[Health Benefit Assessment of Coal-to-electricity Policy on PM2.5 Pollution in Beijing-Tianjin-Hebei Region].

To accurately assess the health benefits of the coal-to-electricity policy during the heating period in the Beijing-Tianjin-Hebei(BTH) Region, the premature deaths caused by PM2.5 before and after the implementation of the coal-to-electricity policy during the heating period in each district and county of the BTH Region were estimated, and the corresponding health loss values were calculated using the willingness to pay method. The results showed that the implementation of the coal-to-electricity policy in the BTH Region brought 1745 cases(95% CI:1443-1907) of health benefits and 2.38 billion yuan(95% CI:1.45-3.06) in economic benefits. In Beijing, Tianjin, and Hebei there were 495 cases(95% CI:436-554), 296 cases(95% CI:238-354), and 954 cases(95% CI:693-1076) of health benefits, respectively. The economic benefits were 0.35 billion yuan(95% CI:0.30-0.39), 0.33 billion yuan(95% CI:0.27-0.40), and 1.70 billion yuan(95% CI:0.88-2.28), respectively, accounting for 0.01%, 0.02%, and 0.04% of GDP in each region. The number of premature deaths due to COPD, LC, ALRI, IHD, and STROKE decreased by 187 cases(95% CI:165-224), 318 cases(95% CI:178-458), 193 cases(95% CI:115-204), 506 cases(95% CI:232-780), and 542 cases(95% CI:463-621), respectively. Areas with relatively high environmental PM2.5 concentrations and concentrated population-intensive pollution emissions can achieve significant health and economic benefits.

Generation of a gene-corrected isogenic iPSC cell line from an X-linked retinoschisis patient with a hemizygous mutation c.304C > T (p.R102W) in RS1 gene.

X-linked retinoschisis (XLRS) is one of the most common retinal genetic diseases with progressive visual impairment in childhood affecting males. It is manifested with macular and/or peripheral schisis in neural retinas with no effective treatment. Previously, we successfully generated a human-induced pluripotent stem cell (iPSC) line from an XLRS patient carrying the hemizygous RS1 c. 304C > T (p.R102W) mutation. Here, we corrected the c.304C > T mutation in the RS1 gene using CRISPR/Cas9 technology to generate an isogenic control. This cell line is valuable for the study of XLRS.

Human leukocyte antigen-G 14 bp insertion/deletion polymorphism contributes to preeclampsia risk in Asian population: A systematic review and meta­analysis.

Preeclampsia remains enigmatic and responsible for vast maternal and fetal morbidity and mortality worldwide. Our objective was to assess the strength of the effect of the 14 bp deletion/insertion polymorphism in exon 8 of the 3'UTR region of the human leukocyte antigen-G (HLA-G) gene on preeclampsia risk across different populations. A systematic review by a meta-analysis was performed to summarize the scattered epidemiologic evidence, which remains inconclusive and controversial. A systematic literature search according to the PRISMA guidelines was conducted to screen relevant publications. Odds ratio and corresponding 95% confidence interval were estimated to measure the magnitude of the association between this polymorphism and preeclampsia onset. Thirty studies comprising 9402 subjects were eligible. Pooled estimates suggested that both fetal and paternal insertion variants were significantly associated with increased odds of this disease. Nevertheless, the presence of the 14 bp insertion sequence in mothers does not seem to increase the risk of preeclampsia. Moreover, the results of subgroup analysis suggested that the fetal, maternal, and paternal polymorphism has a significant deleterious impact on the preeclampsia risk in the Asian population. In addition, the significant association between the paternal polymorphism and preeclampsia in primigravida was observed in the pooled estimation with a small sample size. By summarizing the amount of significant evidence, our study nominated this polymorphism as a potential biomarker for early risk stratification for Asians. Further large-scale validation is needed to establish fully solid and conclusive evidence for the impact of the insertion polymorphism on preeclampsia risk.

PDGF-C promotes cell proliferation partially via downregulating BOP1.

Platelet-derived growth factor C (PDGF-C) is a member of PDGF/VEGF family, which is well-known for important functions in the vascular system. It is widely reported that PDGF-C is able to modulate cell proliferation. However, it is still not very clear about this cell modulating mechanism at the molecular level. In a screening of factors regulated by PDGF-C protein, we fished out a factor called block of proliferation 1 (BOP1), which is a pivotal regulator of ribosome biogenesis and cell proliferation. In this study, we investigated the regulation of BOP1 by PDGF-C and its role in modulating cell proliferation. We found that BOP1 was downregulated at both mRNA and protein levels in cells treated with PDGF-C-containing conditioned medium. On the other hand, BOP1 was upregulated in PDGF-C deficient mice. Furthermore, we confirmed that overexpression of BOP1 inhibited HEK293A cell proliferation, whereas knockdown of BOP1 promoted cell proliferation. The mitogenic effect of PDGF-C could be attenuated by downregulation of BOP1. Our results demonstrate a clear PDGF-C-BOP1 signaling that modulates cell proliferation.

