Search Results (341)

This paper explores novel inequalities for statistical submanifolds within the framework of the Norden golden-like statistical manifold. By leveraging the intrinsic properties of statistical manifolds and the structural richness of Norden golden geometry, we establish fundamental relationships between the intrinsic and extrinsic invariants of submanifolds. The methodology involves deriving generalized Chen-type and $\delta (2,2)$ curvature inequalities using curvature tensor analysis and dual affine connections. A concrete example is provided to verify the theoretical framework. The novelty of this work lies in extending classical curvature inequalities to a newly introduced statistical structure, thereby opening new perspectives in the study of geometric inequalities in information geometry and related mathematical physics contexts. Full article

Large-conductance, voltage- and calcium-activated potassium (BK) channels are crucial regulators of cellular excitability, influenced by various signaling molecules, including heme. The BK channel contains a heme-sensitive motif located at the sequence ⁶¹²CKACH⁶¹⁶, which is a conserved heme regulatory motif (HRM) found in the cytochrome c protein family. This motif is situated within a linker region of approximately 120 residues that connect the RCK1 and RCK2 domains, and it also includes terminal α-helices similar to those found in cytochrome c family proteins. However, much of this region has yet to be structurally defined. We conducted a sequence alignment of the BK linker region with mitochondrial cytochrome c and cytochrome c domains from various hemoproteins to better understand this functionally significant region. In addition to the HRM motif, we discovered that important structural and functional elements of cytochrome c proteins are conserved in the BK RCK1-RCK2 linker. Firstly, the part of the BK region that is resolved in available atomic structures shows similarities in secondary structural elements with cytochrome c domain proteins. Secondly, the Met80 residue in cytochrome c domains, which acts as the second axial ligand to the heme iron, aligns with the BK channel. Beyond its role in electron shuttling, cytochrome c domains exhibit various catalytic properties, including peroxidase activity—specifically, the oxidation of suitable substrates using peroxides. Our findings reveal that the linker region endows human BK channels with peroxidase activity, showing an apparent H₂O₂ affinity approximately 40-fold greater than that of mitochondrial cytochrome c under baseline conditions. This peroxidase activity was reduced when substitutions were made at ⁶¹²CKACH⁶¹⁶ and other relevant sites. These results indicate that the BK channel possesses a novel module similar to the cytochrome c domains of hemoproteins, which may give rise to unique physiological functions for these widespread ion channels. Full article

This research was designed to explore science-fiction and fantasy (SFF) posters, specifically those related to films and television shows, from the perspective of their owners, examining their potential as sources of social and cultural significance and meaning. The research explored these in terms of the content of the poster, placement, media texts they reference, morals, behavior, identity, sense of self, well-being and self-expression. Data collection took place between 2020 and 2022 via an online survey (N = 273) and follow-up semi-structured interviews (N = 28) with adult science-fiction and fantasy film and television show poster owners. The significance and meaning of SFF posters were framed by two conceptual models: ‘The Three Significances’—esthetics, functionality, and significance (both spatial and personal)—and ‘The Big Three’—content, design, and color. Among these, content held the greatest significance for owners. Posters served as tools for self-expression, reflecting their owners’ identities, affinities, and convictions, while also reinforcing their connection to the media they reference. Posters helped to reinforce a sense of self and fan identity and evoke emotional responses, and the space in which they were displayed helped shape their meaning and significance. The paper sets out some suggestions for future research in this important topic. Full article

