ABSTRACT
Degradation of polyolefin (PE) plastic by a traditional chemical method requires a high pressure and a high temperature but generates complex products. Here, sulfur vacancy-rich ZnIn2S4 and hydroxy-rich ZnIn2S4 were rationally fabricated to realize photocatalytic degradation of PE in an aqueous solution under mild conditions. The results reveal that the optimized photocatalyst could degrade PE into CO2 and CO, and PE had a weight loss of 84.5% after reaction for 60 h. Systematic experiments confirm that the synergetic effect of hydroxyl groups and S vacancies contributes to improve the photocatalytic degradation properties of plastic wastes. In-depth investigation illustrates that the active radicals attack (h+ and â¢OH) weak spots (C-H and C-C bonds) of the PE chain to form CO2, which is further selectively photoreduced to CO. Multimodule synergistic tandem catalysis can further improve the utilization value of plastic wastes; for example, product CO2/CO in the plastic degradation process can be converted in situ into HCOOH by coupling with electrocatalytic technology.
ABSTRACT
Large-scale coal mine gas explosion (CMGE) accidents have occurred occasionally and exerted a devastating effect on society. Therefore, it is essential to systematically identify the characteristics and association rules of causes of CMGE accidents through analysis on large-scale CMGE accident reports. In this study, 298 large-scale CMGE accidents in China from 2000 to 2021 were taken as the data sample, and mathematical statistical methods were adopted to analyze their general characteristics, coupling cross characteristics, and characteristics of gas accumulation and ignition sources. Moreover, the text mining technology and the Apriori algorithm were used for exploring the formation mechanism of CMGE accidents, during which 46 main causal factors were identified and 59 strong association rules were obtained. Furthermore, an accident causation network was constructed based on the co-occurrence matrix. The key causal items and sets of CMGE accidents were clarified through network centrality analysis. According to the research results, electrical equipment failure, cable short circuit, mine lamp misfire, hot-line work, and blasting spark are the key ignition sources of CMGE. Fan failure, airflow short circuit, and local ventilation fan damage are the main causes of gas accumulation. Besides, the confidence levels of two association rules of "static spark-fan failure" and "blasting spark-airflow short circuit" are higher than 70%, indicating that they are the two dominant risk-coupling paths of gas explosions. In addition, six causes appear frequently in the shortest risk paths of gas explosion and are closely related to other causes, i.e., fan failure, local ventilation fan damage, static sparks, electrical equipment failure, self-heating ignition, and friction impact sparks. This study provides a new perspective on identifying causes of accidents and their complex association mechanisms from accident report data for practical guidance in risk assessment and accident prevention.
ABSTRACT
Pseudoalteromonas is a genus of marine bacteria and a promising source of natural products with antibacterial, antifungal, and antifouling bioactivities. To accelerate the exploration of new compounds from this genus, we applied the gene-first approach to study 632 public Pseudoalteromonas genomes. We identified 3968 biosynthetic gene clusters (BGCs) involved in the biosynthesis of secondary metabolites and classified them into 995 gene cluster families (GCFs). Surprisingly, only 9 GCFs (0.9 %) included an experimentally identified reference biosynthetic gene cluster from the Minimum Information about a Biosynthetic Gene cluster database (MIBiG), suggesting a striking novelty of secondary metabolites in Pseudoalteromonas. Bioinformatic analysis of the biosynthetic diversity encoded in the identified BGCs uncovered six dominant species of this genus, P. citrea, P. flavipulchra, P. luteoviolacea, P. maricaloris, P. piscicida, and P. rubra, that encoded more than 17 BGCs on average. Moreover, each species exhibited a species-specific distribution of BGC. However, a deep analysis revealed two BGCs conserved across five of the six dominant species. These BGCS encoded an unknown lanthipeptide and the siderophore myxochelin B implying an essential role of antibiotics for Pseudoalteromonas. We chemically profiled 11 strains from the 6 dominant species and identified four new antibiotics, korormicins L-O (1-4), from P. citrea WJX-3. Our results highlight the unexplored biosynthetic potential for bioactive compounds in Pseudoalteromonas and provide an important guideline for targeting exploration.
