Discovery of a New Class of Lipophilic Pyrimidine-Biphenyl Herbicides Using an Integrated Experimental-Computational Approach.

Herbicides are useful tools for managing weeds and promoting food production and sustainable agriculture. In this study, we report on the development of a novel class of lipophilic pyrimidine-biphenyl (PMB) herbicides. Firstly, three PMBs, Ia, IIa, and IIIa, were rationally designed via a scaffold hopping strategy and were determined to inhibit acetohydroxyacid synthase (AHAS). Computational simulation was carried out to investigate the molecular basis for the efficiency of PMBs against AHAS. With a rational binding mode, and the highest in vitro as well as in vivo potency, Ia was identified as a preferable hit. Furthermore, these integrated analyses guided the design of eighteen new PMBs, which were synthesized via a one-step Suzuki-Miyaura cross-coupling reaction. These new PMBs, Iba-ic, were more effective in post-emergence control of grass weeds compared with Ia. Interestingly, six of the PMBs displayed 98-100% inhibition in the control of grass weeds at 750 g ai/ha. Remarkably, Ica exhibited ≥ 80% control against grass weeds at 187.5 g ai/ha. Overall, our comprehensive and systematic investigation revealed that a structurally distinct class of lipophilic PMB herbicides, which pair excellent herbicidal activities with new interactions with AHAS, represent a noteworthy development in the pursuit of sustainable weed control solutions.

Design, step-economical diversity-oriented synthesis of an N-heterocyclic library containing a pyrimidine moiety: discovery of novel potential herbicidal agents.

The synthesis of highly diverse libraries has become of paramount importance for obtaining novel leads for drug and agrochemical discovery. Herein, the step-economical diversity-oriented synthesis of a library of various pyrimidine-N-heterocycle hybrids was developed, in which a 4,6-dimethoxypyrimidine core was incorporated into nine kinds of N-heterocycles. A total of 34 structurally diverse compounds were synthesized via a two-step process from very simple and commercially available starting materials. Further, in vivo biological screening of this library identified 11 active compounds that exhibited good post-emergence herbicidal activity against D. sanguinalis at 750 g ai per ha. More importantly, pyrimidine-tetrahydrocarbazole hybrid 5q showed good to excellent herbicidal activity against five test weeds at the same dosage. Pyrimidine-tetrahydrocarbazole hybrids represent a novel class of herbicidal agents that may become promising lead compounds in the herbicidal discovery process.

A polysaccharide from green tea (Camellia sinensis L.) protects human retinal endothelial cells against hydrogen peroxide-induced oxidative injury and apoptosis.

Oxidative damage of retinal pigment epithelium (RPE) cells is involved in the pathogenesis age related macular degeneration (AMD). The purpose of this study was to evaluate the potential protective effect of a purified green tea polysaccharide (GTWP) against hydrogen peroxide (H2O2) induced oxidative stress and apoptosis in human retinal pigment epithelial cells (ARPE-19 cells). Human ARPE-19 cells were treated with 1 h of 500 µM H2O2 before incubation with GTWP for 24 h. Pretreatment of GTWP decreased H2O2-induced cell death and cell apoptosis, and efficiently suppressed the intracellular ROS production and malondialdehyde (MDA) generation induced by H2O2 treatment. Moreover, a loss of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) activities were restored to normal level in H2O2-induced ARPE-19 cells upon GTWP (100 µg/ml) exposure. Also, the tendency of increased protein expression of Bax and cleaved-caspsae-3, as well as decrease of Bcl-2 protein in ARPE-19 cells challenged with H2O2 was changed to individual opposite way, thus inhibiting the apoptotic cell death. Our results demonstrated that GTWP protected RPE cells against oxidative injury through activation of anti-apoptotic and endogenous antioxidant enzymes signaling pathway, suggesting GTWP has attractive therapeutic potential to AMD.

Comparison of optic nerve morphology in eyes with glaucoma and eyes with non-arteritic anterior ischemic optic neuropathy by Fourier domain optical coherence tomography.

