Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke.

Ferroptosis, a non-apoptotic form of programmed cell death, is triggered by oxidative stress in cancer, heat stress in plants, and hemorrhagic stroke. A homeostatic transcriptional response to ferroptotic stimuli is unknown. We show that neurons respond to ferroptotic stimuli by induction of selenoproteins, including antioxidant glutathione peroxidase 4 (GPX4). Pharmacological selenium (Se) augments GPX4 and other genes in this transcriptional program, the selenome, via coordinated activation of the transcription factors TFAP2c and Sp1 to protect neurons. Remarkably, a single dose of Se delivered into the brain drives antioxidant GPX4 expression, protects neurons, and improves behavior in a hemorrhagic stroke model. Altogether, we show that pharmacological Se supplementation effectively inhibits GPX4-dependent ferroptotic death as well as cell death induced by excitotoxicity or ER stress, which are GPX4 independent. Systemic administration of a brain-penetrant selenopeptide activates homeostatic transcription to inhibit cell death and improves function when delivered after hemorrhagic or ischemic stroke.

Efficient radical-based light-emitting diodes with doublet emission.

Organic light-emitting diodes (OLEDs)1-5, quantum-dot-based LEDs6-10, perovskite-based LEDs11-13 and micro-LEDs14,15 have been championed to fabricate lightweight and flexible units for next-generation displays and active lighting. Although there are already some high-end commercial products based on OLEDs, costs must decrease whilst maintaining high operational efficiencies for the technology to realise wider impact.  Here we demonstrate efficient action of radical-based OLEDs16, whose emission originates from a spin doublet, rather than a singlet or triplet exciton. While the emission process is still spin-allowed in these OLEDs, the efficiency limitations imposed by triplet excitons are circumvented for doublets. Using a luminescent radical emitter, we demonstrate an OLED with maximum external quantum efficiency of 27 per cent at a wavelength of 710 nanometres-the highest reported value for deep-red and infrared LEDs. For a standard closed-shell organic semiconductor, holes and electrons occupy the highest occupied and lowest unoccupied molecular orbitals (HOMOs and LUMOs), respectively, and recombine to form singlet or triplet excitons. Radical emitters have a singly occupied molecular orbital (SOMO) in the ground state, giving an overall spin-1/2 doublet. If-as expected on energetic grounds-both electrons and holes occupy this SOMO level, recombination returns the system to the ground state, giving no light emission. However, in our very efficient OLEDs, we achieve selective hole injection into the HOMO and electron injection to the SOMO to form the fluorescent doublet excited state with near-unity internal quantum efficiency.

Evolutionary game analysis for multi-level collaborative governance under public crisis in China: From a value perception perspective.

In a risk society, the survival and development of humans are facing threats of complex and severe public crisis events. Public participation in collaborative governance (CG) of public crisis events is increasingly recognized as an important direction for the reform of the current and future emergency management system. Previous studies of CG have mainly focused on the macro level and ignored to address micro-level discussions of the behavioral strategy evolution of stakeholders. From a fresh value perception perspective, this study constructs an evolutionary game model to clarify the evolution mechanism of multi-level emergency CG. First, the value perception model is built based on Prospect Theory and Mental Accounting to optimize the traditional game matrix. Second, the evolutionary stability is analyzed to solve the system evolution law. Finally, numerical simulation is conducted in the case of Heilongjiang province, a main region of food and energy supply in China. Results showed that (1) the CG game system has a complex evolutionary path; (2) the behavior of game players is affected by perceived incomes and perceived costs; (3) compared with the reference value and the risk aversion coefficient of income accounts, game players are more sensitive to that of cost accounts; (4) enhancing the perceived value of public psychological satisfaction and government reputation is helpful for the long-term construction of CG. Overall, this study aims to highlight the potential utility of value perception in promoting effective implementations of CG and to provide new insights for the development of CG in China and other countries.

