Prognostic Prediction and Immune Microenvironment Characterization in Uveal Melanoma: A Novel Mitochondrial Metabolism-Related Gene Signature.

Uveal Melanoma (UM), a highly aggressive and metastatic intraocular cancer with a strong propensity for liver metastasis, presents limited therapeutic alternatives and unfavorable survival outcomes. Despite its low incidence, the underlying mechanisms of UM pathogenesis and the precise role of mitochondrial metabolism in UM remain inadequately understood. Utilizing Cox proportional hazards regression analysis was used to assess prognostic relevance, and consensus clustering was employed for molecular subtyping. A risk signature was constructed using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression. We further conducted comparative analyses on clinicopathological characteristics, somatic mutation profiles, drug sensitivity, gene expression patterns, and tumor microenvironment features across different molecular subtypes. Moreover, a nomogram was developed and evaluated. Among 1234 mitochondria metabolism-related genes (MMRGs), 343 were identified as significantly associated with the prognosis of UM. These prognosis-associated MMRGs facilitated the classification of UM into two distinct molecular subtypes, which displayed notable differences in prognosis and pathological staging. Furthermore, an index termed the MMRGs-derived index (MMI) was derived from eight MMRGs, serving as a quantitative measure for poor prognosis risk in UM. MMI demonstrated significant associations with clinicopathological characteristics, somatic mutations, drug responsiveness, and the tumor microenvironment, where higher MMI levels corresponded to worse prognosis, advanced pathological stages, and increased immune cell infiltration. The nomogram built upon MMI provided a potential tool for clinical prognosis assessment in UM patients. This study demonstrated the potential value of MMRGs in predicting prognosis and molecular stratification within UM; however, additional clinical and basic research is warranted to validate their applicability and elucidate the related mechanisms.

The source and accumulation of anthropogenic carbon in the U.S. East Coast.

The ocean has absorbed anthropogenic carbon dioxide (Canthro) from the atmosphere and played an important role in mitigating global warming. However, how much Canthro is accumulated in coastal oceans and where it comes from have rarely been addressed with observational data. Here, we use a high-quality carbonate dataset (1996-2018) in the U.S. East Coast to address these questions. Our work shows that the offshore slope waters have the highest Canthro accumulation changes (ΔCanthro) consistent with water mass age and properties. From offshore to nearshore, ΔCanthro decreases with salinity to near zero in the subsurface, indicating no net increase in the export of Canthro from estuaries and wetlands. Excesses over the conservative mixing baseline also reveal an uptake of Canthro from the atmosphere within the shelf. Our analysis suggests that the continental shelf exports most of its absorbed Canthro from the atmosphere to the open ocean and acts as an essential pathway for global ocean Canthro storage and acidification.

Development of SPEEK-Coated IrOx Sensor for High-Biomass Aquatic pH Monitoring.

Instability is a key challenge for current pH sensors in practical applications, especially in aquatic environments with high biomass and redox substances. Herein, we present a novel approach that uses a highly stable IrOx sensing layer enveloped in a composite film of SPEEK doped with a silicon-stabilized ionic liquid (SP-IrOx). This design mitigates drift due to sensitive layer variations and minimizes interference from complex external conditions. After exhibiting robustness under moderately reducing conditions caused by S2-, I-, and ascorbic acid, the SP-IrOx sensor's efficacy was validated through real-time pH measurements in demanding aquatic settings. These included laboratory algal culture medium, sediment substrates, and mussel aquaculture areas. The sensor sustained accuracy and stability over extended periods of 6-8 days when compared to calibrated commercial electrodes. The deviations from reference samples were minimal, with a variance of no more than 0.03 pH units in mussel aquaculture areas (n = 17) and 0.07 pH units in an algal culture medium (n = 37). As a potentiometric, this solid-state electrode features a compact structure and low energy consumption, making it an economical and low-maintenance solution for precise pH monitoring in diverse challenging environments with high biomass and turbidity.

The microbial carbon pump and climate change.

The ocean has been a regulator of climate change throughout the history of Earth. One key mechanism is the mediation of the carbon reservoir by refractory dissolved organic carbon (RDOC), which can either be stored in the water column for centuries or released back into the atmosphere as CO2 depending on the conditions. The RDOC is produced through a myriad of microbial metabolic and ecological processes known as the microbial carbon pump (MCP). Here, we review recent research advances in processes related to the MCP, including the distribution patterns and molecular composition of RDOC, links between the complexity of RDOC compounds and microbial diversity, MCP-driven carbon cycles across time and space, and responses of the MCP to a changing climate. We identify knowledge gaps and future research directions in the role of the MCP, particularly as a key component in integrated approaches combining the mechanisms of the biological and abiotic carbon pumps for ocean negative carbon emissions.

