The pyroptosis mechanism of ototoxicity caused by unconjugated bilirubin in neonatal hyperbilirubinemia.

When activated by unconjugated bilirubin (UCB), inflammatory mediators such as IL - 18 and TNF contribute to the neurotoxicity and ototoxicity observed in severe neonatal hyperbilirubinemia. However, in cell and molecular level, the regulation and mechanism of UCB-induced ototoxicity are remained unclear. In this study, 7-day-old mammary rats were exposed to various concentrations of UCB to imitate the infant auditory damage. The auditory brainstem response result (ABR) indicated severe hearing loss, which occurred with increasing concentration. Morphological analysis of organotypic cochlear cultures treated with different concentrations of UCB indicated that auditory nerve fibers (ANF) were demyelinated and the density of spiral ganglion neurons (SGN) were decreased. In addition, HEI-OC1 cells treated with different concentrations of UCB showed severe necrosis by Flow Cytometry. The morphologic feature of pyroptosis has been observed by scanning electronic microscope. Cleaved Caspase-1, GSDMD and NLRP3 expression were significantly increased in cochlear explants with UCB-induced. To further clarify the molecular mechanism of UCB-induced inner ear cell pyroptosis, specific inhibitors of pyroptosis were applied, the protein associated with pyrotosis such as Cleaved Caspase-1, GSDMD, ASC, IL-18 and NLRP3 were significantly lower than the group with UCB alone. All the data above indicated that ERK /NLRP3/GSDMD signaling pathway involved in UCB-induced ototoxicity.

New porphyrin photosensitizers-Synthesis, singlet oxygen yield, photophysical properties and application in PDT.

This research on porphyrin-based photosensitizer system has a very important theoretical and practical significance in the photodynamic therapy (PDT) treatment of cancer. Based on this, in this article, a series of porphyrin derivatives were first designed and synthesized, and a "push-pull" porphyrin photosensitizer with two symmetrical ethanethioate groups was finally constructed. Based on the characterization of their chemical structures (1H and13C NMR, MS, IR, and UV-Vis spectroscopy) and the use of the density functional theory (DFT) and time-dependent DFT (TDDFT) to address the nature of the excited states as well as the dark/phototoxicity, the results have indicated the relationship between the porphyrin structure and properties. The experimental and theoretical UV-Vis absorption properties of porphyrins were discussed. The four porphyrin compounds synthesized all demonstrated a high capacity to generate singlet oxygen under long-wavelength (590 nm) light and low dark toxicity. Compared with the conventional porphyrin photosensitizers, P4 with a CT band (from 580 to 750 nm) is beneficial to the penetration of the light, presenting the potential for applications in PDT.

Linear and Nonlinear Photon-Induced Cross Bridge/Space Charge Transfer in STC Molecular Crystals.

In this work, we theoretically studied the optical absorption properties of a layer-stacked cocrystal heterogeneous material Spe-TCNB cocrystal (STC) which is produced by supramolecular self-assembly of organic conjugated monomers SPE and TCNB. The highly ordered aggregate structure in the cocrystal STC will lead to intermolecular interactions such as π∼π, hydrogen bonds and van der Waals forces, resulting in significant charge transfer characteristics and large cross-sectional two-photon absorption characteristics. The physical mechanism of one-photon and two-photon charge transfer of cocrystal molecules is specifically discussed and the interaction between molecules and their role in charge transfer are quantitatively analyzed. We found that the charge transfer between molecular junctions composed of hydrogen bonds is mainly cross-bridge charge transfer, while the charge transfer between molecular junctions caused by accumulation is mainly cross-space charge transfer. This discovery is of great significance to the design of organic photoelectric functional materials.

Dual Gas-responsive Fluorescent Diblock Copolymer Synthesized via RAFT Polymerization.

Stimulus-responsive polymers with luminescence properties have a wide range of applications in the fields of controlled drug release, fluorescent probes, and biological stents. In this paper, carbon dioxide (CO2)/oxygen (O2) dual-responsive fluorescent diblock copolymers were synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization method with two fluorescent monomers synthesized as its luminescence source, DEAEMA (CO2 responsive monomer) and tFMA (O2 responsive monomer). An experimental study demonstrated that the synthesized stimulus-responsive fluorescent polymer had a high sensitivity to CO2; the double-responsive fluorescent diblock copolymer could form and achieve the reversal of polymer micelles in the aqueous solution when it was sequentially subjected to the introduction of CO2 and O2.

Towards multi-label classification: Next step of machine learning for microbiome research.

