Deciphering layer formation in Red Heart Qu: A comprehensive study of metabolite profile and microbial community influenced by raw materials and environmental factors.

Environmental-origin microbiota significantly influences Red Heart Qu (RH_Qu) stratification, but their microbial migration and metabolic mechanisms remain unclear. Using high-throughput sequencing and metabolomics, we divided the stratification of RH_Qu into three temperature-based stages. Phase I features rising temperatures, causing microbial proliferation and a two-layer division. Phase II, characterized by peak temperatures, sees the establishment of thermotolerant species like Bacillus, Thermoactinomyces, Rhodococcus, and Thermoascus, forming four distinct layers and markedly altering metabolite profiles. The Huo Quan (HQ), developing from the Pi Zhang (PZ), is driven by the tyrosine-melanin pathway and increased MRPs (Maillard reaction products). The Hong Xin evolves from the Rang, associated with the phenylalanine-coumarin pathway and QCs (Quinone Compounds) production. Phase III involves the stabilization of the microbial and metabolic profile as temperatures decline. These findings enhance our understanding of RH_Qu stratification and offer guidance for quality control in its fermentation process.

Large-scale bacterial genomic and metagenomic analysis reveals Pseudomonas aeruginosa as potential ancestral source of tigecycline resistance gene cluster tmexCD-toprJ.

BACKGROUND: The global dissemination of the multidrug resistance efflux pump gene cluster tmexCD-toprJ has greatly weakened the effects of multiple antibiotics, including tigecycline. However, the potential origin and transmission mechanisms of the gene cluster remain unclear. METHODS: Here, we concluded a comprehensive bioinformatics analysis on integrated 73,498 bacterial genomes, including Pseudomonas spp., Klebsiella spp., Aeromonas spp., Proteus spp., and Citrobacter spp., along with 1,152 long-read metagenomic datasets to trace the origin and propagation of tmexCD-toprJ. RESULTS: Our results demonstrated that tmexCD-toprJ was predominantly found in Pseudomonas aeruginosa sourced from human hosts in Asian countries and North American countries. Phylogenetic and genomic feature analyses showed that tmexCD-toprJ was likely evolved from mexCD-oprJ of some special clones of P. aeruginosa. Furthermore, metagenomic analysis confirmed that P. aeruginosa is the only potential ancestral bacterium for tmexCD-toprJ. A putative mobile genetic structure harboring tmexCD-toprJ, int-int-hp-hp-tnfxB-tmexCD-toprJ, was the predominant genetic context of tmexCD-toprJ across various bacterial genera, suggesting that the two integrase genes play a pivotal role in the horizontal transmission of tmexCD-toprJ. CONCLUSIONS: Based on these findings, it is almost certain that the tmexCD-toprJ gene cluster was derived from P. aeruginosa and further spread to other bacteria.

Glutathione-depleting polyprodrug nanoparticle for enhanced photodynamic therapy and cascaded locoregional chemotherapy.

Nanomedicines that combine reactive oxygen species (ROS)-responsive polyprodrug and photodynamic therapy have shown great potential for improving treatment efficacy. However, the consumption of ROS by overexpressed glutathione in tumor cells is a major obstacle for achieving effective ROS amplification and prodrug activation. Herein, we report a polyprodrug-based nanoparticle that can realize ROS amplification and cascaded drug release. The nanoparticle can respond to the high level of hydrogen peroxide in tumor microenvironment, achieving self-destruction and release of quinone methide. The quinone methide depletes intracellular glutathione and thus decreases the antioxidant capacity of cancer cells. Under laser irradiation, a large amount of ROS will be generated to induce cell damage and prodrug activation. Therefore, the glutathione-depleting polyprodrug nanoparticles can efficiently inhibit tumor growth by enhanced photodynamic therapy and cascaded locoregional chemotherapy.

Large-Scale Synthesis of Highly Porous CuO/Cu2O/Cu/Carbon Derived from Aerogels for Lithium-Ion Battery Anodes.

