Search Results (34,930)

Molecularly imprinted polymers (MIPs) are synthetic receptors with cavities shaped around a template, combining antibody-like selectivity with chemical, thermal, and mechanical robustness; low cost; and reusability. This Review examines recent advances in MIP-based biosensing, from bulk materials to thin-film, nanostructured, surface-imprinted, and epitope-imprinted architectures designed to improve site accessibility and performance in complex biofluids. We connect polymer chemistry and interface design to molecular recognition and electrochemical, optical, and mass-sensitive transduction. Applications range from small molecules, proteins, nucleic acids, and viruses to whole cells, encompassing miniaturized, wearable, and point-of-care formats. Particular attention is devoted to design assisted by computational methods and machine learning, as well as to the challenges of reproducibility, standardization, metrology, and sustainability that still limit translation. Rather than universal substitutes for antibodies, MIPs are presented as programmable biointerfaces that integrate molecular recognition, signal transduction, device engineering, and the design of low-environmental-impact materials. Full article

Background: Severe COVID-19 reflects a multi-layered host response with systemic inflammation, thrombo-inflammation, tissue damage, oxidative stress and altered antiviral interferon biology. We performed an integrated exploratory analysis of first-wave hospitalized patients to identify biomarker patterns associated with adverse clinical evolution during established admission. Methods: We analyzed 60 hospitalized COVID-19 patients and 18 healthy controls for soluble IFNAR2 (sIFNAR2) comparison. Biomarker samples were obtained during hospitalization, approximately seven days after symptom onset. Outcomes were final clinical status, severe respiratory involvement, post-sampling clinical worsening and death. Analyses included non-parametric testing, false-discovery-rate adjustment, effect-size estimation, exploratory ROC curves, parsimonious regression, penalized internal validation, composite scores and molecular-structure analyses. Results: Final status was favorable outcome in 31 patients, severe non-fatal disease in 22 and death in 7. sIFNAR2 was higher in patients than in healthy controls and highest among non-survivors, but did not distinguish favorably from severe non-fatal disease. The most consistent severity-associated signals were IL-6, D-dimer, total thiols, IL-10, LDH, ferritin, leukocytes and IL-1RA. D-dimer, IL-6 and ferritin yielded the largest exploratory univariable AUCs for severe respiratory involvement, whereas ferritin, IL-10, IL-1RA and sIFNAR2 predominated in event-limited mortality analyses, which were based on only seven deaths. Composite multi-axis scores and PLS-DA were tools requiring external validation. Conclusions: Biomarker patterns during admission were associated with adverse evolution. Conventional markers remained the most practical signals, while cytokines, redox markers and sIFNAR2 provided complementary biological information. sIFNAR2 should be interpreted as an exploratory complementary marker of the interferon receptor axis, mainly linked to mortality, not as a stand-alone clinical test or functional measure of IFNAR signaling. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by excessive extracellular matrix remodeling and limited therapeutic options. Matrix metalloproteinase-2 is involved in extracellular matrix degradation and tissue remodeling, making it a relevant target for antifibrotic drug discovery. In this study, an MMP2-focused ligand-based pharmacophore model was developed and was applied to screen a curated FDA-approved drug library, leading to the identification of 83 pharmacophore-matching compounds. These compounds were subsequently prioritized through molecular docking against the catalytic site of MMP2, and the five best candidates were further evaluated by molecular dynamics (MD) simulations. Because of the biological relevance of MMP3 in pulmonary fibrosis, these five selected compounds were also profiled against MMP3 as a secondary target. Among them, Regorafenib (S1178) and Capmatinib (S2788) showed the most favorable cross-target profiles and were further supported by MD analysis. From these findings, S1178 and S2788 were proposed as promising MMP2-prioritized compounds with potential MMP3 cross-activity, warranting further experimental validation as candidate antifibrotic MMP modulators. Full article