Hemin-Induced Death Models Hemorrhagic Stroke and Is a Variant of Classical Neuronal Ferroptosis.

Ferroptosis is a caspase-independent, iron-dependent form of regulated necrosis extant in traumatic brain injury, Huntington disease, and hemorrhagic stroke. It can be activated by cystine deprivation leading to glutathione depletion, the insufficiency of the antioxidant glutathione peroxidase-4, and the hemolysis products hemoglobin and hemin. A cardinal feature of ferroptosis is extracellular signal-regulated kinase (ERK)1/2 activation culminating in its translocation to the nucleus. We have previously confirmed that the mitogen-activated protein (MAP) kinase kinase (MEK) inhibitor U0126 inhibits persistent ERK1/2 phosphorylation and ferroptosis. Here, we show that hemin exposure, a model of secondary injury in brain hemorrhage and ferroptosis, activated ERK1/2 in mouse neurons. Accordingly, MEK inhibitor U0126 protected against hemin-induced ferroptosis. Unexpectedly, U0126 prevented hemin-induced ferroptosis independent of its ability to inhibit ERK1/2 signaling. In contrast to classical ferroptosis in neurons or cancer cells, chemically diverse inhibitors of MEK did not block hemin-induced ferroptosis, nor did the forced expression of the ERK-selective MAP kinase phosphatase (MKP)3. We conclude that hemin or hemoglobin-induced ferroptosis, unlike glutathione depletion, is ERK1/2-independent. Together with recent studies, our findings suggest the existence of a novel subtype of neuronal ferroptosis relevant to bleeding in the brain that is 5-lipoxygenase-dependent, ERK-independent, and transcription-independent. Remarkably, our unbiased phosphoproteome analysis revealed dramatic differences in phosphorylation induced by two ferroptosis subtypes. As U0126 also reduced cell death and improved functional recovery after hemorrhagic stroke in male mice, our analysis also provides a template on which to build a search for U0126's effects in a variant of neuronal ferroptosis.SIGNIFICANCE STATEMENT Ferroptosis is an iron-dependent mechanism of regulated necrosis that has been linked to hemorrhagic stroke. Common features of ferroptotic death induced by diverse stimuli are the depletion of the antioxidant glutathione, production of lipoxygenase-dependent reactive lipids, sensitivity to iron chelation, and persistent activation of extracellular signal-regulated kinase (ERK) signaling. Unlike classical ferroptosis induced in neurons or cancer cells, here we show that ferroptosis induced by hemin is ERK-independent. Paradoxically, the canonical MAP kinase kinase (MEK) inhibitor U0126 blocks brain hemorrhage-induced death. Altogether, these data suggest that a variant of ferroptosis is unleashed in hemorrhagic stroke. We present the first, unbiased phosphoproteomic analysis of ferroptosis as a template on which to understand distinct paths to cell death that meet the definition of ferroptosis.

Design and characterization of molecular, crystal and interfacial structures of PVDF-based dielectric nanocomposites for electric energy storage.

PVDF-based polymers with polar covalent bonds are next-generation dielectric materials for electric energy storage applications. Several types of PVDF-based polymers, such as homopolymers, copolymers, terpolymers and tetrapolymers, were synthesized by radical addition reactions, controlled radical polymerizations, chemical modifications or reduction with the monomers of vinylidene fluoride (VDF), tetrafluoroethylene (TFE), trifluoroethylene (TrFE), hexafluoropropylene (HFP) and chlorotrifluoroethylene (CTFE). Owing to rich molecular structures and complicated crystal structures, PVDF-based dielectric polymers can show versatile dielectric polarization properties, including normal ferroelectrics, relaxor ferroelectrics, anti-ferroelectrics and linear dielectrics, which are beneficial for designing polymer films with high capacity and high charge-discharge efficiency for capacitor applications. Furthermore, to satisfy the requirements of practical high-capacity capacitors, the polymer nanocomposite method is another promising strategy to achieve high-capacitance dielectric materials by the addition of high-dielectric ceramic nanoparticles, moderate-dielectric nanoparticles (MgO, and Al2O3), high-insulation nanosheets (BN), etc. It is concluded with the current problems and future perspectives of interfacial engineering, such as core-shell strategies and hierarchical interfaces in polymer-based composite dielectrics for high-energy-density capacitor applications. In addition, an in-depth understanding of the roles of interfaces on the dielectric properties of nanocomposites can be achieved by indirect analysis techniques (theoretical simulation) and direct analysis techniques (scanning probe microscopy). Our systematic discussions on molecular, crystal and interfacial structures provide guidance for designing fluoropolymer-based nanocomposites for high-performance capacitor applications.

