Far-UVC Photolysis of Peroxydisulfate for Micropollutant Degradation in Water.

Increasing radical yields to reduce UV fluence requirement for achieving targeted removal of micropollutants in water would make UV-based advanced oxidation processes (AOPs) less energy demanding in the context of United Nations' Sustainable Development Goals and carbon neutrality. We herein demonstrate that, by switching the UV radiation source from conventional low-pressure UV at 254 nm (UV254) to emerging Far-UVC at 222 nm (UV222), the fluence-based concentration of HO• in the UV/peroxydisulfate (UV/PDS) AOP increases by 6.40, 2.89, and 6.00 times in deionized water, tap water, and surface water, respectively, with increases in the fluence-based concentration of SO4•- also by 5.06, 5.81, and 55.47 times, respectively. The enhancement to radical generation is confirmed using a kinetic model. The pseudo-first-order degradation rate constants of 16 micropollutants by the UV222/PDS AOP in surface water are predicted to be 1.94-13.71 times higher than those by the UV254/PDS AOP. Among the tested water matrix components, chloride and nitrate decrease SO4•- but increase HO• concentration in the UV222/PDS AOP. Compared to the UV254/PDS AOP, the UV222/PDS AOP decreases the formation potentials of carbonaceous disinfection byproducts (DBPs) but increases the formation potentials of nitrogenous DBPs.

Rare and common coding variants in lipid metabolism-related genes and their association with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is a complex disease that is influenced by environmental and genetic factors. In this study, we aimed to investigate the relationship between coding variants in lipid metabolism-related genes and CAD in a Chinese Han population. METHODS: A total of 252 individuals were recruited for this study, including 120 CAD patients and 132 healthy control individuals. Rare and common coding variants in 12 lipid metabolism-related genes (ANGPTL3, ANGPTL4, APOA1, APOA5, APOC1, APOC3, CETP, LDLR, LIPC, LPL, PCSK9 and SCARB1) were detected via next-generation sequencing (NGS)-based targeted sequencing. Associations between common variants and CAD were evaluated by Fisher's exact test. A gene-based association test of rare variants was performed by the sequence kernel association test-optimal (SKAT-O test). RESULTS: We found 51 rare variants and 17 common variants in this study. One common missense variant, LIPC rs6083, was significantly associated with CAD after Bonferroni correction (OR = 0.47, 95% CI = 0.29-0.76, p = 1.9 × 10- 3). Thirty-three nonsynonymous rare variants were identified, including two novel variants located in the ANGPTL4 (p.Gly47Glu) and SCARB1 (p.Leu233Phe) genes. We did not find a significant association between rare variants and CAD via gene-based analysis via the SKAT-O test. CONCLUSIONS: Targeted sequencing is a powerful tool for identifying rare and common variants in CAD. The common missense variant LIPC rs6083 confers protection against CAD. The clinical relevance of rare variants in CAD aetiology needs to be investigated in larger sample sizes in the future.

Quantum Simulation of Topological Zero Modes on a 41-Qubit Superconducting Processor.

Quantum simulation of different exotic topological phases of quantum matter on a noisy intermediate-scale quantum (NISQ) processor is attracting growing interest. Here, we develop a one-dimensional 43-qubit superconducting quantum processor, named Chuang-tzu, to simulate and characterize emergent topological states. By engineering diagonal Aubry-André-Harper (AAH) models, we experimentally demonstrate the Hofstadter butterfly energy spectrum. Using Floquet engineering, we verify the existence of the topological zero modes in the commensurate off-diagonal AAH models, which have never been experimentally realized before. Remarkably, the qubit number over 40 in our quantum processor is large enough to capture the substantial topological features of a quantum system from its complex band structure, including Dirac points, the energy gap's closing, the difference between even and odd number of sites, and the distinction between edge and bulk states. Our results establish a versatile hybrid quantum simulation approach to exploring quantum topological systems in the NISQ era.

