Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (28,979)

Search Parameters:
Keywords = protein–protein interaction

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
17 pages, 994 KB  
Article
Serial Presepsin Measurement as a Predictor of In-Hospital Mortality in Older Adults with Hip Fractures
by Bünyamin Arı, Fatmagül Can, Umur Batak and Turan Cihan Dülgeroğlu
Life 2026, 16(8), 1316; https://doi.org/10.3390/life16081316 (registering DOI) - 12 Aug 2026
Abstract
Serial presepsin measurements were evaluated for their prognostic value compared with conventional laboratory markers in predicting in-hospital mortality among older adults with hip fractures. This prospective observational study included 85 patients aged ≥65 years admitted with acute hip fractures between December 2025 and [...] Read more.
Serial presepsin measurements were evaluated for their prognostic value compared with conventional laboratory markers in predicting in-hospital mortality among older adults with hip fractures. This prospective observational study included 85 patients aged ≥65 years admitted with acute hip fractures between December 2025 and May 2026. Residual serum remaining after routine clinical laboratory sampling was obtained on admission (Day 1), Day 3, and Day 5; serum presepsin was measured by commercial ELISA, and routine parameters (C-reactive protein [CRP], white blood cell count, lymphocytes, monocytes, platelets, and liver enzymes) were analysed in the hospital laboratory. Renal function was assessed by serial creatinine and estimated glomerular filtration rate (eGFR). Patients were classified as survivors or non-survivors according to in-hospital outcome. Temporal trajectories were modelled with a linear mixed-effects model fitted to log-transformed presepsin, receiver operating characteristic (ROC) analysis assessed predictive performance, and internal validity was examined by bootstrap resampling. Of the 85 patients, 68 survived and 17 died during hospitalization; all deaths occurred between hospital days 5 and 12. Presepsin diverged progressively between groups, reaching significantly higher concentrations in non-survivors by Day 5 (median 207.70 vs. 147.21 ng/L; p < 0.001), with a Day 5 group-by-time interaction ratio of 1.76 (95% CI 1.38–2.25; p < 0.001). Day 5 presepsin showed the highest predictive accuracy (AUC = 0.868, 95% CI 0.774–0.945; optimism-corrected AUC 0.866), significantly outperforming CRP (AUC = 0.606; p = 0.003) and platelet count (AUC = 0.485; p < 0.001). The association persisted after adjustment for age, ASA class, fracture type, and eGFR, and Day 5 presepsin added discrimination to a baseline clinical model (ΔAUC 0.125; p = 0.015). The Youden-derived cutoff of 169.54 ng/L was unstable across bootstrap resamples (95% range 169.5–207.7 ng/L). Serial presepsin measurement, particularly on Day 5, is associated with in-hospital mortality in this population; these exploratory findings require external validation before any clinical application can be considered. Full article
(This article belongs to the Section Medical Research)
Show Figures

Graphical abstract

27 pages, 12997 KB  
Article
GAMT-GINE: A Graph Isomorphism Network Integrating Continuous Spatial Awareness and Multi-Task Learning for Protein–Ligand Binding Affinity Prediction
by Jiarui Li, Hongquan Li, Di Wu, Wei He, Weinan Cao, Hua Yang and Zhen Hou
Int. J. Mol. Sci. 2026, 27(16), 7196; https://doi.org/10.3390/ijms27167196 (registering DOI) - 12 Aug 2026
Abstract
Protein–ligand interactions (PLIs) play a crucial role in drug discovery, and accurately predicting protein–ligand binding affinity (PLA) remains a central challenge in computer-aided drug design. Although graph neural networks (GNNs) have demonstrated considerable potential in molecular modeling, existing methods still face several limitations, [...] Read more.
Protein–ligand interactions (PLIs) play a crucial role in drug discovery, and accurately predicting protein–ligand binding affinity (PLA) remains a central challenge in computer-aided drug design. Although graph neural networks (GNNs) have demonstrated considerable potential in molecular modeling, existing methods still face several limitations, including excessive reliance on hand-crafted chemical features, loss of spatial information, and difficulties in integrating heterogeneous affinity labels, which restrict their generalization capability in PLA prediction. To address these challenges, we propose GAMT-GINE, a graph isomorphism network that integrates continuous spatial awareness with multi-task learning. The model employs minimalist atomic features and a batch-normalization-free mechanism, together with a multi-task branch that uses a large amount of half-maximal inhibitory concentration (IC50) data as an auxiliary prediction target. Experimental results show that GAMT-GINE achieves a Pearson’s correlation coefficient (Rp) of 0.791 and a root mean square error (RMSE) of 1.403 on the CASF-2013 benchmark dataset. In the generalization evaluation on CASF-2016, Rp further increases to 0.831, while RMSE decreases to 1.227, demonstrating performance comparable to that of current State-of-the-Art models. Furthermore, comprehensive evaluations, including ablation studies, feature importance analysis, analysis of the effects of data filtering on model performance and data composition, and analysis of the influence of training–test data similarity on prediction results, indicate that GAMT-GINE can effectively utilize continuous spatial information and heterogeneous affinity labels, achieving good predictive accuracy and cross-dataset generalization capability. Full article
(This article belongs to the Section Biochemistry)
Show Figures

