The transcription factor hypoxia inducible factor-1α (HIF-1α) mediates adaptive responses to oxidative stress by nuclear translocation and regulation of gene expression. Mitochondrial changes are ...critical for the adaptive response to oxidative stress. However, the transcriptional and non-transcriptional mechanisms by which HIF-1α regulates mitochondria in response to oxidative stress are poorly understood. Here, we examined the subcellular localization of HIF-1α in human cells and identified a small fraction of HIF-1α that translocated to the mitochondria after exposure to hypoxia or H2O2 treatment. Moreover, the livers of mice with CCl4-induced fibrosis showed a progressive increase in HIF-1α association with the mitochondria, indicating the clinical relevance of this finding. To probe the function of this HIF-1α population, we ectopically expressed a mitochondrial-targeted form of HIF-1α (mito-HIF-1α). Expression of mito-HIF-1α was sufficient to attenuate apoptosis induced by exposure to hypoxia or H2O2-induced oxidative stress. Moreover, mito-HIF-1α expression reduced the production of reactive oxygen species, the collapse of mitochondrial membrane potential, and the expression of mitochondrial DNA-encoded mRNA in response to hypoxia or H2O2 treatment independently of nuclear pathways. These data suggested that mitochondrial HIF-1α protects against oxidative stress induced-apoptosis independently of its well-known role as a transcription factor.
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•HIF-1α is recruited to mitochondria in response to oxidative stress.•Mitochondrial HIF-1α protects against oxidative stress induced apoptosis.•HIF-1α in mitochondria reduces ROS levels and reverses mitochondrial damage.•Mitochondrial HIF-1α reduces mtDNA encoded mRNA levels.•Mitochondrial HIF-1α may involve in liver fibrosis.
•CircFOXO3 is upregulated in GC cells and promotes GC malignancy in vitro and in vivo.•CircFOXO3 interacts with miR-143-3p and negatively regulates its expression.•MiR-143-3p interacts with USP44 and ...downregulates its expression in GC cells.•CircFOXO3 promotes the progression of GC by enhancing the output of miR-143-3p-USP44 axis.
Gastric carcinoma (GC) ranks fifth in terms of cancer morbidity and third in cancer-related death worldwide and imposes enormous health and economic burdens. The molecular mechanisms underlying GC formation and progression remain unclear. Our aim was to identify the involvement of circular RNA circFOXO3 in GC, and to determine the underlying mechanisms. In this study, we revealed a stimulatory role of circular RNA circFOXO3 in tumor growth in vivo. CircFOXO3 enhanced GC cell proliferation and migration in vitro and promoted tumor growth of GC cells in vivo. Bioinformatic analysis revealed that circFOXO3 might regulate USP44 expression by specifically binding to microRNA (miR)-143-3p. Existence of circFOXO3-miR-143-3p-USP44 axis in GC cells was confirmed by RNA-binding protein immunoprecipitation, luciferase reporter assay, and an RNA pull-down experiments. All the data indicate that circFOXO3 promotes GC cell proliferation and migration by upregulating USP44 expression via targeting of miR-143-3p.
Purpose
To examine the association between near work, screen time including TV and outdoor time with myopia in children from the Sunflower Myopia Asian Eye Epidemiology Consortium (AEEC).
Methods
We ...analysed AEEC cross‐sectional data (12 241 children) on risk factors (near work, screen time including TV and outdoor time) and myopia of six population‐based studies (China, Hong Kong and Singapore). Cycloplegic refraction and axial length (AL) measurements were included. Risk factors were determined using questionnaires. Data were pooled from each study, and multivariable regression analysis was performed to evaluate the associations between risks factors and myopia, spherical equivalent (SE) and AL.