Glycosylation at Asn254 Is Required for the Activation of the PDGF-C Protein.

Platelet-derived growth factor C (PDGF-C) is a member of the PDGF/VEGF (vascular endothelial growth factor) family, which includes proteins that are well known for their mitogenic effects on multiple cell types. Glycosylation is one of the most important forms of posttranslational modification that has a significant impact on secreted and membrane proteins. Glycosylation has many well-characterized roles in facilitating protein processing and contributes to appropriate folding, conformation, distribution, and stability of proteins that are synthesized intracellularly in the endoplasmic reticulum (ER) and Golgi apparatus. Although the general process and functions of glycosylation are well documented, there are most likely others yet to be discovered, as the glycosylation of many potential substrates has not been characterized. In this study, we report that the PDGF-C protein is glycosylated at three sites, including Asn25, Asn55, and Asn254. However, we found that mutations at any of these sites do not affect the protein expression or secretion. Similarly, disruption of PDGF-C glycosylation had no impact on its progression through the ER and Golgi apparatus. However, the introduction of a mutation at Asn254 (N254 A) prevents the activation of full-length PDGF-C and its capacity for signaling via the PDGF receptor. Our findings reveal that glycosylation affects PDGF-C activation rather than the protein synthesis or processing. This study characterizes a crucial modification of the PDGF-C protein, and may shed new light on the process and function of glycosylation.

Severe fundus lesions induced by ocular jellyfish stings: A case report.

BACKGROUND: Globally, although the jellyfish population has increased in recent years, ocular jellyfish stings remain an uncommon ophthalmic emergency, and have been rarely reported. According to a few previous reports, ocular jellyfish stings may cause anterior segment disorders, and most of these injuries were self-limited and spontaneously resolved within 24 to 48 h. CASE SUMMARY: A brother and sister both presented with severe fundus complications several years after ocular jellyfish stings and both had prolonged blurred vision. To our knowledge, such fundus lesions induced by jellyfish stings have not been reported previously. CONCLUSION: The fundus status of patients following ocular jellyfish stings should be carefully monitored in cases of irreversible ocular damage.

Inhibitory effect of caveolin-1 in vascular endothelial cells, pericytes and smooth muscle cells.

Caveolin-1 (Cav1) is the principle structural protein of caveolae. It plays important roles in the vascular system under both physiological and pathological conditions. Although Cav1 has been shown to inhibit microvascular permeability and has been considered as a tumor-suppressor for years, the underlying cellular mechanism has yet to be discovered. Here, we systematically investigated Cav1 functions in the main types of vascular cells, including endothelial cells (ECs), pericytes (PCs) and smooth muscle cells (SMCs). We synthesized a cell-permeable peptide called cavtratin that is derived from the Cav1 scaffolding domain. We found that cavtratin inhibited ECs in all assays, including survival, proliferation, migration and permeability assays. It also inhibited the proliferation of PCs and SMCs but had no effect on their survival or migration. The inhibitory effect of cavtratin on the proliferation of all vascular cells suggests that Cav1 plays important roles in vascular development and angiogenesis. Under physiological condition, the main function of Cav1 is to inhibit EC permeability.

Caveolin-1 Protects Retinal Ganglion Cells against Acute Ocular Hypertension Injury via Modulating Microglial Phenotypes and Distribution and Activating AKT pathway.

Glaucoma, a group of eye diseases, causes gradual loss of retinal ganglion cells (RGCs) and ultimately results in irreversible blindness. Studies of the underlying mechanisms of glaucoma and clinical trial are far from satisfactory. Results from a genome-wide association study have suggested that the CAV1/CAV2 locus is associated with glaucoma, but this association and its potential underlying mechanisms need to be confirmed and further explored. Here, we studied the function of caveolin-1 (Cav1) in an acute ocular hypertension glaucoma model. Cav1 deficiency caused an aggregated lesion in the retina. In addition, treatment with cavtratin, a membrane permeable Cav1 scaffolding domain peptide, enhanced RGC survival. After cavtratin treatment, microglial numbers decreased significantly, and the majority of them migrated from the inner retinal layer to the outer retinal layers. Furthermore, cavtratin promoted a change in the microglia phenotype from the neurotoxic pro-inflammatory M1 to the neuroprotective anti-inflammatory M2. In a molecular mechanism experiment, we found that cavtratin activated the phosphorylation of both AKT and PTEN in cultured N9 cells. Our data highlights the neuroprotective effect of Cav1 on acute ocular hypertension and suggests that Cav1 may serve as a novel therapeutic target for the treatment of glaucoma. We further propose that cavtratin is a therapeutic candidate for glaucoma clinical trials.