Retinitis pigmentosa (RP) is a photoreceptor-degenerative disease caused by various mutations and is characterized by death of rod photoreceptor cell followed by gradual death of cone photoreceptors. The molecular mechanisms that lead to rod and cone death are not yet fully understood. Neuroinflammation contributes to the progression of many chronic neurodegenerative disorders. However, it remains to be determined how microglia contribute to photoreceptor disruption in RP. In this study, we explored the role of microglia as a contributor to photoreceptor degeneration in the rd10 mouse model of RP. First, we demonstrated that microglia activation was an early alteration in RP retinas. Inhibition of microglia activation by minocycline reduced photoreceptor apoptosis and significantly improved retinal structure and function and visual behavior in rd10 mice. Second, we identified that minocycline exerted its neuroprotective effects through both anti-inflammatory and anti-apoptotic mechanisms. Third, we found that Cx3cr1 deficiency dysregulated microglia activation and subsequently resulted in increased photoreceptor vulnerability in rd10 mice, suggesting that the Cx3cl1/Cx3cr1 signaling pathway might protect against microglia neurotoxicity. We concluded that suppression of neuroinflammatory responses could be a potential treatment strategy aimed at improving photoreceptor survival in human RP.

Objectives To investigate the role of hypoxia in vasculogenic mimicry (VM) of salivary adenoid cystic carcinoma (SACC) and the underlying mechanism involved. Materials and methods Firstly, wound healing, transwell invasion, immunofluorescence and tube formation assays were performed to measure the effect of hypoxia on migration, invasion, EMT and VM of SACC cells, respectively. Then, immunofluorescence and RT‐PCR were used to detect the effect of hypoxia on VE‐cadherin and VEGFA expression. And pro‐vasculogenic mimicry effect of VEGFA was investigated by confocal laser scanning microscopy and Western blot. Moreover, the levels of E‐cadherin, N‐cadherin, Vimentin, CD44 and ALDH1 were determined by Western blot and immunofluorescence in SACC cells treated by exogenous VEGFA or bevacizumab. Finally, CD31/ PAS staining was performed to observe VM and immunohistochemistry was used to determine the levels of VEGFA and HIF‐1α in 95 SACC patients. The relationships between VM and clinicopathological variables, VEGFA or HIF‐1α level were analysed. Results Hypoxia promoted cell migration, invasion, EMT and VM formation, and enhanced VE‐cadherin and VEGFA expression in SACC cells. Further, exogenous VEGFA markedly increased the levels of N‐cadherin, Vimentin, CD44 and ALDH1, and inhibited the expression of E‐cadherin, while the VEGFA inhibitor reversed these changes. In addition, VM channels existed in 25 of 95 SACC samples, and there was a strong positive correlation between VM and clinic stage, distant metastases, VEGFA and HIF‐1α expression. Conclusions VEGFA played an important role in hypoxia‐induced VM through regulating EMT and stemness, which may eventually fuel the migration and invasion of SACC.

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Cenozoic sedimentary successions along the southern margin of the Tarim Basin, western China, reach up to 10 km in thickness. The two studied sections, the Yecheng and Aertashi, comprise c. 4.5 km and c. 7.0 km of clastic sedimentary rocks respectively. The base of the Yecheng section has been dated palaeomagnetically to be about 8 Ma. Age control of the Aertashi section is based on 87Sr/86Sr measurements (for the basal marine bed), together with magnetostratigraphy and regional stratigraphic correlation. The lower part of each section is mainly composed of fine-grained mudstone and fine sandstone, which makes up the Wuqian Group (Miocene). The palaeoenvironment is low-energy, meandering and braided streams. The middle part is composed of red mudstone, sandstone with thin conglomerate beds, which make up the Artux Formation (Pliocene). The palaeoenvironment is a distal- to mid-fan environment. The uppermost part of the section, known as the Xiyu Formation (Plio-Pleistocene), consists of cobble and boulder conglomerate intercalated with massive siltstone lenses, which formed as proximal alluvial fan and aeolian deposits. Neogene red beds passing upward into upward-coarsening conglomerate and debris-flow deposits record the change in palaeoslope related to uplift of the northern margin of Tibetan Plateau.The formation of aeolian dunes at c. 8 Ma, and underlying playa lake deposits (as at Aertashi), may indicate an arid, enclosed basin in the southern Tarim after this time. Sedimentological characteristics, together with grain size distribution and geochemistry of siltstone bands in the Xiyu and Artux Formations, point to an aeolian origin. This indicates that the Taklimakan Desert and the regional climate regime may have been fully developed by the Early Pliocene. The onset of aeolian sedimentation in the southern Tarim Basin coincided with uplift of the northern Tibetan Plateau, as inferred from the lithofacies change. Tibetan Plateau uplift resulted in the shift of sedimentary environments northwards into the southern Tarim Basin, and could well have triggered the onset of full aridity in the Taklimakan region as a whole.