Figure 1

16 pages, 257 KB  
Article
Effect of Genotype and Microbial Inoculants on Quality, Fermentation, and In Vitro Digestibility of Barley at Early Dough Stage of Maturity
by Umair Ahsan, Derya Merve Karagöz, Muhammad Shazaib Ramay, Syed Umer Akhter, Anas Tahir, Bekir Tosun, Ifrah Raza, Murat Er, Muhammad Kashif Yar and Eren Kuter
Fermentation 2026, 12(8), 382; https://doi.org/10.3390/fermentation12080382 (registering DOI) - 12 Aug 2026
Abstract
A 2 × 2 × 2 factorial experiment was conducted to study the individual and combined effects of barley variety (Tarım 92 and Bravo), homofermentative inoculant (HMF; Lactobacillus plantarum and Enterococcus faecium), and heterofermentative inoculant (HTF; Lactobacillus buchneri) on the fermentation [...] Read more.
A 2 × 2 × 2 factorial experiment was conducted to study the individual and combined effects of barley variety (Tarım 92 and Bravo), homofermentative inoculant (HMF; Lactobacillus plantarum and Enterococcus faecium), and heterofermentative inoculant (HTF; Lactobacillus buchneri) on the fermentation characteristics, chemical composition, nutritive value indices, and in vitro digestibility of whole-crop barley silages which were harvested at the early dough stage. Forty-eight laboratory silos (six replicates per treatment) were ensiled for 120 days. Tarım 92 silage exhibited superior fermentation stability across all treatments, with pH ranging from 4.11 to 4.30, Flieg points of 102.94–115.47, and lower NH3-N concentrations (142.01–173.72 mg/kg TN (total nitrogen)), reflecting better protein preservation than Bravo silage. In contrast, the poorest fermentation outcome (pH 5.24; Flieg 47.06; NH3-N 307.48 mg/kg TN) was exhibited by the Bravo silage inoculated with only homofermentative inoculants. Significant three-way interaction effects were detected among barley variety, homofermentative inoculant, and heterofermentative inoculant (p < 0.05). The dual-inoculated Tarım 92 silage showed the optimum in vitro digestibility and nutritional value (TDN 77.14%; NEL 1.81 Mcal kg−1 DM; RFV 176.25; ADF 18.75%; IVOMD 65.72%; predicted DMI 3.06% BW), while higher amounts of butyric acid and NH3-N suggested that better nutritional value was not always accompanied by better protein preservation. The combined inoculation also yielded the best outcomes within Bravo treatments (RFV 144.00), whereas HTF inoculation alone reduced IVDMD and IVOMD below uninoculated controls. Overall, these results show that the response to microbial inoculation is genotype-dependent and a combination of homofermentative and heterofermentative inoculation for high-dry-matter barley varieties can enhance nutritive value and digestibility. However, fermentation quality indicators, particularly butyric acid and NH3-N, require consideration in the selection of technique. Full article
17 pages, 7187 KB  
Article
Silencing of Homeodomain-Interacting Protein Kinase 2 (HIPK2) Induces Anti-Adipogenic Effects in 3T3-L1 Adipocytes
by Anil Kumar Yadav, Nivethasri Lakshmana Perumal, Gi-Young Park and Byeong-Churl Jang
Curr. Issues Mol. Biol. 2026, 48(8), 812; https://doi.org/10.3390/cimb48080812 (registering DOI) - 12 Aug 2026
Abstract
Homeodomain-interacting protein kinase 2 (HIPK2) is an important regulator of various transcription factors and cofactors, which are involved in cell growth, cell death, and embryonic development. Previously, it has been reported that HIPK2 is upregulated during white fat development. However, the expression and [...] Read more.
Homeodomain-interacting protein kinase 2 (HIPK2) is an important regulator of various transcription factors and cofactors, which are involved in cell growth, cell death, and embryonic development. Previously, it has been reported that HIPK2 is upregulated during white fat development. However, the expression and functional role of HIPK2 during adipogenesis remain unclear. Here, we investigated the expression and biological function of HIPK2 during the adipogenesis of 3T3-L1 cells. Importantly, protein and mRNA expression of HIPK2 were significantly upregulated in a time-dependent manner during 3T3-L1 preadipocyte differentiation. Notably, distinct pharmacological inhibitors revealed the pivotal roles of p38 MAPK and PKC in the induction of HIPK2 expression during differentiation of 3T3-L1 cells. Moreover, knockdown of HIPK2 significantly reduced lipid storage and triglyceride (TG) levels without cytotoxicity during 3T3-L1 preadipocyte differentiation. At the mechanistic level, HIPK2 knockdown reduced the expression of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), perilipin A, leptin, and resistin, as well as the phosphorylation of signal transducer and activator of transcription-3 (STAT-3) during 3T3-L1 preadipocyte differentiation. Taken together, these results revealed that HIPK2 expression is significantly upregulated in p38 MAPK- and PKC-dependent manners, and this upregulation of HIPK2 plays a critical role in lipid accumulation during differentiation of 3T3-L1 cells, which is mediated by control of the expression and phosphorylation levels of C/EBP-α, PPAR-γ, STAT-3, FAS, and perilipin A. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Show Figures

