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Concrete face rockfill dams are widely used in hydropower engineering because of their many advantages. As important structures, if the performance of the concrete face slab and the impervious curtain is weakened, leakages and even serious dam failures can occur. Based on an equivalent quasi-continuum medium model, three-dimensional finite-element numerical simulations of the seepage behaviour of Miaojiaba dam, China, are performed. The seepage field and seepage characteristics, including the phreatic line, maximum hydraulic gradient and seepage discharge, are analysed quantitatively and systematically under various abnormal conditions. The results show that cracks in different areas of the face slab and different degrees of degradation in the impervious curtain influence the seepage field in different ways, with cracks in the lower face slab being the most serious. Ensuring that the face slab and impervious curtain are working as intended is very important for the integrity of the dam. Therefore, the design and construction quality of impervious structures should be strictly controlled. Under abnormal conditions, seepage control should be realised to ensure the safety and stability of concrete face rockfill dams.

Vascular calcification (VC) is characterized by pathological depositions of calcium and phosphate in the arteries and veins via an active cell-regulated process, in which vascular smooth muscle cells (VSMCs) transform into osteoblast/chondrocyte-like cells as in bone formation. VC is associated with significant morbidity and mortality in chronic kidney disease (CKD) and cardiovascular disease, but the underlying mechanisms remain unclear. In this study we investigated the role of large-conductance calcium-activated potassium (BK) channels in 3 experimental VC models. VC was induced in vascular smooth muscle cells (VSMCs) by β-glycerophosphate (β-GP), or in rats by subtotal nephrectomy, or in mice by high-dosage vitamin D3. We showed that the expression of BK channels in the artery of CKD rats with VC and in β-GP-treated VSMCs was significantly decreased, which was functionally confirmed by patch-clamp recording. In β-GP-treated VSMCs, BK channel opener NS1619 (20 μM) significantly alleviated VC by decreasing calcium content and alkaline phosphatase activity. Furthermore, NS1619 decreased mRNA expression of ostoegenic genes OCN and OPN, as well as Runx2 (a key transcription factor involved in preosteoblast to osteoblast differentiation), and increased the expression of α-SMA protein, whereas BK channel inhibitor paxilline (10 μM) caused the opposite effects. In primary cultured VSMCs from BK(−/−) mice, BK deficiency aggravated calcification as did BK channel inhibitor in normal VSMCs. Moreover, calcification was more severe in thoracic aorta rings of BK(−/−) mice than in those of wild-type littermates. Administration of BK channel activator BMS191011 (10 mg· kg(−1) ·d(−1)) in high-dosage vitamin D3-treated mice significantly ameliorated calcification. Finally, co-treatment with Akt inhibitor MK2206 (1 μM) or FoxO1 inhibitor AS1842856 (3 μM) in calcified VSMCs abrogated the effects of BK channel opener NS1619. Taken together, activation of BK channels ameliorates VC via Akt/FoxO1 signaling pathways. Strategies to activate BK channels and/or enhance BK channel expression may offer therapeutic avenues to control VC.

Fibrosis is a common pathological feature of organ diseases resulting from excessive production of extracellular matrix, which accounts for significant morbidity and mortality. However, there is currently no effective treatment targeting fibrogenesis. Recently, metabolic alterations are increasingly considered as essential factors underlying fibrogenesis, and especially research on metabolic regulation of amino acids is flourishing. Among them, branched-chain amino acids (BCAAs) are the most abundant essential amino acids, including leucine, isoleucine and valine, which play significant roles in the substance and energy metabolism and their regulation. Dysregulation of BCAAs metabolism has been proven to contribute to numerous diseases. In this review, we summarize the metabolic regulation of fibrosis and the changes in BCAAs metabolism secondary to fibrosis. We also review the effects and mechanisms of the BCAAs intervention, and its therapeutic targeting in hepatic, renal and cardiac fibrosis, with a focus on the fibrosis in liver and associated hepatocellular carcinoma.

The internal environment of the cow's udder directly affects the udder health and milk quality. 16S rDNA sequencing and liquid chromatography-mass spectrometry (LC-MS) methods were used to investigate the significant differences in milk microbial diversity and metabolites among cows that are healthy (H) and those suffering from subclinical mastitis (SM) and clinical mastitis (CM). Results uncovered more than 16 and 192 differently abundant microbiota at the phylum and genus levels, respectively, and 673 different levels of metabolites enriched in 20 pathways in milk among the 3 groups. This study revealed the positive relevance between Staphylococcus and Streptococcus and ceramide in milk from CM cows. Similarly, Acinetobacter and Corynebacterium were positively associated with testosterone glucuronide and 5-methyl-tetrahydrofolate, in milk from SM cows. On the basis of the combined analysis of microbiome and metabolome, this study indicated that, apart from the exogenous pathogens, some beneficial symbiotic bacteria, such as Dietzia, Aeromicrobium, Alistipes, and Sphingobacterium, rarely reported in milk have been found to be significantly reduced during mastitis.

