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Abstract Pregnane X receptor (PXR) has been reported to regulate glycolipid metabolism. The dysfunction of intestinal barrier contributes to metabolic disorders. However, the role of intestinal PXR in metabolic diseases remains largely unknown. Here, we show that activation of PXR by tributyl citrate (TBC), an intestinal-selective PXR agonist, improves high fat diet (HFD)-induced obesity. The metabolic benefit of intestinal PXR activation is associated with upregulation of β-1,3 galactosyltransferase 5 (B3galt5). Our results reveal that B3galt5 mainly expresses in the intestine and is a direct PXR transcriptional target. B3galt5 knockout exacerbates HFD-induced obesity, insulin resistance and inflammation. Mechanistically, B3galt5 is essential to maintain the integrity of intestinal mucus barrier. B3galt5 ablation impairs the O-glycosylation of mucin2, destabilizes the mucus layer, and increases intestinal permeability. Furthermore, B3galt5 deficiency abolishes the beneficial effect of intestinal PXR activation on metabolic disorders. Our results suggest the intestinal-selective PXR activation regulates B3galt5 expression and maintains metabolic homeostasis, making it a potential therapeutic strategy in obesity.

[Objective] This study aimed to investigate the effects of different tillage patterns and biochar addition on soil nitrogen and phosphorus transformation and maize growth and development in farmland in the black soil area. [Methods] Through a field experiment, two tillage treatments (deep tillage and shallow tillage) and five biochar addition treatments (0, 3, 6, 9, and 12 t/hm2) were set up to investigate the combined effects of different tillage patterns and biochar addition on soil nitrogen and phosphorus fractions, enzyme activities, and physiological characteristics of maize. [Results] (1) Deep tillage and shallow tillage in combination with biochar addition could effectively improve soil structure, increase the geometric mean diameter of agglomerates, and reduce the percentage of damage. The deep tillage treatment was more effective than the shallow tillage treatment. (2) The addition of biochar improved soil nitrogen-phosphorus fractions, urease activity, and alkaline phosphatase activity, and the effect of applying biochar at the rate of 9 t/hm2 was the best, which was more pronounced in the deep tillage treatment. (3) The application of biochar up to 9 t/hm2 under deep tillage treatment increased the total nitrogen and phosphorus contents and glutamine synthetase activity of leaves and decreased the acid phosphatase activity. (4) The yield of corn under deep tillage condition with the addition of 9 t/hm2 of biochar was as high as 17.37 t/hm2, which was increased by 28.9% compared with that of 0 of biochar. [Conclusion] The deep-tillage treatment and addition of 9 t/hm2 biochar provided a reference for the nutrient environment and crop growth in agricultural fields in the black soil area.

Abstract Diabetic nephropathy (DN) is a frequent and costly complication of diabetes with limited understandings of mechanisms and therapies. Emerging evidence points to the important roles of interleukin‐33 (IL‐33) in acute kidney injury, yet its contribution to DN is still unclear. We here found a ubiquitous increase of IL‐33 and its receptor (ST2) in murine models and patients with DN. Surprisingly, both IL‐33 and ST2 knockdown aggravated renal lesions in DN, while overexpression of IL‐33 also exacerbated the condition. Further population‐based analyses revealed a positive correlation of IL‐33 expression with renal dysfunction in DN patients. Individuals with high IL‐33 expression‐related polygenic risk score had a higher DN risk. These findings confirmed the harmful effects of IL‐33 on DN. Conversely, endogenous and exogenous partial reduction of IL‐33 signaling conferred renoprotective effects in vivo and in vitro. Mechanistically, IL‐33 induced senescence by regulating cell cycle factors in HK‐2 cells, and accordingly senescence led to renal cell damage through the secretion of senescence‐related secretory phenotype (SASP) including IL‐33 and prostaglandins. Together, elevated IL‐33 accelerates cellular senescence to drive DN possibly by SASP production, while a partial blockage improves renal injury and senescence. Our findings pinpoint a possible and new avenue for DN interventions.

ABSTRACT Aspergillus fumigatus is the predominant pathogen responsible for aspergillosis infections, with emerging drug-resistant strains complicating treatment strategies. The role of mitochondrial functionality in fungal resistance to antifungal agents is well-documented yet not fully understood. In this study, the mitochondrial protein Bcs1A, a homolog of yeast Bcs1, was found to regulate colony growth, ion homeostasis, and the response to antifungal drugs in A. fumigatus. Microscopic observations revealed substantial colocalization of Bcs1A-GFP fusion protein fluorescence with mitochondria. Bcs1A deletion compromised colony growth and the utilization of non-fermentable carbon sources, alongside causing abnormal mitochondrial membrane potential and reduced reactive oxygen species production. These findings underscore Bcs1A’s vital role in maintaining mitochondrial integrity. Phenotypic analysis and determinations of minimum inhibitory concentrations indicated that the Δbcs1A mutant was more resistant to various antifungal agents, such as azoles, terbinafine, and simvastatin, compared to wild-type strain. RNA sequencing and RT-qPCR analysis highlighted an upregulation of multiple efflux pumps in the Δbcs1A mutant. Furthermore, loss of the principal drug efflux pump, mdr1, decreased azole tolerance in the Δbcs1A mutant, suggesting that Bcs1A’s modulated of azoles response via efflux pump expression. Collectively, these results establish Bcs1A as essential for growth and antifungal drug responsiveness in A. fumigatus mediated through mitochondrial regulation.IMPORTANCEDrug resistance presents a formidable obstacle in the clinical management of aspergillosis. Mitochondria are integral to various biochemical pathways, including those involved in fungi drug response, making mitochondrial proteins promising therapeutic targets for drug therapy. This study confirms that Bcs1A, a mitochondrial respiratory chain protein, is indispensable for mitochondrial functionality and multidrug tolerance in Aspergillus fumigatus. Mutation of Bcs1A not only leads to a series of drug efflux pumps upregulated but also shows that loss of the primary efflux pump, mdr1, partial reduction in drug tolerance in the Bcs1A mutant, highlighting that Bcs1A’s significant influence on mitochondria-mediated drug resistance.