In this work, an effective strategy for the large-scale fabrication of highly porous CuO/Cu2O/Cu/carbon (P-Cu-C) has been established. Cu-cross-linked aerogels were first continuously prepared using a continuous flow mode to form uniform beads, which were transformed into P-Cu-C with a subsequent pyrolysis process. Various pyrolysis temperatures were used to form a series of P-Cu-C including P-Cu-C-250, P-Cu-C-200, P-Cu-C-350, and P-Cu-C-450 to investigate suitable pyrolysis conversion processes. The obtained P-Cu-C series were utilized as anodes of lithium-ion batteries, in which P-Cu-C-250 exhibited a higher reversible gravimetric capacity, excellent rate capability, and superior cycle stability. The enhanced behavior of P-Cu-C-250 was benefitted from the synergistic interaction between uniformly dispersed CuO, Cu2O, Cu nanoparticles, and highly graphitized carbon with a large surface area and highly porous structure. More importantly, the preparation of P-Cu-C-250 could be scaled up by taking advantage of the continuous flow synthesis mode, which may provide pilot- or industrial-scale applications. The large-scale fabrication proposed here may give a universal method to fabricate highly porous metal oxide-carbon anode materials for electrochemical energy conversion and storage applications. Porous CuO/Cu2O/Cu/carbon derived from Cu-crosslinked aerogels was used as Li-ion battery anode materials, exhibiting a high reversible areal capacity, large gravimetric capacity, superior cycling performance, and excellent rate capacity. A continuous preparation method is established to ensure the product scaled up.

Argon neuroprotection in ischemic stroke and its underlying mechanism.

Ischemic stroke (IS), primarily caused by cerebrovascular obstruction, results in severe neurological deficits and has emerged as a leading cause of death and disability worldwide. Recently, there has been increasing exploration of the neuroprotective properties of the inert gas argon. Argon has exhibited impressive neuroprotection in many in vivo and ex vivo experiments without signs of adverse effects, coupled with the advantages of being inexpensive and easily available. However, the efficient administration strategy and underlying mechanisms of neuroprotection by argon in IS are still unclear. This review summarizes current research on the neuroprotective effects of argon in IS with the goal to provide effective guidance for argon application and to elucidate the potential mechanisms of argon neuroprotection. Early and appropriate argon administration at as high a concentration as possible offers favorable neuroprotection in IS. Argon inhalation has been shown to provide some long-term protection benefits. Argon provides the anti-oxidative stress, anti-inflammatory and anti-apoptotic cytoprotective effects mainly around Toll-like receptor 2/4 (TLR2/4), mediated by extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor kappa-B (NF-ĸB) and B-cell leukemia/lymphoma 2 (Bcl-2). Therefore, argon holds significant promise as a novel clinical neuroprotective gas agent for ischemic stroke after further researches to identify the optimal application strategy and elucidate the underlying mechanism.

Phosphorylation of Rec8 cohesin complexes regulates mono-orientation of kinetochores in meiosis I.

In meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation) and centromeric cohesion mediated by cohesin is protected in the following anaphase I. The conserved meiosis-specific kinetochore protein meikin (Moa1 in fission yeast) associates with polo-like kinase: Plo1 and regulates both mono-orientation and cohesion protection. Although the phosphorylation of Rec8-S450 by Plo1 associated with Moa1 plays a key role in cohesion protection, how Moa1-Plo1 regulates mono-orientation remains elusive. Here, we identify Plo1 phosphorylation sites in the cohesin subunits, Rec8 and Psm3. The non-phosphorylatable mutations at these sites showed specific defects in mono-orientation. These results enabled the genetic dissection of meikin functions at the centromeres.

BASALT refines binning from metagenomic data and increases resolution of genome-resolved metagenomic analysis.

