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Nitrogen transfer and cross-feeding between Azotobacter chroococcum and Paracoccus aminovorans promotes pyrene degradation
Nitrogen is a limiting nutrient for degraders function in hydrocarbon-contaminated environments. Biological nitrogen fixation by diazotrophs is a natural solution for supplying bioavailable nitrogen. Here, we determined whether the diazotroph Azotobacter chroococcum HN can provide nitrogen to the polycyclic aromatic hydrocarbon-degrading bacterium Paracoccus aminovorans HPD-2 and further explored the synergistic interactions that facilitate pyrene degradation in nitrogen-deprived environments. We found that A. chroococcum HN and P. aminovorans HPD-2 grew and degraded pyrene more quickly in co-culture than in monoculture. Surface-enhanced Raman spectroscopy combined with 15N stable isotope probing (SERS − 15N SIP) demonstrated that A. chroococcum HN provided nitrogen to P. aminovorans HPD-2. Metabolite analysis and feeding experiments confirmed that cross-feeding occurred between A. chroococcum HN and P. aminovorans HPD-2 during pyrene degradation. Transcriptomic and metabolomic analyses further revealed that co-culture significantly upregulated key pathways such as nitrogen fixation, aromatic compound degradation, protein export, and the TCA cycle in A. chroococcum HN and quorum sensing, aromatic compound degradation and ABC transporters in P. aminovorans HPD-2. Phenotypic and fluorescence in situ hybridization (FISH) assays demonstrated that A. chroococcum HN produced large amounts of biofilm and was located at the bottom of the biofilm in co-culture, whereas P. aminovorans HPD-2 attached to the surface layer and formed a bridge-like structure with A. chroococcum HN. This study demonstrates that distinct syntrophic interactions occur between A. chroococcum HN and P. aminovorans HPD-2 and provides support for their combined use in organic pollutant degradation in nitrogen-deprived environments.
On-fiber photonic nanojet enables super-resolution in en face optical coherence tomography and scattering nanoscopy
Photonic nanojet (PNJ) of subwavelength spot-size originating at shadow side of a microsphere is projected as an imperative optical tool for micro-nano optics applications. Lack of a free hold PNJ source limits its vast potential. A state-of-the-art PNJ is introduced on a chemically etched encaved optical fiber nanoprobe holding a microsphere. Nanoprobe generating optical beam of spot-size ~2 μm, is focused on the microsphere resulting in PNJ of varying spot-size, 0.8λ to 0.5λ, over its’ length ~13λ at 660 nm wavelength. A PNJ centered around 840 nm wavelength combined with an effective numerical aperture ~2 results in an en-face optical coherence tomography (OCT) image of lateral resolution ~247 nm and phase map with optical thickness, ~70 nm for a standard DVD. Further, the PNJ based backscattered nanoscopy of silver nano-particles is exhibited with resolution ~40 nm. This commercially viable PNJ head can be an ideal platform for various microscopies and other applications.
Cyclic jetting enables microbubble-mediated drug delivery
The pursuit of targeted therapies capable of overcoming biological barriers, including the blood–brain barrier, has spurred the investigation of stimuli-responsive microagents that can improve therapeutic efficacy and reduce undesirable side effects. Intravenously administered, ultrasound-responsive microbubbles are promising agents with demonstrated potential in clinical trials, but the mechanism underlying drug absorption remains unclear. Here we show that ultrasound-driven single microbubbles puncture the cell membrane and induce drug uptake through stable cyclic microjets. Our theoretical models successfully reproduce the observed bubble and cell dynamic responses. We find that cyclic jets arise from shape instabilities, as opposed to classical inertial jets that are driven by pressure gradients, enabling microjet formation at mild ultrasound pressures below 100 kPa. We also establish a threshold for bubble radial expansion beyond which microjets form and facilitate cellular permeation and show that the stress generated by microjetting outperforms previously suggested mechanisms by at least an order of magnitude. Overall, this work elucidates the physics behind microbubble-mediated targeted drug delivery and provides the criteria for its effective and safe application.
Regulatory T cells-related gene in primary sclerosing cholangitis: evidence from Mendelian randomization and transcriptome data
The present study utilized large-scale genome-wide association studies (GWAS) summary data (731 immune cell subtypes and three primary sclerosing cholangitis (PSC) GWAS datasets), meta-analysis, and two PSC transcriptome data to elucidate the pivotal role of Tregs proportion imbalance in the occurrence of PSC. Then, we employed weighted gene co-expression network analysis (WGCNA), differential analysis, and 107 combinations of 12 machine-learning algorithms to construct and validate an artificial intelligence-derived diagnostic model (Tregs classifier) according to the average area under curve (AUC) (0.959) in two cohorts. Quantitative real-time polymerase chain reaction (qRT-PCR) verified that compared to control, Akap10, Basp1, Dennd3, Plxnc1, and Tmco3 were significantly up-regulated in the PSC mice model yet the expression level of Klf13, and Scap was significantly lower. Furthermore, immune cell infiltration and functional enrichment analysis revealed significant associations of the hub Tregs-related gene with M2 macrophage, neutrophils, megakaryocyte-erythroid progenitor (MEP), natural killer T cell (NKT), and enrichment scores of the autophagic cell death, complement and coagulation cascades, metabolic disturbance, Fc gamma R-mediated phagocytosis, mitochondrial dysfunction, potentially mediating PSC onset. XGBoost algorithm and SHapley Additive exPlanations (SHAP) identified AKAP10 and KLF13 as optimal genes, which may be an important target for PSC.
Paper battery powered iontophoresis microneedles patch for hypertrophic scar treatment
Hypertrophic scar (HS) is a plaque fibrous and indurated dermal lesion that may cause physical, psychological, and cosmetic challenges for patients. Intralesional injection of triamcinolone acetonide (TA) is commonly used in clinical practice, which cause unbearable pain and uneven drug delivery within HS tissue. Herein, we developed a paper battery powered iontophoresis-driven microneedles patch (PBIMNP) for self-management of HS. The high integration of PBIMNP was achieved by incorporating a paper battery as the power source for iontophoresis. The transdermal drug delivery strategy of PBIMNP combined microneedles and iontophoresis techniques, involving “pressing and poking, phase transformation, and diffusion and iontophoresis”, which can actively deliver 90.19% drug into the HS tissue with excellent in vitro drug permeation performance. PBIMNP administration effectively reduced the mRNA and protein levels, leading to a decrease in the expression of TGF-β1 and Col I associated with HS formation, demonstrating its efficacy in HS treatment. The microneedles and wearable design endow the PBIMNP as a highly promising platform for self-administration on HS treatment.
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