Recent advances in moisture-induced electricity generation based on wood lignocellulose: Preparation, properties, and applications.

Moisture-induced electricity generation (MEG), which can directly harvest electricity from moisture, is considered as an effective strategy for alleviating the growing energy crisis. Recently, tremendous efforts have been devoted to developing MEG active materials from wood lignocellulose (WLC) due to its excellent properties including environmental friendliness, sustainability, and biodegradability. This review comprehensively summarizes the recent advances in MEG based on WLC (wood, cellulose, lignin, and woody biochar), covering its principles, preparation, performances, and applications. In detail, the basic working mechanisms of MEG are discussed, and the natural features of WLC and their significant advantages in the fabrication of MEG active materials are emphasized. Furthermore, the recent advances in WLC-based MEG for harvesting electrical energy from moisture are specifically discussed, together with their potential applications (sensors and power sources). Finally, the main challenges of current WLC-based MEG are presented, as well as the potential solutions or directions to develop highly efficient MEG from WLC.

Characterization of a unique catechol-O-methyltransferase as a molecular drug target in parasitic filarial nematodes.

BACKGROUND: Filarial nematodes cause severe illnesses in humans and canines including limb deformities and disfigurement, heart failure, blindness, and death, among others. There are no vaccines, and current drugs against filarial nematodes infections have only modest effects and are prone to complications. METHODOLOGY/PRINCIPAL FINDINGS: We identified a gene (herein called DiMT) encoding an S-adenosyl-L-methionine (SAM)-dependent methyltransferase with orthologs in parasite filarial worms but not in mammals. By in silico analysis, DiMT possesses catalytic sites for binding SAM and catecholamines with high affinity. We expressed and purified recombinant DiMT protein and used it as an enzyme in a series of SAM-dependent methylation assays. DiMT acted specifically as a catechol-O-methyltransferase (COMT), catalyzing catabolic methylation of dopamine, and depicted Michaelis Menten kinetics on substrate and co-substrate. Among a set of SAM-dependent methyltransferase inhibitors, we identified compounds that bound with high affinity to DiMT's catalytic sites and inhibited its enzymatic activity. By testing the efficacy of DiMT inhibitors against microfilariae of Dirofilaria immitis in culture, we identified three inhibitors with concentration- and time-dependent effect of killing D. immitis microfilariae. Importantly, RNAi silencing of a DiMT ortholog in Caenorhabditis elegans has been shown to be lethal, likely as a result of excessive accumulation of active catecholamines that inhibit worm locomotion, pharyngeal pumping and fecundity. CONCLUSIONS/SIGNIFICANCE: Together, we have unveiled DiMT as an essential COMT that is conserved in parasitic filarial nematodes, but is significantly different from mammalian COMTs and, therefore, is a viable target for development of novel drugs against filarial nematode infections.

Signal recognition particle RNA is critical for genetic competence and virulence of Streptococcus pneumoniae.

