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Japanese encephalitis (JE) is a major reason to cause viral encephalitis, with 50% patients suffering from severe neuro-inflammation and permanent neural injury. Effective anti-viral treatment is urgently needed. Here, we found RNA binding protein quaking (QKI) was involved in the progression of JE by regulating migration and anti-viral response of macrophages. After JE virus (JEV) infection, QKI-deficient mice had lower viral loads in the brain and fewer neurological symptoms. In comparison with control mice, proinflammatory cytokines in the brain of QKI-deficient animals revealed distinct patterns, with lower levels of IL-6 (interleukin-6) and IFN-β (interferon-β) at the early stage but higher levels at the end of JE. Then we found infiltration of CCR2 positive ((C-C motif) receptor 2) peripheral macrophages and CCR2 expression on macrophages were inhibited in QKI-deficient mice, while the expression of CCR2 ligands was not changed. Bioinformatical analysis showed that a QRE (quaking response element) located on 3'UTR (untranslated region) of Ccr2. We further verified that QKI was able to interact with Ccr2 mRNA and regulate its degradation in vitro. Additionally, since the IFN-β production was increased in QKI-ablation mice after JEV infection, the anti-viral response was analyzed. Results in QKI-silenced N9 cells showed that the expression of RIG-I (retinoic acid-inducible gene-I) and TBK1 (TANK binding kinase 1) was increased, thus further inducing IRF3 (interferon regulatory factor 3) phosphorylation and interferon activation. Overall, these results revealed QKI mediated the anti-viral process via interfering migration of macrophages to CNS (central nervous system) and enhancing RIG-I/IRF3/IFN-β pathway to restrict virus dissemination.

Jinjie Yu,1,2,* Mengwen Liu,3,* Xiaokaiti Mijiti,4,* Haican Liu,2,* Quan Wang,4 Chunjie Yin,3 Aiketaguli Anwaierjiang,5 Miao Xu,4 Machao Li,2 Lele Deng,2,6 Hui Xiao,3 Xiuqin Zhao,2 Kanglin Wan,2 Guilian Li,2 Xiuqin Yuan1 1School of Public Health, University of South China, Hengyang, 421001, People’s Republic of China; 2State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 3School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 4The Eighth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830049, People’s Republic of China; 5College of Xinjiang Uyghur Medicine, Hetian, 848000, People’s Republic of China; 6National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence:Xiuqin Yuan, School of Public Health, University of South China, Hengyang, 421001, People’s Republic of China, Email wtjysh@126.com;Guilian Li, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China, Email liguilian@icdc.cnBackground: The aim of the present study was to investigate the association between vitamin D receptor (VDR) gene polymorphism and tuberculosis susceptibility, as well as the potential interaction of host genetic factors with the heterogeneity of Mycobacterium tuberculosis in the population from Xinjiang, China.Methods: From January 2019 to January 2020, we enrolled 221 tuberculosis patients as the case group and 363 staff with no clinical symptoms as the control group from four designated tuberculosis hospitals in southern Xinjiang, China. The polymorphisms of Fok I, Taq I, Apa I, Bsm I, rs3847987 and rs739837 in the VDR were detected by sequencing. M. tuberculosis isolates were collected from the case group and identified as Beijing or non-Beijing lineage by multiplex PCR. Propensity score (PS), univariate analysis and multivariable logistic regression models were used to perform the analysis.Results: Our results showed that the allele and genotype frequencies of Fok I, Taq I, Apa I, Bsm I, rs3847987 and rs739837 in VDR were not correlated with tuberculosis susceptibility or lineages of M. tuberculosis. Two out of six loci of the VDR gene formed one haplotype block, and none of the haplotypes was found to correlate with tuberculosis susceptibility or lineages of M. tuberculosis infected.Conclusion: Polymorphisms in the VDR gene may not indicate susceptibility to tuberculosis. There was also no evidence on the interaction between the VDR gene of host and the lineages of M. tuberculosis in the population from Xinjiang, China. Further studies are nonetheless required to prove our conclusions.Keywords: vitamin D receptor, VDR, polymorphism, tuberculosis, Mycobacterium tuberculosis, Beijing lineage

