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The flexible (C3H2O4)2− groups were employed to design a new mixed alkali malonate KLi(C3H2O4)·H2O as an potential UV NLO crystal achieving the balance between strong SHG efficiency and moderate birefringence.

Two tellurium(IV)-based sulfate nonlinear optical (NLO) materials, Te2O3(SO4) and Te(OH)3(SO4)·H3O, were successfully synthesized via the mild hydrothermal method. Te2O3SO4 has a two-dimensional (2D) structure consisting of [Te6O12]∞ layers as well as [SO4] groups. Te(OH)3(SO4)·H3O features a simple 0D structure made up of an isolated [TeO3] pyramid and a [SO4] tetrahedra. Both of them are phase-matching materials and show remarkable powder second harmonic generation (SHG) efficiencies about 6 and 3 times that of KH2PO4 (KDP), respectively, for Te2O3SO4 and Te(OH)3(SO4)·H3O. Especially for Te(OH)3(SO4)·H3O, in addition to a large SHG response, it possesses a short UV cutoff edge (∼233 nm) as well as moderate birefringence (0.052@546.1 nm). Furthermore, theoretical calculations confirmed that their strong SHG effects are due to the synergistic effect of the [TeO3] pyramid and [SO4] tetrahedra.

Two new alkaline earth barbiturates, Ca(H3C4N2O3)2·H2O and Sr(H5C8N4O5)2·4H2O, were synthesized via the mild hydrothermal technique. For Ca(H3C4N2O3)2·H2O, the stacking (H3C4N2O3)- anions along the c axis are interconnected by CaO7 polydedra forming a three-dimensional structure. Also, for Sr(H5C8N4O5)2·4H2O, it has two-dimensional layers composed by SrO7 polyhedra and (H5C8N4O5)- anions. The (H5C8N4O5)- anions can be seen as two (H3C4N2O3)- anions connected each other via the N-C bond. Powder second-harmonic generation (SHG) measurements revealed that Ca(H3C4N2O3)2·H2O is a phase-matchable material with a moderate SHG response (ca. 1.15× that of KDP). Furthermore, the birefringence values of the two crystals were measured as 0.49 and 0.475 at 546.1 nm, respectively. The theoretical calculations showed that the SHG response and large birefringence were primarily caused by the (H3C4N2O3)- and (H5C8N4O5)- groups.

Ionic inorganic-organic ultraviolet (UV) nonlinear optical (NLO) materials have gradually become attractive because they can integrate their advantages into one. In this study, the first noncentros...

The first fluorosulfonic ultraviolet (UV) nonlinear optical (NLO) material, C(NH2 )3 SO3 F, is rationally designed by taking KBe2 BO3 F2 (KBBF) as the parent compound. C(NH2 )3 SO3 F features similar topological layers as KBBF by replacing inorganic (BO3 )3- with organic C(NH2 )3 + trigonal units and BeO3 F with SO3 F- tetrahedra. Therefore, C(NH2 )3 SO3 F is a metal-free UV NLO crystal. Benefiting from the coplanar configuration of the C(NH2 )3 + cationic groups, it possesses a large SHG response of 5×KDP and moderate birefringence of 0.133@1064 nm. Besides, it has a short UV cutoff edge of 200 nm. The calculated results reveal the shortest SHG phase-matching wavelengths can reach 200 nm. These findings highlight the exploration of metal-free compounds as nontoxic and low-cost UV NLO materials as a new research area.

A new tin iodate fluoride, Sn(IO3)2F2, was meticulously designed based on Sn(IO3)4 with an intriguing chemical tailoring transformation from the centrosymmetric to noncentrosymmetric structure. Sn(...

Laser Tweezers Raman Spectroscopy (LTRS) is a combination of laser tweezers and Raman spectroscopy. It is a physical tool based on the mechanical effects of the laser, which can be used to study single living cells in suspension in a fast and non-destructive way. Our work aims to establish a methodology system based on LTRS to rapidly and non-destructively detect the resistance of acute lymphoblastic leukemia (ALL) cells and to provide a new idea for the evaluation of the resistance of ALL cells. Two specific adriamycin-resistant and parental ALL cells BALL-1 and Nalm6 were included in this study. Adriamycin resistant cells can induce the spectral differences, which can be detected by LTRS initially. To ensure the accuracy of the results, we use the principal components analysis (PCA) as well as the classification and regression trees (CRT) algorithms, which show that the specificity and sensitivity of LTRS are above 90%. In addition, to further clarify the chemoresistance status of ALL cells, we used the CRT models and receiver operating characteristic (ROC) curves which are based on the band data to look for some important bands and band intensity ratios that have strong pointing significance. Our work proves that LTRS analysis combined with multivariate statistical analyses have great potential to be a novel analytical strategy at the single-cell level for rapidly evaluating the chemoresistance status of ALL cells.