Metagenomic binning is an essential technique for genome-resolved characterization of uncultured microorganisms in various ecosystems but hampered by the low efficiency of binning tools in adequately recovering metagenome-assembled genomes (MAGs). Here, we introduce BASALT (Binning Across a Series of Assemblies Toolkit) for binning and refinement of short- and long-read sequencing data. BASALT employs multiple binners with multiple thresholds to produce initial bins, then utilizes neural networks to identify core sequences to remove redundant bins and refine non-redundant bins. Using the same assemblies generated from Critical Assessment of Metagenome Interpretation (CAMI) datasets, BASALT produces up to twice as many MAGs as VAMB, DASTool, or metaWRAP. Processing assemblies from a lake sediment dataset, BASALT produces ~30% more MAGs than metaWRAP, including 21 unique class-level prokaryotic lineages. Functional annotations reveal that BASALT can retrieve 47.6% more non-redundant opening-reading frames than metaWRAP. These results highlight the robust handling of metagenomic sequencing data of BASALT.

Knowledge-guided mixture density network for chlorophyll-a retrieval and associated pixel-by-pixel uncertainty assessment in optically variable inland waters.

Machine learning has been increasingly used to retrieve chlorophyll-a (Chl-a) in optically variable waters. However, without the guidance of physical principles or expert knowledge, machine learning may produce biased mapping relationships, or waste considerable time searching for physically infeasible hyperparameter domains. In addition, most Chl-a retrieval models cannot evaluate retrieval uncertainty when ground observations are not available, and the retrieval uncertainty is crucial for understanding the model limitations and evaluating the reliability of retrieval results. In this study, we developed a novel knowledge-guided mixture density network to retrieve Chl-a in optically variable inland waters based on Sentinel-3 Ocean and Land Color Instrument (OLCI) imagery. The proposed method embedded prior knowledge derived from spectral shape classification into the mixture density network. Compared to another deterministic model, the knowledge-guided mixture density network outputted the conditional distribution of Chl-a given an input spectrum, enabling us to estimate the optimal retrieval and the associated uncertainty. The proposed method showed favorable correspondence with the field Chl-a, with root mean square error (RMSE) of 6.56 µg/L, and mean absolute percentage error (MAPE) of 43.64 %. Calibrated against Sentinel-3 OLCI spectrum, the proposed method also performed well when applied to field spectrum (RMSE = 4.58 µg/L, MAPE = 72.70 %), suggesting its effectiveness and good generalization. The proposed method provided the standard deviation of each estimated Chl-a, which enabled us to inspect the reliability of the estimated results and understand the model limitations. Overall, the proposed method improved the Chl-a retrieval in terms of model accuracy and uncertainty evaluation, providing a more comprehensive Chl-a observation of inland waters.

Life-cycle comparisons of economic and environmental consequences for pig production with four different models in China.

China, the world's largest consumer and producer of pork in the world, is attracting increasing attention due to the environmental impacts of its pig production. Previous studies seldom comprehensively compare the environmental impacts of the pig production system with different models, resulting in different intensities of environmental impacts. We aim to comprehensively evaluate Chinese pig production with different breeding models and explore a more sustainable way for pig production. We use life cycle assessment (LCA) to evaluate and compare environmental impacts of pig production system with four main breeding models in China from 1998 to 2020: domestic breeding, small-scale breeding, medium-scale breeding, and large-scale breeding. The life cycle encompasses fertilizer production, feed production, feed processing, pig raising, waste treatment, and slaughtering. The impact categories including energy consumption (EN), global warming (GWP), acidification (AP), eutrophication (EU), water use (WD), and land occupation (LO) are expressed with "100 kg live weight of fattening pig at farm gate." The results show that driven by governmental support, growing meat demand, and cost advantage, the scale breeding especially large-scale breeding simultaneously yielded greater net economic benefit and less environmental impact compared to other breeding models especially the domestic breeding. Due to mineral fertilizer application, feed production contributed over 50% of the total environmental impacts. Notably, the composition of feeds exerted significant influence on the environmental impacts arising from fertilizer production and feed processing. Furthermore, attributable to the substantial use of electricity and heat, as well as the concomitant emissions, pig raising contributed the largest GWP, while ranking second in terms of AP and EU. Notably, waste management constituted the third-largest EU, AP, and WD. In addition to promote scale breeding, we put forth several sustainable measures encompassing feed composition, cultivation practices, fertilizer utilization, and waste management for consideration.

