Transcription factor EB modulates the homeostasis of reactive oxygen species in intestinal epithelial cells to alleviate inflammatory bowel disease.

Transcription factor EB (TFEB), a master lysosomal biogenesis and autophagy regulator, is crucial for cellular homeostasis, and its abnormality is related to diverse inflammatory diseases. Genetic variations in autophagic genes are associated with susceptibility to inflammatory bowel disease (IBD); however, little is known about the role and mechanism of TFEB in disease pathogenesis. In this study, we found that the genetic deletion of TFEB in mouse intestinal epithelial cells (IEC) caused intestinal barrier dysfunction, leading to increased susceptibility to experimental colitis. Mechanistically, TFEB functionally protected IEC in part through peroxisome proliferator-activated receptor gamma coactivator 1alpha (TFEB-PGC1α axis) induction, which consequently suppressed reactive oxygen species. TFEB can directly regulate PGC-1α transcription to control antioxidation level. Notably, TFEB expression is impaired and downregulated in the colon tissues of IBD patients. Collectively, our results indicate that intestinal TFEB participates in oxidative stress regulation and attenuates IBD progression.

A natural biogenic nanozyme for scavenging superoxide radicals.

Biominerals, the inorganic minerals of organisms, are known mainly for their physical property-related functions in modern living organisms. Our recent discovery of the enzyme-like activities of nanomaterials, coined as nanozyme, inspires the hypothesis that nano-biominerals might function as enzyme-like catalyzers in cells. Here we report that the iron cores of biogenic ferritins act as natural nanozymes to scavenge superoxide radicals. Through analyzing eighteen representative ferritins from three living kingdoms, we find that the iron core of prokaryote ferritin possesses higher superoxide-diminishing activity than that of eukaryotes. Further investigation reveals that the differences in catalytic capability result from the iron/phosphate ratio changes in the iron core, which is mainly determined by the structures of ferritins. The phosphate in the iron core switches the iron core from single crystalline to amorphous iron phosphate-like structure, resulting in decreased affinity to the hydrogen proton of the ferrihydrite-like core that facilitates its reaction with superoxide in a manner different from that of ferric ions. Furthermore, overexpression of ferritins with high superoxide-diminishing activities in E. coli increases the resistance to superoxide, whereas bacterioferritin knockout or human ferritin knock-in diminishes free radical tolerance, highlighting the physiological antioxidant role of this type of nanozymes.

Exploring the Specificity of Nanozymes.

Nanozymes, nanomaterials exhibiting enzyme-like activities, have emerged as a prominent interdisciplinary field over the past decade. To date, over 1200 different nanomaterials have been identified as nanozymes, covering four catalytic categories: oxidoreductases, hydrolases, isomerases, and lyases. Catalytic activity and specificity are two pivotal benchmarks for evaluating enzymatic performance. Despite substantial progress being made in quantifying and optimizing the catalytic activity of nanozymes, there is still a lack of in-depth research on the catalytic specificity of nanozymes, preventing the formation of consensual knowledge and impeding a more refined and systematic classification of nanozymes. Recently, debates have emerged regarding whether nanozymes could possess catalytic specificity similar to that of enzymes. This Perspective discusses the specificity of nanozymes by referring to the catalytic specificity of enzymes, highlights the specificity gap between nanozymes and enzymes, and concludes by offering our perspective on future research on the specificity of nanozymes.

A Thrombin-Activated Peptide-Templated Nanozyme for Remedying Ischemic Stroke via Thrombolytic and Neuroprotective Actions.

Ischemic stroke (IS) is one of the most common causes of disability and death. Thrombolysis and neuroprotection are two current major therapeutic strategies to overcome ischemic and reperfusion damage. In this work, a novel peptide-templated manganese dioxide nanozyme (PNzyme/MnO2 ) is designed that integrates the thrombolytic activity of functional peptides with the reactive oxygen species scavenging ability of nanozymes. Through self-assembled polypeptides that contain multiple functional motifs, the novel peptide-templated nanozyme is able to bind fibrin in the thrombus, cross the blood-brain barrier, and finally accumulate in the ischemic neuronal tissues, where the thrombolytic motif is "switched-on" by the action of thrombin. In mice and rat IS models, the PNzyme/MnO2 prolongs the blood-circulation time and exhibits strong thrombolytic action, and reduces the ischemic damages in brain tissues. Moreover, this peptide-templated nanozyme also effectively inhibits the activation of astrocytes and the secretion of proinflammatory cytokines. These data indicate that the rationally designed PNzyme/MnO2 nanozyme exerts both thrombolytic and neuroprotective actions. Giving its long half-life in the blood and ability to target brain thrombi, the biocompatible nanozyme may serve as a novel therapeutic agent to improve the efficacy and prevent secondary thrombosis during the treatment of IS.