CAD/CAM (computer-aided design and computer-aided manufacturing) technology has been widely applied in clinical dentistry, but the material safety remains a concern. To investigate the impacts of CAD/CAM metallic materials on trace metals and biocompatibilities, selective laser melted (SLM) cobalt-chromium (Co-Cr) alloys and computer numeric controlled milled (CNC milled) commercially pure titanium (CP-Ti) were placed on the maxilla of beagle dogs for 6 months. The trace metals in the oral mucosa, blood, liver, kidney, and hair were then determined by inductively coupled plasma mass spectrometry (ICP-MS). The histopathologic changes and biocompatibilities of tissues were examined by hematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) method, immunohistochemistry (IHC) assay, Western blot analysis, and liver and kidney function tests. Our results showed that trace metals released from these two CAD/CAM metallic materials accumulated transiently in the oral mucosa and whole blood. The trace metals released from SLM Co-Cr alloys could also transiently accumulate in the plasm and hair. In addition, these two CAD/CAM metallic materials both induced apoptosis and histopathologic changes in the oral mucosa, with SLM Co-Cr alloys inducing a higher level of apoptosis. In contrast, both materials did not exert autophagic effects on the oral mucosa or affect the trace metals, functions, or biocompatibilities of the liver and kidney. Therefore, this study suggests that CAD/CAM metallic materials should be selected carefully, especially in patients with metal- and apoptosis-related diseases, and CNC-milled CP-Ti can be recommended to patients on account of its better biocompatibility and safety.

Leukemia stem cells (LSCs) have critical functions in acute leukemia (AL) pathogenesis, participating in its initiation and relapse. Thus, identifying new molecules to eradicate LSCs represents a high priority for AL management. This work identified E35, a novel Emodin derivative, which strongly inhibited growth and enhanced apoptosis of AL stem cell lines, and primary stem and progenitor cells from AL cases, while sparing normal hematopoietic cells. Furthermore, functional assays in cultured cells and animals suggested that E35 preferentially ablated primitive leukemia cell populations without impairing their normal counterparts. Moreover, molecular studies showed that E35 remarkably downregulated drug‐resistant gene and dramatically inhibited the Akt/mammalian target of rapamycin signaling pathway. Notably, the in vivo anti‐LSC activity of E35 was further confirmed in murine xenotransplantation models. Collectively, these findings indicate E35 constitutes a novel therapeutic candidate for AL, potentially targeting leukemia stem and progenitor cells., Leukemia stem cells have critical functions in acute leukemia (AL) pathogenesis, participating in its initiation and relapse. This work identified E35, a novel Emodin derivative, ablated primitive leukemia cell populations without impairing their normal counterparts, indicating E35 constitutes a novel therapeutic candidate for AL.

A new mixed alkali hydro-isocyanurate, RbNa(HC3N3O3)·2H2O, with the noncentrosymmetric space group Pna21 (No. 33), has been successfully grown by a hydrothermal method. The structure can be described as 2D wavy [Na(HC3N3O3)O4]∞ layers separated by Rb atoms. The UV-vis diffuse reflection measurement revealed that RbNa(HC3N3O3)·2H2O has a large band gap of 5.10 eV, corresponding to the UV cutoff edge of 241 nm. The polarizing microscope measurement of a micron-sized single crystal shows that RbNa(HC3N3O3)·2H2O has a large birefringence of 0.194. The powder SHG measurement indicated that RbNa(HC3N3O3)·2H2O exhibits a strong SHG effect that is 5.3 times that of KH2PO4 (KDP) and can realize phase-matching in the visible and UV region. Moreover, the differences in the SHG responses between RbNa(HC3N3O3)·2H2O and two isostructural compounds have been investigated, which depend heavily on the structural modulation of the (HC3N3O3)2− group by cations. Meanwhile, the electronic structures and optical properties were well analyzed using DFT methods.