AbstractObjective This study aims to examine the short-term effects of oral metformin (MET) on serum anti-müllerian hormone (AMH) levels and to verify its impact on AMH concentrations in women with polycystic ovary syndrome (PCOS).Methods The literature search, extending from January 2000 to April 2023, was conducted using databases such as PubMed, Embase, and the Cochrane Central, resulting in the inclusion of 20 studies. These selected studies, evaluated for quality using the Newcastle–Ottawa Scale, investigated changes in AMH levels before and after treatment, with durations ranging from less than three months to over six months. The reported outcomes were quantified as standardized mean differences (SMD) with 95% confidence intervals (CI). This comprehensive systematic review and meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42023420705. The statistical analyses were performed using Review Manager 5.4.1.Results ① The study incorporated 20 articles, consisting of 12 prospective studies, 7 randomized controlled trials (RCT), and 1 cross-sectional study. ② Serum AMH levels in patients with PCOS diminish subsequent to the oral administration of MET. ③ Across the spectrum of studies analyzed, a pronounced degree of heterogeneity is evident, potentially ascribed to differential parameters including body mass index (BMI), daily pharmacological dosages, the temporal extent of treatment regimens, criteria of PCOS, and detection Methods. ④ The impact of MET on AMH levels exhibits a dose-responsive trend, with escalating doses of MET being associated with progressively greater declines in AMH concentrations in the patient population. ⑤ For women with PCOS receiving MET therapy, a minimum treatment duration of three months may be necessary to observe a reduction in serum AMH levels.Conclusions The results of this meta-analysis indicate that MET treatment exerts a suppressive effect on serum AMH levels in women with PCOS. It appears that a treatment duration of at least three months is required to achieve a significant decrease in AMH concentrations. Furthermore, the influence of MET on AMH is dose-dependent, with higher doses correlating with more pronounced reductions in AMH levels among the patients studied.

Bacterial assemblages associated with sea urchin are critical to their physiology and ecology within marine ecosystems. In this study, we characterized the bacterial communities in wild sea urchin Anthocidaris crassispina captured in Daya Bay, South China Sea. A total of 363 amplicon sequence variants belonging to nine phyla and 141 genera were classified from intestine, body surface, and surrounding seawater samples. Proteobacteria, Firmicutes, and Bacteroidetes were the dominant bacteria phyla found in this study. A network analysis of bacterial interspecies interactions revealed varying complexity, stability, connectivity, and relationship patterns across the samples, with the most intricate network observed in the surrounding seawater. Metagenomic predictions highlighted the distinct bacterial metabolic pathways, with significant differences between intestine and seawater samples. Notably, pathways associated with polysaccharide degradation, including chitin derivatives, starch, and CoM biosynthesis, were markedly abundant, underscoring the gut microbiota’s key role in digesting algae. In addition, other metabolic pathways in intestine samples were linked to immune response regulation of sea urchins. Overall, this study provides a comprehensive overview of the bacterial community structure and potential functional roles in A. crassispina.

Background Periodic repolarization dynamics (PRD) is an electrocardiographic biomarker that captures repolarization instability in the low frequency spectrum and is believed to estimate the sympathetic effect on the ventricular myocardium. High PRD indicates an increased risk for postischemic sudden cardiac death (SCD). However, a direct link between PRD and proarrhythmogenic autonomic remodeling has not yet been shown. Methods and Results We investigated autonomic remodeling in pigs with myocardial infarction (MI)–related ischemic heart failure induced by balloon occlusion of the left anterior descending artery (n=17) compared with pigs without MI (n=11). Thirty days after MI, pigs demonstrated enhanced sympathetic innervation in the infarct area, border zone, and remote left ventricle paralleled by altered expression of autonomic marker genes/proteins. PRD was enhanced 30 days after MI compared with baseline (pre‐MI versus post‐MI: 1.75±0.30 deg2 versus 3.29±0.79 deg2, P

Study region: In the Yangtze River basin of China. Study focus: Accurate and reliable streamflow forecasting methods are of utmost importance for the sustainable utilization and management of water resources. Recently, machine learning models have been widely used in streamflow forecasting, but greatly focus on the improvement of prediction accuracy and ignore the description of prediction uncertainty. Therefore, we applied bidirectional gated recurrent unit (BIGRU), attention mechanism (AM), and natural gradient boosting (NGB) methods to predict the uncertainty of streamflow in the Yangtze River basin. We propose a novel hybrid streamflow probabilistic prediction model BIGRU-AM-NGB. In addition, the underlying contribution of input features to output was thoroughly analyzed. New hydrological insights for the region: Six state-of-the-art models were compared with the proposed model from three aspects: deterministic prediction, interval prediction, and probability prediction. The results revealed that BIGRU-AM-NGB model can obtain high accuracy point prediction, reliable probability prediction, and appropriate interval prediction. Different input features result in different contribution to output. The runoff of Yichang hydrological station one-day ahead dominated the output, followed by the runoff of Zhutuo hydrological station two-day ahead. This can be attributed to the spatial and temporal distribution of hydrographic stations. Therefore, BIGRU-AM-NGB can achieve high-precision streamflow predictions while quantifying uncertainty, and effectively develop implicit relationships between features and output that obey physical properties.

Communication among the brain, gut and microbiota in the gut is known to affect the susceptibility to stress, but the mechanisms involved are unclear. Here we demonstrated that stress resistance in mice was associated with more abundant Lactobacillus and Akkermansia in the gut, but less abundant Bacteroides, Alloprevotella, Helicobacter, Lachnoclostridium, Blautia, Roseburia, Colidextibacter and Lachnospiraceae NK4A136. Stress-sensitive animals showed higher permeability and stronger immune responses in their colon, as well as higher levels of pro-inflammatory cytokines in serum. Their hippocampus also showed more extensive microglial activation, abnormal interactions between microglia and neurons, and lower synaptic plasticity. Transplanting fecal microbiota from stress-sensitive mice into naïve ones perturbed microglia-neuron interactions and impaired synaptic plasticity in the hippocampus, translating to more depression-like behavior after stress exposure. Conversely, transplanting fecal microbiota from stress-resistant mice into naïve ones protected microglia from activation and preserved synaptic plasticity in the hippocampus, leading to less depression-like behavior after stress exposure. These results suggested that gut microbiota may influence resilience to chronic psychological stress by regulating microglia-neuron interactions in the hippocampus.

Currently, nearly 70% of giant panda populations are facing survival challenges. The introduction of wild individuals can bring vitality to them. To explore this possibility, we hypothetically introduced giant pandas from Tangjiahe and Wanglang into Liziping and Daxiangling Nature Reserves. We collected feces from these areas and analyzed the genetic diversity and population viability before and after introduction using nine microsatellite loci. The results showed the genetic level and viability of the large populations were better than the small populations. We investigated the effects of time intervals (2a, 5a, and 10a; year: a) and gender combinations (female: F; male: M) on the rejuvenation of small populations. Finally, five introduction plans (1F/2a, 2F/5a, 1F1M/5a, 3F/10a, and 2F1M/10a) were obtained to make Liziping meet the long-term survival standard after 100 years, and six plans (1F/2a, 2F/5a, 1F1M/5a, 4F/10a, 3F1M/10a, and 2F2M/10a) were obtained in Daxiangling. The more females were introduced, the greater the impact on the large populations. After introducing individuals, the number of alleles and expected heterozygosity of the Liziping population are at least 6.667 and 0.688, and for the Daxiangling population, they are 7.111 and 0.734, respectively. Our study provides theoretical support for the translocation of giant pandas, a reference for the restoration of other endangered species worldwide.

