Peak Broadening in Photoelectron Spectroscopy of Amorphous Polymers: The Leading Role of the Electrostatic Landscape.

The broadening in photoelectron spectra of polymers can be attributed to several factors, such as light source spread, spectrometer resolution, the finite lifetime of the hole state, and solid-state effects. Here, for the first time, we set up a computational protocol to assess the peak broadening induced for both core and valence levels by solid-state effects in four amorphous polymers by using a combination of density functional theory, many-body perturbation theory, and classical polarizable embedding. We show that intrinsic local inhomogeneities in the electrostatic environment induce a Gaussian broadening of 0.2-0.7 eV in the binding energies of both core and semivalence electrons, corresponding to a full width at half-maximum (FWHM) of 0.5-1.7 eV for the investigated systems. The induced broadening is larger in acrylate-based than in styrene-based polymers, revealing the crucial role of polar groups in controlling the roughness of the electrostatic landscape in the solid matrix.

Prdx6 Regulates Nlrp3 Inflammasome Activation-Driven Inflammatory Response in Lens Epithelial Cells.

The continuum of antioxidant response dysregulation in aging/oxidative stress-driven Nlrp3 inflammasome activation-mediated inflammatory response is associated with age-related diseases. Peroxiredoxin (Prdx) 6 is a key antioxidant that provides cytoprotection by regulating redox homeostasis. Herein, using lens epithelial cells (LECs) derived from the targeted inactivation of Prdx6 gene and aging lenses, we present molecular evidence that Prdx6-deficiency causes oxidative-driven Nlrp3 inflammasome activation, resulting in pyroptosis in aging/redox active cells wherein Prdx6 availability offsets the inflammatory process. We observed that Prdx6-/- and aging LECs harboring accumulated reactive oxygen species (ROS) showed augmented activation of Nlrp3 and bioactive inflammatory components, like Caspase-1, IL-1ß, ASC and Gasdermin-D. Similar to lipopolysaccharide treatment, oxidative exposure led to further ROS amplification with increased activation of the Nlrp3 inflammasome pathway. Mechanistically, we found that oxidative stress enhanced Kruppel-like factor 9 (Klf9) expression in aging/Prdx6-/- mLECs, leading to a Klf9-dependent increase in Nlrp3 transcription, while the elimination of ROS by the delivery of Prdx6 or by silencing Klf9 prevented the inflammatory response. Altogether, our data identify the biological significance of Prdx6 as an intrinsic checkpoint for regulating the cellular health of aging or redox active LECs and provide opportunities to develop antioxidant-based therapeutic(s) to prevent oxidative/aging-related diseases linked to aberrant Nlrp3 inflammasome activation.

The Rydberg 3p multiplet structure of the fenchone C band absorption.

The vibrationally structured 3pz Rydberg excitation is identified and assigned in the VUV absorption spectrum of fenchone with an origin at 6.31 eV, below the prominent 6.4 eV C̃ (nominally 3p) band onset. This feature cannot, however, be observed in (2+1) REMPI spectra, as its relative excitation cross-section is much reduced in a two-photon transition. The 3py and 3px excitation thresholds, found to differ by only 10-30 meV, lie around 6.4 eV corresponding to the first intense C̃ band peak in both VUV and REMPI spectra. Calculations of vertical and adiabatic Rydberg excitation energies, photon absorption cross-sections, and vibrational profiles are used to support these interpretations.

Hydralazine Revives Cellular and Ocular Lens Health-Span by Ameliorating the Aging and Oxidative-Dependent Loss of the Nrf2-Activated Cellular Stress Response.