Carbonate Chemistry and the Potential for Acidification in Georgia Coastal Marshes and the South Atlantic Bight, USA.

In coastal regions and marginal bodies of water, the increase in partial pressure of carbon dioxide (pCO2) in many instances is greater than that of the open ocean due to terrestrial (river, estuarine, and wetland) influences, decreasing buffering capacity and/or increasing water temperatures. Coastal oceans receive freshwater from rivers and groundwater as well as terrestrial-derived organic matter, both of which have a direct influence on coastal carbonate chemistry. The objective of this research is to determine if coastal marshes in Georgia, USA, may be "hot-spots" for acidification due to enhanced inorganic carbon sources and if there is terrestrial influence on offshore acidification in the South Atlantic Bight (SAB). The results of this study show that dissolved inorganic carbon (DIC) and total alkalinity (TA) are elevated in the marshes compared to predictions from conservative mixing of the freshwater and oceanic end-members, with accompanying pH around 7.2 to 7.6 within the marshes and aragonite saturation states (ΩAr) <1. In the marshes, there is a strong relationship between the terrestrial/estuarine-derived organic and inorganic carbon and acidification. Comparisons of pH, TA, and DIC to terrestrial organic material markers, however, show that there is little influence of terrestrial-derived organic matter on shelf acidification during this period in 2014. In addition, ΩAr increases rapidly offshore, especially in drier months (July). River stream flow during 2014 was anomalously low compared to climatological means; therefore, offshore influences from terrestrial carbon could also be decreased. The SAB shelf may not be strongly influenced by terrestrial inputs to acidification during drier than normal periods; conversely, shelf waters that are well-buffered against acidification may not play a significant role in mitigating acidification within the Georgia marshes. Supplementary Information: The online version contains supplementary material available at 10.1007/s12237-023-01261-3.

Soil legacy nutrients contribute to the decreasing stoichiometric ratio of N and P loading from the Mississippi River Basin.

Human-induced nitrogen-phosphorus (N, P) imbalance in terrestrial ecosystems can lead to disproportionate N and P loading to aquatic ecosystems, subsequently shifting the elemental ratio in estuaries and coastal oceans and impacting both the structure and functioning of aquatic ecosystems. The N:P ratio of nutrient loading to the Gulf of Mexico from the Mississippi River Basin increased before the late 1980s driven by the enhanced usage of N fertilizer over P fertilizer, whereafter the N:P loading ratio started to decrease although the N:P ratio of fertilizer application did not exhibit a similar trend. Here, we hypothesize that different release rates of soil legacy nutrients might contribute to the decreasing N:P loading ratio. Our study used a data-model integration framework to evaluate N and P dynamics and the potential for long-term accumulation or release of internal soil nutrient legacy stores to alter the ratio of N and P transported down the rivers. We show that the longer residence time of P in terrestrial ecosystems results in a much slower release of P to coastal oceans than N. If contemporary nutrient sources were reduced or suspended, P loading sustained by soil legacy P would decrease much slower than that of N, causing a decrease in the N and P loading ratio. The longer residence time of P in terrestrial ecosystems and the increasingly important role of soil legacy nutrients as a loading source may explain the decreasing N:P loading ratio in the Mississippi River Basin. Our study underscores a promising prospect for N loading control and the urgency to integrate soil P legacy into sustainable nutrient management strategies for aquatic ecosystem health and water security.

Interannual variability of air-water CO2 flux in a large eutrophic estuary.

Air-water CO2 fluxes in estuarine environments are characterized by high interannual variability, in part due to hydrological variability that alters estuarine carbonate chemistry through multiple physical and biogeochemical processes. To understand the relative contributions of these varied controls on interannual air-water CO2 fluxes in the mainstem Chesapeake Bay, we implemented both hindcast and scenario simulations using a coupled physical-biogeochemical model. Significant spatiotemporal variability in bay-wide fluxes was found over a 10-year period (1996-2005), where the mainstem Bay was primarily a net CO2 sink, except in drought periods. Sensitivity scenario results suggested substantial effects of riverine nutrient and organic matter (OM) inputs to CO2 flux variations. The high correlations between riverine inputs and upper-Bay fluxes were due to elevated respiration under increased OM inputs. The interannual flux variations in the lower Bay was mostly regulated by the nutrient inputs. Both nutrient and OM inputs contributed to the flux variability in the mid Bay. It is found that the interannual CO2 flux of the mainstem was most sensitive to riverine nutrient inputs associated with the hydrological changes. For each hindcast simulation we computed the ratio of organic carbon turnover time to water residence time (λ), a proxy for CO2 efflux potential, and found that the wetter periods had a relatively lower λ. The variability of mainstem CO2 fluxes can be well represented using a generic function of λ. The model results showed that higher river flows would lead to enhanced CO2 sinks into a large eutrophic estuary by promoting net autotrophy.

