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The ensemble Kalman filter (EnKF) is one of the most widely used data assimilation methods. However, it exhibits limitations in handling non-Gaussian problems. To effectively address such issues and accurately describe the connectivity of aquifers, a novel approach named NS-ES-MDA is developed in this study. The proposed NS-ES-MDA synergistically combines the normal-score transformation (NST) with ensemble smoother with multiple data assimilation (ES-MDA). Through comparative experiments, the efficacy of NS-ES-MDA in estimating the hydraulic conductivity of non-Gaussian distributed aquifers is demonstrated. By assimilating the same dataset, NS-ES-MDA exhibits approximately 34% improvement in parameter estimation accuracy and about 35% enhancement in computational efficiency compared to the restart normal-score ensemble Kalman filter (rNS-EnKF). Furthermore, the NS-ES-MDA shows case robustness against the “equifinality” and displays remarkable updating capabilities, which leads to more precise parameter estimates. This study provides an effective solution for parameter estimation in non-Gaussian distributed aquifers.

Hypoxia in the mammary gland epithelial cells of milk buffalo (BMECs) can affect milk yield and composition, and it can even cause metabolic diseases. Nitidine chloride (NC) is a natural alkaloid with antioxidant properties that can scavenge excessive reactive oxygen species (ROS). However, the effect of NC on the hypoxic injury of BMECs and its molecular mechanisms are still unknown. Here, an immunofluorescence assay, transmission electron microscopy (TEM), and flow cytometry, combined with untargeted metabolomics, were used to investigate the protective effect of NC on hypoxic stress injury in BMECs. It was found that NC can significantly reduce cell activity (p < 0.05) and inhibit cellular oxidative stress (p < 0.05) and cell apoptosis (p < 0.05). A significant decrease in mitophagy mediated by the PINK1-Parkin pathway was observed after NC pretreatment (p < 0.05). In addition, a metabolic pathway enrichment analysis demonstrated that the mechanisms of NC against hypoxic stress may be related to the downregulation of pathways involving aminoacyl tRNA biosynthesis; arginine and proline metabolism; glycine, serine, and threonine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. Thus, NC has a protective effect on hypoxic mitochondria, and it can regulate amino acid metabolism in response to hypoxic stress. The present study provides a reference for the application of nitidine chloride to regulate the mammary lactation function of milk buffalo.

ABSTRACT Blast disease caused by Magnaporthe oryzae threatens rice production worldwide, and chemical control is one of the main methods of its management. The high mutation rate of the M. oryzae genome results in drug resistance, which calls for novel fungicide targets. Fungal proteins that function during the infection process might be potential candidates, and Mps1 (M. oryzae mitogen-activated protein kinase 1) is such a protein that plays a critical role in appressorium penetration of the plant cell wall. Here, we report the structure-aided identification of a small-molecule inhibitor of Mps1. High-throughput screening was performed with Mps1 against a DNA-encoded compound library, and one compound, named A378-0, with the best performance was selected for further verification. A378-0 exhibits a higher binding affinity than the kinase cosubstrate ATP and can inhibit the enzyme activity of Mps1. Cocrystallization of A378-0 with Mps1 revealed that A378-0 binds to the catalytic pocket of Mps1, while the three ring-type substructures of A378-0 constitute a triangle that squeezes into the pocket. In planta assays showed that A378-0 could inhibit both the appressorium penetration and invasive growth but not the appressorium development of M. oryzae, which is consistent with the biological function of Mps1. Furthermore, A378-0 exhibits binding and activity inhibition abilities against Mpk1, the Mps1 ortholog of the soilborne fungal pathogen Fusarium oxysporum. Collectively, these results show that Mps1 as well as its orthologs can be regarded as fungicide targets, and A378-0 might be used as a hit compound for the development of a broad-spectrum fungicide. IMPORTANCE M. oryzae is the causal agent of rice blast, one of the most devastating diseases of cultivated rice. Chemical control is still the main strategy for its management, and the identification of novel fungicide targets is indispensable for overcoming existing problems such as drug resistance and food safety. With a combination of structural, biochemical, and in planta assays, our research shows that Mps1 may serve as a fungicide target and confirms that compound A378-0 binds to Mps1 and possesses bioactivity in inhibiting M. oryzae virulence. As fungal orthologs of Mps1 are conserved, A378-0 may serve as a hit for broad-spectrum fungicide development, as evidenced with Mpk1, the Mps1 ortholog of F. oxysporum. Additionally, A378-0 contains a novel chemical scaffold that has not been reported in approved kinase inhibitors, suggesting its potential to be considered the basis for the development of other kinase inhibitors.

