Retinal Organoids over the Decade

Retinal organoids (ROs) are 3D tissue structures derived from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) in vitro, which characterize the structure and function of retina to a certain extent. Since 2011, mouse and human retinal organoids have been available, opening up new avenues for retinal development, disease and regeneration research. Over the decade, great progress has been made in the development of retinal organoids, which is reflected in the improvement of differentiation efficiency and development degree. At the same time, retinal organoids also show broad application prospects, which are widely used in the construction of disease models. On this basis, the mechanism of disease, drug screening and retinal regeneration therapy have been explored. Although retinal organoids have a bright future, the deficiency of their structure and function, the limitations of differentiation and culture, and the difference compared with embryonic retina still remain to be solved

Versatile Genome Engineering Techniques Advance Human Ocular Disease Researches in Zebrafish

Over recent decades, zebrafish has been established as a sophisticated vertebrate model for studying human ocular diseases due to its high fecundity, short generation time and genetic tractability. With the invention of morpholino (MO) technology, it became possible to study the genetic basis and relevant genes of ocular diseases in vivo. Many genes have been shown to be related to ocular diseases. However, the issue of specificity is the major concern in defining gene functions with MO technology. The emergence of the first- and second-generation genetic modification tools zinc-finger nucleases (ZFNs) and TAL effector nucleases (TALENs), respectively, eliminated the potential phenotypic risk induced by MOs. Nevertheless, the efficiency of these nucleases remained relatively low until the third technique, the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, was discovered. This review highlights the application of multiple genome engineering techniques, especially the CRISPR/Cas9 system, in the study of human ocular diseases in zebrafish

(9H-Carbazol-9-ylmeth­yl)diethyl­amine

The asymmetric unit of the title compound, C17H20N2, contains two mol­ecules, whose bond lengths and angles differ only slightly. In the crystal, neighbouring mol­ecules form pillar structures via edge-to-face π–π stacking inter­actions [edge-to-face distances = 3.538 (3) and 3.496 (3)Å]

The Origin of the Prompt Emission for Short GRB 170817A: Photosphere Emission or Synchrotron Emission?

The first gravitational-wave event from the merger of a binary neutron star system (GW170817) was detected recently. The associated short gamma-ray burst (GRB 170817A) has a low isotropic luminosity (~1047 erg s−1) and a peak energy E p ~ 145 keV during the initial main emission between −0.3 and 0.4 s. The origin of this short GRB is still under debate, but a plausible interpretation is that it is due to the off-axis emission from a structured jet. We consider two possibilities. First, since the best-fit spectral model for the main pulse of GRB 170817A is a cutoff power law with a hard low-energy photon index ($\alpha =-{0.62}_{-0.54}^{+0.49}$), we consider an off-axis photosphere model. We develop a theory of photosphere emission in a structured jet and find that such a model can reproduce a low-energy photon index that is softer than a blackbody through enhancing high-latitude emission. The model can naturally account for the observed spectrum. The best-fit Lorentz factor along the line of sight is ~20, which demands that there is a significant delay between the merger and jet launching. Alternatively, we consider that the emission is produced via synchrotron radiation in an optically thin region in an expanding jet with decreasing magnetic fields. This model does not require a delay of jet launching but demands a larger bulk Lorentz factor along the line of sight. We perform Markov Chain Monte Carlo fitting to the data within the framework of both models and obtain good fitting results in both cases

Hederagenin from the leaves of ivy (Hedera helix L.) induces apoptosis in human LoVo colon cells through the mitochondrial pathway

BACKGROUND: Colorectal cancer has become one of the leading cause of cancer morbidity and mortality throughout world. Hederagenin, a derivative of oleanolic acid isolated from the leaves of ivy (Hedera helix L.), has been shown to have potential anti-tumor activity. The study was conducted to evaluate whether hederagenin could induce apoptosis of human colon cancer LoVo cells and explore the possible mechanism. METHODS: MTT assay was used for evaluating cell viability while Annexin V-FITC/PI assay and Hoechst 33342 nuclear stainining were used for the determination of apoptosis and mitochondrial membrane potential. DCFH-DA fluorescence staining and flow cytometry were used to measure ROS generation. Real-time PCR and western blot analysis were performed for apoptosis-related protein expressions. RESULTS: MTT assay showed that hederagenin could significantly inhibit the viability of LoVo cells in a concentration-dependent and time-dependent manner by IC(50) of 1.39 μM at 24 h and 1.17 μM at 48 h. The apoptosis ratio was significantly increased to 32.46% and 81.78% by the induction of hederagenin (1 and 2 μM) in Annexin V-FITC/PI assay. Hederagenin could also induce the nuclear changes characteristic of apoptosis by Hoechst 33342 nuclear stainining under fluorescence microscopy. DCFH-DA fluorescence staining and flow cytometry showed that hederagenin could increase significantly ROS generation in LoVo cells. Real-time PCR showed that hederagenin induced the up-regulation of Bax and down-regulation of Bcl-2, Bcl-xL and Survivin. Western blotting analysis showed that hederagenin decreased the expressions of apoptosis-associated proteins Bcl-2, procaspase-9, procaspase-3, and polyADP- ribosepolymerase (PARP) were increased, while the expressions of Bax, caspase-3, caspase-9 were increased. However, there was no significant change on caspase-8. CONCLUSIONS: These results indicated that the disruption of mitochondrial membrane potential might contribute to the apoptosis of hederagenin in LoVo cells. Our findings suggested that hederagenin might be a promising therapeutic candidate for human colon cancer