A major hallmark of aging-associated diseases is the inability to evoke cellular defense responses. Transcriptional protein Nrf2 (nuclear factor erythroid-derived 2-related factor) plays a pivotal role in the oxidative stress response, cellular homeostasis, and health span. Nrf2's activation has been identified as a therapeutic target to restore antioxidant defense in aging. Here, we demonstrated that FDA-approved drug, hydralazine (Hyd), was a reactivator of the Nrf2/ARE (antioxidant response element) pathway in various ages and types of mouse (m) or human (h) lens epithelial cells (LECs) and mice lenses in-vitro/in-vivo. This led to Hyd-driven abatement of carbonyls, reduced reactive oxygen species (ROS), and reduced 4-HNE/MDA-adducts with cytoprotection, and extended lens healthspan by delaying/preventing lens opacity against aging/oxidative stress. We elucidated that Hyd activated the protective signaling by inducing Nrf2 to traverse from the cytoplasm to the nucleus and potentiated the ARE response by direct interaction of Nrf2 and ARE sequences of the promoter. Loss-of-function study and cotreatment of Hyd and antioxidant, N-acetyl cysteine (NAC) or Peroxiredoxin (Prdx)6, specified that Nrf2/ARE-driven increase in the promoter activity was Hyd-dependent. Our study provides proof-of concept evidence and, thereby, paves the way to repurposing Hyd as a therapeutic agent to delay/prevent aging and oxidative-related disorders.

Susceptibility of male reproductive system to bisphenol A, an endocrine disruptor: Updates from epidemiological and experimental evidence.

Bisphenol A (BPA) is an omnipresent environmental pollutant. Despite being restrictions in-force for its utilization, it is widely being used in the production of polycarbonate plastics and epoxy resins. Direct, low-dose, and long-term exposure to BPA is expected when they are used in the packaging of food products and are used as containers for food consumption. Occupationally, workers are typically exposed to BPA at higher levels and for longer periods during the manufacturing process. BPA is a known endocrine disruptor chemical (EDC), that causes male infertility, which has a negative impact on human life from emotional, physical, and societal standpoints. To minimize the use of BPA in numerous consumer products, efforts and regulations are being made. Despite legislative limits in numerous nations, BPA is still found in consumer products. This paper examines BPA's overall male reproductive toxicity, including its impact on the hypothalamic-pituitary-testicular (HPT) axis, hormonal homeostasis, testicular steroidogenesis, sperm parameters, reproductive organs, and antioxidant defense system. Furthermore, this paper highlighted the role of non-monotonic dose-response (NMDR) in BPA exposure, which will help to improve the overall understanding of the harmful effects of BPA on the male reproductive system.

First report of classical knockdown resistance (kdr) mutation, L1014F, in human head louse Pediculus humanus capitis (Phthiraptera: Anoplura).

There are at least three known knockdown resistance (kdr) mutations reported globally in the human head louse Pediculus humanus capitis De Geer (Phthiraptera: Anoplura) that are associated with reduced sensitivity to pyrethroids. However, the prevalence of kdr mutation in head lice is not known in the Indian subcontinent. To identify kdr mutations in the Indian head lice population, the genomic region of the voltage-gated sodium channel gene encompassing IIS1-2 linker to IIS6 segments was PCR-amplified and sequenced from P. humanus capitis samples collected from different geographic localities of India. DNA sequencing revealed the presence of four kdr mutations: M827I, T929I, L932F and L1014F. The presence of a classical kdr mutation L1014F, the most widely reported mutation across insect-taxa associated with the kdr-trait, is being reported for the first time in P. humanus capitis.

Obligatory Role of AMPK Activation and Antioxidant Defense Pathway in the Regulatory Effects of Metformin on Cellular Protection and Prevention of Lens Opacity.