Hydro power has provided significant economic benefits to society due to its cleanliness and convenience. As the number of hydropower stations has increased, many serious ecological issues have also emerged. This study uses Wan’an Reservoir as its research object and investigates single–multi-objective optimal operation and decision-making regarding reservoirs for ecology-oriented operation, to meet ecological water demand and seek the optimal operation schemes for energy generation and ecological benefits. The full-process research is conducted based on the “objective-modeling constraint optimization scheme decision-making” framework. The Mann–Kendall test and ordered clustering method were used to diagnose the hydrological variation in the basin. Based on this, a hierarchical and phased ecological flow process was derived. The objectives were defined according to the flow process, and optimal operation models were constructed. The differential evolution algorithm (DE) and improved non-dominated sorting genetic algorithm-II (NSGA-II) were used to solve the models. A non-fitting curve method was used to determine the approximate inflection point of the Pareto front curve, and the curve was fitted linearly according to the approximate inflection point to obtain the conversion formula between the objectives. Based on the coefficient of variation and Mahalanobis distance, a new multi-attribute decision-making method for reservoir operation, CV-ITOPSIS, was constructed by improving the traditional TOPSIS. The results show that: (1) There is a piecewise linear contradiction between energy generation and ecological objectives, and the contradiction intensifies with an increase in incoming water frequency. (2) Before the approximate inflection point, the head significantly influences the conversion rate from the energy generation to ecology, while the discharge flow is the major influencing factor after the inflection point. The inflection point and the formula for the piecewise straight line can reveal the conversion law between the two objectives. (3) CV-ITOPSIS considers the degree of differentiation of index data and fully considers the correlation between indicators while retaining the good evaluation performance of the traditional method. It recommends the optimal benefit scheme for a multi-objective non-inferior solution set. The research results provide a theoretical foundation and decision support for the optimal ecological operation of the Ganjiang River Basin.

The Houhai area in Nanshan District of Shenzhen is the base of the headquarters building，where the Shenzhen fault zone and the Pearl River Mouth fault zone meet here. In this region, the bedrock is buried deeply, the faults are well developed, and there is huge thick weathered deep trough. Thus, overlength pile foundation is used in high-rise buildings. In this study, the permanent scatterers interferometric synthetic aperture radar technique was used to monitor the settlement of ground and structures in houhai Deep trough research area, Nanshan District, Shenzhen. The monitoring results show that the settlement of buildings and other structures on deep trough is relatively stable, and the pile foundation construction technology in Houhai research area is safe and effective at present. The grassland of Shenzhen Bay Park and its surrounding areas have a large amount of settlement, which is mainly caused by the settlement of soft land reclaimed from the sea. Compared with the traditional monitoring technology, the monitoring accuracy of InSAR technology meets the requirements. The InSAR technology has advantages for large-scale, low-cost, high-precision and high-efficiency deformation monitoring.

High-precision load forecasting is crucial for the power system planning and electricity market transactions. Recently, deep learning models have been widely used due to their powerful data mining capabilities. However, the existing research mainly focus on model structure adjustment and input feature selection, ignoring the influence of model ensemble on prediction. A single deep learning model is not yet able to address the various complex challenges that arise in short-term load forecasting. To improve the accuracy of short-term load forecasting, this paper proposes a novel multi-scale ensemble method and multi-scale ensemble neural network. This neural network uses long short-term memory, gate recurrent units, and temporal convolutional network as the basic model. By coupling the stochastic weight averaging ensemble method and differential evolution ensemble method, these deep learning networks were assembled from single-model scale and multi-model scale, respectively, thereby effectively improving the model prediction accuracy. For predicting the power load of Hubei Province in China, meteorological features and time features were in consideration. The proposed model was trained and compared with eleven intelligent short-term load forecasting models, including machine learning, deep learning and ensemble deep learning models. Simulations show that the proposed model has the best comprehensive prediction performance. This study highlights the power of ensemble deep learning models coupled with multiple ensemble techniques and the promising prospect of our proposed model in short-term load forecasting.

Diabetic nephropathy is a microvascular complication of diabetes mellitus, threatening the health of millions of people. Herein, we explored a blood glucose independent function of coptisine on diabetic nephropathy. A diabetic rat model was established by intraperitoneal administration of streptozotocin (65 mg/kg). Coptisine treatment (50 mg/kg/day) retarded body weight loss and reduced blood glucose. On the other hand, coptisine treatment also decreased kidney weight and the levels of urinary albumin, serum creatinine, and blood urea nitrogen, indicating an improvement of renal function. Treatment with coptisine also mitigated renal fibrosis, with alleviative collagen deposition. Likewise, in vitro study showed that coptisine treatment decreased apoptosis and fibrosis markers in HK-2 cells treated with high glucose. Furthermore, after coptisine treatment, the activation of NOD-like receptor pyrin domain containing protein 3 (NRLP3) inflammasome was repressed, with decreased levels of NLRP3, cleaved caspase-1, interleukin (IL)-1β, and IL-18, indicating that the repression of NRLP3 inflammasome contributed to the effect of coptisine on diabetic nephropathy. In conclusion, this study revealed that coptisine mitigates diabetic nephropathy via repressing the NRLP3 inflammasome. It is indicated that coptisine may have the potential to be used in the diabetic nephropathy treatment.

