Dissolved organic phosphorus promotes Cyclotella growth and adaptability in eutrophic tropical estuaries.

Dissolved organic phosphorus (DOP) is an important nutrient for phytoplankton growth in oligotrophic oceans. However, little is known about the impact of DOP on phytoplankton growth in eutrophic waters. In the present study, we conducted field monitoring as well as in situ and laboratory experiments in the Pearl River estuary (PRE). Field observations showed an increase in the nitrogen-to-phosphorus ratio and DOP in recent years in the PRE. The phytoplankton community was dominated by nanophytoplankton Cyclotella in the upper and middle estuary, with high concentrations of DOP and light limitation during the ebb stage of the spring to neap tide in summer. The relative abundance of Cyclotella in natural waters was higher after enrichment with estuarine water with a background of 0.40-0.46 µM DOP, even when dissolved inorganic phosphorus was sufficient (0.55-0.76 µM). In addition, the relative abundance of Cyclotella in natural waters was higher after enrichment with phosphoesters. Laboratory culture results also confirmed that phosphoesters can enhance the growth rate of Cyclotella cryptica. Our study highlights that Cyclotella can become the dominant species in estuaries with increased levels of phosphoesters and low and fluctuating light adaptability and under the joint effect of dynamic processes such as upwelling and tides. Our results provide new insights into the role of Cyclotella in biogeochemical cycles affected by DOP utilization and potential applications in relieving the hypoxia of tropical eutrophic estuaries.IMPORTANCEThis study provides evidence that Cyclotella can become the dominant species in estuaries with increased levels of phosphoesters and low and fluctuating light adaptability and under the joint effect of dynamic processes such as upwelling and tides. Our study provides new insights into the role of Cyclotella in biogeochemical cycles affected by dissolved organic phosphorus utilization, especially affected by anthropogenic inputs and climate change. Potential applications include relieving the hypoxia of tropical eutrophic estuaries.

Slit2 suppresses endotoxin-induced uveitis by inhibiting the PI3K/Akt/IKK/NF-κB pathway.

Uveitis is a devastating intraocular inflammatory disease. The secreted leucine-rich repeat protein slit homologue 2 (Slit2) has been found to be an essential regulator of inflammation. This study aimed to analyse the anti-inflammatory effects and the underlying mechanisms of Slit2 in an endotoxin-induced uveitis (EIU) rat model. In this study, rats with EIU pretreated recombinant human Slit2 (rhSlit2) or a control vehicle by intravitreal injection. The clinical scores were graded under a slit lamp. The protein concentrations and total number of cells in the aqueous humour (AqH) were examined, and the retinal expression of various inflammatory mediators was detected. The levels of nuclear factor-kappa B (NF-κB), phosphorylated NF-κB, IkappaB-a (IκB-a), phosphorylated IκB-a, IKK, phosphorylated IKK, PI3Kp85, phosphorylated PI3Kp85, Akt and phosphorylated Akt were evaluated by western blotting. Treatment with rhSlit2 dramatically diminished the clinical scores of EIU, with significant decreases in inflammatory cell infiltration, protein concentrations, cellulose-like exudates, the production of ICAM-1, MCP-1, TNF-α and IL-6 in the AqH; and adhesion of leucocytes. The PI3K/Akt/IKK/NF-κB pathway was found to be activated in EIU. However, the pre-treatment of rhSlit2 significantly inhibited the production of ICAM-1, MCP-1, TNF-α, and IL-6, and inhibited leucocyte adhesion by modulating the PI3K/Akt/IKK/NF-κB pathway. In conclusion, the intravitreal injection of rhSlit2 alleviated EIU-related inflammation in Sprague-Dawley rats by reducing the proinflammatory cytokines and leucocyte adhesion; in particular, rhSlit2 may inhibit LPS-induced inflammation by inhibiting the activation of PI3K/Akt/IKK/NF-κB signalling pathway. Therefore, rhSlit2 shows significant potential for effectively alleviating immune inflammatory responses in vivo.

Post-translational modifications on the retinoblastoma protein.

