Unique Domain Research Articles

The Good, the Bad, and the Ugly: The Journey of an Architect-Researcher in Palliative Environments.

As an architect, I felt a strong moral urge to engage in research aimed at creating more human-centred healthcare environments, particularly in the context of palliative care. Being relatively new to this field 4 years ago, my primary goal then was to develop a deep understanding of these unique contexts, with a special focus on the people involved. To achieve this, I embarked on an immersive ethnographic study over the last few years, involving participant observations in three distinct palliative environments (i.e., day-care centre, hospice, and palliative care unit) and interviews with residents, family members, caregivers, volunteers, and maintenance staff. While preparing to present this study to an ethics panel, I believed I had covered all possible questions until I was unexpectedly asked, "How will you consider your own emotional well-being?" At that moment (in the 1st year of my PhD trajectory), I was unsure how to respond, but today (in the 4th year of my PhD), I would say that my approach was to verbally and visually document the entirety of the experience, including the positive, negative, and challenging aspects. Throughout my journey, I maintained a journal not only to express my thoughts and feelings but also to capture the methodological and ethical insights I had gained while conducting interdisciplinary research on the spatial experiences of individuals within palliative environments. This article serves as a comprehensive overview of all significant events preceding, during, and following the study. The insights were organised according to 'the good, the bad, and the ugly' to shed light on the complexities and nuances of conducting research in this unique and sensitive domain. In doing so, the aim of my contribution is to inspire novice researchers to embark on such research studies and offer them guidance along this undoubtedly beautiful yet occasionally challenging journey.

Medical language model specialized in extracting cardiac knowledge

The advent of the Transformer has significantly altered the course of research in Natural Language Processing (NLP) within the domain of deep learning, making Transformer-based studies the mainstream in subsequent NLP research. There has also been considerable advancement in domain-specific NLP research, including the development of specialized language models for medical. These medical-specific language models were trained on medical data and demonstrated high performance. While these studies have treated the medical field as a single domain, in reality, medical is divided into multiple departments, each requiring a high level of expertise and treated as a unique domain. Recognizing this, our research focuses on constructing a model specialized for cardiology within the medical sector. Our study encompasses the creation of open-source datasets, training, and model evaluation in this nuanced domain.

Deep supercooling solidification towards tuned amorphous/nanocrystalline dual phases for superior magnetic nanocrystalline alloys

Nanocrystalline soft magnetic alloys featuring with amorphous-nanocrystalline dual-phase structure are critical for energy conversion and transportation at elevated frequencies. Their applications however, are refrained by limited saturation magnetic flux density (Bs) due to unavoidable addition of a considerable quantity of non-magnetic elements for glass forming ability (GFA). Furthermore, engineering of the amorphous-nanocrystalline microstructure is critical for the coercivity (Hc), which urges development of advanced approach. In this study, a deep supercooling solidification has been proposed, which not only promotes the formation of short-range packing and icosahedron/icosahedron-like structures for enhanced GFA, but also induces an optimized microstructure consisting of highly disordered amorphous matrix to facilitate nanograin refinement. Based on such strategy, Finemet-based nanocrystalline alloy with superior magnetic properties (Bs = 1.71 T, Hc = 5.0 A/m) has been achieved without additional glass forming element. Such superior performance is correlated to the unique magnetic domain structure involving straight domain walls and smooth movement. The deep supercooling strategy not only breaks the trade-off between the Bs and GFA to allow the design of nanocrystalline alloys with large ferromagnetic content, but also serves as an effective method for microstructure optimization for nanocrystalline alloys.

Polynomial Invariants for Rooted Trees Related to Their Random Destruction

We consider three bivariate polynomial invariants $P$, $A$, and $S$ for rooted trees, as well as a trivariate polynomial invariant $M$. These invariants are motivated by random destruction processes such as the random cutting model or site percolation on rooted trees. We exhibit recursion formulas for the invariants and identities relating $P$, $S$, and $M$. The main result states that the invariants $P$ and $S$ are complete, that is they distinguish rooted trees (in fact, even rooted forests) up to isomorphism. The proof method relies on the obtained recursion formulas and on irreducibility of the polynomials in suitable unique factorization domains. For $A$, we provide counterexamples showing that it is not complete, although that question remains open for the trivariate invariant $M$.

SETDB1 activity is globally directed by H3K14 acetylation via its Triple Tudor Domain.