The aim of this study was to compare the optic nerve head (ONH) and peripapillary retinal nerve fiber layer (RNFL) thickness in eyes with glaucoma and non-arteritic anterior ischemic neuropathy (NAION) by Fourier domain optical coherence tomography (FDOCT), and to evaluate the diagnostic capability of FDOCT in glaucoma and NAION. This study included 26 eyes with glaucoma (36.6%), 15 eyes with NAION (21.1%) and 30 eyes of normal subjects (42.3%). Those with the following conditions were excluded; a visual field defect greater than one hemifield, spherical equivalent (SE) more than ±6 D, or the onset of NAION within 6 months. FDOCT was used to analyze the characteristics of ONH and RNFL thickness. Among the three groups of subjects, glaucomatous eyes had the largest cup area and cup volume, and the smallest rim area, rim volume and disc volume (P<0.05). NAION eyes had the smallest cup area and cup volume (P<0.05), but their rim area, rim volume and disc volume were comparable to those of control eyes (P>0.05). The cup-to-disc (C/D) ratio was increased in glaucomatous eyes but reduced in NAION eyes compared with control eyes. Glaucomatous eyes had the greatest loss of RNFL thickness in the temporal upper (TU), superior temporal (ST) and temporal lower (TL) regions (P<0.05), whereas NAION eyes had the smallest RNFL thickness in the superior nasal (SN) and nasal upper (NU) regions (P<0.05). The areas under the receiver operator characteristic curve (AROCs) of the temporal, superior and inferior RNFL in glaucomatous eyes were greater compared with that of the disc area (P<0.05). In addition, the AROCs of the temporal, superior and inferior RNFL were higher compared with that of nasal RNFL (P<0.05). The AROCs of all parameters for NAION were not significantly different, with the exception of superior, nasal superior and inferior temporal RNFL (P<0.05). In conclusion, FDOCT is able to detect quantitative differences in the optic disc morphology and RNFL thickness between glaucomatous and NAION eyes. These differences may provide new insights into the clinical characteristics and diagnosis of the two diseases.

Endonasal endoscopic treatment of recurrent dacryocystitis.

This report assessed clinical conditions leading to recurrent dacryocystitis and success rates of its treatment by endonasal endoscopic dacryocystorhinostomy. Forty-eight patients with recurrent dacryocystitis underwent endonasal endoscopic surgery and were followed up for at least 6 months. High bone windows, small bone window openings, small lacrimal sac stomas, scar tissues, and organic diseases of the nasal cavity led to fistula closure. Out of 48 patients, 45 (93.8%) patients were cured by endonasal endoscopic surgery. Endonasal endoscopic dacryocystorhinostomy is beneficial for recurrent dacryocystitis.

Analysis and curative effect of ocular ischemic diseases caused by carotid artery stenosis.

Carotid artery stenosis is a notable cause of ocular ischemic disease. To analyze the ocular ischemic diseases caused by carotid artery stenosis and to seek effective treatment, a retrospective review of 182 patients with carotid artery stenosis was performed. These patients were administered medical treatment, carotid artery stenting (CAS) or carotid endarterectomy (CEA) and the curative effects of the three different treatments were compared. The results demonstrated that all three treatments helped to improve the disease. Both carotid endarterectomy and carotid artery stenting were more effective than medical treatment (P<0.05). There was no significant difference between carotid endarterectomy and carotid artery stenting (P>0.05). In conclusion, timely diagnosis and suitable treatment for ocular ischemic diseases caused by carotid artery stenosis are necessary due to the complicated clinical manifestation. This study suggested that carotid endarterectomy and carotid artery stenting are effective techniques that may relieve this disease.

Clinical study in patients with ocular ischemic diseases treated with enhanced external counterpulsation combined with drugs.

The aim of this study was to evaluate the clinical effect in patients with ocular ischemic diseases treated with enhanced external counterpulsation (EECP) combined with drugs. A total of 65 patients with carotid artery stenosis were included in this study. Group A consisted of 31 patients (43 eyes) treated with EECP and medication, and group B consisted of 34 patients (49 eyes) treated with medication alone. The clinical effect was analyzed by comparing the visual acuity, visual fields and optical hemodynamics between the two groups of patients. Ocular ischemic diseases mainly included ischemic optic neuropathy, central (branch) retinal artery occlusion, ophthalmoplegia externa and ocular ischemic syndrome. Significant improvement of visual acuity, visual fields and optical hemodynamics was observed in the patients of group A, and statistically significant differences were found between groups A and B (χ2=4.935, 7.124 and 5.478, respectively; P<0.05). In conclusion, ophthalmologists should observe for ocular ischemic diseases. The symptoms of the disease and the vision of the patient could be effectively improved by EECP, which has no evident complications.