Marine Life Science & Technology最新文献

Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as OX40, plays a crucial role in the regulation of T-cell immune responses under normal physiological conditions. Abnormal expression of OX40 and its cognate ligand OX40L (TNFSF4) have been associated with various autoimmune diseases, indicating that blocking the OX40/OX40L pathway could be a promising strategy for the treatment of a broad range of T cell-mediated autoimmune diseases. Here, we screened and characterized a fully human anti-OX40 antibody (JY007) from a naïve human scFv phage library. JY007 has an affinity constant of 7.71 nmol/L and effectively inhibited the OX40-OX40L interaction at both molecular and cellular levels, with IC₅₀ values of 1.088 and 10.12 nmol/L, respectively. Furthermore, JY007 demonstrated the ability to deplete activated T lymphocytes through antibody-dependent cellular cytotoxicity (ADCC) activity, with an EC₅₀ of 5.592 pmol/L. The combination of ADCC and its antagonist activity against OX40 suggests potential efficacy in suppressing inflammatory responses mediated by the OX40/OX40L pathway. Additionally, we employed molecular docking, site-directed mutagenesis, and competitive ELISA to pinpoint the epitopes on OX40. The results revealed that JY007 binds to Pro³⁷, Ser³⁸, and Asp⁴⁰ of OX40. Interestingly, we also found that the most potent anti-OX40 antibody drug in the clinical stage, KHK4083, binds to different OX40 amino-acid residues, including Asp⁷⁴, Lys⁸², Asp¹¹⁷, Ser¹¹⁸, Tyr¹¹⁹, and Lys¹²⁰. This divergence suggests that the novel monoclonal antibody JY007 holds promise as a potential therapeutic option for patients with atopic dermatitis and may find broad applications in the treatment of autoimmune diseases.

Supplementary information: The online version contains supplementary material available at 10.1007/s42995-025-00284-y.

MS/MS-based molecular networking is an effective strategy to rapidly dereplicate known compounds and to guide the discovery process for new and novel natural products. In the present study, the chemical diversity of indole diterpenoids from the marine-derived fungus Penicillium sp. N4-3 was investigated using molecular networking techniques. Guided by this information, targeted isolation resulted in two new indole diterpenoids shearinines R and S (1, 2) and an oxidative artifact shearinine T (3), together with the verification of two known analogs (4, 5). Furthermore, five indole diterpenoids (6-10), including three putatively new ones, shearinines U-W (6, 9, 10), were predicted from the molecular ion cluster by the combination of GNPS molecular networking and manual analysis of MS/MS fragmentation clusters. Shearinines T (3) and W (10) are characterized by an oxidative cleavage of the C-2-C-18 double bond. Feature fragment ions of these shearinines revealed two type of dominant ions related to the indole moiety and the breaking of C-9 side chain or Ring I. Compound 1 showed antibacterial activities against a panel of pathogenic bacteria with IC₅₀ values ranging from 6.34 to 47.96 μg/mL and inhibited the growth of the human hepatic (HepG2) and gastric (SGC-7901) cancer cells lines with IC₅₀ values of 6.27 and 19.16 μg/mL, respectively.

Supplementary information: The online version contains supplementary material available at 10.1007/s42995-024-00274-6.

Heterotrophic bacterial production and respiration, two important contributors to carbon cycling, play an important role in global biogeochemical cycles. However, recent research suggests that these two processes may be decoupled, and the underlying changes in community structure and their interactions remain unclear. In this study, two research expeditions to the North Pacific Subtropical Gyre (NPSG) during the summer and winter of 2020-2021 revealed seasonal shifts in bacterial metabolism and community structure in response to environmental factors. The findings indicated notable seasonal fluctuations in bacterial abundance and production in the surface waters. Both peaked in winter compared to summer. Alterations in bacterial abundance that were further evident at the community level demonstrated significant seasonal differences in bacterial community structure and diversity and revealed, in particular, the intricacy of the networks and interactions among bacterial communities in winter. Bacterial respiration displayed no significant seasonal variations and was decoupled from bacterial abundance and production. The implication was that bacterial production did not directly dictate bacterial respiration. Specific taxa exerted a more substantial influence on bacterial respiration, potentially including groups with high respiration rates but relatively low abundance, thus challenging the notion that highly abundant taxa are invariably the most metabolically active. Moreover, the interplay between different bacterial taxa and their interactions may also impact the overall strength of bacterial community respiration. These findings significantly enhance our understanding of the decoupling between bacterial production and respiration, which is crucial for unraveling the complex mechanisms underlying carbon cycling and energy flow in marine ecosystems.

Supplementary information: The online version contains supplementary material available at 10.1007/s42995-025-00279-9.