The retinoblastoma protein (pRb) functions as a cell cycle regulator controlling G1 to S phase transition and plays critical roles in tumour suppression. It is frequently inactivated in various tumours. The functions of pRb are tightly regulated, where post-translational modifications (PTMs) play crucial roles, including phosphorylation, ubiquitination, SUMOylation, acetylation and methylation. Most PTMs on pRb are reversible and can be detected in non-cancerous cells, playing an important role in cell cycle regulation, cell survival and differentiation. Conversely, altered PTMs on pRb can give rise to anomalies in cell proliferation and tumourigenesis. In this review, we first summarize recent findings pertinent to how individual PTMs impinge on pRb functions. As many of these PTMs on pRb were published as individual articles, we also provide insights on the coordination, either collaborations and/or competitions, of the same or different types of PTMs on pRb. Having a better understanding of how pRb is post-translationally modulated should pave the way for developing novel and specific therapeutic strategies to treat various human diseases.

Rising temperature contributed to the outbreak of a macrozooplankton Creseis acicula by enhancing its feeding and assimilation for algal food nearby the coastal Daya Bay Nuclear Power Plant.

An outbreak of a macrozooplankton Creseis acicula occurred in the summer of 2020 nearby the Daya Bay Nuclear Power Plant located on the coast of the Daya Bay in the South China Sea. The outbreaks of C. acicula often threaten human health, the marine environment, and other human activities including the safe operation of coastal nuclear power plants. Seawater temperature has been suggested as an important factor influencing such outbreaks. However, the underlying mechanisms through which temperature influences C. acicula remains unknown. Here, we studied the effects of temperature on the ingestion and assimilation of algal food by feeding radiocarbon-labeled algae Chlorella sp. at simulated field temperatures (19-31 °C) to C. acicula collected during the outbreak in the Daya Bay. We also quantified the allocation of the food carbon to dissolved organic carbon (DOC), CO2, and fecal pellets. The results showed that the zooplankton during the same feeding time ingested doubled or tripled algal food at higher temperatures, and it produced and released significantly more DOC, CO2, and fecal pellets with more ingested food carbon. Meanwhile, the assimilation efficiency for the ingested food carbon slightly increased from 48% to 54% with rising temperature. As a result, higher assimilation rates indicating faster growth of C. acicula were observed at higher temperatures. In addition, the high activation energy of 0.908 eV indicated that the assimilation rate was very sensitive to temperature rising. Our results show that relatively rising temperature can enhance C. acicula's ingestion and assimilation rates for algal food, benefit its growth and metabolism, and contribute to its outbreak. This study provides a mechanistic interpretation for the relationship between rising temperature and the outbreaks of C. acicula and suggests that such outbreaks may occur more frequently and widely in the warming ocean.

VEGF-B is a potent antioxidant.

VEGF-B was discovered a long time ago. However, unlike VEGF-A, whose function has been extensively studied, the function of VEGF-B and the mechanisms involved still remain poorly understood. Notwithstanding, drugs that inhibit VEGF-B and other VEGF family members have been used to treat patients with neovascular diseases. It is therefore critical to have a better understanding of VEGF-B function and the underlying mechanisms. Here, using comprehensive methods and models, we have identified VEGF-B as a potent antioxidant. Loss of Vegf-b by gene deletion leads to retinal degeneration in mice, and treatment with VEGF-B rescues retinal cells from death in a retinitis pigmentosa model. Mechanistically, we demonstrate that VEGF-B up-regulates numerous key antioxidative genes, particularly, Gpx1 Loss of Gpx1 activity largely diminished the antioxidative effect of VEGF-B, demonstrating that Gpx1 is at least one of the critical downstream effectors of VEGF-B. In addition, we found that the antioxidant function of VEGF-B is mediated mainly by VEGFR1. Given that oxidative stress is a crucial factor in numerous human diseases, VEGF-B may have therapeutic value for the treatment of such diseases.

Uptake and subcellular distribution of aluminum in a marine diatom.