PRL-3, an oncogenic dual-specificity phosphatase, is overexpressed in 50% of acute myeloid leukemia patients. Stathmin has been identified as a downstream target of PRL-3 in colorectal cancer. However, the correlation between PRL-3 and stathmin in myeloid leukemia is unclear. In this study, we revealed the positive correlation between PRL-3 and stathmin in myeloid leukemia. Knockdown of the PRL-3 gene by shRNA reduced the expression of downstream stathmin, suppressed cell proliferation, induced G2/M arrest and cell apoptosis, and inhibited migration and invasion in myeloid leukemia cells. Moreover, our study was the first to provide evidence that silencing PRL-3 increased the phosphorylation level in Ser16, Ser25, Ser38, and Ser63 of stathmin, and in turn inhibited the STAT3 and STAT5 signaling in myeloid leukemia cells. This evidence points to a promoted role for PRL-3 in the progression of myeloid leukemia, and PRL-3 could be a possible new treatment target.

Background: The D816V mutation of c-KIT can constitutively activate tyrosine kinase, thereby promote core binding factor acute myeloid leukemia (CBF-AML) cell proliferation and inhibit apoptosis. Previous studies have indicated similar proliferation and apoptosis between N822K and D816V mutations.The current study aims to determine the occurrence and potential functions of N822K mutation-induced c-KIT activation in AML cells, and explore possible mechanisms of poor prognosis of CBF-AML. Methods: c-KIT N822K mutation status in AML cells was determined by exon 17 sequencing. The level of c-KIT expression was detected by flow cytometry (FCM) and colony formation was assessed after hu-SCF stimulation. After exposure to sunitinib (a kind of tyrosine kinase inhibitor, TKI), cell proliferation inhibition was tested by MTT, cell cycle and apoptosis were measured by FCM, autophagy was assessed by fluorescence microscopy and immunoblotting. Results: Kasumi-1 cell line was detected to bear c-KIT N822K (T>A) mutation. After hu-SCF stimulation, CD117 expression was decreased and the colony formation efficiency was not altered in Kasumi-1 cells. After sunitinib inhibited the c-KIT activity, the colony formation efficiency was reduced, and the half-maximal inhibitory concentration (IC50) of sunitinib was low (0.44±0.17μM) at 48 hours. Moreover, cells were arrested in G0/G1 phase, corresponding to an increase of apoptosis ratio. Acidic vesicular organelles (AVO) were observed along with an altered expression of autophagy-related proteins in Kasumi-1 cells. Conclusions: Our data indicated that inhibition of N822K T>A mutation-induced constitutive c-KIT activation in AML cells triggered apoptotic and autophagic pathways leading to death, and c-KIT N822K mutation may have clinical application as a CBF-AML treatment target.

The objective of this study is to investigate leaching residual monomer and biological effects of four types of conventional and computer-aided design/computer-aided manufacturing (CAD/CAM) dental polymers on human gingival fibroblasts (HGFs).A total of 540 disk-shaped specimens were fabricated from four different materials (n=135 per group): compression-molding polymethylmethacrylate (PMMA) (conventional denture polymer), CAD/CAM PMMA (CAD/CAM denture polymer), bis-acrylic composite resin (conventional temporary polymer), and CAD/CAM PMMA (CAD/CAM temporary polymer). Specimens were eluted in cell culture medium for 72 h at 37°C, and the residual monomer in eluates subsequently was measured by high-performance liquid chromatography (HPLC). The biological effects of material eluates on HGFs were analyzed by CCK-8 assay, flow cytometry, real-time quantitative PCR, Western blotting, and enzyme-linked immunosorbent assay (ELISA) to identify cell death patterns and its biological mechanism.Methyl methacrylate (MMA) was detected only in compression-molding PMMA, and by-products were detected in bis-acrylic composite resin. The cell proliferation of CAD/CAM denture polymer or CAD/CAM temporary polymer was greater than that of compression-molding PMMA or bis-acrylic composite resin at 72 h in culture. No apoptosis and necrosis were detected in CAD/CAM dental polymers. Apoptosis was detected only in bis-acrylic composite resin and further confirmed by the upregulation of Bax and cleaved Caspase-3, as well as the downregulation of Bcl-2 gene. And no significant variation in inflammatory cytokines secretion was observed in all materials.CAD/CAM dental polymers (including temporary and denture polymers) have favorable biocompatibility due to lower residual monomer, which provides scientific evidence to the controversy of biocompatibility of conventional and CAD/CAM dental polymers.The use of CAD/CAM dental polymers is recommended in the fabrication of temporary restorations and dentures due to their favorable biocompatibility.

