Multi-Component and Nanoporous Design toward RuO2-Based Electrocatalyst with Enhanced Performance for Acidic Water Splitting.

Developing electrocatalysts with excellent activity and stability for water splitting in acidic media remains a formidable challenge due to the sluggish kinetics and severe dissolution. As a solution, a multi-component doped RuO2 prepared through a process of dealloying-annealing is presented. The resulting multi-doped RuO2 possesses a nanoporous structure, ensuring a high utilization efficiency of Ru. Furthermore, the dopants can regulate the electronic structure, causing electron aggregation around unsaturated Ru sites, which mitigates Ru dissolution and significantly enhances the catalytic stability/activity. The representative catalyst (FeCoNiCrTi-RuO2) shows an overpotential of 167 mV at 10 mA cm-2 for oxygen evolution reaction (OER) in 0.5 m H2SO4 solution with a Tafel slope of 53.1 mV dec-1, which is among the highest performance reported. Moreover, it remains stable for over 200 h at a current density of 10 mA cm-2. This work presents a promising approach for improving RuO2-based electrocatalysts, offering a crucial advancement for electrochemical water splitting.

Role of miRNAs in glucose metabolism of mouse cumulus cells†.

It is known that the oocyte has a limited capacity to acquire and metabolize glucose, and it must rely on cumulus cells (CCs) to take up glucose and produce pyruvate for use to produce ATP through oxidative phosphorylation. We therefore propose that miRNAs might regulate glucose metabolism (GM) in CCs and might be used as markers for oocyte quality assessment. Here, mouse CC models with impaired glycolysis or pentose phosphate pathway (PPP) were established, and miRNAs targeting the key enzymes in glycolysis/PPP were predicted using the miRNA target prediction databases. Expression of the predicted miRNAs was compared between CCs with normal and impaired glycolysis/PPP to identify candidate miRNAs. Function of the candidate miRNAs was validated by transfecting CCs or cumulus-oocyte-complexes (COCs) with miRNA inhibitors and observing effects on glucose metabolites of CCs and on competence of oocytes. The results validated that miR-23b-3p, let-7b-5p, 34b-5p and 145a-5p inhibited glycolysis, and miR-24-3p, 3078-3p,183-5p and 7001-5p inhibited PPP of CCs. Our observation using a more physiologically relevant model (intact cultured COCs) further validated the four glycolysis-targeting miRNAs we identified. Furthermore, miR-let-7b-5p, 34b-5p and 145a-5p may also inhibit PPP, as they decreased the production of glucose-6-phosphate. In conclusion, miRNAs play critical roles in GM of CCs and may be used as markers for oocyte quality assessment. Summary sentence:  We identified and validated eight new miRNAs that inhibit glycolysis and/or pentose phosphate pathways in cumulus cells (CCs) suggesting that miRNAs play critical roles in glucose metabolism of CCs and may be used for oocyte quality markers.

Phenotype remodelling of HNSCC cells in the muscle invasion environment.

BACKGROUND: Tumour invading muscle in head and neck squamous cell carcinoma (HNSCC) is often associated with destructive growth and poor prognosis. However, the phenotypic functions and pathological mechanisms of muscle-invasive cancer cells in tumour progress remains unknown. In this study, we aimed to investigate the phenotypic functions of muscle-invasive cancer cells of HNSCC and their potential crosstalk with tumour microenvironment. METHODS: We obtained scRNA-seq data (SC) from GSE103322 (N = 18) and GSE181919 (N = 37), spatial RNA-seq data (ST) from GSE208253 and GSE181300 (N = 4), transcriptomics of human HNSCC samples from GSE42743 (N = 12) and GSE41613 (N = 97). Utilizing the TCGA-HNSC dataset, we conducted univariate and multivariate Cox analyses to investigate the prognostic impact of muscle-invasion in HNSCC, with validation in an additional cohort. Through Stutility and AUCell approaches, we identified and characterized muscle-invasive cancer cell clusters, including their functional phenotypes and gene-specific profiles. Integration of SC and ST data was achieved using Seurat analysis, multimodal intersection analysis, and spatial deconvolution. The results were further validated via in vitro and in vivo experiments. RESULTS: Our analyses of the TCGA-HNSC cohort revealed the presence of muscle-invasion was associated with a poor prognosis. By combining ST and SC, we identified muscle-invasive cancer cells exhibiting epithelial-to-mesenchymal transition (EMT) and myoepithelial-like transcriptional programs, which were correlated with a poor prognosis. Furthermore, we identified G0S2 as a novel marker of muscle-invasive malignant cells that potentially promotes EMT and the acquisition of myoepithelium-like phenotypes. These findings were validated through in vitro assays and chorioallantoic membranes experiments. Additionally, we demonstrated that G0S2-overexpressing cancer cells might attract human ECs via VEGF signalling. Subsequent in vitro and in vivo experiments revealed G0S2 plays key roles in promoting the proliferation and invasion of cancer cells. CONCLUSIONS: In this study, we profiled the transcriptional programs of muscle-invasive HNSCC cell populations and characterized their EMT and myoepithelial-like phenotypes. Furthermore, our findings highlight the presence of muscle-invasion as a predictive marker for HNSCC patients. G0S2 as one of the markers of muscle-invasive cancer cells is involved in HNSCC intravasation, probably via VEGF signalling.

