Regulation of intracellular process by two-component systems: Exploring the mechanism of plasmid-mediated conjugative transfer.

Plasmid-mediated conjugative transfer facilitates the dissemination of antibiotic resistance, yet the comprehensive regulatory mechanisms governing this process remain elusive. Herein, we established pure bacteria and activated sludge conjugation system to investigate the regulatory mechanisms of conjugative transfer, leveraging metformin as an exogenous agent. Transcriptomic analysis unveiled that substantial upregulation of genes associated with the two-component system (e.g., AcrB/AcrA, EnvZ/Omp, and CpxA/CpxR) upon exposure to metformin. Furthermore, downstream regulators of the two-component system, including reactive oxygen species (ROS), cytoplasmic membrane permeability, and adenosine triphosphate (ATP) production, were enhanced by 1.7, 1.4 and 1.1 times, respectively, compared to the control group under 0.1 mg/L metformin exposure. Moreover, flow sorting and high-throughput sequencing revealed increased microbial community diversity among transconjugants in activated sludge systems. Notably, the antibacterial potential of human pathogenic bacteria (e.g., Bacteroides, Escherichia-Shigella, and Lactobacillus) was augmented, posing a potential threat to human health. Our findings shed light on the spread of antibiotic resistance bacteria and assess the ecological risks associated with plasmid-mediated conjugative transfer in wastewater treatment systems.

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Overlooked in-situ sulfur disproportionation fuels dissimilatory nitrate reduction to ammonium in sulfur-based system: Novel insight of nitrogen recovery.

Sulfur-based denitrification is a promising technology in treatments of nitrate-contaminated wastewaters. However, due to weak bioavailability and electron-donating capability of elemental sulfur, its sulfur-to-nitrate ratio has long been low, limiting the support for dissimilatory nitrate reduction to ammonium (DNRA) process. Using a long-term sulfur-packed reactor, we demonstrate here for the first time that DNRA in sulfur-based system is not negligible, but rather contributes a remarkable 40.5 %-61.1 % of the total nitrate biotransformation for ammonium production. Through combination of kinetic experiments, electron flow analysis, 16S rRNA amplicon, and microbial network succession, we unveil a cryptic in-situ sulfur disproportionation (SDP) process which significantly facilitates DNRA via enhancing mass transfer and multiplying 86.7-210.9 % of bioavailable electrons. Metagenome assembly and single-copy gene phylogenetic analysis elucidate the abundant genomes, including uc_VadinHA17, PHOS-HE36, JALNZU01, Thiobacillus, and Rubrivivax, harboring complete genes for ammonification. Notably, a unique group of self-SDP-coupled DNRA microorganism was identified. This study unravels a previously concealed fate of DNRA, which highlights the tremendous potential for ammonium recovery and greenhouse gas mitigation. Discovery of a new coupling between nitrogen and sulfur cycles underscores great revision needs of sulfur-driven denitrification technology.

Effects of clonal fragmentation on Pyrrosia nuda depend on growth stages in a rubber plantation.

Introduction: Clonal fragmentation helps to assess clonal plants' growth resilience to human and environmental disturbance. Although clonal integration in epiphytes in tropical rubber plantations is important to understand their role in enhancing biodiversity and ecosystem services, research on this subject is limited. These plantations are typically monospecific economic forests that face increased anthropogenic disturbances. Methods: In this study, we selected the clonal fern Pyrrosia nuda to study its survival status, biomass, maximum quantum yield of photosystem II (Fv/Fm), and frond length in response to the level of clonal fragmentation in a tropical rubber plantation. Results and discussion: The results showed that (1) clonal fragmentation significantly negatively affected the survival rate, biomass, and frond length of clonal plants, but with minimal effects on Fv/Fm at different growth stages; (2) the performance of a ramet (e.g., biomass or frond length) increased with ramet developmental ages and decreased with the number of ramets in a clonal fragment. The age-dependent impacts of clonal fragmentation provide insights into the biodiversity conservation of epiphytes and forest management in man-made plantations. Therefore, to better conserve the biodiversity in tropical forests, especially in environment-friendly rubber plantations, there is a need to reduce anthropogenic disturbances and alleviate the level of fragmentation.

