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16 pages, 3191 KB  
Article
BBTV Nuclear Shuttle Protein Mediates Banana Ubiquitination Pathway Dysregulation
by Xiaoyan Feng, Muhammad Zeeshan Hyder, Rui Meng, Huixiang Yin, Shuli Xian, Jianhua Wang, Yinxue Li, Xuejun Li, Zhixin Liu and Naitong Yu
Plants 2026, 15(17), 2571; https://doi.org/10.3390/plants15172571 - 24 Aug 2026
Abstract
Banana bunchy top virus (BBTV) is a devastating pathogen threatening global banana production. The plant ubiquitin–proteasome system (UPS) governs immune signaling and is frequently subverted by invading viruses, yet the molecular mechanism through which BBTV interferes with host UPS remains unclear. Here, we [...] Read more.
Banana bunchy top virus (BBTV) is a devastating pathogen threatening global banana production. The plant ubiquitin–proteasome system (UPS) governs immune signaling and is frequently subverted by invading viruses, yet the molecular mechanism through which BBTV interferes with host UPS remains unclear. Here, we show that BBTV nuclear shuttle protein (NSP) serves as the core viral effector to disrupt banana ubiquitination homeostasis. RT-qPCR time-series assays confirmed that BBTV infection dynamically remodels the transcription of eight phylogenetically divergent RING-type E3 ubiquitin ligases: four subfamily I E3-SIS3 paralogs and E3-HIP1 are significantly upregulated at 14 dpi and 21 dpi, while E3-BOI and E3-RHA1B are suppressed at 21 dpi. Transient expression screening of all six BBTV-encoded proteins verified that only NSP reproduces the UPS perturbation signature triggered by viral infection. Cross-species sequence alignment identified an evolutionarily conserved FNGSF motif within NSP orthologs of all Nanoviridae members. Alanine substitution mutagenesis (NSPAAAAA) completely abolished NSP’s capacity to alter E3 ligase transcription. Western blot assays further validated that wild-type NSP induces massive accumulation of ubiquitinated host proteins, whereas the FNGSF-deficient mutant does not disrupt cellular ubiquitination. Phylogenetic analysis revealed that NSP-targeted E3 ligases share low overall sequence similarity but retain conserved catalytic RING domains, indicating that NSP exerts broad-spectrum regulatory effects on host UPS via the FNGSF motif. Collectively, this study reveals a novel pathogenic strategy whereby BBTV NSP recruits diverse host RING E3 ligases via its conserved FNGSF motif to dysregulate plant ubiquitination and elicit plant pathogenicity. Our findings provide two promising targets—the NSP FNGSF motif and defense-associated E3-SIS3 ligases—for developing antiviral agents and breeding BBTV-resistant banana germplasm. Full article
(This article belongs to the Special Issue Virus-Induced Diseases in Horticultural Plants)
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14 pages, 3093 KB  
Communication
Controlling pH-Dependent Nanozyme Activity by Metal Identity in Histidine-Based Nanoarchitectures
by Zsolt M. Horváth, Árpád Turcsányi, Edit Csapó and Ditta Ungor
Nanomaterials 2026, 16(17), 1052; https://doi.org/10.3390/nano16171052 - 24 Aug 2026
Abstract
In this paper, we report a metal-driven structural tuning strategy with the L-histidine (His) ligand to modulate peroxidase-like nanozyme performance. Although the His coordinates with gold(III) ions to form an extended helical coordination polymer, its interaction with Cu(II) ions results in quantum-confined, [...] Read more.
In this paper, we report a metal-driven structural tuning strategy with the L-histidine (His) ligand to modulate peroxidase-like nanozyme performance. Although the His coordinates with gold(III) ions to form an extended helical coordination polymer, its interaction with Cu(II) ions results in quantum-confined, ultrasmall nanoclusters. Based on the optical, structural, and surface analysis, the blue-emitting cores are stabilized by His ligands through imidazole nitrogen coordination, consistent with a Cu-centered coordination environment involved in the observed catalytic activity. According to the catalytic measurements, the His-Cu clusters outperformed the His-Au coordination polymer reference system. Steady-state kinetic modeling and 3D profiling revealed a pronounced shift in the pH optimum: low-valent Cu-containing His-Cu NCs enable efficient peroxide-dependent catalysis under nearly neutral conditions (pH 7.4), whereas His-Au CP exhibits its maximum activity under acidic conditions. Based on these findings, this work highlights nanoscale engineering for tailor-made biomimetic applications. Full article
(This article belongs to the Section Energy and Catalysis)
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19 pages, 6512 KB  
Article
Visible-Light-Driven Selective Oxidation of Toluene to Benzaldehyde over CeO2@NiFe-LDH Heterostructure
by Fang Fang, Dongping Sun and Xinhua Peng
Catalysts 2026, 16(9), 757; https://doi.org/10.3390/catal16090757 - 23 Aug 2026
Abstract
The transformation of toluene to benzaldehyde via green and sustainable routes is of great significance in the fine chemical industry. However, hard activation of benzylic C(sp3)-H bonds and facile overoxidation of the generated benzaldehyde collectively render the selective oxidation of toluene [...] Read more.
