Effects of L-Type Voltage-Gated Calcium Channel (LTCC) Inhibition on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure.

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca2+) and other metal ions, such as zinc (Zn2+) and magnesium (Mg2+), into the cytosol. This Ca2+ influx at the presynaptic terminal triggers the release of Zn2+ and glutamate to the postsynaptic terminal. Zn2+ is then transported to the postsynaptic neuron via LTCCs. The resulting Zn2+ accumulation in neurons significantly increases the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, contributing to reactive oxygen species (ROS) generation and neuronal death. Amlodipine (AML), typically used for hypertension and coronary artery disease, works by inhibiting LTCCs. We explored whether AML could mitigate Zn2+ translocation and accumulation in neurons, potentially offering protection against seizure-induced hippocampal neuronal death. We tested this by establishing a rat epilepsy model with pilocarpine and administering AML (10 mg/kg, orally, daily for 7 days) post-epilepsy onset. We assessed cognitive function through behavioral tests and conducted histological analyses for Zn2+ accumulation, oxidative stress, and neuronal death. Our findings show that AML's LTCC inhibition decreased excessive Zn2+ accumulation, reactive oxygen species (ROS) production, and hippocampal neuronal death following seizures. These results suggest amlodipine's potential as a therapeutic agent in seizure management and mitigating seizures' detrimental effects.

Global transcontinental power pools for low-carbon electricity.

The transition to low-carbon electricity is crucial for meeting global climate goals. However, given the uneven spatial distribution and temporal variability of renewable resources, balancing the supply and demand of electricity will be challenging when relying on close to 100% shares of renewable energy. Here, we use an electricity planning model with hourly supply-demand projections and high-resolution renewable resource maps, to examine whether transcontinental power pools reliably meet the growing global demand for renewable electricity and reduce the system cost. If all suitable sites for renewable energy are available for development, transcontinental trade in electricity reduces the annual system cost of electricity in 2050 by 5-52% across six transcontinental power pools compared to no electricity trade. Under land constraints, if only the global top 10% of suitable renewable energy sites are available, then without international trade, renewables are unable to meet 12% of global demand in 2050. Introducing transcontinental power pools with the same land constraints, however, enables renewables to meet 100% of future electricity demand, while also reducing costs by up to 23% across power pools. Our results highlight the benefits of expanding regional transmission networks in highly decarbonized but land-constrained future electricity systems.

Degradation and lifetime prediction of plastics in subsea and offshore infrastructures.

Engineering and civil developments have relied on synthetic polymers and plastics (including polyethylene, polypropylene, polyamide, etc.) for decades, especially where their durability protects engineering structures against corrosion and other environmental stimuli. Offshore oil and gas infrastructure and renewable energy platforms are typical examples, where these plastics (100,000 s of metric tonnes worldwide) are used primarily as functional material to protect metallic flowlines and subsea equipment against seawater corrosion. Despite this, the current literature on polymers is limited to sea-surface environments, and a model for subsea degradation of plastics is needed. In this review, we collate relevant studies on the degradation of plastics and synthetic polymers in marine environments to gain insight into the fate of these materials when left in subsea conditions. We present a new mathematical model that accounts for various physicochemical changes in the oceanic environment as a function of depth to predict the lifespan of synthetic plastics and the possible formation of plastic debris, e.g., microplastics. We found that the degradation rate of the plastics decreases significantly as a function of water depth and can be estimated quantitatively by the mathematical model that accounts for the effect (and sensitivity) of geographical location, temperature, light intensity, hydrostatic pressure, and marine sediments. For instance, it takes a subsea polyethylene coating about 800 years to degrade on ocean floor (as opposed to <400 years in shallow coastal waters), generating 1000s of particles per g of degradation under certain conditions. Our results demonstrate how suspended sediments in the water column are likely to compensate for the decreasing depth-corrected degradation rates, resulting in surface abrasion and the formation of plastic debris such as microplastics. This review, and the complementing data, will be significant for the environmental impact assessment of plastics in subsea infrastructures. Moreover, as these infrastructures reach the end of their service life, the management of the plastic components becomes of great interest to environmental regulators, industry, and the community, considering the known sizeable impacts of plastics on global biogeochemical cycles.