CRISPR/Cas9 genome-editing technology has revolutionized plant science and holds enormous promise for crop improvement. The exploration of this system received much attention regarding plant genome editing. Here, by editing the NtPDS gene in tobacco, we first verified that incorporating an OsU3-tRNA promoter combination into the CRISPR/Cas9 system contributed to the highest editing efficiency, as the sgRNA expression level was greater than that resulting from the AtU6-tRNA and AtU6 promoters. Then, we optimized the existing tobacco CRISPR/Cas9 system, pORE-Cas9, by using the OsU3-tRNA promoter combination instead of AtU6 and by fusing an AtUb10-Ros1 expression cassette to the T-DNA to monitor the transgene events. The new system was named pOREU3TR. As expected, 49 transgene-free and homozygous gene-edited green plants were effectively screened in the T

2, 3-bisphosphoglycerate-independent phosphoglycerate mutase (iPGAM), is a key enzyme that catalyzes the reversible interconversion of 3-phosphoglycerate and 2-phosphoglycerate in glycolysis. iPGAM has been found to be involved in several physiological processes, including stomatal movement, chlorophyll synthesis, pollen production, chloroplast development and photosynthesis in different plants. However, the roles iPGAM plays in model plant tobacco are still elusive. In the current study, two copies of the iPGAM gene in Nicotiana tabacum were cloned, NtiPGAMa and NtiPGAMb, from the variety “Honghuadajinyuan”. Expression profiles and subcellular localization analyses showed that NtiPGAMa and NtiPGAMb were highly expressed in the anthers and were localized to the nucleus, cytosol and cell membrane. Using the CRISPR/Cas9 system, three mutant lines with mosaic leaves were obtained by targeting the second exon of the iPGAM gene. Based on Sanger sequencing, the mutant lines were chimeric plants and displayed mutation rates ranging from 82.3% to 92.5%. The iPGAM mutations showed significantly decreased photosynthetic pigments, i.e., chlorophyll a, chlorophyll b and carotenoids, thinning or loss of chloroplast thylakoid lamellar structures. RT-PCR analysis showed that the expressions of genes associated with chlorophyll synthesis and photosynthesis were significantly down-regulated in the iPGAM mutant plants compared to wild type. The pollen development was greatly impaired in mutant plants, resulting in reduced and deformed pollens with grains inviable. Our findings indicate that iPGAM is critical for pollen vitality, chlorophyll synthesis and chloroplast morphogenesis in N. tabacum.

Background: Respiratory infectious diseases (RIDs) pose threatens to people’s health, some of them are serious public health problems. The aim of our study was to explore epidemic situations of all notifiable RIDs and the epidemiological characteristics of six most common RIDs in mainland China.Methods: We first collected the surveillance data of all 12 statutory notifiable RIDs for 31 provinces in mainland China that reported between January 1, 2010 and December 31, 2019, and then six most prevalent RIDs were chosen to analyze their spatial, temporal, seasonal and population distribution characteristics. Descriptive analysis was used to present the spatial and population distribution characteristics. Joinpoint regression model was used to explore the temporal trends and seasonal decomposition was used to explore seasonal characteristics.Results: From 2010 to 2019, there were 18 746 367 notifiable cases and 28 816 death cases of RIDs in mainland China. The incidence rate of RIDs increased from 109.85/100 000 in 2010 to 340.94/100 000 in 2019. The mortality of RIDs decreased from 0.24/100 000 in 2010 to 0.23/100 000 in 2019. The six most common RIDs were pulmonary tuberculosis (PTB), seasonal influenza, mumps, pertussis, measles and rubella. From 2010 to 2018, the incidence rates showed decreases in PTB and rubella, increases in pertussis and seasonal influenza, and irregular changes in measles and mumps. The mortality showed an increase in PTB from 2015 to 2018 and irregular change in seasonal influenza. PTB was mainly prevalent among people aged 15 years old and over, while the other five common RIDs mostly occurred among people younger than 15 years old. The incidence of the six common RIDs mostly occurred in winter and spring. The incidence rate of PTB was higher in the northwestern and southwestern China. The incidence rates of pertussis, measles and rubella were relatively lower in whole country.Conclusions: PTB, seasonal influenza and mumps remain the public health problems in China, suggesting that continuous government input, more precise and effective interventions, and a digital/intelligent surveillance and warning system are required to improve RIDs prevention and control efforts.