The transformation of toluene to benzaldehyde via green and sustainable routes is of great significance in the fine chemical industry. However, hard activation of benzylic C(sp3)-H bonds and facile overoxidation of the generated benzaldehyde collectively render the selective oxidation of toluene extremely challenging. In this study, we constructed a core–shell heterostructure photocatalyst, CeO2@NiFe-LDH, employing molecular oxygen as the oxidant. Under mild conditions of room temperature and visible-light illumination, the catalyst achieves a toluene conversion rate of 1.936 mmol·g−1·h−1 with an excellent benzaldehyde selectivity of 81.0%, and its catalytic performance is significantly superior to that of the individual single-phase materials and the simple physical mixture. Optical and electrochemical measurements confirm enhanced visible-light absorption and utilization, as well as greatly improved separation and migration efficiency of photogenerated charge carriers. Furthermore, the CeO2@NiFe-LDH heterostructure features staggered band alignment, promoting S-scheme charge transfer across the heterointerface, thereby substantially boosting the redox capacity of the composite catalyst. Consequently, the photogenerated carriers with high reactivity are fully engaged in catalytic reactions, enabling efficient carrier utilization and ultimately leading to a significantly enhanced photocatalytic performance. This study not only demonstrates the outstanding application potential of CeO2@NiFe-LDH for the visible-light-driven selective oxidation of toluene to benzaldehyde, but also offers a novel strategy for enhancing the photocatalytic performance of LDH-based materials. Full article
(This article belongs to the Section Catalysis for Sustainable Energy)
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54 pages, 875 KB  
Article
Industrial Intellectual Property Upgrading Reform, Inclusive Potential of Regional Innovation Ecosystems, and Low-Carbon Green Energy Eco-Co-Evolution—A Machine Learning-Based Causal Inference Analysis
by Yuzhi Wang and Cong Zhang
Sustainability 2026, 18(16), 8609; https://doi.org/10.3390/su18168609 - 21 Aug 2026
Viewed by 245
Abstract
The core predicament of energy transition lies not in the availability of clean technologies, but in whether an economy possesses the institutional capacity and social foundation to systematically regulate its carbon-energy metabolic processes. Drawing upon co-evolutionary theory from evolutionary economics, this paper constructs [...] Read more.
The core predicament of energy transition lies not in the availability of clean technologies, but in whether an economy possesses the institutional capacity and social foundation to systematically regulate its carbon-energy metabolic processes. Drawing upon co-evolutionary theory from evolutionary economics, this paper constructs a composite indicator of Low-Carbon Green Energy Eco-Co-evolution (LCEE) encompassing three functional dimensions: efficiency advancement, kinetic energy replacement, and boundary adherence. Concurrently, by integrating innovation ecosystem theory with inclusive development theory, we propose the concept of “Inclusive Potential of Regional Innovation Ecosystems” (IEP), characterizing the systemic potential for transforming innovation outcomes into social welfare across four dimensions: Knowledge Matrix Abundance (KMF), Cultural Capillary Permeation (CCP), Technological Community Succession (TCS), and Social Root Nourishment (SRN). Taking China’s 2016 intellectual property (IP) powerhouse construction pilot as the institutional prototype of Industrial Intellectual Property Upgrading Reform (IPR), we incorporate IPR, IEP, and LCEE into a unified causal analytical framework, proposing a testable transmission logic of ‘institutional supply → ecological development → co-evolutionary synergy. Using panel data from 30 Chinese provincial-level administrative regions over 2010–2022, we employ a Spatial Durbin Difference-in-Differences (SDM-DID) model to identify the direct and spatial spillover effects of IPR on LCEE, and embed a Double Machine Learning (DML) framework to test the mediating mechanism of IEP while controlling for high-dimensional nonlinear interference. The findings reveal that IPR exerts a significant and robust direct promoting effect on LCEE, generating positive spatial spillovers to neighboring regions through the public disclosure of patent information. IEP significantly promotes local LCEE, yet its spatial spillover lacks statistical support due to structural conflicts in inter-dimensional transmission attributes. IEP plays a significant partial mediating role between IPR and LCEE, with the indirect effect accounting for over one-third of the total effect, a finding