Magnetic nanomaterials mediate precise magnetic therapy.

Magnetic nanoparticle (MNP)-mediated precision magnet therapy plays a crucial role in treating various diseases. This therapeutic strategy compensates for the limitations of low spatial resolution and low focusing of magnetic stimulation, and realizes the goal of wireless teletherapy with precise targeting of focal areas. This paper summarizes the preparation methods of magnetic nanomaterials, the properties of magnetic nanoparticles, the biological effects, and the measurement methods for detecting magnetism; discusses the research progress of precision magnetotherapy in the treatment of psychiatric disorders, neurological injuries, metabolic disorders, and bone-related disorders, and looks forward to the future development trend of precision magnet therapy. .

Translational PK/PD and the first-in-human dose selection of a PD1/IL15: an engineered recombinant targeted cytokine for cancer immunotherapy.

Introduction: Interleukin 15 (IL-15) is a potential anticancer agent and numerous engineered IL-15 agonists are currently under clinical investigation. Selective targeting of IL-15 to specific lymphocytes may enhance therapeutic effects while helping to minimize toxicities. Methods: We designed and built a heterodimeric targeted cytokine (TaCk) that consists of an anti-programmed cell death 1 receptor antibody (anti-PD-1) and an engineered IL-15. This "PD1/IL15" selectively delivers IL-15 signaling to lymphocytes expressing PD-1. We then investigated the pharmacokinetic (PK) and pharmacodynamic (PD) effects of PD1/IL15 TaCk on immune cell subsets in cynomolgus monkeys after single and repeat intravenous dose administrations. We used these results to determine the first-in-human (FIH) dose and dosing frequency for early clinical trials. Results: The PD1/IL15 TaCk exhibited a nonlinear multiphasic PK profile, while the untargeted isotype control TaCk, containing an anti-respiratory syncytial virus antibody (RSV/IL15), showed linear and dose proportional PK. The PD1/IL15 TaCk also displayed a considerably prolonged PK (half-life range ∼1.0-4.1 days) compared to wild-type IL-15 (half-life ∼1.1 h), which led to an enhanced cell expansion PD response. The PD was dose-dependent, durable, and selective for PD-1+ lymphocytes. Notably, the dose- and time-dependent PK was attributed to dynamic TMDD resulting from test article-induced lymphocyte expansion upon repeat administration. The recommended first-in-human (FIH) dose of PD1/IL15 TaCk is 0.003 mg/kg, determined based on a minimum anticipated biological effect level (MABEL) approach utilizing a combination of in vitro and preclinical in vivo data. Conclusion: This work provides insight into the complex PK/PD relationship of PD1/IL15 TaCk in monkeys and informs the recommended starting dose and dosing frequency selection to support clinical evaluation of this novel targeted cytokine.

Gut microbiota, a key to understanding the knowledge gaps on micro-nanoplastics-related biological effects and biodegradation.

Micro-nanoplastics (MNPs) pollution as a global environmental issue has received increasing interest in recent years. MNPs can enter and accumulate in the organisms including human beings mainly via ingestion and inhalation, and large amounts of foodborne MNPs have been frequently detected in human intestinal tracts and fecal samples. MNPs regulate the structure composition and metabolic functions of gut microbiota, which may cause the imbalance of intestinal ecosystems of the hosts and further mediate the occurrence and development of various diseases. In addition, a growing number of MNPs-degrading strains have been isolated from organismal feces. MNPs-degraders colonize the plastic surfaces and form the biofilms, and the long-chain polymers of MNPs can be biologically depolymerized into short chains. In general, MNPs are gradually degraded into small molecule substances (e.g., N2, CH4, H2O, and CO2) via a series of enzymatic catalyses, mainly including biodeterioration, fragmentation, assimilation, and mineralization. In this review, we outline the current progress of MNPs effects on gut microbiota and MNPs degradation by gut microbiota, which provide a certain theoretical basis for fully understanding the knowledge gaps on MNPs-related biological effect and biodegradation.

What hidden treasure resides beneath the waves?: Phytochemistry, pharmacological properties and uses of Halopteris scoparia (Linnaeus) Sauvageau 1904: An overview.