Lycopene exhibits a broad spectrum of biological activities with potential therapeutic applications. Despite its established antioxidant and anti-inflammatory properties, the molecular basis for its pharmacological actions remains incompletely defined. Here we investigated the molecular targets, pharmacodynamic feasibility, and tissue-specific expression of lycopene targets using a computational pharmacology approach combined with affinity and protein–protein interaction (PPI) analyses. Lycopene-associated human protein targets were predicted using a Swiss target screening platform. Molecular docking was used to estimate binding affinities, and concentration-affinity (CA) ratios were calculated based on physiologically relevant plasma concentrations (75–210 nM). PPI networks of lycopene targets were constructed to identify highly connected targets, and tissue expression analysis was assessed for high-affinity targets using protein-level data from the Human Protein Atlas database. Of the 94 predicted targets, 37% were nuclear receptors and 18% were Family A G Protein Coupled Receptors (GPCRs). Among the top 15 high-affinity targets, nuclear receptors and GPCRs comprised 40% and 26.7%, respectively. Twenty targets had affinities < 10 μM, with six key targets (MAP2K2, SCN2A, SLC6A5, SCN3A, TOP2A, and TRIM24) showing submicromolar binding. CA ratio analysis identified MAP2K2, SCN2A, and SLC6A5 as pharmacodynamically feasible targets (CA > 1). PPI analysis revealed 32 targets with high interaction and 9 with significant network connectivity. Seven targets (TRIM24, GRIN1, NTRK1, FGFR1, NTRK3, CHRNB4, and PIK3CD) showed both high affinity and centrality in the interaction network. The expression profiling of submicromolar targets revealed widespread tissue distribution for MAP2K2 and SCN3A, while SCN2A, TOP2A, and TRIM24 showed more restricted expression patterns. This integrative analysis identifies a subset of lycopene targets with both high affinity and pharmacological feasibility, particularly MAP2K2, SCN2A, and TRIM24. Lycopene appears to exert its biological effects through modulation of interconnected signalling networks involving nuclear receptors, GPCRs, and ion channels. These findings support the potential of lycopene as a multi-target therapeutic agent and provide a rationale for future experimental and clinical validation. Full article

Enzymes, as nature’s precision biocatalysts, hold transformative potential across industrial, environmental, and biomedical sectors. However, their instability, solvent sensitivity, and limited reusability in their free form necessitate advanced immobilization strategies to enhance their robustness and scalability. This review critically examines cutting-edge advancements in enzyme immobilization, focusing on the integration of artificial intelligence (AI), novel nanomaterials, and dynamic carrier systems to overcome the traditional limitations of mass transfer, enzyme leakage, and cost inefficiency. Key innovations such as metal–organic frameworks (MOFs), magnetic nanoparticles, self-healing hydrogels, and 3D-printed scaffolds are highlighted for their ability to optimize enzyme orientation, stability, and catalytic efficiency under extreme conditions. Moreover, AI-driven predictive modeling and machine learning emerge as pivotal tools for rationalizing nanomaterial synthesis, multi-enzyme cascade design, and toxicity assessment, while microfluidic systems enable precise biocatalyst fabrication. This review also explores emerging carrier-free strategies, including cross-linked enzyme aggregates (CLEAs) and DNA-directed immobilization, which minimize diffusion barriers and enhance substrate affinity. Despite progress, challenges persist in regards to eco-friendly nanomaterial production, industrial scalability, and real-world application viability. Future directions emphasize sustainable hybrid material design, AI-aided lifecycle assessments, and interdisciplinary synergies between synthetic biology, nanotechnology, and data analytics. By connecting laboratory innovation with industrial needs, this work provides a forward-thinking framework to harness immobilized enzymes for achieving global sustainability goals, particularly in bioremediation, bioenergy, and precision medicine. Full article

Advanced prostate cancer (PCa) remains lethal despite standard therapies, and immune checkpoint inhibitors offer limited benefit in its “immune-cold” microenvironment. T-cell engagers (TCEs)—bispecific antibodies linking CD3 on T-cells to tumor-associated antigens (TAAs)—provide potent, MHC-independent cytotoxicity, overcoming a key resistance mechanism. While early PSMA-targeted TCEs established proof-of-concept, recent data, notably for six transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeting agents like Xaluritamig, demonstrate more substantial objective responses, highlighting progress through improved target selection and molecular design. This review synthesizes the evolving landscape of TCEs targeting PSMA, STEAP1, and DLL3 in PCa. We critically evaluate emerging clinical evidence, arguing that realizing the significant therapeutic potential of TCEs requires overcoming key challenges, including cytokine release syndrome (CRS), limited response durability, and antigen escape. We contend that future success hinges on sophisticated engineering strategies (e.g., affinity tuning, masking, multispecific constructs) and rationally designed combination therapies tailored to disease-specific hurdles. Strategies for toxicity mitigation, the crucial role of biomarker-driven patient selection, and potential integration with existing treatments are also discussed. Accumulating evidence supports TCEs becoming a new therapeutic pillar for advanced PCa, but achieving this demands sustained innovation focused on optimizing efficacy and safety. This review critically connects molecular engineering advancements with clinical realities and future imperatives. Full article

