Preparation of Xanthene-TEMPO Dyads: Synthesis and Study of the Radical Enhanced Intersystem Crossing.

We prepared a rhodamine-TEMPO chromophore-radical dyad (RB-TEMPO) to study the radical enhanced intersystem crossing (REISC). The visible light-harvesting chromophore rhodamine is connected with the TEMPO (a nitroxide radical) via a C-N bond. The UV-vis absorption spectrum indicates negligible electron interaction between the two units at the ground state. Interestingly, the fluorescence of the rhodamine moiety is strongly quenched in RB-TEMPO, and the fluorescence lifetime of the rhodamine moiety is shortened to 0.29 ns, from the lifetime of 3.17 ns. We attribute this quenching effect to the intramolecular electron spin-spin interaction between the nitroxide radical and the photoexcited rhodamine chromophore. Nanosecond transient absorption spectra confirm the REISC in RB-TEMPO, indicated by the detection of the rhodamine chromophore triplet excited state; the lifetime was determined as 128 ns, which is shorter than the native rhodamine triplet state lifetime (0.58 µs). The zero-field splitting (ZFS) parameters of the triplet state of the chromophore were determined with the pulsed laser excited time-resolved electron paramagnetic resonance (TREPR) spectra. RB-TEMPO was used as a photoinitiator for the photopolymerization of pentaerythritol triacrylate (PETA). These studies are useful for the design of heavy atom-free triplet photosensitizers, the study of the ISC, and the electron spin dynamics of the radical-chromophore systems upon photoexcitation.

Bacterial outer membrane vesicles-cloaked modified zein nanoparticles for oral delivery of paclitaxel.

To improve the aqueous solubility and oral bioavailability of paclitaxel (PTX), a biomimetic system for oral administration of PTX was efficiently developed as an outer membrane vesicle (OMVs) of sodium caseinate (CAS) modified zein nanoparticles (OMVs-Zein-CAS-PTX-NPs) by Escherichia coli. To verify their structure and properties, the designed nanostructures were thoroughly characterized using various characterization techniques. The results indicated that hydrogen bonds and van der Waals forces mainly drove the interaction between PTX and Zein, but the complex is unstable. The physicochemical stability of PTX-loaded zein nanoparticles was improved by the addition of CAS. The biological characteristics of biofilms are reproduced by nanoparticles cloaked with outer membrane vesicles. OMVs-Zein-CAS-PTX-NPs delayed the release of PTX under simulated gastric and intestinal fluids due to OMVs protection. OMVs-Zein-CAS-PTX-NPs exhibited remarkable antitumor ability in vitro and improved the bioavailability of oral administration of PTX in vivo. Therefore, OMVs cloaked in nanoparticles may be a suitable delivery vehicle to provide an efficient application prospect for the oral administration of PTX.

Myeloid dendritic cells are increased in the lesional skin and associated with pruritus in patients with prurigo nodularis.

The number of dermal mDCs (CD11c+ cells) was increased with itch intensity (r = 0.886, p = 0.003) using immunofluorescence (IF). On IF, CD11c+ mDCs expressed IL-31 in lesional PN skin. Fluorescence in situ hybridization combined with IF also confirmed IL-31 mRNA expression by mDCs in PN lesion. Higher population of colocalization of CD11c+ mDCs expressing IL-31 mRNA were more than CD68+ macrophages and CD3+ T cells in consecutive sections of PN skin lesion. HC, healthy control; PN, prurigo nodularis; SPN, PN with severe pruritus (itch NRS score ≥7 points); MPN, PN with mild pruritus (itch NRS score <3 points); NRS, Numeric Rating Scale; AD, atopic dermatitis; mDC, myeloid dendritic cell.

Realization of thousand-second improved confinement plasma with Super I-mode in Tokamak EAST.

Mastering nuclear fusion, which is an abundant, safe, and environmentally competitive energy, is a great challenge for humanity. Tokamak represents one of the most promising paths toward controlled fusion. Obtaining a high-performance, steady-state, and long-pulse plasma regime remains a critical issue. Recently, a big breakthrough in steady-state operation was made on the Experimental Advanced Superconducting Tokamak (EAST). A steady-state plasma with a world-record pulse length of 1056 s was obtained, where the density and the divertor peak heat flux were well controlled, with no core impurity accumulation, and a new high-confinement and self-organizing regime (Super I-mode = I-mode + e-ITB) was discovered and demonstrated. These achievements contribute to the integration of fusion plasma technology and physics, which is essential to operate next-step devices.

Underlying Systemic Diseases in Interstitial Granulomatous Dermatitis and Palisaded Neutrophilic Granulomatous Dermatitis: A Systematic Review.

