Novel Feruloyl Esterase for the Degradation of Polyethylene Terephthalate (PET) Screened from the Gut Microbiome of Plastic-Degrading Mealworms (Tenebrio Molitor Larvae).

Mealworms (Tenebrio molitor) larvae can degrade both plastics and lignocellulose through synergistic biological activities of their gut microbiota because they share similarities in chemical and physical properties. Here, a total of 428 genes encoding lignocellulose-degrading enzymes were screened from the gut microbiome of T. molitor larvae to identify poly(ethylene terephthalate) (PET)-degrading activities. Five genes were successfully expressed in E. coli, among which a feruloyl esterase-like enzyme named TmFae-PETase demonstrated the highest PET degradation activity, converting PET into MHET (0.7 mgMHETeq ·h-1·mgenzyme-1) and TPA (0.2 mgTPAeq ·h-1·mgenzyme-1) at 50 °C. TmFae-PETase showed a preference for the hydrolysis of ferulic acid methyl ester (MFA) in the presence of both PET and MFA. Site-directed mutagenesis and molecular dynamics simulations of TmFae-PETase revealed similar catalytic mechanisms for both PET and MFA. TmFae-PETase effectively depolymerized commercial PET, making it a promising candidate for application. Additionally, the known PET hydrolases IsPETase, FsC, and LCC also hydrolyzed MFA, indicating a potential origin of PET hydrolytic activity from its lignocellulosic-degrading abilities. This study provides an innovative strategy for screening PET-degrading enzymes identified from lignocellulose degradation-related enzymes within the gut microbiome of plastic-degrading mealworms. This discovery expands the existing pool of plastic-degrading enzymes available for resource recovery and bioremediation applications.

Metabolomics Reveals Disturbed Amino Acid Metabolism During Different Stages of RA in Collagen-Induced Arthritis Mice.

Rheumatoid arthritis (RA) is an autoimmune disease featured by chronic synovitis and progressive joint damage. Early treatment before the onset of clinical symptoms (also known as the pre-RA stage) may slow or stop the progression of the disease. We sought to discover the dynamic metabolic changes during the evolution of collagen-induced arthritis (CIA) to better characterize the disease stages. Untargeted metabolomics analysis using gas chromatography-mass spectrometry revealed that the metabolic profiles of CIA mice gradually differed from that of the control group with the progression of the disease. During the induction phase, the CIA group showed some metabolic alterations in galactose metabolism, arginine biosynthesis, tricarboxylic acid cycle (TCA cycle), pyruvate metabolism, and starch/sucrose metabolism. During the early inflammatory phase, no joint swelling was observed in CIA mice, and metabolites changed mainly involving amino acid metabolism (arginine biosynthesis, arginine/proline metabolism, phenylalanine/tyrosine/tryptophan biosynthesis), and glutathione metabolism. During the peak inflammatory phase, severe arthritis symptoms were observed in CIA mice, and there were more extensive metabolic alterations in valine/leucine/isoleucine biosynthesis, phenylalanine/tyrosine/tryptophan biosynthesis, TCA cycle, galactose metabolism, and arginine biosynthesis. Moreover, the reduction of specific amino acids, such as glycine, serine, and proline, during the early stages may result in an imbalance in macrophage polarization and enhance the inflammatory response in CIA mice. Our study confirmed that specific perturbations in amino acid metabolism have occurred in CIA mice prior to the onset of joint symptoms, which may be related to autoimmune disorders. The findings could provide insights into the metabolic mechanism and the diagnosis of pre-RA.

Treatment of eutrophic water in pyrite-filled constructed wetland integrated with microelectrolysis driven by iron/sulfur cycle: Performance and mechanism.