Exosomes derived from vMIP-II-Lamp2b gene-modified M2 cells provide neuroprotection by targeting the injured spinal cord, inhibiting chemokine signals and modulating microglia/macrophage polarization in mice.

Inflammation is one of the key injury factors for spinal cord injury (SCI). Exosomes (Exos) derived from M2 macrophages have been shown to inhibit inflammation and be beneficial in SCI animal models. However, lacking targetability restricts their application prospects. Considering that chemokine receptors increase dramatically after SCI, viral macrophage inflammatory protein II (vMIP-II) is a broad-spectrum chemokine receptor binding peptide, and lysosomal associated membrane protein 2b (Lamp2b) is the key membrane component of Exos, we speculated that vMIP-II-Lamp2b gene-modified M2 macrophage-derived Exos (vMIP-II-Lamp2b-M2-Exo) not only have anti-inflammatory properties, but also can target the injured area by vMIP-II. In this study, using a murine contusive SCI model, we revealed that vMIP-II-Lamp2b-M2-Exo could target the chemokine receptors which highly expressed in the injured spinal cords, inhibit some key chemokine receptor signaling pathways (such as MAPK and Akt), further inhibit proinflammatory factors (such as IL-1ß, IL-6, IL-17, IL-18, TNF-α, and iNOS), and promote anti-inflammatory factors (such as IL-4 and Arg1) productions, and the transformation of microglia/macrophages from M1 into M2. Moreover, the improved histological and functional recoveries were also found. Collectively, our results suggest that vMIP-II-Lamp2b-M2-Exo may provide neuroprotection by targeting the injured spinal cord, inhibiting some chemokine signals, reducing proinflammatory factor production and modulating microglia/macrophage polarization.

The beneficial effect of α-lipoic acid on spinal cord injury repair in rats is mediated through inhibition of oxidative stress: A transcriptomic analysis.

BACKGROUND: Oxidative stress is a crucial factor contributing to the occurrence and development of secondary damage in spinal cord injuries (SCI), ultimately impacting the recovery process. α-lipoic acid (ALA) exhibits potent antioxidant properties, effectively reducing secondary damage and providing neuroprotective benefits. However, the precise mechanism by which ALA plays its antioxidant role remains unknown. METHODS: We established a model of moderate spinal cord contusion in rats. Experimental rats were randomly divided into 3 distinct groups: the sham group, the model control group (SCI_Veh), and the ALA treatment group (SCI_ALA). The sham group rats were exposed only to the SC without contusion injury. Rats belonging to SCI_Veh group were not administered any treatment after SCI. Rats of SCI_ALA group were intraperitoneally injected with the corresponding volume of ALA according to body weight for three consecutive days after the surgery. Subsequently, three days after SCI, spinal cord samples were obtained from three groups of rats: the sham group, model control group, and administration group. Thereafter, total RNA was extracted from the samples and the expression of three sets of differential genes was analyzed by transcriptome sequencing technology. Real-time PCR was used to verify the sequencing results. The impact of ALA on oxidative stress in rats following SCI was assessed by measuring their total antioxidant capacity and hydrogen peroxide (H2O2) content. The effects of ALA on rat recovery following SCI was investigated through Beattie and Bresnahan (BBB) score and footprint analysis. RESULTS: The findings from the transcriptome sequencing analysis revealed that the model control group had 2975 genes with altered expression levels when compared to the ALA treatment group. Among these genes, 1583 were found to be upregulated while 1392 were down-regulated. Gene ontology (GO) displayed significant enrichment in terms of functionality, specifically in oxidative phosphorylation, oxidoreductase activity, and signaling receptor activity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway was enriched in oxidative phosphorylation, glutathione metabolism and cell cycle. ALA was found to have multiple benefits for rats after SCI, including increasing their antioxidant capacity and reducing H2O2 levels. Additionally, it was effective in improving motor function (such as 7 days after SCI, the BBB score for SCI_ALA was 8.400 ± 0.937 compared to 7.050 ± 1.141 for SCI_Veh) and promoting histological recovery after SCI (The results of HE demonstrated that the percentage of damage area in was 44.002 ± 6.680 in the SCI_ALA and 57.215 ± 3.964 in the SCI_Veh at the center of injury.). The sequence data from this study has been deposited into Sequence Read Archive (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242507). CONCLUSION: Overall, the findings of this study confirmed the beneficial effects of ALA on recovery in SCI rats through transcriptome sequencing, behavioral, as well histology analyses.