Wastewater inputs reduce the CO2 uptake by coastal oceans.

Every year a large quantity of wastewater is generated worldwide, but its influence on the carbon dioxide (CO2) uptake by coastal oceans is not well understood. Here, sea surface CO2 partial pressure (pCO2) and air-sea CO2 flux were examined in the Jiaozhou Bay (JZB), a temperate coastal bay strongly disturbed by wastewater inputs. Monthly surveys from April 2014 through March 2015 showed that surface pCO2 in the JZB substantially varied both temporally and spatially between 163 µatm and 1222 µatm, with an annual average of 573 µatm. During April-December, surface pCO2 was oversaturated with respect to the atmosphere, with high values exceeding 1000 µatm in the northeastern part of the bay, where seawater salinity was low mainly due to the inputs of wastewater with salinity close to zero. During January-March, surface pCO2 was undersaturated, with the lowest value of <200 µatm also mainly in the northeastern part because of low water temperature and strong biological production. Over an annual cycle, apparently sea surface temperature dominated the monthly variation of surface pCO2 in this shallow bay, while wastewater inputs and related biological production/respiration dominated its spatial variability. Overall, the JZB was a net CO2 source to the atmosphere, emitting 9.6 ± 10.8 mmol C m-2 d-1, unlike its adjacent western part of the Yellow Sea and most of the temperate coastal oceans which are a net CO2 sink. This was possibly associated with wastewater inputs that cause high sea surface pCO2 via direct inputs of CO2 and degradation of organic matter. Thus, from this viewpoint reducing wastewater discharge or lowering CO2 levels in discharged wastewater may be important paths to enhancing the CO2 uptake by coastal oceans in the future.

Reliability and Agreement of an Integrated Platform for Intelligent Visual Function Measurement.

INTRODUCTION: Phoropters are widely accepted for clinical use in refraction examination and visual function assessment. This study assessed the reliability of the new Inspection Platform of Visual Function (IPVF) in comparison with the conventional equipment phoropter (TOPCON VT-10) in visual function assessment. METHODS: This prospective study enrolled 80 eyes of 80 healthy subjects. The horizontal phoria at distance and near (Phoria_D and Phoria_N, respectively) was measured with the von Graefe method, negative/positive relative accommodation (NRA/PRA) was measured with the positive/negative lens method, and accommodative amplitude (AMP) was measured with the minus lens method. Data of three consecutive measurements with each instrument were evaluated using the intraclass correlation coefficient (ICC) for repeatability, and the agreement of the two instruments was evaluated using a Bland-Altman plot. RESULTS: The ICCs of the three consecutive measurements for phoria, NRA/PRA, and AMP using the IPVF instrument were high (0.87-0.96), indicating high repeatability. The ICCs of the three consecutive measurements using the phoropter were high (0.914-0.983) for phoria, NRA, and AMP, indicating high repeatability, while that of PRA was 0.732 (between 0.4 and 0.75), indicating acceptable repeatability. The 95% limits of agreement of phoria, NRA/PRA, and AMP were narrow, indicating good agreement between the two instruments. CONCLUSION: The repeatability of both instruments was high, and the IPVF instrument was slightly better in terms of PRA repeatability than the phoropter. The agreement of phoria, NRA/PRA, and AMP measured by the new IPVF instrument and phoropter was also satisfactory.