This study developed a microelectrolysis-integrated constructed wetland with pyrite filler around the cathode (e-PCW) to treat eutrophic water. Results indicated that e-PCW effectively enhanced pyrite dissolution, converting solid-phase electron donors into bioavailable forms, thereby facilitating the enrichment of various denitrifying bacteria on pyrite surfaces. Importantly, iron-reducing and sulfur-reducing bacteria attached to the pyrite surfaces enhanced the conversion of ferric iron and sulfate, thereby driving iron and sulfur cycles and promoting electron transfer. Therefore, synergistic effects of pyrite and microelectrolysis made e-PCW achieve higher total nitrogen (TN) and total phosphorus (TP) removal efficiencies. With a hydraulic retention time of 24 h, the highest removal efficiencies of TN and TP achieved 78% and 75%, respectively. Furthermore, when eutrophic water containing high concentration of algae was fed into e-PCW, it consistently demonstrated superior TN and TP removal capabilities. This work provides a valuable approach to optimizing constructed wetland technology for treating eutrophic water.

Environmental risks of mask wastes binding pollutants: Phytotoxicity, microbial community, nitrogen and carbon cycles.

The increasing contamination of mask wastes presents a significant global challenge to ecological health. However, there is a lack of comprehensive understanding regarding the environmental risks that mask wastes pose to soil. In this study, a total of 12 mask wastes were collected from landfills. Mask wastes exhibited negligible morphological changes, and bound eight metals and four types of organic pollutants. Masks combined with pollutants inhibited the growth of alfalfa and Elymus nutans, reducing underground biomass by 84.6 %. Mask wastes decreased the Chao1 index and the relative abundances (RAs) of functional bacteria (Micrococcales, Gemmatimonadales, and Sphingomonadales). Metagenomic analysis showed that mask wastes diminished the RAs of functional genes associated with nitrification (amoABC and HAO), denitrification (nirKS and nosZ), glycolysis (gap2), and TCA cycle (aclAB and mdh), thereby inhibiting the nitrogen transformation and ATP production. Furthermore, some pathogenic viruses (Herpesviridae and Tunggulvirus) were also found on the mask wastes. Structural equation models demonstrated that mask wastes restrained soil enzyme activities, ultimately affecting nitrogen and carbon cycles. Collectively, these evidences indicate that mask wastes contribute to soil health and metabolic function disturbances. This study offers a new perspective on the potential environmental risks associated with the improper disposal of masks.

Effect of Mn-HA on ARGs and MRGs in nitrogen-culturing sludge.

The simultaneous escalation in ARGs (antibiotic resistance genes) and MRGs (metal resistance genes) further complicates the intricate network of factors contributing to the proliferation of microbial resistance. Manganese, which has been reported to affect the resistance of bacteria to antibiotics and metals, plays a vital role in microbial nitrogen metabolism. Moreover, nitrifying and denitrifying populations are potential hosts for ARGs. In this study, manganese was introduced in its prevalent organic chelated form in the environment (Manganese humus chelates, Mn-HA) to a N metabolism sludge to explore the effect of manganese on MRGs and ARGs dissemination. Metagenomics results revealed that manganese availability enhances nitrogen metabolism, while a decrease in ARGs was noted which may be attributed to the inhibition of horizontal gene transfer (HGT), reflected in the reduced integrase -encoded gene int. Population analysis revealed that nitrifier and denitrifier genus harbor MRGs and ARGs, indicating that nitrifier and denitrifier are hosts of MRGs and ARGs. This raises the question of whether the prevalence of ARGs is always increased in metal-contained environments.

Analysis of the acoustoelectric response of SAW gas sensors using a COM model.

Surface acoustic wave (SAW) gas sensors based on the acoustoelectric effect exhibit wide application prospects for in situ gas detection. However, establishing accurate models for calculating the scattering parameters of SAW gas sensors remains a challenge. Here, we present a coupling of modes (COM) model that includes the acoustoelectric effect and specifically explains the nonmonotonic variation in the center frequency with respect to the sensing film's sheet conductivity. Several sensing parameters of the gas sensors, including the center frequency, insertion loss, and phase, were experimentally compared for accuracy and practicality. Finally, the frequency of the phase extremum (FPE) shift was determined to vary monotonically, and the range of selectable test points was wide, making the FPE an appropriate response parameter for leveraging in SAW gas sensors. The simulation results of the COM model were highly consistent with the experimental results. Our study is proposed to provide theoretical guidance for the future development of gas SAW sensors.

Association between red cell distribution width and hypertension: Results from NHANES 1999-2018.

