of SCNT embryos both in vitro and in vivo by reducing the lipid content of the recipient cytoplasm.

Comparison of effectiveness and safety of lasmiditan and CGRP-antagonists for the acute treatment of migraine in adults: systematic review and network meta-analysis of randomised trials.

OBJECTIVE: To compare the outcomes associated with the use of lasmiditan, rimegepant, ubrogepant, and zavegepant for the acute management of migraine headaches. METHODS: We searched four electronic databases from database inception to August 31, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the acute treatment of migraine. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of evidence using the CINeMA approach. We conducted frequentist network meta-analyses (NMA) to summarise the evidence. Data were analyzed using R-4.3.1. RESULTS: A total of 18 eligible studies including 10 different types of interventions with 22,429 migraine patients were included. NMA results showed that compared to ubrogepant (25 mg and 50 mg) and zavegepant, lasmiditan (100 mg and 200 mg) exhibits an elevated probability of achieving pain relief within a 2-hour interval. Similarly, relative to zavegepant, rimegepant (75 mg) and ubrogepant (50 mg and 100 mg) demonstrate an enhanced likelihood of sustaining pain relief over a 24-hour period. Furthermore, in contrast to ubrogepant (25 mg) and lasmiditan (50 mg), rimegepant (75 mg) presents a heightened probability of achieving freedom from photophobia within 2 h. Regarding safety, lasmiditan carries the highest risk of adverse events, which are associated with an increased incidence of adverse effects, including dizziness, somnolence, asthenia, paresthesia, and fatigue. CONCLUSIONS: In this NMA, a spectrum of evidence ranging from very low to high levels underscores the favorable efficacy and tolerability of rimegepant 75 mg and ubrogepant 100 mg, positioning them as potential candidates for the acute management of migraine. Concurrently, lasmiditan (100 mg and 200 mg) exhibits notable efficacy, albeit accompanied by an increased susceptibility to adverse events. These findings should still be approached with caution, primarily due to the intrinsic limitations associated with indirect comparisons.

Trastuzumab deruxtecan effectively controlled recurrent ovarian large-cell neuroendocrine carcinoma with low-level HER-2 expression: a case report.

Large-cell neuroendocrine carcinoma (LCNEC) of the ovary is an extremely rare tumor with invasive clinical behavior and poor outcome. However, there is no consensus on the optimal treatment strategy. Surgery followed by chemotherapy is considered the most common therapeutic option. Here, we report a case of a 55-year-old woman with ovarian LCNEC who relapsed after radical surgery and multiple lines of therapy. The tumor lesions continued to grow, and further immunohistochemistry showed low human epidermal growth factor receptor 2 (HER2) expression. After treatment with the anti-HER2 drug trastuzumab deruxtecan (T-DXd, formerly DS-8201a), the tumor burden was significantly reduced, and the patient achieved a progression-free survival (PFS) of 4 months. Our case provides a potential treatment option for recurrent ovarian LCNEC with low-level HER2 expression.

Erratum: Ecosystem quality-based management and the development of a new eco-friendly economy.

[This corrects the article DOI: 10.1016/j.xinn.2023.100491.].

Determination of Ideal Factors for Early Adoption and Standardization of Metagenomic Next-Generation Sequencing for Respiratory System Infections.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) demonstrates great promise as a diagnostic tool for determining the cause of pathogenic infections. The standard diagnostic procedures (SDP) include smears and cultures and are typically viewed as less sensitive and more time-consuming when compared to mNGS. There are concerns about the logistics and ease of transition from SDP to mNGS. mNGS lacks standardization of collection processes, databases, and sequencing. Additionally, there is the burden of training clinicians on interpreting mNGS results. OBJECTIVE: Until now, few studies have explored factors that could be used as early adoption candidates to ease the transition between SDP and mNGS. This study evaluated 123 patients who had received both SDP and mNGS and compared several variables across a diagnostic test evaluation. METHODS: The diagnostic test evaluation observed metrics such as sensitivity, specificity, positive and negative likelihood ratios (PLR, NLR), positive and negative predictive values (PPV, NPV), and accuracy. Factors included various sample sources such as bronchoalveolar lavage fluid (BALF), lung tissue, and cerebral spinal fluid (CSF). An additional factor observed was the patient's immune status. RESULTS: Pathogen detection was found to be significantly greater for mNGS for total patients, BALF sample source, CSF sample source, and non-immunocompromised patients (p<0.05). Pathogen detection was found to be insignificant for lung tissue sample sources and immunocompromised patients. Sensitivity, PLR, NLR, PPV, NPV, and accuracy appeared to be higher with mNGS for the total patients, BALF sample source, and non-immunocompromised patients when compared with SDP (p<0.05). CONCLUSION: With higher metrics in sensitivity, specificity, PLR, NLR, PPV, NPV, and accuracy for overall patients, mNGS may prove a better diagnostic tool than SDP. When addressing sample sources, mNGS for BALF-collected samples appeared to have higher scores than SDP for the same metrics. When patients were in a non-immunocompromised state, mNGS also demonstrated greater diagnostic benefits to BALF and overall patients compared to SDP. This study demonstrates that using BALF as a sample source and selecting non-immunocompromised patients may prove beneficial as early adoption factors for mNGS standard protocol. Such a study may pave the road for mNGS as a routine clinical method for determining the exact pathogenic etiology of lung infections.

Bta-miR-301a targets ACVR1 to influence cleavage time and blastocyst formation rate of early embryos in cattle.

Accumulating evidence indicates that paternally-derived miRNAs play a crucial role in the development of early embryos and are regarded as the key factor in the successful development of somatic cell cloned embryos. In our previous study, bta-miR-301a was found to be highly expressed in bovine sperm, and was delivered into oocytes during fertilization. In this study, bioinformatics, dual luciferase reporter assays, rescue experiments and gain- and loss-of-function experiments indicated that ACVR1 is the target gene of bta-miR-301a in early bovine embryos. By microinjecting bta-miR-301a mimic into embryos of parthenogenetic or somatic cell nuclear transfer, we observed that bta-miR-301a prolonged the first cleavage time of the embryos and increased the blastocyst formation rate. Thus, this study provides preliminary evidence that bta-miR-301a influences remodeling of the microfilament skeleton, prolongs the first cleavage time, and improves the developmental competence of embryos by negatively regulating ACVR1 translation.

Tuning the apparent hydrogen binding energy to achieve high-performance Ni-based hydrogen oxidation reaction catalyst.

High-performance platinum-group-metal-free alkaline hydrogen oxidation reaction catalysts are essential for the hydroxide exchange membrane fuel cells, which generally require high Pt loadings on the anode. Herein, we report a highly active hydrogen oxidation reaction catalyst, NiCuCr, indicated by the hydroxide exchange membrane fuel cell with a high peak power density of 577 mW cm-2 (18 times as high as the Ni/C anode) and a stability of more than 150 h (a degradation rate slower by 7 times than the Ni/C anode). The spectroscopies demonstrate that the alloy effect from Cu weakens the hydrogen binding, and the surface Cr2O3 species enhance the interfacial water binding. Both effects bring an optimized apparent hydrogen binding energy and thus lead to the high hydrogen oxidation reaction performance of NiCuCr. These results suggest that the apparent hydrogen binding energy determines the hydrogen oxidation reaction performance and that its tuning is beneficial toward high electrocatalytic performance.