SETDB1 (SET domain bifurcated histone lysine methyltransferase 1) is a major protein lysine methyltransferasetrimethylating lysine 9 on histone H3 (H3K9) which isinvolved in heterochromatin formation and silencing of repeat elements (REs). It contains a unique Triple Tudor Domain (3TD), which specifically binds the dual modification of H3K14ac in the presence of H3K9me1/2/3. Here, we explored the role of the 3TD H3-tail interaction for the H3K9 methylation activity of SETDB1. We generated a binding reduced 3TD mutant and demonstrate in biochemical methylation assays on peptides and recombinant nucleosomes containing H3K14ac and H3K14ac analogs, respectively, that H3K14 acetylation is crucial for the 3TD mediated recruitment of SETDB1. We also observe this effect in cells where SETDB1 binding and activity is globally correlated with H3K14ac, and knockout of the H3K14 acetyltransferase HBO1 causes a drastic reduction in H3K9me3 levels at SETDB1 dependent sites. Regions with DNA hypomethylation after SETDB1 knockout also show an enrichment in SETDB1-dependent H3K9me3 and H3K14ac. Further analyses revealed that 3TD is particularly important at specific target regions like L1M REs, where H3K9me3 cannot be efficiently reconstituted by the 3TD mutant of SETDB1. In summary, our data demonstrate that the H3K9me3 and H3K14ac are not antagonistic marks but rather the presence of H3K14ac is required for SETDB1 recruitment via 3TD binding to H3K9me1/2/3-K14ac regionsand establishment of H3K9me3.

Characteristics of deep-sea microbial cellulases: key determinants of the ultimate fate of plant biomass on Earth

Land plants, especially those with significant woody biomass, represent the largest source of biomass on Earth, making the biodegradation of lignocellulosic materials critical to understanding the global carbon cycle. Cellulose, a major component of lignocellulose, is notoriously resistant to degradation due to its highly crystalline structure. While the degradation of cellulose by terrestrial microbes has been extensively studied, the mechanisms of cellulose degradation in deep-sea environments remain largely unexplored. The deep-sea ecosystem depends on organic matter, such as cellulose, that is synthesized in terrestrial environments and surface waters and descends to the deep sea. Recent studies suggest that a significant amount of cellulose is likely to reach the deep sea. Here, we present an in-depth study of cellulases from a novel deep-sea γ-proteobacterial strain TOYAMA8, isolated from Toyama Bay, Japan, using Surface Pitting Observation Technology (SPOT), a highly sensitive assay for enzymatic cellulose hydrolysis. The cellulases of strain TOYAMA8 show similarities to those of a previously reported deep-sea cellulolytic microbe, Marinagarivorans cellulosilyticus strain GE09. Genomic and transcriptomic analyses of these strains reveal novel cellulase genes and mechanisms that differ from terrestrial counterparts, shedding light on the unique adaptations of deep-sea microbes to recalcitrant biomass. In particular, these strains produce high-molecular-weight cellulases with unique domain architectures, likely optimized for membrane anchoring, which prevents enzyme diffusion and ensures efficient localized activity. Our findings provide critical insights into the microbial cellulose degradation in the deep sea, highlighting its role in the fate of organic carbon and the potential for biotechnological applications in biorefineries.

The biosynthesis of the odorant 2-methylisoborneol is compartmentalized inside a protein shell

Terpenoids are the largest class of natural products, found across all domains of life. One of the most abundant bacterial terpenoids is the volatile odorant 2-methylisoborneol (2-MIB), partially responsible for the earthy smell of soil and musty taste of contaminated water. Many bacterial 2-MIB biosynthetic gene clusters were thought to encode a conserved transcription factor, named EshA in the model soil bacterium Streptomyces griseus. Here, we revise the function of EshA, now referred to as Sg Enc, and show that it is a Family 2B encapsulin shell protein. Using cryo-electron microscopy, we find that Sg Enc forms an icosahedral protein shell and encapsulates 2-methylisoborneol synthase (2-MIBS) as a cargo protein. Sg Enc contains a cyclic adenosine monophosphate (cAMP) binding domain (CBD)-fold insertion and a unique metal-binding domain, both displayed on the shell exterior. We show that Sg Enc CBDs do not bind cAMP. We find that 2-MIBS cargo loading is mediated by an N-terminal disordered cargo-loading domain and that 2-MIBS activity and Sg Enc shell structure are not modulated by cAMP. Our work redefines the function of EshA and establishes Family 2B encapsulins as cargo-loaded protein nanocompartments involved in secondary metabolite biosynthesis.