Effects of Pyruvate Kinase M2 (PKM2) Gene Deletion on Astrocyte-Specific Glycolysis and Global Cerebral Ischemia-Induced Neuronal Death.

Ischemic stroke is caused by insufficient blood flow to the brain. Astrocytes have a role in bidirectionally converting pyruvate, generated via glycolysis, into lactate and then supplying it to neurons through astrocyte-neuron lactate shuttle (ANLS). Pyruvate kinase M2 (PKM2) is an enzyme that dephosphorylates phosphoenolpyruvate to pyruvate during glycolysis in astrocytes. We hypothesized that a reduction in lactate supply in astrocyte PKM2 gene deletion exacerbates neuronal death. Mice harboring a PKM2 gene deletion were established by administering tamoxifen to Aldh1l1-CreERT2; PKM2f/f mice. Upon development of global cerebral ischemia, mice were immediately injected with sodium l-lactate (250 mg/kg, i.p.). To verify our hypothesis, we compared oxidative damage, microtubule disruption, ANLS disruption, and neuronal death between the gene deletion and control subjects. We observed that PKM2 gene deletion increases the degree of neuronal damage and impairment of lactate metabolism in the hippocampal region after GCI. The lactate administration groups showed significantly reduced neuronal death and increases in neuron survival and cognitive function. We found that lactate supply via the ANLS in astrocytes plays a crucial role in maintaining energy metabolism in neurons. Lactate administration may have potential as a therapeutic tool to prevent neuronal damage following ischemic stroke.

Environmental trade-offs of direct air capture technologies in climate change mitigation toward 2100.

Direct air capture (DAC) is critical for achieving stringent climate targets, yet the environmental implications of its large-scale deployment have not been evaluated in this context. Performing a prospective life cycle assessment for two promising technologies in a series of climate change mitigation scenarios, we find that electricity sector decarbonization and DAC technology improvements are both indispensable to avoid environmental problem-shifting. Decarbonizing the electricity sector improves the sequestration efficiency, but also increases the terrestrial ecotoxicity and metal depletion levels per tonne of CO2 sequestered via DAC. These increases can be reduced by improvements in DAC material and energy use efficiencies. DAC exhibits regional environmental impact variations, highlighting the importance of smart siting related to energy system planning and integration. DAC deployment aids the achievement of long-term climate targets, its environmental and climate performance however depend on sectoral mitigation actions, and thus should not suggest a relaxation of sectoral decarbonization targets.

Quantity and fate of synthetic microfiber emissions from apparel washing in California and strategies for their reduction.

Synthetic microfibers have been identified as the most prevalent type of microplastic in samples from aquatic, atmospheric, and terrestrial environments across the globe. Apparel washing has shown to be a major source of microfiber pollution. We used California as a case study to estimate the magnitude and fate of microfiber emissions, and to evaluate potential mitigation approaches. First, we quantified synthetic microfiber emissions and fate from apparel washing in California by developing a material flow model which connects California-specific data on synthetic fiber consumption, apparel washing, microfiber generation, and wastewater and biosolid management practices. Next, we used the model to assess the effectiveness of different interventions to reduce microfiber emissions to natural environments. We estimate that in 2019 as much as 2.2 kilotons (kt) of synthetic microfibers were generated by apparel washing in California, a 26% increase since 2008. The majority entered terrestrial environments (1.6 kt), followed by landfills (0.4 kt), waterbodies (0.1 kt), and incineration (0.1 kt). California's wastewater treatment network was estimated to divert 95% of microfibers from waterbodies, mainly to terrestrial environments and primarily via land application of biosolids. Our analysis also reveals that application of biosolids on agricultural lands facilitates a directional flow of microfibers from higher-income urban counties to lower-income rural communities. Without interventions, annual synthetic microfiber emissions to California's natural environments are expected to increase by 17% to 2.1 kt by 2026. Further increasing the microfiber retention efficiency at the wastewater treatment plant would increase emissions to terrestrial environments, which suggests that microfibers should be removed before entering the wastewater system. In our model, full adoption of in-line filters in washing machines decreased annual synthetic microfiber emissions to natural environments by 79% to 0.5 kt and offered the largest reduction of all modeled scenarios.

Accelerating the pace of ecotoxicological assessment using artificial intelligence.