Streptococcus pneumoniae (pneumococcus) causes a wide range of important human infectious diseases, including pneumonia, pneumonia-derived sepsis, otitis media, and meningitis. Pneumococcus produces numerous secreted proteins that are critical for normal physiology and pathogenesis. The membrane targeting and translocation of these secreted proteins are partly mediated by the signal recognition particle (SRP) complex, which consists of 4.5S small cytoplasmic RNA (ScRNA), and the Ffh, and FtsY proteins. Here, we report that pneumococcal ∆scRNA, ∆ffh, and ∆ftsY mutants were significantly impaired in competence induction, competence pili production, exogenous DNA uptake, and genetic transformation. Also, the ∆scRNA mutant was significantly attenuated in the mouse models of bacteremia and pneumonia. Interestingly, unlike the ∆scRNA, both ∆ffh and ∆ftsY mutants had growth defects on Todd-Hewitt Agar, which were alleviated by the provision of free amino acids or serum. Differences in nutritional requirements between ∆ffh and ∆ftsY vs ∆scRNA suggest that Ffh and FtsY may be partially functional in the absence of ScRNA. Finally, the insertase YidC2, which could functionally rescue some SRP mutations in other streptococcal species, was not essential for pneumococcal genetic transformation. Collectively, these results indicate that ScRNA is crucial for the successful development of genetic competence and virulence in pneumococcus. IMPORTANCE: Streptococcus pneumoniae (pneumococcus) causes multiple important infectious diseases in humans. The signal recognition particle (SRP) complex, which comprised 4.5S small cytoplasmic RNA (ScRNA), and the Ffh and FtsY proteins, mediates membrane targeting and translocation of secreted proteins in all organisms. However, the role of SRP and ScRNA has not been characterized during the induction of the competence system for genetic transformation and virulence in pneumococcus. By using a combination of genetic, biochemical, proteomic, and imaging approaches, we demonstrated that the SRP complex plays a significant role in membrane targeting of competence system-regulated effectors important for genetic transformation, virulence during bacteremia and pneumonia infections, and nutritional acquisition.

A Top-Down Approach to the Fabrication of Flame-Retardant Wood Aerogel with In Situ-Synthesized Borax and Zinc Borate.

In this study, a top-down approach was employed for the fabrication of flame-retardant wood aerogels. The process involved the removal of lignin and the removal of hemicellulose utilizing NaOH concomitantly with the incorporation of ZnO and urea. Subsequently, an in situ reaction with boric acid was conducted to prepare flame-retardant wood aerogels. The morphology, chemical composition, thermal stability, and flame retardancy of the samples were studied. The results show that the NaOH treatment transformed the wood into a layered structure, and flame-retardant particles were uniformly distributed on the surface of the aerogel. The peak heat release rate (PHRR) and total heat release (THR) of the flame-retardant aerogel were significantly reduced compared with the control samples. Meanwhile, its vertical burning test (UL-94) rating reached the V-0 level, and the Limiting Oxygen Index (LOI) could exceed 90%. The flame-retardant wood aerogel exhibited excellent flame retardancy and self-extinguishing properties.

A review on the calculation and application of lignin Hansen solubility parameters.

Hansen solubility parameters (HSPs) play a critical role in the majority of processes involving lignin depolymerization, separation, fractionation, and polymer blending, which are directly related to dissolution properties. However, the calculation of lignin HSPs is highly complicated due to the diversity of sources and the complexity of lignin structures. Despite their important role, lignin HSPs have been undervalued, attracting insufficient attention. This review summarizes the calculation methods for lignin HSPs and proposes a straightforward method based on lignin subunits. Furthermore, it highlights the crucial applications of lignin HSPs, such as identifying ideal solvents for lignin dissolution, selecting suitable solvents for lignin depolymerization and extraction, designing green solvents for lignin fractionation, and guiding the preparation of lignin-based composites. For instance, leveraging HSPs to design a series of solvents could potentially achieve sequential controllable lignin fractionation, addressing issues of low value-added applications of lignin resulting from poor homogeneity. Notably, HSPs serve as valuable tools for understanding the dissolution behavior of lignin. Consequently, we expect this review to be of great interest to researchers specializing in lignin and other macromolecules.

Broad-Spectrum Inhibitors for Conserved Unique Phosphoethanolamine Methyltransferases in Parasitic Nematodes Possess Anthelmintic Efficacy.