Chiral metal-organic frameworks incorporating nanozymes as neuroinflammation inhibitors for managing Parkinson's disease.

Nanomedicine-based anti-neuroinflammation strategy has become a promising dawn of Parkinson's disease (PD) treatment. However, there are significant gaps in our understanding of the therapeutic mechanisms of antioxidant nanomedicines concerning the pathways traversing the blood-brain barrier (BBB) and subsequent inflammation mitigation. Here, we report nanozyme-integrated metal-organic frameworks with excellent antioxidant activity and chiral-dependent BBB transendocytosis as anti-neuroinflammatory agents for the treatment of PD. These chiral nanozymes are synthesized by embedding ultra-small platinum nanozymes (Ptzymes) into L-chiral and D-chiral imidazolate zeolite frameworks (Ptzyme@L-ZIF and Ptzyme@D-ZIF). Compared to Ptzyme@L-ZIF, Ptzyme@D-ZIF shows higher accumulation in the brains of male PD mouse models due to longer plasma residence time and more pathways to traverse BBB, including clathrin-mediated and caveolae-mediated endocytosis. These factors contribute to the superior therapeutic efficacy of Ptzyme@D-ZIF in reducing behavioral disorders and pathological changes. Bioinformatics and biochemical analyses suggest that Ptzyme@D-ZIF inhibits neuroinflammation-induced apoptosis and ferroptosis in damaged neurons. The research uncovers the biodistribution, metabolic variances, and therapeutic outcomes of nanozymes-integrated chiral ZIF platforms, providing possibilities for devising anti-PD drugs.

Protein-Nanocaged Selenium Induces t(8;21) Leukemia Cell Differentiation via Epigenetic Regulation.

The success of arsenic in degrading PML-RARα oncoprotein illustrates the great anti-leukemia value of inorganics. Inspired by this, the therapeutic effect of inorganic selenium on t(8; 21) leukemia is studied, which has shown promising anti-cancer effects on solid tumors. A leukemia-targeting selenium nanomedicine is rationally built with bioengineered protein nanocage and is demonstrated to be an effective epigenetic drug for inducing the differentiation of t(8;21) leukemia. The selenium drug significantly induces the differentiation of t(8;21) leukemia cells into more mature myeloid cells. Mechanistic analysis shows that the selenium is metabolized into bioactive forms in cells, which drives the degradation of the AML1-ETO oncoprotein by inhibiting histone deacetylases activity, resulting in the regulation of AML1-ETO target genes. The regulation results in a significant increase in the expression levels of myeloid differentiation transcription factors PU.1 and C/EBPα, and a significant decrease in the expression level of C-KIT protein, a member of the type III receptor tyrosine kinase family. This study demonstrates that this protein-nanocaged selenium is a potential therapeutic drug against t(8;21) leukemia through epigenetic regulation.

Strategies of targeting CYP51 for IFIs therapy: Emerging prospects, opportunities and challenges.

CYP51, a monooxygenase associated with the sterol synthesis pathway, is responsible for the catalysis of the 14-methyl hydroxylation reaction of lanosterol precursors. This enzyme is widely present in microorganisms, plants, and mammals. In mammals, CYP51 plays a role in cholesterol production, oligodendrocyte formation, oocyte maturation, and spermatogenesis. In fungal cells, CYP51 is an enzyme that synthesizes membrane sterols. By inhibiting fungal CYP51, ergosterol synthesis can be inhibited and ergosterol membrane fluidity is altered, resulting in fungal cell apoptosis. Thus, targeting CYP51 is a reliable antifungal strategy with important implications for the treatment of invasive fungal infections (IFIs). Many CYP51 inhibitors have been approved by the FDA for clinical treatment. However, several limitations of CYP51 inhibitors remain to be resolved, including fungal resistance, hepatotoxicity, and drug-drug interactions. New broad-spectrum, anti-resistant, highly selective CYP51 inhibitors are expected to be developed to enhance clinical efficacy and minimize adverse effects. Herein, we summarize the structural features and biological functions of CYP51 and emphatically analyze the structure-activity relationship (SAR) and therapeutic potential of different chemical types of small-molecule CYP51 inhibitors. We also discuss the latest progress of novel strategies, providing insights into new drugs targeting CYP51 for clinical practice.

