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Scientific and accurate forecast of ecological environmental water consumption (EEWC) in the upper Yangtze River basin is of major prominence to the sustainable development of the basin and the formulation of eco-environmental protection policies. Firstly, a two parameter variable weight buffer operator is used to pre-processing the system shock behavior sequence. Then, an improved grey model IGM4 (λ, γ, tα) with four background values is established, introducing power exponential terms and linear correction terms to characterize data series with mixed linear and nonlinear relationships. The particle swarm optimization (PSO) algorithm is employed to find optimal parameters. Additionally, the model's effectiveness is evaluated by comparing the fitting values of models with other grey models. The final results demonstrate that the IGM4(λ, γ, tα) performs best with mean absolute percentage error only 0.0199%. Finally, model IGM4(λ, γ, tα) is utilized to predict the EEWC in the upper Yangtze River basin from 2023 to 2028. The reasonableness of the predicted results is analyzed, and related policy measures are put forward. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease, one of the most common forms of dementia, is characterized by a slow progression of cognitive impairment and neuronal loss. Currently, approved treatments for AD are hindered by various side effects and limited efficacy. Despite considerable research, practical treatments for AD have not been developed. Increasing evidence shows that glial cells, especially microglia and astrocytes, are essential in the initiation and progression of AD. During AD progression, activated resident microglia increases the ability of resting astrocytes to transform into reactive astrocytes, promoting neurodegeneration. Extensive clinical and molecular studies show the involvement of microglia and astrocyte-mediated neuroinflammation in AD pathology, indicating that microglia and astrocytes may be potential therapeutic targets for AD. This review will summarize the significant and recent advances of microglia and astrocytes in the pathogenesis of AD in three parts. First, we will review the typical pathological changes of AD and discuss microglia and astrocytes in terms of function and phenotypic changes. Second, we will describe microglia and astrocytes’ physiological and pathological role in AD. These roles include the inflammatory response, “eat me” and “don’t eat me” signals, Aβ seeding, propagation, clearance, synapse loss, synaptic pruning, remyelination, and demyelination. Last, we will review the pharmacological and non-pharmacological therapies targeting microglia and astrocytes in AD. We conclude that microglia and astrocytes are essential in the initiation and development of AD. Therefore, understanding the new role of microglia and astrocytes in AD progression is critical for future AD studies and clinical trials. Moreover, pharmacological, and non-pharmacological therapies targeting microglia and astrocytes, with specific studies investigating microglia and astrocyte-mediated neuronal damage and repair, may be a promising research direction for future studies regarding AD treatment and prevention. [ABSTRACT FROM AUTHOR]

Introduction: Exercise, health, and the gut microbiota (GM) are strongly correlated. Research indicates that professional athletes, especially ultramarathon runners, have unique GM characteristics. However, more research has focused on elite athletes, with little attention given to amateur sports enthusiasts, especially those in the middle-aged population. Therefore, this study focuses on the impact of long-term running on the composition and potential functions of the GM in middle-aged individuals. Methods: We compared the GM of 25 middle-aged serious runnerswith 22 sedentary healthy controls who had minimal exercise habitsusing 16S rRNA gene sequencing. Additionally, we assessed dietary habits using a food frequency questionnaire. Results and Discussion: Statistical analysis indicates that there is no significant difference in dietary patterns between the control group and serious runners. Diversity analysis results indicate that there is no significant difference in α diversity between the two groups of GM, but there is a significant difference in β diversity. Analysis of the composition of GM reveals that Ruminococcus and Coprococcus are significantly enriched in serious runners, whereas Bacteroides, Lachnoclostridium, and Lachnospira are enriched in the control group. Differential analysis of functional pathway prediction results reveals significant differences in the functional metabolism levels of GM between serious runners and the control group. Further correlation analysis results indicate that this difference may be closely related to variations in GM. In conclusion, our results suggest that long-term exercise can lead to changes in the composition of the GM. These changes have the potential to impact the overall health of the individual by influencing metabolic regulation. [ABSTRACT FROM AUTHOR]