Results
Among the included children, 52.1% were boys, 98.1% were Chinese and 69.7% lived in urban areas. Mean±standard deviation (SD) for age was 8.8 ± 2.9 years, for SE was −0.14 ± 1.8 D and for AL was 23.3 ± 1.1 mm. Myopia prevalence was 30.6%. In multivariate analysis, more reading and writing (OR = 1.17; 95% CI, 1.11–1.24), more total near work (OR = 1.05; 95% CI, 1.02–1.09) and less outdoor time (OR = 0.82, 95% CI, 0.75–0.88) were associated with myopia (p’s < 0.05). These factors were similarly associated with SE and AL (p’s < 0.05), except for total near work and AL (p = 0.15). Screen time including TV was not significantly associated with myopia (p = 0.49), SE (p = 0.49) or AL (p = 0.83).
Conclusion
In this study, increased reading and writing and decreased outdoor time were associated with myopia. Screen time may be a surrogate factor of near work or outdoor time, but further research is needed to assess its role as an independent risk factor for myopia.
To examine the prevalence of refractive errors and prevalence and causes of vision loss among preschool and school children in East China.
Using a random cluster sampling in a cross-sectional ...school-based study design, children with an age of 4-18 years were selected from kindergartens, primary schools, and junior and senior high schools in the rural Guanxian County and the city of Weihai. All children underwent a complete ocular examination including measurement of uncorrected (UCVA) and best corrected visual acuity (BCVA) and auto-refractometry under cycloplegia. Myopia was defined as refractive error of ≤-0.5 diopters (D), high myopia as ≤ -6.0D, and amblyopia as BCVA ≤ 20/32 without any obvious reason for vision reduction and with strabismus or refractive errors as potential reasons.
Out of 6364 eligible children, 6026 (94.7%) children participated. Prevalence of myopia (overall: 36.9 ± 0.6%;95% confidence interval (CI):36.0,38.0) increased (P<0.001) from 1.7 ± 1.2% (95%CI:0.0,4.0) in the 4-years olds to 84.6 ± 3.2% (95%CI:78.0,91.0) in 17-years olds. Myopia was associated with older age (OR:1.56;95%CI:1.52,1.60;P<0.001), female gender (OR:1.22;95%CI:1.08,1.39;P = 0.002) and urban region (OR:2.88;95%CI:2.53,3.29;P<0.001). Prevalence of high myopia (2.0 ± 0.2%) increased from 0.7 ± 0.3% (95%CI:0.1,1.3) in 10-years olds to 13.9 ± 3.0 (95%CI:7.8,19.9) in 17-years olds. It was associated with older age (OR:1.50;95%CI:1.41,1.60;P<0.001) and urban region (OR:3.11;95%CI:2.08,4.66);P<0.001). Astigmatism (≥ 0.75D) (36.3 ± 0.6%;95%CI:35.0,38.0) was associated with older age (P<0.001;OR:1.06;95%CI:1.04,1.09), more myopic refractive error (P<0.001;OR:0.94;95%CI:0.91,0.97) and urban region (P<0.001;OR:1.47;95%CI:1.31,1.64). BCVA was ≤ 20/40 in the better eye in 19 (0.32%) children. UCVA ≤ 20/40 in at least one eye was found in 2046 (34.05%) children, with undercorrected refractive error as cause in 1975 (32.9%) children. Amblyopia (BCVA ≤ 20/32) was detected in 44 (0.7%) children (11 children with bilateral amblyopia).
In coastal East China, about 14% of the 17-years olds were highly myopic, and 80% were myopic. Prevalence of myopia increased with older age, female gender and urban region. About 0.7% of pre-school children and school children were amblyopic.
To conduct a meta-analysis on the effects of orthokeratology in slowing myopia progression.
A literature search was performed in PubMed, Embase, and the Cochrane Library. Methodological quality of ...the literature was evaluated according to the Jadad score. The statistical analysis was carried out using RevMan 5.2.6 software.
The present meta-analysis included seven studies (two randomized controlled trials and five nonrandomized controlled trials) with 435 subjects (orthokeratology group, 218; control group, 217) aged 6 to 16 years. The follow-up time was 2 years for the seven studies. The weighted mean difference was -0.26 mm (95% confidence interval, -0.31 to -0.21; p < 0.001) for axial length elongation based on data from seven studies and -0.18 mm (95% confidence interval, -0.33 to -0.03; p = 0.02) for vitreous chamber depth elongation based on data from two studies.