Over the years, the biological activities of seaweeds could have piqued research interest due to their specific functional phytochemistry, which may not be available in terrestrial plants. Seaweeds produce these compounds to overcome and control stressful biotic and abiotic conditions. Additionally, they are potentially excellent sources of highly useful leads in the development of new drugs. Our study aims to unveil, for the first time, an overview of Halopteris scoparia, a species belonging to the Phaeophyceae class and the Stypocaulacea family, by summarizing all available literature data. In this work, we attempt to shed light on its phytochemistry, nutritional values, pharmacological activities, and industrial uses and applications. To gather information related to H. scoparia, relevant keywords were used to search internet databases including Google Scholar, PubMed, ResearchGate, Web of Science, Algae Database, WoRMS database, and DORIS database. The chemical structures were drawn using Chemdraw and verified using the PubChem database. Chemically, this species contains a wide variety of secondary metabolites, such as terpenoids and phenolic compounds. Additionally, other chemical components with nutraceutical value have been identified, such as carbohydrates, proteins, lipids, pigments, minerals and mycosporine like amino acids. Then, holding several reported pharmacological properties, including antioxidant, anti-inflammatory, cytotoxic, dermoprotective, antidepressive, antibacterial, antibiofilm, antifungal, anti-parasitic activities and acute toxicity. In addition to other their applications such as bioconversion and antifouling activities. To confirm the previous pharmacological properties, more comprehensive and systematic in vivo, preclinical, and clinical studies are needed. Furthermore, research is required to uncover the mechanisms of its active compounds and their potential therapeutic effects in treating other diseases such as atherosclerosis, neurodegenerative diseases, and viral infections.

Plant-derived exosome-like nanovesicles: A novel nanotool for disease therapy.

Exosomes are extracellular vesicles comprising bilayer phospholipid membranes and are secreted by eukaryotic cells. They are released via cellular exocytosis, contain DNA, RNA, proteins, and other substances, and participate in various cellular communications between tissues and organs. Since the discovery of exosomes in 1983, animal-derived exosomes have become a research focus for small-molecule drug delivery in biology, medicine, and other fields owing to their good biocompatibility and homing effects. Recent studies have found that plant-derived exosome-like nanovesicles (PELNVs) exhibit certain biological effects, such as anti-inflammatory and anti-tumor abilities, and have minimal toxic side effects. Because they are rich in active lipid molecules with certain pharmacological effects, PELNVs could be novel carriers for drug delivery. In this review, the biological formation and effects, isolation, and extraction of PELNVs, as well as characteristics of transporting drugs as carriers are summarized to provide new ideas and methods for future research on plant-derived exosome-like nanovesicles.

Extraction, structures, biological effects and potential mechanisms of Momordica charantia polysaccharides: A review.

Momordica charantia L. is a kind of vegetable with medicinal value. As the main component of the vegetable, Momordica charantia polysaccharides (MCPs) mainly consist of galactose, galacturonic acid, xylose, rhamnose, mannose and the molecular weight range is 4.33 × 103-1.16 × 106 Da. MCPs have been found to have various biological activities in recent years, such as anti-oxidation, anti-diabetes, anti-brain injury, anti-obesity, immunomodulatory and anti-inflammation. In this review, we systematically summarized the extraction methods, structural characteristics and physicochemical properties of MCPs. Especially MCPs modulate gut microbiota and cause the alterations of metabolic products, which can regulate different signaling pathways and target gene expressions to exert various functions. Meanwhile, the potential structure-activity relationships of MCPs were analyzed to provide a scientific basis for better development or modification of MCPs. Future researches on MCPs should focus on industrial extraction and molecular mechanisms. In East Asia, Momordica charantia L. is used as both food and medicine. It is not clear whether MCP has its unique biological effects. Further study on the difference between MCPs and other food-derived polysaccharides will be helpful to the development and potential application of Momordica charantia L.

Hyaluronic acid in Dentoalveolar regeneration: Biological rationale and clinical applications.

Background: Hyaluronic acid (HA) is found in different locations in the periodontium, including mineralized tissues (i.e., cementum and alveolar bone) and non-mineralized tissues (i.e., gingiva and periodontal ligament). In addition, it seems to play an essential part in regulating the underlying mechanisms involved in tissue inflammatory reactions and wound healing. HA has the potential to regulate periodontal tissue regeneration and treat periodontal disease. Aim: The current review of the literature was conducted to assess how HA plays its part in periodontal therapy and examine the contemporary literature's viewpoint on its use in periodontal regeneration. Conclusion: HA has a multifunctional character in periodontal regeneration, and healing and appears to provide promising outcomes in different periodontal regenerative applications.

Formation and detection of biocoronas in the food industry and their fate in the human body.