Increasing levels of oxidative-stress due to deterioration of the Nrf2 (NFE2-related factor)/ARE (antioxidant response element) pathway is found to be a primary cause of aging pathobiology. Metformin having anti-aging effects can delay/halt aging-related diseases. Herein, using lens epithelial cell lines (LECs) of human (h) or mouse (m) and aging h/m primary LECs along with lenses as model systems, we demonstrated that Metformin could correct deteriorated Bmal1/Nrf2/ARE pathway by reviving AMPK-activation, and transcriptional activities of Bmal1/Nrf2, resulting in increased antioxidants enzymatic activity and expression of Phase II enzymes. This ensued reactive oxygen species (ROS) mitigation with cytoprotection and prevention of lens opacity in response to aging/oxidative stress. It was intriguing to observe that Metformin internalized lens/LECs and upregulated OCTs (Organic Cation Transporters). Mechanistically, we found that Metformin evoked AMPK activation-dependent increase of Bmal1, Nrf2, and antioxidants transcription by promoting direct E-Box and ARE binding of Bmal1 and Nrf2 to the promoters. Loss-of-function and disruption of E-Box/ARE identified that Metformin acted by increasing Bmal1/Nrf2-mediated antioxidant expression. Data showed that AMPK-activation was a requisite for Bmal1/Nrf2-antioxidants-mediated defense, as pharmacologically inactivating AMPK impeded the Metformin's effect. Collectively, the results for the first-time shed light on the hitherto incompletely uncovered crosstalk between the AMPK and Bmal1/Nrf2/antioxidants mediated by Metformin for blunting oxidative/aging-linked pathobiology.

A clinical study of fetal outcome following early and delayed cord clamping in births associated with anemia in pregnancy.

Background: As there is a risk for infant anaemia, early cord clamping which is usually performed at 10-15 seconds of delivery was changed to delayed cord clamping for at least for 30 seconds Delayed cord clamping (DCC) increases the blood volume and haemoglobin levels in newborns and reduces risk of iron deficiency anaemia in both term and preterm infants.Early clamping allows cord blood collection in benefit for transplantation of stem cells. Research Objective: To compare levels of haemoglobin, hematocrit and serum ferritin at birth and 4 weeks of age in babies as well as neonatal outcome following early and delayed cord clamping in births associated with anaemia in pregnancy. Study Design: An observational study. Participants: Anaemic pregnant women with period of gestation 32-40 weeks admitted in labour room for delivery were enrolled. Intervention: Grouping of the patients was done according to the timing of the umbilical cord clamping. 1. Early cord clamping (< 60 seconds) 2. Delayed cord clamping (1 - 3 minutes) Of which 58 subjects were in ECC (early cord clamping)and 62 were in DCC (delayed cord clamping)group. Results: There was no significance of ECC or DCC in developing polycythemia, IVH or hyperbilirubinemia or increased need of blood transfusion. The levels of haemoglobin, hematocrit and ferritin levels were showing significant increased among DCC as compared to ECC. Conclusion: Delayed cord clamping significantly increases the levels of haemoglobin, Serum ferritin and hematocrit at 4 weeks of age. It should be recommended in routine practice where it is not contraindicated especially in resource- poor settings.

Switching of Redox Signaling by Prdx6 Expression Decides Cellular Fate by Hormetic Phenomena Involving Nrf2 and Reactive Oxygen Species.

Changes in intracellular reactive oxygen species (ROS) levels due to remodeling of antioxidant defense can affect the status of biological homeostasis in aging/oxidative stress. Peroxiredoxin 6 (Prdx6), an antioxidant gene downstream target for the Nrf2 pathway, plays a role in regulating ROS homeostasis. Using aging human (h) lens epithelial cells (LECs) or Prdx6-deficient (Prdx6-/-) mouse (m) LECs, here we showed that dichlorofluorescein (DCF) oxidation or H2O2 were strictly controlled by Prdx6. We observed that a moderate degree of oxidative stress augmented Nrf2-mediated Prdx6 expression, while higher doses of H2O2 (≥100 µM) caused a dramatic loss of Prdx6 expression, resulting in increased DCF oxidation and H2O2 amplification and cell death. Mechanistically, at increased oxidative stress, Nrf2 upregulated transcriptional factor Klf9, and that Klf9 bound to the promoter and repressed the Prdx6 gene. Similarly, cells overexpressing Klf9 displayed Klf9-dependent Prdx6 suppression and DCF oxidation with H2O2 amplification, while ShKlf9 reversed the process. Our data revealed that H2O2 and DCF oxidation levels play a hormetical role, and the Nrf2-Klf9-Prdx6 pathway is pivotal for the phenomena under the conditions of oxidative load/aging. On the whole, the results demonstrate that oxidative hormetical response is essentially based on levels of oxidative triggering and the status of Klf9-Prdx6 pathway activation; thus, Klf9 can be considered as a therapeutic target for hormetic shifting of cellular defense to improve protective resilience to oxidative stress.