Aluminum (Al) is widespread in the environment including the ocean. The effects of Al on marine organisms have attracted more and more attention in recent years. However, the mechanisms of uptake of Al by marine organisms and the subcellular distribution of Al once assimilated are unknown. Here we report the uptake and subcellular distribution of Al in a marine diatom Thalassiosira weissflogii. Short-term (< 120 min) uptake experiments showed that the Al uptake rate by the diatom was 0.033 ±â€¯0.013 fmol-1 cell-1 min-1 (internalization flux normalized to the exposure Al concentration of 2 µM = 0.034 ±â€¯0.013 nmol m-2 min-1 nM-1). Subcellular fractionation experiments showed that the internalized Al was partitioned to subcellular components in the following order: granules (69 ±â€¯5%) > debris (17 ±â€¯4%) > organelles (12 ±â€¯2%) > heat-stable peptides (HSP) (~2%) > heat-denaturable proteins (HDP) (< 1%), indicating that the majority of intracellular Al was detoxified and stored in inorganic forms. The subcellular distribution of Al in the diatom is different from that of Al in freshwater green algae, in which most of the internalized Al is partitioned to organelles. We also evaluated an artificial seawater-based EDTA rinse solution to remove Al adsorbed on the diatom cell surface. Overall, our study provides new information to understand the mechanisms of uptake of Al by marine diatoms, and the mechanisms responsible for the biological effects (both toxic and beneficial) of Al on the growth of marine phytoplankton, especially diatoms.

Mechanisms of mitochondrial resilience in teleostean radial glia under hypoxic stress.

Radial glial cells (RGCs) are remarkable cells, essential for normal development of the vertebrate central nervous system. In teleost fishes, RGCs play a pivotal role in neurogenesis and regeneration of injured neurons and glia. RGCs also exhibit resilience to environmental stressors like hypoxia via metabolic adaptations. In this study, we assessed the physiology of RGCs following varying degrees of hypoxia, with an emphasis on reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), mitophagy, and energy metabolism. Our findings demonstrated that hypoxia significantly elevated ROS production and induced MMP depolarization in RGCs. The mitochondrial disturbances were closely associated with increased mitophagy, based on the co-localization of mitochondria and lysosomes. Key mitophagy-related genes were also up-regulated, including those of the BNIP3/NIX mediated pathway as well as the FUNDC1 mediated pathway. Such responses suggest robust cellular mechanisms are initiated to counteract mitochondrial damage due to increasing hypoxia. A significant metabolic shift from oxidative phosphorylation to glycolysis was also observed in RGCs, which may underlie an adaptive response to sustain cellular function and viability following a reduction in oxygen availability. Furthermore, hypoxia inhibited the synthesis of mitochondrial complexes subunits in RGCs, potentially related to elevated HIF-2α expression with 3 % O2. Taken together, RGCs appear to exhibit complex adaptive responses to hypoxic stress, characterized by metabolic reprogramming and the activation of mitophagy pathways to mitigate mitochondrial dysfunction.

Regime shift in a coastal pelagic ecosystem with increasing human-induced nutrient inputs over decades.

Human-induced nutrient inputs to global coastal waters are leading to increasing nutrients and escalating eutrophication. However, how aquatic ecosystem functioning responds to these changes remains insufficiently studied. Here we report the long-term changes in the nutrient regime and planktonic ecosystem functioning in the Daya Bay, a typical subtropical semi-enclosed bay experiencing rapid economic and social development for several decades. Time-series (from 1991 to 2018) data with a mostly quarterly resolution were collected to depict long-term changes in dissolved inorganic nutrients and plankton abundances, based on which we constructed simplified abundance size spectra (SASS) and plankton abundance ratios to describe the functioning of the planktonic ecosystem. The results revealed a long-term increase in system productivity but a decrease in integrated energy transfer efficiency of the planktonic ecosystem, with rising concentrations of dissolved inorganic nitrogen (DIN). Shifts in the nutrient regime and planktonic ecosystem functioning were detected at a tipping point or threshold around 2006-2007. The shifts were characterized by abrupt changes in the trends of nutrient (phosphate, ammonia, nitrite) concentrations, nutrient ratios (DIN/phosphate, silicate/phosphate), plankton abundance, and total plankton biomass. Compared to the nutrient regime, the planktonic ecosystem functioning shifted several years later. Overall, this study indicates that the pelagic ecosystem regime can shift significantly in response to long-term increasing input of human-induced nutrients in coastal waters such as the Daya Bay. The regime shifts may have profound implications for fishery production, and ecosystem management in the bay.