【Objective】 Rational allocation of agricultural water resources in irrigation areas is essential to improving agricultural water use efficiency, but challenging due to its multi-level, multi-objective and multi-variable characteristics in its operations. The purpose of this paper is to propose a multi-layer and multi-objective coordinated regulation of water resources in irrigation districts with water supply uncertainties considered. 【Method】 Taking Jinxi Irrigation District in Heilongjiang Province as an example, this paper establishes a multi-objective and two-layer cooperative regulation system to optimize the agricultural water resources based on quantitative characterization of the interval uncertainty in water supply fluctuations. The model is to achieve a synergistic enhancement of farmers’ income and economic and social benefits by optimizing the use of surface and groundwater for different crops in the backbone channels of the irrigation district at different water distribution times. The two-layer model has coordinated mutual feedbacks between water supply and water use and is solved by the integration of optimal-disadvantage method, fuzzy mathematical planning, and large system decomposition-coordination method. 【Result】 The economic benefits of the irrigation district varies between 20.52 and 25.03 billion yuan, and the water allocation varies between 475.34 and 512.75 million m3. Compared with business as usual, the proposed method reduced groundwater utilization by 7%, alleviating the over-exploitation of groundwater. The proposed method also increased economic benefit per unit of water by 14.5%, effectively improving water utilization rate. The Gini coefficient of the water allocation is between 0.36 and 0.55, indicating a fair water allocation between different crops in different sub-districts. 【Conclusion】 The model proposed in this paper for coordinating regulation of multiple water sources for different uses in irrigation districts can help sustainable development of irrigation districts, improve water allocation to cope with the impact of changing environments.

As the most important nuclear fuel for nuclear power operation, the safe supply of uranium resources is the key to ensure the sustainable development of nuclear power in China. Uranium extraction from seawater has important and longterm strategic significance to ensure the sustainable development of nuclear power in China. With the updating and development of uranium extraction technology from seawater, the research work of uranium extraction from seawater is facing new opportunities and challenges. Based on the research status of uranium extraction from seawater at home and abroad, this paper puts forward the future plan and prospect of uranium extraction from seawater, which is proposed by “Seawater Uranium Extraction Technology Innovation Alliance” led by China National Nuclear Corporation. It points out the research direction of uranium extraction from seawater in the future, and provides technical support for uranium extraction from seawater to industrialization.

Background/Aim: Polypharmacy is prevalent among older inpatients and associated with adverse outcomes. To determine whether a geriatrician-led multidisciplinary team (MDT) management mode could reduce medications use among older inpatients.Methods: A retrospective cohort study was conducted in a geriatric department of a tertiary hospital in China with 369 older inpatients, including 190 patients received MDT management (MDT cohort), and 179 patients received usual treatment (non-MDT cohort). The primary outcome was to compare the changes of the amount of medications before and after hospitalization in two cohorts.Results: We reported that MDT management significantly reduced the number of medications used in older inpatients at discharge (at home: n = 7 [IQR: 4, 11] vs at discharge: n = 6 [IQR: 4, 8], p < 0.05). Hospitalization with the MDT management had a significant effect on the change in the amount of medications (F = 7.813, partial-η2 = 0.011, p = 0.005). The discontinuance of medications was associated with polypharmacy at home (OR: 96.52 [95% CI: 12.53-743.48], p < 0.001), and the addition of medications was associated with a diagnosis of chronic obstructive pulmonary disease (COPD) (OR: 2.36 [95% CI: 1.02-5.49], p = 0.046).Conclusion: The results indicated that the geriatrician-led MDT mode during hospitalization could reduce the number of medications used by older patients. The patients with polypharmacy were more likely to “deprescription” after MDT management, while the patients with COPD were more likely to be under-prescription at home, polypharmacy which could be made up for after MDT management.

CRELD2, a member of the cysteine-rich epidermal growth factor-like domain (CRELD) protein family, is both an endoplasmic reticulum (ER)-resident protein and a secretory factor. The expression and secretion of CRELD2 are dramatically induced by ER stress. CRELD2 is ubiquitously expressed in multiple tissues at different levels, suggesting its crucial and diverse roles in different tissues. Recent studies suggest that CRELD2 is associated with cartilage/bone metabolism homeostasis and pathological conditions involving ER stress such as chronic liver diseases, cardiovascular diseases, kidney diseases, and cancer. Herein, we first summarize ER stress and then critically review recent advances in the knowledge of the characteristics and functions of CRELD2 in various human diseases. Furthermore, we highlight challenges and present future directions to elucidate the roles of CRELD2 in human health and disease.

Reliable and accurate daily runoff predictions are critical to water resource management and planning. Probability density predictions of daily runoff can provide decision-makers with comprehensive information by quantifying the uncertainty of forecasting. Models based on quantile regression (QR) have been proven to achieve good probabilistic prediction performance, but the predicted quantiles may crossover with each other, seriously reducing the reliability of the prediction. This paper proposes non-crossing quantile regression (NCQR), which guarantees that the intervals between adjacent quantiles are greater than 0, which avoids the occurrence of quantile crossing. In order to apply NCQR to the prediction of nonlinear runoff series, this paper combines NCQR with recurrent neural network (RNN) models. In order to reduce the model training time and further improve the model accuracy, this paper simplifies the minimal gated memory (MGM) model and proposes a new RNN model, called the simplified minimal gated memory (SMGM) model. Kernel density estimation (KDE) is used to transform the discrete quantiles predicted using SMGM-NCQR into a continuous probability density function (PDF). This paper proposes a novel daily density prediction model that combines SMGM-NCQR and KDE. Three daily runoff datasets in the Yangtze River Basin in China are taken as examples and compared with the advanced models in current research in terms of five aspects: point prediction evaluation, interval prediction evaluation, probability density prediction evaluation, the degree of quantile crossing and training time. The experimental results show that the model can provide high-quality and highly reliable runoff probability density predictions.

Recent studies have found that many marine microbial polysaccharides exhibit distinct immune activity. However, there is a relative scarcity of research on the immunomodulatory activity of marine fungal exopolysaccharides. A novel water-soluble fungal exopolysaccharide ASP-1 was isolated from the fermentation broths of marine coral-associated fungus Aspergillus pseudoglaucus SCAU265, and purified by Diethylaminoethyl-Sepharose-52 (DEAE-52) Fast Flow and Sephadex G-75. Structural analysis revealed that ASP-1 had an average molecular weight of 36.07 kDa and was mainly composed of (1→4)-linked α-D-glucopyranosyl residues, along with highly branched heteropolysaccharide regions containing 1,4,6-glucopyranosyl, 1,3,4-glucopyranosyl, 1,4,6-galactopyranosyl, T(terminal)-glucopyranosyl, T-mannopyranosyl, and T-galactopyranosyl residues. ASP-1 demonstrated significant effects on the proliferation, nitric oxide levels, and the secretion of cytokines TNF-α and IL-6 in macrophage RAW264.7 cells. Metabolomic analysis provided insights into the potential mechanisms of the immune regulation of ASP-1, suggesting its involvement in regulating immune function by modulating amino acid anabolism, particularly arginine synthesis and metabolism. These findings provide fundamental scientific data for further research on its accurate molecular mechanism of immunomodulatory activity.

