Two-Phase Electrosynthesis of Dihydroxycoumestans: Discovery of a New Scaffold for Topoisomerase I Poison.

Coumestan represents a biologically relevant structural motif distributed in a number of natural products, and the rapid construction of related derivatives as well as the characterization of targets would accelerate lead compound discovery in medicinal chemistry. In this work, a general and scalable approach to 8,9-dihydroxycoumestans via two-electrode constant current electrolysis was developed. The application of a two-phase (aqueous/organic) system plays a crucial role for success, protecting the sensitive o-benzoquinone intermediates from over-oxidation. Based on the structurally diverse products, a primary SAR study on coumestan scaffold was completed, and compound 3 r exhibited potent antiproliferative activities and a robust topoisomerase I (Top1) inhibitory activity. Further mechanism studies demonstrates that compound 3 r was a novel Top1 poison, which might open an avenue for the development of Top1-targeted antitumor agent.

Electrochemical Synthesis of Phenothiazinone as Fluorophore and Its Application in Bioimaging.

Phenothiazinone is a promising yet underutilized fluorophore, possibly due to the lack of a general accessibility. This study reports a robust and scalable TEMPO-mediated electrochemical method to access a variety of phenothiazinones from 2-aminothiophenols and quinones. The electrosynthesis proceeds in a simple cell architecture under mild condition, and notably carbon-halogen bond in quinones remains compared to conventional methods, enabling orthogonal downstream functionalization. Mechanistic studies corroborate that TEMPO exerts a protective effect in avoiding product decomposition at the cathode. In particular, benzophenothiazinones show intriguing luminescence in both solid and solution state, and thus their photophysical properties are scrutinized in detail. Further bio-imaging of the lipid droplets in living cells highlights the considerable promise of benzophenothiazinones as fluorescent dye in the biomedical fields.

Long-term observation on safety and visual quality of implantable collamer lens V4c implantation for myopia correction: a 5-year follow-up.

AIM: To elucidate the safety and visual quality of implantable collamer lens with central hole (ICL V4c) implantation for correcting moderate and high myopia for at least 5y. METHODS: This retrospective study was conducted on 58 patients (114 eyes) who were followed up for at least 5y after ICL V4c implantation. The observation was done before and on 1d, 1mo, 1 and 5y or more after the surgical procedure. The visual acuity, subjective refraction, intraocular pressure, vault, axial length, central hole position, pupil diameter, visual quality, and adverse events were analyzed. The visual quality includes aberration, the modulation transfer function cutoff frequency (MTF cutoff), objective scattering index (OSI), Stroller's ratio (SR), and visual quality questionnaire. RESULTS: The average follow-up period was 69.25±3.80mo (range 60-82mo) and the preoperative spherical equivalent (SE) was -8.66±1.97 D. At 5y after operation, the safety index was 1.01±0.02 and the efficacy index was 0.99±0.42 and SE was -0.65±0.63 D. The 59.6% of the eyes achieved an uncorrected distance visual acuity of 20/20, 76.3% of the eyes had SE within ±1.0 D at the last visit. The axial length increased by 0.29±0.71 mm 5y after the surgery (t=-3.843, P<0.001). The mean vault at the last follow-up was 510.59±245.61 µm. The central hole was on the temporal side in 80 eyes (84.2%). The visual quality questionnaire showed that 98.2% patients were satisfied with the surgical procedure. Adverse events occurred in 4 eyes (3.5%), including the posttraumatic toric ICL rotation (2 eyes), iris incarceration (1 eye), and posttraumatic ICL displacement (1 eye) at the last follow-up. CONCLUSION: Long-term ICL V4c implantation is safe, effective, and stable for correcting moderate and to high myopia, and the visual quality with patients is excellent and satisfactory, but the progression of axial length still needs attention after surgery.

[Impacts of warming and nitrogen addition on organic fraction release in fresh litter of Larix potaninii in alpine zone of the western Sichuan Province, China]. / å·è¥¿é«˜æµ·æ‹”å¢žæ¸©å’ŒåŠ æ°®å¯¹çº¢æ‰å‡‹è½ç‰©æœ‰æœºç»„åˆ†é‡Šæ”¾çš„å½±å“.

The decomposition dynamics of organic components in fresh litter of Larix potaninii were monitored by in situ litter-bag incubation under four treatments, i.e., field condition (CK), nitrogen addition (AN, 2 g N·m-2), warming by top-open chamber (OTC), nitrogen addition with warming by top-open chamber (OTC+AN), from November to next September. Decomposition of water-soluble sugar, water-soluble phenol and total polyphenol were stimulated significantly under the treatment OTC, AN and OTC+AN during the first four months compared with the CK, but the difference of these components release narrowed with the extension of incubation time. Compared with CK, releases of dichloromethane-extractable fraction, acid soluble carbohydrates, acid soluble lignin, and acid insoluble lignin, were inhibited significantly under OTC, AN, and OTC+AN treatments, and the significance of inhibitory effect under the treatments was: OTC > OTC+AN > AN. Especially, in the treatment of OTC, half-life of dichloromethane-extractable fraction and acid inso-luble lignin in fresh litter were doubled, and that of hot-water soluble component was prolonged by more than 50% compared with CK. Half-life of water-soluble sugar, water-soluble phenol, total polyphenol, acid-soluble carbohydrate and acid-soluble lignin in fresh litter were respectively 182, 159, 127, 154 and 190 d in CK, and these components seem to be easily mineralized organic fraction. Meanwhile, half-life of hot-water soluble components, dichloromethane-extractable fraction, and acid insoluble lignin was 209, 302 and 318 d, respectively, indicating these fractions recalcitrant to decomposing in the fresh litter. Decomposition of all components in L. potaninii litter occurred in cold season from November to next March, which suggested that cold season was the most important period for litter decay in the alpine conifer. Generally it was assumed that microorganisms were inactive and decomposition of organic matters was slow in alpine soil during harsh winter, while the results of fresh litter incubation in situ showed that all components decomposed very fast during the period. Therefore, in alpine treeline, nitrogen deposition and warming would inhibit rather than promote decomposition of fresh litter, which would be conducive to carbon sequestration for the alpine soil ecosystem.