A nomogram clinical prediction model for predicting urinary infection stones: development and validation in a retrospective study.

PURPOSE: This study aimed to develop a nomogram prediction model to predict the exact probability of urinary infection stones before surgery in order to better deal with the clinical problems caused by infection stones and take effective treatment measures. METHODS: We retrospectively collected the clinical data of 390 patients who were diagnosed with urinary calculi by imaging examination and underwent postoperative stone analysis between August 2018 and August 2023. The patients were randomly divided into training group (n = 312) and validation group (n = 78) using the "caret" R package. The clinical data of the patients were evaluated. Univariate and multivariate logistic regression analysis were used to screen out the independent influencing factors and construct a nomogram prediction model. The receiver operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA) and clinical impact curves were used to evaluate the discrimination, accuracy, and clinical application efficacy of the prediction model. RESULTS: Gender, recurrence stones, blood uric acid value, urine pH, and urine bacterial culture (P < 0.05) were independent predictors of infection stones, and a nomogram prediction model ( https://zhaoyshenjh.shinyapps.io/DynNomInfectionStone/ ) was constructed using these five parameters. The area under the ROC curve of the training group was 0.901, 95% confidence interval (CI) (0.865-0.936), and the area under the ROC curve of the validation group was 0.960, 95% CI (0.921-0.998). The results of the calibration curve for the training group showed a mean absolute error of 0.015 and the Hosmer-Lemeshow test P > 0.05. DCA and clinical impact curves showed that when the threshold probability value of the model was between 0.01 and 0.85, it had the maximum net clinical benefit. CONCLUSIONS: The nomogram developed in this study has good clinical predictive value and clinical application efficiency can help with risk assessment and decision-making for infection stones in diagnosing and treating urolithiasis.

Exploration of Imaging Genetic Biomarkers of Alzheimer's Disease Based on a Machine Learning Method.

BACKGROUND: Alzheimer's disease (AD) is an irreversible primary brain disease with insidious onset. The rise of imaging genetics research has led numerous researchers to examine the complex association between genes and brain phenotypes from the perspective of computational biology. METHODS: Given that most previous studies have assumed that imaging data and genetic data are linearly related and are therefore unable to explore their nonlinear relationship, our study applied a joint depth semi-supervised nonnegative matrix decomposition (JDSNMF) algorithm to solve this problem. The JDSNMF algorithm jointly decomposed multimodal imaging genetics data into both a standard basis matrix and multiple feature matrices. During the decomposition process, the coefficient matrix A multilayer nonlinear transformation was performed using a neural network to capture nonlinear features. RESULTS: The results using a real dataset demonstrated that the algorithm can fully exploit the association between strongly correlated image genetics data and effectively detect biomarkers of AD. Our results might provide a reference for identifying biologically significant imaging genetic correlations, and help to elucidate disease-related mechanisms. CONCLUSIONS: The diagnostic model constructed by the top features of the three modality data sets mined by the algorithm has high accuracy, and these features are expected to become new therapeutic targets for AD.

Coherent high-spectral-resolution lidar for the measurement of the atmospheric Mie-Rayleigh-Brillouin backscatter spectrum.

In this study, a 1550 nm coherent high-spectral-resolution lidar (CHSRL) is developed to measure the optical properties of aerosols and atmospheric wind profiles in the atmospheric boundary layer. To determine the optical properties, a coherent frequency discriminator based on the fast Fourier transform is designed in the CHSRL to separate the Mie and the Rayleigh-Brillouin backscatter spectra to fulfill the needs of high-spectral measurements. The atmospheric wind velocity is retrieved using the simultaneously measured Doppler shift. This non-optical frequency discriminator is a feasible and low-cost solution compared to a narrow-bandwidth optical filter, such as a Fabry-Perot interferometer or an atomic filter. However, shot, amplifier spontaneous emission, and detector noise interfere with the Rayleigh-Brillouin spectrum. Therefore, a spectrum correction algorithm is proposed to recover the interfered Rayleigh-Brillouin spectrum, and the measurement results of the spectral line agree well with those modeled with Tenti S6 at different central frequencies. Finally, field observations for comparison are conducted with the co-located CHSRL, Raman lidar, and coherent Doppler wind lidar. The comparison results indicate that the correlation coefficient of the aerosol backscatter coefficient is 0.84. The correlation coefficient and standard deviation of wind velocity are 0.98 and 0.13 m · s-1, respectively.