Size-dependent zoogeographical distribution of gelatinous thaliaceans associated with current velocity and temperature.

Thaliaceans are globally distributed and play an important role in the world's biological carbon pump and marine ecosystems by forming dense swarms with high feeding rates and producing large amounts of fecal pellets and carcasses. The contribution of thaliacean swarms to the downward transport of carbon depends not only on their abundance but also on their body size. However, the key factors influencing the distribution of different-sized thaliaceans remain unstudied. To discriminate thaliacean assemblages and examine the key factors determining the zoogeographical distribution and abundance of different-sized thaliaceans during different monsoon periods, we conducted three cruises in the South China Sea from before the southwest monsoon to the peak of the northeast monsoon. Our results revealed that high thaliacean abundance corresponded to high chlorophyll a concentration, which were associated with hydrodynamic processes, such as upwelling and eddies. Hierarchical partitioning and niche difference analyses demonstrated that current velocity and temperature are key factors that shaped the zoogeographical distribution of different-sized thaliaceans. The global dataset indicated that small-sized thaliacean species tend to occur in coastal areas where the current velocity is generally high, while large-sized species tend to occur in open ocean areas where the current velocity is generally low. The results revealed that global warming-induced changes in surface current velocity and temperature may alter the zoogeographical distribution and abundance of thaliaceans with different sizes, thereby affecting the biological carbon pump and surrounding marine ecosystem. Overall, this study sheds light on the potential responses of pelagic tunicates to global climate change through changes in their hydrodynamic conditions.

Etiology including epigenetic defects of retinoblastoma.

Retinoblastoma (RB), originating from the developing retina, is an aggressive intraocular malignant neoplasm in childhood. Biallelic loss of RB1 is conventionally considered a prerequisite for initiating RB development in most RB cases. Additional genetic mutations arising from genome instability following RB1 mutations are proposed to be required to promote RB development. Recent advancements in high throughput sequencing technologies allow a deeper and more comprehensive understanding of the etiology of RB that additional genetic alterations following RB1 biallelic loss are rare, yet epigenetic changes driven by RB1 loss emerge as a critical contributor promoting RB tumorigenesis. Multiple epigenetic regulators have been found to be dysregulated and to contribute to RB development, including noncoding RNAs, DNA methylations, RNA modifications, chromatin conformations, and histone modifications. A full understanding of the roles of genetic and epigenetic alterations in RB formation is crucial in facilitating the translation of these findings into effective treatment strategies for RB. In this review, we summarize current knowledge concerning genetic defects and epigenetic dysregulations in RB, aiming to help understand their links and roles in RB tumorigenesis.

Improved accuracy of spectral-domain optical coherence tomography and optical coherence tomography angiography for monitoring myopic macular neovascularisation activity.