In humans, nematode infections are prevalent in developing countries, causing long-term ill health, particularly in children. Worldwide, nematode infections are prevalent in livestock and pets, affecting productivity and health. Anthelmintic drugs are the primary means of controlling nematodes, but there is now high prevalence of anthelmintic resistance, requiring urgent identification of new molecular targets for anthelmintics with novel mechanisms of action. Here, we identified orthologous genes for phosphoethanolamine methyltransferases (PMTs) in nematodes within the families Trichostrongylidae, Dictyocaulidae, Chabertiidae, Ancylostomatoidea, and Ascarididae. We characterized these putative PMTs and found that they possess bona fide PMT catalytic activities. By complementing a mutant yeast strain lacking the ability to synthesize phosphatidylcholine, the PMTs were validated to catalyze the biosynthesis of phosphatidylcholine. Using an in vitro phosphoethanolamine methyltransferase assay with PMTs as enzymes, we identified compounds with cross-inhibitory effects against the PMTs. Corroboratively, treatment of PMT-complemented yeast with the PMT inhibitors blocked growth of the yeast, underscoring the essential role of the PMTs in phosphatidylcholine synthesis. Fifteen of the inhibitors with the highest activity against complemented yeast were tested against Haemonchus contortus using larval development and motility assays. Among them, four were found to possess potent anthelmintic activity against both multiple drug-resistant and susceptible isolates of H. contortus, with IC50 values (95% confidence interval) of 4.30 µM (2.15-8.28), 4.46 µM (3.22-6.16), 28.7 µM (17.3-49.5), and 0.65 µM (0.21-1.88). Taken together, we have validated a molecular target conserved in a broad range of nematodes and identified its inhibitors that possess potent in vitro anthelmintic activity.

Blueprint for antibody biologics developability.

Large-molecule antibody biologics have revolutionized medicine owing to their superior target specificity, pharmacokinetic and pharmacodynamic properties, safety and toxicity profiles, and amenability to versatile engineering. In this review, we focus on preclinical antibody developability, including its definition, scope, and key activities from hit to lead optimization and selection. This includes generation, computational and in silico approaches, molecular engineering, production, analytical and biophysical characterization, stability and forced degradation studies, and process and formulation assessments. More recently, it is apparent these activities not only affect lead selection and manufacturability, but ultimately correlate with clinical progression and success. Emerging developability workflows and strategies are explored as part of a blueprint for developability success that includes an overview of the four major molecular properties that affect all developability outcomes: 1) conformational, 2) chemical, 3) colloidal, and 4) other interactions. We also examine risk assessment and mitigation strategies that increase the likelihood of success for moving the right candidate into the clinic.

Bowl-Shaped Bispyrrole-Fused Perylene-diimide and Its Anions.

Incorporating two pyrrole subunits at the bay positions of perylene-diimide has been a long-pursued goal since 2009, but it has not been achieved due to high strain. Herein, via one step Buchwald-Hartwig reaction, PDI-2N was successfully generated with a bowl depth of 1.52 Å. Though with electron-rich pyrrole embedding, PDI-2N's radical anion and dianion were facilely prepared and were investigated both experimentally and theoretically. Moreover, PDI-2N crystallized in different manners under distinct conditions, and it formed tubular crystals with infinite two-directional columnar stacking under DMF conditions. This finding develops a dream bowl-shaped PDI derivative that holds great promise in organoelectronics.

Insights into Photoinduced Carrier Dynamics and Overall Water Splitting of Z-Scheme van der Waals Heterostructures with Intrinsic Electric Polarization.

Using first-principles calculations in combination with nonadiabatic molecular dynamics (NAMD), we propose novel heterostructures of carbon nitride (C7N6) and the Janus GaSnPS monolayer as promising direct Z-scheme photocatalysts for solar-driven overall water splitting. The out-of-plane electric field due to the electric polarization which is dependent on the stacking pattern alters the band alignment and catalytic activity of the heterostructures. The relatively strong interfacial nonadiabatic coupling and long quantum coherence time accelerate the interlayer carrier recombination, enabling a direct Z-scheme photocatalytic mechanism. More importantly, the redox ability of the remanent photogenerated carriers in the Z scheme is strong enough to trigger both the hydrogen evolution reaction (HER) and oxygen reduction reaction (OER) simultaneously without the help of sacrificial agents. Our work reveals a fundamental understanding of ultrafast charge carrier dynamics at vdW heterointerfaces as well as new design prospects for highly efficient direct Z-scheme photocatalysts.

