Simple method for transformation and gene editing in medicinal plants.

A sample delivery method, modified from cut-dip-budding, uses explants with robust shoot regeneration ability, enabling transformation and gene editing in medicinal plants, bypassing tissue culture and hairy root formation. This method has potential for applications across a wide range of plant species.

Therapeutic applications of contact lens-based drug delivery systems in ophthalmic diseases.

Traditional ophthalmic drugs, such as eye drops, gels and ointments, are accompanied by many problems, including low bioavailability and potential drug side effects. Innovative ophthalmic drug delivery systems have been proposed to overcome the limitations associated with traditional formulations. Recently, contact lens-based drug delivery systems have gained popularity owing to their advantages of sustained drug delivery, prolonged drug retention, improved bioavailability, and few drug side effects. Various methods have been successfully applied to drug-loaded contact lenses and prolonged the drug release time, such as chemical crosslinking, material embedding, molecular imprinting, colloidal nanoparticles, vitamin E modification, drug polymer film/coating, ion ligand polymerization systems, and supercritical fluid technology. Contact lens-based drug delivery systems play an important role in the treatment of multifarious ophthalmic diseases. This review discusses the latest developments in drug-loaded contact lenses for the treatment of ophthalmic diseases, including preparation methods, application in ophthalmic diseases and future prospects.

Systematic review and meta-analysis: impact of anti-viral therapy on portal hypertensive complications in HBV patients with advanced chronic liver disease.

BACKGROUND: The efficacy of nucleos(t)ide analogs (NAs) in non-cirrhotic chronic hepatitis B (CHB) patients is well-established. However, their impact on complications of portal hypertension in advanced chronic liver disease (ACLD) is less well characterized. METHODS: MEDLINE/PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and abstracts of major international hepatology meetings were searched for publications from Jan 1, 1995 to Nov 30, 2021. Randomized control trials and observational studies reporting the efficacy of NAs in ACLD patients were eligible. Pooled risk ratios (RRs) for outcomes of interest were calculated with a random-effect or fixed-effect model, as appropriate. RESULTS: Thirty-nine studies including 14,212 ACLD patients were included. NA treatment was associated with reduced risks of overall hepatic decompensation events (RR, 0.51; 95% confidence interval [CI]: 0.37-0.71), such as variceal bleeding (RR, 0.44; 95% CI: 0.26-0.74) and ascites (RR, 0.10; 95% CI: 0.01-1.59), on a trend-wise level. Moreover, the risks of hepatocellular carcinoma (HCC) (RR, 0.48; 95% CI: 0.30-0.75) and liver transplantation/death (RR, 0.36; 95% CI: 0.25-0.53) were also reduced by NA treatment and the first-line NAs were superior to non-first-line NAs in improving these outcomes (RR, 0.85; 95% CI: 0.75-0.97 and RR, 0.85; 95% CI: 0.73-0.99, respectively). CONCLUSION: NA therapy lowers the risk of portal hypertension-related complications, including variceal bleeding, HCC, and liver transplantation/death.

Complex Interplay Between COVID-19 Lockdown and Myopic Progression.

Purpose: To compare the myopic progression before and during strict home confinement when coronavirus disease 2019 (COVID-19) outbreak and explore the potential influencing factors. Methods: A cross-sectional study. One hundred and fifteen myopic children (115 right eyes) who replace their frame-glasses from December 2019 to January 2020 and with complete refractive records in our hospital since myopia were involved in the study. At the beginning of the strict home confinement and after a 3-month strict home confinement during the COVID-19 pandemic, they were invited to our hospital to examine the axial length and refractive errors. And visual functions, convergence insufficiency symptom survey (CISS) scale and questionnaires were also performed. Besides, the axial length and refractive errors before the COVID-19 were got from outpatient case files. The effect of strict home confinement on myopia was assessed by comparing monthly axial elongation before COVID-19 and during strict home confinement. Spearman correlation analysis was performed to explore the correlation between potential influencing factors and myopia progression. Results: Axial length's monthly elongation during strict home confinement was 35% higher than normal periods (0.046 vs. 0.033 mm/month, P = 0.003). The proportion of severe asthenopia doubled (P = 0.020). For myopia progression, heredity, close indoor work time and electronic products were risk factors. Besides, the protective factors were age, rest time after continuous eye usage, sleep time and distance from eye to computer screen. Conclusions: During COVID-19, the decline in outdoor activities and increase of exposure time to digital screens accelerated the progression of myopia by 1/3.

Changes in corneal densitometry after long-term orthokeratology for myopia and short-term discontinuation.