Background: Atrial fibrillation (AF) is the most prevalent clinical arrhythmia with severe cardiovascular complications, yet its metabolic molecular mechanisms remain poorly defined. Omics-based metabolic profiling provides a powerful strategy to systematically decode AF-associated metabolic disorders. Methods: In this work, high-coverage targeted liquid chromatography–tandem mass spectrometry (LC-MS/MS) metabolomics and lipidomics were applied to absolutely quantify 746 serum metabolites from AF patients and healthy controls. Results: We systematically characterized global metabolic perturbations in AF serum, including impaired fatty acid metabolism, suppressed mitochondrial β-oxidation, myocardial lipotoxic lipid accumulation, and systemic depletion of glycerophospholipids. Global multiscale embedded correlation network analysis (MECNA) further identified 11 AF-specific dysregulated metabolic modules and core hub metabolites driving metabolic remodeling. Leveraging binary logistic regression, we constructed and independently validated a two-molecule diagnostic biomarker panel to distinguish AF patients from healthy subjects. The combined biomarkers Phe-Trp and FA 22:5 achieved outstanding diagnostic performance, with area under the curve (AUC) values of 0.964 in the discovery cohort and 0.993 in the validation cohort. Conclusions: Collectively, this study adopts high-depth targeted quantitative omics to comprehensively map AF metabolic signatures, dissect disease-relevant metabolic networks, and establish a robust serum biomarker panel with great translational potential for non-invasive AF clinical diagnosis. Full article

Renewable energy can be harvested from salinity gradients using reverse electrodialysis (RED); however, the open-circuit voltage and power output of this process can be significantly reduced by multivalent ions and natural organic matter found in natural waters. In this work, a tailor-made polyepichlorohydrin-based anion exchange membrane (AEM) surface was modified using an electrophoretic layer-by-layer (LbL) polyelectrolyte assembly. Negatively charged poly(styrene sulfonate) (PSS) and positively charged poly(ethyleneimine) (PEI) were employed to construct three-layer architectures in which PEI served as the interlayer. The results indicate that the molecular weight of the PEI interlayer strongly influences the surface composition and charge of the final AEMs. RED experiments performed in the presence of Na₂SO₄ revealed that AEMs incorporating the high-molecular-weight PEI exhibited enhanced apparent Cl⁻/SO₄²⁻ selectivity and delivered an increased power density. Fouling tests using a real humic–fulvic acid mixture demonstrated that the hydrophilic PSS top layer effectively mitigated organic fouling and preserved RED performance. Furthermore, short-term stability testing provided a preliminary indication of the stability of the polyelectrolyte layers under short-term operating conditions. This study highlights the critical role of interlayer molecular weight in defining the surface chemistry, apparent ion selectivity, and antifouling behavior of LbL-modified tailor-made AEMs, providing important design guidelines for improving RED performance in realistic feedwaters. Full article

Per- and polyfluoroalkyl substances (PFASs) are persistent contaminants that are widely detected in aquatic environments and are difficult to remove because of their stable carbon–fluorine bonds and amphiphilic structures. Metal–organic frameworks (MOFs), with high surface areas, tailorable porous frameworks, diverse metal nodes, and adjustable surface functionalities, provide promising platforms for PFAS adsorption. This review summarizes recent advances in the adsorptive removal of PFASs from water using MIL-, UiO-, ZIF-, and PCN-type MOFs and their derivatives. The effects of hydrophobic interface construction, amine functionalization, fluorination, defect engineering, thermal conversion, and pore regulation on adsorption performance were discussed. PFAS adsorption by MOFs is governed by multiple interactions, including electrostatic attraction, Lewis acid–base interactions, hydrophobic interactions, van der Waals forces, and hydrogen bonding. The impact of solution pH, coexisting ions, natural organic matter, PFAS molecular structures, and MOF structures was also reviewed. In addition, regeneration strategies and PFAS adsorption performance after regeneration were summarized. Despite the advances, challenges persist regarding MOF stability, regeneration, cost-effectiveness, and adsorption performance in real water matrices. Future research should therefore focus on sustainable material design and scalable development of MOF-based treatment systems for effective PFAS remediation. Full article

To further advance the recycling of pavement waste, the secondary-aging and multiple-rejuvenation processes of bitumen are first systematically reviewed. Beginning with primary-aging mechanisms, rejuvenator classification and physicochemical properties are summarized to aid elucidation of primary rejuvenation. Secondary-aging evolution of technical and physicochemical properties of rejuvenated bitumen (RB) is critically analyzed. The aging resistance of virgin bitumen and RB is quantitatively compared via extensive literature data. The background and progress of multiple rejuvenation cycles are also outlined. The existing literature shows that identical aging modes can induce distinct component variations, while degradation patterns remain consistent across modes. Among petroleum-based rejuvenators, those with aromatic content exceeding 60% are widely used, and the polar carboxyl groups of tall oil account for their high efficacy. RB aging resistance strongly correlates with both rejuvenator type and dosage. Most RB outperforms virgin bitumen in aging resistance, and post-aging variation amplitudes of softening point and high-temperature failure temperature are approximately 20% for both, while those of penetration and viscosity range from 60% to 120%. Multiple aging–rejuvenation trends resemble those of primary cycles, with progressive macro- and micro-property deterioration as cycles increase. Future work includes developing high-performance bitumen from aged feedstock, establishing molecular screening systems for fatty acid bio-oil rejuvenators, and advancing multiple rejuvenation via molecular dynamics. Full article

