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Marine microbes drive pivotal transformations in planetary-scale elemental cycles and have crucial impacts on global biogeochemical processes. Metaproteomics is a powerful tool for assessing the metabolic diversity and function of marine microbes. However, hundreds of liters of seawater are required for normal metaproteomic analysis due to the sparsity of microbial populations in seawater, which poses a substantial challenge to the widespread application of marine metaproteomics, particularly for deep seawater. Herein, a sensitive marine metaproteomics workflow, named sensitive marine metaproteome analysis (SMMP), was developed by integrating polycarbonate filter-assisted microbial enrichment, solid-phase alkylation-based anti-interference sample preparation, and narrow-bore nanoLC column for trace peptide separation and characterization. The method provided more than 8500 proteins from 1 L of bathypelagic seawater samples, which covered diverse microorganisms and crucial functions, e.g., the detection of key enzymes associated with the Wood–Ljungdahl pathway. Then, we applied SMMP to investigate vertical variations in the metabolic expression patterns of marine microorganisms from the euphotic zone to the bathypelagic zone. Methane oxidation and carbon monoxide (CO) oxidation were active processes, especially in the bathypelagic zone, which provided a remarkable energy supply for the growth and proliferation of heterotrophic microorganisms. In addition, marker protein profiles detected related to ammonia transport, ammonia oxidation, and carbon fixation highlighted that Thaumarchaeota played a critical role in primary production based on the coupled carbon–nitrogen process, contributing to the storage of carbon and nitrogen in the bathypelagic regions. SMMP has low microbial input requirements and yields in-depth metaproteome analysis, making it a prospective approach for comprehensive marine metaproteomic investigations.

Globally kelp farming is gaining attention to mitigate land-use pressures and achieve carbon neutrality. However, the influence of environmental perturbations on kelp farming remains largely unknown. Recently, a severe disease outbreak caused extensive kelp mortality in Sanggou Bay, China, one of the world’s largest high-density kelp farming areas. Here, through in situ investigations and simulation experiments, we find indications that an anomalously dramatic increase in elevated coastal seawater light penetration may have contributed to dysbiosis in the kelp Saccharina japonica’s microbiome. This dysbiosis promoted the proliferation of opportunistic pathogenic Enterobacterales, mainly including the genera Colwelliaand Pseudoalteromonas. Using transcriptomic analyses, we revealed that high-light conditions likely induced oxidative stress in kelp, potentially facilitating opportunistic bacterial Enterobacterales attack that activates a terrestrial plant-like pattern recognition receptor system in kelp. Furthermore, we uncover crucial genotypic determinants of Enterobacterales dominance and pathogenicity within kelp tissue, including pathogen-associated molecular patterns, potential membrane-damaging toxins, and alginate and mannitol lysis capability. Finally, through analysis of kelp-associated microbiome data sets under the influence of ocean warming and acidification, we conclude that such Enterobacterales favoring microbiome shifts are likely to become more prevalent in future environmental conditions. Our study highlights the need for understanding complex environmental influences on kelp health and associated microbiomes for the sustainable development of seaweed farming.

The microbiomes in macroalgal holobionts play vital roles in regulating macroalgal growth and ocean carbon cycling. However, the virospheres in macroalgal holobionts remain largely underexplored, representing a critical knowledge gap. Here we unveil that the holobiont of kelp (Saccharina japonica) harbors highly specific and unique epiphytic/endophytic viral species, with novelty (99.7% unknown) surpassing even extreme marine habitats (e.g. deep-sea and hadal zones), indicating that macroalgal virospheres, despite being closest to us, are among the least understood. These viruses potentially maintain microbiome equilibrium critical for kelp health via lytic-lysogenic infections and the expression of folate biosynthesis genes. In-situkelp mesocosm cultivation and metagenomic mining revealed that kelp holobiont profoundly reshaped surrounding seawater and sediment virus–prokaryote pairings through changing surrounding environmental conditions and virus–host migrations. Some kelp epiphytic viruses could even infect sediment autochthonous bacteria after deposition. Moreover, the presence of ample viral auxiliary metabolic genes for kelp polysaccharide (e.g. laminarin) degradation underscores the underappreciated viral metabolic influence on macroalgal carbon cycling. This study provides key insights into understanding the previously overlooked ecological significance of viruses within macroalgal holobionts and the macroalgae–prokaryotes–virus tripartite relationship.