Critical Assessment of Structure Prediction 15 (CASP15) added a new category of ligand prediction to promote the development of protein/RNA-ligand modeling methods, which have become important tools in modern drug discovery. A total of 22 targets were released, including 18 protein–ligand targets and 4 RNA-ligand targets. We applied our recently developed template-guided method to the protein– ligand complex structure predictions. The method combined a physicochemical, molecular docking method, and a bioinformatics-based ligand similarity method. The Protein Data Bank was scanned for template structures containing the target protein, homologous proteins, or proteins sharing a similar fold with the target protein. The binding modes of the co-bound ligands in the template structures were used to guide the complex structure prediction for the target. The CASP assessment results show that the overall performance of our method was ranked second when the top predicted model was considered for each target. Here, we analyzed our predictions in detail, and discussed the challenges including protein conformational changes, large and flexible ligands, and multiple diverse ligands in a binding pocket. [ABSTRACT FROM AUTHOR]

As China enters a new stage of high-quality ecological development, higher demands are placed on the ecological effects of coastal protection projects. Because the traditional hard seawall pays little attention to its impact on the coastal ecological environment, the construction of seawalls along the line cuts off the habitats inside and outside the pond, which makes the regional habitats fragmented, and hinders the migration of organisms. In order to restore and protect the coastal zone, build an ecological seawall, improve the seawall's ability to resist typhoon, storm surge, and other marine disasters, and protect the beach wetlands, water quality, and biodiversity along the seawall, this project started with the study of biological channels, and then systematically carried out the investigations, research, and analysis on the biological resources inside and outside the seawall and along the seawall. The results of research and field investigation showed that there were mainly natural plant communities such as Bolboschoenoplectus mariqueter and Phragmites australis on the beach of Jianshan section. The back slope of the pond was the soil slope with human afforestation as the main vegetation, and the foot of the slope was the protection pond river. Crab was the dominant species in beach and intertidal zone. Referring to the domestic and international biological channel cases, we proposed to set up 8 biological channels in the Jianshan section of the pond as a test section without affecting the structural safety of the seawall, and set up video monitoring equipment to evaluate the use of the channels and provided data support for future design or optimization of the channels. [ABSTRACT FROM AUTHOR]

With the expansion of software system scale, the study of software complexity has become a hot topic in software engineering. However, the domestic research on software complexity analysis technology is not mature, especially the measurement and evaluation methods of software complexity are not perfect. In order to solve the problem of prediction and evaluation of program structure complexity in software engineering more effectively, this paper proposed a program complexity measurement technique based on OINK framework. The technology uses the data sharing interface design to analysis target program by extracting the complex relationship between OINK components. On this basis, the technology adopts the layered software architecture to realize the automatic design of the function of the measurement data acquisition module, the complexity measurement module and the data management module of measurement results, thus, the structure complexity of the target program can be analyzed more clearly and accurately. At the same time, this technique applies multiple measurement methods to quantify the complexity of program structure, such as McCabe, HalStead, and Line Count. Experimental results show that this method can effectively measure the complexity of program structure. The solution on software complexity based on the open source ONIK framework will be open up worldwide, and will be continuously supported and improved by global communities and teams under the constraints of common driving forces. [ABSTRACT FROM AUTHOR]

Despite attempts to apply single therapy such as surgical treatment, chemotherapy, or radiotherapy, pancreatic cancer (PC) is still one of the most lethal solid tumors. Moreover, immune checkpoint inhibitors against PD-1/PD-L1, which have shown good efficacies against many other solid tumors, have not shown encouraging results in PC treatment. Therefore, some studies are evaluating the efficacies of combination therapies based on anti-PD-1/PD-L1 for PC. In this review, we summarized the emerging anti-PD-1/PD-L1 combination therapies for PC in these years. We realized that anti-PD-1/PD-L1-based combination therapies have the potential to be efficacious in PC treatment, and further relevant studies are needed. Moreover, we elucidated the reasons for the ineffectiveness of anti-PD-1/PD-L1 alone in PC treatment. We concluded that this was mainly because PC has an immunosuppressive tumor microenvironment and develops drug resistance during treatment. Anti-PD-1/PD-L1-based combination therapeutic regimens that alter the immunosuppressive tumor microenvironment and reduce the development of drug resistance in PC are summarized in this review, and we expect that these regimens will achieve good clinical application prospects. [ABSTRACT FROM AUTHOR]

