Dysregulation of cholesterol homeostasis is an early signal of beta cell proteotoxicity characteristic of type 2 diabetes.

Type 2 diabetes (T2D) is a common metabolic disease due to insufficient insulin secretion by pancreatic beta cells in the context of insulin resistance. Islet molecular pathology reveals a role for protein misfolding in beta cell dysfunction and loss with islet amyloid derived from islet amyloid polypeptide (IAPP), a protein co-expressed and co-secreted with insulin. The most toxic form of misfolded IAPP is intracellular membrane disruptive toxic oligomers present in beta cells in T2D and in beta cells of mice transgenic for human IAPP (hIAPP). Prior work revealed a high degree of overlap of transcriptional changes in islets from T2D and pre-diabetic 9-10-week-old mice transgenic for hIAPP with most changes being pro-survival adaptations and therefore of limited therapeutic guidance. Here we investigated islets from hIAPP transgenic mice at an earlier age (6 weeks) to screen for potential mediators of hIAPP toxicity that precede predominance of pro-survival signaling. We identified early suppression of cholesterol synthesis and trafficking along with aberrant intra-beta cell cholesterol and lipid deposits, and impaired cholesterol trafficking to cell membranes. These findings align with comparable lipid deposits present in beta cells in T2D and increased vulnerability to develop T2D in individuals taking medications that suppress cholesterol synthesis.

Impact of different fracture types in the pyriform buttress area on nasal airway function.

INTRODUCTION: Fractures in the pyriform buttress area adversely affect facial appearance and nasal airway patency. Nasal airway function has received less attention than aesthetic problems in the literature. This retrospective study classified the different fracture types in this area and determined their impact on nasal airway function. MATHODS: Three-dimensional computed tomography images of patients with fractures in the pyriform buttress area were analyzed to identify the exact fracture pattern. The nasal airway functions were evaluated and compared between patients with different fracture patterns using acoustic rhinometry, rhinomanometry, and the nasal obstruction symptom evaluation scale. RESULTS: Overall, 47 patients, including 16 with type I fractures (high fracture line; group I), 16 with type II fractures (intermediate fracture line; group II), and 15 with type III fractures (low fracture line; group III), were included in the study. The mean minimal cross-sectional area (MCA), total nasal inspiratory resistance (Tri) and total nasal expiratory resistance (Tre) of group I were 0.51 ± 0.06 cm2, 1.67 ± 0.11 kPa L-1 s-1, and 1.66 ± 0.12 kPa L-1 s-1, respectively; those of group II were 0.48 ± 0.07 cm2, 1.89 ± 0.15 kPa L-1 s-1, and 1.88 ± 0.14 kPa L-1 s-1, respectively; and those of group III were 0.36 ± 0.04 cm2, 1.94 ± 0.21 kPa L-1 s-1, and 2.01 ± 0.34 kPa L-1 s-1, respectively. The nasal obstruction symptom evaluation (NOSE) scale scores for groups I, II, and III were 7.188, 9.813, and 13.27, respectively. CONCLUSION: Therefore, the severity of the nasal airway obstruction depends on the displacement of the fractured bones in patients with fractures in the pyriform buttress area. The most profound nasal obstruction occurs in patients with the lowest fracture line.

Synergistic Effects of Organic Ligands and Visible Light on the Reductive Dissolution of CeO2 Nanoparticles: Mechanisms and Implications for the Transformation in Plant Surroundings.

Cerium oxide (CeO2) nanoparticles are one of the most important engineered nanomaterials with demonstrated applications in industry. Although numerous studies have reported the plant uptake of CeO2, its fate and transformation pathways and mechanisms in plant-related conditions are still not well understood. This study investigated the stability of CeO2 in the presence of organic ligands (maleic and citric acid) and light irradiation. For the first time, we found that organic ligands and visible light had a synergistic effect on the reductive dissolution of CeO2 with up to 30% Ce releases after 3 days, which is the highest release reported so far under environmental conditions. Moreover, the photoinduced dissolution of CeO2 in the presence of citrate was much higher than that in maleate, which are adsorbed on the surface of CeO2 through inner-sphere and outer-sphere complexation, respectively. A novel ligand-dependent photodissolution mechanism was proposed and highlighted: upon electron-hole separation under light irradiation, the inner-sphere complexed citrate is more capable of consuming the hole, prolonging the life of electrons for the reduction of Ce(IV) to Ce(III). Finally, reoxidation of Ce(III) by oxygen was observed and discussed. This comprehensive work advances our knowledge of the fate and transformation of CeO2 in plant surroundings.

