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Abstract Currently, the concentration of carbon dioxide (CO2) has exceeded 400 ppm in the atmosphere. Thus, there is an urgent need to explore CO2 reduction and utilization technologies. Photocatalytic technology can convert CO2 to valuable hydrocarbons (CH4, CH3OH, and C2H5OH, etc.), realizing the conversion of solar energy to chemical energy as well as solving the problems of fossil fuel shortage and global warming. Graphitic carbon nitride (g‐C3N4), as a two‐dimensional nonmetallic semiconductor material, shows great potential in the field of CO2 photoreduction due to its moderate bandgap, easy synthesis method, low cost, and visible light response properties. This review elaborates the research progress of g‐C3N4‐based photocatalysts for photocatalytic CO2 reduction. The modification strategies (e.g., morphology engineering, elemental doping, crystallinity modulation, cocatalyst modification, and constructing heterojunction) of g‐C3N4‐based photocatalysts for CO2 reduction application have been discussed in detail. Finally, the challenges and development prospects of g‐C3N4‐based photocatalytic materials for CO2 reduction are presented.

Many patients with diabetic eye disease respond inadequately to anti-VEGF therapies, implicating additional vasoactive mediators in its pathogenesis. We demonstrate that levels of angiogenic proteins regulated by HIF-1 and -2 remain elevated in the eyes of people with diabetes despite treatment with anti-VEGF therapy. Conversely, by inhibiting HIFs, we normalized the expression of multiple vasoactive mediators in mouse models of diabetic eye disease. Accumulation of HIFs and HIF-regulated vasoactive mediators in hyperglycemic animals was observed in the absence of tissue hypoxia, suggesting that targeting HIFs may be an effective early treatment for diabetic retinopathy. However, while the HIF inhibitor acriflavine prevented retinal vascular hyperpermeability in diabetic mice for several months following a single intraocular injection, accumulation of acriflavine in the retina resulted in retinal toxicity over time, raising concerns for its use in patients. Conversely, 32-134D, a recently developed HIF inhibitor structurally unrelated to acriflavine, was not toxic to the retina, yet effectively inhibited HIF accumulation and normalized HIF-regulated gene expression in mice and in human retinal organoids. Intraocular administration of 32-134D prevented retinal neovascularization and vascular hyperpermeability in mice. These results provide the foundation for clinical studies assessing 32-134D for the treatment of patients with diabetic eye disease.

The aim of this study was to assess the effectiveness of different biomarkers to identify the levels of protein oxidation in pork patties induced by assorted cooking methods. To achieve this purpose, pork patties prepared from longissimus dorsi were cooked using three methods (frying, steaming, and roasting) at different internal temperatures (60, 70, 80, and 90 °C). Traditional biomarkers including total carbonyl and total thiol and novel biomarkers including α-aminoadipic semialdehyde (AAS) and lysinonorleucine (LNL) were determined. Results demonstrated that total thiol and AAS were the most successful biomarkers in distinguishing the three cooking methods in relation to protein oxidation, with AAS being the most sensitive. Moreover, as indicated by the biomarkers of total thiol and AAS, frying caused the highest level of protein oxidation, while steaming resulted in the lowest level when pork patties were cooked to the internal temperatures of 70 or 80 °C.

Core fucosylation of N-linked glycoproteins has been linked to physiological and pathological processes. Here, the authors develop a mass spectrometry-based method that utilizes Endo F3 followed by PNGase F treatment to quantify site-specific glycoprotein core fucosylation in protein mixtures.