Machine learning facilitating the rational design of nanozymes.

As a component substitute for natural enzymes, nanozymes have the advantages of easy synthesis, convenient modification, low cost, and high stability, and are widely used in many fields. However, their application is seriously restricted by the difficulty of rapidly creating high-performance nanozymes. The use of machine learning techniques to guide the rational design of nanozymes holds great promise to overcome this difficulty. In this review, we introduce the recent progress of machine learning in assisting the design of nanozymes. Particular attention is given to the successful strategies of machine learning in predicting the activity, selectivity, catalytic mechanisms, optimal structures and other features of nanozymes. The typical procedures and approaches for conducting machine learning in the study of nanozymes are also highlighted. Moreover, we discuss in detail the difficulties of machine learning methods in dealing with the redundant and chaotic nanozyme data and provide an outlook on the future application of machine learning in the nanozyme field. We hope that this review will serve as a useful handbook for researchers in related fields and promote the utilization of machine learning in nanozyme rational design and related topics.

One-pot hydrothermal synthesis of metal-doped carbon dot nanozymes using protein cages as precursors.

Metal-doped carbon dots represent a new class of promising nanomaterials with enzyme-like activity, whose properties such as fluorescence properties and enzyme-like activity are determined by the precursors and the conditions used to prepare them. Nowadays, the synthesis of carbon dots using naturally occurring precursors has attracted increasing attention. Here, using metal-loaded horse spleen ferritin as a precursor, we report a facile one-pot hydrothermal strategy to synthesise metal-doped fluorescent carbon dots with enzyme-like activity. The as-prepared metal-doped carbon dots exhibit high water solubility, uniform size distribution, and good fluorescence. In particular, the Fe-doped carbon dots exhibit prominent oxidoreductase catalytic activities, including peroxidase-like, oxidase-like, catalase-like, and superoxide dismutase-like activities. This study provides a green synthetic strategy for developing metal-doped carbon dots with enzymatic catalytic activity.

Edge-Site Engineering of Defective Fe-N4 Nanozymes with Boosted Catalase-Like Performance for Retinal Vasculopathies.

Extensive efforts are devoted to refining metal sites for optimizing the catalytic performance of single-atom nanozymes (SANzymes), while the contribution of the defect environment of neighboring metal sites lacks attention. Herein, an iron-based SANzyme (Fe-SANzyme) is rationally designed by edge-site engineering, which intensively exposes edge-hosted defective Fe-N4 atomic sites anchored in hierarchical mesoporous structures. The Fe-SANzyme exhibits excellent catalase-like activity capable of efficiently catalyzing the decomposition of H2 O2 into O2 and H2 O, with a catalytic kinetic KM value superior to that of natural catalase and reported nanozymes. The mechanistic studies depict that the defects introduce notable charge transfer from the Fe atom to the carbon matrix, making the central Fe more activated to strengthen the interaction with H2 O2 and weaken the OO bond. By performing catalase-like catalysis, the Fe-SANzyme significantly scavenges reactive oxygen species (ROS) and alleviates oxidative stress, thus eliminating the pathological angiogenesis in animal models of retinal vasculopathies without affecting the repair of normal vessels. This work provides a new way to refine SANzymes by engineering the defect environment and geometric structure around metal sites, and demonstrates the potential therapeutic effects of the nanozyme on retinal vasculopathies.

Nanozyme-Based Artificial Organelles: An Emerging Direction for Artificial Organelles.

Artificial organelles are compartmentalized nanoreactors, in which enzymes or enzyme-mimic catalysts exhibit cascade catalytic activities to mimic the functions of natural organelles. Importantly, research on artificial organelles paves the way for the bottom-up design of synthetic cells. Due to the separation effect of microcompartments, the catalytic reactions of enzymes are performed without the influence of the surrounding medium. The current techniques for synthesizing artificial organelles rely on the strategies of encapsulating enzymes into vesicle-structured materials or reconstituting enzymes onto the microcompartment materials. However, there are still some problems including limited functions, unregulated activities, and difficulty in targeting delivery that hamper the applications of artificial organelles. The emergence of nanozymes (nanomaterials with enzyme-like activities) provides novel ideas for the fabrication of artificial organelles. Compared with natural enzymes, nanozymes are featured with multiple enzymatic activities, higher stability, easier to synthesize, lower cost, and excellent recyclability. Herein, the most recent advances in nanozyme-based artificial organelles are summarized. Moreover, the benefits of compartmental structures for the applications of nanozymes, as well as the functional requirements of microcompartment materials are also introduced. Finally, the potential applications of nanozyme-based artificial organelles in biomedicine and the related challenges are discussed.

