Does public health policy quality foster state innovation capacity? Evidence from a global panel data.

The design and implementation of public health policy may shape state innovation capacity with governance effectiveness, political stability, and government integrity. Previous studies, however, failed to incorporate these relationships simultaneously. This study aims to combine two distinct scholarships to examine whether the quality of policies in the public health sector contributes to state innovation capacity. We extracted data from the WHO international health regulatory dataset covering the WHO Member States between 2010 and 2017 to investigate the relationship (N = 145). Our fixed-effects models and regression discontinuity design (RDD) suggest a positive impact of public health policy quality on state innovation capacity. There are several contributions to the study of the relationship between public health and innovation in this study. Firstly, it fills a theoretical void concerning the relationship between policy development and implementation in the public health sector and country-specific innovations. Second, it provides an empirical quantitative analysis of policy quality in the public health sector. Third, this study contributes evidence that public health plays an important role in fostering state innovation beyond urbanization, investment in science and technology, and foreign trade. Furthermore, our quasi-experimental evidence found that this mechanism may be significant only between the more politically stable countries and the most politically stable countries. These contributions have empirical implications for governments across the world that seek to balance public health and innovation capacity in the context of the post-pandemic era.

Investigation of children's habits of smartphone usage and parental awareness of myopia control in underdeveloped areas of China.

AIM: To investigate the behaviors of smartphone usage and parental knowledge of vision health among primary students in the rural areas of China. METHODS: In this school-based, cross-sectional study, a total of 52 606 parents of students from 30 primary schools in the Xingguo County were investigated through an online questionnaire from July 2020 to August 2020. The self-designed questionnaire contained three parts: the demographic factors of both children and parents, parental knowledge and attitude toward myopia, and the preventive treatment of myopia. RESULTS: A total of 52 485 appropriately answered questionnaires were received, showing an effective response rate of 95.1%. The average age of the primary students was 10.1±0.98y and the prevalence of myopia among the primary students was 40.3%. The age of myopia occurrence in elementary students was significantly correlated with the parents' educational level (95%CI: 0.82-0.98, P=0.013), children's gender (95%CI: 1.08-1.20, P<0.001), school location (county or countryside) (95%CI: 0.59-0.66, P<0.001), children's smartphone ownership (95%CI: 1.09-1.26, P<0.001), and the average time spent on smartphone per day (95%CI: 0.78-0.88, P<0.001). School location in the county town, high family income, and high parents' educational level significantly affected both parents' myopia awareness and children's vision-threatening behaviors (P<0.01). Left-behind children showed a higher incidence of vision-threatening habits than those who lived with their parents (P<0.01). CONCLUSION: The results reveal the current situation of myopia development among rural primary school students and their parents. This survey will serve as a guidance for designing myopic prevention policies in the rural areas of China.

A comparative and prospective study of corneal biomechanics after SMILE and FS-LASIK performed on the contralateral eyes of high myopia patients.

Background: To compare the corneal biomechanical changes after small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) with the same programmed optical zone (POZ) and similar refractive correction in patients with high myopia. Methods: In this prospective comparative study of the contralateral eye, 50 patients with high myopia with the same POZ and similar refractive correction who underwent SMILE in one eye and FS-LASIK in the other eye. Corneal biomechanical parameters and central corneal thickness (CCT) were measured using a Corvis ST II. All the patients were evaluated during follow-up visits beyond one year. Additionally, the corneal volume (CV) of the 10-mm diameter region was measured using a Pentacam. Results: Ambrosio relational thickness to the horizontal profile (ARTh) and stiffness parameter A1 (SP-A1) decreased significantly after SMILE and FS-LASIK, whereas deformation amplitude ratio 2.0 mm (DA ratio 2.0 mm) and integrated radius (IR) increased significantly in both groups. The ARTh and SP-A1 were greater after SMILE than those after FS-LASIK at all the follow-up visits. In addition, there were greater amounts of CCT and CV after SMILE compared with that after FS-LASIK. Moreover, a positive correlation was found between ARTh and SP-A1 and postoperative CCT, while a negative correlation was found between IR and DA ratio 2.0 mm and postoperative CCT. A moderate correlation was observed between SP-A1 and CV after both SMILE and FS-LASIK, whereas there were no relationships between CV and ARTh, IR, or DA ratio 2.0 mm. Conclusions: SMILE had greater CCT, CV, ARTh, and SP-A1 than FS-LASIK in high myopia with the same POZ and similar refractive correction. Our results demonstrated that SMILE had lesser effect on corneal biomechanics than FS-LASIK in high myopia. Keywords: Corneal biomechanics; Corvis ST II; small incision lenticule extraction (SMILE); femtosecond laser-assisted in situ keratomileusis (FS-LASIK); high myopia.