Our results suggest that orthokeratology may slow myopia progression in children. Further large-scale studies are needed to substantiate the current result and to investigate the long-term effects of orthokeratology in myopia control.
To assess stereoacuity in a population-based sample of children and to examine ocular and systemic parameters related to stereoacuity.
Using a random cluster sampling method, four- to 18-year-old ...children from kindergartens, elementary schools, junior high schools and senior high schools from a rural area and an urban area in the East Chinese province of Shandong were included in the school-based cross-sectional study. All participants underwent a comprehensive eye examination including assessment of cycloplegic refraction and measurement of stereoacuity using the Titmus Stereo test.
Out of 6364 eligible children, 5780 (90.8%) children with a mean age of 10.1 ± 3.2 years (range: 4 to 18 years) participated. Mean (± standard deviation) stereoacuity was 50.2 ± 50.6 arc seconds. Stereoacuity improved significantly (P<0.01) from the age group of 4 years to the age group of 6 to 7 years, then showed a plateau, deteriorated (P = 0.001) for both sexes from the age group of 9 years to the age group of 12 years (P<0.001), after which it improved (P = 0.001) again in the age group of 16 years or older to the pre-puberty values. In multivariate analysis, larger angle of binocular disparity (i.e., lower stereoacuity) was significantly associated with lower best corrected visual acuity (logMAR; P<0.001), higher intereye difference in refractive error (spherical equivalent) (P<0.001), higher cylindrical refractive error (P<0.001), higher refractive error (spherical value; P<0.001), higher intereye difference in best corrected visual acuity (logMAR) (P = 0.001), higher intereye difference in axial length (P = 0.001), and rural region of habitation (P = 0.006).
Stereoacuity as tested with the Titmus Stereo test improved significantly from an age of 4 years to an age of 6 and 7 years, then remained constant, temporarily deteriorated for both sexes in pre-puberty and puberty, after which it improved again to pre-puberty or better values at the age of 16 years or older. Lower stereoacuity was associated with lower best corrected visual acuity and higher intereye difference in best corrected visual acuity, higher cylindrical and spherical refractive errors, higher inter-eye difference in refractive error, higher intereye difference in axial length, and rural region of habitation.
Pancreatic ductal adenocarcinoma (PDAC) remains a significant public health challenge and is currently the fourth leading cause of cancer-related mortality in developed countries. Despite advances in ...cancer treatment, the 5-year survival rate for patients with PDAC remains less than 5%. In recent years, neoadjuvant therapy (NAT) has emerged as a promising treatment option for many cancer types, including locally advanced PDAC, with the potential to improve patient outcomes. To analyze the role of NAT in the setting of locally advanced PDAC over the past decade, a systematic literature search was conducted using PubMed and Web of Science. The results suggest that NAT may reduce the local mass size, promote tumor downstaging, and increase the likelihood of resection. These findings are supported by the latest evidence-based medical literature and the clinical experience of our center. Despite the potential benefits of NAT, there are still challenges that need to be addressed. One such challenge is the lack of consensus on the optimal timing and duration of NAT. Improved criteria for patient selection are needed to further identify PDAC patients likely to respond to NAT. In conclusion, NAT has emerged as a promising treatment option for locally advanced PDAC. However, further research is needed to optimize its use and to better understand the role of NAT in the management of this challenging disease. With continued advances in cancer treatment, there is hope of improving the outcomes of patients with PDAC in the future.