Purpose: Host immunity influences the impact of cancer therapy but the effect of immune status in radioiodine (RAI)-treated differentiated thyroid cancer (DTC) remains obscure. Here we investigated indoleamine 2,3-dioxygenase (IDO) activity as a biomarker of response to RAI in patients with distant metastatic DTC (dmDTC). Methods: Patients with dmDTC receiving RAI were evaluated for serum IDO activity (kynurenine and kynurenine:tryptophan ratio) at baseline and 3 months after RAI. The optimal cut-off value for these biomarkers to predict response was established by receiver operating characteristic analysis. The relationship between disease outcomes, overall survival (OS) and progression-free survival (PFS), and IDO activity levels was studied. Results: Higher baseline kynurenine:tryptophan ratio (>2.46) was correlated with poorer RAI response as well as shorter median PFS (45 mo versus not reached, p=0.002) and OS (78 mo versus not reached, p=0.035). High baseline kynurenine:tryptophan ratio was also correlated with a reduced number of tumor-infiltrating lymphocytes. Higher post/prekynurenine ratio (>1.69) was associated with survival endpoints: shorter median PFS (48 mo versus not reached, p=0.002) and OS (68 mo versus not reached, p=0.010). Favorable baseline and favorable change corresponded with better PFS and OS. Conclusions: Our results suggest that RAI also alters IDO activity in dmDTC patients. IDO activity could predict progression and survival outcomes for advanced dmDTC patients. Serum IDO biomarker levels could be used to select dmDTC likely to benefit from RAI therapy, although further studies are necessary. [ABSTRACT FROM AUTHOR]

The identification of forest pests is of great significance to the prevention and control of the forest pests' scale. However, existing datasets mainly focus on common objects, which limits the application of deep learning techniques in specific fields (such as agriculture). In this paper, we collected images of forestry pests and constructed a dataset for forestry pest identification, called Forestry Pest Dataset. The Forestry Pest Dataset contains 31 categories of pests and their different forms. We conduct several mainstream object detection experiments on this dataset. The experimental results show that the dataset achieves good performance on various models. We hope that our Forestry Pest Dataset will help researchers in the field of pest control and pest detection in the future. [ABSTRACT FROM AUTHOR]

Funnel plots have been widely used to detect small-study effects in the results of univariate meta-analyses. However, there is no existing visualization tool that is the counterpart of the funnel plot in the multivariate setting. We propose a new visualization method, the galaxy plot, which can simultaneously present the effect sizes of bivariate outcomes and their standard errors in a 2-dimensional space. We illustrate the use of the galaxy plot with 2 case studies, including a meta-analysis of hypertension trials with studies from 1979–1991 (Hypertension. 2005;45(5):907–913) and a meta-analysis of structured telephone support or noninvasive telemonitoring with studies from 1966–2015 (Heart. 2017;103(4):255–257). The galaxy plot is an intuitive visualization tool that can aid in interpreting results of multivariate meta-analysis. It preserves all of the information presented by separate funnel plots for each outcome while elucidating more complex features that may only be revealed by examining the joint distribution of the bivariate outcomes. [ABSTRACT FROM AUTHOR]

Data from the Vaccine Adverse Event Reporting System (VAERS) contain spontaneously reported adverse events (AEs) from the public. It has been a major data source for detecting AEs and monitoring vaccine safety. As one major limitation of spontaneous surveillance systems, the VAERS reports by themselves sometimes do not provide enough information to answer certain research questions. For example, patient level demographics are very limited in VAERS due to the protection of patient privacy, such that investigation of differential AE rates across race/ethnicity groups cannot be conducted using VAERS data only. For many vaccines, racial and ethnical difference in immune responses has been found in studies based on racially diverse cohorts. It is of great interest to characterize the differential AE rates by race and ethnicity groups for vaccines. In this study, we propose a novel statistical method to integrate VAERS data with data from other resources for vaccine pharmacovigilance research. Specifically, we integrate VAERS data with CDC survey data of vaccine coverage and U.S. census data of race/ethnicity distribution to quantify differential AE rates by race/ethnicity groups for HPV vaccine. We utilize the difference of race/ethnicity distributions across U.S. states to investigate the association between AE reporting rate and race/ethnicity groups at the population level. We identify 9 AEs with significantly different reporting rates between non-Hispanic White females and other race/ethnicity groups. [ABSTRACT FROM AUTHOR]