Nitrate Protects Microorganisms and Promotes Formation of Toxic Nitrogenous Byproducts during Water Disinfection by Far-UVC Radiation.

Far-UVC radiation is an emerging tool for combating pathogenic microorganisms in water, but its vulnerability to water matrix components remains unclear. We herein report the critical impacts of nitrate during Far-UVC disinfection of water. Nitrate at environmentally relevant concentrations (0.5-10.0 mg-N L-1) significantly inhibits Escherichia coli inactivation by Far-UVC radiation at 222 nm, via prolonging the "lag phase" of inactivation and reducing the inactivation rate constants by 1.08-2.74 times, while it shows negligible impact on E. coli inactivation by UVC radiation at 254 nm. The inhibitory impact of nitrate on Far-UVC disinfection is attributed to its strong light-shielding effect. Although hydroxyl radicals and reactive nitrogen species are generated from Far-UVC photolysis of nitrate at high concentrations of 10-13 and ∼10-7 M, respectively, those radicals are unable to compensate for the light-shielding effect of nitrate on E. coli inactivation. Moreover, reactive nitrogen species lead to the formation of nitrogenous byproducts, which increase the genotoxicity of the water. The findings advance the fundamental photochemistry and radical chemistry of nitrate at 222 nm and provide useful insights to guide the operation of Far-UVC in treating nitrate-containing water.

Rapid Inactivation of Fungal Spores in Drinking Water by Far-UVC Photolysis of Free Chlorine.

Effective and affordable disinfection technology is one key to achieving Sustainable Development Goal 6. In this work, we develop a process by integrating Far-UVC irradiation at 222 nm with free chlorine (UV222/chlorine) for rapid inactivation of the chlorine-resistant and opportunistic Aspergillus niger spores in drinking water. The UV222/chlorine process achieves a 5.0-log inactivation of the A. niger spores at a chlorine dosage of 3.0 mg L-1 and a UV fluence of 30 mJ cm-2 in deionized water, tap water, and surface water. The inactivation rate constant of the spores by the UV222/chlorine process is 0.55 min-1, which is 4.6-fold, 5.5-fold, and 1.8-fold, respectively, higher than those of the UV222 alone, chlorination alone, and the conventional UV254/chlorine process under comparable conditions. The more efficient inactivation by the UV222/chlorine process is mainly attributed to the enhanced generation of reactive chlorine species (e.g., 6.7 × 10-15 M of Cl•) instead of hydroxyl radicals from UV222 photolysis of chlorine, which is verified through both experiments and a kinetic model. We further demonstrate that UV222 photolysis damages the membrane integrity and benefits the penetration of chlorine and radicals into cells for inactivation. The merits of the UV222/chlorine process over the UV254/chlorine process also include the more effective inhibition of the photoreactivation of the spores after disinfection and the lower formation of chlorinated disinfection byproducts and toxicity.

The relationship between activated H2 bond length and adsorption distance on MXenes identified with graph neural network and resonating valence bond theory.

Motivated by the recent experimental study on hydrogen storage in MXene multilayers [Liu et al., Nat. Nanotechnol. 16, 331 (2021)], for the first time we propose a workflow to computationally screen 23 857 compounds of MXene to explore the general relation between the activated H2 bond length and adsorption distance. By using density functional theory we generate a dataset to investigate the adsorption geometries of hydrogen on MXenes, based on which we train physics-informed atomistic line graph neural networks (ALIGNNs) to predict adsorption parameters. To fit the results, we further derived a formula that quantitatively reproduces the dependence of H2 bond length on the adsorption distance from MXenes within the framework of Pauling's resonating valence bond theory, revealing the impact of transition metal's ligancy and valence on activating dihydrogen in H2 storage.