Abstract Background Endometriosis is a common and challenging disease in women of childbearing age with high personal and social costs. Many molecular differences between ectopic and eutopic endometrium present difficulties in the development of new drug therapies and therapies. Autophagy is a response to stress and has recently been studied in human cancers. Two important autophagy genes, Beclin-1 and LC3, have been reported in several human cancers. However, the reports of Beclin-1 and LC3 in endometriosis are limited and controversial. Methods In this study, we investigated the expression of Beclin-1 and LC3 by Immunohistochemistry. Results We found their downregulation in endometriosis. We also found these two autophagy gene expression are negatively correlated with the stage of endometriosis. Conclusions Decreased expression of Beclin-1 and LC3 may be related to the occurrence and development of endometriosis.

ABSTRACT: The study aimed to examine the effects of unfermented and fermented Andrographis paniculata on growth performance, carcass traits, immune function, and intestinal health in Muscovy ducks. A total of 450 (16-day-old) Muscovy ducks weighing 271.44 ± 8.25 g were randomly assigned to 5 dietary treatments (6 replicate pens of 15 ducks per treatment), consisting of one control treatment (basal diet without A. paniculata), one unfermented A. paniculata treatment (basal diet plus 30 g/kg unfermented A. paniculata) and 3 fermented A. paniculata treatments (basal diet plus 10, 30, and 50 g/kg). 30 g/kg unfermented A. paniculata increased the ADG, thymus index, peripheral blood lymphocyte conversion rate, villi height, intestinal thickness, villi surface area, intraepithelial lymphocytes rate, while decreased the FCR. 10 g/kg fermented A. paniculata markedly boosted ADG, bursa of fabricius index, thymus index, serum lysozyme, lymphocyte conversion rate, villi height, vilii width, intestinal thickness, villi surface area, while decreased the FCR. 30 g/kg fermented A. paniculata clearly improved ADG, bursa of fabricius index, thymus index, serum lysozyme, lymphocyte conversion rate, villi height, vilii width, intestinal thickness, villi surface area, intraepithelial lymphocytes, while decreased FCR. 50 g/kg fermented A. paniculata significantly increased villi height, vilii width, and villi surface area, while clearly reduced BW. Additionally, compared to 30 g/kg unfermented A. paniculata, 30 g/kg fermented A. paniculata obviously increased bursa of fabricius indices, lymphocyte conversion rate, vilii width, villi surface area. On top of that, supplementation with unfermented and fermented A. paniculata (30 g/kg each) decreased the relative abundance of harmful bacteria (Succinivibrio, Succinatimonas, Sphaerochaeta, and Mucispirillum) and increase the abundance of beneficial bacteria (Rikenellaceae, Methanocorpusculum, Fournierella, Ruminococcaceae) in the ceca of the ducks. However, fermented A. paniculata had considerable better effects than unfermented A. paniculate on all above measured indices. Overall, these results revealed that supplementation with unfermented and fermented A. paniculata across different treatments improved growth, immune status, intestinal morphology, and intestinal microbiota composition and structure in Muscovy ducks, making it a potential alternative to antibiotics in poultry production.