Antipeptide Immunocapture with In-Sample Calibration Curve Strategy for Sensitive and Robust LC-MS/MS Bioanalysis of Clinical Protein Biomarkers in Formalin-Fixed Paraffin-Embedded Tumor Tissues.

Despite huge promises, bioanalysis of protein biomarkers in formalin-fixed paraffin-embedded (FFPE) tissues by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for clinical applications is still very challenging. Here, we describe a sensitive and robust LC-MS/MS assay to quantify clinical protein biomarkers in FFPE tumor sections using automated antipeptide antibody immunocapture followed by in-sample calibration curve (ISCC) strategy with multiple isotopologue reaction monitoring (MIRM) technique. ISCC approach with MIRM of stable isotopically labeled (SIL) peptides eliminated the need for authentic matrices for external calibration curves, overcame the matrix effects, and validated the quantification range in each individual sample. Specifically, after deparaffinization, rehydration, antigen retrieval, and homogenization, the protein analytes in FFPE tumor tissues were spiked with a known concentration of one SIL peptide for each analyte, followed by trypsin digestion and antipeptide immunocapture enrichment prior to MIRM-ISCC-based LC-MS/MS analysis. This approach has been successfully used for sensitive quantification of programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) in 15 representative FFPE tumor samples from lung, colorectal, and head and neck cancer patients. Except for one sample, PD-L1 and PD-1 in all samples were quantifiable using this assay with concentrations of 27.85-798.43 (amol/µg protein) for PD-L1 and 16.96-129.89 (amol/µg protein) for PD-1. These results were generally in agreement with the immunohistochemistry (IHC) data but with some exceptions. This approach demonstrated the feasibility to quantify low abundant protein biomarkers in FFPE tissues with improved sensitivity, specificity, and robustness and showed great potential as an orthogonal analytical approach to IHC for clinical applications.

Cirrhotic stiffness affects the migration of hepatocellular carcinoma cells and induces sorafenib resistance through YAP.

A majority of hepatocellular carcinomas (HCCs) combine with liver cirrhosis. The cirrhotic liver has been implicated in interfering with the effects of HCC-targeted drugs, including sorafenib. Alterations in the tumor microenvironment of the cirrhotic liver include both biochemical and biomechanical factors. In this study, we induced sorafenib resistance in HCC cells. We observed changes in cell morphology, cytoskeletal architecture, and cellular stiffness in these sorafenib-resistant cells, resembling those adapted to stiffer substrates. To examine the contribution of mechanical factors in HCC cell growth and drug resistance, we used an in vitro cell culture system with adjustable stiffness mimicking the normal or cirrhotic liver tissues. We identified that mechanical adaptation conferred HCC cells with increased motility and sorafenib resistance. We further reported the mechanism underlying the involvement of the transcription coactivator YAP. Our results underline the important role of mechanical factors in the interaction between tumor cells and their microenvironment.

Superoxide via Sp3 mechanism increases renal renin activity, renal AT1 receptor function, and blood pressure in rats.

We tested a hypothesis that superoxide, by inducing Sp3, increases renal renin activity, renal angiotensin II type 1 receptor (AT1R) function, and blood pressure (BP) in rats. Group 1 rats were treated with vehicle, saline. Group 2 rats were treated with superoxide dismutase (SOD) inhibitor diethylthiocarbamate (DETC). Group 3 rats were treated with DETC and an SOD mimetic, tempol. Group 4 rats were treated with tempol only. All four groups of rats were treated for 2 wk then anesthetized, and BP was recorded. Thereafter, diuresis and natriuresis in response to AT1R blocker candesartan were determined. When compared with vehicle rats, BP increased in DETC rats. The increased BP in DETC rats decreased with tempol. Diuresis and natriuresis in response to candesartan increased in controls, and this further increased in DETC rats and decreased with tempol. A second set of four groups of rats underwent the same treatment as above and were anesthetized, and their kidneys were obtained for biochemical studies. The levels of superoxide but not hydrogen peroxide increased, whereas SOD activities decreased further in the renal cortical tissues of DETC rats than vehicle rats. These effects were attenuated with tempol in DETC rats. Moreover, tissue renin activity and abundance of membranous AT1R proteins increased more in DETC rats than vehicle rats, and decreased with tempol in DETC rats. Furthermore, the levels of lysine-acetylated, but not serine-phosphorylated, Sp3 increased more in the nuclei of DETC rats than vehicle rats. The increased levels of Sp3 lysine acetylation decreased in DETC rats with tempol. Taken together, our results suggest that superoxide activates renal Sp3 via lysine acetylation increasing renin activity, AT1R function, and BP in rats.