Effect of Multimodal Preemptive Analgesia of Flurbiprofen Axetil, Nalbuphine, and Retrobulbar Block on Postoperative Pain and Enhanced Recovery in Patients Undergoing Oculoplastic Day Surgery: A Prospective, Randomized, Double-Blinded Study.

PURPOSE: To evaluate the effect of either flurbiprofen axetil or nalbuphine combined with retrobulbar block (RB) before surgery on postoperative pain control and enhanced recovery in day-care patients undergoing orbital implantation. METHODS: A total of 45 patients undergoing orbital implantation with general anesthesia were randomly divided into three groups: flurbiprofen axetil (1 mg/kg) combined with RB (group F), nalbuphine (0.1 mg/kg) combined with RB (group N), and placebo as normal saline with RB (group C). The primary outcome was the average pain score (numeric rating scale: 0-10) within the first 24 hours. Other outcomes including the peak pain score, paracetamol requirement, quality of recovery (QoR)-15, and adverse effects (AEs) were assessed. RESULTS: The average and peak pain scores within 24 hours after surgery in group F were significantly lower than in other groups ( p < 0.0167). Compared with group C, the NRS scores were significantly decreased at 2 and 4 hours in group F, and 2 hours in group N after surgery ( p < 0.0167), but without significant differences at other measured time points. The time to first paracetamol oral intake displayed a significant difference among the three groups ( p < 0.0167). CONCLUSION: Preemptive use of flurbiprofen axetil 1 mg/kg combined with RB is an optimal choice for multimodal analgesia for day-care patients undergoing orbital implantation in terms of efficient acute pain control, without impeding patient-enhanced recovery.

RST1 Is a FREE1 Suppressor That Negatively Regulates Vacuolar Trafficking in Arabidopsis.

FYVE domain protein required for endosomal sorting1 (FREE1), a plant-specific endosomal sorting complex required for transport-I component, is essential for the biogenesis of multivesicular bodies (MVBs), vacuolar degradation of membrane protein, cargo vacuolar sorting, autophagic degradation, and vacuole biogenesis in Arabidopsis (Arabidopsis thaliana). Here, we report the characterization of RESURRECTION1 (RST1) as a suppressor of free1 that, when mutated as a null mutant, restores the normal MVB and vacuole formation of a FREE1-RNAi knockdown line and consequently allows survival. RST1 encodes an evolutionarily conserved multicellular organism-specific protein, which contains two Domain of Unknown Function 3730 domains, showing no similarity to known proteins, and predominantly localizes in the cytosol. The depletion of FREE1 causes substantial accumulation of RST1, and transgenic Arabidopsis plants overexpressing RST1 display retarded seedling growth with dilated MVBs, and inhibition of endocytosed FM4-64 dye to the tonoplast, suggesting that RST1 has a negative role in vacuolar transport. Consistently, enhanced endocytic degradation of membrane vacuolar cargoes occurs in the rst1 mutant. Further transcriptomic comparison of rst1 with free1 revealed a negative association between gene expression profiles, demonstrating that FREE1 and RST1 have antagonistic functions. Thus, RST1 is a negative regulator controlling membrane protein homeostasis and FREE1-mediated functions in plants.

Enhanced Removal of Hydrophobic Short-Chain n-Alkanes from Gas Streams in Biotrickling Filters in Presence of Surfactant.