Comparison of DNA stability and its related genes of neurons derived from induced pluripotent stem cells and primary retinal neurons.

Maintaining DNA stability in induced pluripotent stem cells (iPSCs) and iPSCs-derived neurons is a challenge in their clinical application. In the present study, we compared DNA stability between primary retinal neurons and differentiated neurons. We found that the basal level of γ-H2AX phosphorylation, a specific marker of DNA breaks, was notably higher (~26-folds) in human iPSCs compared to iPSCs-derived neurons. However, iPSCs-derived neurons are more sensitive to UV treatment compared to primary rat retinal neurons (postnatal Day 1). UV treatment induced a significantly decreasing in the cell viability of iPSCs-derived neurons by ~76.1%, whereas ~20.8% in primary retinal neurons. After analyzing the expression levels of genes involved in DNA stability, such as Brca1, Ligase IV, Ku80, and Mre11, we found that Ku80 and its heterodimeric partner, Ku70 were positive in iPSCs-derived neurons. However, both Ku80 and Ku70 are not expressed in primary retinal neurons and cerebellar neurons. Similarly, both Ku80 and Ku70 are also expressed in 3D retinal organoids from human embryonic stem cells (ESCs), except for a few Map2-negative cells and the hyaloid vessels of mice E12.5 retinas. Hence, Ku80, and Ku70 are specifically expressed in stem cell-derived neurons. Moreover, using the Ku80 inhibitor Compound L, our data showed that Ku80 promotes the DNA stability and cell viability of iPSCs-derived neurons. Thus, our results demonstrated that iPSCs-, ESCs-derived neurons have specific characteristics of DNA stability. This study provides new insights into the neural differentiation of stem cells but might also warrant the future clinical application of stem cells in neurodegenerative diseases.

Tsp-1 is involved in DNA stability through Tgf-ß1 activation domain in cone photoreceptor 661 W cells.

Thrombospondin-1 (Tsp-1), a matricellular protein, could protect retinal neurons from endogenous or exogenous insults; however, its underlying mechanism remains unclear. Thus, this study aimed to investigate Tsp-1-mediated neuron-protection effect in retinal cells. Our data showed that Tsp-1 downregulation would aggravate UV irradiation-induced DNA damage in 661 W cells and cone photoreceptor cells. The increasing levels of poly (ADP ribose) polymer (PAR) and γ-H2AX in Tsp-1-silenced 661 W cells indicate severe DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). By utilizing an error-prone substrate, Tsp-1 silencing significantly increased deleted DNA end joining in 661 W cells with spontaneous DNA damage (SDD). Moreover, Tsp-1 is indirectly involved in DNA stability in 661 W cells as UV treatment caused a significant Tsp-1 decreasing in cytoplasm, but no obvious Tsp-1 alteration in cell nuclear of 661 W cells. Furthermore, our data indicate that Tgf-ß1 activation domain in Tsp-1 plays a critical role in DNA stability in 661 W cells through expressing mutated exogenous Tsp-1 and Tgf-ß inhibitor, LSKL. Therefore, this study provides new insights into the mechanism of the neuroprotective action positively mediated by Tsp-1, which might be a therapeutic target for the treatment of retinal pathology.

Prospective, Randomized, Contralateral Eye Comparison of Functional Optical Zone, and Visual Quality After SMILE and FS-LASIK for High Myopia.