Protein disulfide isomerase regulates renal AT1 receptor function and blood pressure in rats.

The role and mechanism of renal protein disulfide isomerase (PDI) in blood pressure regulation has not been tested before. Here, we test this possibility in Sprague-Dawley rats. Rats were treated with PDI inhibitor bacitracin (100 mg·kg-1 ip·day-1 for 14 days), and then blood pressure and renal angiotensin II type 1 (AT1) receptor function were determined in anesthetized rats. Renal AT1 receptor function was determined as the ability of candesartan (an AT1 receptor blocker) to increase diuresis and natriuresis. A second set of vehicle- and bacitracin-treated rats was used to determine biochemical parameters. Systolic blood pressure as well as diastolic blood pressure increased in bacitracin-treated compared with vehicle-treated rats. Compared with vehicle, bacitracin-treated rats showed increased diuresis and natriuresis in response to candesartan (10-µg iv bolus dose) suggesting higher AT1 receptor function in these rats. These were associated with higher renin activities in the plasma and renal tissues. Furthermore, urinary 8-isoprostane and kidney injury molecule-1 levels were higher and urinary antioxidant capacity was lower in bacitracin-treated rats. Renal protein carbonyl and nitrotyrosine levels also were higher in bacitracin- compared with vehicle-treated rats, suggesting oxidative stress burden in bacitracin-treated rats. Moreover, PDI activity decreased and its protein levels increased in renal tissues of bacitracin-treated rats. Also, nuclear levels of Nrf2 transcription factor, which regulates redox homeostasis, were decreased in bacitracin-treated rats. Furthermore, tissue levels of Keap1, an Nrf2 inhibitory molecule, and tyrosine 216-phosphorylated GSK3ß protein, an Nrf2 nuclear export protein, were increased in bacitracin-treated rats. These results suggest that renal PDI by regulating Keap1-Nrf2 pathway acts as an antioxidant, maintaining redox balance, renal AT1 receptor function, and blood pressure in rats.

CXCR4/Let-7a Axis Regulates Metastasis and Chemoresistance of Pancreatic Cancer Cells Through Targeting HMGA2.

BACKGROUND/AIMS: Pancreatic cancer cells (PCC) is one of the most risky cancers and gemcitabine (GEM) is the standard first-line drug for treating PCC. The PCC will develop drug resistance to GEM after a period of treatment. However, the detailed molecular mechanism of pathogenesis and drug resistance remains unresolved. METHODS: we employed qRT-PCR and western blot to examine the expression level of CXCR4, let-7a and HMGA2. In addition, we used MTT assay to detect cell proliferation and transwell assay to measure migration and invasiveness. The expression level of epithelial marker E-cadherin and mesenthymal marker N-cadherin was detected by western blot. The apoptosis was determined using annexin V-FITC/PI apoptosis detection kit by flow cytometry. RESULTS: we first proved that CXCR4 negatively regulated let-7a in PCC. Next, let-7a was confirmed to play crucial role in tumorigenesis, metastasis and drug resistance of pancreatic cancer cells Bxpc-3 and Panc-1 in vitro and in vivo. Finally, we identified HMGA2 as important downsteam target of let-7a in PCC and overexpression of HMGA2 restores cell proliferation, metastasis and chemosensitivity of GEM inhibited by let-7a. Conlusion: Taken together, we show an important signaling pathway involved in pathogenesis and drug resistance of PCC, thereby providing deeper insight into molecular mechanism by which CXCR4/let-7a regulates tumorigenesis and drug resistance of PCC. These findings will help us develop new strategies for diagnosis and treatment of PCC.

Significant Enhancement of Photocatalytic Reduction of CO2 with H2O over ZnO by the Formation of Basic Zinc Carbonate.

