Integrated analysis of diverse cancer types reveals a breast cancer-specific serum miRNA biomarker through relative expression orderings analysis.

PURPOSE: Serum microRNA (miRNA) holds great potential as a non-invasive biomarker for diagnosing breast cancer (BrC). However, most diagnostic models rely on the absolute expression levels of miRNAs, which are susceptible to batch effects and challenging for clinical transformation. Furthermore, current studies on liquid biopsy diagnostic biomarkers for BrC mainly focus on distinguishing BrC patients from healthy controls, needing more specificity assessment. METHODS: We collected a large number of miRNA expression data involving 8465 samples from GEO, including 13 different cancer types and non-cancer controls. Based on the relative expression orderings (REOs) of miRNAs within each sample, we applied the greedy, LASSO multiple linear regression, and random forest algorithms to identify a qualitative biomarker specific to BrC by comparing BrC samples to samples of other cancers as controls. RESULTS: We developed a BrC-specific biomarker called 7-miRPairs, consisting of seven miRNA pairs. It demonstrated comparable classification performance in our analyzed machine learning algorithms while requiring fewer miRNA pairs, accurately distinguishing BrC from 12 other cancer types. The diagnostic performance of 7-miRPairs was favorable in the training set (accuracy = 98.47%, specificity = 98.14%, sensitivity = 99.25%), and similar results were obtained in the test set (accuracy = 97.22%, specificity = 96.87%, sensitivity = 98.02%). KEGG pathway enrichment analysis of the 11 miRNAs within the 7-miRPairs revealed significant enrichment of target mRNAs in pathways associated with BrC. CONCLUSION: Our study provides evidence that utilizing serum miRNA pairs can offer significant advantages for BrC-specific diagnosis in clinical practice by directly comparing serum samples with BrC to other cancer types.

Feasibility of whole-exome sequencing in fine-needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations.

Genetic profiling is important for assisting the management of papillary thyroid microcarcinoma (PTMC). Although whole-exome sequencing (WES) of surgically resected PTMC tissue has been performed and revealed potential prognostic biomarkers, its application in PTMC fine-needle aspiration (FNA) specimens has not been explored. This study aimed to evaluate the feasibility of WES using FNA specimens of PTMC. Five PTMC patients were enrolled with clinical characteristics gathered. Fine aspiration cytology needle (23 gauges) was used to collect FNA biopsy with ultrasound guidance. WES analysis of FNA specimens from five PTMC patients and matched blood samples was performed. The WES of FNA samples yielded an average sequencing depth of 281× and average coverage of 99.5%. We identified 534 somatic single-nucleotide variants and 13 indels in total, and per sample, we found a mean of 24 exonic mutations, which affected a total of 120 genes. In the PTMC FNA samples, the most frequently mutated genes were BRAF and ANKRD18B, and the four driver genes were BRAF, AFF3, SRCAP, and EGFR. We also identified several germline cancer predisposing gene mutations. The results suggest that WES of FNA specimens is feasible for PTMC and can identify novel genetic mutations.

Antimony Isotope Fractionation during Kinetic Sb(III) Oxidation by Antimony-Oxidizing Bacteria Pseudomonas sp. J1.

Antimony (Sb) isotopic fractionation is frequently used as a proxy for biogeochemical processes in nature. However, to date, little is known about Sb isotope fractionation in biologically driven reactions. In this study, Pseudomonas sp. J1 was selected for Sb isotope fractionation experiments with varying initial Sb concentration gradients (50-200 µM) at pH 7.2 and 30 °C. Compared to the initial Sb(III) reservoir (δ123Sb = 0.03 ± 0.01 ∼ 0.06 ± 0.01‰), lighter isotopes were preferentially oxidized to Sb(V). Relatively constant isotope enrichment factors (ε) of -0.62 ± 0.06 and -0.58 ± 0.02‰ were observed for the initial Sb concentrations ranging between 50 and 200 µM during the first 22 days. Therefore, the Sb concentration has a limited influence on Sb isotope fractionation during Sb(III) oxidation that can be described by a kinetically dominated Rayleigh fractionation model. Due to the decrease in the Sb-oxidation rate by Pseudomonas sp. J1, observed for the initial Sb concentration of 200 µM, Sb isotope fractionation shifted toward isotopic equilibrium after 22 days, with slightly heavy Sb(V) after 68 days. These findings provide the prospect of using Sb isotopes as an environmental tracer in the Sb biogeochemical cycle.