Giant clams are ecologically important coral reef animals, with many species facing imminent local extinction. While many regions have undertaken recent assessments of their biodiversity assets, persistent gaps remain even in otherwise well-surveyed areas. This study sought to understand the geographic distribution of smaller-bodied and morphologically similar giant clams, specifically Tridacna maxima and T. noae, in the eastern Indian Ocean. Due to the difficulties in reliably identifying these species using morphological characters, we confirmed species identity and investigated intraspecific variation using sequence data from the mitochondrial cytochrome C oxidase subunit I gene (COI). Seventy whole animal vouchers were newly sampled from a 1500 km span of remote northwestern Australian coastline over a decade, as part of an ongoing coral reef survey expedition of the Western Australian Museum and partners. Tridacna maxima had a limited distribution and was only genotyped from offshore oceanic reefs in the Rowley Shoals and Cocos Keeling Islands. In contrast, T. noae was well established beyond Ningaloo Reef, and was abundant at inshore sites throughout the Pilbara and Kimberley, and even offshore to Ashmore Reef. Phylogeographically, T. maxima did not group with conspecifics from the Western Pacific Ocean, including the east coast of Australia, but instead clustered with individuals from Malaysia, China, Taiwan, and Indonesia; T. noae exhibited a similar pattern. The affinity of Western Australian individuals with representatives from the Indo-Malay region and not eastern Australia will be an important consideration for these commercially important species. Novel haplotypes in both tested species occur in Western Australia. Continued sampling of eastern and central Indian Ocean giant clams, especially to continue to document the range of T. noae, is encouraged to understand connectivity in this basin. Together, these findings contribute to an improved baseline for conservation initiatives of these iconic coral reef animals in Western Australia. Full article

The accurate segmentation of small target buildings in high-resolution remote sensing images remains challenging due to two critical issues: (1) small target buildings often occupy few pixels in complex backgrounds, leading to frequent background confusion, and (2) significant intra-class variance complicates feature representation compared to conventional semantic segmentation tasks. To address these challenges, we propose a novel Multi-Scale Feature Fusion and Foreground Perception Enhancement Network (MFFP-Net). This framework introduces three key innovations: (1) a Multi-Scale Feature Fusion (MFF) module that hierarchically aggregates shallow features through cross-level connections to enhance fine-grained detail preservation, (2) a Foreground Perception Enhancement (FPE) module that establishes pixel-wise affinity relationships within foreground regions to mitigate intra-class variance effects, and (3) a Dual-Path Attention (DPA) mechanism combining parallel global and local attention pathways to jointly capture structural details and long-range contextual dependencies. Experimental results demonstrate that the IoU of the proposed method achieves improvements of 0.44%, 0.98% and 0.61% compared to mainstream state-of-the-art methods on the WHU Building, Massachusetts Building, and Inria Aerial Image Labeling datasets, respectively, validating its effectiveness in handling small targets and intra-class variance while maintaining robustness in complex scenarios. Full article

Causal discovery involves searching intractably large spaces. Decomposing the search space into classes of observationally equivalent causal models is a well-studied avenue to making discovery tractable. This paper studies the topological structure underlying causal equivalence to develop a categorical formulation of Chickering’s transformational characterization of Bayesian networks. A homotopic generalization of the Meek–Chickering theorem on the connectivity structure within causal equivalence classes and a topological representation of Greedy Equivalence Search (GES) that moves from one equivalence class of models to the next are described. Specifically, this work defines causal models as propable symmetric monoidal categories (cPROPs), which define a functor category ${\mathcal{C}}^P$ from a coalgebraic PROP P to a symmetric monoidal category $\mathcal{C}$. Such functor categories were first studied by Fox, who showed that they define the right adjoint of the inclusion of Cartesian categories in the larger category of all symmetric monoidal categories. cPROPs are an algebraic theory in the sense of Lawvere. cPROPs are related to previous categorical causal models, such as Markov categories and affine CDU categories, which can be viewed as defined by cPROP maps specifying the semantics of comonoidal structures corresponding to the “copy-delete” mechanisms. This work characterizes Pearl’s structural causal models (SCMs) in terms of Cartesian cPROPs, where the morphisms that define the endogenous variables are purely deterministic. A higher algebraic K-theory of causality is developed by studying the classifying spaces of observationally equivalent causal cPROP models by constructing their simplicial realization through the nerve functor. It is shown that Meek–Chickering causal DAG equivalence generalizes to induce a homotopic equivalence across observationally equivalent cPROP functors. A homotopic generalization of the Meek–Chickering theorem is presented, where covered edge reversals connecting equivalent DAGs induce natural transformations between homotopically equivalent cPROP functors and correspond to an equivalence structure on the corresponding string diagrams. The Grothendieck group completion of cPROP causal models is defined using the Grayson–Quillen construction and relate the classifying space of cPROP causal equivalence classes to classifying spaces of an induced groupoid. A real-world domain modeling genetic mutations in cancer is used to illustrate the framework in this paper. Full article