ABSTRACT
Unprecedented progress in immune checkpoint blockade (ICB) therapy has been made in cancer treatment. However, the response to ICB therapy is limited to a small subset of patients. The development of ICB sensitizers to improve cancer immunotherapy outcomes is urgently needed. Berberine (BBR), a well-known phytochemical compound isolated from many kinds of medicinal plants such as Berberis aristata, Coptis chinensis, and Phellondendron chinense Schneid, has shown the ability to inhibit the proliferation, invasion and metastasis of cancer cells. In this study, we investigated whether BBR can enhance the therapeutic benefit of ICB for melanoma, and explored the underlying mechanisms involved. The results showed that BBR could sensitize ICB to inhibit tumor growth and increased the survival rate of mice. Moreover, BBR stimulated intracellular ROS production partially by inhibiting NQO1 activity, which induced immunogenic cell death (ICD) in melanoma, elevated the levels of damage-associated molecular patterns (DAMPs), and subsequently activated DC cells and CD8 + T cells in vitro and in vivo. In conclusion, BBR is a novel ICD inducer. BBR could enhance the therapeutic benefit of ICB for melanoma. These effects were partially mediated through the inhibition of NQO1 and ROS activation.
ABSTRACT
The internal ribosome entry site (IRES) is a cis-regulatory element that can initiate translation in a cap-independent manner. It is often related to cellular processes and many diseases. Thus, identifying the IRES is important for understanding its mechanism and finding potential therapeutic strategies for relevant diseases since identifying IRES elements by experimental method is time-consuming and laborious. Many bioinformatics tools have been developed to predict IRES, but all these tools are based on structure similarity or machine learning algorithms. Here, we introduced a deep learning model named DeepIRES for precisely identifying IRES elements in messenger RNA (mRNA) sequences. DeepIRES is a hybrid model incorporating dilated 1D convolutional neural network blocks, bidirectional gated recurrent units, and self-attention module. Tenfold cross-validation results suggest that DeepIRES can capture deeper relationships between sequence features and prediction results than other baseline models. Further comparison on independent test sets illustrates that DeepIRES has superior and robust prediction capability than other existing methods. Moreover, DeepIRES achieves high accuracy in predicting experimental validated IRESs that are collected in recent studies. With the application of a deep learning interpretable analysis, we discover some potential consensus motifs that are related to IRES activities. In summary, DeepIRES is a reliable tool for IRES prediction and gives insights into the mechanism of IRES elements.
Subject(s)
Deep Learning , Internal Ribosome Entry Sites , RNA, Messenger , RNA, Messenger/genetics , RNA, Messenger/metabolism , Computational Biology/methods , RNA, Viral/genetics , RNA, Viral/metabolism , Humans , Neural Networks, Computer , AlgorithmsABSTRACT
Circular RNAs (circRNAs) in controlling gene expression have been highlighted by increasing evidence, and their dysregulation has been linked to various diseases. However, the limited role of circRNAs in the adipogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) has been explored. High-throughput sequencing of circRNA was carried out on BMSCs and AD induction 7d BMSCs. Then a substantial upregulation of circNDUFA13 was detected among circRNAs in AD induction 7d BMSCs. We found that the adipogenic differentiation of BMSCs was positively linked with circNDUFA13 expression levels. Adipogenesis in BMSCs was effectively inhibited by circNDUFA13 knockdown, whereas overexpression of circNDUFA13 promoted adipogenesis. It was noted that circNDUFA13 regulated the adipogenic differentiation of BMSCs by directly interacting with the signal transducer and activator of transcription 3 (STAT3), which activates CEBPß transcription. The in vitro model also validated the in vivo findings. our results suggest that circNDUFA13 controlled the adipogenic differentiation of BMSCs by targeting STAT3 and CEBPß activation.
Subject(s)
Adipogenesis , CCAAT-Enhancer-Binding Protein-beta , Mesenchymal Stem Cells , RNA, Circular , STAT3 Transcription Factor , Animals , Humans , Adipogenesis/genetics , Bone Marrow Cells/metabolism , Bone Marrow Cells/cytology , CCAAT-Enhancer-Binding Protein-beta/metabolism , CCAAT-Enhancer-Binding Protein-beta/genetics , Cell Differentiation , Cells, Cultured , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , RNA, Circular/genetics , RNA, Circular/metabolism , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/geneticsABSTRACT
Glioblastoma (GBM) is an aggressive brain cancer with limited therapeutic options. Natural killer (NK) cells are innate immune cells with strong anti-tumor activity and may offer a promising treatment strategy for GBM. We compared the anti-GBM activity of NK cells engineered to express interleukin (IL)-15 or IL-21. Using multiple in vivo models, IL-21 NK cells were superior to IL-15 NK cells both in terms of safety and long-term anti-tumor activity, with locoregionally administered IL-15 NK cells proving toxic and ineffective at tumor control. IL-21 NK cells displayed a unique chromatin accessibility signature, with CCAAT/enhancer-binding proteins (C/EBP), especially CEBPD, serving as key transcription factors regulating their enhanced function. Deletion of CEBPD resulted in loss of IL-21 NK cell potency while its overexpression increased NK cell long-term cytotoxicity and metabolic fitness. These results suggest that IL-21, through C/EBP transcription factors, drives epigenetic reprogramming of NK cells, enhancing their anti-tumor efficacy against GBM.
