Tailoring Highly Branched Poly(ß-amino ester)s for Efficient and Organ-Selective mRNA Delivery.

Development of mRNA therapeutics necessitates targeted delivery technology, while the clinically advanced lipid nanoparticles face difficulty for extrahepatic delivery. Herein, we design highly branched poly(ß-amino ester)s (HPAEs) for efficacious organ-selective mRNA delivery through tailoring their chemical compositions and topological structures. Using an "A2+B3+C2" Michael addition platform, a combinatorial library of 219 HPAEs with varied backbone structures, terminal groups, and branching degrees are synthesized. The branched topological structures of HPAEs provide enhanced serum resistance and significantly higher mRNA expression in vivo. The terminal amine structures of HPAEs determine the organ-selectivity of mRNA delivery following systemic administration: morpholine facilitates liver targeting, ethylenediamine favors spleen delivery, while methylpentane enables mRNA delivery to the liver, spleen, and lungs simultaneously. This study represents a comprehensive exploration of the structure-activity relationship governing both the efficiency and organ-selectivity of mRNA delivery by HPAEs, suggesting promising candidates for treating various organ-related diseases.

Regulation of cellulase production via calcium signaling in Trichoderma reesei under PEG8000 stress.

In this study, the effect of polyethylene glycol 8000 (PEG8000) stress on cellulase biosynthesis in Trichoderma reesei CICC2626 via calcium signaling was investigated, and a plausible mechanism by which intracellular Ca2+ regulates the transcription of cellulase genes was proposed. The results indicated that the total cellulase (filter paper-hydrolyzing activity [FPase]), endoglucanase (carboxymethyl cellulase activity [CMCase]), and ß-glucosidase activities of the strain were 1.3-, 1.2-, and 1.3-fold higher than those of the control (no PEG8000 addition) at a final concentration of 1.5% (w/v) PEG8000. Moreover, the transcriptional levels of cellulase genes, protein concentrations, and biomass increased. With the synergistic use of commercial cellulase and T. reesei CICC2626 cellulase to hydrolyze alkali-pretreated rice straw, the released reducing sugar concentration reached 372.7 mg/g, and the cellulose content (22.7%, 0.32 g) was significantly lower than the initial content (62.5%, 1.88 g). Transcriptome data showed that 12 lignocellulose degradation-related genes were significantly upregulated in the presence of 1.5% PEG8000. Furthermore, the addition of Ca2+ inhibitors and deletion of crz1 (calcineurin-responsive zinc finger 1-encoding gene, which is related to the calcium signaling pathway) demonstrated that calcium signaling plays a dominant role in PEG8000-induced cellulase genes overexpression. These results revealed a link between PEG8000 induction and calcium signaling transduction in T. reesei CICC2626. Moreover, this study also provides a novel inducer for enhanced cellulase production. KEY POINTS: • Cellulase biosynthesis in Trichoderma reesei could be enhanced by PEG8000 • PEG8000 could induce a cytosolic Ca2+ burst in Trichoderma reesei • The activated calcium signaling was involved in cellulase biosynthesis.

Influence of polyether ether ketone coping crown on the adaptation of implant abutment.

OBJECTIVE: To evaluate the influence of polyether ether ketone coping crown on the adaptation of implant abutment. Methods: The vitro study was conducted at the department of Prosthodontics, Hainan Stomatological Hospital, China, from October 2021 to March 2022, and comprised patients undergoing implant surgery on first molar. Patients were divided into two groups, with group A patients receiving polyether ether ketone coping crowns, and group B receiving zirconia crowns. Replica technique was used to replicate the gap between the crowns and the abutments. The thickness of the silicone film was measured under the stereomicroscope, and the gap between the groups was compared. Data was analysed using SPSS 22. RESULTS: In group A, mean marginal gap was 82.43±25.00µm, and mean overall gap was 85.45±33.75µm. In group B, the corresponding values were 65.09±11.69µm and 78.04±26.67µm. There was a significant difference in the adaptation between the groups at the marginal and overall measurement points (p<0.05). Conclusion: Marginal and internal adaptations of polyether ether ketone coping crown for abutment could be considered clinically acceptable.

miR397-LACs mediated cadmium stress tolerance in Arabidopsis thaliana.