UHPLC-MS/MS Assay for Quantification of Legubicin, a Novel Doxorubicin-Based Legumain-Activated Prodrug, and Its Application to Pharmacokinetic and Tissue Distribution Studies.

Legubicin, a novel prodrug based on doxorubicin, has both albumin-binding and legumain-activating properties. The aim of this study was to develop and validate a UHPLC-MS/MS method for investigating the in vivo pharmacokinetics and tissue distribution profiles of legubicin in rats and tumor-bearing mice following intravenous administration, and to compare this prodrug with the positive control drug doxorubicin. The study employed a UHLC-MS/MS method to determine the levels of albumin-bound of legubicin and two metabolites (free Leu-DOX and DOX) in plasma, tumor, and tissue samples. This method was validated for good selectivity, high sensitivity, excellent extraction recovery, and short run time. The results showed that legubicin was present in the circulation in vivo mainly in a protein-bound form with larger AUC values and lower clearance and distribution, and essentially released small amounts of doxorubicin. Compared to administration of equimolar doses of doxorubicin, legubicin showed increased exposure of the active drug in the tumor and decreased the level of the active drug in the heart and kidney. This study provides valuable information on the pharmacokinetics and tissue distribution of legubicin, implicating its potential as a novel and effective drug candidate for anti-cancer therapies.

Screening prognostic markers for hepatocellular carcinoma based on pyroptosis-related lncRNA pairs.

BACKGROUND: Pyroptosis is closely related to cancer prognosis. In this study, we tried to construct an individualized prognostic risk model for hepatocellular carcinoma (HCC) based on within-sample relative expression orderings (REOs) of pyroptosis-related lncRNAs (PRlncRNAs). METHODS: RNA-seq data of 343 HCC samples derived from The Cancer Genome Atlas (TCGA) database were analyzed. PRlncRNAs were detected based on differentially expressed lncRNAs between sample groups clustered by 40 reported pyroptosis-related genes (PRGs). Univariate Cox regression was used to screen out prognosis-related PRlncRNA pairs. Then, based on REOs of prognosis-related PRlncRNA pairs, a risk model for HCC was constructed by combining LASSO and stepwise multivariate Cox regression analysis. Finally, a prognosis-related competing endogenous RNA (ceRNA) network was built based on information about lncRNA-miRNA-mRNA interactions derived from the miRNet and TargetScan databases. RESULTS: Hierarchical clustering of HCC patients according to the 40 PRGs identified two groups with a significant survival difference (Kaplan-Meier log-rank, p = 0.026). Between the two groups, 104 differentially expressed lncRNAs were identified (|log2(FC)|> 1 and FDR < 5%). Among them, 83 PRlncRNA pairs showed significant associations between their REOs within HCC samples and overall survival (Univariate Cox regression, p < 0.005). An optimal 11-PRlncRNA-pair prognostic risk model was constructed for HCC. The areas under the curves (AUCs) of time-dependent receiver operating characteristic (ROC) curves of the risk model for 1-, 3-, and 5-year survival were 0.737, 0.705, and 0.797 in the validation set, respectively. Gene Set Enrichment Analysis showed that inflammation-related interleukin signaling pathways were upregulated in the predicted high-risk group (p < 0.05). Tumor immune infiltration analysis revealed a higher abundance of regulatory T cells (Tregs) and M2 macrophages and a lower abundance of CD8 + T cells in the high-risk group, indicating that excessive pyroptosis might occur in high-risk patients. Finally, eleven lncRNA-miRNA-mRNA regulatory axes associated with pyroptosis were established. CONCLUSION: Our risk model allowed us to determine the robustness of the REO-based PRlncRNA prognostic biomarkers in the stratification of HCC patients at high and low risk. The model is also helpful for understanding the molecular mechanisms between pyroptosis and HCC prognosis. High-risk patients may have excessive pyroptosis and thus be less sensitive to immune therapy.

Construct of qualitative diagnostic biomarkers specific for glioma by pairing serum microRNAs.