Cysteine metabolism plays a critical role in cancer cell survival. Cysteine depletion was reported to inhibit tumor growth and induce pancreatic cancer cell ferroptosis. Nevertheless, the effect of cysteine depletion in chronic myeloid leukemia (CML) remains to be explored. In this work, we showed that cysteine depletion can induce K562/G01 but not K562 cell death in the form of ferroptosis. However, the glutathione (GSH)/glutathione peroxidase 4 (GPX4) pathways of the two CML cell lines were both blocked after cysteine depletion. This unexpected outcome guided us to perform RNA-Seq to screen the key genes that affect the sensitivity of CML cells to cysteine depletion. Excitingly, thioredoxin reductase 1 (TXNRD1), which related to cell redox metabolism, was significantly upregulated in K562/G01 cells after cysteine depletion. We further inferred that the upregulation is negatively feedback by the enzyme activity decrease of TXNRD1. Then, we triggered the ferroptosis by applying TXNRD1 shRNA and TXNRD1 inhibitor auranofin in K562 cells after cysteine depletion. In summary, we have reason to believe that TXNRD1 is a key regulator involved in the ferroptosis of CML cells induced by cysteine depletion in vitro. These findings highlight that cysteine depletion serves as a potential therapeutic strategy for overcoming chemotherapy resistance CML.

Multidrug resistance is highly associated with poor prognosis of chronic myeloid leukemia. This work aims to explore whether the laser tweezers Raman spectroscopy (LTRS) could be practical in separating adriamycin-resistant chronic myeloid leukemia cells K562/adriamycin from its parental cells K562, and to explore the potential mechanisms. Detection of LTRS initially reflected the spectral differences caused by chemoresistance including bands assigned to carbohydrates, amino acid, protein, lipids, and nucleic acid. In addition, principal components analysis as well as the classification and regression trees algorithms showed that the specificity and sensitivity were above 90%. Moreover, the band data-based classification and regression tree model and receiver operating characteristic curve further determined some important bands and band intensity ratios to be reliable indexes in discriminating K562 chemoresistance status. Finally, we highlighted three metabolism pathways correlated with chemoresistance. This work demonstrates that the label-free LTRS analysis combined with multivariate statistical analyses have great potential to be a novel analytical strategy at the single-cell level for rapid evaluation of the chemoresistance status of K562 cells.

Background: HuR/ELAVL1 (embryonic lethal abnormal vision 1) protein exerts important prognostic effects of involving in the pathogenesis and development of acute myeloid leukemia (AML). This study aims to investigate the role of HuR targeted by miR-29b-3p in biological behaviors of AML cells and the involvement of the NF-κB and JAK/STAT signaling pathways. Methods: The expressions of HuR and miR-29b-3p were determined using real-time quantitative PCR and Western blot analysis, and the association between them was analyzed using the Spearman’s coefficient correlation. Next, the potential relationship between HuR and miR-29b-3p was predicted based on data from different biological information databases and verified by the Dual-luciferase reporter gene assay. The effect of miR-29b-3p-meidated HuR expressions on the biological behaviors of AML cells was explored after transfecting lentiviruses, mimics, and inhibitors against miR-29b-3p into AML cells. Then, the expression patterns of Bcl-2 and Bax were detected to understand the apoptosis effect of HuR on AML cells. Phosphorylation levels of NF-κB /p65, IκBα, STAT1, STAT3 and STAT5 were determined to assess the influence of HuR on AML as well as the relationship between the NF-κB and JAK/STAT signaling pathways. Results: HuR was negatively correlated with miR-29b-3p, which was thereby identified as a downstream target of miR-29b-3p in AML. When miR-29b-3p was overexpressed in AML cells, HuR expression was lowered, accompanied by inhibited cell proliferation, migration and invasion, decreased Bcl-2 and Bax levels, as well as inhibited phosphorylation levels of p65, IκBα, STAT1, STAT3 and STAT5. Conclusion: HuR is a direct target of miR-29b-3p. Lowered HuR protein expression by miR-29b-3p inhibits the malignant biological behaviors of AML cells via the inactivation of the NF-κB and JAK/STAT pathways. Key words: HuR, miR-29b-3p, malignant biological behaviors, the NF-κB and JAK/STAT signaling pathways, acute myeloid leukemia