Temperature is well known as the major environmental factor that influences survival and growth of fish, which are poikilothermic animals. However, it is still unclear about the mechanism that underscores thermal-controlled fish physiology, especially nutritional utilization and metabolism, which are vitally important in aquaculture. In the present study, juvenile turbot was force-fed with amino acid mixture and its postprandial absorption, nutrient sensing and metabolism under low (12, 15 ℃), optimal (18 ℃) to high (21, 24 ℃) temperatures were explored. Intestinal trypsin and lipase activity were highly sensitive to water temperature, and highest under optimal temperatures for turbot, whereas amylase remained constant. Selective groups of intestinal amino acid transporters were upregulated in cold temperatures, but the amino acid absorption capability was increased with rising temperature. The mechanistic target of rapamycin (mTOR) signaling pathway was most active at optimal temperature. Postprandial muscle protein deposition achieved maximum level under optimal temperature. Amino acid catabolic enzymes branched-chain aminotransferase and branched-chain α-keto acid dehydrogenase activities were increased with rising temperatures. High temperature increased significantly energy metabolism and stimulated cellular stress in liver. These findings highlight the critical role of temperature in modulating amino acid dynamics, metabolic processes and stress responses in juvenile turbot, providing valuable insights for optimizing aquaculture practices.

Supplementary information: The online version contains supplementary material available at 10.1007/s42995-025-00280-2.

Damage to the epithelial barrier is among key processes contributing to initiation and chronic inflammation in inflammatory bowel diseases (IBD). Only management therapy exists for IBD (e.g., anti-inflammatory and immunomodulatory agents, JAK/STAT inhibitors), and while novel therapeutic approaches have shown great potential, issues remain including route of administration, development of resistance to therapy and toxicity. Thus, novel small molecule inhibitors which can alleviate colonic inflammation and restore intestinal barrier functions are needed. Our previous study identified a new quinazolinone derivative MR2938, inspired by marine natural product penipanoid C, displaying impressive anti-inflammatory effects. In vivo efficacy study indicated that MR2938 had a dose-dependent effect on improving colitis symptoms, gut-barrier disruption, and colonic inflammation in an acute dextran sulfate sodium (DSS)-induced murine colitis as a model of epithelial injury relevant to IBD. Evaluation of potential mechanism involved in MR2938 efficacy demonstrated that MR2938 inhibited NF-κB-mediated inflammatory responses, and attenuated intestinal epithelial tight junction damage by restoring the expression of Occludin and ZO-1. Taken together, these data suggest that MR2938 is a promising lead compound for the treatment of IBD.

Supplementary information: The online version contains supplementary material available at 10.1007/s42995-025-00285-x.

As dynamic and functionally active organelles, lipid droplets (LDs) mainly function in lipid anabolism, while recent studies showed that mammalian LDs also actively participated in innate immunity; however, the specific roles and regulation mechanism remain relatively unexplored, and the existing studies were mainly limited to mammals. In the present study, we first found that Vibrio harveyi, a serious pathogen in marine environment, could induce LDs accumulation in the liver of obscure puffer Takifugu obscurus on the histology, morphology and molecular levels, and the induction mainly conducted by promoting the synthesis of neutral lipids. Moreover, the antibacterial activity of LD proteins was significantly enhanced upon V. harveyi stimulation, and showed broad-spectrum characteristic. While the inhibition of LDs formation downregulated the expression of immune-related genes and immune signaling elements, highlighting the potential critical roles of LDs during the bacterial infection. The isolated LDs from obscure puffer liver were examined via proteomic analyses, and the data supported the conservative property of LDs from bacteria to humans, and revealed that numerous innate immune system-related components were enriched on the surface of LDs. These results will deepen the understanding of LDs biology and host immune defense mechanism, shedding light on the new strategies for the development of anti-infective therapies.

Supplementary information: The online version contains supplementary material available at 10.1007/s42995-025-00286-w.

Astome ciliates live in the digestive tract of a broad spectrum of marine, freshwater, and terricolous annelids. In aquatic lumbriculid and criodrilid oligochaetes collected in Central Europe, we rediscovered three insufficiently known astomes: Hoplitophrya secans, Mesnilella clavata, and Buchneriella criodrili. Their morphology was studied using in vivo observation, protargol, and dry silver nitrate impregnation. Multiple nuclear and mitochondrial molecular markers were used to determine their phylogenetic positions and reconstruct their evolutionary history. According to our phylogenetic analyses: (1) mouthless ciliates isolated from annelids form a robustly supported monophylum within the class Oligohymenophorea, (2) the progenitor of astomes invaded the digestive tract of marine polychaetes during the Paleozoic era, (3) lumbricid earthworms likely served as a source of astomes for criodrilid, almid, and megascolecid earthworms, (4) the ancestral host of the earthworm-dwelling astome clade led an endogeic lifestyle, and (5) there were multiple independent transfers of astomes from endogeic to epigeic and anecic earthworms. These findings support previous views of the annelid phylogeny, suggesting that astomes reside and evolve in tandem with annelids for several hundred million years.