Electron-hole pair separation efficiency and adsorption performance of photocatalysts to CO2 are the two key factors affecting the performance of photocatalytic CO2 reduction with H2O. Distinct from conventional promoter addition, this study proposed a novel approach to address these two issues by tuning the own surface features of semiconductor photocatalyst. Three ZnO samples with different morphologies, surface area, and defect content were fabricated by varying preparation methods, characterized by XRD, TEM, and room-temperature PL spectra, and tested in photoreduction of CO2 with H2O. The results show that the as-prepared porous ZnO nanosheets exhibit a much higher activity for photoreduction of CO2 with H2O when compared to ZnO nanoparticles and nanorods attributed to the existence of more defect sites, that is, zinc and oxygen vacancies. These defects would lower the combination rate of electron-hole pair as well as promote the formation of basic zinc carbonate by Lewis acid-base interaction, which is the active intermediate species for photoreduction of CO2. ZnO nanoparticles and ZnO nanorods with few defects show weak adsorption for CO2 leading to the inferior photocatalytic activities. This work provides new insight on the CO2 activation under light irradiation.

Synbiotic dietary supplement affects growth, immune responses and intestinal microbiota of Apostichopus japonicus.

A feeding experiment was conducted to investigate the effects of dietary administration of synbiotic with Bacillus lincheniformis WS-2 (CGMCC No. 12813) and alginate oligosaccharides (AOS) on the growth, innate immune response, and intestinal microbiota of the sea cucumber Apostichopus japonicus and its resistance to Vibrio infection. Sea cucumbers were given a control diet (non-supplemented), pro diet (basal diet plus 1 × 109 cfu (g diet)-1B. lincheniformis WS-2), syn diet (basal diet plus 1 × 109 cfu (g diet)-1B. lincheniformis WS-2 and 10 g (kg diet) -1 AOS) or pre diet (basal diet plus 10 g (kg diet) -1 AOS) over a period of 60 days, and the growth performance and various innate immune parameters of the animals were evaluated after 30 and 60 days of feeding. No significant difference in growth performance was observed between the group fed with the syn and the group fed with the pro diet, but both these groups exhibited significant (P < 0.05) enhancement in growth performance compared to the control group. At the same time, both syn and pro diets also resulted in the animals having significantly higher levels of amylase, protease and alginate lyase activities compared to the con diet. Individuals fed with the syn or pro diet showed enhanced levels of various immune enzyme activities, compared to those fed with the con diet. At the end of the growth period, the sea cucumbers were challenged with Vibrio splendidus via intraperitoneal injection. The survival rates of sea cucumbers fed with the syn, pro or pre diet were significantly improved compared to that of sea cucumbers fed with the con diet, with sea cucumbers fed with synbiotic having the highest survival. In addition, increased proportions of Bacillus and Lactococcus were found in the intestinal tract of sea cucumbers fed with the syn diet (9.5% and 7.3%) compared to those of sea cucumbers fed with the pro diet (6.1% and 4.6%), con diet (4.0% and 3.4%), or pre diet (5.2% and 6.8%) after 60 days of feeding. Furthermore, the proportion of Vibrio in the intestinal tracts of sea cucumbers fed with the pro diet (2%) or syn diet (3.1%) was lower than that of sea cucumbers fed with the con diet (5.5%) or pre diet (3.8%), although no significant difference was detected between the pro diet and syn diet groups (P > 0.05). Overall, the results suggested that dietary synbiotic consisting of Bacillus lincheniformis and alginate oligosaccharides (AOS) could have positive benefit for sea cucumber aquaculture.

Use of Bacteriophages to Control Escherichia coli O157:H7 in Domestic Ruminants, Meat Products, and Fruits and Vegetables.

Escherichia coli O157:H7 is an important foodborne pathogen that causes severe bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. Ruminant manure is a primary source of E. coli O157:H7 contaminating the environment and food sources. Therefore, effective interventions targeted at reducing the prevalence of fecal excretion of E. coli O157:H7 by cattle and sheep and the elimination of E. coli O157:H7 contamination of meat products as well as fruits and vegetables are required. Bacteriophages offer the prospect of sustainable alternative approaches against bacterial pathogens with the flexibility of being applied therapeutically or for biological control purposes. This article reviews the use of phages administered orally or rectally to ruminants and by spraying or immersion of fruits and vegetables as an antimicrobial strategy for controlling E. coli O157:H7. The few reports available demonstrate the potential of phage therapy to reduce E. coli O157:H7 carriage in cattle and sheep, and preparation of commercial phage products was recently launched into commercial markets. However, a better ecological understanding of the phage E. coli O157:H7 will improve antimicrobial effectiveness of phages for elimination of E. coli O157:H7 in vivo.