Redispersion Behavior of 2D MoS2 Nanosheets: Unique Dependence on the Intervention Timing of Natural Organic Matter.

The aggregation-redispersion behavior of nanomaterials determines their transport, transformation, and toxicity, which could be largely influenced by the ubiquitous natural organic matter (NOM). Nonetheless, the interaction mechanisms of two-dimensional (2D) MoS2 and NOM and the subsequent influences on the redispersion behavior are not well understood. Herein, we investigated the redispersion of single-layer MoS2 (SL-MoS2) nanosheets as influenced by Suwannee River NOM (SRNOM). It was found that SRNOM played a decisive role on the redispersion of MoS2 2D nanosheets that varied distinctly from the 3D nanoparticles. Compared to the poor redispersion of MoS2 aggregates in the absence or post-addition of SRNOM to the aggregates, co-occurrence of SRNOM in the dispersion could largely enhance the redispersion and mobility of MoS2 by intercalating into the nanosheets. Upon adsorption to SL-MoS2, SRNOM enhanced the hydration force and weakened the van der Waals forces between nanosheets, leading to the redispersion of the aggregates. The SRNOM fractions with higher molecular mass imparted better dispersity due to the preferable sorption of the large molecules onto SL-MoS2 surfaces. This comprehensive study advances current understanding on the transport and fate of nanomaterials in the water system and provides fresh insights into the interaction mechanisms between NOM and 2D nanomaterials.

Late evening snack and oral amino acid capsules improved respiratory quotient and Fischer ratio in patients with alcoholic liver cirrhosis.

INTRODUCTION AND OBJECTIVES: Appropriate nutritional support may improve energy metabolism in alcoholic liver cirrhosis (ALC) patients. We explored the effect of a late evening snack (LES) and oral amino acid (OAA) capsules on energy metabolism and the Fischer ratio in ALC. PATIENTS AND METHODS: Ninety-one ALC patients were enrolled and randomly divided into three groups: 31 patients in the LES and OAA group, 32 in the LES group, and 28 controls. Respiratory quotient (RQ), carbohydrate oxidation rate (CHO%), fat oxidation rate (FAT%), serum isoleucine and the Fischer ratio were measured at baseline and at months 1, 3, and 6 of follow-up. RESULTS: The RQ in the LES and OAA group was 0.79 ± 0.06, 0.80 ± 0.04, 0.82 ± 0.04, and 0.82 ± 0.04 at baseline and at months 1, 3, and 6 of follow-up, respectively. These values were significantly higher than those in the LES group (P < 0.05). The RQ in the LES group was significantly higher than that in the control group at month 1 and month 6 (P < 0.05). CHO% in the LES and OAA group was significantly increased and FAT% was significantly decreased at month 3 of follow-up (P < 0.05). In the LES and OAA group, serum isoleucine and the Fischer ratio were markedly increased compared with the LES group and control group (P < 0.05). CONCLUSIONS: LES can significantly increase the RQ in ALC. LES and OAA were more effective than LES alone in improving serum isoleucine and the Fischer ratio.

Optical properties and energy transfer performances in high quality Cr,Nd: YAG transparent laser ceramics for solar pumped lasers.

Realizing a high solar light conversion magnitude in Cr,Nd: YAG transparent ceramic is crucial to its applications in solar pumped solid state lasers. In this study, high quality Cr,Nd:YAG transparent laser ceramics with homogeneous microstructure and theoretical transmittance were fabricated, and an efficient laser oscillation of watt-level was realized by pumping ceramic at 808 nm. There were no any characteristic absorptions corresponding to Cr2+ or Cr4+ ions detected, even when the Cr3+ ion doping concentration reached 0.6 at.%. Increasing Cr3+ and Nd3+ doping concentrations significantly enhanced the emission intensity of ceramics at 1.06 µm, and energy transfer efficiency of the 0.3 at.% Cr,Nd: YAG ceramics was increased from 14.9% to 36.9% when increasing Nd3+ ion concentration from 0.3 at.% to 1.0 at.%, with an increasing magnitude of 247.6%. The results indicated that Cr,Nd: YAG transparent ceramic is a promising gain medium for solar pumped solid state lasers.