Supplementary information: The online version contains supplementary material available at 10.1007/s42995-024-00275-5.

Annual bay scallops are commercially significant bivalve species for fisheries and aquaculture, but their small size and severe inbreeding depression impede the development of their industry. Some interspecific hybrids of bay scallops and peruvian scallops show longer lifespans and significantly greater sizes, which may result from the longevity genes in the latter (7-10 years). Sirtuins (SIRTs) play pivotal roles in the genetic control of aging in various model species and human beings. However, the role of SIRTs in longevity has not been systematically studied in aquatic animals. In this study, different gene numbers, sequences, structures and tandem duplications of SIRTs were first identified between the two scallops through genome-wide analysis. Cloning and characteristics of the SIRT1 and SIRT6 ORFs revealed dramatic variations in amino acids between the two scallops, which may cause intrinsic differences in function for longevity regulation. In particular, the amino acid variations in the N-terminus may auto-regulate conformations, causing intrinsic differences in catalytic activity for longevity regulation. The robust expression of SIRT1 and SIRT6-2 in peruvian scallops suggested they may exert a role in extending the lifespan. Nutrient restriction (NR) could promote lifespan in terrestrial model organisms, and the SIRTs and their related genes responded to NR for longevity in scallops; peruvian scallops showed a higher ability of autophagy. This study provides potential biomarkers for breeding long-lived larger scallop hybrids for the sustainability of aquaculture. Moreover, the genetic variation during evolution in the two scallops provides a foundation for further research on the longevity function of the SIRTs.

Supplementary information: The online version contains supplementary material available at 10.1007/s42995-024-00269-3.

Microbial degradation of methylphosphonate (MPn) is an important pathway contributing to the 'methane paradox' in the oxic ocean. Vibrio spp. are suggested to participate in this process. However, little is known about the molecular basis, phylogenetic breadth and catabolic efficiency of methane production in Vibrio species. Here, 18 Vibrionales strains known to be effective in MPn demethylation were obtained. The most effective strains, i.e., Vibrio gallaecicus HW2-07 and HW2-08, can convert 70%-80% of amended MPn into methane in 5 days. Estimations based on quantitative PCR determination indicated that Vibrio spp. were influential contributors to marine methane production. Genes flanking the common phn genes suggested a divergent gene arrangement and grouped the phn operons into nine types. This was consistent with the phylogeny of phnJ and phnL. The phn operons of cluster I and II were identified frequently in Vibrio isolates and were common in coastal seas and the open ocean. Addition of MPn increased expression of the phn genes, as well as an unexpected gene that encodes an acyltransferase (act), which frequently occurred in cluster I-IV operons. This study provided experimental evidence and theoretical support for a further understanding that Vibrio spp. may play important roles in aerobic marine methane production.

Supplementary information: The online version contains supplementary material available at 10.1007/s42995-025-00278-w.

This study demonstrated the design of whey protein isolate (WPI)-mannose (Man) conjugates with triphenylphosphonium bromide (TPP) through self-assembly to prepare macrophage and mitochondrion dual-targeting astaxanthin (AXT) nanoparticles (AXT@TPP-WPI-Man). The nanoparticles displayed spherical structures with a well-dispersed size of approximately 206.1 ± 39.2 nm, with good biocompatibility, stability, and targeting capabilities. In vitro experiments demonstrated the specific accumulation of AXT@TPP-WPI-Man in mitochondria and exhibited good targeting ability toward macrophages. The AXT@TPP-WPI-Man effectively reduced reactive oxygen species and preserved the normal mitochondrial membrane potential. The AXT@TPP-WPI-Man treated ulcerative colitis mice exhibited a 52.32% increase in colon length with significant improvement in weight loss, disease activity index scores, and reduced release of inflammatory cytokines. Immunofluorescence staining indicated AXT@TPP-WPI-Man alleviated ulcerative colitis by reducing M1 polarization in colonic macrophages while promoting M2 polarization. The dual-targeting AXT@TPP-WPI-Man has the potential to improve astaxanthin bioavailability, presenting a promising delivery method for the treatment of ulcerative colitis.

Supplementary information: The online version contains supplementary material available at 10.1007/s42995-024-00255-9.