BACKGROUND: Serum microRNAs (miRNAs) are promising non-invasive biomarkers for diagnosing glioma. However, most reported predictive models are constructed without a large enough sample size, and quantitative expression levels of their constituent serum miRNAs are susceptible to batch effects, decreasing their clinical applicability. METHODS: We propose a general method for detecting qualitative serum predictive biomarkers using a large cohort of miRNA-profiled serum samples (n = 15,460) based on the within-sample relative expression orderings of miRNAs. RESULTS: Two panels of miRNA pairs (miRPairs) were developed. The first was composed of five serum miRPairs (5-miRPairs), reaching 100% diagnostic accuracy in three validation sets for distinguishing glioma and non-cancer controls (n = 436: glioma = 236, non-cancers = 200). An additional validation set without glioma samples (non-cancers = 2611) showed a predictive accuracy of 95.9%. The second panel included 32 serum miRPairs (32-miRPairs), reaching 100% diagnostic performance in training set on specifically discriminating glioma from other cancer types (sensitivity = 100%, specificity = 100%, accuracy = 100%), which was reproducible in five validation datasets (n = 3387: glioma = 236, non-glioma cancers = 3151, sensitivity> 97.9%, specificity> 99.5%, accuracy> 95.7%). In other brain diseases, the 5-miRPairs classified all non-neoplastic samples as non-cancer, including stroke (n = 165), Alzheimer's disease (n = 973), and healthy samples (n = 1820), and all neoplastic samples as cancer, including meningioma (n = 16), and primary central nervous system lymphoma samples (n = 39). The 32-miRPairs predicted 82.2 and 92.3% of the two kinds of neoplastic samples as positive, respectively. Based on the Human miRNA tissue atlas database, the glioma-specific 32-miRPairs were significantly enriched in the spinal cord (p = 0.013) and brain (p = 0.015). CONCLUSIONS: The identified 5-miRPairs and 32-miRPairs provide potential population screening and cancer-specific biomarkers for glioma clinical practice.

Insertion sequence contributes to the evolution and environmental adaptation of Acidithiobacillus.

BACKGROUND: The genus Acidithiobacillus has been widely concerned due to its superior survival and oxidation ability in acid mine drainage (AMD). However, the contribution of insertion sequence (IS) to their biological evolution and environmental adaptation is very limited. ISs are the simplest kinds of mobile genetic elements (MGEs), capable of interrupting genes, operons, or regulating the expression of genes through transposition activity. ISs could be classified into different families with their own members, possessing different copies. RESULTS: In this study, the distribution and evolution of ISs, as well as the functions of the genes around ISs in 36 Acidithiobacillus genomes, were analyzed. The results showed that 248 members belonging to 23 IS families with a total of 10,652 copies were identified within the target genomes. The IS families and copy numbers among each species were significantly different, indicating that the IS distribution of Acidithiobacillus were not even. A. ferrooxidans had 166 IS members, which may develop more gene transposition strategies compared with other Acidithiobacillus spp. What's more, A. thiooxidans harbored the most IS copies, suggesting that their ISs were the most active and more likely to transpose. The ISs clustered in the phylogenetic tree approximately according to the family, which were mostly different from the evolutionary trends of their host genomes. Thus, it was suggested that the recent activity of ISs of Acidithiobacillus was not only determined by their genetic characteristics, but related with the environmental pressure. In addition, many ISs especially Tn3 and IS110 families were inserted around the regions whose functions were As/Hg/Cu/Co/Zn/Cd translocation and sulfur oxidation, implying that ISs could improve the adaptive capacities of Acidithiobacillus to the extremely acidic environment by enhancing their resistance to heavy metals and utilization of sulfur. CONCLUSIONS: This study provided the genomic evidence for the contribution of IS to evolution and adaptation of Acidithiobacillus, opening novel sights into the genome plasticity of those acidophiles.

Spatial structure of the non-integrable discrete defocusing Hirota equation.

In this paper, we investigate the spatial property of the non-integrable discrete defocusing Hirota equation utilizing a planar nonlinear discrete dynamical map method. We construct the periodic orbit solutions of the stationary discrete defocusing Hirota equation. The behavior of the orbits in the vicinity of the special periodic solution is analyzed by taking advantage of the named residue. We characterize the effects of the parameters on the aperiodic orbits with the aid of numerical simulations. A comparison with the non-integrable discrete defocusing nonlinear Schrödinger equation case reveals that the non-integrable discrete defocusing Hirota equation has more abundant spatial properties. Rather an interesting and novel thing is that for any initial value, there exists triperiodic solutions for a reduced map.

Prediction of postoperative hypokalemia in patients with oral cancer undergoing en bloc cancer resection: a retrospective cohort study.