The relationship between red cell distribution width (RDW) and hypertension remains a contentious topic, with a lack of large-scale studies focusing on the adults in the United States. This study aimed to investigate the association between RDW and hypertension among US adults from 1999 to 2018. METHODS: Data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. RDW values were obtained from the Laboratory Data's Complete Blood Count with 5-part Differential-Whole Blood module. Hypertension data were obtained through hypertension questionnaires and blood pressure measurements. Multivariable weighted logistic regression analyses were conducted to assess the association between RDW and hypertension, followed by subgroup and smooth curve analyses. RESULTS: Compared to the non-hypertensive group, the hypertensive group exhibited higher RDW values (13.33±1.38 vs. 12.95±1.27, P <0.001). After adjusting for covariates, weighted multivariable logistic regression analysis revealed a positive correlation between RDW and hypertension prevalence (OR: 1.17, 95% CI 1.13, 1.21, P <0.001). When RDW was included as a categorical variable, participants in the fourth quartile had the highest risk of hypertension (OR: 1.86, 95% CI 1.70, 2.03, P <0.001). Subgroup analysis showed that, except for age, BMI and weak/failing kidneys, gender, race, education level, smoking, alcohol use, congestive heart failure, and stroke did not significantly influence this correlation (all P-values for interaction >0.05).Smooth curve fitting analysis revealed a reverse J-shaped relationship between RDW and hypertension prevalence, with an inflection point at 12.93%. CONCLUSION: We first explored the relationship between RDW and hypertension among US adults and discovered a reverse J-shaped association, providing further insights into the relationship between blood cell counts and hypertension and offering a new foundation for hypertension prevention and control.

Macaque Brainnetome Atlas: A multifaceted brain map with parcellation, connection, and histology.

The rhesus macaque (Macaca mulatta) is a crucial experimental animal that shares many genetic, brain organizational, and behavioral characteristics with humans. A macaque brain atlas is fundamental to biomedical and evolutionary research. However, even though connectivity is vital for understanding brain functions, a connectivity-based whole-brain atlas of the macaque has not previously been made. In this study, we created a new whole-brain map, the Macaque Brainnetome Atlas (MacBNA), based on the anatomical connectivity profiles provided by high angular and spatial resolution ex vivo diffusion MRI data. The new atlas consists of 248 cortical and 56 subcortical regions as well as their structural and functional connections. The parcellation and the diffusion-based tractography were evaluated with invasive neuronal-tracing and Nissl-stained images. As a demonstrative application, the structural connectivity divergence between macaque and human brains was mapped using the Brainnetome atlases of those two species to uncover the genetic underpinnings of the evolutionary changes in brain structure. The resulting resource includes: (1) the thoroughly delineated Macaque Brainnetome Atlas (MacBNA), (2) regional connectivity profiles, (3) the postmortem high-resolution macaque diffusion and T2-weighted MRI dataset (Brainnetome-8), and (4) multi-contrast MRI, neuronal-tracing, and histological images collected from a single macaque. MacBNA can serve as a common reference frame for mapping multifaceted features across modalities and spatial scales and for integrative investigation and characterization of brain organization and function. Therefore, it will enrich the collaborative resource platform for nonhuman primates and facilitate translational and comparative neuroscience research.

Biomineralized manganese oxide mediated nitrogen-contained wastewater treatment.

In recent years, manganese (Mn) has emerged as an accelerator for nitrogen metabolism. However, the bioactivity of manganese is limited by the restricted contact between microbes and manganese minerals in the solid phase and by the toxicity of manganese to microbes. To enhance the bioactivity of solid-phase manganese, biomineralized manganese oxide (MnOx) modified by Lactobacillus was introduced. Nitrogen removal performance have confirmed the effective role of biomineralized MnOx in accelerating the removal of total inorganic nitrogen (TIN). Metagenomic analysis has confirmed the enhancement of the nitrogen metabolic pathway and microbial extracellular electron transfer (MEET) in biomineralized MnOx treatment group (BIOA group). Additionally, the enrichment of manganese oxidation and denitrification genus indicates a coupling between nitrogen metabolism and manganese metabolism. One point of views is that biomineralized MnOx-mediated nitrogen transformation processes could serve as a substitute for traditional nitrogen removal processes.

