Temporal variation of microbial nutrient limitation in citrus plantations: Insights from soil enzyme stoichiometry.

Soil enzyme carbon (C): nitrogen (N): phosphorous (P) stoichiometry and their vector model has been widely used to elucidate the balance between microbial nutrient requirements and soil nutrient availability. However, limited knowledge is available on the dynamics of soil enzyme stoichiometry and microbial nutrient limitation following afforestation, especially in the economic forest. In this study, the effects of citrus plantation on C: N: P stoichiometry were assessed through a comparative study between cropland and citrus plantations with varying durations of afforestation (i.e., 3, 15, 25, and 35 years). It was found that the C, N, and P contents in the soil (SOC, STN, and STP), microbial biomass (MBC, MBN, and MBP), as well as the activities of C-, N-, and P-acquiring enzymes (BG, NAG, and AP), were 1.02-2.51 times higher than those in cropland. Additionally, C, N, and P contents in soil and microbial biomass increased consistently with increasing afforestation time. While the activities of C-, N-, and P-acquiring enzymes increased from 3 years to 25 years and then significantly decreased. In addition to NAG: AP, the stoichiometry of C, N, and P in soil (SOC: STN, SOC: STP, and STN: STP) and microbial biomass (MBC: MBN, MBC: MBP, and MBN: MBP), along with BG: NAG, exhibited a decline of 7.69-27.38% compared to cropland. Moreover, the majority of the C: N: P stoichiometry in soil, microbial biomass, and enzymes consistently decreased with increasing afforestation time, except for SOC: STN and NAG: AP, which exhibited an opposite trend. Furthermore, a significant decrease in microbial carbon limitation and an increase in microbial nitrogen limitation were observed with increasing afforestation time. Collectively, the dynamic of microbial nutrient limitation was primarily influenced by the interaction between soil nutrients and edaphic factors. The findings suggest that with the increasing duration of citrus plantation, it is crucial to focus on nitrogen (N) fertilization while maintaining a delicate balance between fertilization strategies and soil acidity levels.

Adsorption Characterization of Cu(II) and Cd(II) by a Magnetite-Chitosan Composite: Kinetic, Thermodynamic and Equilibrium Studies.

Optimizing the use of magnetite-chitosan composites for heavy metal adsorption has been of great interest due to their environmental friendliness. To gain insights into their potential with green synthesis, this study analyzed one of these composites through X-ray diffraction, Fourier-transform infrared spectroscopy and scanning electron microscopy. Adsorption properties were then explored via static experiments to evaluate the pH dependence, isotherms, kinetics, thermodynamics and regeneration adsorption of Cu(II) and Cd(II). Results disclosed that the optimum pH of adsorption was 5.0, the equilibrium time was about 10 min, and the capacity for Cu(II) and Cd(II) reached 26.28 and 18.67 mg/g, respectively. The adsorption amount of cations increased with temperature from 25 °C to 35 °C and decreased with further increase in temperature from 40 °C to 50 °C, which might be related to the unfolding of chitosan; the adsorption capacity was above 80% of the initial value after two regenerations and about 60% after five regenerations. The composite has a relatively rough outer surface, but its inner surface and porosity are not obvious; it has functional groups of magnetite and chitosan, and chitosan might dominate the adsorption. Consequently, this research proposes the value of maintaining green synthesis research to further optimize the composite system of heavy metal adsorption.

Pharmacokinetics of cyadox and its main metabolites in rats, pigs, chickens, and carps following oral administration at three dosage.

Cyadox (CYA), a 1,4-dioxide quinoxaline, is a safe and effective antibacterial agent with potential use in food-producing animals. The aim of this study was to compare the pharmacokinetics of CYA (Cy0) and its main metabolites [bisdeoxycyadox (Cy1), 4-desoxycyadox (Cy2), N-(quinoxaline-2-methyl)-cyanide acetyl hydrazine (Cy4), quinoxaline-2-carboxylic acid (Cy6), and 2-hydromethyl-3-hydroxy-quinoxaline (Cy12)] after oral administration at three dosages in pigs, chickens, carps, and rats. The concentration vs. time profile in plasma after single oral administration indicated that CYA was rapidly dissociated into its metabolites and showed the widest distribution in all animals, with the highest apparent volume of distribution. Cy0 and Cy6 persisted for the longest time at lower concentration. Cy1and Cy4 concentration was the highest in pig and rat plasma, while Cy1 was undetectable in chickens, and Cy4 was undetectable in carps following administration at three dosages. Different dosage of the CYX and its metabolites had no significant effect on wash-out period. This study revealed obvious species-specific differences in the kinetic behavior of CYA and its metabolites, which may be related to clinical efficacy and toxicity. Our results would facilitate the judicious use of CYA in different animals.

