MREDTA: A BERT and transformer-based molecular representation encoder for predicting drug-target binding affinity.

Drug-target binding affinity (DTA) prediction is vital for drug repositioning. The accuracy and generalizability of DTA models remain a major challenge. Here, we develop a model composed of BERT-Trans Block, Multi-Trans Block, and DTI Learning modules, referred to as Molecular Representation Encoder-based DTA prediction (MREDTA). MREDTA has three advantages: (1) extraction of both local and global molecular features simultaneously through skip connections; (2) improved sensitivity to molecular structures through the Multi-Trans Block; (3) enhanced generalizability through the introduction of BERT. Compared with 12 advanced models, benchmark testing of KIBA and Davis datasets demonstrated optimal performance of MREDTA. In case study, we applied MREDTA to 2034 FDA-approved drugs for treating non-small-cell lung cancer (NSCLC), all of which act on mutant EGFRT790M protein. The corresponding molecular docking results demonstrated the robustness of MREDTA.

Berberine Regulates GPX4 to Inhibit Ferroptosis of Islet ß Cells.

Ferroptosis, as a kind of non-apoptotic cell death, is involved in the pathogenesis of type 1 diabetes mellitus (T1DM). Islet B cells mainly produce insulin that is used to treat diabetes. Berberine (BBR) can ameliorate type 2 diabetes and insulin resistance in many ways. However, a few clues concerning the mechanism of BBR regulating ferroptosis of islet ß cells in T1DM have been detected so far. We measured the effects of BBR and GPX4 on islet ß cell viability and proliferation by MTT and colony formation assays. Western blot and qRT-PCR were utilized to examine GPX4 expression in islet ß cells with distinct treatments. The influence of BBR and GPX4 on ferroptosis of islet ß cells was investigated by evaluating the content of Fe2+ and reactive oxygen species (ROS) in cells. The mechanism of BBR targeting GPX4 to inhibit ferroptosis of islet ß cells was further revealed by the rescue experiment. Our results showed that BBR and overexpression of GPX4 could notably accelerate cell viability and the proliferative abilities of islet ß cells. Moreover, BBR stimulated GPX4 expression to reduce the content of Fe2+ and ROS, thereby repressing the ferroptosis of islet ß cells, which functioned similarly as ferroptosis inhibitor Fer-1. In conclusion, BBR suppressed ferroptosis of islet ß cells via promoting GPX4 expression, providing new insights into the mechanism of BBR for islet ß cells.

Selection Behavior and OBP-Transcription Response of Western Flower Thrips, Frankliniella occidentalis, to Six Plant VOCs from Kidney Beans.

Plant volatile organic compounds (VOCs) are an important link that mediates chemical communication between plants and plants, plants and insects, and plants and natural enemies of insect pests. In this study, we tested the response in the selective behavior of western flower thrips, Frankliniella occidentalis, to the VOCs of kidney bean, Phaseolus vulgaris L., to explore their "attraction" or "repellent" effects regarding their application in integrated pest management (i.e., IPM). The results indicated that 12.7 µL/mL (E, E, E, E)-squalene, 3.2 µL/mL dioctyl phthalate, and 82.2 µL/mL ethyl benzene had a significantly attractive effect on the selective behavior of F. occidentalis, while 10.7 µL/mL and 21.4 µL/mL 2,6-ditert-butyl-4-methyl phenol had a significantly repulsive effect on the selective behavior of F. occidentalis, showing that F. occidentalis responds differently to specific concentrations of VOCs from P. vulgaris plant emissions. Interestingly, the three compounds with the specific above concentrations, after being mixed in pairs, significantly attracted F. occidentalis compared to the control treatment; however, the mixture with the three above compounds had no significant different effect on F. occidentalis compared to the control treatment. It can be seen that the effect with the mixtures of three kinds of VOCs had the same function and may not get better. Simultaneously, the reasons for this result from the transcription levels of odorant-binding protein genes (OBPs) were determined. There were differences in the types and transcription levels of OBPs, which played a major role in the host selection behavior of F. occidentalis under the mixed treatment of different VOCs. It is presumed that there are specific VOCs from P. vulgaris plants that have a good repellent or attracting effect on the selective behavior of F. occidentalis, which can be used for the development of plant-derived insect attractants and repellents to serve as IPM in fields. But attention should be paid to the antagonism between plant-derived preparations and VOCs produced by plants themselves after application.

Inhibition of Oncogenic Src Ameliorates Silica-Induced Pulmonary Fibrosis via PI3K/AKT Pathway.