High MST2 expression regulates lens epithelial cell apoptosis in age-related cataracts through YAP1 targeting GLUT1.

Age-related cataract (ARC) is a severe visual impairment disease and its pathogenesis remains unclear. This study investigated the relevance of MST2/YAP1/GLUT1 in ARC development in vivo and in vitro, and explored the role and possible mechanisms of this pathway in oxidative damage-mediated apoptosis of lens epithelial cells (LECs). Western blot analysis and immunohistochemistry showed that MST2 and phosphorylated (p)-YAP (Ser127) protein levels were increased, and YAP1 and GLUT1 protein levels were decreased in LECs of ARC patients and aged mice. Additionally, differential expression of MST2 and YAP1 was associated with H2O2-induced apoptosis of human lens epithelial B3 (HLE-B3) cells. CCK-8 and Hoechst 33,342 apoptosis assays showed that MST2 and YAP1 were involved in H2O2-induced apoptosis of LECs. Subsequent experiments showed that, during MST2-mediated H2O2-induced apoptosis, p-YAP (Ser127) levels were elevated and immunofluorescence revealed nucleoplasmic translocation and inhibition of YAP1 protein expression. Furthermore, GLUT1 was in turn synergistically transcriptionally regulated by YAP1-TEAD1 in dual luciferase reporter assays. In conclusion, our study indicates that the MST2/YAP1/GLUT1 pathway plays a major role in the pathogenesis of ARC and LECs apoptosis, providing a new direction for future development of targeted inhibitors that block this signaling pathway to prevent, delay, or even cure ARC.

Enhancing the Permselectivity of Thin-Film Composite Membranes Interlayered with MoS2 Nanosheets via Precise Thickness Control.

The demand for highly permeable and selective thin-film composite (TFC) nanofiltration membranes, which are essential for seawater and brackish water softening and resource recovery, is growing rapidly. However, improving and tuning membrane permeability and selectivity simultaneously remain highly challenging owing to the lack of thickness control in polyamide films. In this study, we fabricated a high-performance interlayered TFC membrane through classical interfacial polymerization on a MoS2-coated polyethersulfone substrate. Due to the enhanced confinement effect on the interface degassing and the improved adsorption of the amine monomer by the MoS2 interlayer, the MoS2-interlayered TFC membrane exhibited enhanced roughness and crosslinking. Compared to the control TFC membrane, MoS2-interlayered TFC membranes have a thinner polyamide layer, with thickness ranging from 60 to 85 nm, which can be tuned by altering the MoS2 interlayer thickness. A multilayer permeation model was developed to delineate and analyze the transport resistance and permeability of the MoS2 interlayer and polyamide film through the regression of experimental data. The optimized MoS2-interlayered TFC membrane (0.3-inter) had a 96.8% Na2SO4 rejection combined with an excellent permeability of 15.9 L m-2 h-1 bar-1 (LMH/bar), approximately 2.4 times that of the control membrane (6.6 LMH/bar). This research provides a feasible strategy for the rational design of tunable, high-performance NF membranes for environmental applications.

Tuning phase compositions of MoS2 nanomaterials for enhanced heavy metal removal: performance and mechanism.