A ratiomectic aptasensor with enhanced signals based on peroxidase-like enzymes and NH2-MIL-101@MoS2 for trace detection of deoxynivalenol in traditional Chinese herbs.

The accumulation of the deoxynivalenol (DON) in the human body poses a significant health risk that is often overlooked, and we urgently need an ultra-sensitive rapid detection platform. Due to the porosity of NH2-MIL-101@MoS2, an increased loading of toluidine blue (TB) serves to create a signal reference. Cobalt@carbon (CoC) derived from metal organic frameworks was combined with NH2-MIL-101(NH2-MIL-101@CoC) to form an enzyme-free Nanoprobe (Apt-pro) with significant catalytic properties. The ratio (IBQ /ITB) was changed by varying the electrochemical signal of benzoquinone (BQ) (IBQ) and the amount of TB deposition (ITB). This aptasensor was successfully applied to detect DON in malt and peach seed, which exhibited a great linear range from 1 fg/mL to 10 ng/mL and low detection limit of 0.31 fg/mL for DON.

Identification, functional characterization and expression pattern of interferon-gamma (IFN-γ) and interferon-gamma receptor 1 (IFNGR1) in Nibea albiflora.

Interferon-gamma (IFN-γ) is an inflammatory cytokine that plays a crucial role in regulating both innate and cell-mediated immune responses by binding to a receptor complex made up of IFNGR1 and IFNGR2. In this study, the complete cDNA of IFN-γ and IFNGR1 from Nibea albiflora were cloned and functionally characterized (named NaIFN-γ and NaIFNGR1), whose complete cDNA sequences were 1593 bp and 2792 bp, encoding 201 and 399 amino acids, respectively. Multiple sequence alignment and phylogenetic analysis showed that the concluded amino acids sequences of NaIFN-γ and NaIFNGR1 shared high identity with their teleost orthologues including the IFN-γ signature and nuclear localization signal (NLS) motif in NaIFN-γ and FN Ⅲ domain in NaIFNGR1. Real-time PCR showed that NaIFN-γ and NaIFNGR1 constitutively expressed in all tested tissues, such as the head-kidney, spleen, liver, kidney, gill, muscle, blood, and intestine with the highest expression of NaIFN-γ and NaIFNGR1 appearing in the liver and gill, respectively. After experiencing stimulation with Polyinosinic-polycytidylic acid (Poly (I:C)), Vibrio alginolyticus (V. alginolyticus) or Vibrio parahaemolyticus (V. parahaemolyticus), NaIFN-γ and NaIFNGR1 mRNA were up-regulated with the time-dependent model. Due to the presence of a nuclear localization signal (NLS), the subcellular localization revealed that NaIFN-γ dispersed throughout the cytoplasm and nucleus. NaIFNGR1, as a member of Cytokine receptor family B, was primarily expressed on the cell membrane. When NaIFN-γ and NaIFNGR1 were co-transfected, their fluorescence signals overlapped on the membrane of HEK 293T cells indicating the potential interaction between IFN-γ and IFNGR1. The GST-pull-down results further showed that NaIFN-γ could directly interact with the extracellular region of NaIFNGR1, further confirming the affinity between IFN-γ and IFNGR1. Taken together, the results firstly demonstrated that the NaIFN-γ ligand-receptor system existed in N.albiflora and played a pivotal part in N.albiflora's immune response against pathogenic bacterial infections, which contributed to the better understanding of the role of IFN-γ in the immunomodulatory mechanisms of teleost.

The cold-inducible RNA-binding protein-Thioredoxin 1 pathway ameliorates mitochondrial dysfunction and mitochondrial dynamin-related protein 1 level in the hippocampus of aged mice with perioperative neurocognitive dysfunction.