robust to alternative machine learning algorithms, sample split adjustments, and exclusion of contemporaneous competing policies. Sub-path tests reveal that KMF bears the strongest mediating efficacy, serving as the primary transmission channel, while CCP exhibits full mediation—the institutional effect on LCEE in the cultural dimension depends almost entirely on the mediating transformation through the public cultural service system. Heterogeneity analysis further demonstrates full mediation in the Low-Carbon Green Energy Eco-Kinetic Replacement (KER) dimension, indicating that the institutional catalytic effect on clean energy substitution must be realized through IEP transformation. This paper provides empirical evidence for the proposed causal pathway through which institutional public goods indirectly enhance the synergistic quality of carbon-energy transition via the inclusive potential of innovation ecosystems, providing theoretical foundations and policy implications that, while grounded in China’s institutional context, may offer valuable reference points for emerging market economies facing similar dual pressures of technological constraints and green transition. Full article
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25 pages, 4786 KB  
Review
Recent Progress in the Synthesis, Design, and Electrochemical Applications of Porphyrin/Phthalocyanine-Based Metal–Covalent Organic Frameworks
by Peng Huang, Gaowei Xue, Chengfeng Jiang, Li Hu, Jiahui Yuan, Qiang Huang and Hongxing Jia
Nanomaterials 2026, 16(16), 1036; https://doi.org/10.3390/nano16161036 - 20 Aug 2026
Viewed by 256
Abstract
The limitations of conventional inorganic electrodes call for organic alternatives for advanced energy storage. Metal–covalent organic frameworks (MCOFs) integrate the metal active sites of metal–organic frameworks (MOFs) with the high chemical stability imparted by strong covalent bonds in covalent organic frameworks (COFs) while [...] Read more.
The limitations of conventional inorganic electrodes call for organic alternatives for advanced energy storage. Metal–covalent organic frameworks (MCOFs) integrate the metal active sites of metal–organic frameworks (MOFs) with the high chemical stability imparted by strong covalent bonds in covalent organic frameworks (COFs) while retaining the high specific surface area and tunable porosity of both material classes. Among these, MCOFs constructed from porphyrin and phthalocyanine building units have emerged as a research hotspot in electrochemical energy storage owing to their inherent 18π-conjugated macrocyclic electronic systems, well-defined M–N4 coordination sites, and potential bipolar charge storage characteristics. This review systematically summarizes recent advances in this class of materials. First, from the perspective of metal center introduction timing, three core synthetic strategies—pre-metallation, simultaneous metallation, and post-metallation—are categorized and evaluated in terms of coordination precision, synthetic efficiency, and scalability potential. Second, the regulatory effects of two-dimensional layered and three-dimensional interpenetrated structures on charge transport pathways and structural stability are elucidated. Subsequently, the applications of porphyrin/phthalocyanine-based MCOFs in lithium-based batteries, zinc-based batteries, sodium/potassium-ion batteries, and supercapacitors are reviewed in detail, with emphasis on the key roles of metal active sites in catalytic conversion, chemical anchoring/confinement, interface stabilization, and pseudocapacitive contribution. Finally, future directions to address key performance and mechanistic bottlenecks are discussed. This review aims to provide a systematic reference for the rational design and energy storage applications of high-performance porphyrin/phthalocyanine-based MCOFs. Full article
(This article belongs to the Special Issue Nanomaterials for Renewable Energy Production and Storage)
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19 pages, 14973 KB  
Article
Core–Shell Zn–Co Zeolitic Imidazolate Framework-Derived Catalysts for the Reverse Water–Gas Shift Reaction
by Krittanun Deekamwong, Nichakorn Pornnongsan, Pimrapus Tawachkultanadilok, Yingyot Poo-Arporn, Wanwisa Limphirat, Sirinuch Loiha, Pobporn Promchan, Jatuporn Wittayakun and Sanchai Prayoonpokarach
Catalysts 2026, 16(8), 737; https://doi.org/10.3390/catal16080737 - 19 Aug 2026
Viewed by 164
Abstract
The reverse water–gas shift (RWGS) reaction is a promising route for converting CO2 into CO, an important feedstock for synthetic fuels and chemicals. In this study, Zn–Co zeolitic imidazolate frameworks (ZIFs), including ZIF-8, ZIF-67, ZIF-67-8, and the core–shell structures ZIF-8@67 and ZIF-67@8, [...] Read more.