PURPOSE: To quantify changes in corneal densitometry after long-term orthokeratology treatment in myopic children and to analyze the reversibility one month after discontinuation. METHODS: Seventy-four myopic subjects aged 8-16 years, who wore orthokeratology lenses for two years, were divided into relatively steep- (lens movement within 1.0-1.5 mm, thirty-six participants) and flat-fitting groups (lens movement within 1.5-2.0 mm, thirty-eight participants). Based on refractive errors, they were divided into low and moderate myopia groups (thirty-seven participants in each group). Corneal densitometry was performed using Pentacam (Oculus Optikgeräte GmbH, Wetzlar, Germany) at each follow-up timepoint. Repeated-measures analysis of variance was used to compare the parameters before and after orthokeratology. RESULTS: The corneal densitometry values over the 0-10 mm diameter area increased from 12.84±1.38 grayscale units (GSU) at baseline to 13.59±1.42 GSU after three-month orthokeratology (P = .001) and reached 14.92±1.45 GSU at two years (P < .001). An increase in densitometry began at one month (P = .001) over the 0-2 mm annulus compared with that at three months over the 2-6 mm and 6-10 mm zones (P = .002,.014). The densitometry values significantly increased at three months in the relatively steep-fitting group (P = .003) and at one year in the relatively flat-fitting group (P = .001). After discontinuation of orthokeratology for one month, the values showed no significant decrease. CONCLUSIONS: Long-term orthokeratology treatment causes a small but statistically significant increase in corneal densitometry values. During the first year, the onset of these changes was related to the fitting mode. Corneal densitometry values showed no significant reduction after one-month discontinuation.

Preparation and Evaluation of Starch Hydrogel/Contact Lens Composites as Epigallocatechin Gallate Delivery Systems for Inhibition of Bacterial Adhesion.

Microbial infections caused by wearing contact lenses has become a major health problem, so the design and development of antibacterial contact lenses has attracted widespread attention. To safely and effectively inhibit bacterial adhesion of contact lenses, we have facilely prepared epigallocatechin gallate (EGCG) loaded starch hydrogel/contact lens composites by in-situ free radical polymerization of the mixture containing 2-hydroxylethyl methacrylate, methacrylic acid and ethylene glycol dimethacrylate. The adequate transmittance of the resulting contact lenses was characterized by ultraviolet-visible spectrophotometry, and their satisfactory stability was examined using differential scanning calorimetry and thermogravimetric analysis. Whereafter, cytotoxicity and degradation experiments were performed to investigate the biocompatibility and degradability of the contact lenses. The results showed the nontoxicity and good degradability of the composites. Besides, the capacity of the contact lenses for in vitro release of EGCG was also evaluated, and the results showed that the EGCG in these contact lenses can be sustainably released for at least 14 days. Further bacterial adhesion assay suggested that the EGCG loaded starch hydrogel/contact lenses could significantly reduce the adhesion of Pseudomonas aeruginosa compared to the control. The EGCG loaded starch hydrogel/contact lens composites provide a potential intervention strategy for preventing ocular microbial infections and inhibiting bacterial keratitis.

Gelatin hydrogel/contact lens composites as rutin delivery systems for promoting corneal wound healing.

Corneal wound healing is a highly regulated biological process that is of importance for reducing the risk of blinding corneal infections and inflammations. Traditional eye drop was the main approach for promoting corneal wound healing. However, its low bioavailability required a high therapeutic concentration, which can lead to ocular or even systemic side effects. To develop a safe and effective method for treating corneal injury, we fabricated rutin-encapsulated gelatin hydrogel/contact lens composites by dual crosslinking reactions including in situ free radical polymerization and carboxymethyl cellulose/N-hydroxysulfosuccinimide crosslinking. In vitro drug release results evidenced that rutin in the composites could be sustainedly released for up to 14 days. In addition, biocompatibility assay indicated nontoxicity of the composites. Finally, the effect of rutin-encapsulated composites on the healing of the corneal injury in rabbits was investigated. The injury was basically cured in corneas using rutin-encapsulated composites (healing rate, 98.3% ± 0.7%) at 48 h post-operation, while the damage was still present in corneas using the composite (healing rate, 87.0% ± 4.5%). Further proteomics analysis revealed that corneal wound healing may be promoted by the ERK/MAPK and PI3K/AKT signal pathways. These results inform a potential intervention strategy to facilitate corneal wound healing in humans.

The therapeutic use of quercetin in ophthalmology: recent applications.