BACKGROUND: The factors associated with postoperative hypokalemia in patients with oral cancer remain unclear. We determined the preoperative factors associated with postoperative hypokalemia in patients with oral cancer following en bloc cancer resection and established a nomogram for postoperative hypokalemia prediction. METHODS: Data from 381 patients with oral cancer who underwent en bloc cancer resection were retrospectively analyzed. Univariate and multivariate analyses were performed to identify the risk factors for postoperative hypokalemia. We used receiver operating characteristic (ROC) curves to quantify the factors' effectiveness. A nomogram was created to show each predictor's relative weight and the likelihood of postoperative hypokalemia development. The multinomial regression model's effectiveness was also evaluated. RESULTS: Preoperative factors, including sex, preoperative serum potassium level, and preoperative platelet-to-lymphocyte ratio (PLR), were significantly associated with postoperative hypokalemia. Based on the ROC curve, the preoperative serum potassium and PLR cut-off levels were 3.98 mmol/L and 117, respectively. Further multivariate analysis indicated that female sex, preoperative serum potassium level < 3.98 mmol/L, and preoperative PLR ≥ 117 were independently associated with postoperative hypokalemia. We constructed a predictive nomogram with all these factors for the risk of postoperative hypokalemia with good discrimination and internal validation. CONCLUSIONS: The predictive nomogram for postoperative hypokalemia risk constructed with these factors had good discrimination and internal validation. The developed nomogram will add value to these independent risk factors that can be identified at admission in order to predict postoperative hypokalemia.

Fluorescence determination of glyphosate based on a DNA-templated copper nanoparticle biosensor.

A rapid and convenient fluorescence glyphosate (GLYP) biosensor was developed based on DNA-templated copper nanoparticles (DNA-CuNPs). In the absence of GLYP, the DNA-CuNPs were formed through the reduction of Cu2+ by vitamin C (Vc). The DNA-CuNPs emitted intense fluorescence at 615 nm when being excited at 340 nm. In the presence of GLYP, GLYP can strongly chelate with Cu2+ by the phosphate and carboxyl groups to decrease the amount of free Cu2+. Due to the lack of free Cu2+, DNA-CuNPs cannot be formed, which caused the fluorescence to decrease. The whole detection process of this proposed GLYP biosensor can be completed within 14 min. Titration experiments showed that this biosensor had a linear relationship for GLYP in the range 1 to 18 µM with a limit of detection (LOD) of 0.47 µM. This biosensor showed obvious selectivity among other pesticides, even between GLYP and organophosphorus pesticides. This biosensor performed well for GLYP detection in real samples with recoveries of 88.0-104.0%.

Antimony transformation and mobilization from stibnite by an antimonite oxidizing bacterium Bosea sp. AS-1.

Soils and waters are heavily contaminated by antimony in Xikuangshan (XKS) mine area. It is widely accepted that oxidative dissolution of sulfide minerals and aqueous dissolution are the most prevalent geochemical mechanisms for the release of Sb to the environment. Bosea sp. AS-1 is an antimonite-oxidizer isolated from the mine slag in Xikuangshan Sb mine. Whole genome sequencing revealed the presence of multiple sulfur-oxidizing genes, antimony (Sb) metabolism genes and carbon fixation genes in AS-1's genome. We therefore hypothesized that under oxic conditions, AS-1 could mediate the oxidation of sulfide and Sb(III) in stibnite (Sb2S3) and lead to the release of Sb. Indeed, strain AS-1 was discovered as an autotrophic Sb(III)-oxidizer. Antimony mobilization studies conducted with strain AS-1 showed significantly enhanced mobilization of Sb, and complete oxidation of released Sb and sulfur to Sb(V) and sulfate. In addition, AS-1 induced a faster release of Sb under heterotrophic condition, and new acicular minerals might form. These findings support the hypothesis that microorganisms play an important role in the mobilization and transformation of Sb in XKS mine area and may contribute to our further understanding of the Sb biogeochemical redox cycle in natural environment.