Does air pollution confound associations between environmental noise and cardiovascular outcomes? - A systematic review.

BACKGROUND: Exposure to environmental noise is associated with adverse health effects, but there is potential for confounding and interaction with air pollution, particularly where both exposures arise from the same source, such as transport. OBJECTIVES: To review evidence on confounding and interaction of air pollution in relation to associations between environmental noise and cardiovascular outcomes. METHODS: Papers were identified from similar reviews published in 2013 and 2015, from the systematic reviews supporting the WHO 2018 noise guidelines, and from a literature search covering the period 2016-2022 using Medline and PubMed databases. Additional papers were identified from colleagues. Study selection was according to PECO inclusion criteria. Studies were evaluated against the WHO checklist for risk of bias. RESULTS: 52 publications, 36 published after 2015, were identified that assessed associations between transportation noise and cardiovascular outcomes, that also considered potential confounding (49 studies) or interaction (23 studies) by air pollution. Most, but not all studies, suggested that the associations between traffic noise and cardiovascular outcomes are independent of air pollution. NO2 or PM2.5 were the most commonly included air pollutants and we observed no clear differences across air pollutants in terms of the potential confounding role. Most papers did not appear to suggest an interaction between noise and air pollution. Eight studies found the largest noise effect estimates occurring within the higher noise and air pollution exposure categories, but were not often statistically significant. CONCLUSION: Whilst air pollution does not appear to confound associations of noise and cardiovascular health, more studies on potential interactions are needed. Current methods to assess quality of evidence are not optimal when evaluating evidence on confounding or interaction.

Au Nanoparticles/HfO2/Fully Depleted Silicon-on-Insulator MOSFET Enabled Rapid Detection of Zeptomole COVID-19 Gene With Electrostatic Enrichment Process.

In this work, a novel sensing structure based on Au nanoparticles/HfO2/fully depleted silicon-on-insulator (AuNPs/HfO2/FDSOI) MOSFET is fabricated. Using such a planar double gate MOSFET, the electrostatic enrichment (ESE) process is proposed for the ultrasensitive and rapid detection of the coronavirus disease 2019 (COVID-19) ORF1ab gene. The back-gate (BG) bias can induce the required electric field that enables the ESE process in the testing liquid analyte with indirect contact with the top-Si layer. It is revealed that the ESE process can rapidly and effectively accumulate ORF1ab genes close to the HfO2 surface, which can significantly change the MOSFET threshold voltage ([Formula: see text]). The proposed MOSFET successfully demonstrates the detection of zeptomole (zM) COVID-19 ORF1ab gene with an ultralow detection limit down to 67 zM (~0.04 copy/[Formula: see text]) for a test time of less than 15 min even in a high ionic-strength solution. Besides, the quantitative dependence of [Formula: see text] variation on COVID-19 ORF1ab gene concentration from 200 zM to 100 femtomole is also revealed, which is further confirmed by TCAD simulation.

Authentication of Cyathulae Radix and Cyathulae Capitatae Radix based on the strength of the characteristic component achybidensaponin I.