Nonstrabismic binocular dysfunctions (NBD) are common vision abnormalities. The relevant indicators involved in NBD are accommodative anomalies, convergence and divergence anomalies, and phoria. Convergence and divergence anomalies are disorders of binocular vision that result in either a failure of fusion or an inability to accurately integrate and stabilize retinal images from both eyes into a single representation. Phoria is the tendency of the eyes not to be directed towards the point of fixation, manifested in the absence or prevention of fusion. Measurement of accommodation and phoria are two particularly important components of comprehensive eye examination. Phoropter is widely used in ophthalmic clinics and optical stores for refraction examination and visual function assessment. It largely depends on the examiner's training, skill, and experience, which leads to high inter-examiner variability. In large-scale eye screening or busy hospital hours, examinees have to be inspected one by one using traditional instruments, which can be time consuming and tiring for optometrists, and can cause long queuing time for examinees. In this study, we evaluated the possibility of an alternative automatic diagnostic instrument for the assessment of binocular visual function. The platform is a new type of intelligent visual function inspection equipment with good reliability, and could be an alternative for clinicians to obtain visual function measurements with improved efficiency and fewer subjective errors. The use of this automatic instrument can avoid inter-examiner variability, helping to resolve the shortage problem of optometrists in China and offer a better testing service to eye examinees.

Climate change drives rapid decadal acidification in the Arctic Ocean from 1994 to 2020.

The Arctic Ocean has experienced rapid warming and sea ice loss in recent decades, becoming the first open-ocean basin to experience widespread aragonite undersaturation [saturation state of aragonite (Ωarag) < 1]. However, its trend toward long-term ocean acidification and the underlying mechanisms remain undocumented. Here, we report rapid acidification there, with rates three to four times higher than in other ocean basins, and attribute it to changing sea ice coverage on a decadal time scale. Sea ice melt exposes seawater to the atmosphere and promotes rapid uptake of atmospheric carbon dioxide, lowering its alkalinity and buffer capacity and thus leading to sharp declines in pH and Ωarag. We predict a further decrease in pH, particularly at higher latitudes where sea ice retreat is active, whereas Arctic warming may counteract decreases in Ωarag in the future.

Performance evaluations and applications of a δ13C-DIC analyzer in seawater and estuarine waters.

Dissolved inorganic carbon (DIC) and its stable isotope (δ13C-DIC) are important parameters for studying carbon cycling in aquatic environments. Traditional methods based on isotope-ratio mass spectrometers are labor-intensive and not easily deployable at field sites. Here we report the performance of a method that simultaneously measures DIC concentration and its stable isotope by using a CO2 extraction device and a Cavity Ring-Down Spectroscopy (CRDS) detector. A multi-port valve is used to increase sample throughput and improve precision. The instrument achieves average precisions of better than ±1.95 µmol kg-1 and ±0.06‰, respectively, for DIC and δ13C-DIC in seawater based on three injections for each sample. We also provide recommendations on how to precisely determine δ13C-DIC samples with a wide range of DIC content in different types of waters by examining injection volume and concentration effects. This technique was applied to study carbon cycling in the Delaware Estuary. It demonstrates that a simultaneous and precise determination of both DIC and δ13C-DIC is a powerful and effective approach for constraining the processes controlling aquatic carbon cycling and CO2 fluxes. Both laboratory tests and field applications confirmed that this system can be used with high precision to study carbon cycling in various aquatic environments.

High anti-interference ability induced by the SP/SiOx/ImIL composite film on IrOx pH electrodes.

High concentrations of redox substances in the solution may cause severe electrode potential drift, resulting in the inaccuracy of in situ measurements. Sulfide anion, a highly reductive substance, is the killer of all metal oxide electrodes because of its small size and strong surface activity. We first proposed to use SPEEK (SP) with silica-stabilized imidazole-type ionic liquid (ImIL) to fabricate a composite film (SP/SiOx/ImIL) to achieve a high anti-interference ability for metal electrodes. The composite film was especially designed to address the interference caused by sulfide anions and other small-sized anions (i.e., I-, F- and ascorbic acid). The reduced proton conductivity was restored by introducing ImIL into SPEEK matrix. Open circuit potential tests showed that the potential of the SP/SiOx/ImIL modified IrOx electrode fluctuated within 0.3 mV in 30 min continuous test at a concentration of 10-3 M Na2S, exhibiting good stability in moderately high sulfide solution. It also exhibited fast response and good reversibility. In addition, no potential drift was measured under other anions interferences. XPS survey verified that the Ir4+/Ir3+ ratio of the IrOx electrode did not change before and after application in sulfide-containing solution, indicating that the SP/SiOx/ImIL composite film has good anion isolation capacity.

Seasonal Water Mass Evolution and Non-Redfield Dynamics Enhance CO2 Uptake in the Chukchi Sea.