Probiotics Pediococcus acidilactici GR-1 promotes the functional strains and remodels gut microbiota to reduce the Cr(VI) toxicity in a dual-chamber simulated intestinal system.

Numerous animal studies have demonstrated the toxicity of hexavalent chromium [Cr(VI)] and the bioremediative effects of probiotics on the composition and functions of gut microbiota. Since the precise mechanisms of Cr(VI) detoxification and its interactions with human gut microbiota were unknown, a novel dual-chamber simulated intestinal (DCSI) system was developed to maintain both the stability of the simulated system and the composition of the gut microbiota. Probiotic GR-1 was found to regulate intestinal gut microbiota, thereby reducing the toxicity of Cr(VI) within the DCSI system. The results indicate that Cr(VI) levels were reduced from 2.260 ± 0.2438 µg/g to 1.7086 ± 0.1950 µg/g in the gut microbiota cell pellet, and Cr(VI) permeability decreased from 0.5521 ± 0.1132 µg/L to 0.3681 ± 0.0178 µg/L after 48 h in simulated gut fluid. Additionally, the removal rate of 1,1-Diphenyl-2-picrylhydrazyl (DPPH), reducibility (Vitamin C), and total antioxidant capacity (T-AOC) increased by 50.83%, 31.70%, and 27.56%, respectively, following probiotic treatment. The increase in antioxidant capacity correlated with total Cr removal (P < 0.05, r from -0.80 to 0.73). 16S rRNA sequencing analysis showed that gut microbiota composition was reshaped by the addition of probiotics, which regulated the recovery of the functional gut microbiota to normal levels, rather than restoring the entire gut microbiota composition for community function. Thus, this study not only demonstrates the feasibility and stability of culturing gut microbiota but also offers a new biotechnological approach to synthesizing functional communities with functional strains for environmental risk management.

Ectopic CD4+ T cells in choroid plexus mediate neuropsychiatric lupus symptoms in mice via interferon-γ induced microglia activation.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a disabling and potentially life-threatening complication of SLE. This study aims to investigate whether ectopic CD4+ T cells in the choroid plexus mediate NPSLE in mice. Intracerebroventricular (ICV) injection of anti-CD4 antibody effectively depleted CP-resident CD4+ T cells and alleviated NPSLE-like symptoms in MRL/lpr mice. Following ICV injection, the majority of isolated lupus CD4+ T cells from donor MRL/lpr mice predominantly stayed in the CP for at least 28 days in recipient C57BL/6 mice, while nearly all isolated CD4+ T cells from MRL/MpJ mice disappeared within 7 days. ICV injection of lupus CD4+ T cells resulted in NPSLE-like symptoms, including impaired behavioral performances, increased microglial activation, and abnormal microstructure changes. Flow cytometry analysis revealed that the majority of isolated lupus CD4+ T cells were positive for IFN-γ. Neutralizing intracerebral IFN-γ alleviated NPSLE-like symptoms in MRL/lpr mice. Moreover, ICV injection of anti-IFN-γ antibody or microglial depletion by PLX3397 benefited most NPSLE-like symptoms in lupus CD4+ T-treated mice, while ICV injection of IFN-γ mimicked most NPSLE-like symptoms. In conclusion, CP-resident lupus CD4+ T cells contribute to NPSLE-like symptoms in mice via Interferon-γ induced microglia activation. Depleting CP-resident lupus CD4+ T cells, interferon-γ, or activated microglia may be potential therapeutic targets for NPSLE.

Mechanism and Origin of Stereoselectivity for the NHC-Catalyzed Desymmetrization Reaction for the Synthesis of Axially Chiral Biaryl Aldehydes.