Cadmium (Cd) is a non-essential heavy metal, assimilated in plant tissue with other nutrients, disturbing the ions' homeostasis in plants. The plant develops different mechanisms to tolerate the hazardous environmental effects of Cd. Recently studies found different miRNAs that are involved in Cd stress. In the current study, miR397 mutant lines were constructed to explore the molecular mechanisms of miR397 underlying Cd tolerance. Compared with the genetically modified line of overexpressed miR397 (artificial miR397, amiR397), the lines of downregulated miR397 (Short Tandem Target Mimic miR397, STTM miR397) showed more substantial Cd tolerance with higher chlorophyll a & b, carotenoid and lignin content. ICP-OES revealed higher cell wall Cd and low total Cd levels in STTM miR397 than in the wild-type and amiR397 plants.Further, the STTM plants produced fewer reactive oxygen species (ROS) and lower activity of antioxidants enzymes (e.g., catalase [CAT], malondialdehyde [MDA]) compared with amiR397 and wild-type plants after stress, indicating that silencing the expression of miR397 can reduce oxidative damage. In addition, the different family transporters' gene expression was much higher in the amiR397 plants than in the wild type and STTM miRNA397. Our results suggest that miR397 plays a role in Cd tolerance in Arabidopsis thaliana. Overexpression of miR397 could decrease Cd tolerance in plants by regulating the expression of LAC 2/4/17, changing the lignin content, which may play an important role in inducing different stress-tolerant mechanisms and protecting the cell from a hazardous condition. This study provides a basis to elucidate the functions of miR397 and the Cd stress tolerance mechanism in Arabidopsis thaliana.

Polyurea-Modified Magnetic Particles with Versatile Probes for Chemoselective Capture of Carbonyl Metabolites and Biomarker Discovery.

Playing a great role in human physiologies and pathologies, carbonyl metabolites are intimately associated with a variety of diseases, though the effective analysis method of them remains a challenge. A hydrazide-terminated polyurea-modified magnetic particle (HPMP) with versatile probes is developed to address this issue. The capture ability of HPMPs for carbonyl metabolite is more than 1200 µmol g-1 , which is increased by 4 orders of magnitude via the introduction of polyurea. With a broad linear range of over 4 orders of magnitude, remarkably improved sensitivity, and limit of detection at attomole quantities, HPMPs are applied in relative quantification of more than 1500 carbonyl metabolites in 113 human serum samples with high throughput and high coverage. The combined indicators of these metabolites demonstrates a great diagnostic accuracy for distinguishing between health and disease subjects as well as differentiating the patients with benign lung disease and lung cancer. Combining powerful capture ability, low-cost preparation, and convenient operation, the HPMPs demonstrate extensive application in biomarker discovery and the detailed study of the biochemical landscape.

Engineering siRNA therapeutics: challenges and strategies.

Small interfering RNA (siRNA) is a potential method of gene silencing to target specific genes. Although the U.S. Food and Drug Administration (FDA) has approved multiple siRNA-based therapeutics, many biological barriers limit their use for treating diseases. Such limitations include challenges concerning systemic or local administration, short half-life, rapid clearance rates, nonspecific binding, cell membrane penetration inability, ineffective endosomal escape, pH sensitivity, endonuclease degradation, immunological responses, and intracellular trafficking. To overcome these barriers, various strategies have been developed to stabilize siRNA, ensuring their delivery to the target site. Chemical modifications implemented with nucleotides or the phosphate backbone can reduce off-target binding and immune stimulation. Encapsulation or formulation can protect siRNA from endonuclease degradation and enhance cellular uptake while promoting endosomal escape. Additionally, various techniques such as viral vectors, aptamers, cell-penetrating peptides, liposomes, and polymers have been developed for delivering siRNA, greatly improving their bioavailability and therapeutic potential.

