Visible-Light Induced Thiol–Ene Reaction on Natural Lignin

The current use of lignin as a raw material is very limited and focused only on cheap and poorly defined nonfunctional materials mainly due to challenges in synthetic modification of lignin. Herein, we report a new low energy and environmentally friendly lignin modification method induced by visible blue light. The key modification reaction is a photoredox catalyzed thiol–ene reaction. The lignin was modified to possess alkenes for the thiol–ene reaction. Three photochemical reagentsRu­(bpy)₃Cl₂, Eosin Y, and 2,2-dimethoxy-2-phenylacetophenonewere tested to determine the best thiol–ene modification method. The thiol–ene reaction between lignin–alkene and 1-decanethiol revealed that Ru­(bpy)₃Cl₂ was the most efficient, resulting in conversions of 97% with 2.5 mol % catalyst loading. The Ru­(bpy)₃Cl₂ was further investigated with diverse thiol compounds. All tested thiol–ene reactions showed excellent efficiencies, with conversions of 93–97% under low-energy 3W blue LED light. In particular, thiol terminal poly­(ethylene glycol) also displayed 94% conversion after 80 min of irradiation. The developed photoredox catalyzed thiol–ene modification of lignin was very conveniently controlled by simply turning the light source on and off. Excellent conversion, 95%, of lignin thiol–ene modification was achieved even by natural sunlight after 4 h of irradiation

Additional file 1 of Temporally and spatially resolved molecular profiling in fingerprint analysis using indium vanadate nanosheets-assisted laser desorption ionization mass spectrometry

Supplementary Material 1: Experimental section and additional data (Figure S1–S25, Table S1–S4) associated with this article can be found in the online versio

A simplified prognostic score for T-cell large granular lymphocyte leukaemia

T-cell large granular lymphocyte leukaemia (T-LGLL) generally has a favourable prognosis, but a small proportion of patients are facing a relatively short survival time. This study aimed to identify clinical factors associated with survival in patients with T-LGLL and develop a predictive model for guiding therapeutic decision-making. We conducted a retrospective study on 120 patients with T-LGLL. Lasso regression was performed for feature selection followed by univariate and multivariate Cox regression analysis. A decision tree algorithm was employed to construct a model for predicting overall survival (OS) in T-LGLL. The median age of diagnosis for the entire cohort was 59 years, and 76.7% of patients reported disease-related symptoms. After a median follow-up of 75 months, the median OS was not reached. The 5-year OS rate was 82.2% and the 10-year OS rate was 63.8%. Multivariate analysis revealed that an Eastern Cooperative Oncology Group performance status over two and a platelet count below 100 × 109/L were independently associated with worse OS, leading to the development of a simplified decision tree model. The model’s performance was adequate when internally validated. The median OS of the high- and intermediate-risk- risk groups was 43 and 100 months respectively, whereas the median OS of the low-risk group was not reached. Furthermore, we found that immunosuppressive agent-based conventional treatment was unsatisfactory for our high-risk patients. Our model is an easily applicable clinical scoring system for predicting OS in patients with T-LGLL. However, external validation is essential before implementing it widely.</p

Tenofovir modulates adenosine levels.

<p>After two days of tenofovir pretreatment with (75 mg/kg)), an injection of bleomycin (0.25 U, SubQ) or TAA (100mg/kg, intraperitoneally) was administered to induce an acute toxin-induced adenosine release response. 24 hours later, animals were sacrificed and tissue was collected, adenosine extracted as described in methods and levels were measured by HPLC <b>A)</b> Bar graph of adenosine release in skin. <b>B)</b> Bar graph of adenosine release in liver. Results are expressed as mean±SEM. *p<0.05 compared to vehicle (ANOVA).</p

Tenofovir diminishes myofibroblasts in the skin of bleomycin-treated mice.

<p><b>A)</b> Representative alpha-SMA immunostained images (100x, 200x, and 400x original magnification). Biopsy site is near the site of induration 18 days after treatment. <b>B)</b> Quantitative analysis of positive cells/HPF. Results are expressed as mean±SEM. Scale = 100 μm, ***p<0.001 compared to vehicle (ANOVA).</p

Tenofovir prevents liver and skin fibrosis in two models of adenosine-mediated injury.