Temperature, pH, and oxygen availability contributed to the functional differentiation of ancient Nitrososphaeria.

Ammonia-oxidizing Nitrososphaeria are among the most abundant archaea on Earth and have profound impacts on the biogeochemical cycles of carbon and nitrogen. In contrast to these well-studied ammonia-oxidizing archaea (AOA), deep-branching non-AOA within this class remain poorly characterized because of a low number of genome representatives. Here, we reconstructed 128 Nitrososphaeria metagenome-assembled genomes from acid mine drainage and hot spring sediment metagenomes. Comparative genomics revealed that extant non-AOA are functionally diverse, with capacity for carbon fixation, carbon monoxide oxidation, methanogenesis, and respiratory pathways including oxygen, nitrate, sulfur, or sulfate, as potential terminal electron acceptors. Despite their diverse anaerobic pathways, evolutionary history inference suggested that the common ancestor of Nitrososphaeria was likely an aerobic thermophile. We further surmise that the functional differentiation of Nitrososphaeria was primarily shaped by oxygen, pH, and temperature, with the acquisition of pathways for carbon, nitrogen, and sulfur metabolism. Our study provides a more holistic and less biased understanding of the diversity, ecology, and deep evolution of the globally abundant Nitrososphaeria.

A Case Report of Multidisciplinary Diagnosis and Treatment of a Patient with Tuberous Sclerosis Complex and Multi-Organ Involvement / 罕见病研究

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Size-controllable food-grade nanoparticles based on sea cucumber polypeptide with good anti-oxidative capacity to prolong lifespan in tumor-bearing mice.

Liver cancer, a malignancy with a rising global incidence, poses a significant challenge in achieving effective treatment outcomes. As food-derived nutrient, sea cucumber peptide (SCP) has shown promising anticancer effects. Therefore, we explored the nanodelivery systems to encapsulate SCP to enhance its stability in the gastrointestinal tract and improve absorption within the tumor microenvironment. This study aimed to develop size-controllable multifunctional nanoparticles using SCP, procyanidins (PCs), and vanillin through molecular assembly via a one-pot Mannich condensation approach. These food-grade nanoparticles demonstrated water solubility and exhibited a spherical structure with sizes ranging from 441 to 1360 nm, depending on the concentration of the reactants. In vitro cell experiments demonstrated that SCP nanoparticles modified with PCs effectively reduced the generation of reactive oxygen species from H2O2 and acrylamide while maintaining normal levels of mitochondrial membrane potential. Furthermore, in vivo nutrition intervention studies conducted on tumor-bearing mice revealed that mice treated with SCP nanoparticles exhibited a survival rate of 40 %, which was significantly higher than the 0 % and 20 % survival rates observed in the control and SCP-treated groups, respectively. These findings suggest that SCP nanoparticles, possessing antioxidative properties and controllable sizes, hold potential for precision nutrition in the field of cancer treatment.

Identification of molecular signatures in acute myocardial infarction based on integrative analysis of proteomics and transcriptomics.

