The zinc finger protein ZFYVE21 is involved in immune signaling. Using humanized mouse models, primary human cells, and patient samples, we identified a T cell–autonomous role for ZFYVE21 in promoting chronic vascular inflammation associated with allograft vasculopathy. Ischemia-reperfusion injury (IRI) stimulated endothelial cells to produce Hedgehog (Hh) ligands, which in turn induced the production of ZFYVE21 in a population of T memory cells with high amounts of the Hh receptor PTCH1 (PTCH hi cells, CD3 + CD4 + CD45RO + PTCH1 hi PD-1 hi ), vigorous recruitment to injured endothelia, and increased effector responses in vivo. After priming by interferon-γ (IFN-γ), Hh-induced ZFYVE21 activated NLRP3 inflammasome activity in T cells, which potentiated IFN-γ responses. Hh-induced NLRP3 inflammasomes and T cell–specific ZFYVE21 augmented the vascular sequelae of chronic inflammation in mice engrafted with human endothelial cells or coronary arteries that had been subjected to IRI before engraftment. Moreover, the population of PTCH hi T cells producing high amounts of ZFYVE21 was expanded in patients with renal transplant–associated IRI, and sera from these patients expanded this population in control T cells in a manner that depended on Hh signaling. We conclude that Hh-induced ZFYVE21 activates NLRP3 inflammasomes in T cells, thereby promoting chronic inflammation.

Acute ocular hypertension (AOH) is the most important characteristic of acute glaucoma, which can lead to retinal ganglion cell (RGC) death and permanent vision loss. So far, approved effective therapy is still lacking in acute glaucoma. PANoptosis (pyroptosis, apoptosis, and necroptosis), which consists of three key modes of programmed cell death-apoptosis, necroptosis, and pyroptosis -may contribute to AOH-induced RGC death. Previous studies have demonstrated that melatonin (N-acetyl-5-methoxytryptamine) exerts a neuroprotective effect in many retinal degenerative diseases. However, whether melatonin is anti-PANoptotic and neuroprotective in the progression of acute glaucoma remains unclear. Thus, this study aimed to explore the role of melatonin in AOH retinas and its underlying mechanisms. The results showed that melatonin treatment attenuated the loss of ganglion cell complex thickness, retinal nerve fiber layer thickness, and RGC after AOH injury, and improved the amplitudes of a-wave, b-wave, and oscillatory potentials in the electroretinogram. Additionally, the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells was decreased, and the upregulation of cleaved caspase-8, cleaved caspase-3, Bax, and Bad and downregulation of Bcl-2 and p-Bad were inhibited after melatonin administration. Meanwhile, both the expression and activation of MLKL, RIP1, and RIP3, along with the number of PI-positive cells, were reduced in melatonintreated mice, and p-RIP3 was in both RGC and microglia/macrophage after AOH injury. Furthermore, melatonin reduced the expression of NLRP3, ASC,

Haze pollution in China has reshaped daily life for the Chinese and led to serious health issues. At the same time, the Chinese have enjoyed the rapid economic growth that has contributed to this pollution. While questionnaire-based studies have been conducted within certain regions of China to learn the public's opinions of haze pollution, little work has been done to understand how Chinese citizens value haze treatment in relation to their nation's economic growth at a nationwide scale. To fill this knowledge gap, this project conducted a nationwide investigation of Chinese opinions on the benefits of economic growth versus the disadvantages of haze pollution, as well as their responses to efforts by the Chinese government to combat haze and to the influence of haze on Chinese daily life and on personal health. The study also sought suggestions for combatting haze. In particular, an anonymous questionnaire consisting of 29 questions was given in the summer and fall of 2017 to 1233 people of different genders, ages, child statuses, educational backgrounds, occupations, living areas (rural, suburban, and urban), and living regions. The statistical Chi squared test was then used to identify the demographic group of respondents supporting the economic slowdown policy or requesting more efforts from the Chinese government to combat haze pollution. A multivariate statistical approach-principal component analysis-was further applied to visualize respondents' feedback on the impact of haze on their daily life and personal health, as well as the change of environment and economic conditions in the last 10 years. The results show that more than 50% of respondents, especially those with children, those between the ages of 31 to 50, and those living in high-pollution regions, supported the economic slowdown policy. Totally 40.63% of the entire group of respondents believed the government's efforts to control haze were small or very small. Only 27.84% of respondents held the opposite opinions. In total, 72.91% of respondents believed the environment in China became worse or much worse in the past 10 years; however, most responded positively to the idea of resolving the haze issue within 15 or more years. Haze has caused health issues in and around half of the respondents and has significantly reshaped their outdoor activities.

Purpose This study aimed to investigate the age-dependent anti-angiogenic capability of melatonin in choroidal neovascularization (CNV) and to explore the underlying molecular mechanisms. Methods In the present study, a laser-induced CNV model was established in both young (three months of age) and old (18 months of age) mice, and the size of CNV lesions and vascular leakage was detected by morphological and imaging examination. Next, Western blot and immunostaining were used to observe the levels of M2 markers, senescence-related markers, and molecules involved in IL-10/STAT3 pathway. Additionally, colivelin was used to study the effect of IL-10/STAT3 pathway activation on the expression of M2 markers and senescence-related markers by Western blot and immunostaining. Finally, the effects of colivelin on melatonin-induced reduction of CNV size and vascular leakage in mice at different ages were assessed using morphological and imaging examination. Results Our results revealed that aging promoted M2 macrophage/microglia polarization, and aggravated CNV and vascular leakage. Melatonin significantly inhibited the M2 polarization of senescent macrophage/microglia and reduced the CNV area and vascular leakage. Moreover, melatonin markedly suppressed IL-10/STAT3 pathway activation in the macrophage/microglia of old mice, and STAT3 activator colivelin reversed the suppressive effect of melatonin on M2 polarization of senescent macrophage/microglia and laser-induced CNV in old mice. Conclusions Our data demonstrated that melatonin significantly prevented the M2 polarization of senescent macrophage/microglia by inhibiting the IL-10/STAT3 pathway, and eventually attenuated senescence-associated CNV. These findings suggested that melatonin could serve as a promising therapeutic agent to treat CNV and other age-related ocular diseases.