BackgroundFerroptosis is a recently recognized type of programmed cell death that is involved in the biological processes of various cancers. However, the mechanism of ferroptosis in lung adenocarcinoma (LUAD) remains unclear. This study aimed to determine the role of ferroptosis-associated long non-coding RNAs (lncRNAs) in LUAD and to establish a prognostic model.MethodsWe downloaded ferroptosis-related genes from the FerrDb database and RNA sequencing data and clinicopathological characteristics from The Cancer Genome Atlas. We randomly divided the data into training and validation sets. Ferroptosis-associated lncRNA signatures with the lowest Akaike information criteria were determined using COX regression analysis and the least absolute shrinkage and selection operator. The risk scores of ferroptosis-related lncRNAs were calculated, and patients with LUAD were assigned to high- and low-risk groups based on the median risk score. The prognostic value of the risk scores was evaluated using Kaplan–Meier curves, Cox regression analyses, and nomograms. We then explored relationships between ferroptosis-related lncRNAs and the immune response using gene set enrichment analysis (GSEA).ResultsTen ferroptosis-related lncRNA signatures were identified in the training group, and Kaplan–Meier and Cox regression analyses confirmed that the risk scores were independent predictors of LUAD outcome in the training and validation sets (all P < 0.05). The area under the curve confirmed that the signatures could determine the prognosis of LUAD. The predictive accuracy of the established nomogram model was verified using the concordance index and calibration curve. The GSEA showed that the 10 ferroptosis-related lncRNAs might be associated with tumor immune response.ConclusionWe established a novel signature involving 10 ferroptosis-related lncRNAs (LINC01843, MIR193BHG, AC091185.1, AC027031.2, AL021707.2, AL031667.3, AL606834.1, AC026355.1, AC124045.1, and AC025048.4) that can accurately predict the outcome of LUAD and are associated with the immune response. This will provide new insights into the development of new therapies for LUAD.

Zhiyuan Zheng,1,2,* Donghong Lin,2,* Qiaoqian Chen,2,* Bin Zheng,1 Mingqiang Liang,1 Chun Chen,1 Wei Zheng1 1Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 2Medical Technology and Engineering College of Fujian Medical University, Fuzhou, Fujian, 350004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Zheng; Chun ChenDepartment of Thoracic Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, People’s Republic of ChinaTel +86 591-83357896Fax +86 591-87113828Email zwfjxh@fjmu.edu.cn; ccfjxh@fjmu.edu.cnBackground: We retrospectively analyzed the prognostic value of the albumin-to-fibrinogen ratio (AFR)–neutrophil-to-lymphocyte ratio (NLR) score, comprising preoperative AFR and NLR, in esophageal squamous cell carcinoma (ESCC) patients after radical resection.Patients and Methods: Overall, 215 patients were included. The optimal cutoff value was determined using the receiver operating characteristic (ROC) curve. Based on a low AFR (< 12.06) and high NLR (≥ 1.78), the AFR–NLR score was classified as 2 (both hematological abnormalities present), 1 (one abnormality present), or 0 (both abnormalities absent). Kaplan–Meier curves, Cox regression, and predicted nomogram were used to evaluate the prognostic value of the score.Results: The prognostic value of the AFR–NLR score was better than that of AFR or NLR alone (P < 0.05). Multivariate analysis showed that a high AFR–NLR score was an independent predictor of poor prognosis for overall survival (P < 0.001). Additionally, in the nomogram including the AFR–NLR score, the net reclassification improvement index increased by 35.5% (P < 0.001), and the integrated discrimination improvement index increased by 9.0% (P < 0.001). The predictive accuracy of the established nomogram model was proved using Harrell’s concordance index (0.811, 95% confidence interval: 0.765– 0.856) and calibration curve. Notably, the decision analysis curve showed that the nomogram had a higher net benefit within most of the threshold probability range, indicating better clinical applicability.Conclusion: The AFR–NLR score is a useful predictor of the prognosis of ESCC patients after radical resection, and the nomogram established on the basis of this score has a good prognostic value.Keywords: esophageal squamous cell cancer, AFR–NLR score, prognosis, nomogram