Occupational lead exposure is an independent modulator of hypertension and poor pulmonary function: A cross-sectional comparative study in lead-acid battery recycling workers.

Blood lead level (BLL) is the primary biomarker for lead-exposure monitoring in occupationally exposed workers. We evaluated occupational lead-exposure (OE) impact on cardiopulmonary functions in lead-acid battery recycling unit workers. Seventy-six OE cases and 30 control subjects were enrolled for questionnaire-based socio-demographic, dietary, tobacco usage, and medical history data. Anthropometric measurements, systolic and diastolic blood pressure (SBP and DBP), and pulmonary function tests were performed. Venous blood was collected for BLL, hematological analysis, and biochemical analysis. OE caused a significant increase in BLL, SBP, DBP, and small airways obstruction in lung function tests. It also impaired platelet indices, affected renal and liver biochemical measurements, and promoted oxidative stress and DNA damage. Multilinear regression analysis suggested that BLL affected SBP (ß = 0.314, p = .034) and increased small airways obstruction (FEV1/FVC, ß = -0.37, p = .05; FEV25-75%, ß = -0.351, p = .016). Higher BLL appears to be an independent modulator of hypertension and poor pulmonary function upon occupational lead exposure in lead-acid battery recyclers.

Role of Decorin in the Lens and Ocular Diseases.

Decorin is an archetypal member of the small leucine-rich proteoglycan gene family and is involved in various biological functions and many signaling networks, interacting with extra-cellular matrix (ECM) components, growth factors, and receptor tyrosine kinases. Decorin also modulates the growth factors, cell proliferation, migration, and angiogenesis. It has been reported to be involved in many ischemic and fibrotic eye diseases, such as congenital stromal dystrophy of the cornea, anterior subcapsular fibrosis of the lens, proliferative vitreoretinopathy, et al. Furthermore, recent evidence supports its role in secondary posterior capsule opacification (PCO) after cataract surgery. The expression of decorin mRNA in lens epithelial cells in vitro was found to decrease upon transforming growth factor (TGF)-ß-2 addition and increase upon fibroblast growth factor (FGF)-2 addition. Wound healing of the injured lens in mice transgenic for lens-specific human decorin was promoted by inhibiting myofibroblastic changes. Decorin may be associated with epithelial-mesenchymal transition and PCO development in the lens. Gene therapy and decorin administration have the potential to serve as excellent therapeutic approaches for modifying impaired wound healing, PCO, and other eye diseases related to fibrosis and angiogenesis. In this review, we present findings regarding the roles of decorin in the lens and ocular diseases.

Influence of Vibrational Excitation and Nuclear Dynamics in Multiphoton Photoelectron Circular Dichroism of Fenchone.

We report photoelectron circular dichroism of S-(+)-fenchone enantiomers recorded with state-state vibrational level resolution using picosecond laser (2 + 1) resonance enhanced multiphoton ionization via 3s and 3p Rydberg intermediate states. The 3p state decays to the 3s state on a picosecond time scale so that, above the 3p Rydberg excitation threshold, ionization of vibrationally hot 3s states competes with direct 3p-1 ionization. Complex vibronic dynamics of the 3p → 3s internal conversion weaken the Rydberg Δv = 0 propensity rule in both the 3p-1 and 3s-1 ionization channels. Large variations of the forward-backward chiral asymmetry factors are observed between the Δv = 0 and Δv > 0 vibrational transitions, including dramatic swings from up to ±17%. Such changes of sign indicate complete reversal of the preferred direction for photoelectron emission in the laboratory frame, associated with vibrational motion. These asymmetry switches easily exceed the amplitude and frequency of such vibrationally induced flips previously observed in single photon ionization.