The Ashkenazi-Centric G334R Variant of TP53 is Severely Impaired for Transactivation but Retains Tumor Suppressor Function in a Mouse Model.

Mutations in the TP53 tumor suppressor gene are the most abundant genetic occurrences in cancer. Some of these mutations lead to loss of function of p53 protein, some are gain of function, and some variants are hypomorphic (partially functional). Currently, there is no clinical distinction between different p53 mutations and cancer therapy or prognosis. Mutations in the oligomerization domain of p53 appear to be quite distinct in function, compared to mutations in the DNA binding domain. Here we show that, like other p53 oligomerization domain mutants, the Ashkenazi-specific G334R mutant accumulates to very high levels in cells and is significantly impaired for the transactivation of canonical p53 target genes. Surprisingly, we find that this mutant retains the ability to bind to consensus p53 target sites. A mouse model reveals that mice containing the G334R variant show increased predisposition to cancer, but only a fraction of these mice develop late-onset cancer. We show that the G334R variant retains the ability to interact with the SP1 transcription factor and contributes to the transactivation of joint SP1-p53 target genes. The combined evidence indicates that G334R is a unique oligomerization domain mutant that retains some tumor suppressor function.

Comprehensive Profiling of Roquin Binding Preferences for RNA Stem-Loops.

The cellular levels of mRNAs are controlled post-transcriptionally by cis-regulatory elements located in the 3'-untranslated region. These linear or structured elements are recognized by RNA-binding proteins (RBPs) to modulate mRNA stability. The Roquin-1 and -2 proteins specifically recognize RNA stem-loop motifs, the trinucleotide loop-containing constitutive decay elements (CDEs) and the hexanucleotide loop-containing alternative decay elements (ADEs), with their unique ROQ domain to initiate mRNA degradation. However, the RNA-binding capacity of Roquin towards different classes of stem-loops has not been rigorously characterized, leaving its exact binding preferences unclear. Here, we map the RNA-binding preference of the ROQ domain at nucleotide resolution introducing sRBNS (structured RNA Bind-n-Seq), a customized RBNS workflow with pre-structured RNA libraries. We found a clear preference of Roquin towards specific loop sizes and extended the consensus motifs for CDEs and ADEs. The newly identified motifs are recognized with nanomolar affinity through the canonical RNA-ROQ interface. Using these new stem-loop variants as blueprints, we predicted novel Roquin target mRNAs and verified the expanded target space in cells. The study demonstrates the power of high-throughput assays including RNA structure formation for the systematic investigation of (structural) RNA-binding preferences to comprehensively identify mRNA targets and elucidate the biological function of RBPs.

Detaillierte Analyse der Bindepräferenz von Roquin an RNA‐Stammschleifen

AbstractDie Konzentration von mRNAs in der Zelle wird posttranskriptionell durch cis‐regulierende Elemente in der 3’‐untranslatierten Region gesteuert. Diese linearen oder strukturierten Elemente werden von RNA‐bindenden Proteinen (RBPs) erkannt, um die mRNA‐Stabilität zu kontrollieren. Die Proteine Roquin‐1 und −2 erkennen spezifisch RNA‐Stammschleifenmotive. Mit ihrer einzigartigen ROQ‐Domäne erkennen sie Trinukleotid‐Schleifen enthaltende konstitutive Degradationselemente (engl. constitutive decay elements, CDEs) und Hexanukleotid‐Schleifen enthaltende alternative Degradationselemente (engl. alternative decay elements, ADEs), um den mRNA‐Abbau zu initiieren. Die RNA‐Bindekapazität von Roquin gegenüber verschiedenen Klassen von Stammschleifen ist bis jetzt nicht genau charakterisiert, so dass die genauen Bindepräferenzen unklar sind. Hier katalogisieren wir die RNA‐Bindepräferenz der ROQ‐Domäne auf Nukleotidebene mit sRBNS (engl. structured RNA Bind‐n‐Seq), einem neuartigen und angepassten RBNS Protokoll mit strukturierten RNA‐Bibliotheken. Dadurch konnte eine klare Präferenz von Roquin für bestimmte Schleifengrößen festgestellt werden und die bekannten Konsensusmotive für CDEs und ADEs erweitert werden. Die neu identifizierten Motive werden mit nanomolarer Affinität über die bekannte RNA‐ROQ‐Bindung erkannt. Unter Verwendung dieser neuen Stammschleifenvarianten als Blaupausen haben wir neue Ziel‐mRNAs von Roquin vorhergesagt und den erweiterten Targetraum in Zellen verifiziert. Diese Studie demonstriert die Leistungsfähigkeit von Hochdurchsatzverfahren mit RNA‐Strukturen für die systematische Untersuchung von (strukturellen) RNA‐Bindepräferenzen zur detaillierten Identifizierung von mRNA‐Targets und zur Aufklärung der biologischen Funktion von RBPs.