The value of 99mTc-labeled galactosyl human serum albumin single-photon emission computerized tomography/computed tomography on regional liver function assessment and posthepatectomy failure prediction in patients with hilar cholangiocarcinoma.

BACKGROUND: The aim was to evaluate the value of Tc-labeled galactosyl human serum albumin (Tc-GSA) with single-photon emission computerized tomography (SPECT) in the preoperative assessment of regional liver function and prediction of posthepatectomy liver failure (PHLF) in patients with hilar cholangiocarcinoma (hCCA). METHODS: Patients with hCCA who underwent Tc-GSA SPECT/computed tomography (CT) before hepatectomy were included. The liver functional parameters of functional liver density (FLD) and predictive residual index (PRI) were calculated based on Tc-GSA SPECT/CT. PHLF was defined according to the International Study Group of Liver Surgery criteria. Univariate and multivariate analyses were used to analyze the risk factors for PHLF. The prediction of PHLF was calculated using receiver operating characteristic curve. RESULTS: A total of 34 patients were included, 23 of whom underwent preoperative biliary drainage. FLD was significantly higher in patients with drained lobes than that in patients with undrained lobes (0.615 ± 0.190 versus 0.500 ± 0.211, P < 0.05). Sixteen patients suffered PHLF. The ratio of future remnant to total morphological liver volume, future remnant FLD, and PRI differed significantly in patients with and without PHLF according to univariate analysis. PRI was identified as the only independent factor for prediction of PHLF according to multivariate analysis. With a PRI of 0.78, it was possible to predict PHLF with a sensitivity of 83% and a specificity of 93%. CONCLUSIONS: Tc-GSA SPECT/CT can accurately assess regional liver function and is better able to predict PHLF than conventional methods in patients with hCCA.

Model-Aided Localization and Navigation for Underwater Gliders Using Single-Beacon Travel-Time Differences.

An accurate motion model and reliable measurements are required for autonomous underwater vehicle localization and navigation in underwater environments. However, without a propeller, underwater gliders have limited maneuverability and carrying capacity, which brings difficulties for modeling and measuring. In this paper, an extended Kalman filter (EKF)-based method, combining a modified kinematic model of underwater gliders with the travel-time differences between signals received from a single beacon, is proposed for estimating the glider positions in a predict-update cycle. First, to accurately establish a motion model for underwater gliders moving in the ocean, we introduce two modification parameters, the attack and drift angles, into a kinematic model of underwater gliders, along with depth-averaged current velocities. The attack and drift angles are calculated based on the coefficients of hydrodynamic forces and the sensor-measured angle variation over time. Then, instead of satisfying synchronization requirements, the travel-time differences between signals received from a single beacon, multiplied by the sound speed, are taken as the measurements. To further reduce the EKF estimation error, the Rauch-Tung-Striebel (RTS) smoothing method is merged into the EKF system. The proposed method is tested in a virtual spatiotemporal environment from an ocean model. The experimental results show that the performance of the RTS-EKF estimate is improved when compared with the motion model estimate, especially by 46% at the inflection point, at least in the particular study developed in this article.

A tumor suppressor enhancing module orchestrated by GATA4 denotes a therapeutic opportunity for GATA4 deficient HCC patients.

Rationale: Effective targeting therapies are limited in Hepatocellular carcinoma (HCC) clinic. Characterization of tumor suppressor genes (TSGs) and elucidation their signaling cascades could shed light on new strategies for developing targeting therapies for HCC. Methods: We checked genome-wide DNA copy number variation (CNV) of HCC samples, focusing on deleted genes for TSG candidates. Clinical data, in vitro and in vivo data were collected to validate the tumor suppressor functions. Results: Focal deletion of GATA4 gene locus was the most prominent feature across all liver cancer samples. Ectopic expression of GATA4 resulted in senescence of HCC cell lines. Mechanistically, GATA4 exerted tumor suppressive role by orchestrating the assembly of a tumor suppressor enhancing module: GATA4 directly bound and potently inhibited the mRNA transcription activity of ß-catenin; meanwhile, ß-catenin was recruited by GATA4 to promoter regions and facilitated transcription of GATA4 target genes, which were TSGs per se. Expression of GATA4 was effective to shrink GATA4-deficient HCC tumors in vivo. We also showed that ß-catenin inhibitor was capable of shrinking GATA4-deficient tumors. Conclusions: Our study unveiled a previously unnoticed tumor suppressor enhancing module assembled by ectopically expressed GATA4 in HCC cells and denoted a therapeutic opportunity for GATA4 deficient HCC patients. Our study also presented an interesting case that an oncogenic transcription factor conditionally functioned as a tumor suppressor when recruited by a TSG transcription factor.