Cut-off lows are crucial extratropical circulation systems that can bring weather extremes over large areas, but the mechanism responsible for the life cycle of cut-off lows remains elusive. From a perspective of regional eddy-mean flow interaction, this study investigates the dynamical processes controlling the evolution of early-summer cut-off lows over Northeast Asia using the 6-hourly reanalysis data. Through the diagnostic of local wave activity (LWA) budget, we show that the cut-off low is initialized by a Rossby wave train originated from the subpolar North Atlantic, and then reinforced rapidly by zonal LWA flux convergence and local baroclinic eddy generation, and eventually decayed through energy dispersion by zonal wave activity advection. Furthermore, we show that the evolutions of the above dynamical processes are strongly modulated by the changes of background flow. In early summer, Northeast Asia is located at the eastern exit of the midlatitude jet to the north of the subtropical jet and exhibits a weak meridional gradient of potential vorticity, which favors frequent formation of cyclonic anomaly and energy accumulation. Prior to the onset of cut-off lows by several days, a Rossby wave train propagates along the Eurasian midlatitude jet, which initializes a cyclonic anomaly over Northeast Asia. With the aid of mean flow advection of anomalous zonal momentum, the zonal winds are then decelerated at the midlatitude jet exit and accelerated at the subtropical jet center. The former obstructs the wave packet proceeding downstream and the latter favors stronger baroclinic eddy generation below the subtropical jet. The two processes together maintain and strengthen the cyclonic anomaly in Northeast Asia rapidly.

Due to the noncentered, self-organizing, and self-healing characteristics, mobile ad hoc networks (MANET) have been more and more widely used as an alternative access technology for regions having no fixed infrastructure. On-demand routing protocols (e.g., ad hoc on-demand distance vector (AODV)) are used to cope with the rapidly changing topology of MANET and reduce the network overhead. Taking delay, stability, and remaining energy of nodes into consideration, a fuzzy-logic-assisted AODV (FL-AODV) routing algorithm is proposed in this paper to further improve the reliability of the route in MANET. In the route discovery phase, the node with the highest reliability is selected as the relay node, and the route with the highest accumulated reliability is reserved for data transmission. Simulation results show that, compared with the traditional AODV protocol and the fuzzy logic routing algorithm (FLRA), the proposed routing protocol has higher reliability without increasing delay, i.e., better link connectivity and longer route life. The average routing reliability is about 18% higher than AODV while the average delay is the same low when the number of node greater than 70.

Kidney fibrosis is a common characteristic of chronic kidney disease and while the large conductance voltage and calcium-activated potassium channel (BK) is widely expressed in kidneys, its role in kidney fibrosis is unknown. To evaluate this, we found that BK protein expression was decreased in the fibrotic kidneys. Accompanying this was increased fibrotic marker protein expression of fibronectin, vimentin and α-smooth muscle actin and increased mRNA expressions of fibronectin, α-smooth muscle actin, collagen III and collagen I. These changes occurred in the unilateral ureteral obstruction and folic acid models of fibrosis and were more pronounced in BK knockout than in wild-type mice. Activation of BK activity by chemical NS1619 or BMS191011 channel openers attenuated kidney fibrosis in these two models while protecting kidney function in wild-type mice. BK deficiency up-regulated transforming growth factor-β (TGF-β)/transcription factor Smad2/3 signaling in the fibrotic kidney, whereas activation of BK activity inhibited this signaling pathway both in vivo and in vitro. BK channel activation increased the degradation of TGF-β receptors induced by TGF-β1 in vivo and in vitro. Furthermore, in cell lines HK-2, NRK49, and NRK-52E, BK channel activation by NS1619 led to increased caveolae formation and facilitated localization of TGF-β receptors in the microdomains of lipid rafts. Thus, our data demonstrated that BK activation has an anti-fibrotic effect on kidney fibrosis by inhibiting the TGF-β signaling pathway through accelerating TGF-β receptor degradation via the caveolae route. Hence, our study provides innovative insight into BK as a potential therapeutic target for the treatment of kidney fibrosis.