Two-dimensional MoS2 nanosheets have shown great potential in heavy metal remediation due to their unique properties. MoS2 has two primary phases: 1T and 2H. Each has different physiochemical properties, but the impact of these differences on the overall material's heavy metal removal performance and associated mechanisms is rarely reported. In this study, we synthesized morphologically similar but phase-distinct MoS2 samples via hydrothermal synthesis, which comprised dominantly either a metallic 1T phase or a semiconducting 2H phase. 1T-MoS2 samples exhibited higher removal capacities for Ag+ and Pb2+ cations relative to 2H-MoS2. In particular, an eight-fold increase in the Pb2+ adsorption capacity was observed in the 1T-MoS2 samples (i.e. ∼632.9 mg g-1) compared to the 2H-MoS2 samples (∼81.6 mg g-1). The mechanisms driving the enhanced performance of 1T-MoS2 were investigated through detailed characterization of metal-laden MoS2 samples and DFT modelling. We found that 1T-MoS2 intrinsically had a larger interlayer spacing than 2H-MoS2 because water molecules were retained between the hydrophilic 1T nanosheets during hydrothermal synthesis. The widened interlayer spacing in 1T-MoS2 allowed the diffusion of heavy metal ions into the nanochannels, increasing the number of adsorption sites and total removal capacities. On the other hand, DFT modelling revealed the energy-favorable adsorption complex of Ag+ and Pb2+ for 1T-MoS2, in which each metal atom was bonded with three S atoms leading to much higher adsorption energies relative to 2H-MoS2 for Ag+ and Pb2+. This study unravels the underlying mechanisms of phase-dependent heavy metal remediation by MoS2 nanosheets, providing an important guide for the use of 2D nanomaterials in environmental applications which include heavy metal removal, contaminant sensing, and membrane separation.

Evidence of susceptibility to autism risks associated with early life ambient air pollution: A systematic review.

BACKGROUND: Many studies have found associations between early life air pollution exposure and subsequent onset of autism spectrum disorder (ASD). However, characteristics that affect susceptibility remain unclear. OBJECTIVE: This systematic review examined epidemiologic studies on the modifying roles of social, child, genetic and maternal characteristics in associations between prenatal and early postnatal air pollution exposure and ASD. METHODS: A systematic literature search in PubMed and Embase was conducted. Studies that examined modifiers of the association between air pollution and ASD were included. RESULTS: A total of 19 publications examined modifiers of the associations between early life air pollution exposures and ASD. In general, estimates of effects on risk of ASD in boys were larger than in girls (based on 11 studies). Results from studies of effects of family education (2 studies) and neighborhood deprivation (2 studies) on air pollution-ASD associations were inconsistent. Limited data (1 study) suggest pregnant women with insufficient folic acid intake might be more susceptible to ambient particulate matter less than 2.5 µm (PM2.5) and 10 µm (PM10) in aerodynamic diameter, and to nitrogen dioxide (NO2). Children of mothers with gestational diabetes had increased risk of ozone-associated ASD (1 study). Two genetic studies reported that copy number variations may amplify the effect of ozone, and MET rs1858830 CC genotype may augment effects of PM and near-roadway pollutants on ASD. CONCLUSIONS: Child's sex, maternal nutrition or diabetes, socioeconomic factors, and child risk genotypes were reported to modify the effect of early-life air pollutants on ASD risk in the epidemiologic literature. However, the sparsity of studies on comparable modifying hypotheses precludes conclusive findings. Further research is needed to identify susceptible populations and potential targets for preventive intervention.

Identification and characterization of amphibian SLC26A5 using RNA-Seq.

BACKGROUND: Prestin (SLC26A5) is responsible for acute sensitivity and frequency selectivity in the vertebrate auditory system. Limited knowledge of prestin is from experiments using site-directed mutagenesis or domain-swapping techniques after the amino acid residues were identified by comparing the sequence of prestin to those of its paralogs and orthologs. Frog prestin is the only representative in amphibian lineage and the studies of it were quite rare with only one species identified. RESULTS: Here we report a new coding sequence of SLC26A5 for a frog species, Rana catesbeiana (the American bullfrog). In our study, the SLC26A5 gene of Rana has been mapped, sequenced and cloned successively using RNA-Seq. We measured the nonlinear capacitance (NLC) of prestin both in the hair cells of Rana's inner ear and HEK293T cells transfected with this new coding gene. HEK293T cells expressing Rana prestin showed electrophysiological features similar to that of hair cells from its inner ear. Comparative studies of zebrafish, chick, Rana and an ancient frog species showed that chick and zebrafish prestin lacked NLC. Ancient frog's prestin was functionally different from Rana. CONCLUSIONS: We mapped and sequenced the SLC26A5 of the Rana catesbeiana from its inner ear cDNA using RNA-Seq. The Rana SLC26A5 cDNA was 2292 bp long, encoding a polypeptide of 763 amino acid residues, with 40% identity to mammals. This new coding gene could encode a functionally active protein conferring NLC to both frog HCs and the mammalian cell line. While comparing to its orthologs, the amphibian prestin has been evolutionarily changing its function and becomes more advanced than avian and teleost prestin.