Engineered Sumoylation-Deficient Prdx6 Mutant Protein-Loaded Nanoparticles Provide Increased Cellular Defense and Prevent Lens Opacity.

Aberrant Sumoylation-mediated protein dysfunction is involved in a variety of oxidative and aging pathologies. We previously reported that Sumoylation-deficient Prdx6K(lysine)122/142R(Arginine) linked to the TAT-transduction domain gained stability and protective efficacy. In the present study, we formulated wild-type TAT-HA-Prdx6WT and Sumoylation-deficient Prdx6-loaded poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) to further enhance stability, protective activities, and sustained delivery. We found that in vitro and subconjuctival delivery of Sumoylation-deficient Prdx6-NPs provided a greater protection of lens epithelial cells (LECs) derived from human and Prdx6-/--deficient mouse lenses against oxidative stress, and it also delayed the lens opacity in Shumiya cataract rats (SCRs) than TAT-HA-Prdx6WT-NPs. The encapsulation efficiencies of TAT-HA-Prdx6-NPs were ≈56%-62%. Dynamic light scattering (DLS) and atomic force microscopy (AFM) analyses showed that the NPs were spherical, with a size of 50-250 nm and a negative zeta potential (≈23 mV). TAT-HA-Prdx6 analog-NPs released bioactive TAT-HA-Prdx6 (6%-7%) within 24 h. Sumoylation-deficient TAT-HA-Prdx6-NPs provided 35% more protection by reducing the oxidative load of LECs exposed to H2O2 compared to TAT-HA-Prdx6WT-NPs. A subconjuctival delivery of TAT-HA-Prdx6 analog-NPs demonstrated that released TAT-HA-Prdx6K122/142R could reduce lens opacity by ≈60% in SCRs. Collectively, our results demonstrate for the first time that the subconjuctival delivery of Sumoylation-deficient Prdx6-NPs is efficiently cytoprotective and provide a proof of concept for potential use to delay cataract and oxidative-related pathobiology in general.

Viral load could be an important determinant for fomites based transmission of viral infections.

BACKGROUND AND OBJECTIVE: Fomites are common sources of transmission of certain infections. Infectious pathogens, such as viruses known to cause respiratory tract infections, are common examples of being transmitted by fomites. However, the load of the particular pathogen on these inanimate surfaces is a crucial factor for the transmission. The current study aims at investigating the load of one such viral pathogen on the surfaces of commonly used materials. METHODS: Based on the cycle threshold (Ct) values in the diagnostic system using gene amplification for the considered viral pathogen, we categorized the positive samples for high (17 to < 24), moderate (24 to < 31), or mild (31 to < 38) viral load. Five randomly selected samples from each of these category were smeared on commonly used cardboard surface (absorbent surface) and stainless steel (non-absorbent surface). After an observation duration of 90 min, samples from the surfaces were analyzed again for gene amplification using RT-PCR. RESULTS: Viral load/titter positively correlated with the viral material on either of these investigated surfaces post-observation duration. Higher viral load (low Ct) samples exhibited higher probability of being detected on the surfaces than those samples with lower/moderate (high Ct) viral load. INTERPRETATION AND CONCLUSION: Common inanimate surfaces are potential source of the viral transmission, however the viral load on these surfaces are key determinant of such transmission.

Role of Decorin in Posterior Capsule Opacification and Eye Lens Development.