Enhanced alleviation of aGVHD by TGF-ß1-modified mesenchymal stem cells in mice through shifting MΦ into M2 phenotype and promoting the differentiation of Treg cells.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is the only curative method in treating haematologic malignant diseases. Graft-versus-host disease (GVHD) is a common complication post-allo-HSCT, which can be life-threatening. Mesenchymal stem cells (MSCs) as an adult stem cell with immunoregulatory function have demonstrated efficacy in steroid resistant acute GVHD (aGVHD). However, the outcome of aGVHD treated with MSCs in clinical trials varied and its underlying mechanism is still unclear. TGF-ß1 is a potent cytokine, which plays a key role in immunoregulation. In the present study, we firstly transduced the lentivirus vector containing TGF-ß1 gene with mouse bone marrow-derived MSCs. Then, we investigated the immunosuppressive effect of TGF-ß1 gene-modified MSCs on lymphocytes in vitro and its preventive and therapeutical effects on murine aGVHD model in vivo. Murine MSC was successfully isolated and identified. TGF-ß1 was efficiently transduced into mouse MSCs, and high level TGF-ß1 was detected. MSC-TGF-ß1 shared the same morphology and immunotypic features of normal MSC. In vitro, MSC-TGF-ß1 showed enhanced immunosuppressive function on lymphocyte proliferation. In vivo, MSC-TGF-ß1 showed enhanced amelioration on the severity of aGVHD both in prophylactic and therapeutic murine models. Finally, the macrophages (MØs) derived from MSC-TGF-ß1-treated mice showed a remarkably increasing of anti-inflammatory M2-like phenotype. Furthermore, the differentiation of CD4+ CD25+ Foxp3+ Treg cells was significantly increased in MSC-TGF-ß1-treated group. Taken together, we proved that MSC-TGF-ß1 showed enhanced alleviation of aGVHD severity in mice by skewing macrophages into a M2 like phenotype or increasing the proportion of Treg cells, which opens a new frontier in the treatment of aGVHD.

Autologous Stem Cell Transplantation Is a Viable Postremission Therapy for Intermediate-Risk Acute Myeloid Leukemia in First Complete Remission in the Absence of a Matched Identical Sibling: A Meta-Analysis.

BACKGROUND: The preferred type of postremission therapy (PRT) for intermediate-risk acute myeloid leukemia (AML) in first complete remission (CR1) is a subject of continued debate. Although allogeneic stem cell transplantation (alloSCT) is regarded as a curative strategy for AML, the efficacy of autologous stem cell transplantation (autoSCT) for patients without a matched sibling donor (MSD) has remained controversial. METHODS: To compare survival outcomes after alloSCT versus autoSCT for patients with intermediate-risk AML in CR1, we performed a meta-analysis of 11 clinical studies. The outcomes included relapse-free survival (RFS), overall survival (OS), relapse rate (RR), and treatment-related mortality (TRM). RESULTS: Compared with autoSCT, alloSCT showed better RFS, OS, and RR benefits, but higher TRM. Subgroup analysis based on donor category (MSD and matched unrelated donor [MUD]) of alloSCT showed alloSCT from MSD rather than from MUD had better OS benefits compared to autoSCT. For fms-like tyrosine kinase 3 internal tandem duplications (FLT3-ITD) wild-type patients, alloSCT and autoSCT had comparable RFS and OS outcomes. CONCLUSION: Our results suggest that, in the absence of an available MSD, autoSCT remains a viable PRT alternative for intermediate-risk AML in CR1, especially for FLT3-ITD wild-type patients.

The detoxification potential of ferric ions for bioleaching of the chalcopyrite associated with fluoride-bearing gangue mineral.

Fluoride toxicity to microorganisms was a predominant factor contributing to the failure of a commercial scale bioleach heap. An integrated control strategy for fluoride complexation without jarosite generation by stepwise adding ferric ions was first proposed to enable the bioleaching of the chalcopyrite associated with fluoride-bearing gangue mineral by Acidithiobacillus ferrooxidans. Chemical speciation calculation revealed that with the presence of Fe3+, the concentration of the main lethal fluoride to microorganism, HF, decreased dramatically. The pure culture study showed that the detrimental effect of fluoride on microorganism was eliminated by increasing the molar ratio of Fe3+/F- to 3:1. Furthermore, chalcopyrite bioleaching experiment revealed the minimum Fe3+/F- molar ratio that enabled the bioleaching was 6:1. Stepwise addition was an effective way to promote a balanced system and avoid the formation of jarosite caused by the excessive Fe3+. Above all, the introduction of Fe3+ is a feasible method for reducing the fluoride toxicity during the bioleaching of chalcopyrite, shedding light on the industrial applications.

SIRT1 activator isolated from artificial gastric juice incubate of total saponins in stems and leaves of Panax ginseng.