Background: CRISPR-Cas9 Genome-editing technology has revolutionized the plant science and hold enormous promise in crop improvement. When performing the gene editing system for crops, it is crucial to eliminate of the Cas9/sgRNA T-DNA cassette in the T1 generation. Results: Here, we firstly validated that incorporating an OsU3-tRNA promoter combination in the CRISPR/Cas9 system contributed to the highest mutagenesis efficiency that increased sgRNA expression levels over the AtU6-tRNA and AtU6 promoters by editing the NtPDS gene (Ntab0595110) in tobacco. Then we optimized the existing tobacco CRISPR/Cas9 system by using the OsU3-tRNA promoter combination instead of AtU6, and fusing an AtUb10-Ros1 expression cassette in T-DNA for monitoring the transgene events. The new vector was named as pOREU3TR. As expected, 52 transgene-free and homozygous gene-edited green plants were effectively screened at T1 generation by editing the NtLHT1 gene (Ntab0818090) in tobacco, and the contents of most free amino acids in the T2 mutants ntlht1 leaves were detected significantly different from those in the wild type leaves, demonstrating the highly efficient of the system.Conclusions: This OsU3-tRNA-sgRNA/AtUb10-Ros1 system provides essential improvements to increase the efficiency of plant genome editing.

Respiratory infectious diseases (RIDs) pose threats to people’s health, some of which are serious public health problems. The aim of our study was to explore epidemic situations regarding notifiable RIDs and the epidemiological characteristics of the six most common RIDs in mainland China. We first collected the surveillance data of all 12 statutory notifiable RIDs for 31 provinces in mainland China that reported between 2010 and 2018, and then the six most prevalent RIDs were selected to analyze their temporal, seasonal, spatiotemporal and population distribution characteristics. From 2010 to 2018, there were 13,985,040 notifiable cases and 25,548 deaths from RIDs in mainland China. The incidence rate of RIDs increased from 109.85/100,000 in 2010 to 140.85/100,000 in 2018. The mortality from RIDs ranged from 0.18/100,000 to 0.24/100,000. The most common RIDs in class B were pulmonary tuberculosis (PTB), pertussis, and measles, while those in class C were seasonal influenza, mumps and rubella. From 2010 to 2018, the incidence rate of PTB and rubella decreased; however, pertussis and seasonal influenza increased, with irregular changes in measles and mumps. The mortality from PTB increased from 2015 to 2018, and the mortality from seasonal influenza changed irregularly. PTB was mainly prevalent among people over 15 years old, while the other five common RIDs mostly occurred among people younger than 15 years old. The incidence of the six common RIDs mostly occurred in winter and spring, and they were spatiotemporally clustered in different areas and periods. In conclusion, PTB, seasonal influenza and mumps remain as public health problems in China, suggesting that continuous government input, more precise interventions, and a high-tech digital/intelligent surveillance and warning system are required to rapidly identify emerging events and timely response.

Background With the progress of globalization, the international mobility of population is increasing, which facilitates the cross-border transmission of respiratory infectious diseases (RIDs). The aim of this study is to analyze the epidemiological characteristics and relative factors of imported RIDs for using high-tech and wisdom methods to early find and stop the important RIDs spread to China. Methods The imported RIDs cases from 2014 to 2018 enrolled in this study were screened by the inbound sentinel network of customs and national notifiable disease reporting system in China. The spatial, temporal and population distribution of imported respiratory infectious diseases were analyzed. Seasonal index was calculated to describe the seasonality, and Pearson correlation coefficients were assessed to examine associations between independent variables and imported cases. Data analysis and visualization were carried out with R (version 4.0.5). Results Among 1,409,265,253 inbound travelers, 31,302 (2.22/100,000) imported RIDs cases from 143 countries within 5 continents were reported. The incidence of imported RIDs in 2018 (2.77/100,000) was nearly 5 times that of 2014 (0.56/100,000). Among foreigners, the incidences were higher in male (5.11/100,000), 0–14 year old group (14.06/100,000), and Oceania (10.98/100,000). Influenza accounted for the majority of imported RIDs(90.64%), with obvious seasonality. The spatial distribution of imported RIDs was different between Chinese citizens and foreigners. With the increase of inbound travel volume and the number of influenza cases in source countries, the number of imported RIDs cases increased. Conclusions Our study showed RIDs imported into China from 143 countries around the world. Therefore, it has great potential risks of transmitting important RIDs to China. So, it is urgent to strengthen the surveillance at customs for inbound population, and establish the wisdom surveillance and warning systems for preventing and stop imported RIDs spreading to China.