Figure 1

16 pages, 1871 KB  
Article
The Oligomeric State of Rad6-Rad18 and Its Interactions with Translesion Synthesis Proteins
by Tyler J. Woodward, Brittany M. Ripley, Justin A. Ling and M. Todd Washington
Biomolecules 2026, 16(8), 1172; https://doi.org/10.3390/biom16081172 (registering DOI) - 12 Aug 2026
Abstract
Translesion synthesis is a major DNA damage bypass pathway in which specialized DNA polymerases, such as pol η and Rev1, are recruited to stalled replication forks where they catalyze nucleotide incorporation opposite DNA damage. Translesion synthesis is regulated by the Rad6-Rad18 complex, which [...] Read more.
Translesion synthesis is a major DNA damage bypass pathway in which specialized DNA polymerases, such as pol η and Rev1, are recruited to stalled replication forks where they catalyze nucleotide incorporation opposite DNA damage. Translesion synthesis is regulated by the Rad6-Rad18 complex, which catalyzes PCNA mono-ubiquitylation. Despite its central role in regulating translesion synthesis, its oligomeric state and molecular interactions are poorly understood. Here, we use mass photometry to show that Rad18 co-purifies with Rad6 and forms a series of larger oligomeric complexes. Using yeast two-hybrid studies, we showed that while the full-length Rad18 complex interacts with pol η, its interaction with Rev1 is controlled by auto-inhibition. The release of this auto-inhibition is associated with the dissociation of the Rad6-Rad18 complex, freeing Rad18 monomers and dimers. Because pol η participates in non-mutagenic translesion synthesis, while Rev1 participates in mutagenic translesion synthesis, this auto-inhibition likely allows pol η preferential access to stalled replication forks by delaying Rev1 recruitment. Such an ordered polymerase-recruitment mechanism would reduce the likelihood of mutations. Full article
(This article belongs to the Special Issue Functional Analysis of Genes Related to DNA Damage)
Show Figures

Figure 1

30 pages, 22870 KB  
Article
Preliminary Clinical and Mechanistic Evaluation of Traditional Thai Herbal Cream Containing Cannabis sativa and Curcuma longa for Eczema and Psoriasis
by Julalak Chorachoo Ontong, Chatchai Wattanapiromsakul, Charassri Nualsri, Sudarshan Singh, Popat Mohite, Benjaporn Bourchum, Meadeena Kobmang, Pinyada Subyad, Thanyaphon Pusawiro, Supatina Khan, Nattanon Bunrodchu, Narapat Aunruean, Apiwat Artkaew, Anon Makklay and Thanyaluck Siriyong
Cosmetics 2026, 13(4), 201; https://doi.org/10.3390/cosmetics13040201 - 11 Aug 2026
Abstract
Cannabis sativa and Curcuma longa have traditionally been used for the management of skin disorders; however, scientific evidence supporting their combined topical use in eczema and psoriasis remains limited. To characterize the phytochemical composition, evaluate the biological activities, investigate potential molecular mechanisms, and [...] Read more.
Cannabis sativa and Curcuma longa have traditionally been used for the management of skin disorders; however, scientific evidence supporting their combined topical use in eczema and psoriasis remains limited. To characterize the phytochemical composition, evaluate the biological activities, investigate potential molecular mechanisms, and assess the preliminary clinical performance of a topical herbal cream containing C. sativa and C. longa extracts. Ethanolic extracts were analyzed using UHPLC and GC-MS. Antioxidant, antibacterial, cytotoxicity, and nitric oxide inhibition assays were performed. Molecular docking studies were conducted against inflammation-related protein targets. A pilot clinical study evaluated the effects of the herbal cream in patients with eczema and psoriasis over four weeks using EASI, PASI, and DLQI scores. The herbal formulation contained cannabinoids, terpenoids, and curcuminoids with measurable antioxidant activity. The extract exhibited low cytotoxicity and moderate inhibition of nitric oxide production in LPS-stimulated macrophages (0.0001–0.1 mg/mL). Docking analyses suggested favorable interactions between selected phytochemicals and inflammation-associated targets. Preliminary clinical observations indicated improvements in EASI (from 4.11 ± 3.14 to 1.28 ± 1.46), PASI (from 39 to 16.2), and DLQI (from 6.25 ± 5.25 to 1.00 ± 0.82) scores among study completers. The herbal cream demonstrated antioxidant and anti-inflammatory properties and showed preliminary clinical potential in inflammatory skin disorders. Larger controlled clinical studies are required to confirm efficacy and establish therapeutic value. Full article
(This article belongs to the Section Cosmetic Formulations)
Show Figures