Wind turbine wake visualization and characteristics analysis by Doppler lidar.

Wind power generation is growing fast as one of the most promising renewable energy sources that can serve as an alternative to fossil fuel-generated electricity. When the wind turbine generator (WTG) extracts power from the wind, the wake evolves and leads to a considerable reduction in the efficiency of the actual power generation. Furthermore, the wake effect can lead to the increase of turbulence induced fatigue loads that reduce the life time of WTGs. In this work, a pulsed coherent Doppler lidar (PCDL) has been developed and deployed to visualize wind turbine wakes and to characterize the geometry and dynamics of wakes. As compared with the commercial off-the-shelf coherent lidars, the PCDL in this work has higher updating rate of 4 Hz and variable physical spatial resolution from 15 to 60 m, which improves its capability to observation the instantaneous turbulent wind field. The wind speed estimation method from the arc scan technique was evaluated in comparison with wind mast measurements. Field experiments were performed to study the turbulent wind field in the vicinity of operating WTGs in the onshore and offshore wind parks from 2013 to 2015. Techniques based on a single and a dual Doppler lidar were employed for elucidating main features of turbine wakes, including wind velocity deficit, wake dimension, velocity profile, 2D wind vector with resolution of 10 m, turbulence dissipation rate and turbulence intensity under different conditions of surface roughness. The paper shows that the PCDL is a practical tool for wind energy research and will provide a significant basis for wind farm site selection, design and optimization.

Protective effects of chicken egg yolk antibody (IgY) against experimental Vibrio splendidus infection in the sea cucumber (Apostichopus japonicus).

Vibrio splendidus is one of the most harmful pathogens associated with skin ulceration syndrome in the sea cucumber (Apostichopus japonicus) due to its high virulence and frequency of appearance. The objective of this study was to determine the effectiveness of chicken egg yolk antibody (IgY) against V. splendidus infection in the sea cucumber. Whole V. splendidus cells were used as an immunogen to immunize 20 White Leghorn hens (25 weeks old). IgY was produced from egg yolks obtained from these immunized hens using water dilution, two-step salt precipitation and ultrafiltration. The purity of the IgY produced was approximately 83%. Enzyme-linked Immunosorbent Assay indicated a high specificity for IgY with a maximum antibody titer of 320,000. The growth of V. splendidus in liquid medium was significantly inhibited by IgY in a dose-dependent manner at concentrations ranging from 1 to 10 mg/mL. The protective effects of IgY were evaluated in sea cucumber by intraperitoneally injecting anti-V. splendidus IgY antibodies (10 mg/mL) or immersing the sea cucumber in aqueous IgY (1 g/L) after an intraperitoneal injection of V. splendidus. Intraperitoneal injection resulted in an 80% survival while immersion resulted in a 75% survival during the 11-day experimental period. The survival rates were significantly higher than the positive control and the non-specific IgY group (P < 0.05). As well, the bacterial burden in the respiratory tree, intestine and coelomic liquid was significantly (P < 0.05) lower in sea cucumber treated with specific IgY than those treated with non-specific IgY. The phagocytosis of coelomocytes for V. splendidus in the presence of specific IgY was significantly (P < 0.05) higher than that obtained with non-specific IgY or without IgY, suggesting that specific IgY enhanced phagocytic activity. The current work suggests that specific IgY has potential for protecting sea cucumbers against V. splendidus infection.

Use of phages to control Vibrio splendidus infection in the juvenile sea cucumber Apostichopus japonicus.