Cascade reservoir operation can ensure the optimal use of water and hydro-energy resources and improve the overall efficiency of hydropower stations. A large number of studies have used meta-heuristic algorithms to optimize reservoir operation, but there are still problems such as the inability to find a global optimal solution and slow convergence speed. Lightning search algorithm (LSA) is a new meta-heuristic algorithm, which has the advantages such as high convergence speed and few parameters to be adjusted. However, there is no study on the application of LSA in reservoir operation. In this paper, LSA is used to solve the problem of reservoir operation optimization to verify its feasibility. We also propose an improved LSA algorithm, the frog-leaping–particle swarm optimization–LSA (FPLSA), which was improved by using multiple strategies, and we address the shortcomings of LSA such as low solution accuracy and the tendency to fall into local optima. After preliminary verification of ten test functions, the effect is significantly enhanced. Using the lower Jinsha River–Three Gorges cascade reservoirs as an example, the calculation is carried out and compared with other algorithms. The results show that the FPLSA performed better than the other algorithms in all of the indices measured which means it has stronger optimization ability. Under the premise of satisfying the constraints of cascade reservoirs, an approximate optimal solution could be found to provide an effective output strategy for cascade reservoir scheduling.

Advanced engineering systems possess a large number of components with complicated failure dependencies. To accurately assess the system reliability, the degradation models of components should be known in advance and the model parameters should be accurately estimated via a large quantity of historical time-to-failure data. In real-world situations, due to limited data, lack of knowledge, and vague judgments from experts, components’ degradation model parameters are, however, inevitably encountered with epistemic uncertainty and oftentimes quantified as evidential variables. In this article, upper and lower bounds of system reliability, termed as reliability-box, are estimated when components’ degradation model parameters are elicited from experts and quantified by evidential variables. In the first place, the constrained optimization model is leveraged to assess the reliability-box of each component by giving the evidential variable of the component’s degradation model parameters. Next, based on the system structure, the evidential network of the system is constructed to propagate the epistemic uncertainty from the component level to the system level. Therefore, the focal elements of the evidential variable of system reliability, i.e., the system reliability bounds, can be assessed via the belief and plausibility functions to the mass function of the leaf node of the evidential network. The effectiveness of the proposed methods is demonstrated by a rolling system in the chip cutting detection module.

Objective. To estimate global, regional, and national trends due to ectopic pregnancy as part of the 2019 Global Burden of Disease study. Methods. We systematically reviewed trends in ectopic pregnancy burden using data from the Global Burden of Disease (GBD) database, including 21 regions, 195 countries, and territories over the past 30 years. The trends of ectopic pregnancy-related incidence, mortality, and disability-adjusted life years (DALYs) attributable to all known risk factors were also analyzed. Age-standardized rates (ASRs) and their estimated annual percentage changes (EAPCs) were also calculated. Results. Incident cases, deaths, and DALYs of ectopic pregnancy increased worldwide in the past 30 years. The age-standardized incidence rate (ASIR) was decreasing (EAPC = −1.14, 95% confidence interval (CI): −1.29 to −0.98), and the age-standardized death (EAPC = −0.9, 95% CI: −1.03 to −0.76) and DALY rate decreased generally (EAPC = −0.83, 95% CI: −0.98 to −0.68). In addition, the burden of ectopic pregnancy is lower in areas with higher socioeconomic development, and significant positive correlations between ASRs and sociodemographic index (SDI) were observed, especially among low-middle SDI, and low SDI quintiles carried the majority burden of ectopic pregnancy. Conclusion. Globally, the incidence, mortality, and DALY rate of ectopic pregnancy had been decreasing from 1990 to 2019. Compared with lower and decreasing ASIR in the high SDI region, ASIR in the low SDI region was always high, indicating the need for ectopic pregnancy treatment improvement and the establishment of more targeted and specific strategies in low SDI countries to reduce the incidence of ectopic pregnancy.

Objectives: In older lung cancer patients, polypharmacy and the use of potentially inappropriate medications (PIMs) are commonly reported, but no systematic review or meta-analysis has been carried out to ascertain the prevalence and risk variables in this group. This study aimed to identify the prevalence of polypharmacy, PIMs and associated risk variables in older lung cancer patients.Methods: We searched for articles from the beginning to February 2022 in PubMed, Embase, and Web of Science that related the use of PIMs and polypharmacy by older lung cancer patients (PROSPERO Code No: CRD42022311603). Meta-analysis was performed on observational studies describing the prevalence and correlation of polypharmacy or PIMs in older patients with lung cancer.Results: Of the 387 citations, 6 articles involving 16,890 patients were included in the final sample. In older lung cancer patients pooled by meta-analysis, 38% and 35% of PIMs and polypharmacy, respectively. The prevalence of PIMs was 43%, 49%, and 28%, respectively, according to the 2019 AGS Beers criteria, 2014 screening tool for older people’s prescriptions/screening tool for alerting to the proper therapy (STOPP/START criteria) criteria, and other criteria.Conclusion: This systematic review and meta-analysis demonstrated a high prevalence of polypharmacy and PIMs among older lung cancer patients. Therefore, it is essential to take rational interventions for older lung cancer patients to receive reasonable pharmacotherapy.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022311603].

The effects of neighboring vegetation are important for plant fitness and community assembly under global change. What is less clear is how plant-plant interactions would change along the stress gradient. Our aim is to test the hypothesis that the abiotic stress alleviation induced by nitrogen (N) deposition and climate warming intensified the competitive effects of neighboring vegetation on two degradation indicator species of alpine meadows (i.e., Potentilla anserine and Ligularia virgaurea), as predicted by the popular “stress-gradient hypothesis” (SGH). A neighbor removal experiment was conducted with either N addition or artificial warming as treatments at both an alpine mesophytic meadows site (MESms) and a semi-hydric marsh meadows site (SHMms) on the southeastern Tibetan Plateau. The net neighbor effects on both P. anserine and L. virgaurea were extreme and moderate competition in MESms, respectively, but were mild facilitation in SHMms. In line with the SGH, both N addition and warming intensified the neighbor competitive effects on L. virgaurea in MESms and weakened the neighbor facilitative effects on L. virgaurea in SHMms. However, in contrast to the SGH, the neighbor competitive effects on P. anserine in MESms were weakened by both N addition and warming. Furthermore, the neighbor facilitative effects on P. anserine in SHMms were weakened by N addition but were not changed by warming. These diverse plant interaction-environmental gradient relationships were likely induced by the joint effects of stress type, plant strategy in response to stress and natural intensity of neighbor effects. It may be helpful to take these factors into consideration for further refinement of the SGH.

