The mitigating effects and mechanisms of Bacillus cereus on chronic cadmium poisoning in Litopenaeus vannamei based on histopathological, transcriptomic, and metabolomic analyses.

Shrimp are non-negligible victims of cadmium (Cd) contamination, and there is still a lack of strategies for mitigating Cd toxicity in shrimp. Bacillus cereus, with its significant heavy metal (HM) tolerance and chelating effects, is a representative beneficial bacterium to be investigated for mitigating the toxicity of Cd exposure. This study revealed the effects and potential mechanisms of B. cereus in mitigating chronic Cd toxicity in shrimp by analyzing growth performance, hepatopancreatic Cd accumulation, pathology, as well as comprehensive hepatopancreatic transcriptomics and metabolomics in Litopenaeus vannamei. The results showed that shrimp's growth inhibition, hepatopancreatic Cd accumulation and physiological structure damage in B. cereus+chronic Cd group were effectively alleviated compared with the chronic Cd treatment group. The pathways related to amino acid metabolism, glycolipid metabolism, immune response, and antioxidant stress were significantly activated in the B. cereus+chronic Cd group, including glycolysis, pentose phosphate pathway, oxidative phosphorylation, biosynthesis of amino acids, and biosynthesis of unsaturated fatty acids pathways. The key differentially expressed genes (e.g., macrophage migration inhibitory factor, glycine cleavage system H protein, glycine dehydrogenase, phosphoglucomutase-2, asparaginase, ATP synthase subunit, cytochrome c, and 4-hydroxyphenylpyruvate dioxygenase) and metabolites (e.g., L-leucine, D-ribose, gluconic acid, 6-Phosphogluconic acid, sedoheptulose 7-phosphate, 1-Kestose, glyceric acid, arachidic acid, prostaglandins, 12-Keto-tetrahydro-leukotriene B4, and gamma-glutamylcysteine) associated with the above pathways were significantly altered. This study demonstrated that B. cereus is an effective mitigator for the treatment of chronic Cd poisoning in shrimp. B. cereus may play a role in alleviating the toxicity of Cd by enhancing the antioxidant performance, immune defense ability, metabolic stability, and energy demand regulation of shrimp. The study provides reference materials for the study of B. cereus in alleviating Cd toxicity of shrimp and broadens the application of probiotics in treating HM toxicity.

Discovery of FeP/Carbon Dots Nanozymes for Enhanced Peroxidase-Like Catalytic and Antibacterial Activity.

Iron phosphide/carbon (FeP/C) serving as electrocatalysts exhibit excellent activity in oxygen reduction reaction (ORR) process. H2O2 catalyzed by peroxidase (POD) is similar to the formation of new electron transfer channels and the optimization of adsorption of oxygen-containing intermediates or desorption of products in ORR process. However, it is still a challenge to discover FeP/C with enhanced POD-like catalytic activity in the electrocatalytic database for biocatalysis. The discovery of FeP/carbon dots (FeP/CDs) nanozymes driven by electrocatalytic activity for enhanced POD-like ability is demonstrated. FeP/CDs derived from CDs-Fe3+ chelates show enhanced POD-like catalytic and antibacterial activity. FeP/CDs exhibit enhanced POD-like activities with a specific activity of 31.1 U mg-1 that is double higher than that of FeP. The antibacterial ability of FeP/CDs nanozymes with enhanced POD-like activity is 98.1%. The antibacterial rate of FeP/CDs nanozymes (250 µg mL-1) increased by 5%, 15%, and 36% compared with FeP, Fe2O3/CDs, and Cu3P/CDs nanozymes, respectively. FeP/CDs nanozymes will attract more efforts to discover or screen transition metal phosphide/C nanozymes with enhanced POD-like catalytic activity for biocatalysis in the electrocatalytic database.

Enhanced Immune Responses in Mice by Combining the Mpox Virus B6R-Protein and Aluminum Hydroxide-CpG Vaccine Adjuvants.

Novel adjuvants and innovative combinations of adjuvants (Adjuvant Systems) have facilitated the development of enhanced and new vaccines against re-emerging and challenging pathogenic microorganisms. Nonetheless, the efficacy of adjuvants is influenced by various factors, and the same adjuvant may generate entirely different immune responses when paired with different antigens. Herein, we combined the MPXV-B6R antigen with BC02, a novel adjuvant with proprietary technology, to assess its capability to induce both cellular and humoral immunity in mouse models. Mice received two intramuscular injections of B6R-BC02, which resulted in the production of MPXV-specific IgG, IgG1, and IgG2a antibodies. Additionally, it elicited strong MPXV-specific Th1-oriented cellular immunity and persistent effector memory B-cell responses. The advantages of BC02 were further validated, including rapid initiation of the immune response, robust recall memory, and sustained immune response induction. Although the potential of immunized mice to produce serum-neutralizing antibodies against the vaccinia virus requires further improvement, the exceptional performance of BC02 as an adjuvant for the MPXV-B6R antigen has been consistently demonstrated.