In the present study, we isolated 3 bacteriophages with the ability to control Vibrio splendidus, a bacterium known to cause disease in the juvenile sea cucumber. These bacteriophages were designated as vB_VspS_VS-ABTNL-1 (PVS-1), vB_VspS_VS-ABTNL-2 (PVS-2) and vB_VspS_VS-ABTNL-3 (PVS-3). The ability of the 3 phages to inhibit the growth of V. splendidus VS-ABTNL was tested in vitro using each of the 3 phages individually or in the form of a cocktail of all 3 phages in the proportion of 1:1:1. All treated cultures produced a significant (P < 0.05) inhibition of growth of V. splendidus VS-ABTNL compared with untreated V. splendidus VS-ABTNL with the cocktail being superior to any of the 3 phages used individually. The lytic capability of the 3 phages was subsequently determined with a Spot Assay Technique performed with 4 isolates of V. splendidus, 3 other Vibrio species and 2 environmental isolates. Both PVS-1 and PVS-2 were lytic to all 4 isolates of V. splendidus while PVS-3 only inhibited the growth of 3 of them. V. splendidus VS-ABTNL was more susceptible to phage PVS-2 than the other 2 phages. In an in vivo performance trial, 360 sea cucumbers (23 ± 2 g) were randomly assigned to 1 of 6 treatments. Each treatment was housed in 3 PVC tanks (38 cm × 54 cm × 80 cm) with 20 sea cucumbers per tank. Six diets were prepared including an unsupplemented control diet, antibiotic treatment diet, 3 diets containing 1 of the 3 phages individually and a diet containing a cocktail of all 3 phages. After 60 days of feeding, all sea cucumber were challenged with V. splendidus VS-ABTNL by immersion in sea water containing a bacterial concentration of 6 × 10(6) CFU/mL for 2 days. The survival rate of sea cucumbers during the next 10 days was 18% for the unsupplemented diet, 82% for the antibiotic treatment, 82% for the phage cocktail, 65% for phage PVS-1, 58% for phage PVS-2 and 50% for phage PVS-3. There were no significant differences in weight gain, ingestion rate or feed conversion among sea cucumber fed the 4 phage treatments compared with those fed the unsupplemented diet (P > 0.05). The levels of nitric oxide synthase and acid phosphatase of sea cucumbers fed phage-containing diets were significantly (P < 0.05) increased compared with those fed the control diet. However, no significant differences (P > 0.05) were detected among the 4 phage-fed treatments. An additional study was conducted in which 60 healthy sea cucumbers (23 ± 2 g) were randomly assigned to a control, an untreated group and a test group to investigate the effects of injecting phages by coelomic injection on the survival rate and enzyme activities in the coelomic fluid of the sea cucumbers. The control was injected with 1 ml of sterilized seawater while the untreated group and the test group were injected with the same volume of V. splendidus-ABTNL culture (3 × 10(5) CFU/mL). Then, the test group was injected with 1 ml of the 3 phage cocktail (MOI = 10). After 48 h, the activities of lysozyme, acid phosphatase and superoxide dismutase were elevated in the untreated group while the levels of these enzymes in the test group were similar to the blank control. After 10-day observation, the survival rate of the sea cucumber was 100% for the blank control, 80% for the test group and 20% for the negative control. The overall results of this experiment indicate that phage therapy increased the survival of sea cucumber infected with V. splendidus VS-ABTNL. The above results demonstrate that using phages, especially a combination of different phages, may be a feasible way to control Vibrio infection in the sea cucumber industry.

[Comparison of the Predictive Values of Eight Staging Systems for Primary Liver Cancer in Prognosis of Combined Hepatocellular-cholangiocellular Carcinoma Patients after Surgery].

OBJECTIVE: To compare the predictive values of eight staging systems for primary liver cancer in the prognosis of combined hepatocellular-cholangiocellular carcinoma (cHCC-CC) patients after surgery. METHODS: The clinical data of 54 cHCC-CC patients who underwent hepatectomy or liver transplantation from May 2005 to Augest 2013 in Chinese PLA General Hospital were collected. We evaluated the prognostic value of the Okuda staging system, Cancer of the Liver Italian Program (CLIP) score, French staging system, Barcelona Clinic Liver Cancer (BCLC) staging system, 7th edition of tumour-node-metastasis (TNM) staging system for hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC), Japan Integrated Staging (JIS) score, and Chinese University Prognostic Index. The distribution, Kaplan-Meier method, Log-rank test, and area under a receiver operating characteristic curve were used to compare the prognosis-predicting ability of these different staging systems in 54 cHCC-CC patients after surgery. RESULTS: The TNM staging system for ICC and JIS score had a better distribution of cases. The 12-and 24-month survivals of the entire cohort were 65.5% and 56.3%, respectively. A Log-rank test showed that there was a significant difference existing in the cumulative survival rates of different stage patients when using TNM staging system for ICC (stage 1 vs. stage 2, P=0.012; stage 2 vs. stage 3-4, P=0.002), Okuda staging system (stage 1 vs. stage 2, P=0.025), and French staging system (stage A and stage B, P=0.045). The 12-and 24-month area under curve of TNM staging system for ICC, BCLC staging system, JIS score, and CLIP score were 0.836 and 0.847, 0.744 and 0.780, 0.723 and 0.764, and 0.710 and 0.786, respectively. CONCLUSION: The 7th edition of TNM staging system for ICC has superior prognostic value to other seven staging systems in cHCC-CC patients undergoing surgical treatment.