Decorin (DCN) is involved in a variety of physiological and pathological processes. Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) has been proposed as a major cause for the development of posterior capsule opacification (PCO) after cataract surgery. We investigated the plausible target gene(s) that suppress PCO. The expression of Dcn was significantly upregulated in rat PCO tissues compared to that observed in the control using a microarray-based approach. LECs treated with fibroblast growth factor (FGF) 2 displayed an enhanced level of DCN expression, while LECs treated with transforming growth factor (TGF)ß-2 showed a decrease in DCN expression. The expression of tropomyosin 1 (Tpm1), a marker of lens EMT increased after the addition of TGFß-2 in human LEC; however, upregulation of Tpm1 mRNA or protein expression was reduced in human LECs overexpressing human DCN (hDCN). No phenotypic changes were observed in the lenses of 8- and 48-week-old transgenic mice for lens-specific hDCN (hDCN-Tg). Injury-induced EMT of the mouse lens, and the expression patterns of α smooth muscle actin, were attenuated in hDCN-Tg mice lenses. Overexpression of DCN inhibited the TGFß-2-induced upregulation of Tpm1 and EMT observed during wound healing of the lens, but it did not affect mouse lens morphology until 48 weeks of age. Our findings demonstrate that DCN plays a significant role in regulating EMT formation of LECs and PCO, and suggest that for therapeutic intervention, maintenance of physiological expression of DCN is essential to attenuate EMT progression and PCO formation.

Lens-specific conditional knockout of tropomyosin 1 gene in mice causes abnormal fiber differentiation and lens opacity.

Tropomyosin (Tpm) 1 and 2 are important in the epithelial mesenchymal transition of lens epithelial cells; however, the effect of Tpm1 depletion during aging remains obscure. We analyzed the age-related changes in the crystalline lens of Tpm1- conditional knockout mice (Tpm1-CKO). Floxed alleles of Tpm1 were conditionally deleted in the lens, using Pax6-cre transgenic mice. Lenses of embryonic day (ED) 14, postnatal 1-, 11-, and 48-week-old Tpm1-CKO and wild type mice were dissected to prepare paraffin sections, which subsequently underwent histological and immunohistochemical analysis. Tpm1 and α smooth muscle actin (αSMA) mRNA expression were assessed using RT-PCR. The homozygous Tpm1-CKO (Tpm1-/-) lenses displayed a dramatic reduction in Tpm1 transcript, with no change to αSMA mRNA expression. Tpm1-/- mice had small lenses with disorganized, vesiculated fiber cells, and loss of epithelial cells. The lenses of Tpm1-/- mice had abnormal and disordered lens fiber cells with cortical and peri-nuclear liquefaction. Expression of filamentous-actin was reduced in the equator region of lenses derived from ED14, 1-, 11-, and 48-week-old Tpm1-/- mice. Therefore, Tpm1 plays an integral role in mediating the integrity and fate of lens fiber differentiation and lens homeostasis during aging. Age-related Tpm1 dysregulation or deficiency may induce cataract formation.

Identification of Differential Gene Expression Pattern in Lens Epithelial Cells Derived from Cataractous and Noncataractous Lenses of Shumiya Cataract Rat.

The Shumiya cataract rat (SCR) is a model for hereditary cataract. Two-thirds of these rats develop lens opacity within 10-11 weeks. Onset of cataract is attributed to the synergetic effect of lanosterol synthase (Lss) and farnesyl-diphosphate farnesyltransferase 1 (Fdft1) mutant alleles that lead to cholesterol deficiency in the lenses, which in turn adversely affects lens biology including the growth and differentiation of lens epithelial cells (LECs). Nevertheless, the molecular events and changes in gene expression associated with the onset of lens opacity in SCR are poorly understood. In the present study, a microarray-based approach was employed to analyze comparative gene expression changes in LECs isolated from the precataractous and cataractous stages of lenses of 5-week-old SCRs. The changes in gene expression observed in microarray results in the LECs were further validated using real-time reverse transcribed quantitative PCR (RT-qPCR) in 5-, 8-, and 10-week-old SCRs. A mild posterior and cortical opacity was observed in 5-week-old rats. Expressions of approximately 100 genes, including the major intrinsic protein of the lens fiber (Mip and Aquaporin 0), deoxyribonuclease II beta (Dnase2B), heat shock protein B1 (HspB1), and crystallin γ (γCry) B, C, and F, were found to be significantly downregulated (0.07-0.5-fold) in rat LECs derived from cataract lenses compared to that in noncataractous lenses (control). Thus, our study was aimed at identifying the gene expression patterns during cataract formation in SCRs, which may be responsible for cataractogenesis in SCR. We proposed that cataracts in SCR are associated with reduced expression of these lens genes that have been reported to be related with lens fiber differentiation. Our findings may have wider implications in understanding the effect of cholesterol deficiency and the role of cholesterol-lowering therapeutics on cataractogenesis.