The reverse water–gas shift (RWGS) reaction is a promising route for converting CO2 into CO, an important feedstock for synthetic fuels and chemicals. In this study, Zn–Co zeolitic imidazolate frameworks (ZIFs), including ZIF-8, ZIF-67, ZIF-67-8, and the core–shell structures ZIF-8@67 and ZIF-67@8, were synthesized as catalyst precursors and thermally activated prior to catalytic testing. Transmission electron microscopy and elemental mapping confirmed the formation of well-defined core–shell architectures, while synchrotron X-ray diffraction verified the characteristic sodalite-type framework. Thermogravimetric analysis revealed substantial framework decomposition during activation at 700 °C. In situ time-resolved X-ray absorption spectroscopy (TR-XAS) showed that Zn remained predominantly in the Zn2+ state throughout heating, whereas Co2+ underwent progressive reduction to metallic Co0 at temperatures approaching 600 °C. Ex situ X-ray absorption spectroscopy confirmed the presence of Zn2+ species and metallic cobalt after activation. Catalytic testing of the activated ZIF-derived materials showed that Co-containing catalysts exhibited significantly higher RWGS activity than Zn-only ZIF-8-derived catalyst. Among the investigated samples, ZIF-67@8_C-500 achieved the highest performance, producing 2.50 μmol CO (equivalent to 50 μmol g−1 catalyst) at 600 °C with a H2/CO2 ratio of 2:1. The strong dependence of activity on ZIF-67 core loading indicates that metallic cobalt generated from the Co-rich core plays a dominant role in CO2 conversion. Thermal activation transformed the highly porous ZIF precursors into metallic Co-containing carbonaceous catalysts. The resulting structural evolution, rather than retention of the original porous MOF framework, governed the catalytic performance in the RWGS reaction. Full article
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16 pages, 11288 KB  
Article
Comparative Genomics of the Tea XTH Gene Family Reveals the Involvement of CsXTH27 in Internode Elongation
by Hong Shen, Fengshui Yang, Liping Zhang, Aihua Zhu, Lan Zhang, Xin Li, Peiqiang Wang and Shuixing Zhu
Int. J. Mol. Sci. 2026, 27(16), 7388; https://doi.org/10.3390/ijms27167388 - 18 Aug 2026
Viewed by 212
Abstract
Xyloglucan endotransglucosylase/hydrolases (XTHs) are key cell-wall-remodeling enzymes that mediate xyloglucan modification, cell expansion, and organ elongation, yet the composition and variation in the XTH gene family across tea accessions remain unclear. In this study, we systematically identified and comparatively analyzed the XTH gene [...] Read more.
Xyloglucan endotransglucosylase/hydrolases (XTHs) are key cell-wall-remodeling enzymes that mediate xyloglucan modification, cell expansion, and organ elongation, yet the composition and variation in the XTH gene family across tea accessions remain unclear. In this study, we systematically identified and comparatively analyzed the XTH gene family across the genomes of nine tea accessions, yielding 477 putative XTH genes. Phylogenetic, conserved-motif, protein-domain, and conserved catalytic-motif analyses indicated that the major structural features of tea XTH proteins are broadly conserved, whereas orthogroup-based presence–absence variation (PAV) analysis revealed core, variable, and accession-specific components within the family. Using transcriptomic expression profiles across eight tissues, we selected eight CsXTH genes for internode expression analysis. Reverse transcription quantitative PCR (RT-qPCR) showed that all eight genes were expressed at significantly higher levels in the third internode (I3) than in the second internode (I2) in ‘Longjing 43’ (LJ43), and CsXTH27 retained the same internode-associated expression pattern in ‘Baihaozao’ (BHZ) and ‘Zhongcha 108’ (ZC108), supporting its selection for functional analysis. Transient overexpression of CsXTH27 significantly increased the lengths of I2, I3, and I4, as well as the total length of I1–I4, compared with the empty-vector control. This phenotype was accompanied by significantly increased XTH protein content in stems and an apparent tendency toward larger pith parenchyma cell profiles. Overall, these findings reveal both structural conservation and accession-level variation in the tea XTH gene family and provide preliminary functional evidence linking CsXTH27 to shoot internode elongation. Full article
(This article belongs to the Special Issue Plant Genome Editing: Recent Advances and Future Perspectives)
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26 pages, 9385 KB  
Article
Synthesis and In Vivo Antifungal Evaluation of 3-Acyl-bromoindole Regioisomers: A Multi-Targeting Study on Postharvest Pathogen Control and Molecular Dynamics
by Alejandro Madrid, Valentina Silva, Katy Díaz, Evelyn Muñoz, David Cabezas, Karel Mena-Ulecia, Iván Montenegro, Carmina Sirignano, Enrique Werner and Ximena Besoain
Antibiotics 2026, 15(8), 801; https://doi.org/10.3390/antibiotics15080801 - 18 Aug 2026
Viewed by 202
Abstract
Background/Objectives: Postharvest fungal decay caused by Botrytis cinerea and Monilinia fructicola poses major threats to global fruit security. Driven by the need for sustainable crop protection agents, this work presents the systematic synthesis, biological evaluation, and computational modeling of a comprehensive 33-compound [...] Read more.