Transcriptome analysis of Fusobacterium nucleatum reveals differential gene expression patterns in the biofilm versus planktonic cells.

As a chronic infectious disease, periodontitis can cause gum recession, loss of alveolar bone, loosening of teeth, and even loss of teeth. Dental plaque biofilm is the initiating factor for the occurrence and development of periodontitis. Fusobacterium nucleatum (F. nucleatum) plays a vital role in the structure and ecology of dental plaque biofilms. It is a bridge between early and late colonization bacteria in dental plaque. Understanding the molecular mechanism of F. nucleatum during biofilm development is essential to control periodontitis. This study aimed to determine gene expression profiles of the F. nucleatum strain, ATCC 25586, in the planktonic and biofilm phase through RNA-sequencing approach. The results were confirmed by quantitative reverse transcriptase PCR (RT-qPCR). The results clearly illustrate the difference in gene expression of F. nucleatum under planktonic and biofilms. A total of 110 genes were differentially expressed by F. nucleatum in the biofilm state compared with the planktonic state. The 25 upregulated genes in the biofilm state were mainly related to carbohydrate and amino acid metabolism, while the 85 downregulated genes were primarily associated with cell growth, division, and oxidative stress; most of the upregulated genes of F. nucleatum involved in virulence and oral malodor. Furthermore, the transcriptome analysis and antibacterial activity test also identified Lysine might exhibit the antibacterial and antibiofilm activity of F. nucleatum for the first time. These new findings could provide caveats for future studies on the regulation and maintenance of plaque biofilm and the development of biomarkers for periodontitis.

Improvement of Lignocellulolytic Enzyme Production Mediated by Calcium Signaling in Bacillus subtilis Z2 under Graphene Oxide Stress.

An increase in exoenzyme production can be enhanced by environmental stresses such as graphene oxide (GO) stress, but the link between the two events is still unclear. In this work, the effect of GO as an environmental stress factor on exoenzyme (lignocellulolytic enzyme, amylase, peptidase, and protease) biosynthesis was investigated in Bacillus subtilis Z2, and a plausible mechanism by which cytosolic Ca2+ regulates lignocellulolytic enzyme production in B. subtilis Z2 subjected to GO stress was proposed. The filter paper-hydrolyzing (FPase [representing total cellulase]), carboxymethylcellulase (CMCase [representing endoglucanase]), and ß-glucosidase activities and extracellular protein concentration of the wild-type strain under 10 µg/mL GO stress were 1.37-, 1.64-, 1.24-, and 1.16-fold those of the control (without GO stress), respectively. Correspondingly, the transcription levels of lignocellulolytic enzyme genes, cytosolic Ca2+ level, and biomass concentration of B. subtilis were all increased. With lignocellulolytic enzyme from B. subtilis used to hydrolyze alkali-pretreated rice straw, the released reducing sugar concentration reached 265.53 mg/g, and the removal rates of cellulose, hemicellulose, and lignin were 52.4%, 30.1%, and 7.5%, respectively. Furthermore, transcriptome data revealed that intracellular Ca2+ homeostasis played a key role in regulating the levels of gene transcription related to the synthesis of lignocellulolytic enzymes and exoenzymes. Finally, the use of Ca2+ inhibitors (LaCl3 and EDTA) and deletion of spcF (a calmodulin-like protein gene) further demonstrated that the overexpression of those genes was regulated via calcium signaling in B. subtilis subjected to GO stress. IMPORTANCE To effectively convert lignocellulose into fermentable sugars, high lignocellulolytic enzyme loading is needed. Graphene oxide (GO) has been shown to promote exoenzyme (lignocellulolytic enzyme, amylase, peptidase, and protease) production in some microorganisms; however, the regulatory mechanism of the biosynthesis of lignocellulolytic enzymes under GO stress remains unclear. In this work, the lignocellulolytic enzyme production of B. subtilis under GO stress was investigated, and the potential mechanism by which B. subtilis enhanced lignocellulolytic enzyme production through the calcium signaling pathway under GO stress was proposed. This work revealed the role of calcium signaling in the production of enzymes under external environmental stress and provided a direction to facilitate lignocellulolytic enzyme production by B. subtilis.