Because of the immense difficulty in identifying Cyathulae Capitatae Radix adulteration in Cyathulae Radix, this research aims at fortifying the quality control of Cyathulae Radix and its decoction pieces to guarantee the effectiveness and safety of its clinical use in terms of source material. A method was devised to identify Cyathulae Capitatae Radix adulteration in Cyathulae Radix and its decoction pieces. This research takes achybidensaponin I, that is, the characteristic component of Cyathulae Capitatae Radix, as reference substance and adopts HPLC for detection. The results revealed that, among all samples collected, no trace of achybidensaponin I was found in the 21 batches of Cyathulae Radix, whereas achybidensaponin I was found in all the 14 batches of Cyathulae Capitatae Radix. The research sets 5% as the adulteration limit, that is, 1.45 mg/g Cyathulae Capitatae Radix was detected in 57.14% of the 49 batches of market samples collected and the ratio was 51.02% in the case of 5% adulteration limit. The method is not only precise and reliable but can also be used as a supplement for provisions regarding quality control of Cyathulae Radix and its decoction pieces in Pharmacopoeia of the People's Republic of China, to effectively crack down on Cyathulae Capitatae Radix adulteration in the market.

Cucurbit[8]uril-mediated SERS plasmonic nanostructures with sub-nanometer gap for the identification and determination of estrogens.

The SERS intensity of analytes is primarily influenced by the density and distribution of hotspots, which are often difficult to manipulate or regulate. In this study, cucurbit[8]uril (CB[8]), a kind of rigid macrocyclic molecule, was introduced to achieve ~ 1-nm nanogap between gold nanoparticles to increase the density of SERS hotspots. Three kinds of estrogens (estrone (E1), bisphenol A (BPA), and hexestrol (DES)) which are molecules with weak SERS signals were targeted in the hotspots by CB[8] to further improve the sensitivity and selectivity of SERS. It was demonstrated that CB[8] can link gold nanoparticles together through carbonyl groups. In addition, the host-guest interaction of CB[8] and estrogens was proved from the nuclear magnetic resonance hydrogen and infrared spectra. In the presence of CB[8], the SERS intensities of E1, BPA, and DES were increased to 19-fold, 74-fold, and 4-fold, respectively, and the LOD is 3.75 µM, 1.19 µM, and 8.26 µM, respectively. Furthermore, the proposed SERS method was applied to actual milk sample analysis with recoveries of E1 (85.0 ~ 112.8%), BPA (83.0 ~ 103.7%), and DES (62.6 ~ 132.0%). It is expected that the proposed signal enlarging strategy can be applied to  other analytes after further development.

Differential response to topical lubrication in patient with dry eye disease, based on age.

BACKGROUND: To compare the Ocular surface disease index (OSDI) score, Schirmer I test (SIT), fluorescein break up time (FBUT) and fluorescence staining (FLCS) score of dry eye patients at different ages. METHODS: 90 eyes of 90 patients with mild to moderate dry eye from September 2020 to September 2021 were retrospectively included and were divided into young group (20-39 years, n = 29), middle-age group (40-59 years, n = 30), and elder group (> 60 years, n = 31). Patients were given a 28-day topical lubricating ocular surface and repair-promoting drugs combined with local physical therapy. Patients were followed up at 7, 14 and 28 days. The OSDI score, SIT, FBUT and FLCS score were examined. RESULTS: There were differences between the OSDI score in three groups at each time point (all P < 0.001). SIT were different among the three groups (F = 350.61, P < 0.001), and a time effect was found (F = 80.87, P < 0.001). SIT at 14 and 28 days after treatment in middle-age and elder groups were lower than young group (all P < 0.001). SIT at 7, 14 and 28 days in elder group were lower than middle-age group (all P < 0.001). FLCS score was lower at 28 days than other time points (all P < 0.001). CONCLUSION: Dry eye patients are given a 28-day topical lubricating ocular surface and repair-promoting drugs combined with local physical therapy, which can promote tear secretion, film stability, and the recovery of corneal integrity. Age affects the treatment effect of mild to moderate dry eye, among which tear secretion is the most significant.