Background/Objectives: Postharvest fungal decay caused by Botrytis cinerea and Monilinia fructicola poses major threats to global fruit security. Driven by the need for sustainable crop protection agents, this work presents the systematic synthesis, biological evaluation, and computational modeling of a comprehensive 33-compound library of 3-acyl-bromoindole regioisomers (series 4a–k, 5a–k, and 6a–k) to establish clear structure–activity relationship (SAR) design rules. Methods: The regioisomeric library was assembled via a microwave-assisted catalytic protocol in an ionic liquid, expanding the known chemical space with seven newly synthesized 4-bromoindole derivatives (4d–f, 4h–k). Primary in vitro data were modeled using Hansch QSAR and Principal Component Analysis (PCA). Postharvest in vivo efficacy was evaluated on fresh ‘Lapins’ sweet cherries inoculated with M. fructicola. Molecular docking and 100 ns molecular dynamics (MD) simulations were performed against succinate dehydrogenase (SDH) and M. fructicola catalase 2 (MfCat2). Results: In vitro screening demonstrated marked target selectivity: parent core 4 displayed high mycelial suppression against M. fructicola (EC50 = 7.05 µg/mL), whereas C3-acylation with a four-carbon linear chain (4c) achieved optimal broad-spectrum dual action (98% and 86% spore germination inhibition). In vivo cherry bioassays proved that bromoindoles 4, 6a, and 6d significantly suppressed Brown Rot severity to 44–47% (a 20–27% reduction vs. untreated control). Docking and MD trajectories confirmed stable multi-target binding within SDH and MfCat2 active sites (RMSD < 2.0 Å). Conclusions: Bromine regiochemistry dictates pathogen selectivity and life-stage targeting. The novel 4-bromoindole derivatives and multi-target profile establish these scaffolds as promising leads for postharvest crop protection. Full article
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13 pages, 5325 KB  
Review
Structural and Mechanistic Perspectives on SARS-CoV-2 Nonstructural Protein 14-Mediated Cap Formation and Drug Discovery
by Yifan Zhao, Rhea Guo, Yang Yang and Chang Liu
Microorganisms 2026, 14(8), 1815; https://doi.org/10.3390/microorganisms14081815 - 18 Aug 2026
Viewed by 224
Abstract
SARS-CoV-2 relies on a virus-encoded RNA capping pathway to produce 5′ cap structures that are essential for mRNA stability, efficient translation, and evasion of host innate immune surveillance. Within this pathway, nonstructural protein 14 (nsp14) catalyzes N7 methylation of the guanine cap, a [...] Read more.
SARS-CoV-2 relies on a virus-encoded RNA capping pathway to produce 5′ cap structures that are essential for mRNA stability, efficient translation, and evasion of host innate immune surveillance. Within this pathway, nonstructural protein 14 (nsp14) catalyzes N7 methylation of the guanine cap, a key step that converts the cap core into a functional Cap-0 structure and enables subsequent maturation. Owing to its essential role in viral replication and its high conservation across coronaviruses, nsp14 has emerged as an attractive antiviral target. Recent structural and biochemical studies have elucidated the architecture of the nsp14 N7-methyltransferase domain, revealing an S-adenosyl-L-methionine (SAM)-dependent fold with a defined cofactor-binding site and an adjacent cap-binding pocket that orients the RNA substrate for methyl transfer. These insights have guided the development of diverse inhibitor classes, including SAM-competitive analogs, bisubstrate-like compounds, and non-nucleoside inhibitors identified through screening approaches. While early SAM-like inhibitors demonstrated target tractability, their therapeutic potential has been limited by challenges in selectivity and cellular permeability. More recent inhibitors that target the cap-binding pocket or exploit product-assisted ternary complex mechanisms highlight alternative strategies for achieving improved potency and specificity. Despite these advances, current structural models rely on truncated RNA substrates and isolated protein constructs, which may not fully capture the native catalytic environment. Future efforts to resolve nsp14 within the replication–transcription complex and develop novel inhibition strategies will be critical for advancing mechanistic understanding and antiviral development. Full article
(This article belongs to the Special Issue Structural Studies of RNA Virus Replication)
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22 pages, 5382 KB  
Review
Metal-Graphitic Nanocapsules for Molecular Spectroscopy-Based Chemical Analysis, Biosensing, and Targeted Diagnosis
by Xiaoxu Cao, Shen Wang, Rongshen Guo, Guiyan Zhu, Zhen Ren and Zhuo Chen
Targets 2026, 4(3), 29; https://doi.org/10.3390/targets4030029 - 17 Aug 2026
Viewed by 132
Abstract
Metal-graphitic nanocapsules are an emerging class of metal-graphitic hybrid nanomaterials, typically consisting of a metal core confined within a single- or few-layer graphitic shell. This unique core–shell architecture integrates the tunable physicochemical properties of metal nanomaterials with the chemical stability, Raman activity, fluorescence-quenching [...] Read more.