Toxic effects and mechanisms of chronic cadmium exposure on Litopenaeus vannamei growth performance based on combined microbiome and metabolome analysis.

Cadmium (Cd) pollution seriously affects marine organisms' health and poses a threat to food safety. Although Cd pollution has attracted widespread attention in aquaculture, little is known about the toxic mechanisms of chronic Cd exposure on shrimp growth performance. The study investigated the combined effects of chronic exposure to Cd of different concentrations including 0, 75, 150, and 300 µg/L for 30 days on the growth performance, tissue bioaccumulation, intestinal microbiology, and metabolic responses of Litopenaeus vannamei. The results revealed that the growth was significantly inhibited under exposure to 150 and 300 µg/L Cd2+. The bioaccumulation in gills and intestines respectively showed an increasing and inverted "U" shaped trend with increasing Cd2+ concentration. Chronic Cd altered the intestinal microflora with a significant decrease in microbial richness and increasing trends in the abundances of the potentially pathogenic bacteria Vibrio and Maribacter at exposure to 75 and 150 µg/L Cd2+, and Maribacter at 300 µg/L. In addition, chronic Cd interfered with intestinal metabolic processes. The expressions of certain metabolites associated with growth promotion and enhanced antioxidant power, including N-methyl-D-aspartic acid, L-malic acid, guanidoacetic acid, betaine, and gluconic acid were significantly down-regulated, especially at exposure to 150 and 300 µg/L Cd2+, and were negatively correlated with Vibrio and Maribacter abundance levels. In summary, chronic Cd exposure resulted in severe growth inhibition and increased Cd accumulation in shrimp tissues. Increased levels of intestinal pathogenic bacteria and decreased levels of growth-promoting metabolites may be the key causes of growth inhibition. Harmful bacteria Vibrio and Maribacter may be associated with the inhibition of growth-promoting metabolite expression and may be involved in disrupting intestinal metabolic functions, ultimately impairing shrimp growth potential. This study sheds light on the potential toxicological mechanisms of chronic Cd inhibition on shrimp growth performance, offering new insights into Cd toxicity studies in aquaculture.

Allelopathic Effects of Corn Straw and Its Water Extracts on Four Weed Species and Foxtail Millet.

Straw covering is a protective tillage measure in agricultural production, but there is relatively little research on the allelopathic effects of corn straw on weeds and foxtail millet. This experiment studied the allelopathic effects of corn straw on four weeds (Chenopodium album, Setaria viridis, Echinochloa crus-galli and Amaranthus retroflexus) in foxtail millet fields, and also measured the growth indicators of foxtail millet. The study consisted of Petri dish and field experiments. Five treatments were used in the Petri dish experiment: clear water as control (0 g/L, TCK) and four types of corn straw water extracts. They were, respectively, the stock solution (100 g/L, T1), 10 X dilution (10 g/L, T2), 50 X dilution (2 g/L, T3), and 100 X dilution (1 g/L, T4) of corn straw water extracts. Additionally, seven treatments were set up in the field experiment, consisting of three corn straw covering treatments, with covering amounts of 3000 (Z1), 6000 (Z2) and 12,000 kg/ha (Z3), and four control treatments-one treatment with no corn straw cover (CK) and three treatments involving the use of a black film to create the same shading area as the corn straw covered area, with black film coverage areas of 50% (PZ1), 70% (PZ2), and 100% (PZ3), respectively. The results showed that the corn straw water extract reduced the germination rate of the seeds of the four weeds. The T1 treatment resulted in the allelopathic promotion of C. album growth but the inhibition of S. viridis, E. crus-galli, and A. retroflexus growth. Treatments T2, T3, and T4 all induced the allelopathic promotion of the growth of the four weeds. The order of the effects of the corn straw water extracts on the comprehensive allelopathy index of the four weed seeds was as follows: C. album > S. viridis > A. retroflexus > E. crus-galli. With an increase in the corn straw mulching amount, the density and total coverage of the four weeds showed a gradual downward trend, whereas the plant control effect and fresh weight control effect showed a gradual upward trend. All indices showed the best results under 12,000 kg/ha of mulching and returning to the field. Overall, corn straw coverage significantly impacted the net photosynthetic rate and transpiration rate of foxtail millet and increased the yield of foxtail millet. Under coverages of 6000 and 12,000 kg/ha, the growth of foxtail millet is better. Based on our findings, we recommend a corn straw coverage of 12,000 kg/ha for the allelopathic control of weeds in foxtail millet fields.