A method of fabricating computer aided design-computer aided manufacturing implant-supported provisional restorations with clear aligner attachments: A technical report.

OBJECTIVE: To provide a method of fabricating implant-supported provisional restorations with orthodontic attachments by digital technique. CLINICAL CONSIDERATION: Polymethylmethacrylate (PMMA) provisional restorations are usually necessary when dental implants are serving as anchors for orthodontic treatments. For clear aligner treatment, it is possible to setup the teeth virtually and determine the final position of the implants, indicating that the provisional restorations can be also predetermined. However, attachments on PMMA restorations have a higher risk of debonding due to low bond strength. To fabricate provisional restorations with predetermined shape and position and no risk of attachment debonding immediately after implant placement, a digital workflow is introduced in this article. CONCLUSIONS: By combining "pick-up" technique and prefabricated monolithic PMMA provisional restorations, this technique is recommended for making implant-supported provisional restorations with integrated orthodontic attachments based on the digitally designed positions of the teeth. CLINICAL SIGNIFICANCE: The present protocol describes a digital workflow of designing and manufacturing implant-supported PMMA provisional restorations with orthodontic attachments in the predetermined position of implants, which should lead to more reliable and predictable orthodontic treatment outcomes.

Zwitterionic Phospholipidation of Cationic Polymers Facilitates Systemic mRNA Delivery to Spleen and Lymph Nodes.

Polymers represent a promising therapeutic platform for extrahepatic messenger RNA (mRNA) delivery but are hampered by low in vivo efficacy due to polyplex serum instability and inadequate endosomal escape following systemic administration. Here, we report the rational design and combinatorial synthesis of zwitterionic phospholipidated polymers (ZPPs) via cationic polymer postmodification by alkylated dioxaphospholane oxides to deliver mRNA to spleen and lymph nodes in vivo. This modular postmodification approach readily produces tunable zwitterionic species for serum resistance and introduces alkyl chains simultaneously to enhance endosomal escape, thereby transforming deficient cationic polymers to efficacious zwitterionic mRNA carriers without the need to elaborately synthesize functional monomers. ZPPs mediated up to 39 500-fold higher protein expression than their parent cationic counterparts in vitro and enabled efficacious mRNA delivery selectively in spleen and lymph nodes following intravenous administration in vivo. This zwitterionic phospholipidation methodology provides a versatile and generalizable postmodification strategy to introduce zwitterions into the side chains of cationic polymers, extending the utility of cationic polymer families for precise mRNA delivery and demonstrating substantial potential for immunotherapeutic applications.

Facile Fabrication of Redox-Responsive Covalent Organic Framework Nanocarriers for Efficiently Loading and Delivering Doxorubicin.

Covalent organic frameworks (COFs) as drug delivery systems have shown great promise, but their pharmaceutical applications are often limited by complex building blocks, tedious preparations, irregular shape, and uncontrolled drug release within target cells. Herein, a facile strategy is developed to prepare PEGylated redox-responsive nanoscale COFs (denoted F68@SS-COFs) for efficiently loading and delivering doxorubicin (DOX) by use of FDA-approved Pluronic F68 and commercially available building blocks. The obtained F68@SS-COFs with controlled size, high stability, and good biocompatibility can not only achieve a very high DOX-loading content (about 21%) and very low premature leakage at physiological condition but can also rapidly respond to the tumor intracellular microenvironment and efficiently release DOX to kill tumor cells. Considering the readily available raw materials, simple preparation process, and desirable redox-responsiveness, the strategy provided here opens up a promising avenue to develop well-defined COFs-based nanomedicines for cancer therapy.

A Modified Cosmetic Genioplasty Can Affect Airway Space Positively in Skeletal Class II Patients: Studying Alterations of Hyoid Bone Position and Posterior Airway Space.