Metal-graphitic nanocapsules are an emerging class of metal-graphitic hybrid nanomaterials, typically consisting of a metal core confined within a single- or few-layer graphitic shell. This unique core–shell architecture integrates the tunable physicochemical properties of metal nanomaterials with the chemical stability, Raman activity, fluorescence-quenching capability, and surface functionalization capacity of graphitic materials. In particular, the metal core can provide plasmonic enhancement as well as magnetic or catalytic auxiliary functions, while the chemically protective graphitic shell protects the core from harsh environments and provides intrinsic Raman bands that can serve as internal standards under well-controlled conditions. These features make metal-graphitic nanocapsules highly attractive as robust nanoprobes for molecular spectroscopy-based chemical analysis, biosensing, and targeted diagnosis. In this review, we first summarize the synthesis strategies, formation mechanisms, and key properties of representative metal-graphitic nanocapsules. We then discuss recent advances in their use across representative analytical and biomedical scenarios, with emphasis on the integration of spectroscopic readouts with targeted recognition strategies. Particular attention is given to how the metal core and graphitic shell cooperatively enhance signal generation, molecular enrichment, selective recognition, environmental stability, internal calibration, and reliable in situ diagnosis in real samples and living systems. Finally, we discuss current challenges and future perspectives for developing metal-graphitic nanocapsules as versatile platforms for molecular spectroscopy-based analysis and diagnosis. Full article
(This article belongs to the Special Issue Molecular Spectroscopy-Based Targeted Detection)
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27 pages, 2848 KB  
Article
Unexpected Synthesis of a Furoxan Derivative from 3-Acetyl-2,4,6-Trimethylpyridine: Structural Characterization and Biological Evaluation
by Aida S. Rakhimzhanova, Irina A. Pustolaikina, Alfiya F. Kurmanova, Ruslan A. Muzaparov, Tatyana V. Rybalova, Zarina T. Shulgau, Alena L. Stalinskaya and Ivan V. Kulakov
Molecules 2026, 31(16), 2842; https://doi.org/10.3390/molecules31162842 - 14 Aug 2026
Viewed by 291
Abstract
Herein, we report an unexpected pseudo-multicomponent transformation discovered during attempts to selectively nitrate the pyridine core of 3-acetyl-2,4,6-trimethylpyridine (3). Despite employing standard nitration conditions, including KNO3–H2SO4 and HNO3–H2SO4 mixtures, electrophilic substitution [...] Read more.
Herein, we report an unexpected pseudo-multicomponent transformation discovered during attempts to selectively nitrate the pyridine core of 3-acetyl-2,4,6-trimethylpyridine (3). Despite employing standard nitration conditions, including KNO3–H2SO4 and HNO3–H2SO4 mixtures, electrophilic substitution of the aromatic ring did not occur. Instead, the reaction sequence promoted an in situ nitrozation, dehydration to nitrile oxide intermediates, and subsequent [3+2]-cycloaddition involving two substrate molecules. This process yielded a novel, highly functionalized furoxan derivative, precisely identified as 3,4-bis(2,4,6-trimethylnicotinoyl)-1,2,5-oxadiazole 2-oxide (5). The molecular architecture of compound 5 was established by 1H and 13C NMR spectroscopy, mass spectrometry, elemental analysis, and single-crystal X-ray diffraction (XRD) analysis. To elucidate the stereochemical and electronic features governing compound 5, DFT calculations were performed at the ωB97X-D/6-311++G(d,p) level of theory. The experimental crystallographic disorder of the N-oxide oxygen atom was computationally rationalized by the thermodynamic near-degeneracy (ΔG < 0.63 kcal/mol) of two orientational isomers (5a and 5b). Furthermore, frontier molecular orbital analysis within the framework of perturbation theory accounted for the head-to-tail regioselectivity during cyclization, while wide energy gaps (ΔE = 8.13–8.27 eV) and high chemical hardness (η = 4.07–4.14 eV) underscored the kinetic stability of the heterocycle. Phenotypic and target-specific in silico profiling using PASS Online identified Matrix Metalloproteinase-9 (MMP-9) as a relevant target for potential hemorheological and cardioprotective applications. Validated molecular docking simulations across three human MMP-9 crystallographic domains (PDB: 8K5Y, 6ESM, 4XCT) demonstrated competitive binding affinities and balanced Ligand Efficiency metrics (LE = 0.26–0.29 kcal/mol/heavy atom), anchoring compound 5 within the catalytic pocket via conventional hydrogen bonds and π-mediated interactions. Finally, in vitro evaluations using a blood hyperviscosity model confirmed significant hemorheological efficacy, as compound 5 effectively prevented the rise in blood viscosity, outperforming the reference drug pentoxifylline. The convergence of computational insights and experimental functional activity establishes this novel bis(nicotinoyl)furoxan framework as a promising candidate for further hemorheological and cardioprotective applications. Full article
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15 pages, 3815 KB  
Article
Genome-Wide Identification of the TaBSK Gene Family and Its Salt-Responsive Expression Patterns in Wheat
by Yongtao Zhao, Junsen Wang, Zhongzhou Zhang, Qian Yuan, Shicong Zhen, Hao Guo, Chuan Xia and Zhenchen Xie
Curr. Issues Mol. Biol. 2026, 48(8), 816; https://doi.org/10.3390/cimb48080816 - 12 Aug 2026
Viewed by 143
Abstract
Brassinosteroid signaling kinases (BSKs) act as core signal transducers downstream of Brassinosteroid (BR) perception and integrate plant growth regulation with broad-spectrum biotic and abiotic stress tolerance. Despite well-established functional characterizations of BSK gene families in Arabidopsis thaliana and rice, comprehensive genome-wide profiling and [...] Read more.