An integral method for determining the molecular composition of lignin and its application.

Lignin is a natural and renewable aromatic polymer, but only about 2% of lignin is utilized with high added value. Polydispersity and heterogeneity are the key reasons for the difficulty in separation, fractionation, characterization, purification and utilization of lignin. However, the molecular weight of lignin is still described from the overall perspective of number-/weight-average molecular weight (Mn and Mw), which if far from enough to understand the heterogeneous and dispersed lignin. To provide a tool for understanding the molecular weight of lignin from a molecular perspective, an integral method for quantifying the molecular characteristics of lignin molecules at arbitrary molecular intervals on the molecular weight distribution curve of lignin was established. The molecular contents of wheat straw lignin as well as its soluble and insoluble fractions at different intervals were calculated. The ease of fractionation of small molecules with weights lower than 8000 g/mol into soluble fractions, and that of large molecules with weights higher than 10,000 g/mol into insoluble fractions were quantitatively analyzed. The established integral method will significantly help in the understanding the properties of lignin at the molecular-level, as well as the fractionation and utilization of lignin.

Plasmodium relictum MSP-1 capture antigen-based ELISA for detection of avian malaria antibodies in African penguins (Spheniscus demersus).

Avian malaria, caused by Plasmodium spp. and transmitted by mosquitos, is a leading cause of mortality of captive penguins. Antimalarial drugs are currently used to control infections in penguins. However, the effectiveness of treatment reduces significantly by the time the clinical signs appear, while early and unnecessary treatment interferes with development of protective immunity. Therefore, for suppressing parasitemia without affecting the development of immunity in captive penguins, antimalaria drugs need to be administered at the right time, which requires reliable diagnostic tools that can determine the levels of circulating antimalaria antibodies. In the present study, we have developed an enzyme-linked immunosorbent assay (ELISA) diagnostic assay based on the merozoite surface protein 1 (MSP-1) of P. relictum isolate SGS1 to specifically detect and relatively quantify antimalaria antibodies in penguins. We expressed and purified a truncated P. relictum isolate SGS1 MSP-1 and optimized its biotinylation and subsequent conjugation to streptavidin alkaline phosphatase for signal generation in ELISA. We tested the assay by analyzing sera obtained from penguins at the Baltimore Zoo, from Spring through Fall, and found that levels of detectable antibodies against MSP-1 varied seasonally for individual penguins, consistent with the expected seasonal variations in avian malaria prevalence. Corroboratively, we analyzed the sensitivity of the assay by titrating positive sera and found that the signal intensity generated was serum concentration-dependent, thus validating the ability of the assay to detect and relatively quantify the levels of antimalaria antibodies in penguin sera.

Nobiletin protects retinal ganglion cells in models of ocular hypertension in vivo and hypoxia in vitro.

Glaucoma, a common cause of blindness, is characterized by the progressive loss of retinal ganglion cells (RGCs). Growing evidence suggests that nobiletin (NOB) is a promising neuroprotective drug; however, its effects on glaucomatous neurodegeneration remain unknown. Using rat models of microbead occlusion in vivo and primary RGCs model of hypoxia in vitro, we first demonstrate that NOB reduces RGC apoptosis by a TUNEL assay, Hoechst 33342 staining and FluoroGold (FG) retrograde labeling. This effect does not depend on intraocular pressure (IOP) lowering. Additionally, NOB partially restored the functional and structural damage of inner retinas, attenuated Müller glial activation and oxidative stress caused by ocular hypertension. At 2 weeks after IOP elevation, NOB further enhanced Nrf2/HO-1 pathway in RGCs to withstand the cumulative damage of ocular hypertension. With the administration of HO-1 inhibitor tin-protoporphyrin IX (SnPP), the protective effect of NOB was attenuated. Overall, these results indicate that NOB exerts an outstanding neuroprotective effect on RGCs of glaucomatous neurodegeneration. Besides, interventions to enhance activation of Nrf2/HO-1 pathway can slow the loss of RGCs and are viable therapies for glaucoma.