Organocatalytic desymmetrization reaction is a powerful tool for constructing axial chirality, but the theoretical study on the origin of stereoselectivity still lags behind even now. In this work, the N-heterocyclic carbene (NHC)-catalyzed desymmetrization reaction of biaryl frameworks for the synthesis of axially chiral aldehydes has been selected and theoretically investigated by using density functional theory (DFT). The fundamental pathway involves several steps, i.e., desymmetrization, formation of Breslow oxidation, esterification, and NHC regeneration. The desymmetrization and formation of Breslow processes have been identified as stereoselectivity-determining and rate-determining steps. Further weak interaction analyses proved that the C-H···O hydrogen bond and C-H···π interactions are responsible for the stability of the key stereoselective desymmetrization transition states. This research contributes to understanding the nature of NHC-catalyzed desymmetrization reactions for the synthesis of axially chiral compounds.

A multi-scale approach to arabinoxylan-based emulsions: From molecular features, interfacial properties to emulsion behaviors.

Arabinoxylan (AX) is well-known for its emulsification and beneficial biological activity, but the roles of AX's molecular features and interfacial properties in AX-based emulsion behaviors were unknown. We first used a multi-scale approach to correlate molecular, interfacial, droplet characteristics, and bulk emulsion of AXs from corn and wheat bran (CAXs and WAXs). Our results showed that among CAXs and WAXs solution (1 %, 2 % and 3 %, w/v), 0.25 M NaOH-treated CAX and WAX showed smaller particle sizes (493 nm and 8621 nm), lower interfacial tension and stronger interfacial layer, whose emulsion exhibited smaller initial droplets (541 nm and 660 nm) and better stability. Moreover, WAXs had bigger particle sizes, lower interfacial tension and stronger interfacial layer than CAXs, but CAXs exhibited better emulsifying and emulsion-stabilizing properties than WAXs. There is a satisfactory correlation among CAXs' or WAXs' molecular features, interfacial properties and emulsion behaviors. However, a good correlation from different grains AXs cannot be established.

Catalytic asymmetric dearomatization of phenols via divergent intermolecular (3 + 2) and alkylation reactions.

The catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast to the well-studied indoles and naphthols, phenols have been considered challenging substrates for intermolecular CADA reactions due to the combination of strong aromaticity and potential regioselectivity issue over the multiple nucleophilic sites (O, C2 as well as C4). Reported herein are the chiral phosphoric acid-catalyzed divergent intermolecular CADA reactions of common phenols with azoalkenes, which deliver the tetrahydroindolone and cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields with excellent ee values. Notably, simply adjusting the reaction temperature leads to the chemo-divergent intermolecular (3 + 2) and alkylation dearomatization reactions. Moreover, the stereo-divergent synthesis of four possible stereoisomers in a kind has been achieved via changing the sequence of catalyst enantiomers.

The evolution of nitrogen transformation microorganism consortium under continued manganese domestication conditions.

Manganese redox-stimulated bioremediation of nitrogen wastewater is receiving increasing attention. However, the nitrogen metabolic capacity and community evolution during manganese-mediated nitrogen transformation process under continued manganese domestication conditions are ambiguous. In this study, nitrogen- metabolizing microbial consortiums were incubated with synthesized Mn-humic acid complex (Mn-HA) for one month (M1), three months (M2) and six months (M3), respectively. During the Mn-HA incubation period, Bio-MnOx accompanying with bacterial consortiums (MnOB consortiums) with high TIN removal capacities were obtained. The TIN removal rates in M1, M2 and M3 were 0.220, 1.246 and 4.237 mg·L-1·h-1, respectively, which were 15.961, 90.006 and 1550.006 times higher than CK (Control Check group, no Mn-HA added group) (0.014 mg·L-1·h-1), respectively. Functional genes (amoA, AMX and narG) were most abundant in M3, which was associated with the highest nitrogen removal rate in M3. MnOB1 (bacterial consortium in M1), including Geobactor, Geothrix, Anaeromyxobacter and Bacillus, may be responsible for the Mnammox-NDMO (MnOx reduction coupled to ammonium oxidation - nitrate/nitrite-dependent low-valent Mn oxidation) process. MnOB3 (bacterial consortium in M2) enriched nitrifying bacteria Ellin6067, and denitrifying bacteria Denitratisoma, which dominated nitrogen transformation. MnOB6 (bacterial consortium in M3) enriched denitrifiers Denitratisoma, nitrifiers Ellin6067 and potential anammox bacteria SM1A02, Candidatus_Brocadia. Combined with the reduced abundance of Nitrospirae, a short-cut partial nitrification and denitrification (PND) or partial nitrification, denitrification and anammox (PNDA) could occurred in M2 and M3. It is suggested that community may have evolved into an energetically efficient short-cut nitrification, denitrification and anammox consortium to replace the full-range nitrification and denitrification community in M1 and CK under the continued manganese domestication conditions. Enhanced metabolic pathways of hydroxylamine oxidation and the nitric oxide reduction may confirm that PND or PNDA occurred in M2 and M3.