Graphical abstract

27 pages, 22649 KB  
Article
Combining Triazole Scaffold Repurposing and Generative Transformer Architecture for Structure-Based Inhibitor Design Targeting the LasR Quorum Sensing Receptor of Pseudomonas aeruginosa
by Abbas Khan, Muhammad Ammar Zahid, Anwar Mohammad, Asia Al-Jabiry, Raed M. Al-Zoubi, Mohanad Shkoor, Ameera Al-Jabiry and Abdelali Agouni
Pharmaceuticals 2026, 19(8), 1269; https://doi.org/10.3390/ph19081269 (registering DOI) - 11 Aug 2026
Abstract
Background: The rapid escalation of multidrug-resistant P. aeruginosa necessitates anti-virulence strategies targeting quorum sensing rather than bacterial survival; however, integrating scaffold repurposing with generative AI to inhibit LasR remains underexplored. Here, we address this gap by combining triazole scaffold mining with transformer-based de [...] Read more.
Background: The rapid escalation of multidrug-resistant P. aeruginosa necessitates anti-virulence strategies targeting quorum sensing rather than bacterial survival; however, integrating scaffold repurposing with generative AI to inhibit LasR remains underexplored. Here, we address this gap by combining triazole scaffold mining with transformer-based de novo molecular generation to systematically identify putative LasR inhibitors. Methods: An integrated computational pipeline involving Structure-based inhibitor design using Generative Transformer Architecture, deep learning-assisted GNINA rescoring, density functional theory optimization, and molecular dynamics simulations was employed, followed by MM-GBSA binding free energy estimation. Results: Screening of 2666 triazole derivatives and 19,861 DrugGPT-generated compounds yielded top hits with superior binding affinities (−11.59 to −13.81 kcal/mol) compared to the reference ligand (−8.50 kcal/mol). MD simulations yielded stable protein–ligand complexes with RMSD values of 2.24–3.01 Å, while key interactions involving residues Tyr50, Asp67, and Ser123 were consistently maintained. Binding free energy calculations further confirmed strong thermodynamic stability, with MM-GBSA ΔGbind values significantly favorable, supporting robust ligand–receptor affinity. Conclusions: Collectively, these findings establish a powerful AI-integrated framework for anti-virulence drug discovery and identify structurally diverse, high-affinity triazole-based and de novo compounds as promising lead candidates for disrupting LasR-mediated quorum sensing in P. aeruginosa. Full article
(This article belongs to the Special Issue Computer-Aided Drug Design and Drug Discovery, 2nd Edition)
Show Figures