Flexible Humidity Sensors Based on Multidimensional Titanium Dioxide/Cellulose Nanocrystals Composite Film.

A humidity sensor is a crucial device in daily life; therefore, in the present study, a novel humidity sensor was designed to increase its specific surface area to improve its humid sensing capacity and conductivity. Titanium dioxide nanoparticles (TiNP) consisting of zero-dimensional nanospheres and one-dimensional nanotubes were prepared by anodic oxidation. Rod-shaped cellulose nanocrystals (CNCs) with average length and diameter of 60 nm and 800 nm, respectively, were obtained by enzymatic hydrolysis and high pressure homogenization. TiNP/CNC composite films exhibited superior hydrophilicity and large specific surface areas based on Fourier transform infrared spectroscopy and nitrogen adsorption-desorption results. The humidity sensing characteristics of sensors based on TiNP/CNC flexible composite films with varying contents of TiNP were investigated under a relative humidity range of 11-97%. The 6% TiNP/CNC-based humidity sensor exhibited high humidity response, rapid response/recovery speed, and high stability. Furthermore, the humidity sensing mechanism of TiNP/CNC composite films was analyzed based on the density functional theory. TiNP/CNC-based humidity sensors could be applied in flexible and wearable electronics.

Probing the Intracellular Delivery of Nanoparticles into Hard-to-Transfect Cells.

Hard-to-transfect cells are cells that are known to present special difficulties in intracellular delivery of exogenous entities. However, the special transport behaviors underlying the special delivery problem in these cells have so far not been examined carefully. Here, we combine single-particle motion analysis, cell biology studies, and mathematical modeling to investigate nanoparticle transport in bone marrow-derived mesenchymal stem cells (BMSCs), a technologically important type of hard-to-transfect cells. Tat peptide-conjugated quantum dots (QDs-Tat) were used as the model nanoparticles. Two different yet complementary single-particle methods, namely, pair-correlation function and single-particle tracking, were conducted on the same cell samples and on the same viewing stage of a confocal microscope. Our results reveal significant differences in each individual step of transport of QDs-Tat in BMSCs vs a commonly used model cell line, HeLa cells. Single-particle motion analysis demonstrates that vesicle escape and cytoplasmic diffusion are dramatically more difficult in BMSCs than in HeLa cells. Cell biology studies show that BMSCs use different biological pathways for the cellular uptake, vesicular transport, and exocytosis of QDs-Tat than HeLa cells. A reaction-diffusion-advection model is employed to mathematically integrate the individual steps of cellular transport and can be used to predict and design nanoparticle delivery in BMSCs. This work provides dissective, quantitative, and mechanistic understandings of nanoparticle transport in BMSCs. The investigative methods described in this work can help to guide the tailored design of nanoparticle-based delivery in specific types and subtypes of hard-to-transfect cells.

Inhibition of the NR2B-PSD95 Interaction Exerts Neuroprotective Effects on Retinal Ischemia-Reperfusion Injury.