The optimal scheduling of cascade reservoirs is an important water resource management and regulation method. In the actual operation process, its nonlinear, high-dimensional, and coupled characteristics become increasingly apparent under the influence of multiple constraints. In this study, an integrated multistrategy particle swarm optimization (IMPSO) algorithm is proposed to realize the optimal operation of mid- and long-term power generation in cascade reservoirs according to the solution problem in the scheduling process of cascade reservoirs. In IMPSO, a variety of effective improvement strategies are used, which are combined with the standard PSO algorithm in different steps, among which beta distribution initialization improves population diversity, parameter adaptive adjustment accelerates convergence speed, and the Lévy flight mechanism and adaptive variable spiral search strategy balance the global and local search capabilities of the algorithm. To handle complex constraints effectively, an explicit–implicit coupled constraint handling technique based on constraint normalization is designed to guide the update process into the feasible domain of the search space. The feasibility of the proposed method is verified in the mid- and long-term power generation optimization scheduling of the lower reaches of the Jinsha River–Three Gorges cascade hydropower reservoirs. The results show that the proposed method outperforms the other methods in terms of search accuracy and has the potential to improve hydropower resource utilization and power generation efficiency significantly.

Objective: Quercetin (Que) is a plant-derived polyphenolic compound, that was shown to possess anti-inflammatory activity in myocardial ischemia/reperfusion (I/R) models in vivo; however, detailed mechanisms of its anti-inflammatory effects remain unclear. This study aimed to examine the effects of quercetin postconditioning (QPC) on I/R-induced inflammatory response in a rat model and evaluate the role of the mitochondrial K-ATP (mitoKATP) channels and NO system in this regard. Materials and Methods: In this experimental study, hearts of male Wistar rats (250 ± 20 g) perused by Langendorff apparatus, were subjected to 30 minutes of global ischemia followed by 55 minutes reperfusion, and Que was added to the perfusion solution immediately at the onset of reperfusion. Creatine kinase (CK) levels in the coronary effluent were measured by spectrophotometry. Interleukin-1 (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) levels were analyzed by an enzyme-linked immunosorbent assay (ELISA) rat specific kit to assess the inflammatory condition of the myocardial tissue. Results: Our results showed that QPC significantly improved left ventricular developed pressure (LVDP) (P

Adeno-associated virus (AAV)-mediated delivery of the clustered regularly interspaced short palindromic repeat-CRISPR-associated protein 9 (CRISPR-Cas9) has shown promising results in preclinical models. However, the long-term expression of Cas9 mediated by AAV in the post-mitotic cells raises concerns with specificity and immunogenicity. Thus, it would be advantageous to limit the duration of Cas9 expression following delivery. In this study, we have engineered an all-in-one self-cleavage AAV-CRISPR-Cas9 system to restrict the expression of Cas9 nuclease, which consists of a Cas9 nuclease from Staphylococcus aureus (SaCas9), a chimeric single guide RNA (sgRNA) molecule targeting PCSK9, and flanking sites targeted by this sgRNA. The self-cleavage system generated a negative feedback loop where Cas9 cut both the target genomic locus and the AAV vector, thus self-limiting the expression of Cas9. We demonstrated that this system could reduce ∼60% expression of SaCas9 protein and had a 20-fold reduction in off-target activity at 24 weeks post-vector administration in vivo. Moreover, the on-target editing efficacy was not compromised and resulted in a stable reduction in circulating PCSK9 and serum cholesterol. The inclusion of this self-cleavage system in gene-editing approaches could increase the safety profile of AAV-delivered genome-editing nucleases and thereby promote its clinical transformation.

Objective To investigate the preventive and inhibitory effects of tumor cell lysate(TCL) combined with IL-2 on melanoma and the potential immune mechanism. Methods The B16F10 melanoma TCL cell were prepared using an ultrasonic disruptor. Twenty-four C57BL/6 mice were randomly divided into four groups which were immunized with PBS, IL-2, TCL and TCL+IL-2 for three weeks, and contra lateral tumors were implanted in the fourth week. We observed onset time of tumor and tumor size, collected peripheral blood continuously and monitored the expression of CD4+T and CD8+T cell subsets dynamically by flow cytometry. Spleen and tumor tissues of mice were also tested for CD4+T and CD8+T cell subsets by flow cytometry and immunohistochemistry, respectively. Results The preventive immunization of the TCL+IL-2 group significantly delayed the onset time of tumor (P=0.034); moreover, the tumor volume (P=0.023) and tumor weight (P=0.0015) were also significantly smaller than those in the control group. The expression of CD8+T cell subsets in the TCL+IL-2 group and the TCL-only group were significantly higher than that in the control group (P=0.0016, P=0.012). However, the CD4+T cell subsets of the TCL+IL-2 group decreased after tumor implantation, compared with the control group (P=0.0089). The expression of CD4+T and CD8+T cell subsets in spleen and tumor tissues were as same as those in peripheral blood. Conclusion The tumor vaccine of TCL combined with IL-2 could prevent the occurrence of melanoma in mouse and effectively inhibit tumor growth by activating CD8+T cells.

This paper investigates the transient aerodynamic interference of rotors imposed on fuselage for a quadcopter through Computational Fluid Dynamics (CFD) simulations. The numerical study of transient effects due to rotor rotation is enabled by sliding mesh which defines the rotation domains encompassing rotor blades. The results show that the interference effects of rotor change the aerodynamic forces of the fuselage, causing about 67% in-crease in lift, 13% increase in drag, and 90% increase in pitching up moment on average. The variations of fuselage lift are associated with the pressure distribution changes due to rotors rotation, the high-pressure areas and low-pressure areas over the rotor projects on the arms of the quadcopter causing periodical abrupt changes on the lift, drag and pitching moment.

For an in-depth understanding of the change process of dissolved organic matter(DOM) in water environment of coal mine underground reservoir, this study used the three dimensional fluorescence spectrum(EEMs), combined with PARAFAC model, to analyze changes and components of the DOM in inflows and outflows in Daliuta coal mine underground reservoir.The principal component analysis(pca) was used to analyze the main factors by which the water body of the DOM was influenced.The results showed that the coal mine underground reservoir had a certain purification effect, and the TOC and UV254 of DOM were significantly reduced at the outlet water.The DOM in the water body of underground reservoir can be divided into four components:uv-like fulvic acid(240 nm/380 nm), protein-like tryptophan(275 nm/330 nm), uv-like fulvic acid(255 nm/380 nm) and visible fulvic acid(265 nm, 355 nm/380 nm).Through principal component analysis and the analysis of f470/520, HIX and BIX, the results showed that the source of DOM was a combination of endogenous input and terrestrial input, but with endogenous input as the main feature.The treatment of endogenous pollution should be considered in the operation and management of underground reservoirs.