The effects of high-intensity interval (HIIT) and moderate-intensity continuous training (MICT) on basal autophagy and mitochondrial function in cardiac and skeletal muscle and plasma metabolic phenotypes have not been clearly characterized. Here, we investigated how 10-weeks HIIT and MICT differentially modify basal autophagy and mitochondrial markers in cardiac and skeletal muscle and conducted an untargeted metabolomics study with proton nuclear magnetic resonance (1H NMR) spectroscopy and multivariate statistical analysis of plasma metabolic phenotypes. Male Sprague-Dawley rats were separated into three groups: sedentary control (SED), MICT, and HIIT. Rats underwent evaluation of exercise performance, including exercise tolerance and grip strength, and blood lactate levels were measured immediately after an incremental exercise test. Plasma samples were analyzed by 1H NMR. The expression of autophagy and mitochondrial markers and autophagic flux (LC3II/LC3-I ratio) in cardiac, rectus femoris, and soleus muscle were analyzed by western blotting. Time to exhaustion and grip strength increased significantly following HIIT compared with that in both SED and MICT groups. Compared with those in the SED group, blood lactate level, and the expression of SDH, COX-IV, and SIRT3 significantly increased in rectus femoris and soleus muscle of both HIIT and MICT groups. Meanwhile, SDH and COX-IV content of cardiac muscle and COX-IV and SIRT3 content of rectus femoris and soleus muscle increased significantly following HIIT compared with that following MICT. The expression of LC3-II, ATG-3, and Beclin-1 and LC3II/LC3-I ratio were significantly increased only in soleus and cardiac muscle following HIIT. These data indicate that HIIT was more effective for improving physical performance and facilitating cardiac and skeletal muscle adaptations that increase mitochondrial function and basal autophagic activities. Moreover, 1H NMR spectroscopy and multivariate statistical analysis identified 11 metabolites in plasma, among which fine significantly and similarly changed after both HIIT and MICT, while BCAAs isoleucine, leucine, and valine and glutamine were changed only after HIIT. Together, these data indicate distinct differences in specific metabolites and autophagy and mitochondrial markers following HIIT vs. MICT and highlight the value of metabolomic analysis in providing more detailed insight into the metabolic adaptations to exercise training. [ABSTRACT FROM AUTHOR]

Channa argus, a type of snakehead fish native to China, is a popular food fish in certain Asian countries but is a known destructive invasive species in the US. In this study, the two collagens, i.e. acid-soluble collagen (ASC) and pepsin-solubilized collagen (PSC), were obtained from C. argus skin. The yield of ASC was 28.0% and that of PSC was 16.8% on the dry bases. The collagens were identified as the collagen of type I by SDS-PAGE patterns. The Tds were approximately 27.0 °C. Similar ultraviolet spectra of both collagens were observed. Fourier Transform infrared spectra indicated PSC structure had a little change due to the loss of terminal domains by pepsin digestion. The results of XRD proved that the two collagens retained their helical structures. The results suggest that the collagens isolated from C. argus can potentially be alternative sources of vertebrate collagens for use in the food and other industries. [ABSTRACT FROM AUTHOR]

Objectives: This study proposes a novel Prior knowledge guided Integrated likelihood Estimation (PIE) method to correct bias in estimations of associations due to misclassification of electronic health record (EHR)-derived binary phenotypes, and evaluates the performance of the proposed method by comparing it to 2 methods in common practice.Methods: We conducted simulation studies and data analysis of real EHR-derived data on diabetes from Kaiser Permanente Washington to compare the estimation bias of associations using the proposed method, the method ignoring phenotyping errors, the maximum likelihood method with misspecified sensitivity and specificity, and the maximum likelihood method with correctly specified sensitivity and specificity (gold standard). The proposed method effectively leverages available information on phenotyping accuracy to construct a prior distribution for sensitivity and specificity, and incorporates this prior information through the integrated likelihood for bias reduction.Results: Our simulation studies and real data application demonstrated that the proposed method effectively reduces the estimation bias compared to the 2 current methods. It performed almost as well as the gold standard method when the prior had highest density around true sensitivity and specificity. The analysis of EHR data from Kaiser Permanente Washington showed that the estimated associations from PIE were very close to the estimates from the gold standard method and reduced bias by 60%-100% compared to the 2 commonly used methods in current practice for EHR data.Conclusions: This study demonstrates that the proposed method can effectively reduce estimation bias caused by imperfect phenotyping in EHR-derived data by incorporating prior information through integrated likelihood. [ABSTRACT FROM AUTHOR]

