No abstract

Background: Genetic variants of high temperature requirement factor A1 (HTRA1) associate with AMD risk. Results: Growth differentiation factor 6 (GDF6) gene polymorphism significantly associated with AMD. HTRA1 knock-out mice display reduced blood vessel in retina and up-regulation of GDF6. Conclusion: HTRA1 regulates angiogenesis via TGF-␤ signaling by GDF6, a novel disease gene. Significance: This novel pathway of HTRA1 in regulation of vascularization is critical for understanding AMD pathogenesis.

Sweating during exercise, physical labor, or hot weather leads to a feeling of discomfort. The stuffiness, stickiness, and heaviness brought by sweat may promote negative emotions or disease. Clothing, textiles, and wearable devices exacerbate these problems by restricting evaporation of sweat. Here, a textile that can promote and enhance sweat evaporation by coupling wicking and polarization is reported. The wicking is produced by the wettability gradient and pore size, which make the surface moisture content of the textile in contact with the skin strictly 0%. The polarization is driven by a ferroelectric‐enhanced triboelectric textile. This textile degrades large‐sized water clusters into small‐sized water clusters or water monomers, so that the textiles have an excellent moisture evaporation rate (4.4 and 3.6 times faster than the cotton and polyester textiles, respectively). This work provides a new source of inspiration for quick‐drying textiles and also finds an attractive application for triboelectric technology.

Aberrant activation of β-catenin/Tcf-4 signaling has been implicated in human carcinogenesis, including colorectal cancer. In this study, we compared the effects of Tcf-4 knockdown with β-catenin knockdown on cell proliferation, apoptosis, and chemosensitivity in SW480 and HCT116 colon cancer cells using adenoviral vector-mediated short hairpin RNA (shRNA). Our results show that, compared to β-catenin knockdown, Tcf-4 knockdown more effectively inhibited colony formation, induced apoptosis, and increased 5-FU and oxaliplatin-mediated cytotoxicity in colon cancer cells. We further investigated the mechanisms involved in the different efficacies observed with β-catenin and Tcf-4 knockdown in colon cancer cells. FOXO4 is a member of the subfamily of mammalian FOXO forkhead transcription factors and plays a major role in controlling cellular proliferation, apoptosis, and DNA repair. Our data showed that the protein level of FOXO4 did not change after treatment with both β-catenin and Tcf-4 shRNA. However, β-catenin shRNA was found to increase the accumulation of phosphorylated FOXO4 S193 and decrease the expression of FOXO target genes p27Kip1 and MnSOD, whereas Tcf-4 shRNA showed the opposite effect. Therefore, compared to β-catenin knockdown, Tcf-4 knockdown shows better efficacy for inhibiting proliferation and inducing apoptosis of colorectal cancer cells, which may be related to increased FOXO4 transcriptional activity. These results suggest that Tcf-4 is an attractive potential therapeutic target for colorectal cancer therapy.

Traditional antidepressants are mainly based on the "monoamine hypothesis," aiming to increase dopamine, serotonin, and norepinephrine levels in the brain. [2] However, the slow onset time (≈four weeks) and limited efficacy (≈30% of patients do not respond to at least two antidepressants) cannot meet the growing clinical demand for the treatment of depression. [3] Therefore, it is of great importance and urgency to develop new antidepressants strategies. Accumulating evidence has indicated that inflammation plays an essential role in the pathogenesis of depression. [4] For example, previous studies have shown that patients with various inflammation-related diseases such as postpartum, [5] diabetes, [6] stroke, [7] coronavirus disease-19 (COVID-19) [8] , and cancer treated with interferon-alpha [9] are more likely to develop depression disorder. Peripheral inflammation elicits the secretion of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which can pass the blood-brain barrier (BBB) into the central nervous system, and activate and polarize microglial cells toward the pro-inflammatory M1 phenotype. [10] Then, the M1 polarized microglia cells further produce pro-inflammatory cytokines, which lead to neuronal dysfunction and the progress Increasing evidence suggests that activation of microglia-induced neuroinflammation plays a crucial role in the pathophysiology of depression. Consequently, targeting the central nervous system to reduce neuroinflammation holds great promise for the treatment of depression. However, few drugs can enter the brain via a circulatory route through the blood-brain barrier (BBB) to reach the central nervous system efficiently, which limits the pharmacological treatment for neuropsychiatric diseases. Herein, a light-responsive system named UZPM, consisting of blue-emitting NaYF 4 :Yb,