Revealing Metabolic Dysregulation Induced by Polypropylene Nano- and Microplastics in Nile Tilapia via Noninvasive Probing Epidermal Mucus.

A noninvasive sampling technology was conceived, employing a disposable acupuncture needle in conjunction with high-resolution mass spectrometry (termed as noninvasive direct sampling extractive electrospray ionization mass spectrometry, NIDS-EESI-MS) to scrutinize the epidermal mucus of Nile tilapia for insights into the metabolic dysregulation induced by polypropylene nano- and microplastics. This analytical method initiates with the dispensing of an extraction solvent onto the needles coated with the mucus sample, almost simultaneously applying a high voltage to generate analyte ions. This innovative strategy obliterates the necessitation for laborious sample preparation, thereby simplifying the sampling process. Employing this technique facilitated the delineation of a plethora of metabolites, encompassing, but not confined to, amino acids, peptides, carbohydrates, ketones, fatty acids, and their derivatives. Follow-up pathway enrichment analysis exposed notable alterations within key metabolic pathways, including the biosynthesis of phenylalanine, tyrosine, and tryptophan, lysine degradation, as well as the biosynthesis and metabolism of valine, leucine, and isoleucine pathways in Nile tilapia, consequent to increased concentrations of polypropylene nanoplastics. These metabolic alterations portend potential implications such as immune suppression, among other deleterious outcomes. This trailblazing application of this methodology not only spares aquatic life from sacrifice but also inaugurates an ethical paradigm for conducting longitudinal studies on the same organisms, facilitating detailed investigations into the long-term effects of environmental pollutants. This technique enhances the ability to observe and understand the subtle yet significant impacts of such contaminants over time.

Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization.

Introduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications. Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined. Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1ß and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-ß. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function. Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.

Rapamycin functionalized carbon Dots: Target-oriented synthesis and suppression of vascular cell senescence.

Suppression of vascular cell senescence is of great significance in preventing cardiovascular diseases such as hypertension and atherosclerosis. The oxidative stress damage caused by reactive oxygen species (ROS) can lead to cellular senescence. Rapamycin (Rapa) is well known to suppress cell senescence via mammalian target of rapamycin (mTOR) pathway. However, poor water solubility and lack of ROS scavenging ability limit the further development of Rapa. To improve the solubility of Rapa and endow with ROS scavenging ability, Rapa functionalized carbon dots (Rapa-CDs) are target-oriented synthesized via free radical polymerization combination with hydrothermal carbonization. Rapa-CDs improve the solubility of Rapa and show ROS scavenging abilities. The solubility of Rapa-CDs with 9.41 g is improved 3.6 × 104 times higher than that of Rapa (2.6 × 10-4 g). The half maximal inhibitory concentration (IC50) of Rapa-CDs toward hydroxyl radical (•OH) and 2,2-Diphenyl-1-picrylhydrazyl free radical (DPPH•) are 0.18 and 0.17 mg/mL, respectively. Rapa-CDs show anti-oxidative stress effect in HEVECs (Human Umbilical Vein Endothelial Cells) via reducing ROS levels by 87 %. Rapa-CDs alleviate HUVECs senescence by suppressing mTOR overactivation, attenuate the expression of P53, P21 and P16. The study demonstrates the target-oriented synthesis of drugs functionalized CDs with anti-senescence via dual-pathway of anti-oxidative stress and mTOR.

Three new Furano-lactones from the endophytic fungus Aspergillus nidulans.

Three new furano-lactones, asperilactones A-C (1-3), and two known compounds silvaticol (4) and violaceic acid (5) were isolated from an ethanol extract of Aspergillus nidulans, a fungus isolated from the Annelida Whitmania pigra Whitman (Haemopidae). Their structures were elucidated by a combination of spectroscopy, ECD calculations, comparing optical rotation values, and single-crystal X-ray diffraction analyses. Asperilactone A (1) represented the first example of furano-lactone with an unusual 2-thia-6-oxabicyclo[3.3.0]octane ring system. Asperilactones A and B showed weak toxicity against the HL-60 and RKO.