Iron deficiency (ID) represents one of the most prevalent nutritional disorders worldwide, affecting approximately 1.2 billion individuals. Beyond its well-established hematological consequences, emerging evidence demonstrates that ID profoundly impacts endocrine function across multiple organ systems. Iron serves as an essential cofactor for numerous enzymes involved in hormone synthesis, metabolism, and signaling pathways. This comprehensive review examines the bidirectional relationships between iron deficiency and endocrine pathologies, including thyroid disorders (hypothyroidism, Hashimoto’s thyroiditis, thyroid peroxidase impairment), diabetes mellitus (types 1 and 2), obesity, Polyendocrine Metabolic Ovarian Syndrome (PMOS), male hypogonadism, adrenal insufficiency, growth hormone deficiency, pituitary dysfunction, and parathyroid disorders. We systematically analyze the molecular mechanisms linking iron metabolism to endocrine dysfunction, with particular emphasis on thyroid peroxidase activity, insulin secretion and sensitivity, hepcidin regulation, testosterone synthesis, and cortisol production. Furthermore, we critically evaluate the therapeutic potential of liposomal iron supplementation, a novel delivery system that offers superior bioavailability and gastrointestinal tolerability compared to conventional oral iron formulations. Randomized controlled trials demonstrate that liposomal iron achieves comparable efficacy to intravenous iron while significantly reducing adverse events. This review synthesizes current evidence to provide clinicians with a comprehensive understanding of iron-endocrine interactions and evidence-based recommendations for iron supplementation in endocrine disorders. Recognition of these complex relationships is essential for optimizing diagnostic and therapeutic approaches in patients with concurrent iron deficiency and endocrine dysfunction. Full article

Mosquito-borne viruses, including dengue, Zika and chikungunya viruses, place a substantial burden on diagnostic services, especially where molecular laboratories are inaccessible or slow to return results. Point-of-care biosensors could reduce turnaround times and bring testing closer to patients in primary care, outbreak response, and field settings. This review critically examines nucleic acid amplification, CRISPR-assisted assays, lateral-flow platforms, microfluidic systems, electrochemical and optical biosensors, paper-based devices, and smartphone-enabled readouts. These technologies are evaluated in terms of sample preparation, analytical sensitivity and specificity, matrix interference, multiplexing, workflow integration, cost, and clinical validation. Overall, nucleic-acid-amplification and CRISPR-assisted platforms often achieve low reported detection limits under controlled conditions; lateral-flow and paper-based devices offer relatively simple and minimally instrumented workflows; and microfluidic, electrochemical, and smartphone-enabled systems support increasing levels of workflow integration, quantitative readout, and connectivity. However, few platforms currently integrate these advantages into a fully integrated and clinically validated “sample-to-result” workflow. Due to sample heterogeneity, viral strains, reference methods, assay conditions, and disparities in reporting practices, conducting meaningful cross-study comparisons remains challenging. Limited comparisons and insufficient prospective clinical and field validation further restrict the assessment of practical diagnostic utility. Therefore, strong analytical performance alone should not be interpreted as evidence of clinical validity. Priority directions include unified definitions of performance and reporting units, standardized validation protocols and external quality assessment, prospective multi-site evaluation using representative populations and specimens, and earlier consideration of manufacturing scalability, reagent stability, quality systems, and applicable regulatory requirements. Future platforms should integrate simplified sample preparation, multiplex detection, objective digital or AI-assisted interpretation, and secure connectivity while demonstrating measurable benefits for patient management and outbreak surveillance. Full article