BACKGROUND: Improving the posterior airway space is one of the most important functions of genioplasty. Studies have shown that the posterior airway space (PAS) can play an important role in the evaluation of obstructive sleep apnea syndrome (OSAS). The purpose of this study is to evaluate the airway safety of our modified technology by observing the impact on PAS in skeletal Class II patients without OSAS. METHODS: We have modified a cosmetic genioplasty, which can guarantee the continuity of the lower edge of the bilateral mandible by rotating the chin segment clockwise. Fourteen patients submitted to our modified cosmetic genioplasty alone were included in the study. The facial convexity angle and the ratio of the face were measured by analyzing photographs. The position of the hyoid bone and the width of the PAS were measured by analyzing lateral cephalograms. The volume and the cross-sectional area (CSA) of the PAS were measured using 3D reconstruction. The Wilcoxon signed-rank test and paired samples t test were used to assess the significance of differences of the data (p < 0.05). RESULTS: Soft tissue measurements were statistically different (p = 0.001) and achieved satisfactory results. The position of the hyoid bone moved up (LX: p = 0.004; LML: p = 0.056) and forward (LY: p = 0.001; LCV3: p = 0.016). The increase in the CSA had statistical significance (p < 0.005). There were significant statistical differences in the total airway volume and hypopharynx (p = 0.001), except in the oropharynx (p = 0.096). CONCLUSIONS: Our modified genioplasty not only achieved better cosmetic results by ensuring the continuity of the lower edge of the bilateral mandible but also exerted a significant positive impact on the posterior airway space for patients with skeletal class II, thus helping reduce the prevalence of OSAS. We hence suggest performing this modified cosmetic genioplasty on the skeletal class II patients with/without OSAS if necessary. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Multifunctional oligomer immobilized on quartz crystal microbalance: a facile and stabilized molecular imprinting strategy for glycoprotein detection.

Glycoprotein detection holds great potential for early diagnosis of diverse diseases. For this purpose, the combination of quartz crystal microbalance (QCM) sensor and molecular imprinting has attracted increasing attention. Nonetheless, the recently common imprinted films fabricated on QCM electrode are thick and rigid, lacking flexibility in aqueous phase. Alternatively, small molecules immobilized on the electrode to construct molecular scale film could address this problem, while stabilization of the imprinted sites remains challenging. Herein, a co-assembly complex was obtained by the mixture of template and multifunctional oligomer, which was then immobilized on the amino-modified transducer surface through epoxy-amino reaction to form a protein-imprinted film. Afterward, the remaining epoxy groups in oligomer chains were cross-linked to conserve and stabilize the orientation of imprinted sites after template elution. Template rebinding tests show that cross-linked film has much higher imprinting factors than that of the non-cross-linked counterpart. Furthermore, control proteins that are distinct in properties and structures were employed to demonstrate the selectivity of this approach, and the imprinted assay reveals high affinity and specificity towards template protein. Graphical Abstract.

Zinc Coordinated Cationic Polymers Break Up the Paradox between Low Molecular Weight and High Transfection Efficacy.

Cationic polymers have emerged as appealing nonviral gene vectors for decades, which, however, suffer from the paradox between low molecular weight and high transfection efficacy. Low molecular weight cationic polymers (LCPs) are well cell tolerated but are perplexed by orders-of-magnitude less efficacy compared to their macromolecular counterparts. The deficiency mainly lies in weak DNA binding of polymers and difficulty in endosomal escape of formulated polyplexes. Herein, we demonstrate that, through zinc (Zn) coordinated modification of LCPs, the high transfection efficiency and low molecular weight (thus low cytotoxicity) can be achieved simultaneously. The Zn coordinated ligand shows a high affinity to phosphate components and therefore will largely benefit the DNA packaging and endosomal membrane destabilization, addressing the defects of LCPs in gene delivery. Zn coordinative functionalization of LCPs breaks up the "efficacy-toxicity" paradox and provides great promise for the development of clinically efficient and safe nonviral gene vectors.