Characterization of Organic Anion Transporter 2 (SLC22A7): A Highly Efficient Transporter for Creatinine and Species-Dependent Renal Tubular Expression.

The contribution of organic anion transporter OAT2 (SLC22A7) to the renal tubular secretion of creatinine and its exact localization in the kidney are reportedly controversial. In the present investigation, the transport of creatinine was assessed in human embryonic kidney (HEK) cells that stably expressed human OAT2 (OAT2-HEK) and isolated human renal proximal tubule cells (HRPTCs). The tubular localization of OAT2 in human, monkey, and rat kidney was characterized. The overexpression of OAT2 significantly enhanced the uptake of creatinine in OAT2-HEK cells. Under physiologic conditions (creatinine concentrations of 41.2 and 123.5 µM), the initial rate of OAT2-mediated creatinine transport was approximately 11-, 80-, and 80-fold higher than OCT2, multidrug and toxin extrusion protein (MATE)1, and MATE2K, respectively, resulting in approximately 37-, 1850-, and 80-fold increase of the intrinsic transport clearance when normalized to the transporter protein concentrations. Creatinine intracellular uptake and transcellular transport in HRPTCs were decreased in the presence of 50 µM bromosulfophthalein and 100 µM indomethacin, which inhibited OAT2 more potently than other known creatinine transporters, OCT2 and multidrug and toxin extrusion proteins MATE1 and MATE2K (IC50: 1.3 µM vs. > 100 µM and 2.1 µM vs. > 200 µM for bromosulfophthalein and indomethacin, respectively) Immunohistochemistry analysis showed that OAT2 protein was localized to both basolateral and apical membranes of human and cynomolgus monkey renal proximal tubules, but appeared only on the apical membrane of rat proximal tubules. Collectively, the findings revealed the important role of OAT2 in renal secretion and possible reabsorption of creatinine and suggested a molecular basis for potential species difference in the transporter handling of creatinine.

Improving the quality of Laminaria japonica-based diet for Apostichopus japonicus through degradation of its algin content with Bacillus amyloliquefaciens WB1.

Laminaria japonica feedstuff is used as a substitute for Sargassum thunbergii in the small-scale culturing of Apostichopus japonicus (sea cucumber) because of its abundant sources and low price in China. However, the difficulty associated with the degradation of algin by A. japonicus and, hence, its utilization have limited the practical value of L. japonica feedstuff in sea cucumber farming. In this study, A. japonicus individuals were fed with L. japonica feedstuff pretreated, via fermentation with the algin-degrading bacterial strain, Bacillus amyloliquefaciens WB1, and their growth performance, nonspecific immune responses, and resistance against Vibrio infection were then determined over a 60-day period. Growth performance of these individuals was similar to those fed with a commercial feedstuff made from S. thunbergii (mean weight gain of 5.79 versus 5.69 g on day 60), but was significantly (P < 0.05) increased compared to those fed with untreated L. japonica feedstuff (mean weight gain of 1.31 g). At the same time, they also showed significantly higher levels of amylase, protease, and alginate lyase activities than the other groups. These individuals and those fed with the commercial feedstuff or heat-inactivated but B. amyloliquefaciens WB1-treated L. japonicas feedstuff showed enhanced levels of activities for the immune enzymes nitric oxide synthase, lysozyme, peroxidase, and acid phosphatase, compared to those fed with nontreated L. japonica feedstuff. Furthermore, A. japonicus individuals fed with B. amyloliquefaciens WB1-treated L. japonica feedstuff exhibited greater resistance to disease following Vibrio splendidus challenge, as shown by the much lower cumulative symptom (10 %) compared to the rest, which showed as much as 73 % in the case of individuals fed with the untreated L. japonica feedstuff. Analysis of their intestinal tract revealed a much lower number of total Vibrio sp. These results demonstrated that L. japonica in which the algin content had been degraded by B. amyloliquefaciens WB1 could improve the growth performance of A. japonicus as well its resistance to bacterial infection. It could therefore act as an alternative to S. thunbergii and is economical at the same time.