Chip-level Ce:GdYAG ceramic phosphors with excellent chromaticity parameters for high-brightness white LED device.

Development of ceramic phosphors (CPs) featuring small volume and high efficacy is crucial for miniaturization of white LEDs and their integration in solid state lighting. In this study, the chip-level 2.5×2.5 mm Ce:GdYAG CPs with different thicknesses were packaged to the blue chips, and their luminous characteristics were analyzed under the different radiant flux. Notably, when thickness of the CPs was 1.4 mm, a luminous flux of 2000 lm, a correlated color temperature (CCT) of 6266 K and a color rendering index (CRI) of 70 were obtained under 11.0 W blue power (1.76 W/mm2) excitation. Phenomenon of colorimetric drift was explained simultaneously. These results indicate that Ce:GdYAG CPs is a promising candidate for automotive lighting and high-speed rail lighting.

Broadband emission Gd3Sc2Al3O12:Ce3+ transparent ceramics with a high color rendering index for high-power white LEDs/LDs.

The discovery of single structure Ce3+ doped garnet transparent ceramics (TCs) with a broad full width at half maximum (FWHM) is essential to realize a high CRI for high-power white light emitting diodes (LEDs) and laser diodes (LDs). In this work, by utilizing the ion substitution engineering strategy, pure phase Gd3Sc2Al3O12:Ce3+ (GSAG:Ce) TC with a broad FWHM of 132.4 nm and a high CRI value of 80.7 was fabricated through the vacuum sintering technique for the first time. The optimized in-line transmittance of TCs was 58.4% @ 800 nm. Notably, the GSAG:Ce TCs exhibited a remarkable red shift from 546 nm to 582 nm, with a high internal quantum efficiency (IQE) of 46.91%. The degraded thermal stability in Ce:GSAG TCs was observed compared with that of Ce:YAG TC, owing to the narrowed band gap of GSAG. Additionally, remote excitation white LEDs/LDs were constructed by combining GSAG:Ce TCs with blue LED chips or laser sources. A tunable color hue from yellow to shinning white was achieved in white LEDs, whereas the acquired CRI and CCT of the white LDs were 69.5 and 7766 K, respectively. This work provides a new perspective to develop TCs with high CRI for their real applications in high-power white LEDs/LDs.

Tailoring Defect Density in UiO-66 Frameworks for Enhanced Pb(II) Adsorption.

Defect engineering of metal organic frameworks offers potential prospects for tuning their features toward particular applications. Herein, two series of defective UiO-66 frameworks were synthesized via changing the concentration of the linker and synthetic temperature of the reaction. These defective materials showed a significant improvement in the capability of Pb(II) removal from wastewater. This strategy for defect engineering not only created additional active sites, more open framework, and enhanced porosity but also exposed more oxygen groups, which served as the adsorption sites to improve Pb(II) adsorption. A relationship among degree of defects, texture features, and performances for Pb(II) removal was successfully developed as a proof-of-concept, highlighting the importance of defect engineering in heavy metal remediation. To investigate the kinetic and adsorption isotherms, we performed adsorption experiments influenced by the time and concentration of the adsorbate, respectively. For the practicality of the materials, the most significant parameters such as pH, temperature, adsorbent concentration, selectivity, and recyclability as well as simulated natural surface water were also examined. This study provides a clue for the researchers to design other advanced defective materials for the enhancement of adsorption performance by tuning the defect engineering.

Atomically Dispersed Cobalt Sites on Graphene as Efficient Periodate Activators for Selective Organic Pollutant Degradation.