PURPOSE: To compare the functional optical zone (FOZ) and visual quality after small-incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) in correcting high myopia. METHODS: Ninety-two eyes of 46 high myopic patients with the same programmed optical zone (POZ) received SMILE in one eye and FS-LASIK in the contralateral eye. FOZ was calculated using a refractive power method. The decentration, visual outcomes, wavefront aberrations, contrast sensitivity, and quality of vision (QoV) questionnaire were analyzed at 6 months postoperatively. RESULTS: The postoperative visual and refractive outcomes were comparable between SMILE and FS-LASIK. The FOZ for SMILE (5.62 ± 0.31 mm) was larger than for FS-LASIK (5.35 ± 0.28 mm; P < 0.001). Moreover, the total decentration for SMILE (0.29 ± 0.14 mm) was greater than in FS-LASIK (0.22 ± 0.11 mm; P < 0.001). The induced change in spherical aberration was less for SMILE than for FS-LASIK (P < 0.001). There was better contrast sensitivity under the mesopic condition with glare for SMILE than for FS-LASIK (P = 0.024). However, no significant difference was found in QoV scores between the two groups. CONCLUSIONS: SMILE created a larger FOZ and greater decentration than FS-LASIK when the same POZ was designed in high myopia. Objective and subjective visual symptoms were comparable between SMILE and FS-LASIK. TRANSLATIONAL RELEVANCE: The differences in FOZ and decentration between SMILE and FS-LASIK have little effect on vision outcomes. Surgeons should consider the FOZ and decentration in surgical options in high myopia.

Predictability of Central Corneal Stromal Reduction After SMILE and FS-LASIK for High Myopia Correction: A Prospective Randomized Contralateral Eye Study.

PURPOSE: To compare small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) in terms of the predictability of central stromal thickness reduction in eyes with high myopia. METHODS: In this prospective, randomized contralateral eye trial, 42 patients received SMILE in one eye and FS-LASIK (using the Amaris 750S excimer laser [SCHWIND eye-tech-solutions]) in the fellow eye for the correction of high myopia (manifest refraction spherical equivalent: < -6.00 diopters). Spectral-domain optical coherence tomography was used to measure the central corneal and epithelial thickness. Pre-operative and postoperative values were compared to determine the amount of central stromal reduction achieved. RESULTS: At the 6-month follow-up visit, the amount of central stromal reduction was overestimated by 20.05 ± 5.92 µm in the SMILE group (P < .0001) and underestimated by 8.21 ± 8.14 µm in the FS-LASIK group (P < .0001). The mean actual central stromal reduction achieved with SMILE was significantly less than that achieved with FS-LASIK (10.10 ± 18.01 µm, range: 1.90 to 18.29 µm, P < .001). The discrepancy between the planned and achieved central corneal stromal reduction was not associated with refractive overcorrection or undercorrection in either the SMILE group or the FS-LASIK group (P = .9743 vs P = .0777). CONCLUSIONS: In patients with high myopia, the laser software platform may underestimate and overestimate the amount of actual corneal reduction in eyes treated with FS-LASIK and SMILE, respectively. SMILE required less corneal stroma compared to FS-LASIK in the studied cohort using the Amaris 750S excimer laser when correcting a similar spherical equivalent refraction. [J Refract Surg. 2022;38(2):90-97.].

Soy isoflavones alleviate polycystic ovary syndrome in rats by regulating NF- κB signaling pathway.

Soy isoflavones have been widely used in the treatment of clinical gynecological diseases. The aim of this study was to investigate the therapeutic effect and molecular mechanism of Soy isoflavones on rats with polycystic ovary syndrome (PCOS). Sprague-Dawley rats were orally administered 1 mg/kg letrozole for 21 consecutive days to induce the PCOS rat model. After PCOS induction, Soy isoflavones (100 mg/kg) or metformin (Positive control; 500 mg/kg) was administered continuously for 28 days. Then, H&E staining was used to observe the pathological changes of ovary. The serum hormone levels and the levels of antioxidant and inflammatory cytokines in ovarian tissue were detected. Additionally, the expression of NF-κB signaling pathway protein was detected by Western blot. Our results showed that soy isoflavones treatment significantly reduced the body weight, ovarian volume and weight, and improved estrous cycle in PCOS rats. H&E staining showed that the number of cystic dilated follicles and atretic follicles in ovarian tissue diminished, showing healthy follicles and corpus luteum. In addition, soy isoflavones treatment markedly decreased serum testosterone and luteinizing hormone (LH) levels, as well as oxidative stress levels and inflammation levels, and increased estradiol (E2) and follicle stimulating hormone (FSH) levels. At the same time, Soy isoflavones treatment inhibit the phosphorylation level of NF-κB p65 and increased the IκBα expression in ovarian tissues of PCOS rats. Overall, Soy isoflavones can improve ovarian morphology and hormone disorders in PCOS rats by inhibiting the activity of NF-κB pathway and enhancing anti-inflammatory and antioxidant capacity.