Expression profiling and function analysis identified new genes regulating cumulus expansion and cumulus cell apoptosis in mouse oocytes.

In brief: Genes expressed in cumulus cells might be used as markers for competent oocytes/embryos. This study identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos. Abstract: Studies on the mechanisms behind cumulus expansion and cumulus cell (CC) apoptosis are essential for understanding the mechanisms for oocyte maturation. Genes expressed in CCs might be used as markers for competent oocytes and/or embryos. In this study, both in vitro (IVT) and in vivo (IVO) mouse oocyte models with significant difference in cumulus expansion and CC apoptosis were used to identify and validate new genes regulating cumulus expansion and CC apoptosis of mouse oocytes. We first performed mRNA sequencing and bioinformatic analysis using the IVT oocyte model to identify candidate genes. We then analyzed functions of the candidate genes by RNAi or gene overexpression to select the candidate cumulus expansion and CC apoptosis-regulating genes. Finally, we validated the cumulus expansion and CC apoptosis-regulating genes using the IVO oocyte model. The results showed that while Spp1, Sdc1, Ldlr, Ezr and Mmp2 promoted, Bmp2, Angpt2, Edn1, Itgb8, Cxcl10 and Agt inhibited cumulus expansion. Furthermore, Spp1, Sdc1 and Ldlr inhibited CC apoptosis. In conclusion, by using both IVT and IVO oocyte models, we have identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos and for elucidating the molecular mechanisms behind oocyte maturation.

Stabilizing a 20-Electron Metallaazulyne by Aromaticity.

The 18-electron rule states that metal complexes with 18 valence electron metal centers are thermodynamically stable because nine valence orbitals of transition metals including one s orbital, three p orbitals, and five d orbitals can collectively accommodate 18 electrons, achieving the same electron configuration as the noble gas in the period. Thus, 20-electron compounds are extremely rare due to a violation of such a rule. Here, we demonstrate a 20-electron metallaazulyne via density functional theory calculations stabilized by aromaticity, which was supported by various aromaticity indices including nucleus-independent chemical shift, anisotropy of the induced current density, the isochemical shielding surface, and electron density of delocalized bonds. Interestingly, when a transition metal fragment is first introduced into the aromatic azulyne molecule, the resulting osmaazulyne becomes antiaromatic, in sharp contrast to the previous transformation from pentalyne to metallapentalyne. More interestingly, when osmaazulyne is reduced by two electrons, the resulting 20e osmaazulyne becomes aromatic. Our findings highlight an important application of aromaticity in stabilizing 20e species, inviting experimental verification.

OSCC cell-secreted exosomal CMTM6 induced M2-like macrophages polarization via ERK1/2 signaling pathway.