BACKGROUND: Myocardial infarction (MI) is one of the most serious cardiovascular diseases, characterized by a rapid and irreversible decline in myocardial function. Early detection of patients with MI and prolonging the optimal therapeutic window of acute myocardial infarction (AMI) are particularly important. This study aimed to identify the diagnostic biomarkers and novel therapeutic targets for acute myocardial infarction. METHOD: We generated the AMI mouse models by ligating the proximal left anterior descending coronary artery. Six time points-Sham, AMI 10-min, 1-h, 6-h, 24-h, and 72-h-were chosen to examine the molecular changes that occur during the AMI process. RNA-seq and DIA-MS were performed on the infarcted left ventricular tissues of AMI mice at each time point. Co-expression pattern genes were screened from myocardial infarction samples at different time points by time-series analysis. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to examine these genes. Using the Interactive Gene/Protein Retrieval Tool (STRING) database, the protein-protein interaction network (PPI) was constructed and the hub genes were identified. In order to evaluate the diagnostic value of hub genes, a receiver operating characteristic (ROC) curve was constructed. An independent data set, GSE163772, confirmed the diagnostic value of hub genes further. RESULT: We obtained the expression profiles at different time points after the occurrence of heart failure through high-throughput sequencing, and found 167 genes with similar expression patterns through time series analysis. The immune response and immune-related pathways had the greatest enrichment of these genes. Among them, Itgb2 Syk, Tlr4, Tlr2, Itgax, and Lcp2 may play key roles as hub genes. Combined with the results of proteomic analysis, it was found that the expression of Coro1a in both omics increased with time. The results of external validation showed that TLR2, ITGAX, and LCP2 had good predictive ability for AMI diagnosis. CONCLUSION: Itgb2, Syk, Tlr4, Tlr2, Itgax, Lcp2 and Coro1a are considered to be the seven key genes significantly associated with AMI. Our results may provide potential targets for the prevention of adverse ventricular remodeling and the treatment of AMI.

Inference and reconstruction of the heimdallarchaeial ancestry of eukaryotes.

In the ongoing debates about eukaryogenesis-the series of evolutionary events leading to the emergence of the eukaryotic cell from prokaryotic ancestors-members of the Asgard archaea play a key part as the closest archaeal relatives of eukaryotes1. However, the nature and phylogenetic identity of the last common ancestor of Asgard archaea and eukaryotes remain unresolved2-4. Here we analyse distinct phylogenetic marker datasets of an expanded genomic sampling of Asgard archaea and evaluate competing evolutionary scenarios using state-of-the-art phylogenomic approaches. We find that eukaryotes are placed, with high confidence, as a well-nested clade within Asgard archaea and as a sister lineage to Hodarchaeales, a newly proposed order within Heimdallarchaeia. Using sophisticated gene tree and species tree reconciliation approaches, we show that analogous to the evolution of eukaryotic genomes, genome evolution in Asgard archaea involved significantly more gene duplication and fewer gene loss events compared with other archaea. Finally, we infer that the last common ancestor of Asgard archaea was probably a thermophilic chemolithotroph and that the lineage from which eukaryotes evolved adapted to mesophilic conditions and acquired the genetic potential to support a heterotrophic lifestyle. Our work provides key insights into the prokaryote-to-eukaryote transition and a platform for better understanding the emergence of cellular complexity in eukaryotic cells.

Evidence for nontraditional mcr-containing archaea contributing to biological methanogenesis in geothermal springs.

Recent discoveries of methyl-coenzyme M reductase-encoding genes (mcr) in uncultured archaea beyond traditional euryarchaeotal methanogens have reshaped our view of methanogenesis. However, whether any of these nontraditional archaea perform methanogenesis remains elusive. Here, we report field and microcosm experiments based on 13C-tracer labeling and genome-resolved metagenomics and metatranscriptomics, revealing that nontraditional archaea are predominant active methane producers in two geothermal springs. Archaeoglobales performed methanogenesis from methanol and may exhibit adaptability in using methylotrophic and hydrogenotrophic pathways based on temperature/substrate availability. A five-year field survey found Candidatus Nezhaarchaeota to be the predominant mcr-containing archaea inhabiting the springs; genomic inference and mcr expression under methanogenic conditions strongly suggested that this lineage mediated hydrogenotrophic methanogenesis in situ. Methanogenesis was temperature-sensitive , with a preference for methylotrophic over hydrogenotrophic pathways when incubation temperatures increased from 65° to 75°C. This study demonstrates an anoxic ecosystem wherein methanogenesis is primarily driven by archaea beyond known methanogens, highlighting diverse nontraditional mcr-containing archaea as previously unrecognized methane sources.