Global warming and anthropogenic changes can result in the heterogeneity of water availability in the spatiotemporal scale, which will further affect the allocation of water resources. A lot of researches have been devoted to examining the responses of water availability to global warming while neglected future anthropogenic changes. What’s more, only a few studies have investigated the response of optimal allocation of water resources to the projected climate and anthropogenic changes. In this study, a cascade model chain is developed to evaluate the impacts of projected climate change and human activities on optimal allocation of water resources. Firstly, a large set of global climate models (GCMs) associated with the Daily Bias Correction (DBC) method are employed to project future climate scenarios, while the Cellular Automaton–Markov (CA–Markov) model is used to project future Land Use/Cover Change (LUCC) scenarios. Then the runoff simulation is based on the Soil and Water Assessment Tool (SWAT) hydrological model with necessary inputs under the future conditions. Finally, the optimal water resources allocation model is established based on the evaluation of water supply and water demand. The Han River basin in China was selected as a case study. The results show that: (1) the annual runoff indicates an increasing trend in the future in contrast with the base period, while the ascending rate of the basin under RCP 4.5 is 4.47%; (2) a nonlinear relationship has been identified between the optimal allocation of water resources and water availability, while a linear association exists between the former and water demand; (3) increased water supply are needed in the water donor area, the middle and lower reaches should be supplemented with 4.495 billion m3 water in 2030. This study provides an example of a management template for guiding the allocation of water resources, and improves understandings of the assessments of water availability and demand at a regional or national scale.

Inflammatory bowel disease (IBD) is a refractory chronic inflammatory illness of the gastrointestinal (GI) tract. Macrophage exerts an important role in IBD development. QKI, as an RNA binding protein, was related with inflammatory responses in bacterial infections by regulating the polarization of macrophages. Therefore, we suspected that QKI-regulated macrophages have the potential to play a certain role in IBD and the underlying mechanism. Our results demonstrated that the mice with macrophage-specific deletion of QKI induced with dextran sodium sulfate (DSS) are more susceptible to IBD development, exhibited a severe leaky gut barrier phenotype and higher intense oxidative stress, which are rescued by treating with butylated hydroxyanisole (BHA), an agonist of NRF2. Mechanically, we observed that Keap1 mRNA in the nucleus was exported to the cytoplasm after LPS stimuli in parallel with QKI reductions, and the removal of QKI by shRNA facilitated Keap1 mRNA nuclear exporting and expression in cytoplasm, consequently NRF2 activation in nucleus was weakened, and led to the impaired antioxidant abilities. In addition, mice models of fecal microbiota transplant (FMT) and the co-culturing of mice epithelia cells with feces derived from the DSS-treated QKI-deficit mice revealed consistently aggravated colitis along with a severe oxidative stress; 16S sequencing analysis substantiated the altered compositions of commensal bacteria too. Overall, the current study represents the first effort to explore the anti-oxidant role of QKI in the intestinal macrophage via post-transcriptional regulation of Keap1 mRNA localization and the relevant NRF2 antioxidant signaling, and the disproportional changes in the microbiota were attributable to the mediation of pathogenic damage in the IBD development of QKI-deficit mice.

