Development of an ion-pairing reagent-assisted LC-MS/MS method employing fragmentation with stepped collision energy for monophosphoryl lipid A containing 3-deoxy-D-manno-octulosonic acid and its derivatives.

Clioquinol alleviates Aspergillus fumigatus keratitis through antifungal and anti-inflammatory effects associated with metal chelation and Nrf2/HO-1 signaling.

Synthesis and pharmacodynamics evaluation of cyclobutenamide derivatives against influenza a virus in vitro and in vivo.

Cytotoxic effects of glass ionomer cements modified by metallic agents: A systematic review and meta-analysis.

Disruptions in cellular energy metabolism have emerged as central contributors to a broad spectrum of human diseases. While conventional therapeutic strategies can alleviate symptoms, they typically target downstream disease manifestations and often fail to address the underlying energetic dysregulation fueling disease progression. Bioenergetic organelles-engineered from mitochondria and thylakoids-represent a transformative approach by restoring cellular energy homeostasis. Functioning as autonomous metabolic modules, they generate ATP, reductive equivalents, and oxygen in situ, while concurrently modulating redox balance, oxygen tension, and immune-metabolic signaling to restore cellular homeostasis. Recent preclinical evidence highlights their therapeutic versatility, including alleviating tumor hypoxia, restoring bioenergetic function in myocardial and neuronal tissues, reducing inflammatory damage, and normalizing immune cell metabolism. Unlike nanocarriers that primarily serve as delivery vehicles, these bioenergetic organelles actively remodel pathological microenvironments by integrating metabolic restoration with multi-targeted therapeutic actions. This review outlines the design principles, mechanistic basis, and disease-specific applications of artificial bioenergetic organelles, while also addressing key translational challenges such as targeted delivery, immunocompatibility, functional longevity, critical considerations regarding biological safety, and the long-term metabolic fate of these constructs. Positioned at the convergence of bioenergetics, nanotherapeutics, and synthetic biology, these biomimetic systems offer a flexible platform for redefining disease intervention through precise metabolic regulation.

With the rapid development of Internet of Things and artificial intelligence technologies, flexible wearable sensors have shown great potential in human-machine interaction and health monitoring fields. However, traditional hydrogel sensors face challenges such as water loss, freezing, and the use of toxic initiators during the preparation process, which lead to biological safety issues. To address these challenges, this paper proposes a green, initiator-free polymerization strategy based on the deep eutectic solvent system composed of choline chloride (ChCl) and D-sorbitol. By utilizing the property that the nitrogen-containing quaternary ammonium group in the ChCl molecule can generate free radicals upon ultraviolet irradiation, this study achieves the rapid polymerization of acrylamide in an initiator-free manner. The prepared eutectogel exhibits high transparency (≈96%), skin-fitting elastic modulus, good antifreezing performance, suitable breathability, and broad-spectrum adhesion. The flexible strain sensor constructed based on the eutectogel has high sensitivity, wide detection range, and good fatigue resistance. Combined with machine learning algorithms, this sensor system achieves a high accuracy (98.5%) of recognizing Curwen gestures. This research provides an innovative approach for developing safe, reliable, and environmentally adaptable intelligent wearable devices and has broad application prospects in intelligent music education and modern human-machine interaction.

Full-material upcycling of carbon Fiber/Epoxy waste into cytocompatible Multi-functional aerogels for thermal and acoustic Insulation, and oil spill cleaning.