A bifunctional hepatocyte-mitochondrion targeting nanosystem for effective astaxanthin delivery to the liver.

A bifunctional hepatocyte-mitochondrion targeting nanosystem was prepared for astaxanthin by conjugating lactobionic acid (LA) and triphenylphosphonium-modified 2-hydroxypropyl-ß-cyclodextrin onto sodium alginate. Hepatocyte-targeting evaluation indicated that the fluorescence intensity of HepaRG cells treated with the bifunctional nanosystem increased 90.3%, which was greater than that (38.7%) of the LA-only targeted nanosystem. The Rcoloc was 0.81 for the bifunctional nanosystem in mitochondrion-targeting analysis, which was greater than that (0.62) of the LA-only targeted nanosystem. The reactive oxygen species (ROS) level of the astaxanthin bifunctional nanosystem treated group significantly reduced to 62.20%, lower than that of free astaxanthin (84.01%) and LA-only targeted group (73.83%). Mitochondrial membrane potential recovered 97.35% in the astaxanthin bifunctional nanosystem treated group while the LA-only targeted group recovered 77.45%. The accumulation of bifunctional nanosystem in liver increased by 31.01% compared to the control. These findings indicated that the bifunctional nanosystem was beneficial for astaxanthin delivery in the liver precision nutrition intervention.

Effects of topography and historical disturbance on canopy height structure of tropical forests in Menglun, Xishuangbanna, China.

With the combination of airborne Lidar and panchromatic images in 1981 and 2021, we investigated the canopy height structure of tropical forests in Menglun sub-reserve in the Xishuangbanna National Nature Reserve of Yunnan Province, and analyzed its relationship with environmental factors by using multiple regression tree (MRT) method. The results showed that forests in the Menglun sub-reserve could be clustered into seven types based on canopy height structures, with tropical rainforest, monsoon evergreen broad-leaved forest, secondary forest, and flood plain forest as the main types. The potential solar radiation, altitude, terrain profile curvature, slope and the brightness value of imageries in 1981 and 2021 were main factors that drove the classification. The tropical seasonal rainforest dominated by Pometia pinnata occupied the largest area in valley and low-land. The monsoon evergreen broad-leaved forest dominated by Castanopsis echinocarpa mainly distributed in the ridge and disturbed areas. The secondary forests had homogeneous canopy surface, which was significantly different from the primary forests. The activities of swidden agriculture about three decades ago had legacy impacts on the physiognomy of secondary forests.

Hot spring distribution and survival mechanisms of thermophilic comammox Nitrospira.

The recent discovery of Nitrospira species capable of complete ammonia oxidation (comammox) in non-marine natural and engineered ecosystems under mesothermal conditions has changed our understanding of microbial nitrification. However, little is known about the occurrence of comammox bacteria or their ability to survive in moderately thermal and/or hyperthermal habitats. Here, we report the wide distribution of comammox Nitrospira in five terrestrial hot springs at temperatures ranging from 36 to 80°C and provide metagenome-assembled genomes of 11 new comammox strains. Interestingly, the identification of dissimilatory nitrate reduction to ammonium (DNRA) in thermophilic comammox Nitrospira lineages suggests that they have versatile ecological functions as both sinks and sources of ammonia, in contrast to the described mesophilic comammox lineages, which lack the DNRA pathway. Furthermore, the in situ expression of key genes associated with nitrogen metabolism, thermal adaptation, and oxidative stress confirmed their ability to survive in the studied hot springs and their contribution to nitrification in these environments. Additionally, the smaller genome size and higher GC content, less polar and more charged amino acids in usage profiles, and the expression of a large number of heat shock proteins compared to mesophilic comammox strains presumably confer tolerance to thermal stress. These novel insights into the occurrence, metabolic activity, and adaptation of comammox Nitrospira in thermal habitats further expand our understanding of the global distribution of comammox Nitrospira and have significant implications for how these unique microorganisms have evolved thermal tolerance strategies.