Subject(s)
Brain Neoplasms , CCAAT-Enhancer-Binding Protein-delta , Glioblastoma , Interleukins , Killer Cells, Natural , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Glioblastoma/immunology , Glioblastoma/genetics , Glioblastoma/pathology , Glioblastoma/therapy , Interleukins/genetics , Interleukins/metabolism , Interleukins/immunology , Humans , Animals , Mice , CCAAT-Enhancer-Binding Protein-delta/metabolism , CCAAT-Enhancer-Binding Protein-delta/genetics , Brain Neoplasms/immunology , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/therapy , Cell Line, Tumor , Interleukin-15/genetics , Interleukin-15/metabolism , Interleukin-15/immunology , Xenograft Model Antitumor AssaysABSTRACT
Mesophotic coral ecosystems (MCEs), located at depths ranging from 30-150 m, host some of the most diverse yet least explored marine bioresources, particularly significant for the discovery of new bioactive molecules. The fungus Beauveria sp. NBUF147, associated with an Irciniidae sponge from the mesophotic zone at a depth of 82 m, underwent chemical investigation that led to the identification of one new sterol, beautoide A (1), and one reported sterol, 3ß,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (2). Their structures were determined from analysis of spectroscopic data and X-ray crystallography. Evaluation of biological activity in prednisolone-induced osteoporotic zebrafish showed that 1 was anti-osteoclastogenic in vivo at 3.0 µM.
ABSTRACT
Interstitial lung disease (ILD) has been identified as a prevalent complication and significant contributor to mortality in individuals with pemphigus. In this study, a murine model of pemphigus was developed through the subcutaneous administration of serum IgG obtained from pemphigus patients, allowing for an investigation into the association between pemphigus and ILD. Pulmonary interstitial lesions were identified in the lungs of a pemphigus mouse model through histopathology, RT-qPCR and Sircol assay analyses. The severity of these lesions was found to be positively associated with the concentration of IgG in the injected serum. Additionally, DIF staining revealed the deposition of serum IgG in the lung tissue of pemphigus mice, indicating that the subcutaneous administration of human IgG directly impacted the lung tissue of the mice, resulting in damage. This study confirms the presence of pulmonary interstitial lesions in the pemphigus mouse model and establishes a link between pemphigus and ILD.
Subject(s)
Disease Models, Animal , Immunoglobulin G , Lung Diseases, Interstitial , Pemphigus , Pemphigus/pathology , Animals , Mice , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/pathology , Immunoglobulin G/blood , Humans , Lung/pathology , Skin/pathology , Female , Mice, Inbred BALB CABSTRACT
Recent developments in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy (ACT), have encountered challenges such as immune-related adverse events and resistance, especially in solid tumors. To advance the field, a deeper understanding of the molecular mechanisms behind treatment responses and resistance is essential. However, the lack of functionally characterized immune-related gene sets has limited data-driven immunological research. To address this gap, we adopted non-negative matrix factorization on 83 human bulk RNA sequencing (RNA-seq) datasets and constructed 28 immune-specific gene sets. After rigorous immunologist-led manual annotations and orthogonal validations across immunological contexts and functional omics data, we demonstrated that these gene sets can be applied to refine pan-cancer immune subtypes, improve ICB response prediction and functionally annotate spatial transcriptomic data. These functional gene sets, informing diverse immune states, will advance our understanding of immunology and cancer research.