Species Sensitivity Distribution (SSD) is a key metric for understanding the potential ecotoxicological impacts of chemicals. However, SSDs have been developed to estimate for only handful of chemicals due to the scarcity of experimental toxicity data. Here we present a novel approach to expand the chemical coverage of SSDs using Artificial Neural Network (ANN). We collected over 2000 experimental toxicity data in Lethal Concentration 50 (LC50) for 8 aquatic species and trained an ANN model for each of the 8 aquatic species based on molecular structure. The R2 values of resulting ANN models range from 0.54 to 0.75 (median R2 = 0.69). We applied the predicted LC50 values to fit SSD curves using bootstrapping method, generating SSDs for 8424 chemicals in the ToX21 database. The dataset is expected to serve as a screening-level reference SSD database for understanding potential ecotoxicological impacts of chemicals.

Lifecycle cost and carbon implications of residential solar-plus-storage in California.

Capacities of residential photovoltaics (PV) and battery storage are rapidly growing, while their lifecycle cost and carbon implications are not well understood. Here, we integrate PV generation and load data for households in California to assess the current and future lifecycle cost and carbon emissions of solar-plus-storage systems. Our results show that installing PV reduces $180-$730 and 110-570 kgCO2 per year per household in 2020. However, compared to solar-only system, adding battery storage increases lifecycle costs by 39%-67%, while impact on emissions is mixed (-20% to 24%) depending on tariff structure and marginal emission factors. In 2040, under current decarbonization and cost trajectories, solar-plus-storage leads to up to 31% higher lifecycle costs and up to 32% higher emissions than solar-only systems. Designing a tariff structure with wider rate spreads aligned with marginal carbon emissions, and reducing the costs and embodied emissions of batteries are crucial for broader adoption of low-carbon residential solar-plus-storage.

Economic disparity among generations under the Paris Agreement.

The costs and benefits of climate change mitigation are known to be distributed unevenly across time and space, while their intergenerational distribution across nations has not been evaluated. Here, we analyze the lifetime costs and benefits of climate change mitigation by age cohorts across countries under the Paris Agreement. Our results show that the age cohorts born prior to 1960 generally experience a net reduction in lifetime gross domestic product per capita. Age cohorts born after 1990 will gain net benefits from climate change mitigation in most lower income countries. However, no age cohorts enjoy net benefits regardless of the birth year in many higher income countries. Furthermore, the cost-benefit disparity among old and young age cohorts is expected to widen over time. Particularly, lower income countries are expected to have much larger cost-benefit disparity between the young and the old. Our findings highlight the challenges in building consensus for equitable climate policy among nations and generations.

Achieving net-zero greenhouse gas emission plastics by a circular carbon economy.

Mitigating life-cycle greenhouse gas emissions of plastics is perceived as energy intensive and costly. We developed a bottom-up model that represents the life cycle of 90% of global plastics to examine pathways to net-zero emission plastics. Our results show that net-zero emission plastics can be achieved by combining biomass and carbon dioxide (CO2) utilization with an effective recycling rate of 70% while saving 34 to 53% of energy. Operational costs for net-zero emission plastics are in the same range as those for linear fossil-based production with carbon capture and storage and could even be substantially reduced. Realizing the full cost-saving potential of 288 billion US dollars requires low-cost supply of biomass and CO2, high-cost supply of oil, and incentivizing large-scale recycling and lowering investment barriers for all technologies that use renewable carbon feedstock.

Synthetic microfiber emissions to land rival those to waterbodies and are growing.

Synthetic microfibers are found virtually everywhere in the environment, but emission pathways and quantities are poorly understood. By connecting regionalized global datasets on apparel production, use, and washing with emission and retention rates during washing, wastewater treatment, and sludge management, we estimate that 5.6 Mt of synthetic microfibers were emitted from apparel washing between 1950 and 2016. Half of this amount was emitted during the last decade, with a compound annual growth rate of 12.9%. Waterbodies received 2.9 Mt, while combined emissions to terrestrial environments (1.9 Mt) and landfill (0.6 Mt) were almost as large and are growing. Annual emissions to terrestrial environments (141.9 kt yr-1) and landfill (34.6 kt yr-1) combined are now exceeding those to waterbodies (167.2 kt yr-1). Improving access to wastewater treatment is expected to further shift synthetic microfiber emissions from waterbodies to terrestrial environments. Preventing emissions at the source would therefore be a more effective mitigation measure.