Brassinosteroid signaling kinases (BSKs) act as core signal transducers downstream of Brassinosteroid (BR) perception and integrate plant growth regulation with broad-spectrum biotic and abiotic stress tolerance. Despite well-established functional characterizations of BSK gene families in Arabidopsis thaliana and rice, comprehensive genome-wide profiling and salt response analysis of BSK homologs remain lacking in wheat. In this study, we systematically identified 18 TaBSK family members. Phylogenetic analysis separated wheat TaBSKs into three distinct evolutionary subgroups. The 18 TaBSK loci were unevenly distributed across 14 chromosomes derived from the A, B, and D subgenomes. Motif scanning uncovered 10 universal conserved amino acid motifs, including two signature functional domains: the tetratricopeptide repeat (TPR) and protein kinase catalytic domain (PKc). Intra-genomic collinearity analysis confirmed that segmental duplication constituted the primary evolutionary driver underlying TaBSK family expansion. Extensive cis-regulatory element profiling identified abundant hormone- and stress-responsive cis-motifs. Transcriptome profiling RNA-seq datasets revealed five TaBSK genes exhibiting significant differential transcription under salt stress. Specifically, TaBSK16, TaBSK17, and TaBSK18 were markedly upregulated following salt exposure. Collectively, this study delivers an evolutionary and transcriptional atlas of the wheat TaBSK family and provides candidate genes for functional validation and molecular breeding toward salt-tolerant wheat varieties. Collectively, this study explores the evolution and transcriptional patterns of the wheat TaBSK gene family and provides candidate genes for subsequent functional validation and molecular breeding of salt-tolerant wheat varieties. Full article
(This article belongs to the Special Issue Abiotic Stress in Plants)
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20 pages, 2240 KB  
Article
6-(2-Aminoethyl)-6H-indolo[2,3-b]quinoxalines as Promising Compounds Capable of Binding to FLT3 (D835V) Kinase
by Igor A. Schepetkin, Alexander V. Uvarov, Egor A. Evriinov and Andrei I. Khlebnikov
Biomolecules 2026, 16(8), 1173; https://doi.org/10.3390/biom16081173 - 12 Aug 2026
Viewed by 302
Abstract
Indolo[2,3-b]quinoxalines, along with their N-substituted derivatives, exhibit pronounced anticancer activity, although the mechanisms of their biological action may vary. Herein, a panel of sixty-five 6-(2-aminoethyl)-6H-indolo[2,3-b]quinoxaline derivatives comprising eight series with distinct amine moieties connected to the [...] Read more.