Panax ginseng as a traditional Chinese medicine has been extensively used for the treatment of many diseases, especially in prolonging life and anti-tumor. Dammarane-type triterpenoids from P. ginseng have diverse beneficial effects and their chemical structures can be modified in the gastrointestinal tract after oral administration. In this paper, the dammarane-type triterpenoids were isolated from artificial gastric juice incubate of total saponins in the stems and leaves of P. ginseng through column chromatographic methods and their chemical structures were determined based on spectral data. Two new dammarane-type triterpenoids named ginsenotransmetins B (1) and C (2), along with twenty-nine known compounds (3-31), were obtained. All 31 compounds isolated were investigated for their activities of SIRT1 using SIRT1 fluorometric drug discovery assay kit. Among them, compounds 11, 17, 18, 20, 23, 24, 28, and 29, which were found to be potential as SIRT1 activators, exhibited significant stimulation of SIRT1 activity. The results showed that these compounds may be considered to be a useful medicinal resource for prolonging life and anti-tumor. In addition, the results were helpful to explain the longevity effect of ginseng from the new field of view.

Interleukin-10 Gene-Modified Dendritic Cell-Induced Type 1 Regulatory T Cells Induce Transplant-Tolerance and Impede Graft Versus Host Disease After Allogeneic Stem Cell Transplantation.

BACKGROUND/AIMS: Tr1 cells can induce peripheral tolerance to self- and foreign antigens, and have been developed as a therapeutic tool for the induction of tolerance to transplanted tissue. We explored the feasibility of generating Tr1 cells by using IL-10 gene-modified recipient DCs (DCLV-IL-10) to stimulate donor naive CD4+ T cells. We also investigated some biological properties of Tr1 cells. METHODS: DCLV-IL-10 were generated through DCs transduced with a lentivirus vector carrying the IL-10 gene, and Tr1 cells were produced by using DCLV-IL-10 to stimulate naive CD4+ T cells. The effects of Tr1 cells on T-cell proliferation and the occurrence of graft versus host disease (GVHD) following allogeneic stem-cell transplantation (allo-HSCT) were investigated. RESULTS: The DCLV-IL-10-induced Tr1 cells co-expressed LAG-3 and CD49b. Moreover, they also expressed CD4, CD25, and IL-10, but not Foxp3, and secreted significantly higher levels of IL-10 (1,729.36 ± 185.79 pg/mL; P < 0.001) and INF-γ (1,524.48 ± 168.65 pg/mL; P < 0.01) than the control T cells upon the stimulation by allogeneic DCs. Tr1 cells markedly suppressed T-lymphocyte proliferation and the mixed lymphocytic response (MLR) in vitro. The mice used in the allo-HSCT model had longer survival times and lower clinical and pathological GVHD scores than the control mice. CONCLUSION: IL-10 gene-modified DC-induced Tr1 cells may be used as a potent cellular therapy for the prevention of GVHD after allo-HSCT.

TGF-ß1-silenced leukemia cell-derived exosomes target dendritic cells to induce potent anti-leukemic immunity in a mouse model.

Tumor-derived exosomes (TEX) can induce a specific antitumor immune response and have been developed as a promising tumor vaccine. Despite promising preclinical data, TEX exhibit relatively low efficacy and limited clinical benefit in clinical trials. In the present study, we investigated whether exosomes from the TGF-ß1 silenced L1210 cells (LEXTGF-ß1si) can enhance the efficacy of DC-based vaccines. We silenced TGF-ß1 in L1210 cells with a lentiviral shRNA vector and prepared the LEXTGF-ß1si. It was shown that LEXTGF-ß1si can significantly decrease TGF-ß1 expression of dendritic cells (DC) and effectively promote their maturation and immune function. In addition, DC pulsed with LEXTGF-ß1si (DCLEX-TGF-ß1si) more effectively promoted CD4+ T cell proliferation in vitro and Th1 cytokine secretion and induced tumor-specific CTL response. This response was higher in potency compared to that noted by the other two formulations. Moreover, DCLEX-TGF-ß1si inhibited tumor growth more efficiently than other formulations did as the preventive or therapeutic tumor vaccine. Accordingly, these findings revealed that DCLEX-TGF-ß1si induced a more potent antigen-specific anti-leukemic immunity than DC pulsed with exosomes from non-manipulated L1210 cells. This indicated that the targeting of DC by LEXTGF-ß1si may be used as a promising approach for leukemia immunotherapy.