BACKGROUND Studies assessing the efficacy of therapies for neovascular age-related macular degeneration (nvAMD) have demonstrated that aflibercept may have a longer treatment interval than its less-expensive alternative, bevacizumab. However, whether this benefit justifies the additional cost of aflibercept remains under debate. We have recently reported that a treat-and-extend-pause/monitor approach can be used to successfully wean 31% of patients with nvAMD off anti-VEGF therapy. Here, we examined whether the choice of therapy influences the outcomes of this approach.METHODS In this retrospective analysis, 122 eyes of 106 patients with nvAMD underwent 3 consecutive monthly injections with either aflibercept (n = 70) or bevacizumab (n = 52), followed by a treat-and-extend protocol, in which the decision to extend the interval between treatments was based on visual acuity, clinical exam, and the presence or absence of fluid on optical coherence tomography. Eyes that remained stable 12 weeks from their prior treatment were given a 6-week trial of holding further treatment, followed by quarterly monitoring. Treatment was resumed for worsening vision, clinical exam, or optical coherence tomography findings.RESULTS At the end of 1 year, eyes receiving bevacizumab had similar vision but required more injections (8.7 ± 0.3 treatments vs. 7.2 ± 0.3 treatments) compared with eyes receiving aflibercept. However, eyes treated with aflibercept were almost 3 times more likely to be weaned off treatment (43% vs. 15%) compared with eyes treated with bevacizumab at the end of 1 year.CONCLUSION These observations expose an advantage of aflibercept over bevacizumab and have important clinical implications for the selection of therapy for patients with nvAMD.FUNDING This work was supported by the National Eye Institute, NIH grants R01EY029750 and R01EY025705, Research to Prevent Blindness, the Alcon Young Investigator Award from the Alcon Research Institute, and the Branna and Irving Sisenwein Professorship in Ophthalmology.

Summary: Tight glycemic control (TGC), the cornerstone of diabetic management, reduces the incidence and progression of diabetic microvascular disease. However, TGC can also lead to transient episodes of hypoglycemia, which have been associated with adverse outcomes in patients with diabetes. Here, we demonstrate that low glucose levels result in hypoxia-inducible factor (HIF)-1-dependent expression of the glucose transporter, Glut1, in retinal cells. Enhanced nuclear accumulation of HIF-1α was independent of its canonical post-translational stabilization but instead dependent on stimulation of its translation and nuclear localization. In the presence of hypoxia, this physiologic response to low glucose resulted in a marked increase in the secretion of the HIF-dependent vasoactive mediators that promote diabetic retinopathy. Our results provide a molecular explanation for how early glucose control, as well as glycemic variability (i.e., oscillating serum glucose levels), contributes to diabetic eye disease. These observations have important implications for optimizing glucose management in patients with diabetes.

Most patients with neovascular age-related macular degeneration (nvAMD), the leading cause of severe vision loss in elderly US citizens, respond inadequately to current therapies targeting a single angiogenic mediator, vascular endothelial growth factor (VEGF). Here, we report that aqueous fluid levels of a second vasoactive mediator, angiopoietin-like 4 (ANGPTL4), can help predict the response of patients with nvAMD to anti-VEGF therapies. ANGPTL4 expression was higher in patients who required monthly treatment with anti-VEGF therapies compared with patients who could be effectively treated with less-frequent injections. We further demonstrate that ANGPTL4 acts synergistically with VEGF to promote the growth and leakage of choroidal neovascular (CNV) lesions in mice. Targeting ANGPTL4 expression was as effective as targeting VEGF expression for treating CNV in mice, while simultaneously targeting both was more effective than targeting either factor alone. To help translate these findings to patients, we used a soluble receptor that binds to both VEGF and ANGPTL4 and effectively inhibited the development of CNV lesions in mice. Our findings provide an assay that can help predict the response of patients with nvAMD to anti-VEGF monotherapy and suggest that therapies targeting both ANGPTL4 and VEGF will be a more effective approach for the treatment of this blinding disease.

Background To reduce the treatment burden for patients with neovascular age-related macular degeneration (nvAMD), emerging therapies targeting vascular endothelial growth factor (VEGF) are being designed to extend the interval between treatments, thereby minimizing the number of intraocular injections. However, which patients will benefit from longer-acting agents is not clear.Methods Eyes with nvAMD (n = 122) underwent 3 consecutive monthly injections with currently available anti-VEGF therapies, followed by a treat-and-extend protocol. Patients who remained quiescent 12 weeks from their prior treatment entered a treatment pause and were switched to pro re nata (PRN) treatment (based on vision, clinical exam, and/or imaging studies). Proteomic analysis was performed on aqueous fluid to identify proteins that correlate with patients’ response to treatment.Results At the end of 1 year, 38 of 122 eyes (31%) entered a treatment pause (≥30 weeks). Conversely, 21 of 122 eyes (17%) failed extension and required monthly treatment at the end of year 1. Proteomic analysis of aqueous fluid identified proteins that correlated with patients’ response to treatment, including proteins previously implicated in AMD pathogenesis. Interestingly, apolipoprotein-B100 (ApoB100), a principal component of drusen implicated in the progression of nonneovascular AMD, was increased in treated patients who required less frequent injections. ApoB100 expression was higher in AMD eyes compared with controls but was lower in eyes that develop choroidal neovascularization (CNV), consistent with a protective role. Accordingly, mice overexpressing ApoB100 were partially protected from laser-induced CNV.Funding This work was supported by the National Eye Institute, National Institutes of Health grants R01EY029750, R01EY025705, and R01 EY27961; the Research to Prevent Blindness, Inc.; the Alcon Research Institute; and Johns Hopkins University through the Robert Bond Welch and Branna and Irving Sisenwein professorships in ophthalmology.Conclusion Aqueous biomarkers could help identify patients with nvAMD who may not require or benefit from long-term treatment with anti-VEGF therapy.