Figure 1

28 pages, 1421 KB  
Article
Trifluoromethyl-Benzimidazole-Hydrazone Derivatives as Promising Selective Anticancer Agents: Synthesis, Cytotoxicity, and Molecular Docking Insights
by Musa Özil, Eyüp Önelge, Mustafa Emirik, Kübra Acikalin Coskun and Yusuf Tutar
Pharmaceuticals 2026, 19(8), 1270; https://doi.org/10.3390/ph19081270 - 11 Aug 2026
Abstract
Background/Objectives: Benzimidazole and hydrazone scaffolds are widely investigated in anticancer drug discovery because of their structural versatility and capacity to interact with multiple cancer-related targets. This study aimed to synthesize a series of trifluoromethyl-substituted benzimidazole-hydrazone derivatives, evaluate their antiproliferative activity and cancer-cell selectivity, [...] Read more.
Background/Objectives: Benzimidazole and hydrazone scaffolds are widely investigated in anticancer drug discovery because of their structural versatility and capacity to interact with multiple cancer-related targets. This study aimed to synthesize a series of trifluoromethyl-substituted benzimidazole-hydrazone derivatives, evaluate their antiproliferative activity and cancer-cell selectivity, and explore their potential interactions with breast cancer-associated molecular targets. Methods: A series of benzimidazole-hydrazone derivatives were prepared through a four-step synthetic route using both conventional and microwave-assisted procedures. The structures of the synthesized compounds were characterized using spectroscopic and analytical methods. Antiproliferative activity was evaluated in estrogen receptor-positive MCF-7 human breast cancer cells using the MTT assay after 48 h of exposure. Selected active compounds were additionally tested against non-tumorigenic hTERT cells to determine their selectivity indices. In silico analyses were performed against estrogen receptor alpha in antagonist and selective estrogen receptor degrader conformations, bromodomain-containing protein 4, and the mTOR kinase domain. Results: Microwave irradiation substantially reduced reaction times from 12–24 h to 4–6 min and increased isolated yields by 7–24 percentage points compared with conventional conditions. Compounds 4, 7, 9, and 11 reduced MCF-7 cell viability below 50% at 20 μM. Compound 7 showed the highest antiproliferative activity, with an IC50 value of 7.5 ± 0.8 μM, and the greatest selectivity toward MCF-7 cells over hTERT cells, with a selectivity index of 12.66. Molecular docking, MD simulation, and MM/GBSA calculations predicted that compound 7 would effectively bind to the investigated targets, particularly estrogen receptor alpha, as well as the BRD4 and mTOR kinase domains. Conclusions: Compound 7 represents a selective, mid-micromolar benzimidazole-hydrazone lead against MCF-7 breast cancer cells. Its predicted molecular interactions warrant further target-based, mechanistic, pharmacokinetic, and in vivo evaluation. Full article
(This article belongs to the Special Issue Computer-Aided Drug Design and Drug Discovery, 2nd Edition)
23 pages, 1418 KB  
Review
Toward a Unified Neuroimmune Framework for Infection-Associated Psychiatric Disorders
by Manuela Arbune, Pantelie Nicolcescu, Anamaria Ciubara, Pompiliu Mircea Bogdan, Constantin-Marinel Vlase and Anca-Adriana Arbune
Diseases 2026, 14(8), 290; https://doi.org/10.3390/diseases14080290 - 11 Aug 2026
Abstract
Background/Objectives: Neuroinflammation is increasingly recognized as a key mechanism linking infectious diseases with psychiatric disorders through interactions between peripheral immune activation, metabolic pathways, and brain network alterations. This review aimed to synthesize current evidence on the neuroimmune mechanisms and biomarkers underlying infection-associated psychiatric [...] Read more.
Background/Objectives: Neuroinflammation is increasingly recognized as a key mechanism linking infectious diseases with psychiatric disorders through interactions between peripheral immune activation, metabolic pathways, and brain network alterations. This review aimed to synthesize current evidence on the neuroimmune mechanisms and biomarkers underlying infection-associated psychiatric disorders. Methods: A narrative literature review structured according to the SANRA (Scale for the Assessment of Narrative Review Articles) criteria was conducted using the Web of Science Core Collection, PubMed/MEDLINE, Scopus and PsycINFO databases. Boolean search strategies identified studies investigating neuroinflammatory biomarkers, neuroimmune mechanisms, and psychiatric outcomes associated with infectious diseases. The search (January 2022–30 June 2026) included 76 studies in the final qualitative analyses. Results: The reviewed evidence consistently identified inflammatory cytokines and chemokines, complement proteins, blood–brain barrier markers, glial activation biomarkers, neuroaxonal injury markers, kynurenine pathway metabolites, neurotrophic factors, and neuroimaging markers as complementary indicators of infection-induced neuroimmune dysfunction. Across diverse bacterial, viral, parasitic, and systemic infections, these mechanisms converged on peripheral immune activation, blood–brain barrier disruption, microglial activation, kynurenine pathway dysregulation, impaired neurotrophic signaling, synaptic dysfunction, and altered brain network connectivity, contributing to depression, anxiety, psychosis, cognitive impairment, and fatigue. Based on these findings, a unified neuroimmune model integrating peripheral and central mechanisms is proposed. Conclusions: Neuroinflammation emerges as a shared biological pathway linking infections with transdiagnostic psychiatric phenotypes. Although no single biomarker currently demonstrates sufficient diagnostic specificity, integrated multimodal biomarker panels may improve biological stratification, facilitate earlier identification of high-risk patients, and support the development of mechanism-based precision approaches—including candidate anti-inflammatory pharmacological strategies currently under clinical investigation—for infection-associated psychiatric disorders. Full article
Show Figures