BACKGROUND: As a multi-disease model, neuroinflammation, mitochondrial dysfunction, and oxidative stress might be involved in the pathogenic process of perioperative neurocognitive dysfunction (PND). Dynamin-related protein 1 (Drp1) could mediate mitochondrial fission and play important roles in mitochondrial dynamic homeostasis and mitochondria function. The Drp1 may be involved in PND development. The cold-inducible RNA-binding protein (Cirbp) could bind to the 3'-UTR of the thioredoxin 1 (Trx1) mRNA, control oxidative stress, and improve mitochondrial function. In this study, we hypothesized that the Cirbp-Trx1 pathway could ameliorate mitochondrial dysfunction and Drp1 levels in PND mice. METHODS: Differentially expressed genes were screened using the Gene Expression Omnibus (GEO) database GSE95426 and validated using PCR. Eighteen-month-old C57BL/6 mice were subjected to tibial fracture surgery to generate a PND model. Cirbp was upregulated by hippocampal stereotaxic injections of over-Cirbp plasmid according to the manufacturer's instructions for the in vivo DNA transfection reagent. Cirbp expression was measured using western blot (WB) and immunofluorescence (IF). The Morris water maze (MWM) was used to assess cognitive function. After behavioral testing, the hippocampal tissue was extracted to examine changes in mitochondrial Drp1, mitochondrial function, neuroinflammation, and oxidative stress. RESULTS: Differential gene screening showed that Cirbp expression was significantly downregulated (fold change >1.5, p = 0.003272) in the PND model. In this study, we also found that Cirbp protein levels were downregulated, accompanied by an impairment of cognition, a decrease in superoxide dismutase (SOD) activity, and an increase in malondialdehyde (MDA) content, mitochondrial Drp1 levels, neuroinflammation, and apoptosis. Cirbp overexpression increased Trx1 protein levels and reversed the damage. However, this protective effect was abolished by PX-12 treatment with a Trx1 inhibitor. CONCLUSIONS: The Cirbp-Trx1 pathway may regulate mitochondrial dysfunction and mitochondrial Drp1 expression in the hippocampus of PND mice to ameliorate cognitive dysfunction.

Coupling of cylindrospermopsin and pho-harboring Verrucomicrobia supports the formation of Raphidiopsis blooms in low-phosphorus waters.

Cylindrospermopsin (CYN) can induce phytoplankton community to secrete alkaline phosphatase (ALP), which is one of the important strategies for the bloom-forming cyanobacterium Raphidiopsis to thrive in extremely low-phosphorus (P) waters. However, how bacterioplankton community, another major contributor to ALPs in waters, couples to Raphidiopsis through CYN, and the role of this coupling in supporting the dominance of Raphidiopsis in nature remain largely unknown. Here, we conducted microcosm experiments to address this knowledge gap, using a combination of differential filtration-based and metagenomics-based methods to identify the sources of ALPs. We found that, compared with algal-derived ALPs, bacteria-derived ALPs exhibited a more pronounced and sensitive response to CYN. This response to CYN was enhanced under low-P conditions. Interestingly, we found that Verrucomicrobia made the largest contribution to the total abundance of pho genes, which encode ALPs. Having high gene abundance of the CYN-sensing PI3K-AKT signaling pathway, Verrucomicrobia's proportion increased with higher concentrations of CYN under low-P conditions, thereby explaining the observed increase in pho gene abundance. Compared with other cyanobacterial genera, Raphidiopsis had a higher abundance of the pst gene. This suggests that Raphidiopsis exhibited a greater capacity to uptake the inorganic P generated by ALPs secreted by other organisms. Overall, our results reveal the mechanism of CYN-induced ALP secretion and its impact on planktonic P-cycling, and provide valuable insights into the role of CYN in supporting the formation of Raphidiopsis blooms.

FOXG1 regulates the proliferation and apoptosis of human lung cancer cells.