Synaptosomal actin dynamics are essential for synaptic structural stability. Whether actin dynamics are involved in structural and functional synaptic plasticity within the primary visual cortex (V1) ...or behavioral visual acuity in rats has still not been thoroughly investigated.PurposeSynaptosomal actin dynamics are essential for synaptic structural stability. Whether actin dynamics are involved in structural and functional synaptic plasticity within the primary visual cortex (V1) or behavioral visual acuity in rats has still not been thoroughly investigated.Synaptosome preparation and western blot analysis were used to analyze synaptosomal actin dynamics. Transmission electron microscopy was used to detect synaptic density and mitochondrial area alterations. A visual water maze task was applied to assess behavioral visual acuity. Microinjection of the actin polymerization inhibitor or stabilizer detected the effect of actin dynamics on visual function.MethodsSynaptosome preparation and western blot analysis were used to analyze synaptosomal actin dynamics. Transmission electron microscopy was used to detect synaptic density and mitochondrial area alterations. A visual water maze task was applied to assess behavioral visual acuity. Microinjection of the actin polymerization inhibitor or stabilizer detected the effect of actin dynamics on visual function.Actin dynamics, the mitochondrial area, and synaptic density within the area of V1 are increased during the critical period for the development of binocularity. Microinjection of the actin polymerization inhibitor cytochalasin D into the V1 decreased the mitochondrial area, synaptic density, and behavioral visual acuity. Long-term monocular deprivation reduced actin dynamics, the mitochondrial area, and synaptic density within the V1 contralateral to the deprived eye compared with those ipsilateral to the deprived eye and impaired visual acuity in the amblyopic eye. In addition, the mitochondrial area, synaptic density, and behavioral visual acuity were improved by stabilization of actin polymerization by jasplakinolide microinjection.ResultsActin dynamics, the mitochondrial area, and synaptic density within the area of V1 are increased during the critical period for the development of binocularity. Microinjection of the actin polymerization inhibitor cytochalasin D into the V1 decreased the mitochondrial area, synaptic density, and behavioral visual acuity. Long-term monocular deprivation reduced actin dynamics, the mitochondrial area, and synaptic density within the V1 contralateral to the deprived eye compared with those ipsilateral to the deprived eye and impaired visual acuity in the amblyopic eye. In addition, the mitochondrial area, synaptic density, and behavioral visual acuity were improved by stabilization of actin polymerization by jasplakinolide microinjection.During the critical period of visual development of binocularity, synaptosomal actin dynamics regulate synaptic structure and function and play roles in behavioral visual acuity in rats.ConclusionsDuring the critical period of visual development of binocularity, synaptosomal actin dynamics regulate synaptic structure and function and play roles in behavioral visual acuity in rats.
Uniform alignment of rigid-rod liquid crystal (LC) molecules under applied voltage is critical for achievement of high-quality display for thin-film transistor-driven liquid crystal display devices ...(TFT-LCDs). The polymeric components that can induce the alignment of randomly aligned LC molecules are called alignment layers (ALs). In the current work, a series of organo-soluble polyimide (SPI) ALs were designed and prepared from an alicyclic dianhydride, hydrogenated 3,3',4,4'-biphenyltetracarboxylic dianhydride (HBPDA), and various aromatic diamines, including 4,4'-methylenedianiline (MDA) for SPI-1, 4,4'-aminodianiline (NDA) for SPI-2, 3,3',5,5'-tetramethyl-4,4'-diaminodiphenylmethane (TMMDA) for SPI-3, and 3,3'-diethyl-5,5'-dimethyl-4,4'-diaminodiphenylmethane (DMDEDA) for SPI-4. The derived SPI resins were all soluble in N-methyl-2-pyrrolidone (NMP). Four SPI alignment agents with the solid content of 6 wt.% were prepared by dissolving the SPI resins in the mixed solvent of NMP and butyl cellulose (BC) (NMP/BC = 80:20, weight ratio). Liquid crystal minicells were successfully fabricated using the developed SPI varnishes as the LC molecule alignment components. The SPI ALs showed good alignment ability for the LC molecules with the pretilt angles in the range of 1.58°-1.97°. The LC minicells exhibited good optoelectronic characteristics with voltage holding ratio (VHR) values higher than 96%. The good alignment ability of the SPI ALs is mainly attributed to the good comprehensive properties of the SPI layers, including high volume resistivity, high degree of imidization at the processing temperature (230 °C), good rubbing resistance, good thermal stability with glass transition temperatures (T
s) higher than 260 °C, and excellent optical transparency with the transmittance higher than 97% at the wavelength of 550 nm.
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