Effects of school-based neuromuscular training on fundamental movement skills and physical fitness in children: a systematic review.

Objectives: The primary purpose of this review was to clarify the effects of school-based integrated neuromuscular training (INT) on fundamental movement skills and physical fitness in children. The secondary purpose was to examine whether school-based INT intervention is superior to physical education (PE) intervention in enhancing motor skills and fitness. Methods: A systematic literature search was performed in four electronic databases: PubMed, Web of Science, MEDLINE (EBSCOhost), and Cochrane Central Register of Controlled Trials. The last search was performed on December 21, 2021, and was limited to the English language, human species, and peer reviewed journals. Randomized controlled trials and cluster randomized controlled trials that examine the effects of school-based INT on motor skills and/or fitness in healthy children who were aged up to 14 years old were included. Moreover, studies included in this study should compare school-based INT-induced adaptions with those generated by PE interventions. Studies that involve athletic children and additional exercise training were excluded. The Physiotherapy Evidence Database (PEDro) scale was used to assess the quality of the study. Results: Of 1,026 studies identified, seven original trials that meet the inclusion criteria were included in this review. Based on the PEDro scale, the PEDro score of seven studies was between six and eight points with a mean score of 5.29. Among the seven studies included in this study, four studies assessed physical fitness including muscular fitness (n = 4), speed (n = 3), endurance (n = 2), and flexibility (n = 2). Three studies examined the effects of INT on postural control and three studies explored its effects on motor skills. Concerning movement competence, significant and greater improvements in postural control and fundamental motor skills were observed following school-based INT interventions compared to PE intervention in two and three studies, respectively. Regarding physical fitness, neuromuscular training significantly increased muscular fitness, speed, endurance, flexibility in three, two, one, and one studies, respectively. However, only greater improvements in muscle fitness were observed in school-based INT group compared to PE group. The main limitations of this review were the lack of descriptions of training intensity and volume and the low methodological quality of the included studies. Conclusion: This review provides evidence that school-based neuromuscular training programs are superior to PE lessons in improving postural control, fundamental motor skills and muscular strength. Therefore, INT could be incorporated into traditional physical education classes in school. Trial registration number: CRD42022297349.

Plant green pigment of chlorophyllin attenuates inflammatory bowel diseases by suppressing autophagy activation in mice.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are intestinal complications characterized by chronic inflammation, autophagy abnormality, and lysosomal stress, which are derived from genetic predisposition and environmental risk factors. It is generally precepted that dietary green vegetable is beneficial for physiological homeostasis. In this study, we found that dextran sulfate sodium (DSS)-induced colitis and altered intestinal epithelia in mice were attenuated by oral administration of chlorophyllin (CHL), a water-soluble derivate of chlorophyll. In DSS-treated mice, autophagy was persistently activated in intestinal tissues and associated with bowel disorders. Conversely, supplement of CHL in diet or gavage suppressed intestinal inflammation, downregulated autophagy flux in intestinal tissue, and relieved endoplasmic reticulum stress. In vitro studies show that CHL could activate Akt and mTOR pathways, leading to downregulation of autophagic and lysosomal flux. Thus, consumption of green vegetables and chlorophyllin may be beneficial for IBD recovery in part through alleviation of inflammation and autolysosomal flux.NEW & NOTEWORTHY Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal disease, while the etiology remains poorly understood. Dietary composition and lifestyle are crucial for pathogenesis and progression of IBD. In this study, we observed that autophagy in the intestinal tissue was persistently activated in IBD mice. Chlorophyllin (CHL), a water-soluble derivate of chlorophyll, can attenuate colitis by regulating autophagy and inflammation. Thus, consumption of green vegetables and chlorophyllin may be beneficial for IBD recovery.

Bioinspired copper single-atom nanozyme as a superoxide dismutase-like antioxidant for sepsis treatment.