Schwann cell (SC)-based therapy is currently being debated as an approach to promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). The main limitation of SC transplantation in MS patients is the short-term functional activity of SCs in the CNS environment. The goal of this study was to determine phenotypic, functional, and signaling changes in human SCs treated with CSF samples from MS patients in vitro, and to characterize the molecular mechanisms underlying SC injury response in the model MS microenvironment. We demonstrated that SC proliferation and motility were suppressed, while the expression of both pro-myelinating genes and negative regulators of myelination was up-regulated in cells incubated with CSF from MS patients. This was associated with active phosphorylation of ERK and c-Jun, and inhibition of these signaling pathways prevented SC changes. The overall analysis of detected abnormalities and SC markers indicates that SCs do not exhibit either a ‘classic’ dedifferentiation-repair-like phenotype or a myelin-forming maturation phenotype when placed in MS-like conditions. They demonstrate an uncommon pattern of cellular signaling reprogramming, associated with decreased motility and potentially decreased myelination. We thus suggest that ERK- and JNK-modulated SCs should be further investigated as a potential cell source for CNS repair in MS. Full article

Komagataeibacter species are among the highest-yielding bacterial cellulose producers and offer a promising platform for the genetic engineering of functionalized bacterial cellulose. However, routine strain engineering remains limited by inefficient screening of genomic integrants and acidic culture conditions that inhibit acid-sensitive cellulose modifications. Here, we exploited the reduced-acidification phenotype of a Komagataeibacter sucrofermentans glucose dehydrogenase deletion mutant (Δgdh) to overcome both limitations. We developed a simple phenotypic screen based on reduced acidification to identify candidate colonies for subsequent molecular confirmation. We further exploited this phenotype by constructing a Δgdh::tyr1 strain that, after optimizing culture conditions, produced melanated bacterial cellulose in a single step, without the manual pH neutralization required by previous methods. Together, these results establish reduced acidification as a practical engineering phenotype that simplifies strain engineering and enables acid-sensitive modification of bacterial cellulose, thereby expanding the range of bacterial cellulose modifications achievable in Komagataeibacter. Full article

Rising drug resistance undermines current anti-influenza virus therapies. Although targeting the hemagglutinin (HA)–sialic acid receptor interaction is a promising strategy, progress is impeded by the lack of subtype-independent screening models. Herein, we established a fluorescence-based cell high-throughput model using fluorescein isothiocyanate-conjugated Sambucus Nigra Lectin (FITC-SNA) as a stable HA surrogate and α-2,6-sialyltransferase (ST6GAL1)-overexpressing MDCK cells to mimic the HA–receptor interface. This platform was designed to serve as an efficient primary screening tool to rapidly filter large compound libraries for potential binders to the receptor-binding interface. Screening 10,000 compounds identified Obatoclax Mesylate and Ethylparaben as primary hits. Both exhibited broad-spectrum HA inhibition activity, validating the model’s capability to identify compounds interfering with viral attachment. Further cellular antiviral assays revealed cytotoxicity for both compounds, resulting in low selectivity indexes (SIs), indicating that while these molecules effectively target the interaction site, they require substantial structural optimization for therapeutic use. Molecular docking confirmed their binding to type A H1N1, H3N2, and B/Victoria HA proteins, while ADMET predictions highlighted specific structural optimization needs to mitigate toxicity. In conclusion, this subtype-independent, highly specific high-throughput screening (HTS) model provides an efficient and reliable platform for early-stage influenza drug discovery and lead compound development. Full article

Sperm cryopreservation is crucial for artificial propagation and the long-term preservation of valuable germplasm resources. This study aimed to establish an effective ultra-low temperature sperm cryopreservation protocol for Hefang bream (HFB), a novel hybrid bream variety developed through distant hybridization between blunt snout bream (Megalobrama amblycephala) and topmouth culter (Culter alburnus) followed by two rounds of backcrossing. Different combinations of extenders and cryoprotectants were evaluated based on post-thaw sperm motility and motion parameters to identify the optimal cryoprotective formulation for HFB sperm, with untreated fresh sperm as the control. Fresh sperm exhibited a total motility (MOT) of 98.87 ± 1.40%, curvilinear velocity (VCL) of 118.87 ± 5.38 μm/s, straight-line velocity (VSL) of 86.18 ± 5.67 μm/s, and average path velocity (VAP) of 107.48 ± 4.23 μm/s. The optimal formulation consisted of D15 extender (composed of 8 g/L NaCl, 0.5 g/L KCl and 15 g/L glucose) supplemented with 10% dimethyl sulfoxide (DMSO). Using a fresh sperm-to-cryoprotective medium ratio of 1:5 and a stepwise cooling procedure, post-thaw MOT, VCL, VSL, and VAP were 43.77 ± 13.85%, 37.54 ± 3.06 μm/s, 29.82 ± 1.98 μm/s, and 31.99 ± 2.14 μm/s, respectively. Further analyses revealed that the plasma membrane integrity (PMI), DNA integrity (DI) and mitochondrial activity (MA) of cryopreserved sperm were 43.40 ± 2.01%, 57.10 ± 4.79%, and 42.00 ± 1.65%, respectively, all of which were significantly lower than those of fresh sperm (p < 0.05). Ultrastructural analyses using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that cryopreserved spermatozoa exhibited structural abnormalities, including plasma membrane disruption, flagellar fragmentation, and mitochondrial damage. Artificial insemination experiments showed that the fertilization and hatching rates of the cryopreserved sperm group were 55.10 ± 3.30% and 81.50 ± 3.29%, respectively, indicating that the established protocol could effectively support artificial reproduction in HFB. Furthermore, proteomic analysis was performed to investigate cryopreservation-induced molecular damage, identifying 7 cryopreservation-associated leakage proteins that were mainly enriched in pathways related to energy metabolism, cytoskeletal organization, and oxidative stress response. This study establishes an effective sperm cryopreservation protocol for HFB and provides insights into the cellular and molecular mechanisms underlying cryopreservation-induced sperm damage, offering a valuable reference for the development of sperm cryopreservation technologies in other economically important fish species. Full article