BACKGROUND/AIMS: To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD OCT) combined with OCT angiography (OCTA) for myopic myopic macular neovascularisation (MNV) activity. METHODS: Both eyes of patients with myopic MNV diagnosed with fluorescein angiography (FA), SD OCT and OCTA were assessed by unmasked investigators. The images were deidentified and randomised before graded by masked investigators, who determined the presence of active myopic MNV by using SD OCT together with OCTA without FA and by FA alone, respectively. The findings of masked investigators were compared with unmasked investigators. RESULTS: 213 eyes of 110 patients comprising 499 imaging episodes were eligible for grading. For diagnosing new-onset myopic MNV without FA, combined use of SD OCT and OCTA had a sensitivity of 0.94, specificity of 0.84 and area under the curve (AUC) of 0.92. FA had a sensitivity of 0.52 (p<0.01), specificity of 0.80 (p=0.38) and AUC of 0.66 (p<0.01). For recurrent myopic MNV, the combination of SD OCT and OCTA had a sensitivity of 0.98, specificity of 0.78 and AUC of 0.88. FA had a sensitivity of 0.50 (p=0.04), specificity of 0.76 (p=0.85) and AUC of 0.63 (p=0.01). Myopic traction maculopathy was more frequently associated with recurrent myopic MNV (p<0.01). CONCLUSION: SD OCT with dense volumetric scan was highly sensitive for diagnosing myopic MNV. The addition of OCTA improved the diagnostic specificity without FA. Monitoring of the longitudinal changes on SD OCT and judicious use of FA is a reliable surveillance strategy for myopic MNV.

MIR34A modulates lens epithelial cell apoptosis and cataract development via the HK1/caspase 3 signaling pathway.

Cataracts are the leading cause of blindness in the world. Age is a major risk factor for cataracts, and with increasing aging, the burden of cataracts will grow, but the exact details of cataractogenesis remain unclear. A recent study showed that microRNA-34a (MIR34A) is involved in the development of cataracts, but the underlying pathogenesis remains obscure. Here, our results of microRNA target prediction showed that hexokinase 1 (HK1) is one of the genes targeted by MIR34A. Based on this finding, we focused on the function of MIR34A and HK1 in the progress of cataracts, whereby the human lens epithelial cell line SRA01/04 and mouse lens were treated with MIR34A mimics and HK1 siRNA. We found that HK1 mRNA is a direct target of MIR34A, whereby the high expression of MIR34A in the cataract lens suppresses the expression of HK1. In vitro, the upregulation of MIR34A together with the downregulation of HK1 inhibits the proliferation, induces the apoptosis of SRA01/04 cells, and accelerates the opacification of mouse lenses via the HK1/caspase 3 signaling pathway. In summary, our study demonstrates that MIR34A modulates lens epithelial cell (LEC) apoptosis and cataract development through the HK1/caspase 3 signaling pathway.

Emerging Roles of cGAS-STING Signaling in Mediating Ocular Inflammation.

Cyclic GMP-AMP (cGAMP) synthase (cGAS), a sensor of cytosolic DNA, recognizes cytoplasmic nucleic acids to activate the innate immune responses via generation of the second messenger cGAMP and subsequent activation of the stimulator of interferon genes (STINGs). The cGAS-STING signaling has multiple immunologic and physiological functions in all human vital organs. It mediates protective innate immune defense against DNA-containing pathogen infection, confers intrinsic antitumor immunity via detecting tumor-derived DNA, and gives rise to autoimmune and inflammatory diseases upon aberrant activation by cytosolic leakage of self-genomic and mitochondrial DNA. Disruptions in these functions are associated with the pathophysiology of various immunologic and neurodegenerative diseases. Recent evidence indicates important roles of the cGAS-STING signaling in mediating inflammatory responses in ocular inflammatory and inflammation-associated diseases, such as keratitis, diabetic retinopathy, age-related macular degeneration, and uveitis. In this review, we summarize the recently emerging evidence of cGAS-STING signaling in mediating ocular inflammatory responses and affecting pathogenesis of these complex eye diseases. We attempt to provide insightful perspectives on future directions of investigating cGAS-STING signaling in ocular inflammation. Understanding how cGAS-STING signaling is modulated to mediate ocular inflammatory responses would allow future development of novel therapeutic strategies to treat ocular inflammation and autoimmunity.

Growth hormone releasing hormone signaling promotes Th17 cell differentiation and autoimmune inflammation.