The Chukchi Sea is an increasing CO2 sink driven by rapid climate changes. Understanding the seasonal variation of air-sea CO2 exchange and the underlying mechanisms of biogeochemical dynamics is important for predicting impacts of climate change on and feedbacks by the ocean. Here, we present a unique data set of underway sea surface partial pressure of CO2 (pCO2) and discrete samples of biogeochemical properties collected in five consecutive cruises in 2014 and examine the seasonal variations in air-sea CO2 flux and net community production (NCP). We found that thermal and non-thermal effects have different impacts on sea surface pCO2 and thus the air-sea CO2 flux in different water masses. The Bering summer water combined with meltwater has a significantly greater atmospheric CO2 uptake potential than that of the Alaskan Coastal Water in the southern Chukchi Sea in summer, due to stronger biological CO2 removal and a weaker thermal effect. By analyzing the seasonal drawdown of dissolved inorganic carbon (DIC) and nutrients, we found that DIC-based NCP was higher than nitrate-based NCP by 66%-84% and attributable to partially decoupled C and N uptake because of a variable phytoplankton stoichiometry. A box model with a non-Redfield C:N uptake ratio can adequately reproduce observed pCO2 and DIC, which reveals that, during the intensive growing season (late spring to early summer), 30%-46% CO2 uptake in the Chukchi Sea was supported by a flexible stoichiometry of phytoplankton. These findings have important ramification for forecasting the responses of CO2 uptake of the Chukchi ecosystem to climate change.

Responses of the marine carbonate system to a green tide: A case study of an Ulva prolifera bloom in Qingdao coastal waters.

As an environmental nuisance, Ulva prolifera green tides have occurred annually in the southern Yellow Sea since 2007. While it is expected that high levels of biological activity during these blooms can alter seawater carbonate chemistry, there has been little research on the responses of marine carbonate system to green tides. Here, the effects of the bloom on the carbonate system were examined on three cruises in June, July, and September, corresponding to the early-, late-, and after-bloom periods of the U. prolifera bloom in Qingdao coastal waters in 2018. Among these three stages, the pH (National Bureau of Standards scale), dissolved inorganic carbon (DIC), total alkalinity (TA), and partial pressure of CO2 (pCO2) were all affected by bloom, with the highest pH and lowest DIC and TA concentrations of the surface seawater occurring at the late-bloom stage. While pCO2 continuously increased from the beginning to the end of the bloom. TA increased by ∼40 µmol kg-1 between the early- and after-bloom periods likely due to the shifts in the carbonate system equilibrium caused by increased CO32- concentrations and the organic matter released by U. prolifera during decomposition. Compared to nearby areas with no U. prolifera bloom, the green tide, along with increasing temperature, reduced the pH and DIC but increased the TA and pCO2. This large-scale bloom also turned the coastal waters from being an atmospheric CO2 sink to a strong source, with the estimation of air-sea CO2 fluxes about 1.69 ± 1.70, 2.28 ± 1.16, and 7.44 ± 5.84 mmol m-2 d-1 during the early-, late-, and after-bloom periods, respectively. This bloom event also promoted the formation of CaCO3 and was an important source of low molecular weight organic acids. These new findings provide nuances for the current conversations on the role of biological processes in modulating marine carbonate system and the contribution of organic matter to alkalinity.

MAPK inhibitors protect against early­stage osteoarthritis by activating autophagy.

Osteoarthritis (OA) is a chronic, age­related osteoarthropathy that causes a considerable decline in quality of life, as well as economic losses due to its high incidence and poor prognosis. Mitogen­activated protein kinases (MAPKs) regulate multiple cellular processes, including proliferation, differentiation and apoptosis, in certain diseases, such as cancer, diabetes and Alzheimer's disease. The present study aimed to investigate the regulatory role of the MAPK signaling pathway in early­stage OA. A rabbit model of early­stage OA was induced by treatment with the enzyme papain. U0126 [an extracellular signal­regulated kinase (ERK) inhibitor], SP600125 [a Jun NH2­terminal kinase (JNK) inhibitor] and SB203580 (a p38 inhibitor) were administered to the rabbits via intra­articular injection. The severity of OA was assessed by histological examination using H&E, toluidine blue and safranin­O/fast green staining, as well by analyzing the glycosaminoglycan (GAG) content and determining the OA Research Society International (OARSI) score. Western blotting was used to detect the protein expression levels of matrix metalloproteinase­3 (MMP3), ERK, phosphorylated (p)­ERK, p38, p­p38, JNK, p­JNK, Beclin1, UNC­51­like kinase 1 (ULK1) and microtubule­associated protein 1 light chain 3 (LC3)II/I. U0126, SP600125 or SB203580 treatment significantly decreased the OARSI scores and significantly increased the GAG levels in the cartilaginous tissues of OA model rabbits. These results indicated that the MAPK inhibitors reduced the severity of OA­induced injury at the early stage. Western blotting results demonstrated that MAPK inhibition significantly decreased the protein expression levels of MMP3 in OA cartilage. The protective effect of MAPK inhibitors in OA was mediated via the activation of autophagy, as demonstrated by the increased protein expression levels of LC3II/I, ULK1 and Beclin1. Overall, the data indicated that MAPK inhibitors may exert a protective effect against OA by restoring compromised autophagy. Furthermore, the present study suggested that MAPK inhibitors may represent a potential pharmacological strategy for treating OA in the future.