The combination of reactive oxygen species (ROS)-induced chemodynamic therapy (CDT) and photothermal therapy (PTT) holds a promising application prospect for their superb anticancer efficiency. Herein, we created a novel Fe3O4@polydopamine (PDA)@bovine serum albumin (BSA)-Bi2S3composite as a theranostic agent, by chemically linking the Fe3O4@PDA with BSA-Bi2S3via the amidation between the carboxyl groups of BSA and the amino groups of PDA. In this formulation, the Fe3O4NPs could not only work as a mimetic peroxidase to trigger Fenton reactions of the innate H2O2in the tumor and generate highly cytotoxic hydroxyl radicals (•OH) to induce tumor apoptosis but also serve as the magnetic resonance imaging (MRI) contrast agent to afford the precise cancer diagnosis. Meanwhile, the PDA could prevent the oxidization of Fe3O4, thus supporting the long-term Fenton reactions and the tumor apoptosis in the tumor. The Bi2S3component exhibits excellent photothermal transducing performance and computed tomography (CT) imaging capacity. In addition, the PDA and Bi2S3endow the Fe3O4@PDA@BSA-Bi2S3composite with an excellent photothermal transforming ability which could lead to tumor hyperthermia. All of these merits play the synergism with the tumor microenvironment and qualify the Fe3O4@PDA@BSA-Bi2S3NPs for a competent agent in the MRI/CT-monitored enhanced PTT/CDT synergistic therapy. Findings in this research will evoke new interests in future cancer therapeutic strategies based on biocompatible nanomaterials.

Alginate-Ca2+hydrogel has been used to immobilize photothermal materials as well as chemotherapy drugs at lesion sites to prevent their entry into the bloodstream. However, the alginate-Ca2+gelation mechanism may result in hardening of the blood vessels because of Ca2+migration to the lesion site. In this study, a unique and facile one-pot formation of chemotherapeutic (doxorubicin, DOX) and polypyrrole-containing alginate hydrogel was designed by introducing Fe3+, which can synchronously induce the polymerization of pyrrole and gelatinization of alginate, into the DOX/pyrrole/alginate solution. The formed composite hydrogel was endowed with superior photothermal conversion properties in both the NIR-I (650–950 nm) and NIR-II (1000–1700 nm) biowindows and light-to-heat conversion efficiency higher than 50%, which enabled effective tumor hyperthermia treatment. Besides, near-infrared (NIR) irradiation could be used as a remote controller to trigger the DOX-release because of the heat generation, thus achieving continuous and on-demand tumor chemotherapy. The composite polymer hydrogels exhibited favorable hemo-, cyto-, and histocompatibility, as well as simple and cost-effective preparation and good clinical prospects.

The overproduction of reactive oxygen species (ROS) is central to the progression of inflammatory bowel disease (IBD), which may be the potential therapeutic target. Prussian blue (PB) nanoparticles with good biosafety can act as an artificial nanozyme, effectively scavenging ROS. To date, PB-based nanomaterials have not been developed and utilized for treatment of IBD. In this study, poly(vinylpyrrolidone)-modified Prussian blue (PPB) nanoparticles are constructed with good physiological stability and biosafety by a simple and efficient method. The prepared PPBs with capabilities of scavenging ROS and inhibiting proinflammatory cytokine significantly reduce colitis in mice without distinct side effects via intravenous administration. This report provides a demonstration of the protective effect of PB-based nanomedicine against IBD in living animals, offering hope and a potential alternative treatment option for patients suffering from IBD.