Paper mill sludge-based carbon quantum dots as a specifically ratiometric fluorescent probe for the sensitive and selective detection of coptisine.

Coptisine (COP), one of the bioactive components in Rhizoma Coptidis, has many pharmacological effects. Meanwhile, the determination of COP is essential in pharmacological and clinical applications. Herein, we prepared carbon quantum dots (CQDs) by one-step oil-thermal method using paper mill sludge (PMS) as precursor, and developed a ratiometric fluorescence method for the determination of COP. The structural and optical properties of PMS-CQDs were evaluated through high-resolution transmission electron microscopy (HRTEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray powder diffraction (XRD), ultraviolet-visible (UV-vis), fluorescence, zeta potential and fluorescence lifetime experiments. Fluorescence intensity ratio at 550 nm and 425 nm (I550 /I425 ) was recorded as an index for quantitative detection of COP. The detection concentration of COP ranges from 0.1 to 50 µM in good linear correlation (R2  = 0.9974) with a limit of detection of 0.028 µM (3σ/k). The quenching mechanism was deduced to be inner filter effect and static quenching. The ratiometric fluorescent probe showed impressive selectivity and sensitivity towards COP, and was successfully applied to the detection of COP in human urine with expected recoveries (95.22-111.00%) and relative standard deviations (0.46-2.95%), indicating that our developed method has a great application prospect in actual sample detection.

Trimester effects of source-specific PM10 on birth weight outcomes in the Avon Longitudinal Study of Parents and Children (ALSPAC).

BACKGROUND: Evidence suggests that exposure to particulate matter with aerodynamic diameter less than 10 µm (PM10) is associated with reduced birth weight, but information is limited on the sources of PM10 and exposure misclassification from assigning exposures to place of residence at birth. METHODS: Trimester and source-specific PM10 exposures (PM10 from road source, local non-road source, and total source) in pregnancy were estimated using dispersion models and a full maternal residential history for 12,020 births from the Avon longitudinal study of parents and children (ALSPAC) cohort in 1990-1992 in the Bristol area. Information on birth outcomes were obtained from birth records. Maternal sociodemographic and lifestyle factors were obtained from questionnaires. We used linear regression models for continuous outcomes (birth weight, head circumference (HC), and birth length (BL) and logistic regression models for binary outcomes (preterm birth (PTB), term low birth weight (TLBW) and small for gestational age (SGA)). Sensitivity analysis was performed using multiple imputation for missing covariate data. RESULTS: After adjustment, interquartile range increases in source specific PM10 from traffic were associated with 17 to 18% increased odds of TLBW in all pregnancy periods. We also found odds of TLBW increased by 40% (OR: 1.40, 95%CI: 1.12, 1.75) and odds of SGA increased by 18% (OR: 1.18, 95%CI: 1.05, 1.32) per IQR (6.54 µg/m3) increase of total PM10 exposure in the third trimester. CONCLUSION: This study adds to evidence that maternal PM10 exposures affect birth weight, with particular concern in relation to exposures to PM10 from road transport sources; results for total PM10 suggest greatest effect in the third trimester. Effect size estimates relate to exposures in the 1990s and are higher than those for recent studies - this may relate to reduced exposure misclassification through use of full residential history information, changes in air pollution toxicity over time and/or residual confounding.

The effect of loteprednol suspension eye drops after corneal transplantation.