Correcting a major error in assessing organic carbon pollution in natural waters.

Microbial degradation of dissolved organic carbon (DOC) in aquatic environments can cause oxygen depletion, water acidification, and CO2 emissions. These problems are caused by labile DOC (LDOC) and not refractory DOC (RDOC) that resists degradation and is thus a carbon sink. For nearly a century, chemical oxygen demand (COD) has been widely used for assessment of organic pollution in aquatic systems. Here, we show through a multicountry survey and experimental studies that COD is not an appropriate proxy of microbial degradability of organic matter because it oxidizes both LDOC and RDOC, and the latter contributes up to 90% of DOC in high-latitude forested areas. Hence, COD measurements do not provide appropriate scientific information on organic pollution in natural waters and can mislead environmental policies. We propose the replacement of the COD method with an optode-based biological oxygen demand method to accurately and efficiently assess organic pollution in natural aquatic environments.

Carbonate chemistry variability in the southern Yellow Sea and East China Sea during spring of 2017 and summer of 2018.

Marginal seas are highly productive and disproportionately large contributors to global air-sea CO2 fluxes. Due to complex physical and biogeochemical conditions, the southern Yellow-East China Sea is an ideal site for studying carbonate chemistry variability. The carbonate system was investigated in the area in spring of 2017 and summer of 2018. Dissolved inorganic carbon (DIC) and total alkalinity (TA) concentrations were higher in the SYS than the ECS due to material from carbonate weathering and erosion carried by the Yellow River. High pH and low DIC and TA were observed in the Zhe-Min Coastal Current in spring due to high primary productivity caused by Changjiang River input and the Taiwan Warm Current. Temperature and biological activity were the primary drivers controlling the partial pressure of CO2 (pCO2) in the SYS, pCO2 was controlled by primary productivity related to nutrients carried by the Changjiang River and physical mixing in the Changjiang River plume and inner/middle shelves of the ECS, whereas temperature was the dominant factor determining pCO2 distributions in the ECS outer shelf waters influenced by the Kuroshio Current. Overall, the entire study area shifted from a CO2 sink (-4.18 ± 5.60 mmol m-2 d-1) to a weak source (1.02 ± 4.87 mmol m-2 d-1) from spring to summer. Specifically, the SYS and ECS offshore waters changed from CO2 sinks in spring to sources in summer, while the Changjiang River plume was always a CO2 sink.

Natural and Anthropogenic Drivers of Acidification in Large Estuaries.

Oceanic uptake of anthropogenic carbon dioxide (CO2) from the atmosphere has changed ocean biogeochemistry and threatened the health of organisms through a process known as ocean acidification (OA). Such large-scale changes affect ecosystem functions and can have impacts on societal uses, fisheries resources, and economies. In many large estuaries, anthropogenic CO2-induced acidification is enhanced by strong stratification, long water residence times, eutrophication, and a weak acid-base buffer capacity. In this article, we review how a variety of processes influence aquatic acid-base properties in estuarine waters, including coastal upwelling, river-ocean mixing, air-water gas exchange, biological production and subsequent aerobic and anaerobic respiration, calcium carbonate (CaCO3) dissolution, and benthic inputs. We emphasize the spatial and temporal dynamics of partial pressure of CO2 (pCO2), pH, and calcium carbonate mineral saturation states. Examples from three large estuaries-Chesapeake Bay, the Salish Sea, and Prince William Sound-are used to illustrate how natural and anthropogenic processes and climate change may manifest differently across estuaries, as well as the biological implications of OA on coastal calcifiers.