Machine learning (ML) has been widely used in microbiome research for biomarker selection and disease prediction. By training microbial profiles of samples from patients and healthy controls, ML classifiers constructs data models by community features that highly correlated with the target diseases, so as to determine the status of new samples. To clearly understand the host-microbe interaction of specific diseases, previous studies always focused on well-designed cohorts, in which each sample was exactly labeled by a single status type. However, in fact an individual may be associated with multiple diseases simultaneously, which introduce additional variations on microbial patterns that interferes the status detection. More importantly, comorbidities or complications can be missed by regular ML models, limiting the practical application of microbiome techniques. In this review, we summarize the typical ML approaches of single-label classification for microbiome research, and demonstrate their limitations in multi-label disease detection using a real dataset. Then we prospect a further step of ML towards multi-label classification that potentially solves the aforementioned problem, including a series of promising strategies and key technical issues for applying multi-label classification in microbiome-based studies.

High-Flux Positively Charged Nanocomposite Nanofiltration Membranes Filled with Poly(dopamine) Modified Multiwall Carbon Nanotubes.

The poor dispensability of pristine carbon nanotubes in water impedes their implications in thin-film nanocomposite membranes for crucial utilities such as water purification. In this work, high-flux positively charged nanocomposite nanofiltration membranes were exploited by uniformly embedding poly(dopamine) modified multiwall carbon nanotubes (PDA-MWCNTs) in polyamide thin-film composite membranes. With poly(dopamine) modification, fine dispersion of MWCNTs in polyethyleneimine (PEI) aqueous solutions was achieved, which was interracially polymerized with trimesoyl chloride (TMC) n-hexane solutions to prepare nanocomposite membranes. The compatibility and interactions between modified MWCNTs and polyamide matrix were enhanced, attributed to the poly(dopamine) coatings on MWCNT surfaces, leading to significantly improved water permeability. At optimized conditions, pure water permeability of the PEI/PDA-MWCNTs/TMC nanofiltration membrane (M-4) was 15.32 L m(-2) h(-1) bar(-1), which was ∼1.6 times increased compared with that of pristine PEI/TMC membranes. Salt rejection of M-4 to different multivalent cations decreased in the sequence ZnCl2 (93.0%) > MgCl2 (91.5%) > CuCl2 (90.5%) ≈ CaCl2, which is well-suited for water softening and heavy metal ion removal.

Zn-doped CaTiO3:Eu(3+) red phosphors for enhanced photoluminescence in white LEDs by solid-state reaction.

Zn-doped CaTiO3:Eu(3+) red phosphors for enhanced photoluminescence in white light-emitting diodes (LEDs) were synthesized by a solid-state method. The structure and morphology of the obtained phosphor samples were observed by X-ray diffraction (XRD) and scanning electron microscopy (SEM), and the impact of Ca, Zn and Eu content on their photoluminescence properties was studied. The results indicated that Zn not only participates in the formation of defects in suitable lattice matrices but also has a role in flux in the transformation from ZnO to Zn2TiO4, which is beneficial for the enhancement of photoluminescence properties. Photoluminescence test data showed that the Zn-doped phosphor is excited efficiently by near-ultraviolet (NUV) light at wavelengths around 398 nm and emits an intense red light with a broad peak around 616 nm corresponding to the (5) D0 →(7) F2 transition of Eu(3+). The intensity of this phosphor emission is three times stronger than that without Zn-doping. Furthermore, this phosphor has very good thermal stability, high color purity and a low sintered temperature, all of which suggest its potential as a promising red phosphor for white LEDs.

Enhanced migration and CXCR4 over-expression in fibroblasts with telomerase reconstitution.

Telomerase reconstitution shows great potential for cell treatment and tissue engineering. Although the effects of telomerase on cell lifespan are well documented, the effects of telomerase on cellular biological characteristics, such as cellular migration, are relatively unknown. In this study, we tried to investigate if telomerase is involved in the regulation of fibroblast migration and the mechanism behind it. We found that when stimulated with a chemokine, CXCL12, the rate of migration was significantly higher in fibroblasts with telomerase reconstitution than that in fibroblasts without. Furthermore, the CXCL12 receptor, CXCR4, and multiple down-stream factors (Rho family members), were upregulated in the telomerase reconstituted fibroblasts. We concluded for the first time that telomerase reconstitution increased fibroblast migration through activation of CXCL12/CXCR4 axis and Rho family. The finding that fibroblasts with telomerase reconstitution have enhanced migration may have broad implications for cell therapy.