Pollutant degradation via periodate (IO4-)-based advanced oxidation processes (AOPs) provides an economical, energy-efficient way for sustainable pollution control. Although single-atomic metal activation (SMA) can be exploited to optimize the pollution degradation process and understand the associated mechanisms governing IO4--based AOPs, studies on this topic are rare. Herein, we demonstrated the first instance of using SMA for IO4- analysis by employing atomically dispersed Co active sites supported by N-doped graphene (N-rGO-CoSA) activators. N-rGO-CoSA efficiently activated IO4- for organic pollutant degradation over a wide pH range without producing radical species. The IO4- species underwent stoichiometric decomposition to generate the iodate (IO3-) species. Whereas Co2+ and Co3O4 could not drive IO4- activation; the Co-N coordination sites exhibited high activation efficiency. The conductive graphene matrix reduced the contaminants/electron transport distance/resistance for these oxidation reactions and boosted the activation capacity by working in conjunction with metal centers. The N-rGO-CoSA/IO4- system exhibited a substrate-dependent reactivity that was not caused by iodyl (IO3·) radicals. Electrochemical experiments demonstrated that the N-rGO-CoSA/IO4- system decomposed organic pollutants via electron-transfer-mediated nonradical processes, where N-rGO-CoSA/periodate* metastable complexes were the predominant oxidants, thereby opening a new avenue for designing efficient IO4- activators for the selective oxidation of organic pollutants.

Synergistic Effect of Metal Cations and Visible Light on 2D MoS2 Nanosheet Aggregation.

Aggregation significantly influences the transport, transformation, and bioavailability of engineered nanomaterials. Two-dimensional MoS2 nanosheets are one of the most well-studied transition-metal dichalcogenide nanomaterials. Nonetheless, the aggregation behavior of this material under environmental conditions is not well understood. Here, we investigated the aggregation of single-layer MoS2 (SL-MoS2) nanosheets under a variety of conditions. Trends in the aggregation of SL-MoS2 are consistent with classical Derjaguin-Landau-Verwey-Overbeek (DLVO) colloidal theory, and the critical coagulation concentrations of cations follow the order of trivalent (Cr3+) < divalent (Ca2+, Mg2+, Cd2+) < monovalent cations (Na+, K+). Notably, Pb2+ and Ag+ destabilize MoS2 nanosheet suspensions much more strongly than do their divalent and monovalent counterparts. This effect is attributable to Lewis soft acid-base interactions of cations with MoS2. Visible light irradiation synergistically promotes the aggregation of SL-MoS2 nanosheets in the presence of cations, which was evident even in the presence of natural organic matter. The light-accelerated aggregation was ascribed to dipole-dipole interactions due to transient surface plasmon oscillation of electrons in the metallic 1T phase, which decrease the aggregation energy barrier. These results reveal the phase-dependent aggregation behaviors of engineered MoS2 nanosheets with important implications for environmental fate and risk.

RNA sequencing and bioinformatics analysis of human lens epithelial cells in age-related cataract.

BACKGROUND: Age-related cataract (ARC) is the main cause of blindness in older individuals but its specific pathogenic mechanism is unclear. This study aimed to identify differentially expressed genes (DEGs) associated with ARC and to improve our understanding of the disease mechanism. METHODS: Anterior capsule samples of the human lens were collected from ARC patients and healthy controls and used for RNA sequencing to detect DEGs. Identified DEGs underwent bioinformatics analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Subsequently, reverse transcription quantitative RT-qPCR was used to validate the different expression levels of selected genes. RESULTS: A total of 698 up-regulated DEGs and 414 down-regulated DEGs were identified in ARC patients compared with controls by transcriptome analysis. Through GO and KEGG bioinformatics analysis, the functions of significantly DEGs and their possible molecular mechanisms were determined. Sequencing results were verified by RT-qPCR as being accurate and reliable. CONCLUSIONS: This study identified several genes associated with ARC, which improves our knowledge of the disease mechanism.

Dose-Dependent Pattern of Cochlear Synaptic Degeneration in C57BL/6J Mice Induced by Repeated Noise Exposure.