Background: The impact of ruptured hepatocellular carcinoma (HCC) on a patients outcome after hepatic resection remains insufficient. We aimed to identify the independent predictive factors of spontaneous tumor rupture (STR) for curative resection of HCC and to investigate the impact of STR of HCC on long-term survival after resection. Patients and methods: The clinicopathological parameters of 106 patients with ruptured HCC and 201 patients with non-ruptured HCC who underwent hepatic resection from 2007 to 2011 were investigated. Clinical features and factors associated with the clinical outcomes were compared between both groups. Results: Of 774 HCC patients who underwent surgical resection, 106 (13.7%) had tumor rupture. Multivariate stepwise logistic regression analysis revealed hypertension, liver cirrhosis, total bilirubin (TB), tumor size and ascites to be independent prognostic factors for patients with ruptured HCC. The overall survival (OS) of patients in the ruptured HCC group was significantly poorer compared with those in the non-ruptured HCC group. The 1-, 3- and 5-year OS rates were 77.7%, 56.9% and 41.6%, respectively, in the non-ruptured HCC group and 37.7%, 19.7%, 14.%, respectively, in the ruptured HCC group (P<0.001). Similar OS rates were found in patients with non-ruptured and ruptured HCC; patients in the non-ruptured HCC group had a significantly better recurrence-free survival (RFS) rate compared with those in the ruptured group (P=0.016). Conclusion: The presence of hypertension, liver cirrhosis, higher TB levels, tumor size >5 cm and ascites are the independent indicators of poorer prognosis for patients undergoing hepatic resection after ruptured HCC. The present study confirmed that tumor rupture itself had a negative impact on patient survival, but hepatic resection, when technically feasible, is safe and appropriate in selected patients and can result in OS and RFS rates comparable to that of patients with non-ruptured HCC. [ABSTRACT FROM AUTHOR]

This paper presents a technique for calculating tracks of striations observed in the plot of acoustic intensity versus range and frequency. The striations result from the interference in acoustic propagation below the critical depth. The key of this technique is modeling Lloyd’s-mirror interference fringes based on the ray-based description of the normal modes. Then, as the striations are interpreted as sampling fringes at different frequencies and ranges, a method to calculate their tracks is proposed based on the fringe model. Finally, experimental observations of striations are compared with results from the presented technique. [ABSTRACT FROM AUTHOR]

Inertial navigation system needs to be initialized through the alignment process, before the transition into the navigation stage can be made. In this article, a robust cascaded strategy of alignment which aims to provide an automatic operating alignment strategy for different application scenarios is proposed. The robust cascaded strategy of alignment utilizes the advantages of several alignment methods to form a cascaded alignment strategy. As a result, the robust cascaded strategy of alignment can be utilized in applications with different grade inertial measurement units under complex dynamic condition. In addition, several control measures are added into the robust cascaded strategy of alignment process to increase its robustness and to ensure that acceptable performance may be attained. A filed test using two inertial measurement units (tactical-grade FSAS and micro-electro-mechanical-system-grade SBG) shows that the proposed robust cascaded strategy of alignment can achieve alignment under various dynamic conditions, such as low speed motion, turns, stationary positions, and straight motion. The mean heading error and level angle error are 0.10° and -0.08° for the FSAS, respectively, and -0.44° and -0.02° for the SBG, respectively. The root mean square of the heading error and level angle error for the FSAS are 2.08° and 0.50°, respectively, while those for the SBG are 2.95° and 1.44°, respectively. [ABSTRACT FROM AUTHOR]

Carbonization of Radix Rehmanniae Preparata (Shu Dihuangtan) via stir-frying could increase its homeostasis maintaining and antidiarrheal effects. To ensure these pharmacological functions, the quality of the raw material (processed Rehmanniae Radix) must be well controlled. Therefore, we analyzed the effects of different degrees of processing and adjuvants on processed Rehmanniae Radix (Shu Dihuang) by High Performance Liquid Chromatography (HPLC) chromatographic fingerprints, thermal gravimetric analysis and Fourier transform infrared spectroscopy (FTIR). Based on the results from HPLC fingerprints combined with similarity analysis (SA) and hierarchical cluster analysis (HCA) the optimum processing method for Shu Dihuang was five cycles of steaming and polishing, which follows the ancient processing theory. The intensity of thermal weight loss rate peaked near 210.33 ± 4.32 °C or 211.33 ± 2.62 °C, which was an important indicator for the degree of processing of Shu Dihuang. A temperature near 290.89 ± 2.51 °C was the upper limit for carbonizing Shu Dihuangtan. FTIR spectroscopy analysis showed that the overall chemical composition of Shu Dihuangtan was affected by both the degree of processing and adjuvant, which are very important for its quality. [ABSTRACT FROM AUTHOR]