Tunable AICPL of (S)-Binaphthyl-Based Three-Component Polymers via FRET Mechanism.

Five three-component chiral polymers incorporating (S)-1,1'-binaphthyl, tetraphenylethene (TPE) and fluorene moieties are designed and synthesized by Pd-catalyzed Sonogashira reaction. All these polymers show obvious aggregation induced emission enhancement response behavior in the fluorescence emission region of 460-480 nm. Interestingly, three of them show aggregation-induced circularly polarized luminescence (AICPL) signals in tetrahydrofuran-H2 O mixtures. Most importantly, these AICPL signals can be tuned by changing the molar ratios of TPE and fluorene components through fluorescence resonance energy transfer and give the highest glum = ±4.0 × 10-3 . This work provides a novel strategy for developing AICPL-enhanced materials.

Zwitterionic materials for nucleic acid delivery and therapeutic applications.

Nucleic acid therapeutics have demonstrated substantial potential in combating various diseases. However, challenges persist, particularly in the delivery of multifunctional nucleic acids. To address this issue, numerous gene delivery vectors have been developed to fully unlock the potential of gene therapy. The advancement of innovative materials with exceptional delivery properties is critical to propel the clinical translation of nucleic acid drugs. Cationic vector materials have received extensive attention, while zwitterionic materials remain relatively underappreciated in delivery. In this review, we outline a diverse range of zwitterionic material nucleic acid carriers, predominantly encompassing zwitterionic lipids, polymers and peptides. Their respective chemical structures, synthesis approaches, properties, advantages, and therapeutic applications are summarized and discussed. Furthermore, we highlight the challenges and future opportunities associated with the development of zwitterionic vector materials. This review will aid to understand the zwitterionic materials in aiding gene delivery, contributing to the continual progress of nucleic acid therapeutics.

An overview of lipid constituents in lipid nanoparticle mRNA delivery systems.

mRNA therapeutics have shown great potential for a broad spectrum of disease treatment. However, the challenges of mRNA's inherent instability and difficulty in cellular entry have hindered its progress in the biomedical field. To address the cellular barriers and deliver mRNA to cells of interest, various delivery systems are designed. Among these, lipid nanoparticles (LNPs) stand out as the most extensively used mRNA delivery systems, particularly following the clinical approvals of corona virus disease 2019 (COVID-19) mRNA vaccines. LNPs are comprised of ionizable cationic lipids, phospholipids, cholesterol, and polyethylene glycol derived lipids (PEG-lipids). In this review, we primarily summarize the recent advancements of the LNP mRNA delivery technology, focusing on the structures of four lipid constituents and their biomedical applications. We delve into structure-activity relationships of the lipids, while also exploring the future prospects and challenges in developing more efficacious mRNA delivery systems. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Combined exposure with microplastics increases the toxic effects of PFOS and its alternative F-53B in adult zebrafish.

Microplastics (MPs) can adsorb and desorb organic pollutants, which may alter their biotoxicities. Although the toxicity of perfluorooctane sulfonate (PFOS) and its alternative 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) to organisms has been reported, the comparative study of their combined toxic effects with MPs on aquatic organisms is limited. In this study, adult female zebrafish were exposed to 10 µg/L PFOS/F-53B and 50 µg/L MPs alone or in combination for 14 days to investigate their single and combined toxicities. The results showed that the presence of MPs reduced the concentration of freely dissolved PFOS and F-53B in the exposure solution but did not affect their bioaccumulation in the zebrafish liver and gut. The combined exposure to PFOS and MPs had the greatest impact on liver oxidative stress, immunoinflammatory, and energy metabolism disorders. 16S rRNA gene sequencing analysis revealed that the combined exposure to F-53B and MPs had the greatest impact on gut microbiota. Functional enrichment analysis predicted that the alternations in the gut microbiome could interfere with signaling pathways related to immune and energy metabolic processes. Moreover, significant correlations were observed between changes in gut microbiota and immune and energy metabolism indicators, highlighting the role of gut microbiota in host health. Together, our findings demonstrate that combined exposure to PFOS/F-53B and MPs exacerbates liver immunotoxicity and disturbances in energy metabolism in adult zebrafish compared to single exposure, potentially through dysregulation of gut microbiota.