BACKGROUND: CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) is a critical regulator of tumor immunology among various cancers. However, the role and underlying molecular mechanism of CMTM6 in oral squamous cell carcinoma (OSCC) progression remains unclear. METHODS: The expression of CMTM6, PD-L1 and CD163 in OSCC tissues were detected by immunohistochemistry on tissue microarray. The effect of CMTM6 knockdown on OSCC cells and macrophage polarization were analyzed by CCK-8 assay, apoptotic assay, would-healing assay, transwell assay and qPCR. OSCC cell derived exosomes were obtained by ultracentrifugation and the mechanistic studies were conducted by qPCR and Western Blot. 4-Nitroquinoline N-oxide (4NQO) induced OSCC mice were used for verifying the effect of CMTM6 downregulation on M2 macrophage infiltration and tumor growth. RESULTS: In OSCC samples, higher CMTM6 expression has been obviously associated with higher pathological stage of OSCC patients, CD163 + macrophages infiltration and PD-L1 expression. CMTM6 knockdown of OSCC cells inhibited proliferative, migrative and invasive abilities of OSCC cells, as well as inhibited M2 macrophage polarization in vitro with downregulating PD-L1 expression. Importantly, exosomes from OSCC cells shuttled CMTM6 to macrophages and promoted M2-like macrophage polarization through activating ERK1/2 signaling. In addition, in 4NQO-induced OSCC mice, CMTM6 level was positively associated with CD163, CD206 and PD-L1 as well as M2-like macrophage infiltration. CONCLUSION: OSCC cell-secreted exosomal CMTM6 induces M2-like macrophages polarization to promote malignant progression via ERK1/2 signaling pathway, revealing a novel crosstalk between cancer cells and immune cells in OSCC microenvironment.

What makes leader cells arise: Intrinsic properties and support from neighboring cells.

Cancer cells collectively invading as a cohesive and polarized group is termed collective invasion, which is a fundamental property of many types of cancers. In this multicellular unit, cancer cells are heterogeneous, consisting of two morphologically and functionally distinct subpopulations, leader cells and follower cells. Leader cells at the invasive front are responsible for exploring the microenvironment, paving the way, and transmitting information to follower cells. Here, in this review, we will describe the important role of leader cells in collective invasion and the emerging underlying mechanisms of leader cell formation including intrinsic properties and the support from neighboring cells. It will help us to elucidate the essence of collective invasion and provide new anticancer therapeutic clues.

Theoretical study on the stability and aromaticity in silapentafulvenes towards triplet ground state species.

Pentafulvenes are dipolar hydrocarbons since they shift their π-electrons to achieve Hückel aromaticity and thus the electron donating groups at the exocyclic position can enhance their aromaticity. Silapentafulvenes are analogues of pentafulvene formed by the replacement of the carbon atoms at the exocyclic C[double bond, length as m-dash]C double bond with a silicon atom in pentafulvene. It remains unclear how the aromaticity of 5-silapentafulvenes and 6-silapentafulvenes can be changed due to the polarization of the C[double bond, length as m-dash]Si double bond. Here we perform density functional theory calculations and reveal the increased aromatic character in 6-silapentafulvenes and the reduced aromaticity of 5-silapentafulvenes in the ground state. In addition, the origin of the relative thermodynamic stability of the silapentafulvene isomers can be attributed to the bond dissociation energy (BDE) of the exocyclic bond. More interestingly, some triplet ground state 5-silapentafulvene species are predicted by introducing amino groups on the ring, which is supported by the coupled cluster calculations. Our findings could be useful for experimentalists to realize silaaromatics.

Restraint stress and elevation of corticotrophin-releasing hormone in female mice impair oocyte competence through activation of the tumour necrosis factor α (TNF-α) system.

Studies have observed that restraint stress (RS) and the associated elevation in corticotrophin-releasing hormone (CRH) impair oocyte competence by triggering apoptosis of ovarian cells but the underlying mechanisms are largely unclear. Although one study demonstrated that RS and CRH elevation triggered apoptosis in ovarian cells and oocytes via activating Fas/FasL signalling, other studies suggested that RS might damage cells by activating other pathways as well as Fas signalling. The objective of this study was to test whether RS and CRH elevation impairs oocytes by activating tumour necrosis factor α (TNF-α) signalling. Our invivo experiments showed that RS applied during oocyte prematuration significantly increased expression of TNF-α and its receptor (TNFR1) while inducing apoptosis in both oocytes and mural granulosa cells (MGCs). Invitro treatment of MGCs with CRH significantly increased their apoptotic percentages and levels of TNF-α and TNFR1 expression. Invitro knockdown by interfering RNA, invivo knockout of the TNF-α gene or injection of TNF-α antagonist etanercept significantly relieved the adverse effects of RS and CRH on apoptosis of MGCs and/or the developmental potential and apoptosis of oocytes. The results suggest that RS and CRH elevation in females impair oocyte competence through activating TNF-α signalling and that a TNF-α antagonist might be adopted to ameliorate the adverse effects of psychological stress on oocytes.

Multiple Treatment Meta-Analysis of Intra-Articular Injection for Temporomandibular Osteoarthritis.