Understanding the formation and evolution mechanisms of Ural blocking (UB) is of great importance for the prediction of UB and relevant extremes in east Asia. Using the 6-hourly ERA-Interim reanalysis data, this study quantifies the conservative and nonconservative processes in the lifecycle of UB through the lens of the hybrid Eulerian-Lagrangian local finite-amplitude wave activity (LWA) diagnostics. It is found that (i) as a wave activity source, eddy heat flux works to not only initiate the UB, but also prevent the wave activity of the blocking from dispersing downstream---the key characteristic of blocking; (ii) both the wave propagation and wave advection mechanisms are indispensable for the evolution of UB, playing a tug-of-war on the downstream development of wave activity; (iii) throughout the lifespan of UB, diabatic heating provides the most important damping mechanism for the wave activity both upstream and downstream.

As seawater pumped storage systems (S-PSSs) have attracted more global attention, the leakage of basins from upper reservoirs has been noted. The study of reservoir basin leakage is very important because this issue not only affects vegetation in shallow areas but also negatively affects the safety of the ecosystem and the engineering stability of the reservoir when seepage into groundwater occurs. This research aims to study seawater ion (chloride ion (Cl-) and total dissolved solid (TDS)) transport and movement laws in the Okinawa S-PSS reservoir basin and its engineering-derived seepage stability under different reservoir basin anti-seepage schemes. This study shows an anti-seepage scheme that effectively reduces leakage, lowers the infiltration line, and reduces the influence range of seawater ion migration. Under the anti-seepage scheme, the influence of range of seawater ion pollution is reduced by approximately 90%, and the safety factor is increased by 84%. Compared to reinforced concrete faces (RCFs), asphalt concrete faces (ACFs) are more suitable for engineering applications. This article verifies that the ethylene-propylene-diene monomer (EPDM) scheme for the upper reservoir almost entirely prevents leakage in the Okinawa S-PSS and provides relevant experience for the vast development of S-PSSs across China and the world.

Additional file 1 Table S1 TMR Ingredient and nutrient component (% of DM). Table S2 Criteria to judge California mastitis test (CMT) results. Table S3 Basic information and grouping of experimental cows. Table S4 Rumen microbial composition and relative abundances of cows with different udder health states (phylum level). Table S5 Rumen microbial composition and relative abundances of cows with different udder health states (genus level). Table S6 Differentially abundant KEGG function abundance among health, subclinical and clinical mastitis groups at level 2. Table S7 Differentially abundant KEGG function abundance among health, subclinical and clinical mastitis groups at level 3. Table S8 Correlation analysis between the differentially abundant bacteria and parameters of rumen fermentation as well as lactation performance. Table S9 Significantly different metabolites between rumen fluid samples from healthy and clinical mastitis cows, udder positive ion mode. Table S10 Significantly different metabolites between rumen fluid samples from healthy and clinical mastitis cows, udder negative ion mode. Table S11 Significantly different metabolites between rumen fluid samples from healthy and subclinical mastitis cows, udder positive ion mode. Table S12 Significantly different metabolites between rumen fluid samples from healthy and subclinical mastitis cows, udder negative ion mode. Table S13 Significantly different metabolites between rumen fluid samples from subclinical and clinical mastitis, udder positive ion mode. Table S14 Significantly different metabolites between rumen fluid samples from subclinical and clinical mastitis cows, udder negative ion mode. Table S15 Correlation analysis of differential metabolites and index of lactation and rumen fermentation. Table S16 Correlation analysis of differential bacteria genus and differential metabolites in rumen samples.

Additional file 2 Fig. S1 Pan-Species curve of OTU number in the cows with different udder health status. Pan species was the sum of all the species in a sample, which was used to observe the increase in the total number of species as the number of samples increases. H, healthy; SM, subclinical mastitis; CM, clinical mastitis. Fig. S2 Rarefaction curve of OUT number in the cows with different udder health status. H, healthy; SM, subclinical mastiti; CM, clinical mastitis. Fig. S3 Rumen microbial community composition analysis. a At phylum level. b At genus level. H, healthy; SM, subclinical mastitis; CM, clinical mastitis. Fig.S4 Hierarchical cluster analysis (HCA) of rumen bacteria at genus level. Each row in the figure represents a sample, each column represents a genus, and the color indicates the relative abundance of bacteria measured in the group. Red indicates the high relative abundance, and the green indicates low relative abundance. H, healthy; SM, subclinical mastitis; CM, clinical mastitis. Fig. S5 Linear discriminant analysis effect size (LEfse) analysis of multilevel species differences in ruminal microbiota. a Cladogram; b LEfSe Bar graph. H, healthy; SM, subclinical mastitis; CM, clinical mastitis; LDA, linear discriminant analysis. Fig. S6 The total ion chromatograms (TIC) plot of quality control (QC) samples in a positive ion mode and b negative ion mode. Fig. S7 Orthogonal partial least squares discriminant analysis (OPLS-DA) (a, c, e) and response permutation testing (RPT) (b, d, f) of rumen metabolites between H, SM and CM groups in positive ion mode. H, healthy; SM, subclinical mastitis; CM, clinical mastitis. R2X and R2Y represent the interpretation rate of the built model to the X and Y matrix, R2X (cum) and R2Y (cum) represent the cumulative interpretation rate; Q2 indicates the predictive power of the model. Fig. S8 Orthogonal partial least squares discriminant analysis (OPLS-DA) (a, c, e) and response permutation testing (RPT) (b, d, f) plots of rumen metabolites between H, SM and CM groups in negative ion mode. H, healthy; SM, subclinical mastitis; CM, clinical mastitis. R2X and R2Y represent the interpretation rate of the built model to the X and Y matrix, R2X (cum) and R2Y (cum) represent the cumulative interpretation rate; Q2 indicates the predictive power of the model. Fig. S9 HMDB compound classification (Superclass level) of significantly differential metabolites between a CM and H groups, b SM and H groups and c CM and SM groups. HMDB, Human Metabolome Database; H, healthy; SM, subclinical mastitis; CM, clinical mastitis.