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 loaded by vectors could induce high rates of specific site genome editing and correct disease-causing mutations. However, most monogenic genetic diseases such as hemophilia are caused by different mutations dispersed in one gene, instead of an accordant mutation. Vectors developed for correcting specific mutations may not be suited to different mutations at other positions. Site-specific gene addition provides an ideal solution for long-term, stable gene therapy. We have demonstrated SaCas9-mediated homology-directed factor IX (FIX) in situ targeting for sustained treatment of hemophilia B. In this study, we tested a more efficient dual adeno-associated virus (AAV) strategy with lower vector dose for liver-directed genome editing that enables CRISPR-Cas9-mediated site-specific integration of therapeutic transgene within the albumin gene, and we aimed to develop a more universal gene-targeting approach. We successfully achieved coagulation function in newborn and adult hemophilia B mice by a single injection of dual AAV vectors. FIX levels in treated mice persisted even after a two-thirds partial hepatectomy, indicating stable gene integration. Our results suggest that this CRISPR-Cas9-mediated site-specific gene integration in hepatocytes could transform into a common clinical therapeutic method for hemophilia B and other genetic diseases.

This paper takes the support structure of a low-pressure rotor system of a marine gas turbine as the background.Considering the heel angle of the rotor system,a dynamic model of the rotor supported by asymmetric rolling bearing is established. The variable-step fourth-order Runge-Kutta method was used to solve the system’ s dynamic equations,and the nonlinear theory were used to analyze the simulation results. The study shows that the heel angle has no effect on the stability of the system at low rotational speeds. At high rotational speed,the heel angle mainly affects the 1/2 harmonic of the system,and the system has a single chaotic island or two chaotic islands. When the left or right tilt angle of the rotor system is the same,the heel angle has the same effect on the nonlinear dynamics of the system. The research results can provide a theoretical basis for the design,monitoring and fault diagnosis of the rotor system.

Reliability of safety instrumented systems (SISs) is a critical measure to ensure production safety of many industries. This paper focus on low-demand SISs. The reliability of these SISs is quantified by evaluating their probability of failure on demand (PFD). However, due to lack of knowledge, and/or vague judgments from experts, epistemic uncertainty associated with the parameters of components' degradation models is inevitable. Meanwhile, common cause failure (CCF) of two or more components caused by shared environments, often exists in SISs, reliability assessment for a SIS, therefore, becomes a challenging task. In this paper, fuzzy reliability assessment for SISs is conducted by taking account of the CCF among components of a SIS. The fuzzy Markov model is utilized to characterize the degradation process of components under fuzzy environment. The fuzzy state probability distribution of components is, then, calculated by formulating a set of constrained optimization models. Based on the fault tree of a SIS, the fuzzy PFD of the entire SIS with CCFs is formulated by using the $\beta $ -factor to quantify the CCFs. The fuzzy PFD at any $\alpha $ -cut level is, therefore, computed by a constrained optimization model. According to the optimization of parameters of SIS, the lower bound and upper bound of fuzzy PFD of SIS can be determined. Finally, we can quantify the effectiveness of CCF event for assessing the fuzzy PFD of SIS.

Hydropower, as a kind of clean energy, has the characteristics of rapid response to load changes, and is often used to undertake peak regulation and frequency regulation tasks. However, due to the uncertainties of reservoir inflow and runoff, the relative lag of power grid outgoing channels, and the interconnection of intermittent new energy, such as wind power and solar energy, the hydropower system is facing enormous peak regulation pressure and the continuous prominent problem of discarding water. In the study, aiming at the problem of risk control of discarding water in power generation process of hydropower station, a practical calculation method of risk of discarding water in power generation is proposed based on the analysis of frequency of runoff. Taking the Ertan hydropower station as an example, the corresponding water level processes of different discarding water risks under the control of pre-flood falling water level, flood limit water level and storage water level after flood season are deduced, and in the routine dispatching process, the water level operation control guidance corresponding to different discarding risk is introduced. The simulation results show that the proposed discarding water risk control method is practical and effective, and can provide guidance for discarding water risk control in the actual dispatching process of hydropower station.

Microglia exert diverse functions by responding in diverse ways to different stimuli, yet little is known about the plasticity of various phenotypes that microglia display. We used interferon (IFN)-γ, interleukin (IL)-4 and IL-10 to induce different phenotypes in mouse primary microglia. RNA sequencing was used to identify genes differentially expressed in response to stimulation, and the different stimulated populations were compared in terms of morphology, proliferative capacity, phagocytic ability and neurotoxicity. IFN-γ induced an “immunodefensive” phenotype characterizing both induction of filopodia and upregulation of inducible nitric oxide synthase (iNOS) and tumor necrosis factor α. Microglia with this phenotype mediated an acute inflammatory response accompanied by excellent proliferative capacity and neurotoxicity, and remained susceptible to remodeling for up to 48 h after initial stimulation. IL-4 induced an enduring “neuroimmunoregulatory” phenotype involving induction of lamellipodium and persistent upregulation of arginase (Arg)-1 and YM-1 expression. Microglia with this phenotype remained susceptible to remodeling for up to 24 h after initial stimulation. IL-10 induced an “immunosuppressive” phenotype involving induction of ameba-like morphology and upregulation of transforming growth factor β and IL-10 as well as inhibition of inflammation. This phenotype was accompanied by inhibition of self-proliferation, while its morphology, molecular properties and function were the least susceptible to remodeling. IFN-γ, IL-4, or IL-10 appear to induce substantially different phenotypes in microglia. The immunodefensive microglia induced by IFN-γ showed remarkable plasticity, which may help repair CNS inflammation damage under pathological condition. Chronic activation with IL-10 decreases microglial plasticity, which may help protect the brain form the immune response. Our research justifies and guides further studies into the molecular pathways that operate in each phenotype to help multitasking microglia regulate homeostasis in the brain.