Emissions of n-alkanes are facing increasingly stringent management challenges. Biotrickling filtration in the presence of surfactants is a competitive alternative for the enhanced removal of n-alkanes. Herein, sodium dodecyl benzene sulfonate (SDBS) was added into the liquid phase feeding a biotrickling filter (BTF) to enhance the removal of various short-chain n-alkanes from n-hexane (C6) to methane (C1). The removal performance of C6-C1 and microbial response mechanisms were explored. The results showed that the removal efficiency (RE) of n-alkanes decreased from 77 ± 1.3 to 35 ± 5.6% as the carbon chain number of n-alkanes decreased from C6 to C1, under the conditions of an n-alkane inlet load of 58 ± 3.0 g/m3·h and EBCT of 30 s. The removal performance of n-alkanes was enhanced significantly by the introduction of 15 mg/L SDBS, as the RE of C6 reached 99 ± 0.7% and the RE of C1 reached 74 ± 3.3%. The strengthening mechanisms were that the apparent Henry's law coefficient of n-alkanes decreased by 11 ± 1.4-30 ± 0.3%, and the cell surface hydrophobicity of microorganisms improved from 71 ± 5.6 to 87 ± 4.0% with the existence of SDBS. Moreover, the presence of SDBS promoted the succession and activity of the microbial community. The activities of alkane hydroxylase and alcohol dehydrogenase were 5.8 and 5.9 times higher than those without SDBS, and the concentration of the cytochrome P450 gene was improved 2.2 times. Therefore, the addition of SDBS is an effective strategy that makes BTF suitable for the removal of various n-alkanes from waste gas streams.

Reactive Nitrogen Species Mediated Inactivation of Pathogenic Microorganisms during UVA Photolysis of Nitrite at Surface Water Levels.

UVA photolysis of nitrite (NO2-) occurs in a number of natural and engineered aquatic systems. This study reports for the first time that pathogenic microorganisms can be effectively inactivated during the coexposure of UVA irradiation and NO2- under environmentally relevant conditions. The results demonstrated that more than 3 log inactivation of Escherichia coli K-12, Staphylococcus aureus, and Spingopyxis sp. BM1-1 was achieved by UVA photolysis of 2.0 mg-N L-1 of NO2- in synthetic drinking water and real surface water. The inactivation was mainly attributed to the reactive species generated from UVA photolysis of NO2- rather than UVA irradiation or NO2- oxidation alone. The inactivation was predominantly contributed by the reactive nitrogen species (NO2• and ONOO-/HOONO) instead of the reactive oxygen species (HO• or O2•-). A kinetic model to simulate the reactive species generation from UVA photolysis of NO2- was established, validated, and used to predict the contributions of different reactive species to the inactivation under various environmental conditions. Several advanced tools (e.g., D2O - labeling with Raman spectroscopy) were used to demonstrate that the inactivation by the UVA/NO2- treatment was attributed to the DNA destruction by the reactive nitrogen species, which completely suppressed the viable but nonculturable (VBNC) states and the reactivation of bacteria. This study highlights a novel process for the inactivation of pathogenic microorganisms in water and emphasizes the critical role of reactive nitrogen species in water disinfection and purification.

Association of lipid metabolism-related gene promoter methylation with risk of coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is a complex disease that is influenced by environmental and genetic factors. Lipid levels are regarded as a major risk factor for CAD, and epigenetic mechanisms might be involved in the regulation of CAD development. This study was designed to investigate the association between the DNA methylation status of 8 lipid metabolism-related genes and the risk of CAD in the Chinese Han population. METHODS: A total of 260 individuals were sampled in this study, including 120 CAD cases and 140 normal healthy controls. DNA methylation status was tested via targeted bisulfite sequencing. RESULTS: The results indicated a significant association between hypomethylation of the APOC3, CETP and APOC1 gene promoters and the risk of CAD. Individuals with higher methylation levels of the APOA5 and LIPC gene promoters had increased risks for CAD. In addition, ANGPTL4 methylation level was significantly associated with CAD in males but not females. There were no significant differences in the methylation levels of the APOB and PCSK9 gene promoters between CAD patients and controls. CONCLUSIONS: The methylation status of the APOC3, APOA5, LIPC, CETP and APOC1 gene promoters may be associated with the development of CAD.

A moderate dosage of coffee causes acute retinal capillary perfusion decrease in healthy young individuals.