Metagenomic Discovery of "Candidatus Parvarchaeales"-Related Lineages Sheds Light on Adaptation and Diversification from Neutral-Thermal to Acidic-Mesothermal Environments.

"Candidatus Parvarchaeales" microbes, representing a DPANN archaeal group with limited metabolic potential and reliance on hosts for their growth, were initially found in acid mine drainage (AMD). Due to the lack of representatives, however, their ecological roles and adaptation to extreme habitats such as AMD as well as how they diverge across the lineage remain largely unexplored. By applying genome-resolved metagenomics, 28 Parvarchaeales-associated metagenome-assembled genomes (MAGs) representing two orders and five genera were recovered. Among them, we identified three new genera and proposed the names "Candidatus Jingweiarchaeum," "Candidatus Haiyanarchaeum," and "Candidatus Rehaiarchaeum," with the former two belonging to a new order, "Candidatus Jingweiarchaeales." Further analyses of the metabolic potentials revealed substantial niche differentiation between Jingweiarchaeales and Parvarchaeales. Jingweiarchaeales may rely on fermentation, salvage pathways, partial glycolysis, and the pentose phosphate pathway (PPP) for energy conservation reservation, while the metabolic potentials of Parvarchaeales might be more versatile. Comparative genomic analyses suggested that Jingweiarchaeales favor habitats with higher temperatures and that Parvarchaeales are better adapted to acidic environments. We further revealed that the thermal adaptation of these lineages, especially Haiyanarchaeum, might rely on genomic features such as the usage of specific amino acids, genome streamlining, and hyperthermophile featured genes such as rgy. Notably, the adaptation of Parvarchaeales to acidic environments was possibly driven by horizontal gene transfer (HGT). The reconstruction of ancestral states demonstrated that both may have originated from thermal and neutral environments and later spread to mesothermal and acidic environments. These evolutionary processes may also be accompanied by adaptation to oxygen-rich environments via HGT. IMPORTANCE "Candidatus Parvarchaeales" microbes may represent a lineage uniquely distributed in extreme environments such as AMD and hot springs. However, little is known about the strategies and processes of how they adapted to these extreme environments. By the discovery of potential new order-level lineages, "Ca. Jingweiarchaeales," and in-depth comparative genomic analysis, we unveiled the functional differentiation of these lineages. Furthermore, we show that the adaptation of these lineages to high-temperature and acidic environments was driven by different strategies, with the former relying more on genomic characteristics such as genome streamlining and amino acid compositions and the latter relying more on the acquisition of genes associated with acid tolerance. Finally, by the reconstruction of the ancestral states of the optimal growth temperature (OGT) and isoelectric point (pI), we showed the potential evolutionary process of Parvarchaeales-related lineages with regard to the shift from the high-temperature environment of their common ancestors to low-temperature (potentially acidic) environments.

Hyperactive nanobacteria with host-dependent traits pervade Omnitrophota.

Candidate bacterial phylum Omnitrophota has not been isolated and is poorly understood. We analysed 72 newly sequenced and 349 existing Omnitrophota genomes representing 6 classes and 276 species, along with Earth Microbiome Project data to evaluate habitat, metabolic traits and lifestyles. We applied fluorescence-activated cell sorting and differential size filtration, and showed that most Omnitrophota are ultra-small (~0.2 µm) cells that are found in water, sediments and soils. Omnitrophota genomes in 6 classes are reduced, but maintain major biosynthetic and energy conservation pathways, including acetogenesis (with or without the Wood-Ljungdahl pathway) and diverse respirations. At least 64% of Omnitrophota genomes encode gene clusters typical of bacterial symbionts, suggesting host-associated lifestyles. We repurposed quantitative stable-isotope probing data from soils dominated by andesite, basalt or granite weathering and identified 3 families with high isotope uptake consistent with obligate bacterial predators. We propose that most Omnitrophota inhabit various ecosystems as predators or parasites.