Figure 1

28 pages, 1748 KB  
Article
PET Micro/Nanoplastic–Tetracycline Co-Exposure in Defibrinated Blood: Exploratory Spectroscopic, Redox, and Escherichia coli Responses
by Asli Baysal, Hasan Saygin and Elif Aydin
Microplastics 2026, 5(3), 160; https://doi.org/10.3390/microplastics5030160 - 11 Aug 2026
Abstract
Previous studies have indicated that polyethylene terephthalate (PET) micro/nanoplastics (MNPs) may coexist with antibiotics in environmental and biological matrices; however, their combined behavior in blood remains insufficiently characterized. This study examined PET MNPs prepared from water bottles at 0.5, 2.5, and 7.5 mg/mL [...] Read more.
Previous studies have indicated that polyethylene terephthalate (PET) micro/nanoplastics (MNPs) may coexist with antibiotics in environmental and biological matrices; however, their combined behavior in blood remains insufficiently characterized. This study examined PET MNPs prepared from water bottles at 0.5, 2.5, and 7.5 mg/mL together with tetracycline (2–50 µg/mL) in defibrinated horse blood. After 24 h exposure and particle removal, UV–visible absorbance, intrinsic fluorescence, redox indicators, and subsequent Escherichia coli responses were evaluated. The blood biochemical results showed condition-dependent changes in hemoglobin-associated absorbance, tryptophan-dominated fluorescence, reactive oxygen species, reduced glutathione, superoxide dismutase, and lipid peroxidation. When treated blood supernatants were applied to Escherichia coli, tetracycline alone reduced bacterial OD600, whereas selected PET MNP–tetracycline co-exposures partially restored bacterial proliferation and modified oxidative-stress responses. ATR–FTIR analysis of Escherichia coli pellets showed dose-dependent modulation of phosphate-, lipid-, and protein-associated bands, indicating changes in bacterial biochemical fingerprints under specific exposure combinations. Overall, the findings suggest that PET MNPs can modify tetracycline-associated spectral, redox, and bacterial response patterns in a blood matrix. Future studies incorporating adsorption assays, free tetracycline quantification, protein-corona profiling, time-course exposure designs, and antibiotic susceptibility testing would further clarify the mechanistic basis and biological relevance of these matrix-dependent interaction effects. Full article
Show Figures

Figure 1

44 pages, 11117 KB  
Article
A Propeller with a Flexible Twist: A Computational Analysis of Intrinsically Disordered Regions in PIEZO Gating and PIEZO-Associated Channelopathies
by Shivam Shukla, Mason Elzy, Abiral Shrestha and Vladimir N. Uversky
Proteomes 2026, 14(3), 41; https://doi.org/10.3390/proteomes14030041 - 11 Aug 2026
Abstract
Background: Mechanosensitive ion channels PIEZO1 and PIEZO2 are key mediators of mechanotransduction, which converts physical forces into cellular signals involved in proprioception, touch, vascular function, and other physiological processes. Mutations in human PIEZO proteins are linked to various diseases, such as hereditary xerocytosis, [...] Read more.
Background: Mechanosensitive ion channels PIEZO1 and PIEZO2 are key mediators of mechanotransduction, which converts physical forces into cellular signals involved in proprioception, touch, vascular function, and other physiological processes. Mutations in human PIEZO proteins are linked to various diseases, such as hereditary xerocytosis, lymphatic dysplasia, and proprioceptive dysfunction. However, the role of intrinsic disorder in the regulation of these proteins and their susceptibility for disease-associated mutations remains unclear. Methods: We analyzed canonical human PIEZO1 and PIEZO2 protein sequences using machine learning, neural network, and energy-based disorder predictors, together with the prediction of disorder-mediated binding regions, phase separation propensity, interaction networks, evolutionary conservation, clinically annotated human variants, and peptide structural modeling. Results: Both proteins showed moderate intrinsic disorder, with PIEZO2 having slightly greater disorder propensity and higher predicted phase separation potential. Intrinsically disordered regions frequently overlapped binding-prone segments and post-translational modification sites, supporting regulatory functions. Evolutionary comparisons showed strong conservation of PIEZO proteins, while selected disordered regions retained disorder propensity despite greater sequence variability. Disease-causing variants mainly affected the ordered regions of both proteins, whereas disordered regions contained proportionally more benign variants and relatively few pathogenic mutations. The modeling of mutations within disordered hotspots showed altered local conformational tendencies, indicating that some disease variants may disrupt dynamic interaction interfaces rather than global structure. Interaction network analysis linked both proteins to enriched mechanotransduction, ion transport, and cytoskeletal pathways. Conclusions: Overall, our findings identify intrinsic disorder as an underappreciated feature of PIEZO channel biology and provide a framework for interpreting PIEZO-associated channelopathies. PIEZO proteins also perfectly illustrate the proteoform concept, where one gene yields a highly diverse kit of mechanosensitive molecular tools. While humans only have two primary PIEZO genes (PIEZO1 and PIEZO2), the body generates a vast array of functional variations. Full article
Show Figures