The objective of the present study was to construct an alginate (AG)-based phase-changeable and injectable hydrogel for imaging-guided tumor hyperthermia and chemotherapy. Based on the binding between the α-l-guluronic blocks of AG and calcium ions, the AG/MoS2/Bi2S3-poly(ethylene glycol) (MBP)/doxorubicin (DOX) solution formed a cross-linked hydrogel to simultaneously encapsulate MBP nanosheets and DOX within the hydrogel matrix. The in situ formed hydrogel can act as a reservoir to control the release of entrapped drug molecules, and the doped MBP nanosheets and DOX can realize computed tomography/photoacoustic dual-modal imaging-guided in vivo tumor photothermal therapy and chemotherapy, respectively. The AG/MBP/DOX hydrogel exhibited excellent photothermal conversion properties with mass extinction coefficient of 45.1 L/g/cm and photothermal conversion efficiency of 42.7%. Besides, the heat from the photothermal transformation of MBP can promote drug diffusion from the hydrogel to realize on-demand drug release. Additionally, the hydrogel system can restrain MBP and DOX from entering into the blood stream during therapy, and therefore substantially decrease their side effects on normal organs. More importantly, the drug loading of the AG hydrogel was general and can be extended to the encapsulation of antibiotics, such as amoxicillin, for the prevention of postoperative infections.

In this study, a polyvinylpyrrolidone (PVP)‐decorated MoSe2(MoSe2‐PVP) nanoparticle with excellent photothermal transforming ability and chlorin E6 (Ce6) loading capacity is designed for combined tumor photothermal therapy (PTT), tumor photodynamic therapy (PDT), and immunotherapy. The light‐to‐heat conversion efficiency under irradiation with an 808 nm near‐infrared laser is as high as 59.28%. The MoSe2‐PVP NPs could function as an artificial catalase and catalyze the decomposition of H2O2. Their catalytic activity and thermal durability are higher than the native catalase, which relieve the tumor hypoxia status and sensitize the tumor PDT. The data show that the synthetic MoSe2‐PVP is biodegradable, owing to the oxidation of the Mo4+to Mo6+. Moreover, its degradation products could increase the proportion of mature dendritic cells and CD8+thymus (T) cells and promote the infiltration of active CD8+T cells in tumors. The immune checkpoint inhibitor, programmed cell death protein 1 monoclonal antibody is combined with MoSe2‐PVP and it is found that its degradation product could efficiently change the immune microenvironment of the tumor. A biodegradable polyvinylpyrrolidone‐decorated MoSe2nanoparticle with excellent photothermal transforming ability and chlorin E6 loading capacity is designed for combined tumor photothermal therapy, tumor photodynamic therapy, and immunotherapy. Its degradation products could increase the proportion of mature dendritic cells and CD8+thymus (T) cells, promote the infiltration of active CD8+T cells in tumors, and change the immune microenvironment of tumors.

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ABSTRACTAlthough the oral administration of Bifidobacterium longum(B. longum) relieves the signs of irritable bowel syndrome (IBS) in clinical settings, the mechanisms underlying its effects are unclear. In this study, we evaluated the precise effects of B. longumon IBS via regulation of Paneth cell function. We confirmed the beneficial effects of B. longumon defecation habits and visceral hypersensitivity in WAS rats. Further analysis revealed that B. longumenhanced mucosal repair, promoted lysozyme production, and ameliorated dysbiosis of the microbiota in WAS rats. These processes are closely correlated with Paneth cell functions. In vitro, we incubated primary cultured enteroids with B. longumand found that B. longumpromoted the proliferation of these organoids; this may be attributed to the upregulation of the stem niche factors WNT3A and TGF-β, which are secreted by Paneth cells. Based on our findings, we propose that B. longumrelieves IBS by restoring the antimicrobial activity and stem niche maintenance function of Paneth cells.