Sepsis is a systemic inflammatory response syndrome with high morbidity and mortality mediated by infection-caused oxidative stress. Early antioxidant intervention by removing excessively produced reactive oxygen and nitrogen species (RONS) is beneficial to the prevention and treatment of sepsis. However, traditional antioxidants have failed to improve patient outcomes due to insufficient activity and sustainability. Herein, by mimicking the electronic and structural characteristics of natural Cu-only superoxide dismutase (SOD5), a single-atom nanozyme (SAzyme) featuring coordinately unsaturated and atomically dispersed Cu-N4 site was synthesized for effective sepsis treatment. The de novo-designed Cu-SAzyme exhibits a superior SOD-like activity to efficiently eliminate O2 •-, which is the source of multiple RONS, thus blocking the free radical chain reaction and subsequent inflammatory response in the early stage of sepsis. Moreover, the Cu-SAzyme effectively harnessed systemic inflammation and multi-organ injuries in sepsis animal models. These findings indicate that the developed Cu-SAzyme possesses great potential as therapeutic nanomedicines for the treatment of sepsis.

Target languages, types of activities, engagement, and effectiveness of extramural language learning.

Since Sundqvist introduced the term "extramural English" in 2009, empirical research on extramural language learning has continued to expand. However, the expanding empirical research has yet yielded incommensurate review studies. To present a timely picture of the field of extramural language learning, this study conducts a review of 33 relevant articles retrieved from Scopus and Web of Science databases. The results showed the five types of target languages frequently investigated in this field (i.e., English, German, French, Chinese, and Japanese) and seven main types of extramural learning activities (i.e., playing digital games, watching videos, reading, listening to audios, having technology-enhanced socialisation, having face-to-face socialisation, and writing compositions). People's engagement in extramural language learning was overall high, especially listening to audios and playing digital games, mediated by the relationship between the difficulty of the activities and people's target language proficiency levels, gender, and the interactive environment. Extramural language learning was overall effective for language development and enhancing affective states in language learning. The effectiveness may be influenced by the involvement of language inputs and outputs and the amount of engagement time. Implications for practitioners were suggested concerning encouraging digital gameplay, emphasising formal language instruction, and creating positive interactive environments for extramural language learning.

Superoxide dismutase nanozymes: an emerging star for anti-oxidation.

Superoxide dismutases (SODs) are a group of metalloenzymes that catalyze the dismutation of superoxide radicals (O2˙-) into hydrogen peroxide (H2O2) and oxygen (O2). As the first line of defense against reactive oxygen species (ROS)-mediated damage, SODs are expected to play an important role in the treatment of oxidative stress-related diseases. However, the clinical applications of SODs have been severely limited by their structural instability and high cost. Compared with natural enzymes, nanozymes, nanomaterials with enzyme-like activity, are more stable, and economical, can be easily modified and their activities can be adjusted. Due to their excellent characteristics, nanozymes have attracted widespread attention in recent years and are expected to become effective substitutes for natural enzymes in many application fields. Importantly, some nanozymes with SOD-like activity have been developed and proved to have a mitigating effect on diseases caused by oxidative stress. These studies on SOD-like nanozymes provide a feasible strategy for breaking through the dilemma of SOD clinical applications. However, at present, the specific catalytic mechanism of SOD-like nanozymes is still unclear, and many important issues need to be resolved. Although there are many comprehensive reviews to introduce the overall situation of the nanozyme field, the research on SOD-like nanozymes still lacks a systematic review. From the structure and mechanism of natural SOD enzymes to the structure and regulation of SOD-like nanozymes, and then to the measurement and application of nanozymes, this review systematically summarizes the recent progress in SOD-like nanozymes. The existing shortcomings and possible future research hotspots in the development of SOD-like nanozymes are summarized and prospected. We hope that this review would provide ideas and inspirations for further research on the catalytic mechanism and rational design of SOD-like nanozymes.

Nanocage-Based Capture-Detection System for the Clinical Diagnosis of Autoimmune Disease.

The detection of autoantibodies is critical for diagnosis of autoimmune diseases. However, the sensitivity is often limited by the properties of the antigens and the detection systems such as enzyme-linked immunosorbent assay (ELISA). Here, employing the multidisplay ability of ferritin, a highly sensitive nanocage-based capture-detection system is designed, of which the sensitivity is 100-1000-fold higher than that of conventional ELISA methods. The capture nanocages are constructed by displaying the primary Sjögren's syndrome (pSS)-related antigenic peptides on ferritin nanocage, which present epitopes effectively and high affinity, leading to tenfold higher capture capability for autoantibodies. Human IgG Fc-binding peptides are also engineered on ferritin nanocage, which enable high binding affinity and efficient horseradish peroxidase (HRP)-labeling. Compared with commercial HRP-conjugated anti-human IgG antibody, the nanocage-based detecting probe exhibited more than tenfold increased sensitivity. Autoantibodies are then examined in 91 sera from patients with pSS, 51 from rheumatoid arthritis, 54 from systemic lupus erythematosus, and 55 from healthy individuals by using the nanocage-based ELISA. The results indicate that the nanocage-based capture-detection system is an effective detection platform and provide a novel and more sensitive method for the diagnosis of autoimmune diseases.