Structural Studies on Mycobacterial NudC Reveal a Class of Zinc Independent NADH Pyrophosphatase

Non-tuberculous mycobacteria (NTM) have emerged as an increasing threat to public health, due to the extreme antibiotic resistance. NADH pyrophosphatase (NudC) was proposed involving in mycobacterial resistance to the first line anti-tubercular drug isoniazid (INH) or its analog ethionamide (ETH), by hydrolyzing their NAD modified active forms (NAD-INH and NAD-ETH). In this study, we performed enzymatic and structural studies on NudC from M. abscessus (NudCMab), which is highly resistant to isoniazid and emerging as the most worrisome NTM. We determined the crystal structures of NudCMab in apo form, substrate NAD-bound form and product AMP-bound form. We observed the mode for the Nudix motif of NudCMab capturing the pyrophosphate group of NAD mediated by three divalent cation ions, which provides details for understanding the mechanism on NudC hydrolyzing NAD(H) or NAD-capped substrate. Interestingly, our structures revealed a novel subclass NudC from mycobacteria characterized by a unique arginine residue on the conserved QPWPFPxS motif, as well as a unique tower domain that replaces a well-defined zinc-binding motif in E.coli NudC and catalytic domain of mammalian Nudt12. Thus, our structural studies on NudCMab not only present a class of zinc independent NADH pyrophosphatase in mycobacteria, but also may facilitate the design of NudC inhibitors for the treatment of mycobacteria infections in combination with INH or ETH.

Domain architecture of the Mycobacterium tuberculosis MabR (Rv2242), a member of the PucR transcription factor family

MabR (Rv2242), a PucR-type transcription factor, plays a crucial role in regulating mycolic acid biosynthesis in Mycobacterium tuberculosis. To understand its regulatory mechanisms, we determined the crystal structures of its N-terminal and C-terminal domains. The N-terminal domain adopts a globin-like fold, while the C-terminal domain comprises an α/β GGDEF domain and an all-α effector domain with a helix-turn-helix DNA-binding motif. This unique domain combination is specific to Actinomycetes. Biochemical and computational studies suggest that full-length MabR forms both dimeric and tetrameric assemblies in solution. Structural analysis revealed two distinct dimerization interfaces within the N- and C-terminal domains, further supporting a tetrameric organization. These findings provide valuable insights into the domain architecture, oligomeric state, and potential regulatory mechanisms of MabR.

Substrate binding and catalytic mechanism of UDP-α-D-galactofuranose: β-galactofuranoside β-(1→5)-galactofuranosyltransferase GfsA.

UDP-α-D-galactofuranose (UDP-Galf): β-galactofuranoside β-(1→5)-galactofuranosyltransferase, known as GfsA, is essential in synthesizing β-(1→5)-galactofuranosyl oligosaccharides that are incorporated into the cell wall of pathogenic fungi. This study analyzed the structure and function of GfsA from Aspergillus fumigatus. To provide crucial insights into the catalytic mechanism and substrate recognition, the complex structure was elucidated with manganese (Mn2+), a donor substrate product (UDP), and an acceptor sugar molecule (β-galactofuranose). In addition to the typical GT-A fold domain, GfsA has a unique domain formed by the N and C termini. The former interacts with the GT-A of another GfsA, forming a dimer. The active center that contains Mn2+, UDP, and galactofuranose forms a groove structure that is highly conserved in the GfsA of Pezizomycotina fungi. Enzymatic assays using site-directed mutants were conducted to determine the roles of specific active-site residues in the enzymatic activity of GfsA. The predicted enzyme-substrate complex model containing UDP-Galf characterized a specific β-galactofuranosyltransfer mechanism to the 5'-OH of β-galactofuranose. Overall, the structure of GfsA in pathogenic fungi provides insights into the complex glycan biosynthetic processes of fungal pathogenesis and may inform the development of novel antifungal therapies.