Climate change mitigation potential of carbon capture and utilization in the chemical industry.

Chemical production is set to become the single largest driver of global oil consumption by 2030. To reduce oil consumption and resulting greenhouse gas (GHG) emissions, carbon dioxide can be captured from stacks or air and utilized as alternative carbon source for chemicals. Here, we show that carbon capture and utilization (CCU) has the technical potential to decouple chemical production from fossil resources, reducing annual GHG emissions by up to 3.5 Gt CO2-eq in 2030. Exploiting this potential, however, requires more than 18.1 PWh of low-carbon electricity, corresponding to 55% of the projected global electricity production in 2030. Most large-scale CCU technologies are found to be less efficient in reducing GHG emissions per unit low-carbon electricity when benchmarked to power-to-X efficiencies reported for other large-scale applications including electro-mobility (e-mobility) and heat pumps. Once and where these other demands are satisfied, CCU in the chemical industry could efficiently contribute to climate change mitigation.

Uncertainty Implications of Hybrid Approach in LCA: Precision versus Accuracy.

The hybrid approach in Life Cycle Assessment (LCA) that uses both input-output and process data has been discussed in the context of mitigating truncation error and burdens of data collection. However, the implication of introducing input-output data on the overall uncertainty of an LCA result has been debated. In this study, we selected an existing process LCA, performed a Monte Carlo simulation after hybridizing each truncated flow at a time, and analyzed the dispersion and position of the distribution in the results. The results showed that hybridization effectively moved the mean of the life cycle greenhouse gas (GHG) emissions 38% higher while maintaining the standard deviation within the 0.62-0.78 range (relative standard deviation, 3-4%). We identified key activities contributing to the overall uncertainty and simulated the potential effect of collecting higher quality supplier-specific data for those activities on the overall uncertainty. The results showed that replacing as few as 10 of the largest uncertainty contributors with high precision supplier-specific data substantially narrowed the distribution. Our results suggest that hybridizing truncated inputs improves accuracy of LCA results without compromising their precision, and prioritizing supplier-specific data collection can further enhance precision in a cost-effective manner.

Health risks of chemicals in consumer products: A review.

Increasingly diverse chemicals are used in consumer products, while our understanding of their exposure pathways and associated human health risks still lags behind. This paper aims to identify the dominant patterns of exposure pathways and associated health risks of chemicals used in consumer products reported in the peer-reviewed literature. We analyzed 342 articles covering 202 unique chemicals, and distilled the information on the functional uses, product applications, exposure routes, exposure pathways, toxicity endpoints and their combinations. We found that the volume of the literature addressing human health risks of chemicals in consumer products is increasing. Among others, phthalates, bisphenol-A, and polybrominated diphenyl ethers were the most frequently discussed chemical groups in the literature reviewed. Emerged from our review were a number of frequently reported functional use/product application combinations, including plasticizers, polymers/monomers, and flame retardants used in food contact products, personal care products, cosmetics, furniture, flooring, and electronics. We also observed a strong tendency that the number of publications on a chemical surges following major regulatory changes or exposure incidents associated with the chemical. We highlight the need to develop the capacity and the mechanism through which human health risks of chemicals in consumer products can be identified prior to their releases.

Insulin induces phosphorylation of pyruvate dehydrogenase through RhoA activation pathway in HepG2 cells.