We present SNIPSNP (crisprtools.org/snipsnp), a comprehensive bioinformatics pipeline for designing experiments for CRISPR-induced homology-directed repair (HDR). The tool addresses the critical challenge of Cas9 re-cleavage by simplifying the selection of "blocking" silent variants that are effective at inhibiting RNP binding upon donor-templated editing. SNIPSNP handles complex edits, including indels, and uses multi-objective optimization to balance editing efficiency with biological safety. From user-defined wild-type and desired HDR alleles, the pipeline identifies candidate guides, annotating them with integrated efficiency scores and genome-wide off-target assessments. Uniquely, SNIPSNP evaluates guide binding against the post-edit genome to determine whether the therapeutic variant alone disrupts repeated Cas9 recognition. When necessary, it introduces synonymous blocking variants, prioritizing PAM and seed regions to minimize re-cleavage probability and editing of the wild-type (WT) allele when editing heterozygous variants. All candidate modifications undergo safety profiling and prioritization of known benign variants from dbSNP. We experimentally validated SNIPSNP and benchmarked it on pathogenic inborn error of immunity variants in primary patient T-cells. Across loci, SNIPSNP-designed templates outperform standard "correction-only" strategies, demonstrating enhanced precision editing, and reduced re-cleavage, establishing SNIPSNP as a robust platform for genome editing and disease modeling.

The precision diagnosis and effective treatment of neurological diseases have long been hampered by the blood-brain barrier (BBB). Nanomaterials capable of crossing the BBB, endowed with unique advantages such as targeted delivery and transbarrier penetration, provide a crucial solution for overcoming this bottleneck, thereby significantly enhancing the precision and effectiveness of diagnosis and treatment. This review is based on the systematic collection and analysis of recent literature. On this basis, this review summarizes the core characteristics and relative advantages of several major penetration mechanisms: receptor-mediated penetration relies on specific binding to receptors, featuring high targeting specificity and low toxicity; adsorption-mediated penetration depends on surface interactions, with broad universality and simple preparation; and carriermediated penetration achieves transport via carriers, exhibiting high drug-loading capacity but moderate targeting specificity. Correspondingly, different types of nanomaterials have distinct focuses on their applicable scenarios: metallic nanomaterials are suitable for imaging diagnosis, tumor hyperthermia, etc.; polymeric nanomaterials are applicable for drug delivery, gene therapy, etc.; lipid-based nanomaterials are appropriate for small-molecule drug delivery, brain-targeted drug administration, etc. Nanomaterials capable of crossing the BBB share common limitations. For example, these include the long-term biological safety of nanomaterials, challenges in improving targeting efficiency, and hurdles in large-scale preparation. To address the aforementioned limitations, we propose specific and forward-looking future research directions. These include the development of intelligent responsive nanocarriers and the establishment of a standardized toxicity assessment system, which are expected to provide constructive insights for advancing the clinical translation of BBB-crossing nanomaterials in neurological disease diagnosis and treatment.

Optimizing post-polymerization atmospheres is critical for improving the clinical performance and durability of DLP-printed denture base resins. This study evaluated the effects of post-polymerization atmospheres and thermal aging on the mechanical, physical, and biological properties of denture base resins fabricated by digital light processing (DLP). A milled denture base resin served as the control (M), and DLP-printed specimens were post-polymerized under three atmospheric conditions: air (A), vacuum (V), and nitrogen (N). Vickers hardness, flexural strength, and flexural modulus were evaluated before and after thermal aging, while polymerization efficiency and cytocompatibility were further analyzed. Statistical analysis was performed using one-way analysis of variance (ANOVA), with the significance level set at P < 0.05. The M group consistently exhibited superior mechanical properties and aging stability, with flexural strength decreasing from 110.92 ± 5.01 to 104.40 ± 1.79MPa and Vickers hardness from 21.41 ± 0.65 to 19.31 ± 0.28 VHN after aging. Among the DLP groups, the A group showed higher flexural strength and hardness, decreasing from 95.78 ± 1.45 to 83.63 ± 3.73MPa and from 19.96 ± 1.55 to 12.67 ± 1.83 VHN, respectively. Thermal aging significantly reduced flexural strength, flexural modulus, and hardness in all groups (P < 0.05). However, all DLP groups showed acceptable degree of conversion and cytocompatibility, with relative cell viability exceeding 70% and meeting ISO 10993-5 requirements. Therefore, optimization of post-polymerization conditions is essential to improve long-term clinical performance without compromising biological safety.