Exploring Double Composed Partial Metric Spaces: A Novel Approach to Fixed Point Theorems

This paper innovatively extends partial metric spaces to introduce double composed partial metric space (DCPMS). Unlike traditional metrics, DCPMS replaces the triangle inequality with a nuanced form, integrating control functions into the metric. Building upon Ayoob et al.’s work, this novel generalization focuses on establishing fixed point theorems for DCPMS, contributing to the evolving landscape of mathematical analysis in this unique domain.

The centralizer of a locally nilpotent R-derivation of the polynomial R-algebra in two variables

Let R be an integral domain containing Q and ξ be an irreducible nontrivial locally nilpotent R-derivation of the polynomial R-algebra A in two variables. In this paper we investigate the group AutR(A,ξ) of R-automorphisms of A which commute with ξ. In the case R is a unique factorization domain and the plinth ideal of ξ is principal we give a complete description of the subgroup SAutR(A,ξ) of AutR(A,ξ) consisting of Jacobian one automorphisms. If moreover R contains a field K such that the group of units of R is K⋆ we prove that AutR(A,ξ)=SAutR(A,ξ).

Structural and functional insights from the sequences and complex domain architecture of adhesin-like proteins from Methanobrevibacter smithii and Methanosphaera stadtmanae.

Methanogenic archaea, or methanogens, are crucial in guts and rumens, consuming hydrogen, carbon dioxide, and other fermentation products. While their molecular interactions with other microorganisms are not fully understood, genomic sequences provide information. The first genome sequences of human gut methanogens, Methanosphaera stadtmanae and Methanobrevibacter smithii, revealed genes encoding adhesin-like proteins (ALPs). These proteins were also found in other gut and rumen methanogens, but their characteristics and functions remain largely unknown. This study analyzes the ALP repertoire of M. stadtmanae and M. smithii using AI-guided protein structure predictions of unique ALP domains. Both genomes encode more than 40 ALPs each, comprising over 10% of their genomes. ALPs contain repetitive sequences, many of which are unmatched in protein domain databases. We present unique sequence signatures of conserved ABD repeats in ALPs and propose a classification based on domain architecture. Our study offers insights into ALP features and how methanogens may interact with other microorganisms.

Pan-cancer and single-cell analysis reveal dual roles of lymphocyte activation gene-3 (LAG3) in cancer immunity and prognosis

Lymphocyte activating gene-3 (LAG3) is a distinctive T cell co-receptor that is expressed on the surface of lymphocytes. It plays a special inhibitory immune checkpoint role due to its unique domain and signaling pattern. Our aim is to explore the correlation between LAG3 in cancers and physiological processes related to a range of cancers, as well as build LAG3-related immunity and prognostic models. By comprehensively using of datasets and methods from TCGA, GTE-x and GEO databases, cBioPortal, HPA, Kaplan-Meier Plotter, Spearman, CellMinerTM, we delved deeper into the potential impact of the LAG3 in cancer development. These include expression differences, Localization of tumor cell subsets, immune infiltration, matrix infiltration, gene mutations, DNA methylation, signaling pathways and prognosis. Furthermore, we explored LAG3 interactions with different drugs. LAG3 is highly expressed in ACC (p < 0.001), BRCA (p < 0.001), DLBC (p < 0.001), ESCA (p < 0.001), GBM (p < 0.001), HNSC (p < 0.001), KIRC (p < 0.001), LGG (p < 0.001), LUAD (p < 0.01), LUSC (p < 0.001), PAAD (p < 0.001), PCPG (p < 0.01), SKCM (p < 0.001), STAD (p < 0.001), TGCT (p < 0.001) and THCA (p < 0.05), while lowly expressed in COAD (p < 0.001), LIHC (p < 0.05), OV (p < 0.001), PRAD (p < 0.001), READ (p < 0.001), UCEC (p < 0.001) and UCS (p < 0.001). High expression of LAG3 correlates with longer overall survival (OS) in BLCA (HR = 0.67, p < 0.05), CESC (HR = 0.3, p < 0.001), HNSC (HR = 0.67, p < 0.01), LUSC (HR = 0.71, p < 0.05), OV (HR = 0.65, p < 0.01), STAD (HR = 0.68, p < 0.05), and UCEC (HR = 0.57, p < 0.01). Conversely, in KIRC (HR = 1.85, p < 0.001), KIRP (HR = 2.81, p < 0.001), and THYM (HR = 8.92, p < 0.001), high LAG3 expression corresponds to shorter OS. Comprehensive results for recurrence-free survival (RFS) indicate that LAG3 acts as a protective factor in BLCA, CESC, OV, and UCEC. Moreover, LAG3 is widely expressed in tumor-associated lymphocytes, positively correlating with tumor immune scores and stromal scores, and significantly present in the C2 immune subtype across various tumors. High LAG3 expression correlates with increased immune infiltration. LAG3 shows associations with MSI, TMB, and the MMR system, participating in multiple signaling pathways including the T cell receptor pathway. It also demonstrates positive correlations with sensitivity to eleven different drugs. Unlike traditional inhibitory immune checkpoints, LAG3 exhibits dual roles in clinical and immune prognostication across pan-cancers, making it a significant predictive factor. In some cancers, LAG3 serves as a risk factor, indicating adverse clinical outcomes. Conversely, in BLCA, CESC, OV, and UCEC, LAG3 acts as a protective factor associated with longer patient survival. LAG3 demonstrates strong associations within tumor immunity, participating in a range of immune and inflammatory signaling pathways. Elevated levels of LAG3 are linked not only to T cell exhaustion but also to increased immune infiltration and polarization towards M1 macrophages.