AIM: Caffeinated beverages are very popular across populations and cultures, but quantitative evidence of the acute effects of moderate coffee doses on retinal perfusion is sparse and contradicting. Thus, the aim of this randomized, cross-over and parallel-group design study was to investigate whether moderate consumption of coffee alters macular retinal capillary perfusion in young healthy individuals. METHODS: Twenty-seven young healthy individuals were recruited for this study. Acute changes in retinal microvasculature were assessed using spectral-domain optical coherence tomography angiography (SD-OCTA) at baseline, 0.5 h, and 2 h after intake of coffee, or water. Meanwhile, cerebral blood flow (CBF) and retina-choroid blood flow were evaluated in a parallel-group design (4 participants each in coffee or water group) using magnetic resonance imaging (MRI) with pseudo-continuous arterial spin labeling sequences. RESULTS: Two hours after coffee intake, blood caffeine concentration increased from 0 to 5.05 ± 1.36 µg/mL. Coffee caused a significant decrease in retinal vessel diameter index (VDI) (19.05 ± 0.24 versus [vs] 19.13 ± 0.26; p < 0.001) and CBF in the frontal lobe (77.47 ± 15.21 mL/100 mL/min vs. 84.13 ± 15.55 mL/100 mL/min; p < 0.05) 2 h after intake. However, it significantly increased retina-choroid blood flow after 0.5 and 2 h (163.18 ± 61.07 mL/100 mL/min vs. 132.68 ± 70.47 mL/100 mL/min, p < 0.001, and 161.21 ± 47.95 vs. 132.68 ± 70.47; p < 0.001, respectively). CONCLUSION: This is the first study to demonstrate the acute effects of daily dose coffee consumption on retinal capillary perfusion using SD-OCTA combinate with blood flow MRI. The findings imply that although moderate coffee intake caused a significant increase in retina-choroid blood flow, there was a significant acute decrease both in macular retinal capillary perfusion and CBF.

Early Retinal Microvasculopathy in Prediabetic Patients and Correlated Factors.

INTRODUCTION: We aimed to detect early retinal microcirculation changes in prediabetic patients and investigate their correlation with clinical examinations. METHODS: Forty-seven prediabetic individuals, 29 controls, and 81 type 2 diabetic mellitus (T2DM) patients were enrolled in this study. A review of clinical data and spectral-domain optical coherence tomography angiography (SD-OCTA) parameters of macular vessel diameter (VD), foveal avascular zone (FAZ), and macular vessel area density (VAD) was performed. RESULTS: Levels of low-density lipoprotein cholesterol and triglycerides in prediabetes and T2DM groups were significantly higher than those in the control group. Urine microalbumin-to-creatinine ratio (ACR) was mildly and moderately increased in the prediabetes and T2DM groups, respectively. Estimated glomerular filtration rate of the three groups were within the normal range. SD-OCTA showed that VAD in the superficial macular area was decreased in the prediabetes group compared to the control group (p=0.01). The FAZ size, particularly in the deep layer, was expanded in the prediabetes group. In the deep retinal layer of the macular area, VD and FAZ size in the prediabetes group were larger than those in the control group. In the prediabetes group, the axial length was significantly correlated with macular VD and FAZ size (p<0.05), and ACR was correlated with FAZ size (p<0.05). Age had a negative correlation with VAD (p<0.01). ACR had a positive correlation with FAZ size (p<0.05). CONCLUSIONS: Enlargement and irregularity of the FAZ area, deep capillary dilation, and decrease in VAD occur in the retina of prediabetes patients with mild kidney function impairment.

A Nomogram for Predicting Acute Respiratory Failure After Cervical Traumatic Spinal Cord Injury Based on Admission Clinical Findings.