Summary: The symmetric tissue and body plans of animals are paradoxically constructed with asymmetric cells. To understand how the yin-yang duality of symmetry and asymmetry are reconciled, we asked whether apical polarity proteins orchestrate the development of the mirror-symmetric zebrafish neural tube by hierarchically modulating apical cell-cell adhesions. We found that apical polarity proteins localize by a pioneer-intermediate-terminal order. Pioneer proteins establish the mirror symmetry of the neural rod by initiating two distinct types of apical adhesions: the parallel apical adhesions (PAAs) cohere cells of parallel orientation and the novel opposing apical adhesions (OAAs) cohere cells of opposing orientation. Subsequently, the intermediate proteins selectively augment the PAAs when the OAAs dissolve by endocytosis. Finally, terminal proteins are required to inflate the neural tube by generating osmotic pressure. Our findings suggest a general mechanism to construct mirror-symmetric tissues: tissue symmetry can be established by organizing asymmetric cells opposingly via adhesions. : Ichthyology; Developmental Neuroscience; Evolutionary Developmental Biology Subject Areas: Ichthyology, Developmental Neuroscience, Evolutionary Developmental Biology

1,3-Propanediol (1,3-PDO) is an important compound that is mainly used in industry for polymer production. Fermentation of 1,3-PDO from glycerol by Klebsiella pneumoniae is accompanied by formation of 2,3-butanediol (2,3-BDO) as one of the main byproduct. The first step in the formation of 2,3-BDO from pyruvate is catalyzed by acetolactate synthase (ALS), an enzyme that competes with 1,3-PDO oxidoreductase for the cofactor NADH. This study aimed to analyze the impact of engineering the 2,3-BDO formation pathway via inactivation of ALS on 1,3-PDO fermentation by K. pneumoniae HSL4. An ALS mutant was generated using Red recombinase assisted gene replacement. The ALS specific activities of K. pneumoniae ΔALS were notably lower than that of the wild-type strain. Fed-batch fermentation of the mutant strain resulted in a 1,3-PDO concentration, productivity and conversion of 72.04 g L-1, 2.25 g L-1 h-1, and 0.41 g g-1, increase by 4.71%, 4.65% and 1.99% compared with the parent strain. Moreover, inactivation of ALS decreased meso-2,3-BDO formation to trace amounts, significantly increased 2S,3S-BDO and lactate production, and a pronounced redistribution of intracellular metabolic flux was apparent.

Grouper (Epinephelus spp.) is a group of fish species with great economic importance in Asian countries. A novel hybrid grouper, generated by us and called the Hulong grouper (Hyb), has better growth performance than its parents, E. fuscoguttatus (Efu, ♀) and E. lanceolatus (Ela, ♂). We previously reported that the GH/IGF (growth hormone/insulin-like growth factor) system in the brain and liver contributed to the superior growth of the Hyb. In this study, using transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR), we analyzed RNA expression levels of comprehensive genes in the muscle of the hybrid and its parents. Our data showed that genes involved in glycolysis and calcium signaling in addition to troponins are up-regulated in the Hyb. The results suggested that the activity of the upstream GH/IGF system in the brain and liver, along with the up-regulated glycolytic genes as well as ryanodine receptors (RyRs) and troponins related to the calcium signaling pathway in muscle, led to enhanced growth in the hybrid grouper. Muscle contraction inducing growth could be the major contributor to the growth superiority in our novel hybrid grouper, which may be a common mechanism for hybrid superiority in fishes.