FOXG1, a transcriptional factor belonging to the Forkhead Box (Fox) superfamily, is highly expressed in the brain tissue during brain development and plays an important role in cellular proliferation. Recently, FOXG1 was reported to play important roles in oncogenesis, wherein its abnormal expression regulates tumor cell proliferation. However, the expression and role of FOXG1 in lung cancer remain largely unknown. This study investigated the clinical significance, expression, and role of FOXG1 in lung cancer. We found that FOXG1 was highly expressed in lung cancer tissues. MTT, CCK-8 and colony formation assays showed that FOXG1 overexpression could enhance the proliferation of A549 lung cancer cells. Flow cytometry analysis revealed that FOXG1 promoted the cell cycle and suppressed cell apoptosis. Additionally, the expression levels of PTEN, phosphorylated AKT, mTOR, p53, and Bax were significantly altered in response to changes in FOXG1 expression, indicating that FOXG1 regulated the PI3K pathway. Furthermore, in the xenograft mouse model, the upregulated FOXG1 expression strongly promoted tumor growth. In conclusion, these results suggested that FOXG1 was a critical regulator of the proliferation of lung cancer cells and enhanced tumor growth in vivo.

Visible Light-Accelerated Palladium-Catalyzed Thiocarbonylation Using Oxalic Acid Monothioester with Aryl/Alkenyl Sulfonium Salts.

Herein, we present a decarboxylative thiocarbonylation of aryl and alkenyl sulfonium salts with oxalic acid monothioethers (OAMs), which can be achieved by visible light-accelerated palladium catalysis. Sulfonium salts are widely available, and OAM is an easily accessible and stored reagent; this mild reaction method can also be used for the synthesis of different types of thioester compounds. The reaction represents a new application of visible light-accelerated palladium catalysis in catalytic decarboxylative cross-couplings.

An Electrochemical Sensor Based on Cu-MOF-199@MWCNTs Laden with CuNPs for the Sensitive Detection of Creatinine.

In this study, the synthesis of Cu-MOF-199@multiwalled carbon nanotubes (Cu-MOF-199@MWCNTs) composites was achieved and utilized to create an advanced electrochemical sensor for creatinine (Cre) detection. The composites were modified on a glassy carbon electrode surface through direct drip coating, followed by the deposition of copper nanoparticles (CuNPs) via constant potential deposition. Characterized by various techniques and electrochemical analyses, the Cu-MOF-199@MWCNTs composite increased the CuNPs load, improving the detection sensitivity for Cre. Under optimal conditions, the modified electrode exhibited good linearity across a broad range of Cre concentrations (0.05-40.0 µM) with a low detection limit of 11.3 nM. The developed sensor demonstrated remarkable stability, reproducibility, and selectivity, showing promise in sensitive and accurate Cre detection in serum samples.

MWCNTs and ZnO-based Ce-MOF nanocomposites as enhanced sensing platform for electrochemical detection of carbendazim in Chinese traditional herbs samples.

A facile and novel Ce-MOF@MWCNTs@ZnO-modified glassy carbon electrode was prepared through drop coating and used for accurate and sensitive electrochemical detection of carbendazim. The modification of ZnO nanospheres and Ce-based metal-organic frameworks (Ce-MOFs), which possess vast surface/bulk ratio, large surface area, and excellent catalytic ability, provided more active sites for reaction. The combination of multi-walled carbon nanotubes endowed the modified electrode with excellent conductivity and greatly accelerated the electron transfer. The promotion of electrochemical response and the significant improvement of peak current indicated the outstanding electrocatalytic ability of the modified electrode. The oxidation peak current of carbendazim which was measured by DPV in a potential range from 0.5 to 1.0 V produced a good linear relationship in the concentration ranges 0.05-10.0 µM and 10.0-50.0 µM under  optimized experimental conditions. The detection limit was 13.2 nM (S/N = 3). The constructed electrode was successfully applied to the detection of carbendazim in Lithospermum and Glycyrrhiza uralensis real samples and exhibited satisfactory RSD (2.7-3.6% and 1.6-4.8%, respectively) and recovery (102-106% and 97.7-107%, respectively).