Background: The increasing global incidence of breast cancer calls for the identification of new therapeutic targets and the assessment of possible neem-derived inhibitors by means of computational modeling and integrated genomic research. Methods: Originally looking at 59,424 genes throughout 42 samples, we investigated gene expression data from The Cancer Genome Atlas—Breast Cancer (TCGA-BRCA) dataset. We chose 286 genes for thorough investigation following strict screening for consistent expression. R’s limma package was used in differential expression analysis. The leading candidate’s protein modeling was done with Swiss-ADME and Discovery Studio. Molecular docking studies, including 132 neem compounds, were conducted utilizing AutoDock Vina. Results: Among the 286 examined, mitochondrially encoded cytochrome C oxidase III (MT—CO3) turned out to be the most greatly overexpressed gene, showing consistent elevation across all breast cancer samples. Protein modeling revealed a substantial hydrophobic pocket (volume: 627.3 ų) inside the structure of MT—CO3. Docking investigations showed five interesting neem-derived inhibitors: 7-benzoylnimbocinol, nimolicinol, melianodiol, isonimocinolide, and stigmasterol. Strong binding affinities ranging from −9.2 to −11.5 kcal/mol and diverse interactions with MT—CO3, mostly involving the residues Phe214, Arg221, and Trp58, these molecules displayed. With hydrophobic interactions dominant across all chemicals, fragment contribution analysis revealed that scaffold percentage greatly influences binding effectiveness. Stigmasterol revealed greater drug-likeness (QED = 0.79) despite minimal interaction variety, while 7-benzoylnimbocinol presented the best-balanced physicochemical profile. Conclusion: Connecting traditional medicine with current genomics and computational biology, this work proposes a methodology for structure-guided drug design and development using neem-derived chemicals and finds MT—CO3 as a potential therapeutic target for breast cancer. Full article

Hyperspectral image (HSI) clustering has drawn more and more attention in recent years as it frees us from labor-intensive manual annotation. However, current works cannot fully enjoy the rich spatial and spectral information due to redundant spectral signatures and fixed anchor learning. Moreover, the learned graph always obtains suboptimal results due to the separate affinity estimation and graph symmetry. To address the above challenges, in this paper, we propose large-scale hyperspectral image-projected clustering via doubly stochastic graph learning (HPCDL). Our HPCDL is a unified framework that learns a projected space to capture useful spectral information, simultaneously learning a pixel–anchor graph and an anchor–anchor graph. The doubly stochastic constraints are conducted to learn an anchor–anchor graph with strict probabilistic affinity, directly providing anchor cluster indicators via connectivity. Meanwhile, when using label propagation, pixel-level clustering results are obtained. An efficient optimization strategy is proposed to solve our HPCDL model, requiring monomial linear complexity concerning the number of pixels. Therefore, our HPCDL has the ability to deal with large-scale HSI datasets. Experiments on three datasets demonstrate the superiority of our HPCDL for both clustering performance and the time burden. Full article

T-follicular helper (Tfh) cells, a specialized subset of CD4⁺ cells, are the immune mediators connecting cellular and humoral immunity, as they lead B-cell proliferation within germinal centers, and orchestrate their response, including activation, class switching, and production of a diverse array of high-affinity antibodies. Their interactions with B cells is regulated by a wide complex of transcriptional and cytokine-driven pathways. A major contribution of Tfh cells to autoimmune diseases is through their production of cytokines, particularly IL-21, which supports the proliferation and differentiation of autoreactive B cells. Elevated levels of circulating Tfh-like cells and IL-21 have been observed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) correlating strongly with disease severity and autoantibody levels. The feedback loop between Tfh cells and IL-21 or other signal pathways, such as Bcl-6, ICOS, and PD-1, not only sustains Tfh cell function but also drives the continuous expansion of autoreactive B cells, leading to chronic inflammation through the production of high-affinity pathogenic autoantibodies. By understanding these interactions, Tfh pathways may serve as potential therapeutic targets, with IL-21, ICOS, and PD1 blockades emerging as promising innovative therapeutic strategies to manage autoimmune diseases. Although a variety of studies have been conducted investigating the role of Tfh cells in SLE and RA, this review aims to reveal the gap in the literature regarding the role of such subpopulations in the pathogenesis of other autoimmune diseases, such as Anca-associated vasculitis (AAV), and express the need to conduct similar studies. Tfh cell-related biomarkers can be used to assess disease activity and transform autoimmune disease treatment, leading to more personalized and effective care for patients with chronic autoimmune conditions. Full article