ABSTRACT: Earthworm has a variety of molecular biological characteristic, for example, growth promotion, antioxidant, and anti-bacteria. Thus, we decomposed earthworm by earthworm's own protease for preparing of earthworm hydrolysate. Muscovy ducks were fed with basal diet that formulated to contain 1.5% and 2.5% earthworm hydrolysate. Then, we investigated the influences of earthworm hydrolysate on growth performance in Muscovy ducks by performance terminology and measurement for poultry (NY/T 823-2020). The morphology of duodenum and number of intraepithelial lymphocytes were tested by HE staining and immunohistochemical method. Serum biochemical parameters and antioxidant capacity were also determined. High-throughput sequencing technology can sequence 16S rDNA of cecal contents from experimental Muscovy ducks. Results showed that 1.5% earthworm hydrolysate increased ADG (16–70 days old), ALB, HDL-C, T-AOC, CAT, SOD, GSH-PX, villi length, intestine thickness and surface area of villi (P < 0.05 or P < 0.01), and reduced FCR (16–70 days old), UREA, CRE, LDL-C, MDA (P < 0.05 or P < 0.01). Meanwhile, 2.5% improved ADG (16–70 days old), abdominal fat yield, breast muscle yield, heart index, spleen index, ALP, UA, T-AOC, CAT, SOD, GSH-PX, villi length, crypt depth, intestine thickness, surface area of villi, the percentage of intraepithelial lymphocytes (P < 0.05 or P < 0.01), and decreased FCR (42–70 days old and 16–70 days old), UREA, UA, MDA (P < 0.05 or P < 0.01). The sequencing results of gut flora demonstrated that earthworm hydrolysate improved variety of the gut flora in the V4 area of ducks immensely. In a word, our results provide the foundation for preliminary researching the potential principles of earthworm hydrolysate in promoting production performance, adjusting antioxidant function and intestinal functions in the Muscovy duck industry.

Dairy mastitis is an inflammatory reaction caused by mechanical injury and stress within the mammary gland, during which microbial changes and abnormal lipid metabolism occur. However, the underlying mechanism is still unclear. The present study used a combination of 16S rDNA sequencing technology and lipidomics techniques to reveal the effects of mastitis on lactic microbiota and metabolites in the milk of dairy cows. Twenty multiparous Holstein dairy cows (2–3 parities) with an average body weight of 580 ± 30 kg were selected for this study. The dairy cows were allocated to control group (4 cells /mL)) and mastitis group (>5 × 106 cells /mL) based on the somatic cell count. The results showed that mastitis caused a decrease trend in milk production (p = 0.058). The results of the 16 s sequencing indicated a significant decrease (p < 0.05) in the number of Proteobacteria, Tenericutes colonized in mastitis milk, and the number of Firmicutes, Bacteroidetes and Actinobacteria communities increased significantly (p < 0.05). The lipidomics results revealed that the changes in lipid content in mastitis milk were correlated with arachidonic acid metabolism, α -linolenic acid metabolism and glycerol phospholipid metabolism. The results showed that mastitis may cause abnormal lipid metabolism in milk by regulating the diversity of milk microflora, and ultimately affect the milk quality.

Hypoxia exposure can cause a series of physiological and biochemical reactions in the organism and cells. Our previous studies found the milk fat rate increased significantly in hypoxic dairy cows, however, its specific metabolic mechanism is unclear. In this experiment, we explored and verified the mechanism of hypoxia adaptation based on the apparent and omics results of animal experiments and in vitro cell model. The results revealed that hypoxia exposure was associated with the elevation of AGPAT2-mediated glycerophospholipid metabolism. These intracellular metabolic disorders consequently led to the lipid disorders associated with apoptosis. Our findings update the existing understanding of increased adaptability of dairy cows exposure to hypoxia at the metabolic level.

In high-altitude area, hypoxia is a serious stress for humans and other animals, disrupting oxygen homeostasis and thus affecting tissue metabolism. Up to now, there are few reports on the metabolic changes of dairy cows at different altitudes. In this experiment, metabonomics technology and blood biochemical indexes were used to study the metabolic changes of dairy cows in different altitudes. The results showed that the different metabolites were mainly enriched in amino acid metabolism and sphingolipid metabolism, and sphingolipid metabolism showed a negative correlation with increased altitude. The results of this study will enrich the hypoxia-adaptive mechanism of dairy cows in high-altitude areas and provide a theoretical basis for the nutritional regulation of performance and disease treatment of dairy cows in high-altitude areas.