In situ meta-omic insights into the community compositions and ecological roles of hadal microbes in the Mariana Trench.

The low temperature and elevated hydrostatic pressure in hadal trenches at water depths below 6000 m render sample collection difficult. Here, in situ hadal water microbial samples were collected from the Mariana Trench and analysed. The hadal microbial communities at different depths were revealed to be consistent and were dominated by heterotrophic Marinimicrobia. Thirty high-quality metagenome-assembled genomes (MAGs) were retrieved to represent the major hadal microbes affiliated with 12 prokaryotic phyla. Most of the MAGs were newly reported and probably derived from novel hadal inhabitants as exemplified by a potentially new candidate archaeal phylum in the DPANN superphylum. Metabolic reconstruction indicated that a great number of the MAGs participated in nitrogen and sulfur cycling, in which the nitrification process was driven sequentially by Thaumarchaeota and Nitrospirae and sulfur oxidization by Rhodospirillales in the Alphaproteobacteria class. Moreover, several groups of hadal microbes were revealed to be potential carbon monoxide oxidizers. Metatranscriptomic result highlighted the contribution of Chloroflexi in degrading recalcitrant dissolved organic matter and Marinimicrobia in extracellular protein decomposition. The present work provides an in-depth view on the hadal microbial communities regarding their endemism and element cycles.

Genomics insights into ecotype formation of ammonia-oxidizing archaea in the deep ocean.

Various lineages of ammonia-oxidizing archaea (AOA) are present in deep waters, but the mechanisms that determine ecotype formation are obscure. We studied 18 high-quality genomes of the marine group I AOA lineages (alpha, gamma and delta) from the Mariana and Ogasawara trenches. The genomes of alpha AOA resembled each other, while those of gamma and delta lineages were more divergent and had even undergone insertion of some phage genes. The instability of the gamma and delta AOA genomes could be partially due to the loss of DNA polymerase B (polB) and methyladenine DNA glycosylase (tag) genes responsible for the repair of point mutations. The alpha AOA genomes harbour genes encoding a thrombospondin-like outer membrane structure that probably serves as a barrier to gene flow. Moreover, the gamma and alpha AOA lineages rely on vitamin B12 -independent MetE and B12 -dependent MetH, respectively, for methionine synthesis. The delta AOA genome contains genes involved in uptake of sugar and peptide perhaps for heterotrophic lifestyle. Our study provides insights into co-occurrence of cladogenesis and anagenesis in the formation of AOA ecotypes that perform differently in nitrogen and carbon cycling in dark oceans.

Correction: Tumor driven by gain-of-function HER2 H878Y mutant is highly sensitive to HER2 inhibitor.

[This corrects the article DOI: 10.18632/oncotarget.5221.].

Correction: Overexpression of wildtype EGFR is tumorigenic and denotes a therapeutic target in non-small cell lung cancer.

[This corrects the article DOI: 10.18632/oncotarget.6461.].

Correction: EGFR kinase domain mutation positive lung cancers are sensitive to intrapleural perfusion with hyperthermic chemotherapy (IPHC) complete treatment.

[This corrects the article DOI: 10.18632/oncotarget.6491.].

Author Correction: Efficient Generation of Mice with Consistent Transgene Expression by FEEST.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Author Correction: Identification of urine protein biomarkers with the potential for early detection of lung cancer.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

GATA4 inhibits cell differentiation and proliferation in pancreatic cancer.