Figure 1

38 pages, 24236 KB  
Article
Integrated Multi-Omics Analysis and Experimental Validation Identify Acetylation-Related Genes as Potential Regulators in Osteoarthritis
by Qiaojun Huang, Xiaoyi Zhao, Dianbo Long, Ming Li, Yiyi Jiang, Hengyi Diao, Weishen Chen and Fangang Meng
Biomedicines 2026, 14(8), 1806; https://doi.org/10.3390/biomedicines14081806 - 11 Aug 2026
Abstract
Background: Osteoarthritis (OA) is a prevalent degenerative joint disease with a complex molecular basis. This study aims to identify key molecules involved in OA pathogenesis, focusing on the role of acetylation-related gene expression. Methods: Public microarray datasets GSE82107 and GSE169077 were integrated to [...] Read more.
Background: Osteoarthritis (OA) is a prevalent degenerative joint disease with a complex molecular basis. This study aims to identify key molecules involved in OA pathogenesis, focusing on the role of acetylation-related gene expression. Methods: Public microarray datasets GSE82107 and GSE169077 were integrated to construct a differential expression landscape between OA patients and healthy controls. Acetylation-linked differentially expressed genes (acetylation-DEGs, ARDEGs) were extracted by intersecting DEGs with a curated set of acetyltransferases, deacetylases and acetylation substrates. A protein–protein interaction (PPI) network was built and subjected to LASSO-penalized regression to prioritise hub genes. Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Set Variation Analysis (GSVA) were performed to characterize biological themes. Immune infiltration was quantified with CIBERSORTx and single-sample Gene Set Enrichment Analysis (ssGSEA). Single-cell RNA-seq data (GSE216651) were employed for orthogonal validation. For experimental corroboration, synovial tissue was collected from OA patients undergoing arthroplasty; mRNA and protein levels of hub genes were determined by qRT-PCR, Western blot and immunofluorescence. The destabilisation of the medial meniscus (DMM) mouse model was used for in vivo verification. Results: Twenty-one high-confidence ARDEGs were identified. Analysis of the PPI network yielded ten hub nodes, six of which (EGR1, PFKFB3, HDAC4, MMP13, PDK4 and ACADL) retained non-zero coefficients in the least absolute shrinkage and selection operator (LASSO) model. Enrichment analyses implicated these genes in embryonic development, collagen-containing extracellular matrix remodeling and PI3K–Akt signaling. Immune infiltration analysis showed potential differences in immune cell abundance between OA and healthy controls. Single-cell dataset analysis verified the expression patterns of key genes in different cell types. Concordant dysregulation of EGR1, PFKFB3, HDAC4, MMP13 and PDK4 was observed at both mRNA and protein levels in human OA synovium and DMM mouse joints. Conclusion: This comprehensive analysis identified acetylation-related genes and analyzed their potential biological roles in OA. The identified ARDEGs may provide new insights into OA diagnosis and treatment. Full article
(This article belongs to the Section Gene and Cell Therapy)
Show Figures

Figure 1

21 pages, 11792 KB  
Article
Bio–Tillage Mediated by Root–AMF Synergy Promotes the Amelioration of the Compacted Soil Environment and Soybean Growth Under Conservation Management
by Shaofei Wang, Xiaozhe Ma, Suisitong Zhou, Yuhang Zhang, Haobing Zhao, Dayan Shang, Chuanqi Shi, Junnan Ding, Lingbo Meng and Shumin Li
Agronomy 2026, 16(16), 1537; https://doi.org/10.3390/agronomy16161537 - 11 Aug 2026
Abstract
Bio–tillage can continuously regulate the soil environment through plant roots and rhizosphere biological activities and is considered a low disturbance tillage practice that can alleviate soil compaction. However, long term chemical fertilization alone may limit rhizosphere carbon supply and weaken root–microbe interactions. Whether [...] Read more.
Bio–tillage can continuously regulate the soil environment through plant roots and rhizosphere biological activities and is considered a low disturbance tillage practice that can alleviate soil compaction. However, long term chemical fertilization alone may limit rhizosphere carbon supply and weaken root–microbe interactions. Whether conservation management can coordinate root adaptation and arbuscular mycorrhizal fungal (AMF) responses to ameliorate the compacted soil environment and improve crop growth remains unclear. This study compared five treatments: chemical fertilizer alone (CN), straw return (SR), organic manure application (OM), straw return combined with organic manure application (SROM), and green manure intercropping (GM). SROM and GM showed the most pronounced soil amelioration effects. Compared with CN, SROM enhanced root tensile strength and elongation at break, increased the relative abundances of Glomus and Claroideoglomus and the accumulation of easily extractable and total glomalin–related soil protein (EE–GRSP and T–GRSP), reduced soil bulk density (BD) by 10.68% and 6.57% in the 0–20 and 20–40 cm soil layers, respectively, and increased MWD and GMD by 78.49–82.08%. The effects of GM were concentrated in the 20–40 cm soil layer, where enhanced soybean root Young’s modulus and complementary interspecific root distribution reduced BD by 7.36% and increased total porosity (TP) by 9.36%. GM also increased AMF root colonization, the relative abundance of Claroideoglomus, and soil nutrient availability. Additionally, SROM generally maintained the highest aboveground dry matter accumulation and exhibited the highest instantaneous growth rate, whereas the current–season growth benefit under GM was relatively limited. These findings highlight the key roles of roots and AMF in soil amelioration and soybean growth and provide a reference for optimizing low disturbance soil management in compacted black soil regions. Full article
(This article belongs to the Section Innovative Cropping Systems)
Show Figures