Abstract Background Maternal undernutrition programs fetal energy homeostasis and increases the risk of metabolic disorders later in life. This study aimed to identify the signs of hepatic metabolic programming in utero and during the juvenile phase after intrauterine undernutrition during midgestation. Methods Fifty-three pregnant goats were assigned to the control (100% of the maintenance requirement) or restricted (60% of the maintenance requirement from day 45 to day 100 of midgestation and realimentation thereafter) group to compare hepatic energy metabolism in the fetuses (day 100 of gestation) and kids (postnatal day 90). Results Undernutrition increased the glucagon concentration and hepatic hexokinase activity, decreased the body weight, liver weight and hepatic expression of G6PC, G6PD, and PGC1α mRNAs, and tended to decrease the hepatic glycogen content and ACOX1 mRNA level in the dams. Maternal undernutrition decreased the growth hormone (GH) and triglyceride concentrations, tended to decrease the body weight and hepatic hexokinase activity, increased the hepatic PCK1, PCK2 and PRKAA2 mRNAs levels and glucose-6-phosphatase activity, and tended to increase the hepatic PRKAB1 and CPT1α mRNAs levels in the male fetuses. In the restricted female fetuses, the hepatic hexokinase activity and G6PC mRNA level tended to be increased, but PKB1 mRNA expression was decreased and the ACACA, CPT1α, NR1H3 and STK11 mRNA levels tended to be decreased. Maternal undernutrition changed the hepatic metabolic profile and affected the metabolic pathway involved in amino acid, glycerophospholipid, bile acid, purine, and saccharide metabolism in the fetuses, but not the kids. Additionally, maternal undernutrition increased the concentrations of GH and cortisol, elevated the hepatic glucose-6-phosphate dehydrogenase activity, and tended to decrease the hepatic glycogen content in the male kids. No alterations in these variables were observed in the female kids. Conclusions Maternal undernutrition affects the metabolic status in a sex- and stage-specific manner by changing the metabolic profile, expression of genes involved in glucose homeostasis and enzyme activities in the liver of the fetuses. The changes in the hormone levels in the male fetuses and kids, but not the female offspring, represent a potential sign of metabolic programming.

In this paper, taking desulphurizing ratio and economic cost as two objectives, a ten-input two-output prediction model was structured and validated for desulphurization system. Cerebellar model articulation controller (CMAC) neural network and genetic algorithm (GA) were used for model building and optimization of cost respectively. In the model building process, the grey relation entropy analysis and uniform design method were used to screen the input variables and study the model parameters separately. Traditional regression analysis and proposed location number analysis method were adopted to analyze output errors of experiment group and predict the results of test group. Results show that regression analyses keep high fit degree with experiment group results while the fitting accuracies for test group are quite different. As for location number analysis, a power function between output errors and location numbers was fitted well with the data of experiment group and test group for SO2. Prediction model was initialized by location number analysis method. Model was validated and cost optimization case was performed with GA subsequently. The result shows that the optimal cost obtained from GA could be reduced by more than 30% compared with original optimal operating parameters under same constraints.

The object of this study was to evaluate the effect of different sources and supplementation levels of yeast culture on in vitro fermentation characteristics of goats. The present study was performed in a 3×4 factorial design to examine the impacts of inclusion of three kinds of yeast culture (Se-enriched, Cr-enriched, Zn-enriched yeast culture) at four dose (0, 0.1%, 0.25%, 0.40% and 0.55%) on the in vitro fermentation characteristics of cereal straw. For maize stover, the results shown that the average values of in vitro gas production, DM and NDF disappearance, pH and the ratio of acetate to propionate were increased (P

Protein nutrition is particularly important for the self-renewal processes of gastrointestinal epithelial cells. The self-renewal of cells is inseparable from the interaction between apoptosis and autophagy. However, there are few reports on the relationship between different nitrogen sources and apoptosis/autophagy. In this study, the relative protein expression of Bcl-2-associated X protein(Bax), caspase-3, and p62 was significantly higher (p < 0.05), while that of Bcl-xl, Bcl-2, Beclin1, and Microtuble-associated protein light chain 3 (LC3-II) was significantly lower (p < 0.05), in the NH4Cl group in comparison with the NH4Cl + 4-phenylbutyric acid (4PBA) group. In addition, the relative protein expression of Bax and caspase-3 was significantly higher (p < 0.05), while that of Bcl-2 and Bcl-xl was decreased significantly (p < 0.05), in the NH4Cl + 3-Methyladenine (3-MA) group and the methionine (Met) + 3-MA group in comparison with the NH4Cl group. Furthermore, the relative protein expression of Beclin1 and LC3B-II was significantly lower (p < 0.05), while that of p62 was significantly higher (p < 0.05), in the NH4Cl + Z-VAD-FMK group and the Met + Z-VAD-FMK group in comparison with the NH4Cl group. In conclusion, our results suggested that endoplasmic reticulum (ER) stress played a critical role in the crosstalk between apoptosis and autophagy induced by NH4Cl and Met. Autophagy had a more obvious ameliorative effect on ruminal epithelial cell apoptosis after treatment with nonprotein nitrogen than after treatment with protein nitrogen. These findings may reveal the molecular mechanism of apoptosis and autophagy induced by nonprotein nitrogen and protein nitrogen.