OBJECTIVES: Acute respiratory failure (ARF) is a common medical complication in patients with cervical traumatic spinal cord injury (TSCI). To identify independent predictors for ARF onset in patients who underwent cervical TSCI without premorbid respiratory diseases and to apply appropriate medical supports based on accurate prediction, a nomogram relating admission clinical information was developed for predicting ARF during acute care period. METHODS: We retrospectively reviewed clinical profiles of patients who suffered cervical TSCI and were emergently admitted to Qingdao Municipal Hospital from 2014 to 2020 as the training cohort. Univariate analysis was performed using admission clinical variables to estimate associated factors and a nomogram for predicting ARF occurrence was generated based on the independent predictors from multivariate logistic regression analysis. This nomogram was assessed by concordance index for discrimination and calibration curve with internal-validated bootstrap strategy. Receiver operating characteristic curve was conducted to compare the predictive accuracy between the nomogram and the traditional gold standard, which combines neuroimaging and neurological measurements by using area under the receiver operating characteristic curve (AUC). An additional 56-patient cohort from another medical center was retrospectively reviewed as the test cohort for external validation of the nomogram. RESULTS: 162 patients were eligible for this study and were included in the training cohort, among which 25 individuals developed ARF and were recorded to endure more complications. Despite the aggressive treatments and prolonged intensive care unit cares, 14 patients insulted with ARF died. Injury level, American Spinal Injury Association Impairment Scale (AIS) grade, admission hemoglobin (Hb), platelet to lymphocyte ratio, and neutrophil percentage to albumin ratio (NPAR) were independently associated with ARF onset. The concordance index of the nomogram incorporating these predictors was 0.933 in the training cohort and 0.955 in the test cohort, although both calibrations were good. The AUC of the nomogram was equal to concordance index, which presented better predictive accuracy compared with previous measurements using neuroimaging and AIS grade (AUC 0.933 versus 0.821, Delong's test p < 0.001). Similar significant results were also found in the test cohort (AUC 0.955 versus 0.765, Delong's test p = 0.034). In addition, this nomogram was translated to a Web-based calculator that could generate individual probability for ARF in a visualized form. CONCLUSIONS: The nomogram incorporating the injury level, AIS grade, admission Hb, platelet to lymphocyte ratio, and NPAR is a promising model to predict ARF in patients with cervical TSCI who are absent from previous respiratory dysfunction. This nomogram can be offered to clinicians to stratify patients, strengthen evidence-based decision-making, and apply appropriate individualized treatment in the field of acute clinical care.

MiR-574-5p promotes the differentiation of human cardiac fibroblasts via regulating ARID3A.

Cardiac fibrosis after myocardial infarction (MI) is mainly associated with cardiac fibroblasts and its differentiation is the key pathological process. However, the cellular mechanism of fibroblast-to-myofibroblast conversion has not been clarified and a deeper mechanistic understanding is needed. We found that miR-574-5p was up-regulated in TGF-ß-induced myofibroblast differentiation. Silencing transiently miR-574-5p in HCFs, we found that suppression of miR-574-5p decreased myofibroblasts differentiation as validated by expression levels of fibrosis related genes, EDU imaging assay, wound healing assay and transwell assays. Conversely, overexpression of miR-574-5p displayed opposite results. ARID3A was verified as a direct target gene of miR-574-5p and decreased level of ARID3A forced fibroblast-to-myofibroblast differentiation of TGF-ß-induced HCFs. Our data suggests that miR-574-5p plays a pivotal role in human cardiac fibroblasts (HCFs) myofibroblast differentiation and demonstrates that miR-574-5p and arid3a may be a novel therapeutic target for cardiac fibrosis.

KPC1 alleviates hypoxia/reoxygenation-induced apoptosis in rat cardiomyocyte cells though BAX degradation.