BACKGROUND: To compare the effect of loteprednol suspension eye drops after corneal transplantation with the effect of prednisolone acetate eye drops. METHODS: A total of 234 patients (234 eyes) who underwent penetrating keratoplasty (PKP) and lamellar keratoplasty (LKP) were retrospectively included. Patients who received 1 % prednisolone acetate eye drops were defined as 1 % prednisolone acetate eye drop group (n = 96), and patients who received 0.5 % loteprednol suspension eye drops were defined as 0.5 % loteprednol suspension eye drop group (n = 138). RESULTS: 35 cases in 1 % prednisolone acetate eye drops group and 27 cases in 0.5 % loteprednol suspension eye drops group developed corticosteroid-induced ocular hypertension, and were defined as prednisolone acetate group and loteprednol group. No significant differences were observed in the average intraocular pressure (IOP) at 1 week, 1 month, 3 months or 12 months postoperatively. There were significant differences in the average IOP between the two groups at 6 months postoperatively (P = 0.001). There were no significant differences in the average best corrected visual acuity (BCVA) at 1, 3 and 12 months postoperatively between two groups. The average 6-month postoperative BCVA was significantly higher in the prednisolone acetate group than the loteprednol group (P < 0.05). There were no significant differences in the postoperative graft rejection rates between the two groups (P > 0.05). CONCLUSIONS: 0.5 % loteprednol suspension eye drops may be considered for long-term use after corneal transplantation.

Comparative Study on the Efficacy of Frozen Amniotic Membrane Transplantation and Lamellar Keratoplasty in the Treatment of Mooren Ulcer.

OBJECTIVE: To compare of the clinical efficacy of frozen amniotic membrane transplantation (AMT) and lamellar keratoplasty (LKP) in the treatment of Mooren ulcer. METHOD: Forty patients (42 eyes) with Mooren's ulcer in our hospital from January 2010 to January 2019 were divided into frozen AMT group (20 eyes) and LKP group (22 eyes). Comparative observation of post-operative best corrected visual acuity (BCVA), corneal epithelial healing time, corneal epithelialization time, ulcer healing, corneal transparency, corneal graft transparency, neovascularization and original disease recurrence were observed. RESULTS: The average BCVA at post-operative 6 and 12 months in LKP group were significantly lower than AMT group (P < 0.05). The ulcer healing rates in LKP group (63.6) were significantly higher than AMT group (30) (P < 0.05). The corneal epithelialization time of LKP group were 9.55 ±â€Š1.26 days. The corneal epithelial healing time of AMT group were 13.50 ±â€Š2.21 days. Nine cases were corneal graft transparency grade 0, and 13 cases were grade I. Three eyes in AMT group were corneal transparency grade 0, 7 were grade I and 10 were grade II. Corneal neovascularization were observed in 3 eyes in AMT group and 4 eyes in LKP group. The original disease recurrence rates in LKP group (50) were significantly higher than AMT group (20) (P < 0.05). Four cases of primary corneal transplantation failure were observed in LKP group. CONCLUSION: Lamellar keratoplasty group obtained significantly better BCVA during follow-up and faster healing time than the frozen AMT group while frozen AMT group had lower original disease recurrence rates than LKP group.

The drug adaptaquin blocks ATF4/CHOP-dependent pro-death Trib3 induction and protects in cellular and mouse models of Parkinson's disease.

Identifying disease-causing pathways and drugs that target them in Parkinson's disease (PD) has remained challenging. We uncovered a PD-relevant pathway in which the stress-regulated heterodimeric transcription complex CHOP/ATF4 induces the neuron prodeath protein Trib3 that in turn depletes the neuronal survival protein Parkin. Here we sought to determine whether the drug adaptaquin, which inhibits ATF4-dependent transcription, could suppress Trib3 induction and neuronal death in cellular and animal models of PD. Neuronal PC12 cells and ventral midbrain dopaminergic neurons were assessed in vitro for survival, transcription factor levels and Trib3 or Parkin expression after exposure to 6-hydroxydopamine or 1-methyl-4-phenylpyridinium with or without adaptaquin co-treatment. 6-hydroxydopamine injection into the medial forebrain bundle was used to examine the effects of systemic adaptaquin on signaling, substantia nigra dopaminergic neuron survival and striatal projections as well as motor behavior. In both culture and animal models, adaptaquin suppressed elevation of ATF4 and/or CHOP and induction of Trib3 in response to 1-methyl-4-phenylpyridinium and/or 6-hydroxydopamine. In culture, adaptaquin preserved Parkin levels, provided neuroprotection and preserved morphology. In the mouse model, adaptaquin treatment enhanced survival of dopaminergic neurons and substantially protected their striatal projections. It also significantly enhanced retention of nigrostriatal function. These findings define a novel pharmacological approach involving the drug adaptaquin, a selective modulator of hypoxic adaptation, for suppressing Parkin loss and neurodegeneration in toxin models of PD. As adaptaquin possesses an oxyquinoline backbone with known safety in humans, these findings provide a firm rationale for advancing it towards clinical evaluation in PD.