PURPOSE: The purpose of the present study was to compare the efficacy of intra-articular injections of different agents for temporomandibular osteoarthritis (TMJOA) using a network meta-analysis. MATERIALS AND METHODS: A comprehensive search strategy was performed in multiple English and Chinese language electronic databases. Randomized controlled trials comparing the effect of intra-articular injections of different agents to treat TMJOA were included in accordance with the inclusion and exclusion criteria. The bias of risk in each study was assessed, with data extraction performed independently by 2 reviewers. The primary outcomes included pain intensity and maximal mouth opening. RESULTS: A total of 11 trials were included in the present study, and 10 different agents (ie, hyaluronic acid, dexamethasone, prednisolone, betamethasone, betamethasone plus hyaluronic acid, morphine, tramadol, platelet-derived growth factor [PDGF], placebo, arthrocentesis alone) administered using intra-articular injections were assessed. The evidence from the direct comparisons showed that arthrocentesis plus sodium hyaluronate resulted in significantly better pain relief outcomes compared with arthrocentesis alone. Also, the visual analog scale score was further reduced to 1.27 by PDGF injection after arthrocentesis (arthrocentesis plus PDGF) compared with arthrocentesis alone. Morphine and tramadol had a high probability of being the best treatment for pain control, with PDGF ranked third. When considering pain relief, arthrocentesis plus sodium hyaluronate resulted in a better outcome than arthrocentesis alone, and arthrocentesis plus PDGF was better than arthrocentesis plus placebo. PDGF injections had the greatest probability of being the best treatment for improving joint opening, followed by sodium hyaluronate. CONCLUSIONS: Tramadol, morphine, and PDGF injections after arthrocentesis were effective in the treatment of TMJOA with excellent effects in reducing pain and improving joint opening. Hyaluronic acid injections were effective for improving the maximal mouth opening of patients with TMJOA in the short-term. The combination of a corticosteroid and hyaluronic acid injection reduced the symptoms of TMJOA more than corticosteroid injections alone, but not of hyaluronic acid alone.

MIF promotes perineural invasion through EMT in salivary adenoid cystic carcinoma.

Macrophage migration inhibitory factor (MIF) is a prominent orchestrator during the onset and progression of cancer. Recently, MIF was detected in salivary adenoid cystic carcinoma (SACC). However, its functional effect in perineural invasion (PNI) of SACC remained unknown. To illuminate the effect of MIF in genesis of PNI in SACC, we examined the expression of MIF, epithelial-to-mesenchymal transition (EMT)-related markers, and Schwann cell markers by immunohistochemical analysis in 158 cases of SACC samples. Meanwhile, the correlation between MIF and PNI of SACC species was analyzed. Our data indicated that MIF expression was associated with PNI of SACC significantly. In vitro, the silence and overexpression experiments of MIF were performed in SACC cell lines. The ability of migration, invasion and PNI could be inhibited significantly by siRNA-mediated MIF silence, and the occurrence of EMT and Schwann-like cell differentiation was also inhibited by MIF silence in SACC-LM cells. Overexpression of MIF in SACC-83 cells using expressive plasmid showed the opposite effects. Our findings identified that an association between PNI and MIF expression existed. MIF may promote PNI of SACC by participating in cytoskeletal reorganization and pseudo foot formation induced by EMT and the Schwann-like cell differentiation of SACC cells.

Macrophage migration inhibitory factor promotes the invasion and metastasis of oral squamous cell carcinoma through matrix metalloprotein-2/9.

Macrophage migration inhibitory factor (MIF) has been shown to closely associate with the malignant progression of a variety of human carcinomas. However, the role and its underlying molecular mechanisms of MIF in the invasion and metastasis of oral squamous cell carcinoma (OSCC) still remains unclear. Here, we found that MIF silencing reduced the cell proliferation, migration, and invasion, as well as matrix metalloprotein-2 (MMP-2) and MMP-9 in OSCC cells. Overexpression of MMP-2 or MMP-9 restored the migration and invasion of MIF-knockdown cells, indicating that MMP-2 and MMP-9 are downstream targets of MIF. In the xenograft model, MIF silencing inhibited tumor growth and in lymph metastasis model, MIF silencing reduced tumor metastasis. More importantly, immunohistochemistry staining in a tissue microarray (TMA) demonstrated that MIF expression was positively correlated with clinic stage, recurrence, metastasis, and poor prognosis of patients with OSCC as well as with the levels of MMP-2 or MMP-9 in TMA. Therefore, our findings suggest that MIF may promote the invasion and metastasis of OSCC through the activation of MMP-2 and MMP-9 and prompt further investigation into the therapeutic value of MIF for OSCC treatment.