Quercetin is a natural flavonol antioxidant found in various plant sources and food samples. It is well known for its notable curative effects on the treatment of ophthalmic diseases due to various biological activities, such as antioxidant, anti-inflammatory, and anti-fibrosis activities. This review will discuss the latest developments in therapeutic quercetin for the treatment of keratoconus, Graves' orbitopathy, ocular surface, cataracts, glaucoma, retinoblastoma, and other retinal diseases.

Generating Novel Male Sterile Tomatoes by Editing Respiratory Burst Oxidase Homolog Genes.

Hybrid breeding of tomatoes (Solanum lycopersicum), an important vegetable crop, is an effective way to improve yield and enhance disease and stress resistance. However, the efficiency of tomato hybridization is hindered by self-fertilization, which can be overcome using male sterile lines. It has been reported that reactive oxygen species (ROS) act as a key regulator for anther development, mediated by RBOH (Respiratory Burst Oxidase Homolog) genes. Here, two tomato anther-expressed genes, LeRBOH (Solyc01g099620) and LeRBOHE (Solyc07g042460), were selected to cultivate novel tomato male sterile strains. By using a CRISPR/Cas9 system with a two-sgRNA module, the lerboh, lerbohe, and lerboh lerbohe mutant lines were generated, among which the lerbohe and lerboh lerbohe mutants displayed complete male sterility but could accept wild-type pollens and produce fruits normally. Further analysis uncovered significantly decreased ROS levels and abnormal programmed cell death in lerboh lerbohe anthers, indicating a key role of ROS metabolism in tomato pollen development. Taken together, our work demonstrates a successful application of gene editing via CRISPR/Cas9 in generating male sterile tomatoes and afforded helpful information for understanding how RBOH genes regulating tomato reproduction process.

Research Development, Optimization and Modifications of Anti-cancer Peptides.

Anti-cancer peptides play an important role in the area of cancer inhibition. A variety of anti- cancer peptides have emerged through the extraction and structural modification of peptides from biological tissues. This review provides the research background of anti-cancer peptides, the introduction of the mechanism of anti-cancer peptides for inhibition of cancers, the discovery and development along with optimization and modifications of these peptides in the clinical application. In conclusion, it can be said that anti-cancer peptides will play a major role in the future oncologic clinic.

Development and Challenges of the Discovery of HER2 Inhibitors.

The treatment of cancer has always been a major problem in the world. Some cancers cannot be treated with surgery, but only with cancer drugs. Among many cancer drugs, small molecule inhibitors play an irreplaceable role. HER2 is one of the HER families, and the development of HER2 inhibitors has made a huge contribution to the treatment of cancer. Some HER2 inhibitors are already on the market, and some HER2 inhibitors are undergoing clinical research. The design, synthesis and development of new HER2 inhibitors targeting different targets are also ongoing, and some are even under clinical research. The HER2 inhibitors that are on the market have developed resistance, which brings great challenges to the HER2 inhibitor development in the future. This article reviews the development and challenges of the discovery of HER2 inhibitors.

Extended Contact Lens Wear Promotes Corneal Norepinephrine Secretion and Pseudomonas aeruginosa Infection in Mice.

Purpose: Extended contact lens (CL) wear predisposes the wearer to Pseudomonas aeruginosa infection of the cornea, but the mechanism involved remains incompletely understood. The purpose of this study was to investigate the role of the stress hormone norepinephrine (NE) in the pathogenesis of CL-induced P. aeruginosa keratitis. Methods: A total 195 adult C57BL/6 mice were used in this study. Corneal NE content was measured after 48 hours of sterile CL wear in mice. The effect of NE on P. aeruginosa adhesion and biofilm formation on the CL surface was examined in vitro. Moreover, mouse eyes were covered with P. aeruginosa-contaminated CLs, and either 500-µM NE was topically applied or the eyes were subconjunctivally injected with 100 µg of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to deplete local NE. Clinical scores, neutrophil infiltration, proinflammatory cytokine levels, and bacterial load on the corneas and CLs were evaluated. Results: Corneal NE content was elevated with extended CL wear in mice. In vitro, NE promoted the adhesion and biofilm formation of P. aeruginosa on the CL surface. In mice, topical application of NE aggravated P. aeruginosa infection, accompanied with increased clinical scores, neutrophil infiltration, proinflammatory cytokine expression, and bacterial burden on the corneas and CLs. However, pre-depletion of local NE with DSP-4 significantly alleviated the severity of P. aeruginosa keratitis. Conclusions: Extended CL wear elevates corneal NE content, which promotes the pathogenesis of CL-induced P. aeruginosa keratitis in mice. Targeting NE may provide a potential strategy for the treatment of CL-related corneal infection caused by P. aeruginosa.