Polyvinyl alcohol: a high-resolution hydrogel resist for humidity-sensitive micro-/nanostructure.

A high-resolution nanopatterning technique is desirable with the present rapid development of hydrogel nanodevices. Here, we demonstrate that polyvinyl alcohol (PVA), a popular polymeric hydrogel, can function as the negative-tone resist for electron beam lithography (EBL) with a resolution capability as narrow as 50 nm half-pitch. Furthermore, the hydrophilic groups of PVA are stable after EBL exposure, and thus the pattern still shows rapid responsivity to humidity change. An aqueous nanopatterning process including dissolution, spin-coating and development is setup, which is friendly for organic device fabrication free of organic solvent. This high-resolution nanopatterning technique with PVA is helpful for the design and realization of hydrogel-related nanodevices in the future.

Comparison of the Clinical Efficacy of Boston Keratoprosthesis Type I and Repetitive Penetrating Keratoplasty for Refractory Keratopathy.

OBJECTIVE: To compare the clinical efficacy of Boston Keratoprosthesis type I (B-KProI) and penetrating keratoplasty (PKP) for patients with refractory keratopathy after 1failed PKP in China. METHOD: The 42 consecutive cases with refractory keratopathy after 1 failed PKP, from July 2010 to December 2014, were divided into 2 groups according to the surgical method: KPro group (n = 21) and PKP group (n = 21). Visual acuity (LogMAR), corneal graft transparency, postoperative complications and corneal graft survival rate were observed. The follow-up time was 2 years. The Kaplan-Meier curve was used to analyze the survival rate of the two groups of corneal grafts. RESULTS: The average best corrected visual acuity (BCVA) at 1, 6, 12, 18, and 24 months in KPro group were significantly lower than PKP group (P < 0.01). The best postoperative visual acuity and BCVA at postoperative 2 years in KPro group were lower than PKP group. The success rate of KPro group (86%) were significantly higher than PKP group (43%) (P < 0.01). There were no significant differences in indicate of complications in 2 groups including secondary glaucoma, secondary infectious corneal ulcer, corneal graft melting and endophthalmitis (P > 0.05). CONCLUSION: Compared with repetitive PKP, B-KProI had a higher success rate, improved postoperative visual acuity, reduced postoperative corneal transplant rejection rates and improved corneal graft survival rate.

Hydrophilic Nanocomposite Functionalized by Carrageenan for the Specific Enrichment of Glycopeptides.

A hydrophilic nanocomposite was synthesized by an easy route to improve glycopeptides enrichment efficiency. This new composite, prepared with a method based on electrostatic interaction, was demonstrated to be efficient for immobilization of carrageenan on graphene oxide/poly(ethylenimine) support (denoted as GO-PEI-Carr). Carrageenan, which has a large number of hydroxyl groups and is fully negatively charged, is a new modified phase of hydrophilic materials in glycoproteomics. The introduction of carrageenan provided the composite not only a perfect surface charge but also a greater ability to enrich glycosylated peptides. Thirty-four glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were obviously observed with greatly improved signal-to-noise (S/N) ratio. A good selectivity was still kept even when the molar ratio of IgG and bovine serum albumin (BSA) tryptic digest mixtures reached to 1:500. Meanwhile, 76 glycopeptides derived from 56 glycoproteins with 83 N-glycosylation sites were identified from human serum and 149 glycopeptides derived from 129 glycoproteins with 157 N-glycosylation sites were identified from mouse liver tissues, which showed the ability to enrich glycopeptides from complex biological samples. In addition, GO-PEI-Carr exhibited a unique repeatability and stability even after enrichment of glycopeptides for 20 times. It also performed a higher sensitivity (1 fmol/µL IgG), a better enrichment capacity (up to ∼300 mg/g), and an ideal enrichment recovery (90.8% and 109.5%) for glycopeptides enrichment, indicating a great potential for the application of glycoproteomic research.