Pancreatic ductal carcinoma (PDAC) is a common malignant tumor of the digestive system. GATA4 is one of the transcriptional regulatory factors, which regulates the development of endoderm-derived organs, including heart and gut. GATA4 may act as a putative tumor suppressor gene. However, the role of GATA4 in pancreatic carcinogenesis is not yet clarified. This study showed that GATA4 was highly expressed in pancreatic cancer tissues, and its expression level was positively related to the grade of pathological differentiation, suggesting that it may contribute to the progression of pancreatic neoplasia. Ectopic expression of GATA4 gene reduced cell viability and interference of GATA4 expression significantly increased the colony formation ability of pancreatic cancer cells. Furthermore, GATA4 inhibited tumor growth in xenograft mice. Agilent expression microarray profiling analysis indicated that the genes with significant levels of differential expression in GATA4 over-expressing cells were enriched in the cell differentiation process. Analysis of KEGG signaling pathway demonstrated that the regulated genes were partially enriched in MAPK and JAK-STAT signaling pathways. Re-expression of GATA4 up-regulated P53 gene expression. Our data indicate that GATA4 gene might play a role in cell proliferation and differentiation during the progression of pancreatic cancer.

In situ splitting after selective partial portal vein ligation or simultaneous hepatic artery ligation promotes liver regeneration.

This study seeks to compare the impact of selective partial portal vein ligation (PPVL) or the combination of simultaneous hepatic artery ligation (PPVAL) with in situ splitting (ISS) on liver regeneration and injury. Rats were randomized into three groups; namely: selective PVL, PPVL + ISS and PPVAL + ISS. The changes in hepatic hemodynamics, liver regeneration and hepatocytic injury were examined. Blood flow to the left portal branch and the microcirculation of the left median lobe after PPVL or PPVAL was significantly reduced. Liver regeneration of PPVAL + ISS group was more pronounced than that in the PPVL + ISS and PVL groups at 48 and 72 hours as well as 7 d postoperatively. The serum biochemical markers and histopathological examination demonstrated reduced levels of liver injury in the PPVL + ISS group. Injury to hepatocytes was more pronounced with PPVAL + ISS than PVL. HGF, TNF-α and IL-6 expression in the regenerated lobes in both PPVAL + ISS and PPVL + ISS groups increased significantly when compared to the PVL group. We demonstrated that both PPVL + ISS and PPVAL + ISS were effective and feasible means of inducing remnant liver hypertrophy and could serve as a rapid clinical application for qualified patients.

Synthesis of tritium-labeled cyadox, a promising antimicrobial growth-promoting agent with high specific activity.

Cyadox is a new antimicrobial growth-promoting agent for food-producing animals. Studies on radiolabeled compounds enable the use of sensitive radiometric analytical methods and help in the elucidation of metabolic and elimination pathways. In the present study, 6-[3H]-cyadox with a high specific activity of 2.08 Ci/mmol was prepared by the catalytic bromine-tritium exchange of 4-bromo-2-nitroaniline followed by a three-step microscale synthesis, giving a high yield between 36.16% and 94.75%.

Quantified postsurgical small cell size CTCs and EpCAM+ circulating tumor stem cells with cytogenetic abnormalities in hepatocellular carcinoma patients determine cancer relapse.

Detection of hepatocellular carcinoma circulating tumor cells performed with conventional strategies, is significantly limited due to inherently heterogeneous and dynamic expression of EpCAM, as well as degradation of cytokeratins during epithelial-to-mesenchymal transition, which inevitably lead to non-negligible false negative detection of such "uncapturable and invisible" CTCs. A novel SE-iFISH strategy, improved for detection of HCC CTCs in this study, was applied to comprehensively detect, in situ phenotypically and karyotypically characterize hepatocellular and cholangiocarcinoma CTCs (CD45-/CD31-) in patients subjected to surgical resection. Clinical significance of diverse subtypes of CTC was systematically investigated. Existence of small cell size CTCs (≤5 µm of WBCs) with cytogenetic abnormality of aneuploid chromosome 8, which constituted majority of the detected CTCs in HCC patients, was demonstrated for the first time. The stemness marker EpCAM+ aneuploid circulating tumor stem cells (CTSCs), and EpCAM- small CTCs with trisomy 8, promote tumor growth. Postsurgical quantity of small triploid CTCs (≥5 cells/6 ml blood), multiploid (≥pentasomy 8) CTSCs or CTM (either one ≥ 1) significantly correlated to HCC patients' poor prognosis, indicating that detection of those specific subtypes of CTCs and CTSCs in post-operative patients help predict neoplasm recurrence.

A simple rat model of in situ reversible obstructive jaundice in situ reversible obstructive jaundice model.