Fossil energy and water resources are both important for economic and social development in China, and they are tightly interlinked. Fossil energy production consumes large amounts of water, and it is essential to investigate the water footprint of fossil energy production (WFEP) in China. In addition, fossil energy is supplied to consumers in China by both domestic and foreign producers, and understanding the water footprint of fossil energy supply (WFES) is also highly significant for water and energy development programs in the long-term. The objectives of this paper were to provide an estimation of the blue component of WFEP and WFES in China for the period from 2001 to 2014, and to evaluate the impact on water resources from energy production, the contribution of internal and external WFES, and water-energy related issues of the international energy trade by applying water footprint analysis based on the bottom-up approach. The results indicate that generally, the WFEP and WFES in China both maintained steady growth before 2013, with the WFEP increasing from approximately 3900 million m³/year to 10,400 million m³/year, while the WFES grew from 3900 million m³/year to 11,600 million m³/year. The fossil energy production caps of the 13th Five Year Plan can bring the water consumed for fossil energy production back to a sustainable level. Over the long-term, China’s energy trade plan should also consider the water and energy resources of the countries from which fossil energy is imported. [ABSTRACT FROM AUTHOR]

This paper presents a joint estimation method of source range and depth using a bottom-deployed vertical line array (VLA). The method utilizes the information on the arrival angle of direct (D) path in space domain and the interference characteristic of D and surface-reflected (SR) paths in frequency domain. The former is related to a ray tracing technique to backpropagate the rays and produces an ambiguity surface of source range. The latter utilizes Lloyd's mirror principle to obtain an ambiguity surface of source depth. The acoustic transmission duct is the well-known reliable acoustic path (RAP). The ambiguity surface of the combined estimation is a dimensionless ad hoc function. Numerical efficiency and experimental verification show that the proposed method is a good candidate for initial coarse estimation of source position. [ABSTRACT FROM AUTHOR]

This paper presents an expression for the attenuation of sound energy in an ocean surface duct due to energy leakage outside the duct. Dominant parameters determining the attenuation are the sound frequency and the surface duct thickness. The attenuation is found to be exponentially dependent on a scaled frequency that combines the two parameters. Data from experiments in low-latitude oceans with three different surface duct thicknesses are used to verify the exponential expression derived for the attenuation. [ABSTRACT FROM AUTHOR]

This paper presents a method for estimating bottom geoacoustic properties especially the sediment attenuation from information contained in normal modes of a broadband signal. Propagating modes are resolved using the time-warping technique applied to signals from light bulb sound sources deployed at ranges of 5 and 7 km in the Shallow Water '06 experiment. A sequential inversion approach is designed that uses specific features of the acoustic data that are highly sensitive to specific geoacoustic model parameters. The first feature is the modal group speed, which is inverted for seabed sound speed, density, and sediment thickness. The second feature is the modal depth function for inverting receiver depths. The third feature is related to the modal coefficient spectra, and this is inverted for source depth and sediment attenuation. In each subsequent stage, estimates from the previous stage(s) are used as known values. The sequential inversion is stable and generates estimates for the geoacoustic model parameters that agree very well with results from other experiments carried out in the same region. Notably, the inversion obtains an estimated attenuation of 0.078 dB//? in the band 120-180 Hz for the de-watered marine sediment characteristic of the continental shelf at the site. [ABSTRACT FROM AUTHOR]