N-acetylcysteine targets 5 lipoxygenase-derived, toxic lipids and can synergize with prostaglandin E2 to inhibit ferroptosis and improve outcomes following hemorrhagic stroke in mice.

OBJECTIVES: N-acetylcysteine (NAC) is a clinically approved thiol-containing redox modulatory compound currently in trials for many neurological and psychiatric disorders. Although generically labeled as an "antioxidant," poor understanding of its site(s) of action is a barrier to its use in neurological practice. Here, we examined the efficacy and mechanism of action of NAC in rodent models of hemorrhagic stroke. METHODS: Hemin was used to model ferroptosis and hemorrhagic stroke in cultured neurons. Striatal infusion of collagenase was used to model intracerebral hemorrhage (ICH) in mice and rats. Chemical biology, targeted lipidomics, arachidonate 5-lipoxygenase (ALOX5) knockout mice, and viral-gene transfer were used to gain insight into the pharmacological targets and mechanism of action of NAC. RESULTS: NAC prevented hemin-induced ferroptosis by neutralizing toxic lipids generated by arachidonate-dependent ALOX5 activity. NAC efficacy required increases in glutathione and is correlated with suppression of reactive lipids by glutathione-dependent enzymes such as glutathione S-transferase. Accordingly, its protective effects were mimicked by chemical or molecular lipid peroxidation inhibitors. NAC delivered postinjury reduced neuronal death and improved functional recovery at least 7 days following ICH in mice and can synergize with clinically approved prostaglandin E2 (PGE2 ). INTERPRETATION: NAC is a promising, protective therapy for ICH, which acted to inhibit toxic arachidonic acid products of nuclear ALOX5 that synergized with exogenously delivered protective PGE2 in vitro and in vivo. The findings provide novel insight into a target for NAC, beyond the generic characterization as an antioxidant, resulting in neuroprotection and offer a feasible combinatorial strategy to optimize efficacy and safety in dosing of NAC for treatment of neurological disorders involving ferroptosis such as ICH. Ann Neurol 2018;84:854-872.

Topographic location of unisolated pontine infarction.

BACKGROUND: The topographic location of acute pontine infarction is associated with clinical syndromes and prognosis. Previous studies focused on isolated pontine infarction, but the topographic location of unisolated pontine infarction has remained unclear. METHODS: This was a prospective, multicenter, longitudinal registry study. Patients with acute pontine infarction confirmed by magnetic resonance imaging (MRI) were enrolled. Based on the territory of the pontine artery, the topographic location was divided into anteromedial, anterolateral, tegmental, bilateral and unilateral multiple infarctions. RESULTS: From May 1, 2003, to Oct 31, 2017, 1003 patients were enrolled, and 330 had unisolated pontine infarction. For isolated pontine infarction, 44.9, 19.8, 16.0, 13.1 and 6.2% of patients had anteromedial, anterolateral, tegmental, bilateral and unilateral multiple pontine infarctions, respectively. For unisolated pontine infarction, 30.3, 19.7, 24.5, 15.2 and 10.3% of patients had anteromedial, anterolateral, tegmental, bilateral and unilateral multiple pontine infarctions, respectively. CONCLUSION: In this large series study, our data revealed fewer anteromedial infarctions and more tegmental and unilateral multiple infarctions in patients with unisolated pontine infarction than in patients with isolated pontine infarction.