Hepatitis B Virus X Protein (HBx) Suppresses Transcription Factor EB (TFEB) Resulting in Stabilization of Integrin Beta 1 (ITGB1) in Hepatocellular Carcinoma Cells.

Hepatitis B virus (HBV) infection is a major etiological risk for the incidence of hepatocellular carcinoma (HCC), and HBV X protein (HBx) is essential for oncogenic transformation. It is not known that if HBx can sabotage the lysosomal system for transformation and tumorigenesis, or its mechanism if it does have an effect. Examining clinical data, we observed that the downregulation of lysosomal components and transcription factor EB (TFEB) was associated with a poor prognosis of HCC patients. In HCC cells, we found that expression of HBx suppressed TFEB, impaired biogenesis of autophagic-lysosome, and promoted cellular dissemination. HBx mediated downregulation of TFEB led to impairment of autophagic/lysosomal biogenesis and flux, and consequently, accumulation of integrin beta 1 (ITGB1) for motility of HCC cells. Conversely, TFEB, in a steady-state condition, through induction of lysosomal biogenesis restrained ITGB1 levels and limited mobility of HCC cells. Specifically, overexpression of TFEB upregulated and activated the cysteine proteases including cathepsin L (CTSL) to degrade ITGB1. Conversely, expression of cystatin A (CSTA) or cystatin B (CSTB), the cellular inhibitors of lysosomal cysteine proteinases, spared ITGB1 from degradation and promoted dissemination of HCC cells. Taken together, this study suggests a potential mechanism for HBV-mediated malignancy, showing that HBx mediated downregulation of TFEB leads to accumulation of ITGB1 for HCC cell migration.

Persistent luminescence-polypyrrole nanocomposite for dual-modal imaging and photothermal therapy of mammary cancer.

Multifunctional nanocomposites that possess imaging and high-performance therapeutic features are experiencing a surge in interest in the precision clinical anticancer treatment. In this work, we reported the fabrication and bio-application of a novel persistent luminescence-polypyrrole nanocomposite (LPLNP@SPP) for photoacoustic/persistent luminescence (PA/PL) dual-modal imaging guided photothermal therapy (PTT). The construction of LPLNP@SPP avoids the PL quenching of LPLNP-OH by the polypyrrole-coating, and thus enables the combination of PL and PTT. The LPLNP@SPP shows excellent biocompatibility, long lasting near-infrared (NIR) PL emitting without in situ excitation and high-contrast PA signals. Meanwhile, this nanocomposite exhibits strong NIR absorbance and exceptional photothermal conversion capability, which provides notable potential for imaging-guided antitumor therapy. Thus, our work highlights the dual-functional core-shell LPLNP@SPP as a feasible theranostic nanoplatform for cancer diagnosis and therapy.

Game-based self-regulated language learning: Theoretical analysis and bibliometrics.

Game-based learning and self-regulated learning have long been valued as effective approaches to language education. However, little research has been conducted to investigate their integration, namely, game-based self-regulated language learning (GBSRLL). This study aims to conceptualise GBSRLL based on the combination of theoretical analysis, thematic evolution analysis, and social network analysis on the research articles in the fields of game-based language learning and self-regulated language learning. The results show that GBSRLL is a new interdisciplinary field emerging since the period from 2018 to 2019. Self-regulated learning strategies that can be performed in GBSRLL, the effects of GBSRLL on learners' affective states, and the features in GBSRLL were the prominent research topics in this field. Its theoretical foundation centres on the positive correlations between learner motivation, self-efficacy, and autonomy and the implementation of game-based learning and self-regulated learning. It is feasible to conduct GBSRLL due to the strong supportiveness of game mechanics for various phases and strategies of self-regulated learning. More contributions to this new interdisciplinary field are called for, especially from the aspects of the long-term effects of GBSRLL on academic performance and the useful tools and technologies for implementing GBSRLL.