The rapid advancement of nanotechnology has opened up new avenues for applications in all stages of the food industry. Over the past decade, extensive research has emphasized that when nanoparticles (NPs) enter organisms, they spontaneously adsorbed biomolecules, leading to the formation of biocorona. This paper provided a detailed review of the process of biocorona formation in the food industry, including their classification and influencing factors. Additionally, various characterization methods to investigated the morphology and structure of biocoronas were introduced. As a real state of food industry nanoparticles in biological environments, the biocorona causes structural transformations of biomolecules bound to NPs, thus affecting their fate in the body. It can either promote or inhibit enzyme activity in the human environment, and may also positively or negatively affect the cellular uptake and toxicity of NPs. Since NPs present in the food industry will inevitably enter the human body, further investigations on biocoronas will offer valuable insights and perspectives on the safety of incorporating more NPs into the food industry.

A review of the occurrence and degradation of biodegradable microplastics in soil environments.

The use of plastics for manufacturing of products and packaging has become ubiquitous. This is because plastics are cheap, pliable, and durable. However, these characteristics of plastics have also led to their disposal in landfill, where they persist. To overcome the environmental challenge posed by conventional plastics (CPs), biodegradable plastics (BDPs) are increasingly being used. However, BDPs form residual microplastics (MPs) at a rate that far exceeds that of CPs, and MPs have negative impacts on the soil environment. This review aimed to evaluate whether the move away from CPs to BDPs is having an overall positive impact on the environment considering the formation of MPs. Topics focused on in this review include the degradation of BDPs in the soil environment and the impacts of MPs originating from BDPs on soil physical and chemical properties, microbial communities, animals, and plants. The information collated in this review can provide scientific guidance for sustainable development of the BDPs industry.

Biological effect abundance analysis of hemolytic pathogens based on engineered biomimetic sensor.

Conventional pathogen detection strategies based on the molecular structure or chemical characteristics of biomarkers can only provide the "physical abundance" of microorganisms, but cannot reflect the "biological effect abundance" in the true sense. To address this issue, we report an erythrocyte membrane-encapsulated biomimetic sensor cascaded with CRISPR-Cas12a (EMSCC). Taking hemolytic pathogens as the target model, we first constructed an erythrocyte membrane-encapsulated biomimetic sensor (EMS). Only hemolytic pathogens with biological effects can disrupt the erythrocyte membrane (EM), resulting in signal generation. Then the signal was amplified by cascading CRISPR-Cas12a, and more than 6.67 × 104-fold improvement in detection sensitivity compared to traditional erythrocyte hemolysis assay was achieved. Notably, compared with polymerase chain reaction (PCR) or enzyme linked immunosorbent assay (ELISA)-based quantification methods, EMSCC can sensitively respond to the pathogenicity change of pathogens. For the detection of simulated clinical samples based on EMSCC, we obtained an accuracy of 95% in 40 samples, demonstrating its potential clinical value.

Integrated metabolomics, transcriptomics, and proteomics analyses reveal co-exposure effects of polycyclic aromatic hydrocarbons and cadmium on ryegrass (Lolium perenne L.).

Cadmium (Cd) and polycyclic aromatic hydrocarbons (PAHs) are prominent soil contaminants found in industrial sites, and their combined effects on plants are not yet fully understood. To investigate the mechanisms underlying the co-exposure of Cd and PAHs and identify key biomarkers for their co-effects, an integrated analysis of metabolomics, transcriptomics, and proteomics was conducted on ryegrass leaves cultivated in soil. In nontarget metabolomics analysis, nine differentially expressed metabolites that were specifically induced by the compound exposure were identified. When combined with the analysis of differentially expressed genes and proteins, it was determined that the major pathways involved in the response to the co-stress of Cd and PAHs were linoleic acid metabolism and phenylpropanoid biosynthesis. The upregulation of 12,13-dihydroxy-9Z-octadecenoic acid and the downregulation of sinapyl alcohol were identified as typical biomarkers, respectively. Compared to scenarios of single exposures, the compound exposure to Cd and PAHs disrupted the oxidation of linoleic acid, leading to alterations in the profiles of linoleate metabolites. Additionally, it intensified hydroxylation, carboxylation, and methylation processes, and interfered with reactions involving coenzyme A, thus inhibiting lignin production. As a result, oxidative stress was elevated, and the cell wall defense system in ryegrass was weakened. The findings of this study highlight the ecological risks associated with unique biological responses in plants co-exposed to Cd and PAHs in polluted soils.

DNA Adductomics for the Biological Effect Assessment of Contaminant Exposure in Marine Sediments.