Insulin is a critical signaling molecule in reducing blood glucose levels, and pyruvate dehydrogenase (PDH) is an essential enzyme in regulating glucose metabolism. However, the insulin effect on PDH function has not been well established. We observed that insulin attenuated the phosphorylation (p) of Ser264 (p-Ser264) in the PDH E1α subunit (PDHA1) in normal rat hepatocyte. In contrast, insulin induced an increase of p-Ser264 PDHA1 levels in hepatocellular carcinoma HepG2 and Huh7 cells. Insulin activated RhoA and Rho-dependent coiled coil kinase, an effector protein of active RhoA, which regulated p-Ser264 PDHA1 levels, along with both p-Ser9 and p-Tyr216 forms of glycogen synthase kinase-3ß (GSK-3ß) in HepG2 cells. Only p-Tyr216 GSK-3ß, the active form was involved in an increase of p-Ser264 PDHA1. Akt was also engaged in p-Ser9 of GSK-3ß, but neither in p-Tyr216 of GSK-3ß nor p-Ser264 of PDHA1 upon insulin. Reconstituted dephospho-mimic forms PDHA1 S264A and GSK-3ß Y216F impaired, but wild-types PDHA1 and GSK-3ß and phospho-mimic forms PDHA1 S264D and GSK-3ß Y216E increased cell proliferation upon insulin through expression of c-Myc and cyclin D1. Therefore, we propose that insulin-mediated p-PDHA1 is involved in the regulation of HepG2 cell proliferation through RhoA signaling pathway.-Islam, R., Kim, J.-G., Park, Y., Cho, J.-Y., Cap, K.-C., Kho, A.-R., Chung, W.-S., Suh, S.-W., Park, J.-B. Insulin induces phosphorylation of pyruvate dehydrogenase through RhoA activation pathway in HepG2 cells.

Does the use of pre-calculated uncertainty values change the conclusions of comparative life cycle assessments? - An empirical analysis.

In life cycle assessment (LCA), performing Monte Carlo simulation (MCS) using fully dependent sampling typically involves repeated inversion of a technology matrix for a sufficiently large number of times. As the dimension of technology matrices for life cycle inventory (LCI) databases grows, MCS using fully dependent sampling is becoming a computational challenge. In our previous work, we pre-calculated the distribution functions of the entire LCI flows in the ecoinvent ver. 3.1 database to help reduce the computation time of running fully dependent sampling by individual LCA practitioners. However, it remains as a question whether the additional errors due to the use of pre-calculated uncertainty values are large enough to alter the conclusion of a comparative study, and, if so, what is the odds of such cases. In this study, we empirically tested the probability of altering the conclusion of a comparative LCA due to the use of pre-calculated uncertainty values. We sampled 10,000 random pairs of elementary flows of ecoinvent LCIs (ai and bi) and ran MCSs (1) using pre-calculated uncertainty values and (2) using fully dependent sampling. We analyzed the distribution of the differences between ai and bi (i.e., ai-bi) of each run, and quantified the probability of reversing (e.g., ai > bi became ai < bi) or moderating the conclusion (e.g., ai > bi became ai ≈ bi). In order to better replicate the situation under a comparative LCA setting, we also sampled 10,000 random pairs of elementary flows from the processes that produce electricity, and repeated the same procedure. The results show that no LCIs derived using pre-calculated uncertainty values constitute large enough differences from those using fully dependent sampling to reverse the conclusion. However, in 5.3% of the cases, the conclusion from one approach is moderated under the other approach or vice versa. When elementary flow pairs are sampled only from the electricity-producing processes, the probability of moderating the conclusions increases to 10.5%, while that of reversing the conclusions remains nil. As the number of unit processes in LCI databases increases, running full MCSs in a PC-environment will continue to be a challenge, which may lead some LCA practitioners to avoid uncertainty analysis altogether. Our results indicate that pre-calculated distributions for LCIs can be used as a proxy for comparative LCA studies in the absence of adequate computational resources for full MCS. Depending on the goal and scope of the study, LCA practitioners should consider using pre-calculated distributions if the benefits of doing so outweighs the associated risks of altering the conclusion.

Environmental governance in China: Interactions between the state and "nonstate actors".

In the West, limited government capacity to solve environmental problems has triggered the rise of a variety of "nonstate actors" to supplement government efforts or provide alternative mechanisms for addressing environmental issues. How does this development - along with our efforts to understand it - map onto environmental governance processes in China? China's efforts to address environmental issues reflect institutionalized governance processes that differ from parallel western processes in ways that have major consequences for domestic environmental governance practices and the governance of China "going abroad." China's governance processes blur the distinction between the state and other actors; the "shadow of the state" is a major factor in all efforts to address environmental issues. The space occupied by nonstate actors in western systems is occupied by shiye danwei ("public service units"), she hui tuanti ("social associations") and e-platforms, all of which have close links to the state. Meanwhile, international NGOs and multinational corporations are also significant players in China. As a result, the mechanisms of influence that produce effects in China differ in important ways from mechanisms familiar from the western experience. This conclusion has far-reaching implications for those seeking to address global environmental concerns, given the importance of China's growing economy and burgeoning network of trade relationships.