ABSTRACT
Neurodegenerative diseases involve progressive neuronal death. Traditional treatments often struggle due to solubility, bioavailability, and crossing the Blood-Brain Barrier (BBB). Nanoparticles (NPs) in biomedical field are garnering growing attention as neurodegenerative disease drugs (NDDs) carrier to the central nervous system. Here, we introduced computational and experimental analysis. In the computational study, a specific IFPTML technique was used, which combined Information Fusion (IF) + Perturbation Theory (PT) + Machine Learning (ML) to select the most promising Nanoparticle Neuronal Disease Drug Delivery (N2D3) systems. For the application of IFPTML model in the nanoscience, NANO.PTML is used. IF-process was carried out between 4403 NDDs assays and 260 cytotoxicity NP assays conducting a dataset of 500,000 cases. The optimal IFPTML was the Decision Tree (DT) algorithm which shown satisfactory performance with specificity values of 96.4% and 96.2%, and sensitivity values of 79.3% and 75.7% in the training (375k/75%) and validation (125k/25%) set. Moreover, the DT model obtained Area Under Receiver Operating Characteristic (AUROC) scores of 0.97 and 0.96 in the training and validation series, highlighting its effectiveness in classification tasks. In the experimental part, two samples of NPs (Fe3O4_A and Fe3O4_B) were synthesized by thermal decomposition of an iron(III) oleate (FeOl) precursor and structurally characterized by different methods. Additionally, in order to make the as-synthesized hydrophobic NPs (Fe3O4_A and Fe3O4_B) soluble in water the amphiphilic CTAB (Cetyl Trimethyl Ammonium Bromide) molecule was employed. Therefore, to conduct a study with a wider range of NP system variants, an experimental illustrative simulation experiment was performed using the IFPTML-DT model. For this, a set of 500,000 prediction dataset was created. The outcome of this experiment highlighted certain NANO.PTML systems as promising candidates for further investigation. The NANO.PTML approach holds potential to accelerate experimental investigations and offer initial insights into various NP and NDDs compounds, serving as an efficient alternative to time-consuming trial-and-error procedures.
Subject(s)
Nanoparticles , Nanoparticles/chemistry , Machine Learning , Algorithms , Animals , Neurodegenerative Diseases/drug therapy , Neurosciences/methods , Computer Simulation , Humans , Blood-Brain Barrier/metabolism , Drug Delivery Systems/methods , Drug Carriers/chemistryABSTRACT
Overexposure of sewage workers to bioaerosol released from wastewater treatment plants (WWTPs) can cause serious infections, but practical method for controlling their health risk is lacking. In this study, reverse quantitative microbial risk assessment was used to estimate the daily critical exposure time (CET) of sewage workers exposing to Staphylococcus aureus bioaerosol emitted by three emission sources facilities in a WWTP based on either U.S. EPA or WHO benchmark, and sensitivity analysis was conducted to analyze the influence of various parameters on the outcomes of CET. The results showed that the CET of females was always 1.12-1.29 times that of males. In addition, the CET after wearing face masks was 28.28-52.37 times as long as before. The working time can be determined based on the CET results of male workers wearing face masks exposed to the inverted-umbrella aeration tank (14.73-550.98 min for U.S. EPA benchmark and 55.07-1972.24 min for WHO benchmark). In each scenario, the variable parameter exposure concentration (ec) always showed the most influence on the CET results. After wearing the face masks, the removal fraction by employing face masks also had a significant effect on the results, only second to ec. Therefore, the wearing of face mask is the most convenient and effective measure to prolong the CET. Furthermore, practical methods to reducing bioaerosol concentration in WWTPs exposure are also necessary to extend CET and safeguard worker health. This study enriches the application range of reverse quantitative microbial risk assessment framework and provides theoretical support for stakeholders to establish reasonable working time threshold guidelines, and practical method and novel perspective to protect the on-site health risks of sewage workers exposing to various facilities.
ABSTRACT
OBJECTIVE: To explore the potential mechanism of lysionotin in treating glioma. METHODS: First, target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of lysionotin. The binding between 5-lipoxygenase (5-LO) and lysionotin was detected by surface plasmon resonance (SPR) and molecular docking, and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis, respectively. Furthermore, the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry (LC-MS/MS). The protein expression, intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot, flow cytometry and fluorescence labeling, respectively. RESULTS: Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO, a key enzyme involved in the arachidonic acid metabolism pathway, to inhibit the proliferation of glioma. Molecular docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds, forming bonds with His600, Gln557, Asn554, and His372. SPR analysis further confirmed the interaction between 5-LO and lysionotin. Furthermore, enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50% inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58 µmol/L, respectively, and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid (P<0.05), and moreover, the LC-MS/MS results indicated that lysionotin can enter glioma cells well (P<0.01) and inhibit their proliferation. Western blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO (P<0.05) and downstream leukotriene B4 receptor (P<0.01). In addition, the results showed that lysionotin affected intracellular calcium ion concentration by inhibiting 5-LO to affect the cytoskeleton, as determined by flow cytometry and fluorescence labeling. CONCLUSION: Lysionotin binds to 5-LO could suppress glioma by inhibiting arachiodonic acid metabolism pathway.