Silicosis is a refractory disease. Previous studies indicate that damaged alveolar epithelial cells act as a driver in pulmonary fibrosis. Our results show that epithelial cells that acquire the mesenchymal phenotype are associated with the pathogenesis of silicosis. c-Src kinase, a non-receptor tyrosine kinase, has been shown to be a positive regulator of organ fibrosis, but specific mechanisms remain unclear and rarely researched in silicosis. The activated Phosphatidylinositol-3 kinases/AKT(PI3K/AKT) pathway promotes fibrosis. We aimed to determine whether c-Src regulates fibrosis via the PI3K/AKT signaling pathway in the development of silicosis. C57/BL mice were intratracheally perfused with 10 mg silica suspension to establish a model of silicosis. In vivo, silica particles induced lung fibrosis. The profibrotic cytokine transforming growth factor-ß1 (TGF-ß1) exhibited a high expression in pulmonary fibrosis. The phosphorylated c-Src protein was increased and the PI3K/AKT pathway was activated in model lung tissue. In vitro, silica increased the expression of TGF-ß1- and TGF-ß1-induced mesenchymal phenotype and fibrosis in a mouse epithelial cells line. siRNA-Src inhibited the c-Src, the phosphorylation of the PI3K/AKT pathway, and the mesenchymal phenotype induced by TGF-ß1. LY294002, a specific inhibitor of PI3K, suppressed the phosphorylation of PI3K/AKT but did not affect Src activation. SU6656, a selective Src inhibitor, attenuated fibrosis in silicosis model. In summary, c-Src promotes fibrosis via the PI3K/AKT pathway in silica-induced lung fibrosis, and Src kinase inhibitors are potentially effective for silicosis treatment.

Long-term outcomes of Oxane Hd as intraocular tamponade in the treatment of complicated retinal detachment.

BACKGROUND: To evaluate the efficacy and safety of heavy silicone oil Oxane Hd as intraocular tamponade in the treatment of complicated retinal detachment (RD). METHODS: Forty eyes of 40 patients with complicated RD were recruited for this prospective study. Inclusion criteria were proliferative vitreoretinopathy grade > or = CP2, mainly inferior and posterior retinal breaks, or superior retinal breaks with patient's inability to posture. Oxane Hd was used as intraocular tamponade. The retinal status, the best-corrected visual acuity (BCVA) results, and any complications were observed. RESULTS: The mean duration of Oxane Hd endotamponade was 87.9 +/- 10.4 days, and the mean follow-up time after Oxane Hd removal was 438.1 +/- 153.7 days. The primary anatomical success rate after Oxane Hd removal was 87.5%, and with further intervention 97.5%. The BCVA significantly improved, from mean logMAR 2.12 +/- 0.60 to 1.38 +/- 0.59 (P < 0.001). The postoperative complications included temporary inflammatory reaction, moderately high intraocular pressure, heavy silicone oil emulsification, lens opacity and retinal proliferative membranes. CONCLUSIONS: Without a requirement for postoperative prone position, heavy silicone oil Oxane Hd is effective and safe for the treatment of complicated RD with inferior and posterior breaks. Larger groups and a longer follow-up period will be included to further evaluate the efficacy with Oxane Hd in superior retinal breaks.

Long-term anatomic and visual outcomes of initially closed macular holes.

PURPOSE: To evaluate the anatomic and visual outcomes in patients with initially closed macular holes after vitreoretinal surgery and with 1 to 7 years of follow-up. DESIGN: Retrospective, noncomparative, consecutive case series. METHODS: Eighty-seven consecutive eyes of 79 patients with previous closure of the macular holes and with at least 1 year of follow-up were reviewed in this retrospective clinical study. Main outcome measures included the rate of macular hole reopening and visual acuity outcomes. RESULTS: The mean age of enrolled patients was 63.1 ± 6.2 years (range, 49 to 74 years); the mean duration of macular hole was 5.6 ± 9.7 months (range, 0.25 to 60 months); and the mean follow-up interval was 38.4 ± 19.7 months (range, 12 to 86 months). All eyes underwent internal limiting membrane peeling during the vitrectomy, and 64 (73.6%) of 87 eyes underwent cataract extraction. No reopening of initially closed macular holes was observed in any eyes. Slight perifoveal epiretinal membranes were observed by optical coherence tomography in 32.2% of cases (28/87). The final best-corrected visual acuity improved to 0.47 ± 0.39 logarithm of the minimal angle of resolution units, which was significantly higher than preoperative visual acuity of 1.01 ± 0.36 logarithm of the minimal angle of resolution units (t = -12.532; P = .000). Multiple linear regression analysis demonstrated that the final best-corrected visual acuity was affected by the macular hole stage, preoperative best-corrected visual acuity, and cataract exaction (F = 19.858; P = .000). CONCLUSIONS: The stable closure of macular holes is achieved after vitrectomy with internal limiting membrane peeling. Phacoemulsification cataract surgery with intraocular lens implantation for improvement of visual function is not responsible for the reopening of previously closed macular holes.