Enantioselective construction of stereogenic-at-sulfur(IV) centres via catalytic acyl transfer sulfinylation.

Chiral sulfur pharmacophores are crucial for drug discovery in bioscience and medicinal chemistry. While the catalytic asymmetric synthesis of sulfoxides and sulfinate esters with stereogenic-at-sulfur(IV) centres is well developed, the synthesis of chiral sulfinamides remains challenging, which has primarily been attributed to the high nucleophilicity and competing reactions of amines. In this study, we have developed an efficient methodology for the catalytic asymmetric synthesis of chiral sulfinamides and sulfinate esters by the sulfinylation of diverse nucleophiles, including aromatic amines and alcohols, using our bifunctional chiral 4-arylpyridine N-oxides as catalysts. The remarkable results are a testament to the efficiency, versatility and broad applicability of the developed synthetic approach, serving as a valuable tool for the synthesis of sulfur pharmacophores. Mechanistic experiments and density functional theory calculations revealed that the initiation and stereocontrol of this reaction are induced by an acyl transfer catalyst. Our research provides an efficient approach for the construction of optically pure sulfur(IV) centres.

Lens regeneration in situ using hESCs-derived cells -similar to natural lens.

Lens itself has limited regeneration functionality, thus we aimed to create regenerated lens with biological function to treat cataracts rather than the intraocular lens used in cataract surgery. We induced exogenous human embryonic stem cells to directionally differentiate into lens fate like cells in vitro, mixed these cells with hyaluronate, and then implanted the mixture into lens capsule to regenerate in vivo. We successfully achieved near-complete lens regeneration, and the thickness of the regenerated lens reached 85% of the contralateral eye, showing the characteristics of biconvex shape, transparency, and a thickness and diopter close to that of natural lenses. Meanwhile, the participation of Wnt/PCP pathway in lens regeneration was verified. The regenerated lens in this study was the most transparent, thickest, and most similar to the original natural lens that has thus far been reported. Overall, these findings offer a new therapeutic strategy for cataracts and other lens diseases.

Comparison of femtosecond laser-assisted cataract surgery and conventional phacoemulsification on corneal impact: A meta-analysis and systematic review.

This meta-analysis aims to compare corneal injuries and function after femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification surgery (CPS). A comprehensive literature search of PubMed, EMBASE, and the Cochrane Controlled Trials Register was conducted to identify randomized controlled trials (RCT) and high-quality prospective comparative cohort studies comparing FLACS with CPS. Endothelial cell loss percentage (ECL%), central corneal thickness (CCT), endothelial cell density (ECD), endothelial cell loss (ECL), percentage of the hexagonal cell (6A), and coefficient of variance (CoV) were used as an indicator of corneal injury and function. Totally 42 trials (23 RCTs and 19 prospective cohort studies), including 3916 eyes, underwent FLACS, and a total of 3736 eyes underwent CPS. ECL% is significantly lower in the FLACS group at 1-3 days (P = 0.005), 1 week (P = 0.004), 1 month (P<0.0001), 3 months (P = 0.001), and 6 months (P = 0.004) after surgery compared to CPS. ECD and ECL appeared no statistically significant difference between the two groups, except for the significant reduction of ECD at 3 months in the CPS group (P = 0.002). CCT was significantly lower in the FLACS group at 1 week (P = 0.05) and 1 month (P = 0.002) early postoperatively. While at 1-3 days (P = 0.50), 3 months (P = 0.18), and 6 months (P = 0.11), there was no difference between the FLACS group and the CPS group. No significant difference was found in the percentage of hexagonal cells and the coefficient of variance. FLACS, compared with CPS, reduces corneal injury in the early postoperative period. Corneal edema recovered faster in the FLACS group in the early postoperative period. In addition, FLACS may be a better option for patients with corneal dysfunction.

Cell Wall Destruction and Internal Cascade Synergistic Antifungal Strategy for Fungal Keratitis.

Fungal keratitis is one of the most common blindness-causing diseases, but clinical antifungal treatment remains a challenge. The fungal cell wall and biofilm matrix which severely confine the drug preparation are the critical obstructive factors to therapeutic effects. Herein, we report ethylenediaminetetraacetic acid (EDTA) modified AgCu2O nanoparticles (AgCuE NPs) to disrupt the cell wall and then eradicate C. albicans through the internal cascade synergistic effects of ion-released chemotherapy, chemodynamic therapy, photodynamic therapy, and mild photothermal therapy. AgCuE NPs exhibited excellent antifungal activity both in preventing biofilm formation and in destroying mature biofilms. Furthermore, AgCuE NP based gel formulations were topically applied to kill fungi, reduce inflammation, and promote wound healing, using optical coherence tomography and photoacoustic imaging to monitor nanogel retention and therapeutic effects on the infected murine cornea model. The AgCuE NP gel showed good biosafety and no obvious ophthalmic and systemic side effects. This study suggests that the AgCuE NP gel is an effective and safe antifungal strategy for fungal keratitis with a favorable prognosis and potential for clinical translation.