Subject(s)
Arachidonate 5-Lipoxygenase , Cell Proliferation , Glioma , Lipoxygenase Inhibitors , Molecular Docking Simulation , Glioma/drug therapy , Glioma/pathology , Glioma/metabolism , Glioma/enzymology , Arachidonate 5-Lipoxygenase/metabolism , Humans , Lipoxygenase Inhibitors/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Calcium/metabolism , Tandem Mass SpectrometryABSTRACT
Cancer continues to pose a significant threat to global health, with its status as a leading cause of death remaining unchallenged. Within the realm of cancer research, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) stands out as a critical player, having been identified in the 1990s as the tenth member of the TNF family. This review examines the pivotal role of TRAIL in cancer biology, focusing on its ability to induce apoptosis in malignant cells through both endogenous and exogenous pathways. We provide an in-depth analysis of TRAIL's intracellular signaling and intercellular communication, underscoring its potential as a selective anticancer agent. Additionally, the review explores TRAIL's capacity to reshape the tumor microenvironment, thereby influencing cancer progression and response to therapy. With an eye towards future developments, we discuss the prospects of harnessing TRAIL's capabilities for the creation of tailored, precision-based cancer treatments, aiming to enhance efficacy and improve patient survival rates.
ABSTRACT
Ferroptosis is a novel and iron-dependent form of programmed cell death, which has been implicated in the pathogenesis of various human cancers. EBV is a well-recognized oncogenic virus that controls multiple signaling pathways within the host cell, including ferroptosis signaling. Recent studies show that inducing ferroptosis could be an efficient therapeutic strategy for EBV-associated tumors. This review will firstly describe the mechanism of ferroptosis, then summarize EBV infection and EBV-associated tumors, as well as the crosstalk between EBV infection and the ferroptosis signaling pathway, and finally discuss the role and potential application of ferroptosis-related reagents in EBV-associated tumors.
ABSTRACT
Nowadays, biochar is extensively used in wastewater remediation with the aim of achieving water security and circularity with minimal impacts on ecosystems and the environment. In this study, digestate biochar was prepared and modified using different methods and then employed as a peroxymonosulfate (PMS) activator to oxidize oxytetracycline, a model antibiotic pollutant in wastewater. The optimal biochar catalyst was characterized, spin trapping tests were carried out to confirm the dominant catalytic mechanism, and in silico toxicity prediction was conducted based on structure-activity relationships. Assessment of the catalytic performance of the pristine and engineered biochar showed that nitrogen doping increased oxytetracycline degradation efficiency by 1.92-fold (i.e., 100% oxytetracycline degradation with the engineered biochar compared to 52% with pristine biochar), while pyrrolic nitrogen was identified as a major PMS activation site. It was discovered that several parameters, such as catalyst dose, pH, PMS concentration, and competing ions, affected oxytetracycline degradation efficiencies. Additionally, the toxicity of the degradation intermediate was studied. Scavenger trapping tests showed that 1O2 and SO4â¢- were the most prevalent species during oxytetracycline degradation in the system, with four possible degradation pathways proposed, including secondary alcohol oxidation, hydroxylation, dehydration, and deamidation. Overall, it is anticipated that this study would contribute to our understanding of metal-free biochar activation of PMS as an attractive treatment scheme for antibiotic-polluted water.
ABSTRACT
Near-infrared photosensitizers are valuable tools to improve treatment depth in photodynamic therapy (PDT). However, their low singlet oxygen (1O2) generation ability, indicated by low 1O2 quantum yield, presents a formidable challenge for PDT. To overcome this challenge, the heptamethine cyanine was decorated with biocompatible S (Scy7) and Se (Secy7) atom. We observe that Secy7 exhibits a redshift in the main absorption to ~840 nm and an ultra-efficient 1O2 generation capacity. The emergence of a strong intramolecular charge transfer effect between the Se atom and polymethine chain considerably narrows the energy gap (0.51 eV), and the heavy atom effect of Se strengthens spin-orbit coupling (1.44 cm-1), both of which greatly improved the high triplet state yield (61%), a state that determines the energy transfer to O2. Therefore, Secy7 demonstrated excellent 1O2 generation capacity, which is ~24.5-fold that of indocyanine green, ~8.2-fold that of IR780, and ~1.3-fold that of methylene blue under low-power-density 850 nm irradiation (5 mW cm-2). Secy7 exhibits considerable phototoxicity toward cancer cells buried under 12 mm of tissue. Nanoparticles formed by encapsulating Secy7 within amphiphilic polymers and lecithin, demonstrated promising antitumor and anti-pulmonary metastatic effects, exhibiting remarkable potential for advancing PDT in deep tissues.