Figure 1

24 pages, 1502 KB  
Article
Curcumin Nanoemulsion: Characterization and Effect on Cataracts in an In Vivo Animal Model and Ex Vivo Human Model
by Ana G. Castillo-Olmos, Abigail Varela-Pérez, Hugo S. García-Galindo, Joaquín A. Quiroz-Mercado, Kimberly Castañeda-Gutiérrez, Carlos Amero, Enrique Rudiño-Piñera, Mizraim Morales-Mendoza and Cynthia Cano-Sarmiento
Biomolecules 2026, 16(8), 1166; https://doi.org/10.3390/biom16081166 - 11 Aug 2026
Abstract
Cataracts are the leading cause of reversible blindness worldwide; this condition results from the aggregation of lens proteins. Currently, surgery remains the only treatment; however, there is growing interest in non-surgical approaches, including the use of bioactive compounds incorporated into nanostructured systems designed [...] Read more.
Cataracts are the leading cause of reversible blindness worldwide; this condition results from the aggregation of lens proteins. Currently, surgery remains the only treatment; however, there is growing interest in non-surgical approaches, including the use of bioactive compounds incorporated into nanostructured systems designed to enhance solubility, enable controlled release, and improve bioavailability and bioactivity. Among the bioactive compounds investigated, curcumin has attracted considerable attention due to its antioxidant and anti-inflammatory properties, positioning it as a potential anticataractogenic agent. In the present study, curcumin-loaded nanoemulsion was developed via ultrasonication and characterized by average particle size, D90 percentile, ζ potential, and rheological behavior. In addition, its anti-cataract efficacy was evaluated both using an in vivo model in rats and an ex vivo model employing human cataract samples. The resulting curcumin-loaded nanoemulsion exhibited an average particle size of 152 ± 19.79 nm with a monomodal distribution, along with good physical stability over time. The nanoemulsion exhibited apparent viscosity between 30 and 25 mPa·s, at shear rate values (100 to 0 s−1), indicating slight shear-thinning behavior. Regarding the effect on cataracts, in the in vivo model, cataract reversal was observed. Furthermore, ex vivo isothermal titration calorimetry (ITC) analyses indicated exothermic heat exchange between the curcumin nanoemulsions and cataract fragments, consistent with binding interactions occurring within lens components, likely involving crystallin proteins. These findings provide biophysical and in vivo evidence that intravitreally administered curcumin-loaded nanoemulsions not only prevent but actively reverse lens opacity, positioning them as a promising non-surgical therapeutic approach for cataract treatment. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
Show Figures

Graphical abstract

15 pages, 1101 KB  
Article
Macronutrient-Based Dietary Patterns and the Risk of Muscle Mass Decline in Middle-Aged and Older Adults: A Prospective Community-Based Cohort Study
by Yuji Jeong, Seok-Won Son, Se-Hong Kim and Ha-Na Kim
Metabolites 2026, 16(8), 568; https://doi.org/10.3390/metabo16080568 - 11 Aug 2026
Abstract
Background/Objectives: Loss of skeletal muscle mass is linked to functional decline and adverse health outcomes. Evidence on long-term associations between macronutrient-based dietary patterns and muscle mass decline remains limited. This study examined this association in a prospective cohort of Korean adults aged [...] Read more.
Background/Objectives: Loss of skeletal muscle mass is linked to functional decline and adverse health outcomes. Evidence on long-term associations between macronutrient-based dietary patterns and muscle mass decline remains limited. This study examined this association in a prospective cohort of Korean adults aged 40–69 years. Methods: Participants were categorized into four groups by macronutrient energy proportion: high-carbohydrate (HCHO, carbohydrate > 65% of total energy), high-fat (HF, fat > 30%), high-protein (HP, protein > 20%), and normal diets (ND). Cox models estimated associations between dietary patterns and decline in height-adjusted skeletal muscle mass, including sensitivity analyses using stricter decline thresholds (≥3%, ≥5%, and a reduction exceeding the least significant change); linear mixed-effects models evaluated longitudinal muscle mass changes. Results: A total of 9516 adults were included. During a median follow-up of 5.6 years (IQR 3.8–9.8), 6971 participants developed a decline in skeletal muscle mass relative to baseline. Adjusted hazards were higher for HCHO (aHR 1.12, 95% CI 1.04–1.21) and HP (aHR 1.20, 95% CI 1.01–1.42) versus ND, whereas HF showed no significant association (aHR 0.73, 95% CI 0.46–1.15). These associations were attenuated and no longer significant under stricter thresholds. Mixed-effects models showed no significant group effects or group-by-time interactions. Conclusions: HCHO and HP patterns were associated with a higher risk of muscle mass decline, but this was not consistent under stricter thresholds, and longitudinal trajectories did not differ across patterns. These findings should be considered preliminary. Further studies should clarify the roles of macronutrient quality, food sources, and overall dietary patterns in muscle health. Full article
Show Figures

Figure 1

Back to TopTop