Recent Advances of Intraocular Lens Materials and Surface Modification in Cataract Surgery.

Advances in cataract surgery have increased the demand for intraocular lens (IOL) materials. At present, the progress of IOL materials mainly contains further improving biocompatibility, providing better visual quality and adjustable ability, reducing surgical incision, as well as dealing with complications such as posterior capsular opacification (PCO) and ophthalmitis. The purpose of this review is to describe the research progress of relevant IOL materials classified according to different clinical purposes. The innovation of IOL materials is often based on the common IOL materials on the market, such as silicon and acrylate. Special properties and functions are obtained by adding extra polymers or surface modification. Most of these studies have not yet been commercialized, which requires a large number of clinical trials. But they provide valuable thoughts for the optimization of the IOL function.

Safety of femtosecond laser-assisted cataract surgery versus conventional phacoemulsification for cataract: A meta-analysis and systematic review.

Purpose: To compare the complications of femtosecond laser-assisted cataract surgery (FLACS) with those of conventional phacoemulsification surgery (CPS) for age-related cataracts. Methods: PubMed, Cochrane Library, and EMBASE were systematically searched for studies comparing FLACS and CPS. Outcomes were operative complications, including the intraoperative capsule tear, postoperative corneal edema, macular edema, uncontrolled IOP, etc. The effect measures were weighted with odds ratios with 95% CIs. Results: Nineteen RCTs and 18 cohort studies, including 24,806 eyes (11,375 of the FLACS group and 13,431 of the CPS group), were identified. There were no significant differences between the two groups in anterior capsule tear, corneal edema, macular edema, uncontrolled IOP, vitreous loss, posterior vitreous detachment, etc. Posterior capsule tear rate showed a significantly lower in RCT subgroups (P â€‹= â€‹0.04) and without differences in total (P â€‹= â€‹0.63). Significant differences were observed in the incidence of descemet membrane tear/trauma (P â€‹= â€‹0.02) and IFIS/iris trauma (P â€‹= â€‹0.04. Additionally, The FLACS specific complications showed a significantly higher rate of miosis (P â€‹< â€‹0.0001), corneal epithelial defect (P â€‹= â€‹0.001), corneal haze (P â€‹= â€‹0.002), and subconjunctival hemorrhage (P â€‹= â€‹0.01). Conclusions: FLACS maintains the same safety compared with CPS in terms of all intraoperative and postoperative complications. Although FLACS did show a statistically significant difference for several FLACS specific complications, it would not influence the visual outcome and heal itself.

Acetal-linked polymeric prodrug micelles based on aliphatic polycarbonates for paclitaxel delivery: preparation, characterization, in vitro release and anti-proliferation effects.

Acidic tumor microenvironment has been extensively explored to design pH-responsive paclitaxel prodrug micelles for cancer therapy. The object of this study is to investigate the pH-responsive drug release behavior and the anti-proliferation capacity of acetal-linked paclitaxel polymeric prodrug micelles. The prodrug was synthesized and evaluated for paclitaxel content. The prodrug micelles were fabricated and characterized for morphology, size, in vitro pH-responsive paclitaxel release, cellular uptake, and anti-proliferation. Paclitaxel content was 33 wt%. The prodrug micelles exhibited spherical structure with the hydrodynamic diameter of 154 nm. Besides, the in vitro paclitaxel release behavior was verified to be pH-responsive, and 77%, 38%, and 17% of parent free paclitaxel was released from the nano-sized prodrug micelles in 13 h at pH 5.5, 6.5, and 7.4, respectively. The cellular uptake assessment demonstrated the time-dependent internalization of prodrug micelles. Meanwhile, CCK-8 analysis showed that prodrug micelles possessed the potent anti-proliferation effects. Prodrug micelles based on aliphatic polycarbonates present a promising platform for cancer chemotherapy due to the pH-responsive characteristics of acetal bond, potent anti-proliferation effects, and outstanding cytocompatibility of aliphatic polycarbonates.

Intraocular Lens power calculation after laser refractive surgery: A Meta-Analysis.

There are an increasing number of people who have had refractive surgery now developing cataract. To compare the accuracy of different intraocular lens (IOL) power calculation formulas after laser refractive surgery (photorefractive keratectomy or laser in situ keratomileusis), a comprehensive literature search of PubMed and EMBASE was conducted to identify comparative cohort studies and case series comparing different formulas: Haigis-L, Shammas-PL, SRK/T, Holladay 1 and Hoffer Q. Seven cohort studies and three observational studies including 260 eyes were identified. There were significant differences when Hoffer Q formula compared with SRK/T, Holladay 1. Holladay 1 formula produced less prediction error than SRK/T formula in double-K method. Hoffer Q formula performed best among SRK/T and Holladay 1 formulas in total and single-K method. In eyes with previous data, it is recommended to choose double-K formula except SRK/T formula. In eyes with no previous data, Haigis-L formula is recommended if available, if the fourth formula is unavailable, single-k Hoffer Q is a good choice.