ABSTRACT
Healthcare facilities produce millions of tons of waste annually, with a significant portion consisting of diagnostic plasticware. Here, we introduce a new detection platform that completely replaces traditional assay plates with a piece of membrane, offering a much greener and more sustainable alternative. The membrane, integrated within the portable vortex fluidic device (P-VFD), enables rapid detection of a clinically relevant protein biomarker, urinary p75ECD. This biomarker is utilized to evaluate the prognosis, disease severity, and progression of amyotrophic lateral sclerosis (ALS). This assay has a limit-of-detection (LOD) of 4.03â pg, which is comparable to the plate-based assay (2.24â pg) and has been optimised through a full factorial design of experiments (DOE) and response surface methodology (RSM). P-VFD has great potential in quantifying p75ECD in human biofluids and can significantly reduce the assay time to 5â min compared to the current plate-based p75ECD ELISA assay (3â days), with at least a 4.4-fold reduction in the usage of the detection antibody.
ABSTRACT
Myopia represents a widespread global public health concern influenced by a combination of environmental and genetic factors. The prevailing theory explaining myopia development revolves around scleral extracellular matrix (ECM) remodeling, characterized by diminished Type I collagen (Col-1) synthesis and increased degradation, resulting in scleral thinning and eye axis elongation. Existing studies underscore the pivotal role of scleral hypoxia in myopic scleral remodeling. This study investigates the peroxidase-like activity and catalytic performance of octahedral Palladium (Pd) nanocrystals, recognized as nanozymes with antioxidative properties. We explore their potential in reducing oxidative stress and alleviating hypoxia in human scleral fibroblasts (HSF) and examine the associated molecular mechanisms. Our results demonstrate the significant peroxidase-like activity of Pd nanocrystals. Furthermore, we observe a substantial reduction in oxidative stress in HSF under hypoxia, mitigating cellular damage. These effects are linked to alterations in Nrf-2/Ho-1 expression, a pathway associated with hypoxic stress. Importantly, our findings indicate that Pd nanocrystals contribute to attenuated scleral matrix remodeling in myopic guinea pigs, effectively slowing myopia progression. This supports the hypothesis that Pd nanocrystals regulate myopia development by controlling oxidative stress associated with hypoxia. Based on these results, we propose that Pd nanocrystals represent a novel and potential treatment avenue for myopia through the modulation of scleral matrix remodeling. This study introduces innovative ideas and directions for the treatment and prevention of myopia.
ABSTRACT
Methicillin-resistant Staphylococcus aureus (MRSA) can easily form biofilms on food surfaces, thus leading to cross-contamination, which is difficult to remove. Therefore, there is an urgent need to find alternatives with good antibacterial and antibiofilm effects. In this study, two indole sesquiterpene compounds, xiamycin (1) and chlorinated metabolite chloroxiamycin (2), were isolated from the fermentation liquid of marine Streptomyces sp. NBU3429 for the first time. The chemical structures of the two compounds were characterized by spectroscopic data interpretation, including 1D NMR and HRESIMS analysis. Antimicrobial test showed that chloroxiamycin (2) (minimum inhibitory concentration, MIC = 16 µg/mL) exhibited superior antibacterial activity than xiamycin (1) (MIC = 32 µg/mL) against MRSA ATCC43300. Moreover, compound (2) decreased the biofilm formation rate of MRSA ATCC43300 by 12.7%-84.6% in the concentration range of 32-512 µg/mL, which is relatively stronger than xiamycin (1) (4.1%-49.9%) as well. Antibacterial/antibiofilm mechanism investigation indicated that chloroxiamycin (2) could disrupt the cell wall and membrane of MRSA, inhibiting the production of biofilm extracellular polysaccharides. All these results illustrated that chloroxiamycin (2) is an effective antibacterial/antibiofilm agent, which makes it an attractive candidate for food preservatives.