The high proportion of distributed photovoltaics (PVs) connected to distribution substation areas causes complex operation of the medium- and low-voltage distribution network. New power electronic devices represented by soft open point (SOP) can achieve a flexible interconnection between distribution substation areas. In this paper, a cooperative operation optimization method for medium- and low-voltage distribution networks considering flexible interconnected distribution substation areas is proposed. Firstly, interval affine is used to model the resource aggregation and obtain the flexibility region constraints of distribution substation areas. Then, a multi-scale cooperative operation framework for medium- and low-voltage distribution networks is constructed. The medium-voltage distribution network adopts the centralized method to solve and issue operation strategy instructions. The distribution substation area generates a voltage-reactive power adaptive regulation curve and performs intra-day rolling control. Finally, the case studies show that the proposed method has efficient operation strategy of medium- and low-voltage distribution networks and can alleviate the voltage fluctuation caused by high integration of PVs. Full article

The middle–upper Eocene successions of northwest Fayum, Egypt, provide a crucial archive for reconstructing paleoenvironmental conditions and paleobiogeographical patterns of the southern Tethys realm. Stratigraphically, the investigated section is subdivided into three rock units: the Gehannam Formation (Bartonian-Priabonian), the Birket Qarun Formation, and the Qasr El Sagha Formation (Priabonian). A total of 101 benthic foraminiferal taxa, representing 31 genera, 23 families, 13 superfamilies, and four suborders, were identified. The middle–late Eocene age is primarily determined by the co-occurrence of index spinose planktonic foraminifera (Acarinina spp., Morozovelloides spp., and Globigerinatheka semiinvoluta) and benthic foraminiferal assemblages, further supported by the presence of the nannofossil marker Chiasmolithus oamaruensis. Four local benthic biozones are identified and correlated with coeval zones in nearby areas. Quantitative analyses of benthic foraminiferal individuals, diversity indices, ecological parameters, and the benthic foraminiferal oxygen index (BFOI) reveal distinct environmental shifts. The rock unit occupied by the late middle Eocene assemblages is diversified and dominated by calcareous infaunal taxa (e.g., Bolivina spp., Fursenkoina spp., and Nonionella spp.), indicative of low-oxygen outer neritic conditions associated with elevated organic influx. In contrast, the late Eocene Birket Qarun and Qasr El Sagha showed an increase in epifaunal forms and reduced diversity, suggesting a transition to dysoxic-oxic conditions. Paleobiogeographical analysis indicates a strong affinity with the Tethyan realm, with potential faunal exchange through the Trans-Saharan Seaway. These findings enhance our understanding of Paleogene marine connections between the Tethyan and Indo-Pacific realms, contributing to broader discussions on Eocene paleobiogeography and depositional dynamics in North Africa. Full article

This editorial presents 26 research articles published in the Special Issue entitled Differentiable Manifolds and Geometric Structures of the MDPI Mathematics journal, which covers a wide range of topics particularly from the geometry of (pseudo-)Riemannian manifolds and their submanifolds, providing some of the latest achievements in different areas of differential geometry, among which is counted: the geometry of differentiable manifolds with curvature restrictions such as Golden space forms, Sasakian space forms; diffeological and affine connection spaces; Weingarten and Delaunay surfaces; Chen-type inequalities for submanifolds; statistical submersions; manifolds endowed with different geometric structures (Sasakian, weak nearly Sasakian, weak nearly cosymplectic, LP-Kenmotsu, paraquaternionic); solitons (almost Ricci solitons, almost Ricci–Bourguignon solitons, gradient r-almost Newton–Ricci–Yamabe solitons, statistical solitons, solitons with semi-symmetric connections); vector fields (projective, conformal, Killing, 2-Killing) [...] Full article