Ubiquitination-Related miRNA-mRNA Interaction Is a Potential Mechanism in the Progression of Retinoblastoma.

Purpose: Retinoblastoma (RB) is the most common primary malignant intraocular cancer. The etiology of RB is complex, and the mechanisms driving its progression remain unclear. Here, we used a series of bioinformatics approaches and experimental methods to investigate the potential regulatory mechanism involved in RB progression. Methods: The common differentially expressed genes were obtained from the public dataset GSE97508. Protein-protein interaction (PPI) network, correlation, and functional enrichment analyses were carried out. The candidate genes were verified in different RB cell lines, and ARPE19 cells served as control. miRNA-mRNA interaction analysis was performed and confirmed by real-time PCR. The CCK-8 assay was conducted to detect cell viability, and the transwell assay was utilized for evaluating the abilities of cell migration and invasion. Results: Overall, a total of 258 common differentially expressed genes associated with RB progression were screened out. The PPI network analysis further identified eight downregulated genes mainly enriched in the protein ubiquitination pathway. Moreover, we confirmed UBE2E1, SKP1, FBXO9, FBXO15, and RNF14 from among eight genes through experimental validation in vitro. Furthermore, miRNA-mRNA interaction and real-time PCR analysis of five hub genes revealed that ubiquitination-related miR-548k was involved in RB progression. Loss- and gain-of-function experiments demonstrated that miR-548k and its targets were essential for cell viability, migration, and invasion in the RB cells. Conclusions: Our data indicate that the dysregulation of protein ubiquitination may play an important role in RB progression, and ubiquitination-related miR-548k may be a promising therapeutic target for RB.

Retinoblastoma cell-derived exosomes promote angiogenesis of human vesicle endothelial cells through microRNA-92a-3p.

Exosomes derived from tumor cells play a key role in tumor development. In the present study, we identified the bioactivity of exosomes released from WERI-Rb1 retinoblastoma cells in tumor angiogenesis, as well as the underlying mechanism, through biochemical methods and animal experiments. Our in vitro data showed that exosomes could be engulfed by human vesicle endothelial cells (HUVECs), significantly promote cell viability and induce an inflammatory response in HUVECs by increasing the expression of a series of related genes, such as IL-1, IL-6, IL-8, MCP-1, VCAM1, and ICAM1. Significant increases in migration and tube formation were also observed in the HUVECs incubated with exosomes. Moreover, experiments with a nude mouse xenotransplantation model showed that exosomes injected near tumors could be strongly absorbed by tumor cells. The numbers of endothelial cells and blood vessels were significantly increased in tumor tissues treated with exosomes compared to control tissues. Furthermore, to reveal the mechanism underlying exosome-mediated angiogenesis in retinoblastoma, we analyzed the levels of 12 microRNAs in the exosomes. Specifically, our data showed that miR-92a-3p was enriched in RB exosomes. Accordingly, miR-92a-3p was increased in the HUVECs incubated with these exosomes. After treatment with a miR-92a-3p inhibitor, the promoting effect of exosomes on the migration and tube formation of HUVECs was significantly abrogated. The expression of the angiogenesis-related genes mentioned above was markedly decreased in HUVECs. Similarly, treatment with a microRNA mimic also demonstrated that miR-92a-3p was involved in the angiogenesis of HUVECs. More importantly, bioinformatics analysis predicted that Krüppel-like factor 2 (KLF2), a member of the KLF family of zinc-finger transcription factors, might be an active target of miR-92a-3p. Notably, this prediction was confirmed both in vitro and in vivo. Thus, our work suggests that exosomal miR-92a-3p is involved in tumor angiogenesis and might be a promising therapeutic candidate for retinoblastoma.

Tetramethylpyrazine attenuates endotoxin-induced retinal inflammation by inhibiting microglial activation via the TLR4/NF-κB signalling pathway.