Effects of Moringa oleifera Seed Oil on Cultured Human Sebocytes In Vitro and Comparison with Other Oil Types.

The seeds of Moringa oleifera (horseradish tree) contain about 40% of one of the most stable vegetable oils (Moringa seed oil). Therefore, the effects of Moringa seed oil on human SZ95 sebocytes were investigated and were compared with other vegetable oils. Immortalized human SZ95 sebocytes were treated with Moringa seed oil, olive oil, sunflower oil, linoleic acid and oleic acid. Lipid droplets were visualized by Nile Red fluorescence, cytokine secretion via cytokine antibody array, cell viability with calcein-AM fluorescence, cell proliferation by real-time cell analysis, and fatty acids were determined by gas chromatography. Statistical analysis was performed by the Wilcoxon matched-pairs signed-rank test, the Kruskal-Wallis test and Dunn's multiple comparison test. The vegetable oils tested stimulated sebaceous lipogenesis in a concentration-dependent manner. The pattern of lipogenesis induced by Moringa seed oil and olive oil was comparable to lipogenesis stimulated by oleic acid with also similar fatty acid secretion and cell proliferation patterns. Sunflower oil induced the strongest lipogenesis among the tested oils and fatty acids. There were also differences in cytokine secretion, induced by treatment with different oils. Moringa seed oil and olive oil, but not sunflower oil, reduced the secretion of pro-inflammatory cytokines, in comparison to untreated cells, and exhibited a low n-6/n-3 index. The anti-inflammatory oleic acid detected in Moringa seed oil probably contributed to its low levels of pro-inflammatory cytokine secretion and induction of cell death. In conclusion, Moringa seed oil seems to concentrate several desired oil properties on sebocytes, such as high content level of the anti-inflammatory fatty acid oleic acid, induction of similar cell proliferation and lipogenesis patterns compared with oleic acid, lipogenesis with a low n-6/n-3 index and inhibition of secretion of pro-inflammatory cytokines. These properties characterize Moringa seed oil as an interesting nutrient and a promising ingredient in skin care products.

Microelectrolysis-integrated constructed wetland with sponge iron filler to simultaneously enhance nitrogen and phosphorus removal.

Integrating sponge iron (SI) and microelectrolysis individually into constructed wetlands (CWs) to enhance nitrogen and phosphorus removal are challenged by ammonia (NH4+-N) accumulation and limited total phosphorus (TP) removal efficiency, respectively. In this study, a microelectrolysis-assisted CW using SI as filler surrounding the cathode (e-SICW) was successfully established. Results indicated that e-SICW reduced NH4+-N accumulation and intensified nitrate (NO3--N), the total nitrogen (TN) and TP removal. The concentration of NH4+-N in the effluent from e-SICW was lower than that from SICW in the whole process with 39.2-53.2 % decrease, and as the influent NO3--N concentration of 15 mg/L and COD/N ratio of 3, the removal efficiencies of NO3--N, TN and TP in e-SICW achieved 95.7 ± 1.9 %, 79.8 ± 2.5 % and 98.0 ± 1.3 %, respectively. Microbial community analysis revealed that hydrogen autotrophic denitrifying bacteria of Hydrogenophaga was highly enriched in e-SICW.

Manganese-mediated ammonium removal by a bacterial consortium from wastewater: Experimental proof and biochemical mechanisms.