Adaptive Evolution of Extreme Acidophile Sulfobacillus thermosulfidooxidans Potentially Driven by Horizontal Gene Transfer and Gene Loss.

Recent phylogenomic analysis has suggested that three strains isolated from different copper mine tailings around the world were taxonomically affiliated with Sulfobacillusthermosulfidooxidans Here, we present a detailed investigation of their genomic features, particularly with respect to metabolic potentials and stress tolerance mechanisms. Comprehensive analysis of the Sulfobacillus genomes identified a core set of essential genes with specialized biological functions in the survival of acidophiles in their habitats, despite differences in their metabolic pathways. The Sulfobacillus strains also showed evidence for stress management, thereby enabling them to efficiently respond to harsh environments. Further analysis of metabolic profiles provided novel insights into the presence of genomic streamlining, highlighting the importance of gene loss as a main mechanism that potentially contributes to cellular economization. Another important evolutionary force, especially in larger genomes, is gene acquisition via horizontal gene transfer (HGT), which might play a crucial role in the recruitment of novel functionalities. Also, a successful integration of genes acquired from archaeal donors appears to be an effective way of enhancing the adaptive capacity to cope with environmental changes. Taken together, the findings of this study significantly expand the spectrum of HGT and genome reduction in shaping the evolutionary history of Sulfobacillus strains.IMPORTANCE Horizontal gene transfer (HGT) and gene loss are recognized as major driving forces that contribute to the adaptive evolution of microbial genomes, although their relative importance remains elusive. The findings of this study suggest that highly frequent gene turnovers within microorganisms via HGT were necessary to incur additional novel functionalities to increase the capacity of acidophiles to adapt to changing environments. Evidence also reveals a fascinating phenomenon of potential cross-kingdom HGT. Furthermore, genome streamlining may be a critical force in driving the evolution of microbial genomes. Taken together, this study provides insights into the importance of both HGT and gene loss in the evolution and diversification of bacterial genomes.

Effects of pyrite and sphalerite on population compositions, dynamics and copper extraction efficiency in chalcopyrite bioleaching process.

This study used an artificial microbial community with four known moderately thermophilic acidophiles (three bacteria including Acidithiobacillus caldus S1, Sulfobacillus thermosulfidooxidans ST and Leptospirillum ferriphilum YSK, and one archaea, Ferroplasma thermophilum L1) to explore the variation of microbial community structure, composition, dynamics and function (e.g., copper extraction efficiency) in chalcopyrite bioleaching (C) systems with additions of pyrite (CP) or sphalerite (CS). The community compositions and dynamics in the solution and on the ore surface were investigated by real-time quantitative PCR (qPCR). The results showed that the addition of pyrite or sphalerite changed the microbial community composition and dynamics dramatically during the chalcopyrite bioleaching process. For example, A. caldus (above 60%) was the dominant species at the initial stage in three groups, and at the middle stage, still dominated C group (above 70%), but it was replaced by L. ferriphilum (above 60%) in CP and CS groups; at the final stage, L. ferriphilum dominated C group, while F. thermophilum dominated CP group on the ore surface. Furthermore, the additions of pyrite or sphalerite both made the increase of redox potential (ORP) and the concentrations of Fe3+ and H+, which would affect the microbial community compositions and copper extraction efficiency. Additionally, pyrite could enhance copper extraction efficiency (e.g., improving around 13.2% on day 6) during chalcopyrite bioleaching; on the contrary, sphalerite restrained it.

Electrically Modulated Localized Surface Plasmon around Self-Assembled-Monolayer-Covered Nanoparticles.

This article reports the observation of electrical modulation of localized surface plasmon around self-assembled monolayer (SAM)-modified gold nanoparticles and the establishment of a new spectroscopy technique, that is, dynamic electro-optical spectroscopy (DEOS). The gold nanoparticles are deposited onto a transparent conductive substrate, and an electrical bias applied on the conductive substrate can cause shift of resonance plasmon response, where the direction of peak shift is related to the polarity of applied bias. The peak shift observed at 2.4 V is approximately ten times larger than those reported in previous work. It is postulated that significant peak shift is the result of reorientation of adsorbed water on electrode, which can change local dielectric environment of nanoparticles. An energy barrier is identified when adsorbed water molecules are turned from oxygen-down to oxygen-up. Frequency-dependent peak shifts on surface-modified gold nanoparticles show that reorientation is a fast reversible process with rich dynamics.