Growing evidence demonstrates that various large DNA viruses could encode microRNAs (miRNAs) that regulate host and viral genes to achieve immune evasion. In this study, we report that miR-homoHSV, an miRNA encoded by Singapore grouper iridovirus (SGIV), can attenuate SGIV-induced cell death. Mechanistically, SGIV miR-homoHSV targets SGIV ORF136R, a viral gene that encodes the pro-apoptotic lipopolysaccharide-induced TNF-α (LITAF)-like factor. miR-homoHSV suppressed exogenous and endogenous SGIV LITAF expression, and thus inhibited SGIV LITAF-induced apoptosis. Meanwhile, miR-homoHSV expression was able to attenuate cell death induced by viral infection, presumably facilitating viral replication through the down-regulation of the pro-apoptotic gene SGIV LITAF. Together, our data suggest miR-homoHSV may serve as a feedback regulator of cell death during viral infection. The findings of this study provide a better understanding of SGIV replication and pathogenesis.

Neovascular age-related macular degeneration (nvAMD) is the leading cause of severe vision loss in the elderly in the developed world. While the introduction of therapies targeting vascular endothelial growth factor (VEGF) has provided the first opportunity to significantly improve vision in patients with nvAMD, many patients respond inadequately to current anti-VEGF therapies. It was recently demonstrated that expression of a second angiogenic mediator, angiopoietin-like 4 (ANGPTL4), synergizes with VEGF to promote choroidal neovascularization (CNV) in mice and correlates with reduced response to anti-VEGF therapy in patients with nvAMD. Here, we report that expression of ANGPTL4 in patients with nvAMD increases following treatment with anti-VEGF therapy and that this increase is dependent on accumulation of hypoxia-inducible factor (HIF)-1a in response to inhibition of VEGF/KDR signaling in the retinal pigment epithelium (RPE). We therefore explored HIF-1 inhibition with 32-134D, a recently developed pharmacologic HIF-inhibitor, for the treatment of nvAMD. 32-134D prevented the expression of both VEGF and ANGPTL4 and was at least as effective as aflibercept in treating CNV in mice. Moreover, by preventing the increase in HIF-1a accumulation in the RPE in response to anti-VEGF therapy, combining 32-134D with aflibercept was more effective than either drug alone for the treatment of CNV. Collectively, these results help explain why many patients with nvAMD respond inadequately to anti-VEGF therapy and suggest that the HIF inhibitor 32-134D will be an effective drug--alone or in combination with current anti-VEGF therapies--for the treatment of patients with this blinding disease. [ABSTRACT FROM AUTHOR]

It has previously been reported that antioxidant vitamins can help reduce the risk of vision loss associated with progression to advanced age-related macular degeneration (AMD), a leading cause of visual impairment among the elderly. Nonetheless, how oxidative stress contributes to the development of choroidal neovascularization (CNV) in some AMD patients and geographic atrophy (GA) in others is poorly understood. Here, we provide evidence demonstrating that oxidative stress cooperates with hypoxia to synergistically stimulate the accumulation of hypoxia-inducible factor (HIF)-1a in the retinal pigment epithelium (RPE), resulting in increased expression of the HIF-1-dependent angiogenic mediators that promote CNV. HIF-1 inhibition blocked the expression of these angiogenic mediators and prevented CNV development in an animal model of ocular oxidative stress, demonstrating the pathological role of HIF-1 in response to oxidative stress stimulation in neovascular AMD. While human-induced pluripotent stem cell (hiPSC)-derived RPE monolayers exposed to chemical oxidants resulted in disorganization and disruption of their normal architecture, RPE cells proved remarkably resistant to oxidative stress. Conversely, equivalent doses of chemical oxidants resulted in apoptosis of hiPSC-derived retinal photoreceptors. Pharmacologic inhibition of HIF-1 in the mouse retina enhanced--while HIF-1 augmentation reduced--photoreceptor apoptosis in two mouse models for oxidative stress, consistent with a protective role for HIF-1 in photoreceptors in patients with advanced dry AMD. Collectively, these results suggest that in patients with AMD, increased expression of HIF-1a in RPE exposed to oxidative stress promotes the development of CNV, but inadequate HIF-1a expression in photoreceptors contributes to the development of GA. [ABSTRACT FROM AUTHOR]