It is widely accepted that even a single acute noise exposure at moderate intensity that induces temporary threshold shift (TTS) can result in permanent loss of ribbon synapses between inner hair cells and afferents. However, effects of repeated or chronic noise exposures on the cochlear synapses especially medial olivocochlear (MOC) efferent synapses remain elusive. Based on a weeklong repeated exposure model of bandwidth noise over 2-20 kHz for 2 hours at seven intensities (88 to 106 dB SPL with 3 dB increment per gradient) on C57BL/6J mice, we attempted to explore the dose-response mechanism of prolonged noise-induced audiological dysfunction and cochlear synaptic degeneration. In our results, mice repeatedly exposed to relatively low-intensity noise (88, 91, and 94 dB SPL) showed few changes on auditory brainstem response (ABR), ribbon synapses, or MOC efferent synapses. Notably, repeated moderate-intensity noise exposures (97 and 100 dB SPL) not only caused hearing threshold shifts and the inner hair cell ribbon synaptopathy but also impaired MOC efferent synapses, which might contribute to complex patterns of damages on cochlear function and morphology. However, repeated high-intensity (103 and 106 dB SPL) noise exposures induced PTSs mainly accompanied by damages on cochlear amplifier function of outer hair cells and the inner hair cell ribbon synaptopathy, rather than the MOC efferent synaptic degeneration. Moreover, we observed a frequency-dependent vulnerability of the repeated acoustic trauma-induced cochlear synaptic degeneration. This study provides a sight into the hypothesis that noise-induced cochlear synaptic degeneration involves both afferent (ribbon synapses) and efferent (MOC terminals) pathology. The pattern of dose-dependent pathological changes induced by repeated noise exposure at various intensities provides a possible explanation for the complicated cochlear synaptic degeneration in humans. The underlying mechanisms remain to be studied in the future.

High-expression of ROCK1 modulates the apoptosis of lens epithelial cells in age-related cataracts by targeting p53 gene.

BACKGROUND: Age-related cataract (ARC) is a serious visual impairment disease, and its pathogenesis is unclear. This article aims to investigate the role of ROCK1 in the apoptosis of lens epithelial cells (LECs) in age-related cataracts. METHODS: We collect anterior capsule samples from normal people, patients with age-related cataracts, young mice and naturally aging cataract mice. The oxidative stress-induced apoptosis model was constructed by cultivating HLE-B3 cells with H2O2. MTT, Hoechst 33342, and TUNEL assay were performed to explore proliferation and apoptosis. HE assay was used to observe cell morphology. The gene and protein expression were assessed by quantitative real-time PCR, western blot, immunofluorescence, and immunohistochemical staining. RESULT: The results from the clinic and mice experiments showed that the numbers of lens epithelial cells from cataract individuals were less than the control individuals. In vitro, the apoptotic cells were increased in lens epithelial cells under H2O2 treatment. The ROCK1 protein level increased in the lens epithelial cells from age-related cataract patients and the old mice, respectively. Meanwhile, the up-regulation of the ROCK1 gene was associated with H2O2-induced HLE-B3 cells apoptosis. MTT and apoptosis assay showed ROCK1 was necessary in mediating H2O2-induced lens epithelial cells apoptosis through ROCK1 over-expression and knockdown experiment, respectively. Further investigation showed that p53 protein levels had been increased during ROCK1-mediated apoptosis in response to H2O2. Besides, ROCK1 phosphorylated p53 at ser15 to up-regulate its protein level. CONCLUSIONS: This study established the novel association of ROCK1/p53 signaling with lens epithelial cells apoptosis and age-related cataract genesis.

MDM2 phosphorylation mediates H2O2-induced lens epithelial cells apoptosis and age-related cataract.

Lens epithelial cells (LECs) apoptosis induced by oxidative stress is a major factor in age-related-cataract (ARC) pathogenesis, but there are still many blind nodes in this progress. This study aimed to investigate the effects of MDM2 phosphorylation in ARC and H2O2-induced lens epithelial cells apoptosis. Our results confirmed that the levels of p-MDM2 (Ser166) and p-MDM2 (Ser186) in the anterior lens capsules of human cataracts were reduced compared to that in normal capsules. Similarly, in naturally aging cataract mice, the level of MDM2 phosphorylation also decreased. Oxidative stress-induced apoptosis model was constructed by cultivating HLE-B3 cells with 200 µM H2O2. It was confirmed that MDM2 could regulate lens epithelial cell apoptosis, and MDM2 inhibitors could partly inhibited AKT's role in suppressing apoptosis induced by H2O2. Besides, we examed the decreased level of p-AKT(Ser473) in apoptosis of lens epithelial cells and ARC. Our study revealed that MDM2 phosphorylation mediated H2O2-induced lens epithelial cells apoptosis and ARC, which could provide new ideas for the clinical treatment of ARC.