Glaucoma is a neurodegenerative disease characterized by progressive retinal ganglion cell (RGC) death. Recently, many studies have reported that the N-methyl D-aspartate receptor 2B (NR2B) subunit is excitotoxic in the pathogenesis of glaucoma, but the molecular mechanism should be further explored. In our present study, we investigated the involvement of the NR2B-postsynaptic density protein-95 (PSD95) complex in RGC apoptosis in an experimental glaucoma animal model and determined whether inhibition of the NR2B-PSD95 interaction protected RGCs. We found that levels of NR2B, phosphorylated NR2B (p-NR2B) and PSD95 were significantly increased after 12 h of reperfusion, and the protein expression levels were maintained after 24 h of reperfusion in the ischemia-reperfusion (I/R) injury model. Immunohistochemical staining showed that NR2B and PSD95 partially colocalized in the ganglion cell layer (GCL). Increased levels of NR2B and p-NR2B were also detected in the rat chronic ocular hypertension (COH) model, while decreased PSD95 levels accompanied by severe injury were observed. Tat-NR2B9c treatment significantly increased RGC survival in the I/R injury model by disrupting the NR2B-PSD95 interaction, as confirmed by Brn3A fluorescent labelling and TdT-mediated dUTP nick-end labelling (TUNEL) assays. Levels of the apoptosis-related proteins Bax and cleaved caspase-3 decreased as the number of surviving RGCs increased. Together, our results suggest that the NR2B-PSD95 complex was involved in RGC death in the retinal I/R injury model. Tat-NR2B9c exerted a neuroprotective effect on RGC survival in the retinal I/R injury model by disrupting the NR2B-PSD95 interaction.

Cryptosporidium parvum Pyruvate Kinase Inhibitors With in vivo Anti-cryptosporidial Efficacy.

Cryptosporidium parvum is a highly prevalent protozoan parasite that causes a diarrheal disease in humans and animals worldwide. Thus far, the moderately effective nitazoxanide is the only drug approved by the United States Food and Drug Administration for treating cryptosporidiosis in immunocompetent humans. However, no effective drug exists for the severe disease seen in young children, immunocompromised individuals and neonatal livestock. C. parvum lacks the Krebs cycle and the oxidative phosphorylation steps, making it dependent solely on glycolysis for metabolic energy production. Within its glycolytic pathway, C. parvum possesses two unique enzymes, the bacterial-type lactate dehydrogenase (CpLDH) and the plant-like pyruvate kinase (CpPyK), that catalyze two sequential steps for generation of essential metabolic energy. We have previously reported that inhibitors of CpLDH are effective against C. parvum, both in vitro and in vivo. Herein, we developed an in vitro assay for the enzymatic activity of recombinant CpPyK protein and used it to screen a chemical compound library for inhibitors of CpPyK's activity. The identified inhibitors were tested (at non-toxic concentrations) for efficacy against C. parvum using in vitro assays, and an in vivo mouse infection model. We identified six CpPyK inhibitors that blocked in vitro growth and proliferation of C. parvum at low micromolar concentrations (EC50 values ranging from 10.29 to 86.01 µM) that were non-toxic to host cells. Among those six compounds, two (NSC252172 and NSC234945) were found to be highly efficacious against cryptosporidiosis in immunocompromised mice at a dose of 10 mg/kg body weight, with very significant reduction in parasite load and amelioration of intestinal pathologies. Together, these findings have unveiled inhibitors for an essential molecular target in C. parvum and demonstrated their efficacy against the parasite in vitro and in vivo. These inhibitors are, therefore, potential lead-compounds for developing efficacious treatments for cryptosporidiosis.

Remarkable SERS Detection by Hybrid Cu2O/Ag Nanospheres.

Cu2O nanospheres (NSs) were synthesized by modifying the glucose reduction method. Based on this method, Cu2O/Au (Ag) NSs were further prepared by in situ reduction of HAuCl4 (via electron beam evaporation of Ag). With Rhodamine 6G (R6G) as probe, the surface-enhanced Raman scattering (SERS) characteristics of the three samples were systematically studied. The experiment results showed that the enhancement factor (EF) of Cu2O/Au (Ag) NSs as 1.25 × 108 (2.74 × 109) and the ultralow detection limit (LOD) as 8.07 × 10-12 (1.13 × 10-13) M for R6G. The excellent performance of SERS may be due to the charge transfer (CT) between metal-semiconductor (MS) molecules and the strong electromagnetic field (E-field) of each hot spot. In addition, discrete dipole approximation (DDA) simulations were performed to simulate the E-field enhancement of the Cu2O and Cu2O/Au (Ag) NSs in a three-dimensional (3D) configuration. These further supported that the high SERS performance for R6G is because of the powerful E-field coupling between neighboring Au (Ag) NPs and the surface plasmon resonance (SPR) effect. The Cu2O/Ag NSs have potential in applications such as biomedicine, food safety, and environmental monitoring because of their high sensitivity and good reproducibility.