Despite the widespread use of 3D printing, the toxicological profile of commercially available filaments remains largely uncharacterized across both consumer and scientific communities. The persistent lack of comprehensive toxicological data regarding proprietary industrial additives in standard safety sheets raises significant concerns. To address this critical knowledge gap, this in vitro study systematically evaluated the biological impact of short-term (24 h) and long-term (7 days) exposure to 16 commercially available filaments-representing 8 polymer types (PLA, PETG, CPE, PC, ABS, ASA, PP, and FLEX)-on primary human dermal fibroblasts, to simulate prolonged skin contact typical for wearable and biomedical applications. By integrating standard ISO 10993-5 viability assays with high-resolution respirometry (HRR), we identified critical instances of "hidden cytotoxicity." Our findings reveal severe, material-specific metabolic disruptions in specific commercial formulations of widely used polymers, such as the tested FLEX, PETG, PC, and PP filaments. The most substantial metabolic dysfunction was recorded in the evaluated FLEX (TPU) filament, which exhibited acute toxicity characterized by immediate and progressive biological deterioration from the onset of exposure, ultimately culminating in a critical bioenergetic impairment by day 7. In contrast, a distinct toxicological paradox emerged in the evaluated PETG, PC, and PP samples. These materials triggered stress-induced compensatory hyperproliferation, characterized by an increased cell population that masked a severe, progressive decline in single-cell metabolic activity (SCMA) and single-cell fluorescence (SCF). Conversely, the tested commercial ABS, CPE, PLA, and ASA filaments demonstrated robust cytocompatibility, maintaining stable metabolic and mitochondrial functions throughout the entire long-term (7 days) exposure period. PLA exhibited a more nuanced profile: while generally supporting high overall cell viability, it induced noticeable sub-lethal metabolic stress, which we hypothesize reflects a combined effect of proprietary additives and bioenergetic alterations linked to lactate release during polymer hydrolysis. Furthermore, a certified "medical-grade" ABS variant paradoxically induced significant metabolic dysfunction, underperforming compared to standard industrial ABS. These results demonstrate that the biological safety of a 3D-printed construct cannot be extrapolated merely from its polymer base, as cytotoxicity is hypothesized to be primarily driven by proprietary additives (e.g., plasticizers, stabilizers, and pigments) and thermal degradation by-products likely generated during the 3D printing process. We conclude that the standard ISO 10993-5 viability threshold (≥70%) is insufficiently sensitive to capture latent, sub-lethal metabolic stress, underscoring the need for the adoption of more rigorous, multi-parametric screening protocols.

NIR-responsive MnO2-functionalized mesoporous silica hydrogel: Fabrication and antibacterial activity evaluation.

With the increasing incidence of inflammatory bowel disease (IBD), antioxidant therapies aimed at scavenging excess reactive oxygen species (ROS) are considered promising treatment options. However, current strategies, such as the use of natural antioxidants or synthetic nanozymes, are often limited by inefficient biological delivery and potential safety concerns. To address these challenges, we developed OFn-EcN (OmpA-Ferritin nanozymes expressed in EcN), a novel biosynthetic system that integrates natural ferritin nanozymes with the beneficial probiotic Escherichia coli Nissle 1917 (EcN). Specifically, biosynthesized ferritin nanozymes exhibit superoxide dismutase- and catalase-like activities to scavenge ROS in a cascade. Upon oral administration, OFn-EcN effectively neutralizes excessive ROS in the gut, protecting against probiotics and breaking the vicious cycle of inflammation and oxidative damage. Furthermore, the system restores intestinal barrier integrity, enhances nutrient absorption, and reestablishes a healthy microbial balance with a low risk of extraintestinal dissemination and high biosafety. In preclinical models, OFn-EcN effectively prevented the onset of DSS-induced colitis. Thus, this innovative approach offers a promising strategy for the prevention and effective alleviation of IBD.