HSP27 associates with epithelial-mesenchymal transition, stemness and radioresistance of salivary adenoid cystic carcinoma.

Epithelial-mesenchymal transition (EMT) has been shown to associate with cancer stem cells and radioresistance. However, it is obscure whether EMT itself or specific EMT regulators play causal roles in these properties of salivary adenoid cystic carcinoma (SACC). Here, we exhibited that overexpression of HSP27 drove the migration and invasion, induced EMT, as well as mediated TGF-ß1-induced EMT in SACC cells, accompanying the up-regulation of Snail1 and Prrx1. Conversely, HSP27 silencing reduced the migration and invasion and contributed to MET of SACC cells. HSP27 indirectly down-regulates the expression of E-cadherin through activating Snail1 and Prrx1 expressions. Overexpression of Snail1 or Prrx1 restored the migration and invasion in HSP27 knockdown cells. Enforced expression of HSP27 enhanced colony formation, CD133+ /CD44+ population and radioresistance of SACC cell lines. In addition, HSP27 expression was positively associated with radioresistance and poor prognosis of SACC patients as well as with the expression of Prrx1 or Snail1 in SACC tissues. The data confirm an important function for HSP27 in SACC progression through regulating EMT and stemness, and they imply the possible association between EMT and radioresistance of SACC.

Is There a Difference in Intra-Articular Injections of Corticosteroids, Hyaluronate, or Placebo for Temporomandibular Osteoarthritis?

PURPOSE: Corticosteroids are widely used for treatment of temporomandibular joint (TMJ) osteoarthritis (OA). This study investigated the effects of corticosteroids on TMJOA compared with placebo or hyaluronate. MATERIALS AND METHODS: The authors designed and implemented a systematic review and meta-analysis to compare the effects of intra-articular injection of corticosteroid, hyaluronate, or placebo for patients with TMJOA. The authors searched related randomized controlled studies electronically in multiple English- and Chinese-language electronic databases. The predictor variable was intra-articular injection with corticosteroid, hyaluronate, or placebo. Primary outcome variables were pain intensity and maximal mouth opening. Other variables included success rate and adverse events. Meta-analyses were performed with Rev Man 5.3. RESULTS: Eight studies met the inclusion criteria. Meta-analysis showed that corticosteroid injections after arthrocentesis were superior to placebo in relieving pain as assessed with the visual analog scale (mean difference [MD], -0.74; 95% confidence interval [CI], -1.34 to -0.13; P = .02; I2 = 0%) in the long-term, but was inferior in increasing maximal mouth opening (MD, -2.06; 95% CI, -2.76 to -1.36; P < .00001; I2 = 28%). Although corticosteroid and hyaluronate injections without arthrocentesis decreased pain and improved maximal mouth opening, the corticosteroid group had a significantly lower success rate (odds ratio = 0.41; 95% CI, 0.17-1.00; P = .05; I2 = 0%) than the hyaluronate group in the short term. CONCLUSION: Corticosteroid injections after arthrocentesis are recommended for patients with TMJOA to relieve joint pain rather than increase maximal mouth opening. Corticosteroid and hyaluronate have marked effectiveness on TMJOA; however, hyaluronate might be the better alternative to some extent.

Long noncoding RNAs: emerging regulators of tumor angiogenesis.

Long noncoding RNAs (lncRNAs) participate in multiple biological processes especially human diseases, of which, tumor seems to be one of the most significant. Angiogenesis has been deemed to have a pivotal role in a series of tumor biological behaviors in tumorigenesis, progression and prognosis. Emerging evidences suggested that lncRNAs are involved in tumor angiogenesis and lncRNAs have already been verified to be potential biomarkers and promising therapeutic targets. This review summarized emerging angiogenesis-related lncRNAs, discussed their mechanisms interacting with cytokines, cancer stem cells, miRNAs and tumor hypoxia microenvironment, and demonstrated if lncRNAs could be new candidate targets of antiangiogenesis therapy.

The role of tumor microenvironment in collective tumor cell invasion.