BACKGROUND: Interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic granulomatous dermatitis (PNGD) are uncommon presentations of reactive granulomatous dermatitis. Histologic lesions characterized by IGD/PNGD patterns have been associated with systemic diseases, causing an unmet need for revealing clinical correlates. OBJECTIVE: The aim of this study was to unravel the systemic diseases beyond dermatitis of IGD/PNGD. METHODS: This study analyzed data from case studies, case series, and retrospective cohorts by searching PubMed, Embase, Web of Science, and the Cochrane Library, with no start date or language restrictions on Sep 4, 2021. RESULTS: One hundred ninety-six publications were included (458 cases in total, 216 with details). Systemic diseases associated with IGD/PNGD were classified into 5 groups. Autoimmune disorders (n = 103, 47.6%) including rheumatoid arthritis (n = 51, 23.6%), systemic lupus erythematosus (n = 20, 9.3%), and others were the most common across all underlying diseases, followed by drug eruption (n = 52, 24.1%) such as tumor necrotic factor inhibitor reaction (n = 18, 8.3%) and malignancies (n = 27, 12.5%) such as hematologic malignancy (n = 20, 9.3%). The rest were infectious diseases (n = 12, 5.6%) and accidental conditions (n = 3, 1.4%). CONCLUSION: IGD/PNGD might be associated with autoimmune disorders, drug eruption, malignancies, infectious diseases, and accidental conditions. Patients with IGD/PNGD need further follow-up.

Successful Treatment of a Patient with Pyoderma Gangrenosum, Plaque Psoriasis and Palmoplantar Pustulosis with Adalimumab.

Pyoderma gangrenosum (PG) is a rare autoinflammatory skin disorder, which is characterised by rapidly developing and tender cutaneous ulcers. The treatment of PG is challenging. Palmoplantar pustulosis (PPP) is also an autoinflammatory dermatosis with sterile pustules on the palms and/or the soles. We demonstrated a 68-year-old patient with coexisting autoinflammatory diseases including PG, 1-year history of plaque psoriasis and PPP, recovered after treatment with adalimumab. We also reviewed published reports of PG-associated autoinflammatory syndromes with adalimumab.

Biofilm-encapsulated nano drug delivery system for the treatment of colon cancer.

AIM: In this study, 5-fluorouracil (5-FU) is delivered to target colon without the interference of mononuclear phagocyte system (MPS). METHODS: Outer membrane vesicles (OMVs) were used as the biological shield to disguise mesoporous silica (MSN) and 5-FU. OMVs-MSN-5-FU were prepared by high pressure co-extrusion, and characterised on the basis of size, drug loading, transmission electron microscope, infra-red spectroscopy, differential scanning calorimetry, thermal gravity analysis, % in vitro release, MTT assay, cell uptake and in vivo imaging. RESULTS: OMVs-MSN-5-FU with -18.22 ± 0.17 mV zeta potential and 90.4 ± 9.1 nm size were used for oral treatment of colon cancer. Drug loading of the drug was 50.22%±0.17 (w/w). The cumulative release of OMVs-MSN-5-FU reached 75.07%±0.94 in tumour microenvironment. The percentage of cell viability of OMVs-MSN-5-FU was 33.75%±2.73. In vivo experiments results confirmed that OMVs-MSN-5-FU could be taken up by colon cancer cells. CONCLUSIONS: The study provided a promising nano platform for the targeting treatment of colon cancer.

Preparation and evaluation of long circulating erythrocyte membrane-cloaked anti-cancer drug delivery system.

Recently, biomimetic hybrid drug delivery systems, especially erythrocyte membrane-based drug delivery systems, have been utilized to achieve high bioavailability, and biocompatibility, in the meantime, to reduce immunogenicity and effectively evade phagocytosis of the host immune system. Here, we developed a novel drug delivery system of red blood cell membrane-derived vesicles (RDVs) cloaked poly (acrylic acid)-cystamine hydrochloride-D-α-tocopherol succinate (PAAssVES) nanoparticles. The PAAssVES nanoparticles were prepared via emulsification and solvent volatilization method, followed by loading of the model anti-cancer drug, sorafenib (SFN). Then RDVs and SFN-PAAssVES nanoparticles were uniformly mixed and co-extruded through polycarbonate membrane. The prepared RDV-coated nanoparticles (RDV-NPs) had good stability, with a zeta potential of - 10.7 mV and particle size of 113.5 nm. MTT assay was used to analyze the effects of RDV-NPs on cell viability in two kinds of gastric cancer cell lines BGC-823 and MKN-45. The results showed that RDV-NPs significantly decreased cell viability. In vitro drug release investigation showed that RDV-NPs had good sustained release properties and the cumulative release was 71.5% in 72 h. In pharmacokinetic studies, SD male rats' intravenous injection with RDV-NP solution showed a more smooth plasma concentration-time profile. Compared with free SFN treatment and SFN-PAAssVES group, RDV-NPs enhanced the AUC by about 4.1-fold and 2.0-fold. The MRT and t1/2 of RDV-NPs were increased to 23.670 ± 2.347 h and 24.450 ± 2.652 h. Our study demonstrated the promise of using RDV-NPs as a long circulating anti-cancer drug delivery system. Graphical abstract.