Two new alkaline earth barbiturates, Ca(H

The first alkali-metal nitrate isocyanurates, A(H

The application of digitally manufactured dental metals has aroused the attention on their biocompatibilities. Three-dimensional oral mucosal model (3D OMM) would provide excellent assessments to the biocompatibility. In the current study, we set to measure metal ion release levels in the extracts of cast gold-platinum alloy (Au-Pt), differently manufactured cobalt-chromium alloy (Co-Cr) and commercially pure titanium (cp-Ti). We further tested two scaffold materials of 3D OMM to determine the better one for the succedent work. Lastly, we evaluated the apoptotic and autophagic effects of cast Au-Pt, and differently manufactured Co-Cr and cp-Ti on mucosal cells based on 3D OMM. We found that, in the construction of 3D OMM, Matrigel showed better performance than bovine acellular dermal matrix. Thus, Matrigel was chosen to construct the 3D OMM in the succedent studies. The results of ion release and biological assessments showed that, firstly, cast Au-Pt and cp-Ti triggered less early apoptotic cells and ion release than cast Co-Cr, implying better chemical stability and biocompatibility of them; secondly, digitally manufactured (including CAD/CAM milling and SLM) Co-Cr showed significantly lower ion release levels and lesser early apoptotic effects on 3D OMM as compared to the cast one. Although cast cp-Ti released much more ions than CAD/CAM milling one, manufacturing methods had no impact on apoptotic effect of cp-Ti. Therefore, we believe that digital methods possess same or even better chemical stability and biocompatibility than conventional casting one. Thirdly, although increased autophagic levels are observed in all test groups, so far there is no evidence that the test metals trigger different levels of autophagy as compared to each other. In addition, correlation analysis indicates that Co, W, and Mn appear to be the potential inducements for the apoptotic and autophagic effects of Co-Cr.

A novel mixed alkali hydro-isocyanurate, KLi(HC3N3O3)·2H2O was first prepared in AOH-BOH-H3C3N3O3 (A/B = Li/Na/K/Rb/Cs) system via a solvent-drop grinding method. KLi(HC3N3O3)·2H2O shows a large second harmonic generation response (5.3 × KH2PO4) with an ultraviolet cutoff edge of 237 nm. More importantly, the bulk single crystal can be readily grown through water solution technique. Characterization of these crystals indicates that KLi(HC3N3O3)·2H2O has a high laser damage threshold (LDT) (4.76 GW/cm2) and exhibits a large birefringence (Δn = 0.186@514 nm), which reduces Type I phase-matching to 246 nm.

A new series of dihydro-isocyanurates, namely, RE(H2C3N3O3)2·(OH)·xH2O (RE = La, Y and Gd) was readily obtained by a mild hydrothermal technique using lithium hydroxide as a deprotonation agent. La(H2C3N3O3)2·OH·2H2O and Re(H2C3N3O3)2·OH·5H2O (Re = Y, Gd) crystallized in the centrosymmetric (CS) space groups P21/c and P1[combining macron], respectively. Their intricate 3D frameworks were built by cationic polyhedrons (LaO8N/ReO8) and (H2C3N3O3)- groups. The experiments and theoretical studies demonstrated that these compounds possessed short ultraviolet cut-off edges (≤240 nm) and large birefringences (Δn≥ 0.257@546.1 nm). In addition, the theoretical studies further revealed that the (H2C3N3O3)2- group plays a pivotal role in strengthening the optical anisotropy for all compounds.

The frequency of N822K mutation is high in the A-loop region of c-KIT which is highly associated with poor prognosis of core binding factor acute myeloid leukemia. The current work used common assays including cell cycle, apoptosis, clone formation and western blot to perform cytological detection for HL60 (wild type), NB4 (carrying t[15;17] chromosome translocation) and Kasumi-1 (with c-KIT N822K mutation); and meanwhile, the laser tweezers Raman spectroscopy (LTRS) was also used to perform label-free detection of single living cells. The results demonstrated that Kasumi-1 cell line bearing c-KIT N822K mutation has a stable cell cycle, while there was a significant difference between early and late apoptosis within 48 hours. The LTRS detection initially reflected the spectral differences induced by genetic abnormalities and highlighted progressive patterns of DNA and amino acids band contents which were appropriately consistent with that of cell clone ratio and the c-KIT phosphorylation level. It is concluded that methodology of LTRS-based single living cell characterization could be potential and effective to reveal gene mutation-induced cell differentiation.