<p><b>A)</b> C57BL/6 mice treated with tenofovir therapy (intraperitoneal injections) are protected against bleomycin-induced dermal fibrosis. Bleomycin (0.25 U; SubQ injections, daily for 18 days) was used to induce fibrosis in C57BL/6 mice. Intraperitoneal tenofovir therapy (75 mg/kg) was administered during bleomycin challenge. <b>B)</b> C57BL/6 mice treated with 3TC therapy are not protected against bleomycin-induced dermal fibrosis. Images from representative hematoxylin and eosin stained slides are presented. Skin thickness measurements were performed as described in materials and methods. Breaking tension results were performed with a tensiometer and the recording at the point of maximal stress before tearing of the biopsy was recorded. <b>C)</b> Picrosirius red staining of fibrotic liver. TAA (100 mg/kg; intraperitoneal injections, alternate days for 8 weeks) was administered to induce fibrosis in C57BL/6 mice. Subcutaneous tenofovir therapy (75 mg/kg) was administered during TAA challenge. Paraffin-embedded liver tissue sections were stained in 1% Sirius red and collagen-positive sites were indicated in red. Digitized images (10x and 40x) are presented and show representative liver sections (n = 5–10). <b>D)</b> Quantification of picrosirius red staining was performed digitally using SigmaScan Pro v.5.0.0; data represent the percentage of total liver area stained by picrosirius red. Results are expressed as mean±SEM. Scale = 100 μm. **p<0.005, ***p<0.001 compared to vehicle (ANOVA).</p

Tenofovir inhibits ATP export via Pannexin-1.

<p><b>A)</b><i>In vitro</i> ATP determination assays were performed with RAW264.7 cells according to manufacturer’s protocol. Tenofovir dose-response effects are shown. Data represents the mean results of 5 separate experiments carried out in duplicate. <b>B)</b> ATP determination assay was performed in the presence of Pannexin-1 or Connexin-43 knock-down (KD) RAW264.7 cells. Pannexin-1 and Connexin-43 knockdown protein expression in shRNA RAW264.7 cells. <b>C)</b> ATP determination assay was performed in the presence of Pannexin-1, AK4 or NME2 knock-down (KD) HepG2 cells. Pannexin-1, AK4 and NME2 knockdown protein expression in shRNA HepG2. Data is a representative experiment of two, performed in triplicate. Results are expressed as mean±SEM. **p<0.005, ***p<0.001 compared to vehicle in RAW264.7 or HepG2 cells (ANOVA).</p

Organic Cyanide Decorated SERS Active Nanopipettes for Quantitative Detection of Hemeproteins and Fe³⁺ in Single Cells

It is challenging to develop a robust nanoprobe for real-time operational and accurate detection of heavy metals in single cells. Fe-CN coordination chemistry has been well studied to determine the structural characteristics of hemeproteins by different techniques. However, the frequently used cyanide ligands are inorganic molecules that release cyanide anion under particular conditions and cause cyanide poisoning. In the present study, organic cyanide (4-mercaptobenzonitrile, MBN) was utilized for the first time in developing a facile nanoprobe based on surface-enhanced Raman scattering (SERS) for quantitative detection of hemeproteins (oxy-Hb) and trivalent iron (Fe³⁺) ions. The nanoprobe prepared by coating the glass capillary tip (100 nm) with a thin gold film, which enables highly localized study in living cell system. The cyanide stretching vibration in MBN was highly sensitive and selective to Fe³⁺ and oxy-Hb with excellent binding affinity (<i>K</i>_d 0.4 pM and 0.1 nM, respectively). The high sensitivity of the nanoprobe to analyte (Fe³⁺) was attributed to the two adsorption conformations (−SH and −CN) of MBN to the gold surface. Therefore, MBN showed an exceptional dual-peak (2126 and 2225 cm^–1) behavior. Furthermore, the special Raman peaks of cyanide in 2100–2300 cm^–1 (silent region of SERS spectra) are distinguishable from other biomolecules characteristic peaks. The selective detection of Fe³⁺ in both free and protein-bound states in aqueous solution is achieved with 0.1 pM and 0.08 μM levels of detection limits, respectively. Furthermore, practical applicability of fabricated nanoprobe was validated by detection of free Fe³⁺ in pretreated living HeLa cells by direct insertion of a SERS active nanoprobe. Regarding the appropriate precision, good reproducibility (relative standard deviation, RSD 7.2–7.6%), and recyclability (retain good Raman intensity even after three renewing cycles) of the method, the developed sensing strategy on a nanopipette has potential benefits for label-free, qualitative and quantitative recognition of heavy metal ions within nanoliter volumes