Manganese-redox-mediated nitrogen transformation is promising for ammonium wastewater treatment. However, due to the limited contact between insoluble Mn and the microbe, extracellular electron transfer (EET) inefficiencies become a technical bottleneck in the technical practical application. To overcome this obstacle, humic acid (HA) was introduced to synthesize manganese-humic acid complex (Mn-HA) to increase Mn solubility. The TIN (Total Inorganic Nitrogen) removal rate constant k was 3.18, 1.08, 3.56, 1.13 and 1.05 times higher than CK (Control group) at 10, 15, 20, 40 and 60 mg/L influent nitrate in the MH group, respectively. Mn-HA was inferred to stimulated the nitrogen removal by providing more reaction active sites, bridging Mn-O bonds to transfer electrons and playing a redox role in the respiratory chain. A Mnammox-NDMO (manganese oxide reduction-coupled ammonium oxidation - nitrate/nitrite- dependent manganese oxidation) bacteria consortium was enriched in MH group, containing Mnammox bacteria Geothrix, Geobacter and NDMO bacteria Pseudomonas and Bacillus.

Toxicity of ionic liquids against earthworms (Eisenia fetida).

Ionic liquids (ILs) are widely used in frontier fields because of their highly tunable properties. Although ILs may have adverse effects on organisms, few studies have focused on their effect on earthworm gene expression. Herein we investigated the toxicity mechanism of different ILs towards Eisenia fetida using transcriptomics. Earthworms were exposed to soil containing different concentrations and types of ILs, and behavior, weight, enzymatic activity and transcriptome were analyzed. Earthworms exhibited avoidance behavior towards ILs and growth was inhibited. ILs also affected antioxidant and detoxifying enzymatic activity. These effects were concentration and alkyl chain length-dependent. Analysis of intrasample expression levels and differences in transcriptome expression levels showed good parallelism within groups and large differences between groups. Based on functional classification analysis, we speculate that toxicity mainly occurs through translation and modification of proteins and intracellular transport functions, which affect protein-related binding functions and catalytic activity. KEGG pathway analysis revealed that ILs may damage the digestive system of earthworms, among other possible pathological effects. Transcriptome analysis reveals mechanisms that cannot be observed by conventional toxicity endpoints. This is useful to evaluate the potential environmental adverse effects of the industrial use of ILs.

HS 3D-SeboSkin Model Enables the Preclinical Exploration of Therapeutic Candidates for Hidradenitis Suppurativa/Acne Inversa.

Despite the rapid development in hidradenitis suppurativa (HS) research, the immediate introduction of potent therapeutic compounds in clinical trials and the lack of definitive outcome measures have led to the discontinuation of potential therapeutic compound studies. HS is a solely human disease, and therefore, the search for preclinical human models has been given priority. The 3D-SeboSkin model, a co-culture of human skin explants with human SZ95 sebocytes as a feeder layer, has been shown to prevent the rapid degeneration of human skin in culture and has been validated for HS preclinical studies. In this work, the HS 3D-SeboSkin model has been employed to characterize cellular and molecular effects of the EMA- and FDA-approved biologic adalimumab. Adalimumab, a tumor necrosis factor-α inhibitor, was shown to target inflammatory cells present in HS lesions, inducing a prominent anti-inflammatory response and contributing to tissue regeneration through a wound healing mechanism. Adalimumab inhibited the lesional tissue expression of TNF-α, IL-3, IL-15, and MCP-3 and downregulated the secretion of IL-1α, IL-5, RANTES, MCP-2, TNF-α, TNF-ß, TGF-ß, and IFN-γ. In contrast, IL-6 was stimulated. The compound failed to modify abnormal epithelial cell differentiation present in the HS lesions. Patients with Hurley stage II lesions exhibited stronger expression of autophagy proteins in perilesional than in lesional skin. Adalimumab modified the levels of the pro-apoptotic proteins LC3A, LC3B, and p62 in an individual, patient-dependent manner. Finally, adalimumab did not modify the NFκB signal proteins in SZ95 sebocytes and NHK-19 keratinocytes, used to study this specific pathway. The administration of the validated HS 3D-SeboSkin model in ex vivo studies prior to clinical trials could elucidate the individual pathogenetic targets of therapeutic candidates and, therefore, increase the success rates of clinical studies, minimizing HS drug development costs.