As one of the most crucial indices of sustainable development and water security, water resources carrying capacity (WRCC) has been a pivotal and hot-button issue in water resources planning and management. Quantifying WRCC can provide useful references on optimizing water resources allocation and guiding sustainable development. In this study, the WRCCs in both current and future periods were systematically quantified using set pair analysis (SPA), which was formulated to represent carrying grade and explore carrying mechanism. The Soil and Water Assessment Tool (SWAT) model, along with water resources development and utilization model, was employed to project future water resources scenarios. The proposed framework was tested on a case study of China&rsquo, s Han River basin. A comprehensive evaluation index system across water resources, social economy, and ecological environment was established to assess the WRCC. During the current period, the WRCC first decreased and then increased, and the water resources subsystem performed best, while the eco-environment subsystem achieved inferior WRCC. The SWAT model projected that the amount of the total water resources will reach about 56.9 billion m3 in 2035s, and the water resources development and utilization model projected a rise of water consumption. The declining WRCC implies that the water resources are unable to support or satisfy the demand of ecological and socioeconomic development in 2035s. The study furnishes abundant and valuable information for guiding water resources planning, and the core idea of this model can be extended for the assessment, prediction, and regulation of other systems.

Joint and optimal impoundment operation of the large-scale reservoir system has become more crucial for modern water management. Since the existing techniques fail to optimize the large-scale multi-objective impoundment operation due to the complex inflow stochasticity and high dimensionality, we develop a novel combination of parameter simulation optimization and classification-aggregation-decomposition approach here to overcome these obstacles. There are four main steps involved in our proposed framework: (1) reservoirs classification based on geographical location and flood prevention targets; (2) assumption of a hypothetical single reservoir in the same pool; (3) the derivation of the initial impoundment policies by the non-dominated sorting genetic algorithm-II (NSGA-II); (4) further improvement of the impoundment policies via Parallel Progressive Optimization Algorithm (PPOA). The framework potential is performed on China's mixed 30-reservoir system in the upper Yangtze River. Results indicate that our method can provide a series of schemes to refer to different flood event scenarios. The best scheme outperforms the conventional operating rule, as it increases impoundment efficiency from 89.50 % to 94.16 % and hydropower generation by 7.70 billion kWh (or increase 3.79 %) while flood control risk is less than 0.06.

The dataset contains reservoir characteristic parameters, streamflow series of reservoirs in the upper Yangtze River, the standard operating rules (SORs) and the seasonal top of buffer pools (seasonal TBPs) for these reservoirs, which were provided by the Yangtze River Commission. Moreover, annual hydropower of these reservoirs is tested to evaluate operation performance. These research materials are related to the research article in Advances in Water Resources, entitled ‘Optimal impoundment operation for cascade reservoirs coupling parallel dynamic programming with importance sampling and successive approximation’ (He et al., 2019). The dataset could be used to derive optimal operating rules to explore the potential benefits of water resources via our proposed algorithm (importance sampling – parallel dynamic programming, IS-PDP) in different runoff scenarios. It can also be further applied for water resources management and other potential users. Keywords: Cascade reservoirs, Impoundment operation, Yangtze river basin, Streamflow observation, Parallel dynamic programming, Importance sampling, Seasonal top of buffer pools

Water environmental capacity (WEC) is an essential indicator for effective environmental management. The designed low water flow condition is a prerequisite to determine WEC and is often based on the stationarity assumption of low water flow series. As the low water flow series has been remarkably disturbed by climate change as well as reservoirs operation and water acquisition, the stationarity assumption might bring risk for WEC planning. As the reservoir operation and water acquisition under climate change can be simulated by a water resources allocation model, the low water flow series outputted from the model are the simulations of the disturbances and often show nonstationary conditions. After estimating the designed low water flow through nonstationary frequency analysis from these low water flow series, the WEC under the nonstationary conditions can be determined. Thus, the impacts of water resources allocation on WEC under climate change can be quantitatively assessed. The mid-lower reaches of the Hanjiang River basin in China were taken as a case study due to the intensive reservoir operation and water acquisition under the climate change. A representative concentration pathway scenario (RCP4.5) was employed to project future climate, and a Soil and Water Assessment Tool (SWAT) model was employed to simulate water availability for driving the Interactive River-Aquifer Simulation (IRAS) model for allocating water. Water demand in 2016 and 2030 were selected as baseline and future planning years, respectively. The results show that water resources allocation can increase the amount of WEC due to amplifying the designed low water flow through reservoir operation. Larger regulating capacities of water projects can result in fewer differences of WEC under varied water availability and water demand conditions. The increasing local water demand will decrease WEC, with less regulating capacity of the water projects. Even the total available water resources will increase over the study area under RCP4.5. More water deficit will be found due to the uneven temporal-spatial distribution as well as the increasing water demand in the future, and low water flow will decrease, which further leads to cut down WEC. Therefore, the proposed method for determining the WEC can quantify the risk of the impacts of water supply and climate change on WEC to help water environmental management.