Chronological skin aging is a complex biological process characterized by progressive collagen degradation and cellular senescence. Among the molecular regulators implicated in these hallmarks, miR-34a has emerged as a critical mediator linking inflammation and senescence pathways. Consequently, this study aimed to investigate the anti-aging potential of Helix aspersa snail mucus, with particular emphasis on its modulation of miR-34a-associated molecular mechanisms, and to explore liposomal encapsulation as a strategy to improve its topical performance and user acceptability. Snail mucus was collected and characterized using LC–ESI–QTOF–MS/MS, while its antioxidant activity was assessed by DPPH and FRAP assays. Afterward, mucus-loaded liposomes were developed and optimized. Aged mice were assigned to control aged, Lipo, free mucus, and Lipo-mucus groups, alongside a young control group. Anti-aging efficacy was evaluated through wrinkle grading, skin moisture determination, histological examination, and collagen assessment by Masson’s trichome staining. miR-34a-5p, its target genes, and related aging-associated genes were also determined, followed by upstream regulatory network prediction using X2Kweb. The optimized formulation exhibited nanoscale particle size, high encapsulation efficiency, enhanced skin retention, and improved spreadability. Compared with free mucus, Lipo-mucus significantly increased the epidermal and dermal deposition of total protein and allantoin. Both treatments exerted remarkable anti-aging effects, evidenced by improved skin architecture and enhanced collagen deposition. These effects were associated with modulation of the miR-34a-5p-driven senescence hub. Collectively, liposomal encapsulation enhanced the cutaneous delivery, cosmetic properties, and anti-aging efficacy of H. aspersa mucus, supporting its potential as a mechanism-based cosmeceutical intervention for chronological skin aging. Full article

Genetic neurodevelopmental disorders (NDDs) encompass a heterogeneous group of conditions characterized by impaired cognitive, behavioral, and neurological development resulting from pathogenic variants affecting brain development and synaptic function. Advances in molecular genetics and next-generation sequencing have significantly expanded the understanding of the genetic architecture underlying disorders such as Rett syndrome (RTT), Fragile X syndrome (FXS), Angelman syndrome (AS), and autism spectrum disorders. Beyond these classical neurodevelopmental disorders, spinal muscular atrophy (SMA) is included as a paradigmatic example of successful RNA-based therapeutic translation. Concurrently, RNA-based therapeutics have emerged as promising precision medicine strategies capable of modulating gene expression at the transcriptional and post-transcriptional levels. These approaches include antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), messenger RNA (mRNA) therapies, RNA editing technologies, and splice-modulating agents. Recent clinical successes, particularly in spinal muscular atrophy, have demonstrated the transformative potential of RNA therapeutics in neurological disease. However, substantial challenges remain, including BBB penetration, long-term safety, immune activation, and genotype-specific variability in therapeutic response. This review summarizes current advances in RNA-based therapeutics for genetic NDDs, highlighting molecular mechanisms, disease-specific therapeutic strategies, translational progress, delivery challenges, and future directions. Overall, continued progress will depend on the integration of disease biology, rational RNA therapeutic design, and effective CNS-targeted delivery, supporting the broader implementation of precision RNA medicine for genetic neurodevelopmental disorders. Full article