Exposure to chemical pollution can induce genetic and epigenetic alterations, developmental changes, and reproductive disorders, leading to population declines in polluted environments. These effects are triggered by chemical modifications of DNA nucleobases (DNA adducts) and epigenetic dysregulation. However, linking DNA adducts to the pollution load in situ remains challenging, and the lack of evidence-based DNA adductome response to pollution hampers the development and application of DNA adducts as biomarkers for environmental health assessment. Here, we provide the first evidence for pollution effects on the DNA modifications in wild populations of Baltic sentinel species, the amphipod Monoporeia affinis. A workflow based on high-resolution mass spectrometry to screen and characterize genomic DNA modifications was developed, and its applicability was demonstrated by profiling DNA modifications in the amphipods collected in areas with varying pollution loads. Then, the correlations between adducts and the contaminants level (polycyclic aromatic hydrocarbons (PAHs), trace metals, and pollution indices) in the sediments at the collection sites were evaluated. A total of 119 putative adducts were detected, and some (5-me-dC, N6-me-dA, 8-oxo-dG, and dI) were structurally characterized. The DNA adductome profiles, including epigenetic modifications, differed between the animals collected in areas with high and low contaminant levels. Furthermore, the correlations between the adducts and PAHs were similar across the congeners, indicating possible additive effects. Also, high-mass adducts had significantly more positive correlations with PAHs than low-mass adducts. By contrast, correlations between the DNA adducts and trace metals were stronger and more variable than for PAHs, indicating metal-specific effects. These associations between DNA adducts and environmental contaminants provide a new venue for characterizing genome-wide exposure effects in wild populations and apply DNA modifications in the effect-based assessment of chemical pollution.

Molecular properties and biotoxicity of dissolved organic matter leached from microplastic (MP-DOM) during typical hydrothermal treatment of sewage sludge.

Microplastic-derived dissolved organic matter (MP-DOM) is crucial for assessing ecological and environmental impact of microplastics. However, the factors that influence the ecological effects of MP-DOM are yet to be determined. This study investigated the influence of plastic type and leaching conditions (thermal hydrolysis, TH; hydrothermal carbonization, HTC) on the molecular properties and toxicity of MP-DOM using spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Results revealed that plastic type was the main factor affecting the chemodiversity of MP-DOM, compared to leaching conditions. Polyamide 6 (PA6) dissolved the largest number of DOM due to the presence of heteroatoms, followed by polypropylene (PP) and polyethylene (PE). From TH to HTC processes, the molecular composition of PA-DOM remained constant, with CHNO compounds being dominant, and labile compounds (lipids-like, and protein/amino sugar-like compounds) accounting for >90 % of the total compounds. In polyolefin-sourced DOM, CHO compounds were dominant, and the relative concentration of labile compounds decreased dramatically, resulting in the higher degree of unsaturation and humification than PA-DOM. The mass difference network analysis showed that the main reaction in PA-DOM and PE-DOM was oxidation while in PP-DOM, it was the carboxylic acid reaction. However, plastic type and leaching conditions jointly influenced the toxic effects of MP-DOM. PA-DOM was bioavailable, while polyolefin-sourced DOM leached under HTC treatment exhibited toxicity, with lignin/CRAM-like compounds being the dominant toxic compounds. Notably, the 2-fold higher relative intensity of the toxic compounds and the 6-fold higher abundance of highly unsaturated and phenolic-like compounds in PP-DOMHTC resulted in the higher inhibition rate than PE-DOMHTC. Toxic molecules in PE-DOMHTC mainly directly dissolved from PE polymers, while almost 20 % of toxic molecules in PP-DOMHTC resulted from molecular transformation, where dehydration (-H2O) was the core reaction. These findings offer advanced insights into the management and treatment of MPs in sludge.

Low-dose radiotherapy effects the progression of anti-tumor response.

The history of low-dose radiotherapy (LDRT or LDR) as a treatment modality for malignant tumors dates back to the 1920s. Even with the minimal total dose administered during treatment, LDRT can result in long-lasting remission. Autocrine and paracrine signaling are widely recognized for fostering the growth and development of tumor cells. LDRT exerts systemic anti-tumor effects through various mechanisms, such as enhancing the activity of immune cells and cytokines, shifting the immune response towards an anti-tumor phenotype, influencing gene expression, and blocking crucial immunosuppressive pathways. Additionally, LDRT has been demonstrated to enhance the infiltration of activated T cells and initiate a series of inflammatory processes while modulating the tumor microenvironment. In this context, the objective of receiving radiation is not to directly kill tumor cells but to reprogram the immune system. Enhancing anti-tumor immunity may be a critical mechanism by which LDRT plays a role in cancer suppression. Therefore, this review primarily focuses on the clinical and preclinical efficacy of LDRT in combination with other anti-cancer strategies, such as the interaction between LDRT and the tumor microenvironment, and the remodeling of the immune system.