In the field of nanomedicine, nanoparticles have gained increasing attention due to their potential as therapeutic and diagnostic tools across a wide range of biomedical applications. However, despite their growing popularity and promising results, understanding their biological interactions and accurately evaluating their safety and efficacy remain significantly challenging. In this context, the invertebrate model organism Caenorhabditis elegans (C. elegans) provides an ideal toxicological model system because of its favorable characteristics. In this research, we used C. elegans to investigate the effects of potentially toxic iron-doped zinc oxide nanoparticles (ZnO NPs) and their biocompatible counterpart, lipid-coated ZnO (L-ZnO NPs). In addition, we combine these NPs with physical stimulation, i.e., ultrasound, to which these NPs are responsive, aiming to evaluate possible combined treatments in animals. The toxicity of ZnO and L-ZnO NPs was evaluated on this invertebrate model. In addition, external acoustic pressure stimulation was studied, evaluating the sole effects of ultrasound stimulation and its combined application with NPs. Multiple biological parameters were analyzed to assess treatment effects, including viability, biodistribution, egg-laying, body bends, and production of radical species associated with oxidative stress. This study demonstrates that L-ZnO NPs exhibit greater biological safety than ZnO NPs, while their combined application with ultrasound does not result in an additive effect. Additionally, the results highlight the potential of using C. elegans as a primary model to evaluate nanomedicine treatments and obtain initial insights into the effects of nanoparticles in animal systems.

Forty four bacterial candidates isolated from Egyptian atrazine polluted soil sites, were examined to select atrazine bio-degraders. Among them thirty four were proved their ability to use it as nitrogen source. Strains HA19 and A7 gave the highest efficient rate to biodegrade atrazine with efficiency of 81% and 81.3%. They were identified and belonging taxonomically to Klebsiella sp. and Ochrobactrum sp. according to sequencing of 16S rRNA and phylogenetic analysis. Both of them confirmed their possession of atrazine degrading genes like atzA, atzC and atzD while atzB was appeared as faint band with strain A7 only. HPLC analysis indicated that the two strains degraded atrazine via the pathway of producing deethylatrazine as an important intermediate. Thus interesting data revealed the possibility of acquisition of these strains for two couples of atrazine degrading mechanisms located on chromosomal and plasmid sites. Applying the advanced statistical method of response surface methodology (RSM) based on central composite design (CCD) model has contributed to increase the biodegradation process with both strains by a rate of (94.2%) and (96.7%) on respectively. For our knowledge this article is one of condensed work and applicable way that will introduce bio safety solution for bioremediating atrazine and reducing its toxicity in agricultural polluted fields, as there is little reports from Egypt published before concerning atrazine bioremediation.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-026-55623-5.

Secukinumab, an interleukin-17A inhibitor widely used in psoriasis and related disorders, has been linked to opportunistic infections. Candida infections are a key safety concern, yet their real-world clinical profiles, risk distribution, and onset patterns remain insufficiently characterized. To evaluate the clinical characteristics, severity, onset patterns, and risk factors of Candida infections associated with secukinumab, thereby informing risk stratification and patient management. A retrospective pharmacovigilance analysis was performed using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) from Q1 2004 to Q1 2025. Secukinumab reports were retrieved, and Candida-related adverse events were identified using a predefined Candida-specific MedDRA Preferred Term dictionary. Disproportionality analyses were conducted using reporting odds ratios (RORs) with 95% confidence intervals (CIs). Event severity, subgroup characteristics, and time-to-onset were assessed, and Weibull shape parameter modeling was used to characterize risk patterns. We identified 1,075 Candida events (0.8% of all secukinumab reports). Oral, esophageal, and vulvovaginal candidiasis predominated. All eight focal PTs showed significant disproportionality, with genital candidiasis yielding the strongest signal (ROR 19.85; 95% CI 12.91-30.53). Over half of events met criteria for serious outcomes. Stronger reporting signals were observed in females and adults aged 18-64 years. Median onset was 2-3 months, and Weibull β < 1 indicated an early-failure pattern, suggesting heightened risk shortly after treatment initiation. Candida infections during secukinumab therapy are uncommon but often severe, particularly in defined high-risk groups. Early onset highlights the importance of vigilant monitoring during initial treatment months. Real-world pharmacovigilance remains essential for optimizing biologic safety. Not applicable.