Response and adaptation mechanisms of Apostichopus japonicus to single and combined anthropogenic stresses of polystyrene microplastics or cadmium.

Microplastics (MPs) have become pervasive in marine ecosystems, exerting detrimental effects on marine life. The concurrent presence and interaction of MPs and heavy metals in aquatic environments could engender more insidious toxicological impacts. This study aimed to elucidate the potential impacts and underlying mechanisms of polystyrene microplastics (PS-MPs), cadmium (Cd), and their combined stress (MPs-Cd) on sea cucumbers (Apostichopus japonicus). It focused on the growth, Cd bioaccumulation, oxidative stress responses, immunoenzymatic activities, and metabolic profiles, specifically considering PS-MPs sizes preferentially ingested by these organisms. The high-dose MPs (MH) treatment group exhibited an increase in cadmium bioavailability within the sea cucumbers. Exposure to PS-MPs or Cd triggered the activation of antioxidant defenses and immune responses. PS-MPs and Cd exhibited a synergistic effect on lysozyme (LZM) activity. A total of 149, 316, 211, 197, 215, 619, 434, and 602 differentially expressed metabolites were identified, distinguishing the low-dose MPs (ML), high-dose MPs (MH), low-dose Cd (LCd), low-dose MPs and low-dose Cd (MLLCd), high-dose MPs and low-dose Cd (MHLCd), high-dose Cd (HCd), low-dose MPs and high-dose Cd (MLHCd), high-dose MPs and high-dose Cd (MHHCd) groups, respectively. Metabolomic analyses revealed disruptions in lipid metabolism, nervous system function, signal transduction, and transport and catabolism pathways following exposure to PS-MPs, Cd, and MPs-Cd. Correlation analyses among key differentially expressed metabolites (DEMs) underscored the interregulation among these metabolic pathways. These results offer new perspectives on the distinct and synergistic toxicological impacts of microplastics and cadmium on aquatic species, highlighting the complex interplay between environmental contaminants and their effects on marine life.

Polyethylene microplastic modulates lettuce root exudates and induces oxidative damage under prolonged hydroponic exposure.

Root exudates are pivotal in plant stress responses, however, the impact of microplastics (MPs) on their release and characteristics remains poorly understood. This study delves into the effects of 0.05 % and 0.1 % (w/w) additions of polyethylene (PE) MPs on the growth and physiological properties of lettuce (Lactuca sativa L.) following 28 days of exposure. The release characteristics of root exudates were assessed using UV-vis and 3D-EEM. The results indicated that PE increased leaf number but did not significantly affect other agronomic traits or pigment contents. Notably, 0.05 % PE increased the total root length and surface area compared to the 0.1 % addition, while a non-significant trend towards decreased root activity was observed with PE MPs. PE MPs with 0.1 % addition notably reduced the DOC concentration in root exudates by 37.5 %, while 0.05 % PE had no impact on DOC and DON concentrations. PE addition increased the SUVA254, SUVA260, and SUVA280 values of root exudates, with the most pronounced effect seen in the 0.05 % PE treatment. This suggests an increase of aromaticity and hydrophobic components induced by PE addition. Fluorescence Regional Integration (FRI) analysis of 3D-EEM revealed that aromatic proteins (region I and II) were dominant in root exudates, with a slight increase in fulvic acid-like substances (region III) under 0.1 % PE addition. Moreover, prolonged PE exposure induced ROS damage in lettuce leaves, evidenced by a significant increase in content and production rate of O2·-. The decrease in CAT and POD activities may account for the lettuce's response to environmental stress, potentially surpassing its tolerance threshold or undergoing adaptive regulation. These findings underscore the potential risk of prolonged exposure to PE MPs on lettuce growth.