Molecular characteristics and biological effects of dissolved organic matter leached from microplastics during sludge hydrothermal treatment.

Previous knowledge of dissolved organic matter leached from microplastics (MP-DOM) was mainly based on the aquatic environment. The molecular characteristics and biological effects of MP-DOM in other environments have rarely been examined. In this work, FT-ICR-MS was applied to identify MP-DOM leached from sludge hydrothermal treatment (HTT) at different temperatures, and the plant effects and acute toxicity were investigated. The results showed that the molecular richness and diversity of MP-DOM increased with rising temperature, accompanied by molecular transformation in the meantime. The oxidation was crucial whereas the amide reactions mainly occurred at 180-220 oC. MP-DOM promoted root development of Brassica rapa (field mustard) by affecting the expression of genes and the effect was enhanced with rising temperature. Specifically, the lignin-like compounds in MP-DOM down-regulated Phenylpropanoids biosynthesis, while CHNO compounds up-regulated the nitrogen metabolism. Correlation analysis presented that alcohols/esters leached at 120-160 oC were responsible for the promotion of root, while glucopyranoside leached at 180-220 oC was vital for root development. However, MP-DOM produced at 220 oC showed the acute toxicity to luminous bacteria. Considering the further-treatment of sludge, the optimum HTT temperature could be controlled at 180 oC. This work provides novel insight into the environmental fate and eco-environmental effects of MP-DOM in sewage sludge.

Lithium and Microorganisms: Biological Effects and Mechanisms.

This review covers the lithium effects on microorganisms, including gut and soil bacteria. Available studies of the biological effects of lithium salts have revealed a wide range of different effects of lithium cations on various microorganisms, but so far, the study of this direction has not been summarized enough. Here we consider the confirmed and various plausible mechanisms of lithium action on microorganisms. Special emphasis is placed on assessing the effect of lithium ions under oxidative stress and adverse environmental conditions. The impact of lithium on the human microbiome is also being reviewed and discussed. Controversial effects of lithium have been shown, including the inhibitory and stimulating effects of lithium on bacterial growth.

Statistical Amplification of the Effects of Weak Magnetic Fields in Cellular Translation.

We assume that the enzymatic processes of recognition of amino acids and their addition to the synthesized molecule in cellular translation include the formation of intermediate pairs of radicals with spin-correlated electrons. The mathematical model presented describes the changes in the probability of incorrectly synthesized molecules in response to a change in the external weak magnetic field. A relatively high chance of errors has been shown to arise from the statistical enhancement of the low probability of local incorporation errors. This statistical mechanism does not require a long thermal relaxation time of electron spins of about 1 µs-a conjecture often used to match theoretical models of magnetoreception with experiments. The statistical mechanism allows for experimental verification by testing the usual Radical Pair Mechanism properties. In addition, this mechanism localizes the site where magnetic effects originate, the ribosome, which makes it possible to verify it by biochemical methods. This mechanism predicts a random nature of the nonspecific effects caused by weak and hypomagnetic fields and agrees with the diversity of biological responses to a weak magnetic field.

Biological Effects and Toxicity of Compounds Based on Cured Epoxy Resins.

The aim of this work was to investigate selected biological and toxicity properties of cured epoxy resin-based compounds based on a bisphenol A epoxy resin, cold-cured by a polyamide and containing two types of metal powders (aluminum and copper). This study involved cytotoxicity analysis, pH measurements, absorbance measurements and sterilization. The cytotoxicity analysis was conducted to determine the harmful degree of the cured epoxy resin. Aimed at identifying toxic agents in cured compounds, the cytotoxicity analysis involved absorbance measurements in an entire wavelength range. Cytotoxicity and absorbance results demonstrated that the extracts of all the tested resin samples had no cytotoxic effects on the cells of living organisms. The absorbance values obtained over the entire wavelength range did not point to the formation of aggregations, which proved that no toxic agents harmful to living organisms were extracted from the resin samples. Based on the results obtained, it can be concluded that all tested compounds, based on epoxy resins, which are also used as adhesives in various applications, are essentially safe materials when using such formulations in a cured state.