Experimental and Theoretical Investigation of the 3sp(d) Rydberg States of Fenchone by Polarized Laser Resonance-Enhanced-Multiphoton-Ionization and Fourier Transform VUV Absorption Spectroscopy.

The VUV absorption spectrum of fenchone is re-examined using synchrotron radiation Fourier transform spectrometry, revealing new vibrational structure. Picosecond laser (2+1) resonance enhanced multiphoton ionization (REMPI) spectroscopy complements this, providing an alternative view of the 3spd Rydberg excitation region. These spectra display broadly similar appearance, with minor differences that are largely explained by referring to calculated one- and two-photon electronic excitation cross-sections. Both show good agreement with Franck-Condon simulations of the relevant vibrational structures. Parent ion REMPI ionization yields with both femtosecond and picosecond excitation laser pulses are studied as a function of laser polarization and intensity, the latter providing insight into the relative two-photon excitation and one-photon ionization rates. The experimental circular-linear dichroism observed in the parent ion yields varies strongly between the 3s and 3p Rydberg states, in good overall agreement with the calculated two-photon excitation circular-linear dichroism, while corroborating other evidence that the 3pz sub-state plays no more than a very minor role in the (2+1) REMPI spectrum. Vibrationally resolved photoelectron spectra are recorded with picosecond pulse duration (2+1) REMPI at selected intermediate vibrational excitations. The 3s intermediate state displays a very strong Δv=0 propensity on ionization, but the 3p intermediate evidences more complex vibronic dynamics, and we infer some 3p→3s internal conversion prior to ionization.

Clock Protein Bmal1 and Nrf2 Cooperatively Control Aging or Oxidative Response and Redox Homeostasis by Regulating Rhythmic Expression of Prdx6.

Many disorders of aging, including blinding-diseases, are associated with deficiency of brain and muscle arnt-like protein 1 (Bmal1) and, thereby, dysregulation of antioxidant-defense pathway. However, knowledge is limited regarding the role of Bmal1 regulation of antioxidant-pathway in the eye lens/lens epithelial cells (LECs) at the molecular level. We found that, in aging human (h)LECs, a progressive decline of nuclear factor erythroid 2-related factor 2 (Nrf2)/ARE (antioxidant response element)-mediated antioxidant genes was connected to Bmal1-deficiency, leading to accumulation of reactive oxygen species (ROS) and cell-death. Bmal1-depletion disrupted Nrf2 and expression of its target antioxidant genes, like Peroxiredoxin 6 (Prdx6). DNA binding and transcription assays showed that Bmal1 controlled expression by direct binding to E-Box in Prdx6 promoter to regulate its transcription. Mutation at E-Box or ARE reduced promoter activity, while disruption of both sites diminished the activity, suggesting that both sites were required for peak Prdx6-transcription. As in aging hLECs, ROS accumulation was increased in Bmal1-deficient cells and the cells were vulnerable to death. Intriguingly, Bmal1/Nrf2/Prdx6 and PhaseII antioxidants showed rhythmic expression in mouse lenses in vivo and were reciprocally linked to ROS levels. We propose that Bmal1 is pivotal for regulating oxidative responses. Findings also reveal a circadian control of antioxidant-pathway, which is important in combating lens/LECs damage induced by aging or oxidative stress.