Indolo[2,3-b]quinoxalines, along with their N-substituted derivatives, exhibit pronounced anticancer activity, although the mechanisms of their biological action may vary. Herein, a panel of sixty-five 6-(2-aminoethyl)-6H-indolo[2,3-b]quinoxaline derivatives comprising eight series with distinct amine moieties connected to the tetracyclic indoloquinoxaline core via a dimethylene linker was evaluated as drug-like candidates for kinase binding and cytotoxic activity. The ADME (Absorption, Distribution, Metabolism, and Excretion) properties of the compounds included in this set were preliminarily determined using the SwissADME tool. Analysis revealed that the library of quinoxaline derivatives largely complies with the drug-likeness rule for kinase-targeted compounds. As part of the biological screening, the compounds were initially tested on two cell lines MonoMac-6 and THP-1 (both derived from patients with acute monocytic leukemia) using sunitinib, a known antitumor agent acting as a multi-target receptor tyrosine kinase inhibitor, as a reference compound. Compound 3g, which demonstrated the highest activity in the cytotoxicity analysis (IC50 = 1.9 and 3.5 μM for the MonoMac-6 and THP-1 cell lines, respectively), was screened using the Eurofins DiscoverX scanEDGE panel, comprising 97 distinct kinases representing all known kinase families. Subsequently, the compound was tested using the Eurofins DiscoverX scanTK™ panel, covering 135 distinct receptor and non-receptor tyrosine kinases. Based on initial screening results, compound 3g exhibits relatively high binding activity against fourteen tyrosine kinases, including TYK2, ZAP70, eight mutant forms of ABL1, two mutant forms of FLT3, and one mutant form of ALK, and demonstrates relatively high binding selectivity with respect to non-mutant tyrosine kinases (S-score: 0.024). Secondary screening of nine selected analogs of compound 3g led to the identification of compound 3h, which demonstrates relatively high binding affinity for FLT3 (D835V) (Kd = 0.41 μM). Molecular modeling suggested modes of binding interaction of the compounds 3h and 3g in the FLT3 (D835V) catalytic site. Our results demonstrate that 6-(2-aminoethyl)-6H-indolo[2,3-b]quinoxaline derivatives could be potential candidates for developing anticancer drugs. Full article
(This article belongs to the Section Enzymology)
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24 pages, 26164 KB  
Review
Cancer-Derived Exosomes: A Cross-Cancer Comparative Analysis of Exosomal Proteins and MicroRNAs
by Jong Hyun Kim
Int. J. Mol. Sci. 2026, 27(15), 7057; https://doi.org/10.3390/ijms27157057 - 6 Aug 2026
Viewed by 421
Abstract
Exosomes are small extracellular vesicles that mediate intercellular communication and, in cancer, carry cargo that both reflects the donor tumor cell and influences recipient cells within local and distant microenvironments. Exosomal proteins and microRNAs have been reported individually across many cancer types, but [...] Read more.
Exosomes are small extracellular vesicles that mediate intercellular communication and, in cancer, carry cargo that both reflects the donor tumor cell and influences recipient cells within local and distant microenvironments. Exosomal proteins and microRNAs have been reported individually across many cancer types, but rarely compared on a common basis; in this review, previously reported molecules from eight cancer categories—blood, breast, colon, kidney, liver, lung, prostate, and stomach—were compiled from curated repositories and re-analyzed within a single functional framework. In total, 3643 exosomal proteins (523 hematologic, 3120 solid-tumor) and 627,225 miRNA–target pairs, derived from 350 unique microRNAs, were organized using Gene Ontology, KEGG, and PANTHER annotation. Across cancers, proteins converged on a reproducible core—signaling, transport, cytoskeletal organization, and extracellular interaction—dominated by binding, catalytic, and transporter functions localized to membrane, vesicle, and extracellular compartments. Comparisons between hematologic and solid malignancies revealed both shared cancer-associated functions and context-dependent patterns linked to tissue origin and disease ecology. Together, these findings indicate that integrated protein-and-microRNA profiling offers a useful framework for understanding tumor communication, refining cancer classification, and advancing biomarker discovery, while underscoring that harmonized workflows, independent validation, and mechanistic follow-up remain necessary before descriptive enrichment outputs can support clinically robust applications. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Cancer and Tumor Microenvironment)
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21 pages, 7217 KB  
Review
Genetic and Molecular Regulation of Ecdysone Biosynthesis During Insect Metamorphosis
by Jie Zhang and Guanfeng Xu
Insects 2026, 17(8), 817; https://doi.org/10.3390/insects17080817 - 6 Aug 2026
Viewed by 370
Abstract
Steroid hormones govern diverse physiological processes during juvenile-to-adult development across vertebrates and invertebrates, ranging from pubertal initiation in mammals to metamorphosis in insects. Ecdysteroids, the collective name for many moulting hormones in insects, act as master effectors driving metamorphic development. Their biosynthesis begins [...] Read more.
Steroid hormones govern diverse physiological processes during juvenile-to-adult development across vertebrates and invertebrates, ranging from pubertal initiation in mammals to metamorphosis in insects. Ecdysteroids, the collective name for many moulting hormones in insects, act as master effectors driving metamorphic development. Their biosynthesis begins with dietary cholesterol as the direct precursor (phytosterols are converted as needed) and is driven by a series of enzymatic reactions catalyzed by the evolutionarily conserved Halloween genes to produce ecdysone, which is ultimately converted into its potent metabolite 20-hydroxyecdysone (20E) in target tissues to induce extensive morphological and physiological changes. The precise temporal pattern of molting and metamorphosis is dictated by periodic ecdysone surges originating from the prothoracic gland. Given the extensive utility of Drosophila as a major model organism for investigating systemic growth and developmental timing, this review synthesizes recent insights into the regulatory mechanisms underlying ecdysone biosynthesis. In this review, we begin by outlining the ecdysteroid biosynthetic cascade and core catalytic enzymes in the prothoracic gland, followed by a systematic discussion of diverse regulatory strata, encompassing substrate availability, transcriptional regulation and chromatin accessibility, and their vital contributions to the control of ecdysteroid production. Full article
(This article belongs to the Section Insect Molecular Biology and Genomics)
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