Syringeable hydrogels have emerged as transformative tools for precise drug delivery and controlled release, capitalizing on their exceptional injectability, shape adaptability, and localized retention. This review provides an overview of the recent advancements in hydrogel-based cargo delivery systems, focusing on injectable hydrogelators with immunomodulatory functions. Design principles tailored to optimizing the gelification process are presented, compared, and discussed following detailed structural analysis, with an emphasis on hydrogel formation mechanisms and biointeractions. Next, we summarize key applications, including adoptive cell therapy, catalytic immunotherapy, cancer vaccination, proteolysis-targeting chimeras, and immunometabolic intervention. To achieve a high therapeutic index while minimizing systemic side effects, the underlying mechanisms governing the spatiotemporal release of immunomodulators are presented as well. Finally, this review systematically discusses the persistent obstacles concerning manufacturing, biological safety, and clinical translation of these regulatory frameworks.

Safety of Non-MS Biologics in Patients with Multiple Sclerosis: A Multi-center Retrospective Study of MS Patients with Co-morbid Autoimmune Conditions (S40.007)

Inflammatory bowel diseases (IBD) induce serious symptoms, but the current treatment approaches suffer from low bioavailability, poor patient compliance, and limited efficacy. Therefore, the development of advanced drug delivery systems for oral drugs is urgently needed. In this study, a hypoxia-responsive drug delivery platform was designed using Co2+ and olsalazine (OL) as the building blocks, followed by coating with dopamine-modified hyaluronic acid (HA-DA), yielding CoOL-HA-DA. The HA-DA coating achieves gastric acid protection and an extended intestinal residence time for 48 h with a colon-specific adhesion ability. The negative charge of CoOL-HA-DA enables targeted delivery to inflammatory sites and significant biological safety through the repulsion with the negative charge of the mucus layer. Yet, at diseased sites featuring reactive oxygen species (ROS), CoOL can eliminate ROS and release 5-aminosalicylic acid (5-ASA) to treat IBD under conditions of intestinal hypoxia. Both in vitro and in vivo results show that the CoOL-HA-DA improved the sustained release of 5-ASA, demonstrating its potent efficacy in IBD treatment with reduced side effects. Collectively, CoOL-HA-DA, as a hypoxia-responsive drug delivery platform, provides another medical approach for IBD and other gut disease management.

In cartilage tissue engineering, successfully mimicking the natural extracellular matrix is essential for promoting hyaline cartilage regeneration. The triple-helix structure of collagen has been identified as a critical element in this process, though preserving this structure while minimizing immunogenicity remains a significant challenge. This study employed high-precision enzymatic digestion technology to specifically remove immunogenic terminal fragments from collagen while preserving its functional triple-helix configuration. The resulting collagen-based hydrogel was engineered with thermosensitive properties, enabling it to adaptively fill irregular cartilage defects and undergo rapid gelation at body temperature. The modified collagen hydrogel demonstrated significantly improved biological safety, with complement activation levels substantially decreasing following removal of terminal peptide segments-confirming the immunogenic role of these regions. Mechanically, the hydrogel successfully replicated the viscoelastic characteristics of natural cartilage, exhibiting matched dynamic mechanical properties capable of cushioning shear-induced damage. Its porous architecture facilitated accelerated nutrient transport while supporting effective cell adhesion and guiding organized proteoglycan deposition with minimal fibrosis. In vivo evaluation revealed a 30.7% higher MOCART score in the experimental group compared to controls, with mechanical properties closely approximating those of healthy native cartilage. Collagen hydrogels that maintain the triple-helix structure represent a highly promising biomaterial platform for cartilage regeneration, combining excellent biocompatibility, functional mechanical properties, and significant tissue repair capability while effectively addressing the critical challenge of immunogenicity through targeted terminal peptide removal.