For many cancer types, cancer cells invade into surrounding tissues by collective movement of cell groups that remain connected via cell-cell junctions. This migration is completely distinguished from single-cell migration, in which cancer cells disrupt the tight intercellular junctions and gain a mesenchymal phenotype. Recently, emerging evidence has revealed that collective cell invasion depends on not only cell-intrinsic mechanisms but also on extracellular mechanisms by bidirectional interplay between the tumor cell and the tumor environment. Herein, in this review we discuss the role and underline mechanisms of tumor microenvironment in collective tumor cell invasion, particularly focusing on extracellular matrix remodeling and cross-talk between tumor and stromal cells.

Improving Antifreeze Proteins Prediction with Protein Language Models and Hybrid Feature Extraction Networks.

Accurate identification of antifreeze proteins (AFPs) is crucial in developing biomimetic synthetic anti-icing materials and low-temperature organ preservation materials. Although numerous machine learning-based methods have been proposed for AFPs prediction, the complex and diverse nature of AFPs limits the prediction performance of existing methods. In this study, we propose AFP-Deep, a new deep learning method to predict antifreeze proteins by integrating embedding from protein sequences with pre-trained protein language models and evolutionary contexts with hybrid feature extraction networks. The experimental results demonstrated that the main advantage of AFP-Deep is its utilization of pre-trained protein language models, which can extract discriminative global contextual features from protein sequences. Additionally, the hybrid deep neural networks designed for protein language models and evolutionary context feature extraction enhance the correlation between embeddings and antifreeze pattern. The performance evaluation results show that AFP-Deep achieves superior performance compared to state-of-the-art models on benchmark datasets, achieving an AUPRC of 0.724 and 0.924, respectively.

SPP1+ TAM subpopulations in tumor microenvironment promote intravasation and metastasis of head and neck squamous cell carcinoma.

Macrophages are heterogeneous cells that play multifaceted roles in cancer progression and metastasis. However, the phenotypic diversity of tumor-associated macrophages (TAMs) in head and neck squamous carcinomas (HNSCC) remains poorly characterized. Here, we comprehensively analyzed the HNSCC single-cell transcriptomic dataset (GSE172577) and identified 5 subsets of myeloid-driven cells as TAMs using Seurat. Deciphering the lineage trajectory of TAMs, we revealed that FCN1+ TAMs could give rise to pro-angiogenesis SPP1+CCL18+ and SPP1+FOLR2+ populations through SPP1-CCL18+ and CXCL9+CXCL10+ TAMs. SPP1+CCL18+ and SPP1+FOLR2+ TAMs harbored pro-angiogenic and metastatic transcriptional programs and were correlated with poor survival of HNSCC patients. Our immunostaining examination revealed that infiltration of SPP1+ TAMs is associated with lymph node metastasis and poor prognosis in patients with HNSCC. Cell-cell communication analysis implied that SPP1+ TAM populations may employ SPP1 signaling to activate metastasis-related ECs. In vitro and in vivo studies, we demonstrated that SPP1hi TAMs enhanced tumor intravasation and metastasis in HNSCC in a manner dependent on the secretion of SPP1, CCL18, and CXCL8. Taken together, our study characterized the cellular heterogeneity of TAM populations and identified two SPP1+ TAM populations that play key roles in HNSCC intravasation and metastasis and serve as predictive markers for patients with HNSCC.

Prediction of protein-ATP binding residues using multi-view feature learning via contextual-based co-attention network.

Accurately predicting protein-ATP binding residues is critical for protein function annotation and drug discovery. Computational methods dedicated to the prediction of binding residues based on protein sequence information have exhibited notable advancements in predictive accuracy. Nevertheless, these methods continue to grapple with several formidable challenges, including limited means of extracting more discriminative features and inadequate algorithms for integrating protein and residue information. To address the problems, we propose ATP-Deep, a novel protein-ATP binding residues predictor. ATP-Deep harnesses the capabilities of unsupervised pre-trained language models and incorporates domain-specific evolutionary context information from homologous sequences. It further refines the embedding at the residue level through integration with corresponding protein-level information and employs a contextual-based co-attention mechanism to adeptly fuse multiple sources of features. The performance evaluation results on the benchmark datasets reveal that ATP-Deep achieves an AUC of 0.954 and 0.951, respectively, surpassing the performance of the state-of-the-art model. These findings underscore the effectiveness of assimilating protein-level information and deploying a contextual-based co-attention mechanism grounded in context to bolster the prediction performance of protein-ATP binding residues.