Dysregulation of Th17 cell differentiation and pathogenicity contributes to multiple autoimmune and inflammatory diseases. Previously growth hormone releasing hormone receptor (GHRH-R) deficient mice have been reported to be less susceptible to the induction of experimental autoimmune encephalomyelitis. Here, we show GHRH-R is an important regulator of Th17 cell differentiation in Th17 cell-mediated ocular and neural inflammation. We find that GHRH-R is not expressed in naïve CD4+ T cells, while its expression is induced throughout Th17 cell differentiation in vitro. Mechanistically, GHRH-R activates the JAK-STAT3 pathway, increases the phosphorylation of STAT3, enhances both non-pathogenic and pathogenic Th17 cell differentiation and promotes the gene expression signatures of pathogenic Th17 cells. Enhancing this signaling by GHRH agonist promotes, while inhibiting this signaling by GHRH antagonist or GHRH-R deficiency reduces, Th17 cell differentiation in vitro and Th17 cell-mediated ocular and neural inflammation in vivo. Thus, GHRH-R signaling functions as a critical factor that regulates Th17 cell differentiation and Th17 cell-mediated autoimmune ocular and neural inflammation.

Quantification of the carbon released by a marine fish using a carbon release model and radiocarbon.

Here we propose a carbon release model that divides fish-released carbon into two sources (ingested food and the fish body), and three forms (dissolved organic carbon (DOC), CO2, and particulate carbon (PC)). We quantified the daily carbon budget of a marine fish Oryzias melastigma by feeding the fish radiocarbon-labeled living rotifer. We found that 91%-92%, 25%-47%, 28%-50%, 20%-31%, and 8%-9% of the ingested food carbon was absorbed, assimilated, and released as DOC, CO2, and PC, respectively. Fish body carbon dissimilated/catabolized and released as 0.053-0.12 d-1 at two daily food rations. DOC, CO2, and PC accounted for 39%-42%, 39%-45%, and 16%-19% of the released fish body carbon, respectively. Our study shows that the fish transformed substantial fractions of their daily ingested food and dissimilated body carbon into DOC, and fish may be an important source of DOC in the ocean.

Epigallocatechin-3-Gallate Protects Trabecular Meshwork Cells from Endoplasmic Reticulum Stress.

Primary open-angle glaucoma (POAG) is the most common form of glaucoma, for which elevated intraocular pressure (IOP) is a major risk factor. IOP is mainly regulated by dynamic balance of aqueous humor (AH) production and outflow via the conventional trabecular meshwork/Schlemm's canal (TM/SC) pathway. Dysfunctions of TM cells due to endoplasmic reticulum (ER) stress have been demonstrated to increase the resistance of AH outflow, resulting in IOP elevation. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic component in green tea, has been shown to alleviate ER stress in several diseases while its potential roles in alleviating ER stress in TM cells have not been determined. In this study, we investigate the mitigation of tunicamycin-induced ER stress in TM cells by EGCG. MTT assay was used to measure the cell viability of human TM (HTM) cells and primary porcine TM (PTM) cells. ER stress levels in both HTM cells and primary PTM cells were detected by quantitative real-time PCR. The primary PTM cells isolated from porcine TM tissues were characterized by immunostaining. We found that 40 µM and 80 µM EGCG pretreatment substantially promoted HTM cell survival under 3 µM tunicamycin-induced ER stress. Pretreatment of 40 µM EGCG markedly reduced the expression of ER stress markers ATF4, HSPA5, and DDIT3, evoked by 3 µM tunicamycin in HTM cells. Furthermore, 40 µM EGCG pretreatment significantly decreased the expressions of ATF4, HSPA5, and DDIT3 at the mRNA level induced by 3 µM tunicamycin and improved cell viability in primary PTM cells. Our results show that EGCG is capable of protecting TM cells from ER stress. EGCG provides a promising therapeutic option for POAG treatment.

Chaperonin-Containing TCP1 Subunit 5 Protects Against the Effect of Mer Receptor Tyrosine Kinase Knockdown in Retinal Pigment Epithelial Cells by Interacting With Filamentous Actin and Activating the LIM-Kinase 1/Cofilin Pathway.