PURPOSE: To develop a simple and reliable rat model of in situ reversible obstructive jaundice with low morbidity and mortality rates. METHODS: Rats were divided into 4 groups with 8 rats each: the sham-operated (SH) group only underwent laparotomy, the control internal drainage (ID-C) group underwent choledochoduodenostomy, the new internal drainage (ID-N) group and the long-term internal drainage (ID-L) group underwent choledochocholedochostomy. Common bile duct ligation was performed in all the drainage groups 7 days before reversal procedures. All rats were sacrificed for samples 7 days after the last operation except rats of the ID-L group that survived 28 days before sacrifice. Body weight, liver function, histopathological changes, morbidity and mortality were assessed. RESULTS: One rat died and 2 rats had complications with tube blockage in the ID-C group. No death or complications occurred in the ID-N and ID-L groups. The drainage tube remained patent in the long-term observation ID-L group. Body weight showed no significant difference between the ID-C and ID-N groups after 7 days drainage. Liver function was not fully recovered in the ID-C and ID-N groups after 7 days drainage, but statistical differences were only observed in the ID-C group compared with the SH and ID-L groups. Periportal inflammation and bile duct proliferation showed severer in the ID-C group than in the ID-N group. CONCLUSION: The present study provided an efficient, simple, and reliable rat model that is especially suitable for long-term or consecutive studies of reversible obstructive jaundice.

A Direct Test of Selection in Cell Populations Using the Diversity in Gene Expression within Tumors.

Although intratumor diversity driven by selection has been the prevailing view in cancer biology, recent population genetic analyses have been unable to reject the neutral interpretation. As the power to reject neutrality in tumors is often low, it will be desirable to have an alternative means to test selection directly. Here, we utilize gene expression data as a surrogate for functional significance in intra- and intertumor comparisons. The expression divergence between samples known to be driven by selection (e.g., between tumor and normal tissues) is always higher than the divergence between normal samples, which should be close to the neutral level of divergence. In contrast, the expression differentiation between regions of the same tumor, being lower than the neutral divergence, is incompatible with the hypothesis of selectively driven divergence. To further test the hypothesis of neutral evolution, we select a hepatocellular carcinoma tumor that has large intratumor SNV and CNV (single nucleotide variation and copy number variation, respectively) diversity. This tumor enables us to calibrate the level of expression divergence against that of genetic divergence. We observe that intratumor divergence in gene expression profile lags far behind genetic divergence, indicating insufficient phenotypic differences for selection to operate. All these expression analyses corroborate that natural selection does not operate effectively within tumors, supporting recent interpretations of within-tumor diversity. As the expected level of genetic diversity, hence the potential for drug resistance, would be much higher under neutrality than under selection, the issue is of both theoretical and clinical significance.

Perioperative and long-term outcomes of liver resection for hepatitis B virus-related hepatocellular carcinoma without versus with hepatic inflow occlusion: study protocol for a prospective randomized controlled trial.

BACKGROUND: The high prevalence of hepatitis B virus (HBV) imposes a huge burden of hepatocellular carcinoma (HCC) in Asia. Surgical resection remains an important therapeutic strategy for HCC. Hepatic inflow occlusion, known as the Pringle maneuver, is the most commonly used method of reducing blood loss during liver parenchymal transection. A major issue with this maneuver is ischemia-reperfusion injury to the remnant liver, and the hemodynamic disturbance it induces in the tumor-bearing liver raises an oncological concern. Given the technical advances in living donor liver transplantation, vascular occlusion in liver resection can be avoided in experienced hands. The aim of this study is to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC without versus with hepatic inflow occlusion. METHODS/DESIGN: This study will include eligible patients with HBV-related HCC elected for liver resection. Fifty-seven patients will be enrolled in each randomization arm to detect a 20 % difference in the serum level of total bilirubin on postoperative day 5 (80 % power and α = 0.05). The secondary endpoints include procedural parameters, perioperative liver function and inflammatory response, postoperative morbidity and mortality, and long-term outcomes. Patients will be followed for up to 5 years. Data will be statistically analyzed on an intention-to-treat basis. DISCUSSION: This prospective randomized controlled trial is designed to compare the perioperative and long-term outcomes of liver resection for HBV-related HCC without versus with vascular occlusion. The clinical implications of these outcomes may change current surgical practice and fill the oncological gaps therein. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02563158 . Registered on 28 September 2015.