Metformin is a widely-used antidiabetic drug with hypoglycemic activity and previously described anti-inflammatory properties. Previous studies have demonstrated that metformin attenuates endotoxic hepatitis, however the mechanisms remain unclear. Inflammation and coagulation are closely associated pathological processes, therefore the potential effects of metformin on key steps in activation of the coagulation system were further investigated in endotoxic hepatitis induced by lipopolysaccharide/D-galactosamine (LPS/D-Gal). The current study demonstrated that treatment with metformin significantly suppressed the upregulation of tissue factor and plasminogen activator inhibitor-1 in LPS/D-Gal-exposed mice. In addition, a reduction in the expression of interleukin 6 and inhibition of nuclear translocation of nuclear factor-κB were observed. These data indicate that the LPS/D-Gal-induced elevation of the stable protein level of hypoxia inducible factor 1a, the mRNA level of erythropoietin, vascular endothelial growth factor and matrix metalloproteinase-3, and the hepatic level of lactic acid were also suppressed by metformin. The current study indicates that the suppressive effects of metformin on inflammation-induced coagulation may be an additional mechanism underlying the hepatoprotective effects of metformin in mice with LPS/D-Gal-induced fulminant hepatitis. [ABSTRACT FROM AUTHOR]

The localization of low-frequency coherent sources requires a proper aperture to ensure a high spatial resolution. Attaining a large aperture is difficult in practice when the conditions involved are limited. This letter investigated a compressive beamforming-based passive synthetic aperture approach with a reference sensor in a fixed position. Localization findings on acoustic sources in a semi-anechoic chamber were compared with conventional beamforming, compressive beamforming, passive synthetic aperture, and compressive beamforming-based passive synthetic aperture. Results suggest that the proposed method can produce a higher spatial resolution and higher detection ability than the others. [ABSTRACT FROM AUTHOR]

Localizing a source of radial movement at moderate range using a single hydrophone can be achieved in the reliable acoustic path by tracking the time delays between the direct and surface-reflected arrivals (D-SR time delays). The problem is defined as a joint estimation of the depth, initial range, and speed of the source, which are the state parameters for the extended Kalman filter (EKF). The D-SR time delays extracted from the autocorrelation functions are the measurements for the EKF. Experimental results using pseudorandom signals show that accurate localization results are achieved by offline iteration of the EKF. [ABSTRACT FROM AUTHOR]

A narrowband source at moderate range can be localised in a deep ocean using a near-surface vertical linear array without knowing the bottom properties. By casting the localisation as separate estimations of the source range and source depth, the performance is much better than that of the matched-field-processing (MFP) technique with the Bartlett processor. Source range estimation is based on the weighted subspace fitting technique with modification to consider the array tilt. Source depth estimation is based on the time delay of multipath arrivals. Experimental results using explosive sources are shown. The presented method shows a significant improvement in performance. [ABSTRACT FROM AUTHOR]

Background This work aimed to synthesize a cathepsin B (CTSB)-cleavable tumor-targeting prodrug peptide doxorubicin (PDOX) and study the in vivo efficacy and toxicities on an animal model of gastric peritoneal carcinomatosis (PC). Methods PDOX was synthesized using doxorubicin (DOX) attaching to a CTSB-cleavable dipeptide Ac-Phe-Lys and a para-amino-benzyloxycarbonyl (PABC) spacer. PC model was established by injecting VX2 tumor cells into the gastric sub-mucosa of 40 rabbits, which then were randomized into 4 groups: the Control (n = 10) without treatment, the HIPEC (n = 10) receiving cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the PDOX (n = 10) and the DOX (n = 10) receiving systemic chemotherapy with PDOX 50.0 mg/kg or DOX 5.0 mg/kg, respectively, after CRS + HIPEC. Results The median overall survivals (OS) were 23.0 d (95% CI: 19.9 d - 26.1 d) in the Control, 41.0 d (36.9 d - 45.1 d) in the HIPEC, 65.0 d (44.1 d - 71.9 d) in the PDOX, and 58.0 d (39.6 d - 54.4 d) in the DOX. Compared with the Control, the OS was extended by 70% in the HIPEC (p < 0.001) and further extended by 40% in the DOX (p = 0.029) and by 58% in the PDOX (p = 0.021), and the PC severity was decreased in the HIPEC and further decreased in the PDOX and DOX. Animals receiving DOX treatment showed hematological toxicities with marked reduction of white blood cells and platelets, as well as cardiac toxicities with significant increases in creatine kinase mb isoenzyme, evident myocardium coagulation necrosis, significant nuclear degeneration, peri-nucleus mitochondria deletion, mitochondria-pyknosis, and abnormal intercalated discs. But these toxicities were not evident in the PDOX. Conclusions PDOX is a newly synthesized tumor-targeting prodrug of DOX. Compared with DOX, PDOX has similar efficacy but reduced hematological and cardiac toxicities in treating rabbit model of gastric PC. [ABSTRACT FROM AUTHOR]