As one core of the Guangdong–Hong Kong–Macao Greater Bay Area (GBA), Guangdong is facing some serious coastal environmental problems. Fungi are more vulnerable to changes in coastal environments than bacteria and archaea. This study investigated the fungal diversity and composition by high-throughput sequencing and detected basic parameters of seven environmental factors (temperature, dissolved oxygen, pH, salinity, total organic carbon, total nitrogen, and total phosphorus) at 11 sites. A total of 2056 fungal operational taxonomic units (OTUs) belonging to 147 genera in 6 phyla were recovered; Archaeorhizomyces (17.5%) and Aspergillus (14.19%) were the most dominant genera. Interestingly, a total of 14 genera represented the first reports of coastal fungi in this study. Furthermore, there were nine genera of fungi that were significantly correlated with environmental factors. FUNGuild analysis indicated that saprotrophs and pathogens were the two trophic types with the highest proportions. Saprotrophs were significantly correlated with total organic carbon (TOC), total nitrogen (TN), and total phosphorus (TP), while pathogens were significantly correlated with pH. This study provides new scientific data for the study of the diversity and composition of fungal communities in coastal ecosystems.

This paper presents a power-based analysis through 3D Reynolds-averaged Navier–Stokes simulations for a typical transonic transport aircraft resented by the DLR-F6 model. Two configurations were employed in CFD simulations. The original F6 model geometry was defined as the wing body configuration, and a wake-filling actuator disc was added to the F6 model to establish the BLI configuration. This study proposes a segregated 3D computational domain in RANS simulations to track the change in power terms in the flow field so that the power conversion process can be studied and visualized. For the wing body configuration, the power-based analysis illustrated the power conversion process, showing that about 35% of the total power input remains in the form of the mechanical power of aircraft wake at the outlet plane. For the BLI configuration, 22% of the total power input was left in the form of the mechanical power of downstream flow mixed with the wake and jet at the outlet plane. This study elaborates on the error of the mechanical power imbalance, showing that the convergence in aircraft drag does not necessarily lead to a small error in 3D RANS simulations. The high value of power imbalance error is associated with the wing.

With the completion of the Lianghekou Reservoir, with a multiyear regulation capacity, the operation relationship of the cascade reservoirs in the Yalong River is becoming increasingly complex. In order to study an optimal operation mode of the cascade reservoirs in the Yalong River under different inflow frequencies, based on the shortcomings of the existing single reservoir operation mode and the local joint operation mode of the cascade reservoirs, this paper first proposed a global joint operation mode for the cascade reservoirs to develop the power generation potential of daily regulating reservoirs and then gave a solution method for the cascade reservoirs’ operational model based on an improved stochastic fractal search (ISFS) algorithm. Finally, taking the maximum power generation as the goal and the inflow data of five typical years as the model inputs, this paper analyzed the differences in the power generation and water abandonment results of the cascade reservoirs in the middle and lower reaches of the Yalong River under the above three operation modes. The results show that (1) compared with the stochastic fractal search (SFS) algorithm and the particle swarm optimization (PSO) algorithm, the ISFS algorithm had faster convergence speed and higher precision; (2) the global joint operation mode had a more significant optimization effect in the year with more inflow, followed by the local joint operation mode, and the single reservoir operation mode had the worst; however, the difference in the results of the three operation modes gradually decreased as the inflows gradually decreased.

Reservoir optimal operation (ROO) needs to coordinate various profit-making objectives, which is a typical multiobjective optimization problem (MOP) with complex constraints. With the development of multiobjective evolutionary algorithms (MOEAs) in the past decades, more and more research has focused on MOEAs to solve MOP. Considering that multiobjective ROO is also a typical multi-stage Markov decision-making problem, this paper introduces the application of multiobjective dynamic programming (MODP) for multiobjective ROO in detail. On this basis, an improved MODP with selection mechanism of non-dominated solutions based on reference lines (MODP-BRL) is proposed to improve the convergence efficiency of MODP. The experimental results show that the proposed MODP-BRL is a reliable and effective tool in solving multiobjective ROO. In addition, MODP-BRL has better performance in convergence effect and efficiency in comparison experiments with NSGAII, NSGAIII, and SPEA2. It is noteworthy that MODP and MODP-BRL are very sensitive to the discrete step. With the decrease of the discrete step (the higher the discrete precision), the computing time increases nonlinearly. The appropriate discrete step of the state variable is key presets to balance the superiority and computational efficiency of non-dominated solutions with the application of MODP and MODP-BRL.

Obtaining optimal operation rules for cascade reservoirs is crucial for making the most of the comprehensive benefits of reservoirs. However, the operation of cascade reservoirs is generally complex, which involves with challenges including various decision variables, multiple conflicting objectives and constraints. In this paper, a new algorithm named multi-objective tangent algorithm (MOTA) is proposed for optimizing operation rules of cascade reservoirs with the objectives of hydropower generation, ecology and navigation. The performance of MOTA is firstly validated through several well-known benchmark problems. Then it is applied to a case study of cascade reservoirs optimization in China's Pearl River. Using observed inflow data (1956-2015) of cascade reservoirs, a uniform Pareto front is obtained eventually via MOTA after 1000 generations. The optimal operation rules fully considers the comprehensive benefits of hydropower generation, ecology and navigation in China's Pearl River. The optimal operation rules can be used as a guidance tool for decision makers, through the objectives' tradeoff without having to embed a priori preferences in the decision process. Finally, this paper use observed inflow data (2016) of cascade reservoirs for examining the operational rule to comprehend the analysis under different optimal operation rules. The obtained results show that MOTA can be a viable alternative for generating optimal operation rules for cascade reservoirs planning and management.

Human activities change the natural ecosystem and cause the decline of the intact ecosystem. Establishing an applicable and efficient human activity monitoring indicator system benefits China’s ambitious national park system construction. In this study, we established a refined technique for ecological intactness scores (EIS) and applied it in the area of Giant Panda National Park (GPNP) from 1980 to 2020 by quantifying four types of human interferences including land use and cover change (LUCC), road construction, water reservoir and hydropower construction, and mining. The results show the following: (1) Under the ecological intactness score range of 0–10, the GPNP with about 92.6% area of the EIS was above 6.0, and the mean baseline level of intactness was 7.1 when it was established in 2018. (2) The EIS in the east of Qionglaishan and south of Minshan were relatively lower than the rest of the study area. (3) During the past 40 years, 80% of the GPNP’s ecological intactness has remained stable. (4) In total, 14% of the GPNP was degraded mainly in the areas below 1200 m with severe human activities. (5) LUCC and road construction were the main driving factors for the decrease of ecological intactness in the GPNP. (6) The habitat of the giant panda is mainly distributed in the areas with an EIS above 6.0, and this is a key link between ecological intactness and habitat suitability. Our research proved that the ecological intactness score (EIS) is an effective indicator for monitoring and assessing the impact of human activities on the regional natural ecosystem and could be helpful for ecological restoration and human activities management GPNP in the future.