Switchable Electromagnetically Induced Transparency with Toroidal Mode in a Graphene-Loaded All-Dielectric Metasurface.

Active photonics based on graphene has attracted wide attention for developing tunable and compact optical devices with excellent performances. In this paper, the dynamic manipulation of electromagnetically induced transparency (EIT) with high quality factors (Q-factors) is realized in the optical telecommunication range via the graphene-loaded all-dielectric metasurface. The all-dielectric metasurface is composed of split Si nanocuboids, and high Q-factor EIT resonance stems from the destructive interference between the toroidal dipole resonance and the magnetic dipole resonance. As graphene is integrated on the all-dielectric metasurface, the modulation of the EIT window is realized by tuning the Fermi level of graphene, engendering an appreciable modulation depth of 88%. Moreover, the group velocity can be tuned from c/1120 to c/3390. Our proposed metasurface has the potential for optical filters, modulators, and switches.

Particle trapping and beaming using a 3D nanotip excited with a plasmonic vortex.

Recent advances in nanotechnology have prompted the need for tools to accurately and noninvasively manipulate individual nano-objects. Among the possible strategies, optical forces have been widely used to enable nano-optical tweezers capable of trapping or moving a specimen with unprecedented accuracy. Here, we propose an architecture consisting of a nanotip excited with a plasmonic vortex enabling effective dynamic control of nanoparticles in three dimensions. The structure illuminated by a beam with angular momentum can generate an optical field that can be used to manipulate single dielectric nanoparticles. We demonstrate that it is possible to stably trap or push the particle from specific points, thus enabling a new, to the best of our knowledge, platform for nanoparticle manipulation.

Neuroprotective effects of DAAO are mediated via the ERK1/2 signaling pathway in a glaucomatous animal model.

Neuronal excitotoxicity caused by over activation of N -Methyl-D-Aspartate (NMDA) receptors is an important risk factor for the retinal ganglion cells (RGCs) death in glaucoma. D-serine played a role as a key co-agonist for NMDA receptor activity and neurotoxicity. Our previous studies have demonstrated that increased D-serine and serine racemase (SR) expression in the retina of the chronic intraocular hypertension (COH) model were detected. D-amino acid oxidase (DAAO) treatment significantly increased RGCs survival in the glaucomatous eyes. However, the molecular mechanism remains unclear. In the present study, we investigated the extracellular signal-regulated protein kinase1/2 (ERK1/2) signaling pathway involved in DAAO neuroprotective effects on RGC survival and explore the effect of inhibited ERK1/2 phosphorylation on RGC survival and Müller cell activation in a COH rat model. We found that ERK1/2 phosphorylation and p38 kinase (p38) phosphorylation increased in the COH model, while c-Jun N-terminal kinase (JNK) phosphorylation didn't change. DAAO treatment induced ERK-1/2 MAP kinase phosphorylation and its upstream regulator, p-MEK increased in the COH model. The increased p-ERK was mainly located in retinal Müller cells. In contrast, p-JNK and p-p38 protein expression was not significantly different under these conditions. Quantitative analysis of RGC survival by fluorescent labeling and TdT-mediated dUTP nick-end labeling (TUNEL) assays confirmed that p-ERK1/2 inhibition by PD98059 attenuates DAAO-mediated reductions in RGC apoptosis. Additionally, p-ERK1/2 inhibition induced elevated glial fibrillary acidic protein (GFAP) expression in Müller cells in the COH model. Together, these results suggest that the ERK1/2 signaling pathway is involved in DAAO's neuroprotective effects on RGC survival.