Retinitis pigmentosa (RP), characterized by the gradual loss of rod and cone photoreceptors that eventually leads to blindness, is the most common inherited retinal disorder, affecting more than 2.5 million people worldwide. However, the underlying pathogenesis of RP remains unclear and there is no effective cure for RP. Mutations in the Mer receptor tyrosine kinase (MERTK) gene induce the phagocytic dysfunction of retinal pigment epithelium (RPE) cells, leading to RP. Studies have indicated that filamentous actin (F-actin)-which is regulated by chaperonin-containing TCP1 subunit 5 (CCT5)-plays a vital role in phagocytosis in RPE cells. However, whether CCT5/F-actin signaling is involved in MERTK-associated RP remains largely unknown. In the present study, we specifically knocked down MERTK and CCT5 through siRNA transfection and examined the expression of CCT5 and F-actin in human primary RPE (HsRPE) cells. We found that MERTK downregulation inhibited cell proliferation, migration, and phagocytic function; significantly decreased the expression of F-actin; and disrupted the regular arrangement of F-actin. Importantly, our findings firstly indicate that CCT5 interacts with F-actin and is inhibited by MERTK siRNA in HsRPE cells. Upregulating CCT5 using CCT5-specific lentiviral vectors (CCT5-Le) rescued the cell proliferation, migration, and phagocytic function of HsRPE cells under the MERTK knockdown condition by increasing the expression of F-actin and restoring its regular arrangement via the LIMK1/cofilin, but not the SSH1/cofilin, pathway. In conclusion, CCT5 protects against the effect of MERTK knockdown in HsRPE cells and demonstrates the potential for effective treatment of MERTK-associated RP.

Effects of terrestrial inputs and seawater intrusion on zooplankton community structure in Daya Bay, South China Sea.

Daya Bay is a eutrophic coastal region with dynamic physico-chemical conditions influenced by terrestrial inputs and seawater intrusion. Zooplankton is a crucial trophic intermediary for energy transfer and fishery resources. In this study, we assessed the distribution and composition of zooplankton in Daya Bay during summer and winter of 2015. We found that zooplankton diversity was the lowest and dominated by small copepods (Acartia spp. and Paracalanus spp.) and gelatinous Oikopleura spp. under terrestrial inputs in the Dan'ao River estuary and Aotou barbour. The highest zooplankton diversity was observed at the bay mouth that influenced by salty intruded seawater, and the dominant oceanic species (such as Euchaeta concinna and Subeucalanus subcrassus invaded into the top of the bay in winter. The dominant species in the estuary shift from Penilia avirostris to Acartia spp. compared with historical researches, indicating the effect of human activities on the succession of dominant species.

Role of VEGFR2 in Mediating Endoplasmic Reticulum Stress Under Glucose Deprivation and Determining Cell Death, Oxidative Stress, and Inflammatory Factor Expression.

Retinal pigment epithelium (RPE), a postmitotic monolayer located between the neuroretina and choroid, supports the retina and is closely associated with vision loss diseases such as age-related macular degeneration (AMD) upon dysfunction. Although environmental stresses are known to play critical roles in AMD pathogenesis and the roles of other stresses have been well investigated, glucose deprivation, which can arise from choriocapillary flow voids, has yet to be fully explored. In this study, we examined the involvement of VEGFR2 in glucose deprivation-mediated cell death and the underlying mechanisms. We found that VEGFR2 levels are a determinant for RPE cell death, a critical factor for dry AMD, under glucose deprivation. RNA sequencing analysis showed that upon VEGFR2 knockdown under glucose starvation, endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are reduced. Consistently, VEGFR2 overexpression increased ER stress under the same condition. Although VEGFR2 was less expressed compared to EGFR1 and c-Met in RPE cells, it could elicit a higher level of ER stress induced by glucose starvation. Finally, downregulated VEGFR2 attenuated the oxidative stress and inflammatory factor expression, two downstream targets of ER stress. Our study, for the first time, has demonstrated a novel role of VEGFR2 in RPE cells under glucose deprivation, thus providing valuable insights into the mechanisms of AMD pathogenesis and suggesting that VEGFR2 might be a potential therapeutic target for AMD prevention, which may impede its progression.