Bax triggers cell apoptosis by permeabilizing the outer mitochondrial membrane, leading to membrane potential loss and cytochrome c release. However, it is unclear if proteasomal degradation of Bax is involved in the apoptotic process, especially in heart ischemia-reperfusion (I/R)-induced injury. In the present study, KPC1 expression was heightened in left ventricular cardiomyocytes of patients with coronary heart disease (CHD), in I/R-myocardium in vivo and in hypoxia and reoxygenation (H/R)-induced cardiomyocytes in vitro. Overexpression of KPC1 reduced infarction size and cell apoptosis in I/R rat hearts. Similarly, the forced expression of KPC1 restored mitochondrial membrane potential (MMP) and cytochrome c release driven by H/R in H9c2 cells, whereas reducing cell apoptosis, and knockdown of KPC1 by short-hairpin RNA (shRNA) deteriorated cell apoptosis induced by H/R. Mechanistically, forced expression of KPC1 promoted Bax protein degradation, which was abolished by proteasome inhibitor MG132, suggesting that KPC1 promoted proteasomal degradation of Bax. Furthermore, KPC1 prevented basal and apoptotic stress-induced Bax translocation to mitochondria. Bax can be a novel target for the antiapoptotic effects of KPC1 on I/R-induced cardiomyocyte apoptosis and render mechanistic penetration into at least a subset of the mitochondrial effects of KPC1.

Thymoquinone protects human retinal pigment epithelial cells against hydrogen peroxide induced oxidative stress and apoptosis.

Oxidative stress in retinal pigment epithelium (RPE) cells may contribute to the progression of age-related macular degeneration. Thymoquinone (TQ), an active component derived from Nigella sativa, possesses antioxidative effect. However, the role of TQ in RPE cells under oxidative stress condition remains unclear. The present study aimed to examine the protective effect of TQ against hydrogen peroxide (H2 O2 )-induced oxidative stress in human RPE cells. Our results showed that TQ improved the cell viability and apoptosis in H2 O2 -induced ARPE cells. We also found that the levels of reactive oxygen species and malondialdehyde induced by H2 O2 were reduced after the pretreatment of TQ. In addition, the inhibitory effect of H2 O2 on the glutathione (GSH) level and superoxide dismutase activity was markedly attenuated by TQ pretreatment. Moreover, TQ enhanced the activation of Nrf2/heme oxygenase 1 (HO-1) signaling pathway in H2 O2 -induced ARPE cells. Knockdown of Nrf2 abolished the protective effect of TQ on H2 O2 -induced oxidative damage. These results suggested that TQ protected ARPE cells from H2 O2 -induced oxidative stress and apoptosis via the Nrf2/HO-1 signaling pathway.

RGC-32 (Response Gene to Complement 32) Deficiency Protects Endothelial Cells From Inflammation and Attenuates Atherosclerosis.

OBJECTIVE: The objective of this study is to determine the role and underlying mechanisms of RGC-32 (response gene to complement 32 protein) in atherogenesis. APPROACH AND RESULTS: RGC-32 was mainly expressed in endothelial cells of atherosclerotic lesions in both ApoE-/- (apolipoprotein E deficient) mice and human patients. Rgc-32 deficiency (Rgc32-/-) attenuated the high-fat diet-induced and spontaneously developed atherosclerotic lesions in ApoE-/- mice without affecting serum cholesterol concentration. Rgc32-/- seemed to decrease the macrophage content without altering collagen and smooth muscle contents or lesional macrophage proliferation in the lesions. Transplantation of WT (wild type) mouse bone marrow to lethally irradiated Rgc32-/- mice did not alter Rgc32-/--caused reduction of lesion formation and macrophage accumulation, suggesting that RGC-32 in resident vascular cells, but not the macrophages, plays a critical role in the atherogenesis. Of importance, Rgc32-/- decreased the expression of ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) in endothelial cells both in vivo and in vitro, resulting in a decrease in TNF-α (tumor necrosis factor-α)-induced monocyte-endothelial cell interaction. Mechanistically, RGC-32 mediated the ICAM-1 and VCAM-1 expression, at least partially, through NF (nuclear factor)-κB signaling pathway. RGC-32 directly interacted with NF-κB and facilitated its nuclear translocation and enhanced TNF-α-induced NF-κB binding to ICAM-1 and VCAM-1 promoters. CONCLUSIONS: RGC-32 mediates atherogenesis by facilitating monocyte-endothelial cell interaction via the induction of endothelial ICAM-1 and VCAM-1 expression, at least partially, through NF-κB signaling pathway.

