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Ocular diseases featuring pathologic neovascularization are the leading cause of blindness, and anti-VEGF agents have been conventionally used to treat these diseases. Recently, regulating factors upstream of VEGF, such as HIF-1α, have emerged as a desirable therapeutic approach because the use of anti-VEGF agents is currently being reconsidered due to the VEGF action as a trophic factor. Here, we report a novel scaffold discovered through the complete structure−activity relationship of ring-truncated deguelin analogs in HIF-1α inhibition. Interestingly, analog 6i possessing a 2-fluorobenzene moiety instead of a dimethoxybenzene moiety exhibited excellent HIF-1α inhibitory activity, with an IC 50 value of 100 nM. In particular, the further ring-truncated analog 34f, which showed enhanced HIF-1α inhibitory activity compared to analog 2 previously reported by us, inhibited in vitro angiogenesis and effectively suppressed hypoxia-mediated retinal neovascularization. Importantly, the heteroatom-substituted benzene ring as a key structural feature of analog 34f was identified as a novel scaffold for HIF-1α inhibitors that can be used in lieu of a chromene ring.

Direct-writing systems will be leading the future of additive manufacturing in that they have simple and cost-effective processes. There are various types of direct-writing systems, such as the roll-to-roll (R2R), microdispensing deposition write (MDDW), maskless mesoscale materials deposition (M3D), and ink-jet systems. These technologies are being used for the production of radio frequency identification tags (RFIDs), organic lightemitting diodes (OLEDs), light-emitting diodes (LEDs), flexible electronics, solar cells, antennas, etc. Recently, the standardization of printing materials and equipment has become a key issue in the printed electronics industry. The standardization of printed electronics can be categorized into four parts: equipment, materials, testing methods, and the education of this technology.

Removable partial denture (RPD) frameworks have been traditionally produced with the lost-wax casting technique, although the process is complex because the metal is melted at around 1400 C and the emission of toxic gasses requires a rigorous safety protocol. 1 The accuracy and reliability of RPD framework production can be problematic. 2 In the past 20 years, digital technologies have improved in accuracy, reliability, and repeatability, and currently computer-aided design and computer-aided manufacturing (CAD-CAM), including selective laser melting (SLM), plays an important role in the production of dental prostheses. [3][4][5] SLM 3D printers are used to fabricate metal crowns, copings, and fixed partial denture frameworks, which are typically small components that are not severely deformed by residual heat stress. 6 The deformation of prostheses between the casting and SLM processes has been compared. However, deformation of larger RPD frameworks made by SLM has been described, with physical distortion and bending being observed, a deformation that originates from the residual heat stress caused by thermal expansion of the metal during the laser melting process. 7 Therefore, heat treatment after processing is essential to release the residual heat stress from the 3D-printed metal parts. This process influences the mechanical properties of the metal specimens, and therefore, the method of heat treatment Supported by the Ministry of Trade, Industry and Energy (MOTIE, Korea) (grant number 20001221).

No abstract