This paper concentrates on the flight control of a novel tiltrotor aircraft with fixed wings. This kind of aircraft has two flight modes and a transition mode. In the phase of vertical take off and landing (VTOL), the aircraft can operate as a quadrotor helicopter. And in the phase of horizontal flight, the aircraft is in the normal airplane mode. The transition mode is between these two flight modes. In this part of work, a novel tiltrotor aircraft was presented since transition mode is achieved by tilting the front dual tiltrotor (DTR) and the mathematical model was established. The classical PID method was used during the phase of VTOL and the numerical results were given and the simulation shows good control effect. A nonlinear control law based on backstepping was proposed to achieve a stable transition from vertical flight to horizontal flight. And the numerical results show that the flight mode could transit stably which shows the effectiveness of the control approach. Finally, the vertical flight experiment has been carried out on DTR aircraft and the attitude was stable.

Changes in the environment such as high-altitude hypoxia (HAH) high-altitude hypoxia can lead to adaptive changes in the blood system of mammals. However, there is limited information about the adaptation of Holstein dairy cows introduced to high-altitude areas. This study used 12 multiparous Holstein dairy cows (600 ± 55 kg, average three years old) exposed to HAH conditions in Nyingchi of Tibet (altitude 3000 m) and HAH-free conditions in Shenyang (altitude 50 m). The miRNA microarray analysis and iTRAQ proteomics approach (accepted as more suitable for accurate and comprehensive prediction of miRNA targets) were applied to explore the differences in the plasma proteomic and miRNA profiles in Holstein dairy cows. A total of 70 differential miRNAs (54 up-regulated, Fold change (FC) FC > 2, and 16 down-regulated, FC < 0.5) and 226 differential proteins (132 up-regulated, FC > 1.2, and 94 down-regulated, FC < 0.8) were found in the HAH-stressed group compared with the HAH-free group. Integrative analysis of proteomic and miRNA profiles demonstrated the biological processes associated with differential proteins were the immune response, complement activation, protein activation, and lipid transport. The integrative analysis of canonical pathways were most prominently associated with the APR signaling (z = 1.604), and LXR/RXR activation (z = 0.365), and FXR/RXR activation (z = 0.446) pathways. The current results indicated that Holstein dairy cows exposed to HAH could adapt to high-altitude hypoxia by up-regulating the APR, activating the LXR/RXR and FXE/RXR pathways.

Nutritional status during mid-gestation is often ignored under extensive husbandry. This study aimed to examine the effect of maternal undernutrition during mid-gestation on kid meat production under an extensive system. Twenty-seven goats (45 ± 3 d of gestation) were randomly assigned to an unrestricted group (100% of nutrient requirements), or a restricted group (60% of nutrient requirements from 45 to 100 d of gestation, and then re-alimented to 100%). Among the offspring, 16 eligible kids (eight per treatment) were selected, based on birth type and survival, and were harvested to evaluate the meat yield, quality, and composition at 90 d after birth. Maternal undernutrition reduced the body weight and size, average daily gain and hot carcass weight of the kids (p < 0.05). The lightness of the meat at 45 min postmortem was increased (p = 0.029) in the restricted kids. Apart from an increase in tyrosine concentration (p = 0.046), the proximate composition and the amino acid and fatty acid profiles were unaffected in the restricted kids (p > 0.05). Overall, maternal undernutrition during mid-gestation decreased the yield of kid meat, but did not significantly modify the quality and composition. These results highlight the importance of nutrient status during mid-gestation in the meat production of small ruminants under an extensive regime.