Hydro-meteorological datasets are key components for understanding physical hydrological processes, but the scarcity of observational data hinders their potential application in poorly gauged regions. Satellite-retrieved and atmospheric reanalysis products exhibit considerable advantages in filling the spatial gaps in in-situ gauging networks and are thus forced to drive the physically lumped hydrological models for long-term streamflow simulation in data-sparse regions. As machine learning (ML)-based techniques can capture the relationship between different elements, they may have potential in further exploring meteorological predictors and hydrological responses. To examine the application prospects of a physically constrained ML algorithm using earth observation data, we used a short-series hydrological observation of the Hanjiang River basin in China as a case study. In this study, the prevalent modèle du Génie Rural à 9 paramètres Journalier (GR4J-9) hydrological model was used to initially simulate streamflow, and then, the simulated series and remote sensing data were used to train the long short-term memory (LSTM) method. The results demonstrated that the advanced GR4J9–LSTM model chain effectively improves the performance of the streamflow simulation by using more remote sensing data related to the hydrological response variables. Additionally, we derived a reservoir operation model by feeding the LSTM-based simulation outputs, which further revealed the potential application of our proposed technique.

Iron (Fe) is an essential micronutrient for humans, and iron deficiency is the most common micronutrient deficiency worldwide. Research on the genetic basis of iron concentration in maize kernels will provide guidance for the development of iron-rich crops, a major breeding goal to address iron deficiency. The maize Yellow Stripe 1 (ZmYS1) gene encodes a specific transporter that takes up Fe(III)-phytosiderophore complexes into roots. Here, we re-sequenced ZmYS1 gene in 88 elite maize inbred lines and detected the association between the nucleotide polymorphisms and micronutrient concentrations in maize kernels. Our analyses detected a total of 71 sequence variants in ZmYS1, including 61 single nucleotide polymorphisms (SNPs) and 10 insertions and deletions (indels), from the tested population. Fourteen haplotypes, which encode 13 different ZmYS1 proteins, are classified based on the polymorphism in the coding region. Numerous polymorphic sites in maize ZmYS1 locus were found in linkage disequilibrium (LD) that decay with increasing physical distance, and at least 14 recombination events have contributed to the LD and haplotype diversity of this gene. Additionally, our data show that a non-synonymous site in the ZmYS1 gene is associated with the maize kernel Fe concentration, and two other non-synonymous sites with Zinc (Zn) concentration. These findings suggest that the polymorphism in maize ZmYS1 locus may be used for biofortifying kernel mineral concentrations in maize breeding programs.

The optimal impoundment operation of cascade reservoirs can dramatically improve the utilization of water resources. However, their complex non-convexity and computational costs pose challenges to optimal hydroelectricity output and limit further development of joint operation within larger-scale cascade reservoirs. In recent decades, parallel dynamic programming (PDP) has emerged as a means of alleviating the ‘curse of dimensionality’ in the mid-long term reservoir operation with more involved computing processors. But it still can't effectively solve the daily impoundment operation of more than three reservoirs. Here, we propose a novel method called importance sampling-PDP (IS-PDP) algorithm in which the merits of PDP are integrated with importance sampling and successive approximation strategy. Importance sampling is first used to construct the state vectors of each period by introducing ‘Manhattan distance’ in the discrete state space. Then the PDP recursive equation is used to find an improved solution during the iteration. The IS-PDP method is tested to optimize hydropower output for the joint operation of an 11-reservoir system located in the upper Yangtze River basin of China after establishing impoundment operation by advancing impoundment timings and rising water levels. We find that our methodology could effectively deal with the ‘curse of dimensionality’ for such mega reservoir systems and make better use of water resources in comparison to the Standard Operation Policy (SOP). Given its computational efficiency and robust convergence, the methodology is an attractive alternative for non-convex operation of large-scale cascade reservoirs.