Ocular inflammation is a common pathological condition of a series of retinal degenerative diseases. Tetramethylpyrazine (TMP), a Chinese herbal extraction, is widely used in the treatment of several ocular diseases in Eastern countries. However, the exact mechanisms correlating the vision protective effects of TMP have not been elucidated. Thus, this study aimed to investigate TMP's molecular targets in anti-inflammatory activity in endotoxin lipopolysaccharide (LPS)-induced retinal inflammation both in vitro and in vivo. The primary cultured retinal microglial cells were pretreated with TMP and then activated by LPS. We found pretreatment with TMP significantly inhibited LPS-induced upregulation of CD68, a marker of mononuclear microglia activation. The morphological changes induced by LPS were also inhibited by the TMP pretreatment. Moreover, Toll like receptor 4 (TLR4), phosphorylation of inhibitor of NF-κB alpha (p-IκB-α) and the translocation of nuclear factor kappa B p65 (NF-κB p65) were significantly downregulated in retinal microglial cells with TMP pretreatment, which indicated that TMP might suppress LPS-induced retinal microglial activation through TLR4/NF-κB signalling pathway. And these results were confirmed in vivo. Pretreatment with TMP inhibited microglial activation, migration and regeneration, especially in ganglion cell layer (GCL). In addition to the inhibition of TLR4, TMP significantly inhibited the translocation of NF-κB p-65 to the nucleus in vivo. The downstream genes of NF-κB, such as the pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and interleukin-1ß (IL-1ß), were significantly downregulated by TMP pretreatment in the retina. Accordingly, the increased expression of cleaved caspase-3 and the decreased ratio of B-cell lymphoma-2 (Bcl-2) to Bcl-2 associated X Protein (Bax) were significantly attenuated by TMP. TUNEL assay also demonstrated that TMP exerted neuroprotective effects in the retina. Therefore, this study elucidated a novel mechanism that TMP inhibits retinal inflammation by inhibiting microglial activation via a TLR4/NF-κB signalling pathway.

Subchronic toxicity and hepatocyte apoptosis of dietary olaquindox in common carp (Cyprinus carpio).

Olaquindox as one of the effective antimicrobial agents and growth-promoting feed additives, had been widely used in animal and fish production. However, few studies have been done to unveil its possible toxic effect and tissue injury on aquatic animal. In this study, the toxic effect and underlying mechanisms of olaquindox toxicity were investigated in common carp when feed with different doses of olaquindox for 90 days. The morbidity and mortality, pathological changes, hematology parameters, residue concentration in the tissues of common carp were assessed, hepatocyte apoptosis was detected through ultrastructural observation and flow cytometry methods. The results showed that the morbidity and mortality increased with the increasing dosages of dietary olaquindox, subchronic exposure to olaquindox caused remarkably pathological changes, including congestion and bleeding, intramuscular edema, vacuolar degeneration, degeneration and deformation in renal tubules architecture, respiratory epithelium fusion and intestinal epithelial microvilli disintegration. Besides, dietary olaquindox led to significant changes in blood biochemical parameters including red blood cell, hemoglobin, alanine aminotransferase and aspartate aminotransferase, an elevated residue concentration of olaquindox was detected in liver and kidney after exposure, hepatocyte apoptosis and necrosis were observed. Moreover, insulin-like growth factor I (IGF-I) mRNA level in liver was higher than normal level with the dose below 25 mg/kg olaquindox and was lower than normal level with the dose above 50 mg/kg. Our results demonstrated that dietary olaquindox may pose subchronic toxicity and residue in fish organs and provided scientific data for the safe application of olaquindox in fish.

Acute and Subacute toxicity study of Olaquindox by feeding to common carp (Cyprinus carpio L.).

Olaquindox, is a growth-promoting feed additive for food-producing animals. As the banned medicinal feed additive, olaquindox in animal feed and water must be concerned as an important hazard index. To improve studies of the toxicity of olaquindox, we provide a toxicological effects of olaquindox on a common freshwater fish, Cyprinus carpio L. The results of acute toxicity tests showed that the 7d-LD50 of olaquindox administered by feeding for common carp was determined to be 3746.3 mg/kg. We also found that the accumulation coefficient of olaquindox in carp was 1.45-1.9. Based on the studied hematological and blood biochemical parameters (RBCs count, hemoglobin content, ALT, AST and SOD activity), we found that olaquindox induced significant alterations in all studied parameters. Regarding bioaccumulation, the results showed that olaquindox had more efficiency to internalize fish tissues (liver, kidneys and muscle). The histopathological investigation of tissues from poisoning fish revealed various alterations that varied between adaptation responses and permanent tissue damage. Our results indicate that olaquindox are toxic to common carp and have obvious accumulation, and all the data from acute and subacute toxicity experiments in common carp may provide a useful tool for assessing the toxicity of olaquindox to aquatic organisms.