High-fat diet-disturbed gut microbiota-colonocyte interactions contribute to dysregulating peripheral tryptophan-kynurenine metabolism.

BACKGROUND: Aberrant tryptophan (Trp)-kynurenine (Kyn) metabolism has been implicated in the pathogenesis of human disease. In particular, populations with long-term western-style diets are characterized by an excess of Kyn in the plasma. Host-gut microbiota interactions are dominated by diet and are essential for maintaining host metabolic homeostasis. However, the role of western diet-disturbed gut microbiota-colonocyte interactions in Trp metabolism remains to be elucidated. RESULTS: Here, 4-week-old mice were fed with a high-fat diet (HFD), representing a typical western diet, for 4 weeks, and multi-omics approaches were adopted to determine the mechanism by which HFD disrupted gut microbiota-colonocyte interplay causing serum Trp-Kyn metabolism dysfunction. Our results showed that colonocyte-microbiota interactions dominated the peripheral Kyn pathway in HFD mice. Mechanistically, persistent HFD-impaired mitochondrial bioenergetics increased colonic epithelial oxygenation and caused metabolic reprogramming in colonites to support the expansion of Proteobacteria in the colon lumen. Phylum Proteobacteria-derived lipopolysaccharide (LPS) stimulated colonic immune responses to upregulate the indoleamine 2,3-dioxygenase 1 (IDO1)-mediated Kyn pathway, leading to Trp depletion and Kyn accumulation in the circulation, which was further confirmed by transplantation of Escherichia coli (E.coli) indicator strains and colonic IDO1 depletion. Butyrate supplementation promoted mitochondrial functions in colonocytes to remodel the gut microbiota in HFD mice, consequently ameliorating serum Kyn accumulation. CONCLUSIONS: Our results highlighted that HFD disrupted the peripheral Kyn pathway in a gut microbiota-dependent manner and that the continuous homeostasis of gut bacteria-colonocytes interplay played a central role in the regulation of host peripheral Trp metabolism. Meanwhile, this study provided new insights into therapies against western diet-related metabolic disorders. Video Abstract.

Long-read metagenomic sequencing reveals that high-copy small plasmids shape the highly prevalent antibiotic resistance genes in animal fecal microbiome.

The emergence and prevalence of animal-derived antibiotic resistance genes (ARGs) pose a great threat to public health globally. Long-read metagenomic sequencing is increasingly being used to decipher the fate of environmental ARGs. However, the investigations of the distribution, co-occurrence patterns, and host information of animal-derived environmental ARGs with long-read metagenomic sequencing have received little attention. To cover the gap, we employed a novel QitanTech nanopore long-read metagenomic sequencing method to perform a comprehensive and systematic investigation of the microbial communities and antibiotic resistance profiles, as well as to analyze the host information and genetic structures of ARGs in the feces of laying hens. Our results showed that highly abundant and diverse ARGs were detected in the feces of different ages of laying hens, indicating that feeding animal feces was an important reservoir for the enrichment and maintenance of ARGs. The distribution pattern of chromosomal ARGs was more strongly associated with fecal microbial communities than plasmid-mediated ARGs. Further long-read host tracking analysis revealed that ARGs from Proteobacteria are commonly located on plasmids, whereas in Firmicutes, they are usually carried by chromosomes. Co-occurrence analysis displayed that co-selection phenomena of different ARGs were common occurrences and highly active insertion sequences (ISs) could result in the serious prevalence of many ARGs. Notably, small high-copy plasmids played a significant role in the dissemination of several ARGs, such as floR and tet(L), which could disturb the compositions of fecal ARGs. Overall, our findings significantly expand our knowledge of the comprehensive landscape of feeding animal feces resistome, which is important for the prevention and management of multi-drug resistant bacteria in laying hens.