Mechanism and regulation of kinesin motors.

Kinesins are a diverse superfamily of microtubule-based motors that perform fundamental roles in intracellular transport, cytoskeletal dynamics and cell division. These motors share a characteristic motor domain that powers unidirectional motility and force generation along microtubules, and they possess unique tail domains that recruit accessory proteins and facilitate oligomerization, regulation and cargo recognition. The location, direction and timing of kinesin-driven processes are tightly regulated by various cofactors, adaptors, microtubule tracks and microtubule-associated proteins. This Review focuses on recent structural and functional studies that reveal how members of the kinesin superfamily use the energy of ATP hydrolysis to transport cargoes, depolymerize microtubules and regulate microtubule dynamics. I also survey how accessory proteins and post-translational modifications regulate the autoinhibition, cargo binding and motility of some of the best-studied kinesins. Despite much progress, the mechanism and regulation of kinesins are still emerging, and unresolved questions can now be tackled using newly developed approaches in biophysics and structural biology.

Structural and functional insights into the T-even type bacteriophage topoisomerase II.

T-even type bacteriophages are virulent phages commonly used as model organisms, playing a crucial role in understanding various biological processes. One such process involves the regulation of DNA topology during phage replication upon host infection, governed by type IIA DNA topoisomerases. In spite of various studies on prokaryotic and eukaryotic counterparts, viral topoisomerase II remains insufficiently understood, especially the unique domain composition of T4 phage. In this study, we determine the cryo-EM structures of topoisomerase II from T4 and T6 phages, including full-length structures of both apo and DNA-binding states which have never been determined before. Together with other conformational states, these structures provide an explicit blueprint of mechanisms of phage topoisomerase II. Particularly, the asymmetric dimeric interactions observed in cryo-EM structures of T6 phage topoisomerase II ATPase domain and central domain bound with DNA shed light on the asynchronous ATP usage and asynchronous cleavage of the G-segment DNA, respectively. The elucidation of phage topoisomerase II's structures and functions not only enhances our understanding of mechanisms and evolutionary parallels with prokaryotic and eukaryotic homologs but also highlights its potential as a model for developing type IIA topoisomerase inhibitors.

Adoption and Continuance in the Metaverse

The burgeoning metaverse market, encompassing virtual and augmented reality, gaming, and manufacturing processes, presents a unique domain for studying user behavior. This study delineates a research framework to investigate the antecedents of behavioral intention, bifurcating users into inexperienced and experienced cohorts. Utilizing a cross-sectional survey, empirical data were amassed and analyzed using structural equation modeling, encompassing 372 responses from 131 inexperienced and 241 experienced users. For inexperienced users, the analysis underscored the significant impact of perceived usefulness on both satisfaction and adoption intention, while perceived enjoyment was found to bolster only satisfaction. Innovativeness and satisfaction do not drive adoption intention. Conversely, for experienced users, satisfaction was significantly influenced by perceived ease of use, perceived usefulness, and perceived enjoyment. Continuance intention was positively affected by perceived usefulness, perceived enjoyment, trust, innovativeness, and satisfaction. This research extends valuable insights for both theoretical advancements and practical implementations in the burgeoning metaverse landscape.