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Granulocyte colony-stimulating factor (G-CSF) was reported to have a neuroprotective effect in a rat model of anterior ischemic optic neuropathy (rAION model). However, the therapeutic window and anti-inflammatory effects of G-CSF in a rAION model have yet to be elucidated. Thus, this study aimed to determine the therapeutic window of G-CSF and investigate the mechanisms of G-CSF via regulation of optic nerve (ON) inflammation in a rAION model. Rats were treated with G-CSF on day 0, 1, 2 or 7 post-rAION induction for 5 consecutive days, and a control group were treated with phosphate-buffered saline (PBS). Visual function was assessed by flash visual evoked potentials at 4 weeks post-rAION induction. The survival rate and apoptosis of retinal ganglion cells were determined by FluoroGold labeling and TUNEL assay, respectively. ON inflammation was evaluated by staining of ED1 and Iba1, and ON vascular permeability was determined by Evans Blue extravasation. The type of macrophage polarization was evaluated using quantitative real-time PCR (qRT-PCR). The protein levels of TNF-α and IL-1β were analyzed by western blotting. A therapeutic window during which G-CSF could rescue visual function and retinal ganglion cell survival was demonstrated at day 0 and day 1 post-infarct. Macrophage infiltration was reduced by 3.1- and 1.6-fold by G-CSF treatment starting on day 0 and 1 post-rAION induction, respectively, compared with the PBS-treated group (P<0.05). This was compatible with 3.3- and 1.7-fold reductions in ON vascular permeability after G-CSF treatment compared with PBS treatment (P<0.05). Microglial activation was increased by 3.8- and 3.2-fold in the early (beginning treatment at day 0 or 1) G-CSF-treated group compared with the PBS-treated group (P<0.05). Immediate (within 30 mins of infarct) treatment with G-CSF also induced M2 microglia/macrophage activation. The cytokine levels were lower in the group that received immediate G-CSF treatment compared to those in the later G-CSF treatment group (P<0.05). Early treatment with G-CSF stabilized the blood–ON barrier to reduce macrophage infiltration and induced M2 microglia/macrophage polarization to decrease the expressions of pro-inflammatory cytokines in this rAION model.

To investigate the effects of cerebrolysin (Cbl) on optic nerves (ON) and retinal ganglion cells (RGC) in a rat model of ON crush. Rats received intravitreal injection of Cbl (n=20), intra‐ON injection of Cbl (n=20), intraperitoneal injection (IPI) of Cbl (n=20), or phosphate buffered saline (PBS; n=20) every day for 2 weeks after ON crush injury. At 3 weeks post‐trauma, RGC density was counted by retrograde labeling with FluoroGold and visual function was assessed by flash visual‐evoked potentials. Activities of microglia after insults were quantified by immunohistochemical analysis of the presence of ED1 in the optic nerve. At 3 weeks postcrush, the densities of RGCs in the Cbl‐IVI group (1125 ± 166/mm2) and in the Cbl‐IPI treatment group (1328 ± 119/mm2) were significantly higher than those in the PBS group (641 ± 214/mm2). The flash visual‐evoked potential measurements showed that latency of the P1 wave was significantly shorter in the Cbl‐IVI‐ and Cbl‐IPI‐treated groups (105 ± 4 ms and 118 ± 26 ms, respectively) than in the PBS‐treated group (170 ± 20 ms). However, only Cbl IPI treatment resulted in a significant decrease in the number of ED1‐positive cells at the lesion sites of the ON (5 ± 2 cells/vs. 30 ± 4 cells/high‐power field in control eyes). Treatment with intra‐ON injection of Cbl was harmful to the optic nerve in the crush model. Systemic administration of Cbl had neuroprotective effects on RGC survival and visual function in the optic nerve crush model.

The tumor-suppressive activity of prostate apoptosis response-4 (Par-4) has been demonstrated in a variety of human cancers. In this study, for the first time to our knowledge, we demonstrated that a higher intensity of Par-4 was significantly correlated with a better response in patients with hypopharyngeal carcinoma undergoing radiotherapy alone or concurrent chemoradiotherapy. Mechanistically, an elevated expression of Par-4 induced apoptosis of hypopharyngeal carcinoma cells and sensitized cells toward chemotherapeutic agents or X-ray irradiation. Along with apoptotic incitation, intriguingly, autophagic flux also increased on Par-4 stimulation and contributed to cell death. Moreover, the expressions of multiple common regulators involved in apoptosis and autophagy were regulated by Par-4. Taken together, our results suggested a prognostic role of Par-4 in hypopharyngeal carcinoma and showed novel activity of Par-4 in apoptosis and autophagy induction.

As lithography moves into lower k1imaging, traditional illumination "source" shapes may perform marginally in resolving complex layouts. Subsequently hot-spots or warm-spots can result, leading to yield loss in production. Typically, lithographers solve such problems by modifying the local layout instead of optimizing the DOE (diffractive optical element) illumination shape. FlexRayTMcan easily implement freeform source shapes and allows a high degree of freedom in source optimization. Therefore, it becomes practical to use pixelated freeform sources to resolve hot spots or warm spots. In this paper, we investigate the use of freeform source optimization (SO) on a critical dynamic random access memory (DRAM) layer with warm spots to verify the effectiveness of a SO only flow using Tachyon SMO. In order to improve the warm spots without changing baseline performance for other patterns, we optimized not only the warm spot patterns of concern but also the critical reference patterns. Since the optimization minimizes EPE (edge placement error) and maximizes imaging quality for all enclosed patterns, the final optimized source shape performs similar to the baseline source for the base patterns while improving the performance of the warm spot pattern areas. Although the SO source is similar in shape to the baseline source, the optimized source provides enhanced depth of focus (DoF) for all warm spot patterns without suffering degradation in the normalized image log-slope (NILS) performance. Evaluation of the optimized SO source shows no obvious negative impact on modeled CDs across an array of L/S pattern combinations which cover all the pitches appearing in the periphery. Finally, the optimized source is demonstrated using ASML's FlexRayTMfor on-wafer evaluation. According to the observations from on-wafer experiments, consistent results to simulation are verified. Overall DoF for the identified warm spot patterns is definitely improved and no obvious pattern shape changes are found, as well. From the positive demonstration in simulation and on-wafer verification, the vast flexibility of the freeform source enables the SO flow with more powerful capability to improve local hot spot or warm spot problems without negatively impacting the other patterns.

The fluorescent reaction is that an organism or dye, excited by UV light (200-405 nm), emits a specific frequency of light; the light is usually a visible or near infrared light (405-900 nm). During the UV light irradiation, the photosensitive agent will be induced to start the photochemical reaction. In addition, the fluorescence image can be used for fluorescence diagnosis and then photodynamic therapy can be given to dental diseases and skin cancer, which has become a useful tool to provide scientific evidence in many biomedical researches. However, most of the methods on acquiring fluorescence biology traces are still stay in primitive stage, catching by naked eyes and researcher's subjective judgment. This article presents a portable camera to obtain the fluorescence image and to make up a deficit from observer competence and subjective judgment. Furthermore, the portable camera offers the 375nm UV-LED exciting light source for user to record fluorescence image and makes the recorded image become persuasive scientific evidence. In addition, when the raising the rate between signal and noise, the signal processing module will not only amplify the fluorescence signal up to 70 %, but also decrease the noise significantly from environmental light on bill and nude mouse testing.