Retinitis pigmentosa (RP) is a rare heterogeneous genetic retinal dystrophy disease, and despite years of research, known genetic mutations can explain only approximately 60% of RP cases. We sought to identify the underlying genetic mutations in a cohort of fourteen Indian autosomal recessive retinitis pigmentosa (arRP) families and 100 Indian sporadic RP cases. Whole-exome sequencing (WES) was performed on the probands of the arRP families and sporadic RP patients, and direct Sanger sequencing was used to confirm the causal mutations identified by WES. We found that the mutations of EYS are likely pathogenic mutations in two arRP families and eight sporadic patients. Specifically, we found a novel pair of compound heterozygous mutations and a novel homozygous mutation in two separate arRP families, and found two novel heterozygous mutations in two sporadic RP patients, whereas we found six novel homozygous mutations in six sporadic RP patients. Of these, one was a frameshift mutation, two were stop-gain mutations, one was a splicing mutation, and the others were missense mutations. In conclusion, our findings expand the spectrum of EYS mutations in RP in the Indian population and provide further support for the role of EYS in the pathogenesis and clinical diagnosis of RP.

Environmental performance is becoming increasingly essential for promoting local officials in China; thus, their pursuit of promotion may affect agricultural output. This study spatially matched Chinese local official promotion data, regional agricultural output, river-water-quality-monitoring stations, and riverside enterprise discharge data. Based on the difference-in-difference model, the exogenous impact of the natural experiment based on the promotion of officials is quantified as how the promotion behavior of local officials in pursuit of environmental achievements affects agricultural output. This was examined under the decentralization system of China’s environmental governance. The results show that local officials improve agricultural production by controlling environmental pollution through promotion incentives. However, since the central government can observe the regulatory effect of upstream officials through the readings of water monitoring stations, upstream officials strictly enforce the central environmental regulations due to promotion motivation, while downstream officials do not strictly enforce their counterparts. This can result in differentiated impacts on agriculture in upstream and downstream regions. We also carried out a parallel test, placebo test, and measurement error test for the quasi-natural experiment, and the conclusions derived from the analysis remained robust. Our study has important implications for designing compatible environmental governance contracts and incentive policies for promoting agricultural production.

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Environmental performance is increasingly important in promoting officials, whose pursuit of promotions and related behavior may affect the health of residents in their jurisdictions. In this study, we spatially matched Chinese river water quality monitoring station data, enterprise pollution emission data, and resident health data and quantified how Chinese officials pursuing promotions based on environmental performance affected resident health using a regression discontinuity design and difference-in-difference with interaction terms design strategy. The results show that the upstream–downstream disparity of environmental governance and pollutant emissions affects the residents’ health, medical treatment behavior, and medical expenditure. Furthermore, we identified the causal relationship between official promotion and upstream–downstream disparity and estimated the marginal effect of promotion on residents’ health. The study suggests that local officials limit the pollution emissions of enterprises in the upstream river to achieve environmental performance and relax the pollution restrictions of firms in the downstream river to achieve economic performance, such that the health of residents near the river is differentially affected.

Objectives: To explore the effects and mechanisms of different concentrations of uric acid on skeletal muscle cells. Methods: C2C12 myoblasts were differentiated into myotubes and then exposed to medium containing uric acid (0 μM, 200 μM, 400 μM, 600 μM, 800 μM, 1000 μM, 1200 μM, 1400 μM). The myotube diameters was observed under light microscopy; the expression of myosin heavy chain (MyHC), autophagy-related proteins (LC3BII/LC3BI, P62), cGAS, and p-sting/sting proteins was analysed using Western blotting or immunoprecipitation, and oxidative stress and mitochondrial damage were evaluated using ROS, mtDNA and JC-1 assays. Cell viability was measured via CCK8 assay, and 1000 μM uric acid was selected for follow-up experiments. Furthermore, C2C12 myotubes were divided into a blank control (Ctrl) group, a high-uric-acid group (HUA) and an HUA plus cGASn inhibitor (HUA+RU.521) group. Then, the myotube diameter was observed, oxidative stress and mitochondrial damage were evaluated, and MyHC and autophagy-related protein expression was analysed. Results: C2C12 myotubes cultured in 400 μM uric acid medium had the greatest myotube diameter and the highest MyHC protein expression. At 1000 μM uric acid, the diameter and MyHC protein expression were significantly decreased, LCB3II/LCB3I expression was notably increased, and the expression levels of p62 protein expression was considerably decreased. RU.521 partially alleviated the HUA-induced C2C12 myotubes changes. Conclusions: Uric acid bidirectionally affected C2C12 myotubes: 400 μΜ uric acid promoted myotube growth, while 1000 μΜ uric acid triggered myotube atrophy with increased autophagy. Inhibiting cGAS-sting signalling attenuated HUA-induced C2C12 myotube autophagy and atrophy.