Panguiarchaeum symbiosum, a potential hyperthermophilic symbiont in the TACK superphylum.

The biology of Korarchaeia remains elusive due to the lack of genome representatives. Here, we reconstruct 10 closely related metagenome-assembled genomes from hot spring habitats and place them into a single species, proposed herein as Panguiarchaeum symbiosum. Functional investigation suggests that Panguiarchaeum symbiosum is strictly anaerobic and grows exclusively in thermal habitats by fermenting peptides coupled with sulfide and hydrogen production to dispose of electrons. Due to its inability to biosynthesize archaeal membranes, amino acids, and purines, this species likely exists in a symbiotic lifestyle similar to DPANN archaea. Population metagenomics and metatranscriptomic analyses demonstrated that genes associated with amino acid/peptide uptake and cell attachment exhibited positive selection and were highly expressed, supporting the proposed proteolytic catabolism and symbiotic lifestyle. Our study sheds light on the metabolism, evolution, and potential symbiotic lifestyle of Panguiarchaeum symbiosum, which may be a unique host-dependent archaeon within the TACK superphylum.

Hepatic-targeted delivery of astaxanthin for enhanced scavenging free radical scavenge and preventing mitochondrial depolarization.

Astaxanthin (AST), as natural hydrophobic nutrition, has exhibited health-promoting benefits for its outstanding antioxidant property. However, most studies tend to enhance its stability and solubility while the targeted delivery of AST is limited. In this study, liver-targeted nanocarriers were designed and prepared by lactobionic acid-modified (2-hydroxypropyl-ß-cyclodextrin) for efficient controlled delivery of AST. The minimum average size of AST nanoparticles was about 98 nm with a polydispersity index (PDI) of 0.41. The lactobionic acid-modified AST nanoparticles exhibited significant cellular uptake, and an admirable ability to scavenge free radicals for H2O2-induced HepaRG cells in preventing mitochondrial depolarization. Moreover, accumulation of AST nanoparticles in liver was observed due to the modification of lactobionic acid (LA) of the nanocarriers through the specific binding of LA-asialoglycoprotein receptors. The results in this study provided a new idea for liver-specific nutrition delivery of AST in developing functional food for liver disease nutrition intervention.

ROS-triggered self-disintegrating and pH-responsive astaxanthin nanoparticles for regulating the intestinal barrier and colitis.

Smart delivery systems with stimuli-responsive capability are able to improve the bioaccessibility through increasing the solubility, physicochemical stability and biocompatibility of bioactive compounds. In this study, the astaxanthin nanoparticles with reactive oxygen species (ROS) and pH dual-response function were design and constructed using poly (propylene sulfide) covalently modified sodium alginate as carriers based on ultrasonic assisted self-assembly strategy. Atomic force microscope and scanning electron microscope analysis showed that the nanoparticles were spherical in shape with a size of around 260 nm. Meanwhile, the astaxanthin nanoparticles showed both pH and ROS stimuli-responsive release characteristics. In vitro cell experiments showed that astaxanthin nanoparticles significantly inhibited the production of ROS and mitochondrial depolarization induced by oxidative stress. In vivo colitis experiment of mice revealed that astaxanthin nanoparticles could significantly relieve colitis, protect the integrity of colon tissue and restore the expression of tight junction proteins ZO-1 and occludin. The abundance of Lactobacillus and Lachnospiraceae, and the ratio of Firmicutes/Bacteroidota of gut microbiota were significantly improved after intervention of the stimuli-responsive astaxanthin nanoparticles. This work provided a simple strategy for constructing ROS/pH dual response delivery system, which provided an experimental basis for improving the oral bioavailability of hydrophobic active compounds.