Effect of Cooling Rate on the Microstructure and Mechanical Property of Nickel-Based Superalloy MAR-M247.

Heat treatment is an important process for optimizing the microstructures of superalloys, and the cooling rate after solid solution treatment is one of the most critical parameters. In this work, we treated solid solution MAR-M247 alloys with water quenching, air cooling, and furnace cooling. Microstructure characterization, hardness, and room temperature tensile tests were conducted to investigate the effect of cooling rate on the microstructure and mechanical properties of MAR-M247 alloys. The results showed that the cooling rate after solid solution treatment mainly affected the precipitation behavior of the secondary γ' phase, but it had few effects on other microstructure characterizations, including grain size, γ/γ' eutectic, and MC carbide. The water-quenched sample had the highest cooling rate (400 °C/s) and hardness (400 HV) but suffered from premature fracture because of quenching cracks. A further decrease in cooling rate from 1.5 °C/s to 0.1 °C/s deteriorated hardness (384 HV to 364 HV) and yield strength (960 MPa to 771 MPa) but increased elongation (8.5% to 13.5%). Moreover, the deformation mechanism was transformed from dislocation shearing to Orowan bypassing. The decreased yield strength was mainly due to the weakened precipitation strengthening resulting from γ'-phase coarsening. The improved elongation was attributed to not only the higher work-hardening index caused by interface dislocation networks but also the more uniform deformation, which delayed necking.

Predicting the current fishable habitat distribution of Antarctic toothfish (Dissostichus mawsoni) and its shift in the future under climate change in the Southern Ocean.

Global warming continues to exert unprecedented impacts on marine habitats. Species distribution models (SDMs) are proven powerful in predicting habitat distribution for marine demersal species under climate change impacts. The Antarctic toothfish, Dissostichus mawsoni (Norman 1937), an ecologically and commercially significant species, is endemic to the Southern Ocean. Utilizing occurrence records and environmental data, we developed an ensemble model that integrates various modelling techniques. This model characterizes species-environment relationships and predicts current and future fishable habitats of D. mawsoni under four climate change scenarios. Ice thickness, depth and mean water temperature were the top three important factors in affecting the distribution of D. mawsoni. The ensemble prediction suggests an overall expansion of fishable habitats, potentially due to the limited occurrence records from fishery-dependent surveys. Future projections indicate varying degrees of fishable habitat loss in large areas of the Amery Ice Shelf's eastern and western portions. Suitable fishable habitats, including the spawning grounds in the seamounts around the northern Ross Sea and the coastal waters of the Bellingshausen Sea and Amundsen Sea, were persistent under present and future environmental conditions, highlighting the importance to protect these climate refugia from anthropogenic disturbance. Though data deficiency existed in this study, our predictions can provide valuable information for designing climate-adaptive development and conservation strategies in maintaining the sustainability of this species.

A Single Latent Plant Growth-Promoting Endophyte BH46 Enhances Houttuynia cordata Thunb. Yield and Quality.

Plant growth-promoting endophytes (PGPE) can effectively regulate plant growth and metabolism. The regulation is modulated by metabolic signals, and the resulting metabolites can have considerable effects on the plant yield and quality. Here, tissue culture Houttuynia cordata Thunb., was inoculated with Rhizobium sp. (BH46) to determine the effect of BH46 on H. cordata growth and metabolism, and elucidate associated regulatory mechanisms. The results revealed that BH46 metabolized indole-3-acetic acid and induced 1-aminocyclopropane-1-carboxylate deaminase to decrease ethylene metabolism. Host peroxidase synthesis MPK3/MPK6 genes were significantly downregulated, whereas eight genes associated with auxins, cytokinins, abscisic acid, jasmonic acid, and antioxidant enzymes were significantly upregulated. Eight genes associated with flavonoid biosynthesis were significantly upregulated, with the CPY75B1 gene regulating the production of rutin and quercitrin and the HCT gene directly regulating the production of chlorogenic acid. Therefore, BH46 influences metabolic signals in H. cordata to modulate its growth and metabolism, in turn, enhancing yield and quality of H. cordata.