Background Due to the high prevalence and complex etiology, bovine mastitis (BM) is one of the most important diseases to compromise dairy cow health and milk quality. The shift in milk compositions has been widely investigated during mastitis, but recent studies suggested that gastrointestinal microorganism also has a crucial effect on the inflammation of other peripheral tissues and organs, including the mammary gland. However, research focused on the variation of rumen inner-environment during mastitis is still limited. Therefore, the ruminal microbial profiles, metabolites, and milk compositions in cows with different udder health conditions were compared in the present study. Furthermore, the correlations between udder health status and ruminal conditions were investigated. Based on the somatic cell counts (SCC), California mastitis test (CMT) parameters and clinical symptoms of mastitis, 60 lactating Holstein dairy cows with similar body conditions (excepted for the udder health condition) were randomly divided into 3 groups (n = 20 per group) including the healthy (H) group, the subclinical mastitis (SM) group and the clinical mastitis (CM) group. Lactation performance and rumen fermentation parameters were recorded. And rumen microbiota and metabolites were also analyzed via 16S rRNA amplicon sequencing and untargeted metabolomics, respectively. Results As the degree of mastitis increased, rumen lactic acid (LA) (P P P P = 0.039), Moraxella (FDR-adjusted P = 0.011) and Neisseriaceae (FDR-adjusted P = 0.036), etc., were accompanied by a significant increase in 12-oxo-20-dihydroxy-leukotriene B4 (FDR-adjusted P = 5.97 × 10− 9) and 10beta-hydroxy-6beta-isobutyrylfuranoeremophilane (FDR-adjusted P = 3.88 × 10− 10). Meanwhile, in the rumen of SM cows, the Ruminiclostridium_9 (FDR-adjusted P = 0.042) and Enterorhabdus (FDR-adjusted P = 0.043) were increased along with increasing methenamine (FDR-adjusted P = 6.95 × 10− 6), 5-hydroxymethyl-2-furancarboxaldehyde (5-HMF) (FDR-adjusted P = 2.02 × 10− 6) and 6-methoxymellein (FDR-adjusted P = 2.57 × 10− 5). The short-chain fatty acids (SCFAs)-producing bacteria and probiotics in rumen, including Prevoterotoella_1 (FDR-adjusted P = 0.045) and Bifidobacterium (FDR-adjusted P = 0.035), etc., were significantly reduced, with decreasing 2-phenylbutyric acid (2-PBA) (FDR-adjusted P = 4.37 × 10− 6). Conclusion The results indicated that there was a significant shift in the ruminal microflora and metabolites associated with inflammation and immune responses during CM. Moreover, in the rumen of cows affected by SM, the relative abundance of several opportunistic pathogens and the level of metabolites which could produce antibacterial compounds or had a competitive inhibitory effect were all increased.

The traditional infrared dim and small target detection algorithm is generally implemented by DSP (Digital Signal Processing) processor, which is complex and has poor real-time performance. In this paper, a FAST (Features from Accelerated Segment Test) algorithm of adaptive threshold based on FPGA (Field Programmable Gate Array) is proposed to detect infrared dim and small target. Based on the characteristics of FPGA parallel processing, the hardware acceleration of algorithm is realized by pipeline design. The improved adaptive threshold method can generate appropriate thresholds according to different environments, and avoid the loss or redundancy of dim and small infrared targets due to improper threshold selection. At last, two different groups of infrared images are used for experiment, the results show that the algorithm can detect the dim and small targets in the infrared image in real time, and can achieve high detection rate and low false alarm rate, which meets the requirements of real-time and effectiveness.