Oxyresveratrol protects human lens epithelial cells against hydrogen peroxide-induced oxidative stress and apoptosis by activation of Akt/HO-1 pathway.

Oxidative stress induced by hydrogen peroxide (H2O2) triggers human lens epithelial cell (HLEC) apoptosis and initiates cataract formation. Oxyresveratrol (Oxy) was reported to possess antioxidant and free radical scavenging activities. Herein, we investigated the effects of Oxy on H2O2-induced oxidative stress and apoptosis in HLECs and the associated mechanisms. Cell viability was detected by MTT assay. The oxidative damage was assessed by measuring the activities of superoxide dismutases-1 (SOD-1), catalase (CAT), glutathione reductase (GSH), and malondialdehyde (MDA). Apoptosis was analyzed by flow cytometry analysis. The changed expressions of heme oxygenase-1 (HO-1) and protein kinase B (Akt) pathways were evaluated by qRT-PCR and western blot. We found that exposure to H2O2 dose-dependently reduced cell viability, and induced oxidative stress and apoptosis in HLECs, which were reversed by pretreatment with Oxy. Oxy increased p-Akt and HO-1 expressions in H2O2-stimulated HLECs. Akt and HO-1 expressions form a regulatory axis and Oxy activated the Akt/HO-1 pathway in H2O2-stimulated HLECs. Inhibition of the Akt/HO-1 pathway by LY294002 or ZnPP attenuated the effects of Oxy on oxidative stress and apoptosis in H2O2-stimulated HLECs. In conclusion, Oxy protected H2O2-induced oxidative stress and apoptosis through activating the Akt/HO-1 pathway, suggesting the protective effect of Oxy against H2O2-induced cataract.

The diagnostic accuracy of an intelligent and automated fundus disease image assessment system with lesion quantitative function (SmartEye) in diabetic patients.

BACKGROUND: With the diabetes mellitus (DM) prevalence increasing annually, the human grading of retinal images to evaluate DR has posed a substantial burden worldwide. SmartEye is a recently developed fundus image processing and analysis system with lesion quantification function for DR screening. It is sensitive to the lesion area and can automatically identify the lesion position and size. We reported the diabetic retinopathy (DR) grading results of SmartEye versus ophthalmologists in analyzing images captured with non-mydriatic fundus cameras in community healthcare centers, as well as DR lesion quantitative analysis results on different disease stages. METHODS: This is a cross-sectional study. All the fundus images were collected from the Shanghai Diabetic Eye Study in Diabetics (SDES) program from Apr 2016 to Aug 2017. 19,904 fundus images were acquired from 6013 diabetic patients. The grading results of ophthalmologists and SmartEye are compared. Lesion quantification of several images at different DR stages is also presented. RESULTS: The sensitivity for diagnosing no DR, mild NPDR (non-proliferative diabetic retinopathy), moderate NPDR, severe NPDR, PDR (proliferative diabetic retinopathy) are 86.19, 83.18, 88.64, 89.59, and 85.02%. The specificity are 63.07, 70.96, 64.16, 70.38, and 74.79%, respectively. The AUC are PDR, 0.80 (0.79, 0.81); severe NPDR, 0.80 (0.79, 0.80); moderate NPDR, 0.77 (0.76, 0.77); and mild NPDR, 0.78 (0.77, 0.79). Lesion quantification results showed that the total hemorrhage area, maximum hemorrhage area, total exudation area, and maximum exudation area increase with DR severity. CONCLUSIONS: SmartEye has a high diagnostic accuracy in DR screening program using non-mydriatic fundus cameras. SmartEye quantitative analysis may be an innovative and promising method of DR diagnosis and grading.