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BackgroundAntibody-drug conjugates (ADCs) have emerged as the focus and hotspots in the cancer field, yet the accompanying ocular toxicity has often been underestimated. We aimed to comprehensively and comparatively analyze the risk of ocular toxicity associated with various ADCs using the FDA Adverse Event Reporting System (FAERS) database.MethodsData were extracted from the FAERS database from Q3 2011 to Q3 2023. We analyzed the clinical characteristics of ADCs-related ocular adverse events (AEs). These data were further mined by proportional analysis and Bayesian approach to detect signals of ADCs-induced ocular AEs. Moreover, the time to onset of ocular toxicity was also evaluated.ResultsA total of 1,246 cases of ocular AEs were attributed to ADCs. Ocular toxicity signals were observed in patients treated with belantamab mafodotin, brentuximab vedotin, enfortumab vedotin, mirvetuximab soravtansine, sacituzumab govitecan, trastuzumab deruxtecan, and trastuzumab emtansine. Of these, belantamab mafodotin, trastuzumab emtansine, and mirvetuximab soravtansine, whose payloads are microtubule polymerization inhibitors, were more susceptible to ocular toxicity. The ten most common ADCs-related ocular AEs signals are keratopathy [ROR = 1,273.52, 95% CI (1,129.26–1,436.21)], visual acuity reduced [ROR = 22.83, 95% CI (21.2–24.58)], dry eye [ROR = 9.69, 95% CI (8.81–10.66)], night blindness [ROR = 259.87, 95% CI (228.23–295.89)], vision blurred [ROR = 1.78, 95% CI (1.57–2.02)], photophobia [ROR = 10.45, 95% CI (9.07–12.05)], foreign body sensation in eyes [ROR = 23.35, 95% CI (19.88–27.42)], ocular toxicity [ROR = 144.62, 95% CI (117.3–178.32)], punctate keratitis [ROR = 126.21, 95% CI (101.66–156.69)], eye disorder [ROR = 2.71, 95% CI (2.21–3.32)]. In terms of onset time, sacituzumab govitecan displayed an earlier onset of 21 days, while trastuzumab deruxtecan exhibited the latest onset of 223 days.ConclusionADCs may increase the risk of ocular toxicity in cancer patients, leading to serious mortality. With the widespread application of newly launched ADCs, combining the FAERS data with other data sources is crucial for monitoring the ocular toxicity of ADCs. In addition, novel ocular toxicity signals not documented in product labeling were detected. Further research will be necessary to validate our findings in the future.

Culm color variation is an interesting phenomenon that contributes to the breeding of new varieties of ornamental plants during domestication. De-domesticated variation is considered ideal for identifying and interpreting the molecular mechanisms of plant mutations. However, the variation in culm color of bamboo remains unknown. In the present study, yellow and green culms generated from the same rhizome of Phyllostachys vivax cv. Aureocaulis (P. vivax) were used to elucidate the molecular mechanism of culm color formation. Phenotypic and physiological data showed that environmental suitability was higher in green culms than in yellow culms. High-throughput sequencing analysis showed 295 differentially expressed genes (DEGs) and 22 differentially expressed miRNAs (DEMs) in two different colored bamboo culms. There were 103 DEM-DEG interaction pairs, of which a representative “miRNA-mRNA” regulatory module involved in photosynthesis and pigment metabolism was formed by 14 DEM-DEG pairs. The interaction of the three key pairs was validated by qPCR and dual-luciferase assays. This study provides new insights into the molecular mechanism of miRNAs involved in P. vivax culm color formation, which provides evidence for plant de-domestication and is helpful for revealing the evolutionary mechanism of bamboo.

Plants employ an array of photoprotection mechanisms to alleviate the harmful effects of high light intensity. The violaxanthin cycle, which is associated with non-photochemical quenching (NPQ), involves violaxanthin de-epoxidase (VDE), and zeaxanthin epoxidase (ZEP) and is one of the most rapid and efficient mechanisms protecting plants under high light intensity. Woody bamboo is a class of economically and ecologically important evergreen grass species widely distributed in tropical and subtropical areas. However, the function of VDE in bamboo has not yet been elucidated. In this study, we found that high light intensity increased NPQ and stimulated the de-epoxidation of violaxanthin cycle components in moso bamboo (Phyllostachys edulis), whereas, samples treated with the VDE inhibitor (dithiothreitol) exhibited lower NPQ capacity, suggesting that violaxanthin cycle plays an important role in the photoprotection of bamboo. Further analysis showed that not only high light intensity but also extreme temperatures (4 and 42°C) and drought stress upregulated the expression of PeVDE in bamboo leaves, indicating that PeVDE is induced by multiple abiotic stresses. Overexpression of PeVDE under the control of the CaMV 35S promoter in Arabidopsis mutant npq1 mutant could rescue its NPQ, indicating that PeVDE functions in dissipating the excess absorbed light energy as thermal energy in bamboo. Moreover, compared with wild-type (Col-0) plants, the transgenic plants overexpressing PeVDE displayed enhanced photoprotection ability, higher NPQ capacity, slower decline in the maximum quantum yield of photosystem II (Fv/Fm) under high light intensity, and faster recovery under optimal conditions. These results suggest that PeVDE positively regulates the response to high light intensity in bamboo plants growing in the natural environment, which could improve their photoprotection ability through the violaxanthin cycle and NPQ.