Background: Hepatocellular carcinoma (HCC) causes death mainly by disseminated metastasis progression and major challenge of clinical management is to distinguish lethal metastatic stage from indolent stage. It is shown that metastatic progression is closely related to cellular metabolism. But detailed metabolic alterations and molecular mechanisms still kept unclear between subtypes of different lung metastatic potentials. Methods: The current work used NMR-based metabolomics in the study of HCC cells with high malignancy but differed in lung metastatic potentials. Cell extracts and cultured media from MHCC97L and MHCC97H were utilized to reveal metabolic alterations related to metastatic potentials. Multivariate analyses were performed to identify characteristic metabolites which were used subsequently to draw the map of relative biochemical pathways by combining KEGG database. Results: The NMR spectra of both MHCC97L and MHCC97H include various signals from necessary nutritional components and metabolic intermediates. A series of characteristic metabolites were determined from both cell extracts and media. The ability on nutrient uptake varied from cell lines. Most of amino acids decreased in high metastatic cell line, so altered amino acid metabolisms and energy metabolism were revealed in high metastatic MHCC97H cell line. The majority pathways involved six essential amino acids in which the observed branched-chain amino acids together with lysine contributed to biosynthesis or degradation. Basically MHCC97H cell line could induce more active events than that of MHCC97L to progress to high metastasis with certain molecular events. Characteristic metabolites-derived classifiers performed robustly during prediction and confirmed their critical role in supporting metastasis progression. Conclusions: Our results provide evidence that NMR-metabolomics analyses of cells are able to understand metastatic characteristics accountable for biological properties. The proposed characteristic metabolites will help to understand HCC metastatic characterizations and may be filtered as potential biomarkers.

Background Long noncoding RNAs (lncRNAs) are rapidly emerging as a novel class of transcripts associated with tumorigenesis and prognosis of oral tongue squamous cell carcinoma (OTSCC). The goal of this study was to perform a meta-analysis of the prognostic utility of tumorigenic lncRNAs as novel biomarkers of OTSCC and their associations with the clinicopathological features of OTSCC. Methods Online databases were searched for eligible studies. The hazard ratio (HR) with 95% CI was used to predict survival. The individual p-values for clinicopathological features were respectively combined using Fisher's method. Results A total of 11 studies covering 1,138 OTSCC cases were included for quantitative data synthesis. Oncogenic lncRNA expression signature was closely related to shortened overall survival (OS) of patients with OTSCC (HR = 1.85, 95% CI: 1.45 - 2.37, p = 0.001; I2 = 64.9%; p = 0.002). Stratified analysis based on clinicopathological features showed that abnormally expressed lncRNAs were significantly associated with clinical stage (p = 0.000), node metastasis (p = 0.025), T stage (p = 0.000), and nodal stage (p = 0.000). Conclusions Collectively, oncogenic lncRNAs were implicated in the development and progression of OTSCC, and may serve as novel biomarkers for predicting the prognosis of OTSCC patients.

ABSTRACT Background Capsule is an vital virulence factor in Cryptococcus neoformans infection. Recent studies show CAP10 is a key gene in capsular formation. However, the role of CAP10 in the pathophysiology of cryptococcosis is still not well understood. This study aims to investigate the association of CAP10 expression with the immune responses to infected mice. Methods The shRNA expression plasmid was designed to interfere with the synthesis of CAP10. The animal model was established with C. neoformans wt strain H99, cap10-shRNA C. neoformans and PBS control in the respiratory tract. On the 7 days and 21 days after infection, mice lung histopathological examination and homogenate culture were performed, and cytokines expression level in the serum of mice were quantitatively detected. Results The lower degree of edema and infiltration of inflammatory cells were observed in cap10-shRNA group. The growth rate of cap10-shRNA strain was significantly reduced. In addition, interference with CAP10 altered the expression profile of Th1, Th2, Th17 and Treg type cytokine. Down-regulation of CAP10 was beneficial to the balance of Th1/Th2, Th17/Treg ratio. Conclusions Taken together, our results indicated the expression of the CAP10 was associated with an antifungal immune response to mice infected with C. neoformans. CAP10 might play an important role in regulating the inflammatory response, and could expected to be a new molecular therapeutic target in cryptococcosis.

A new series of dihydro-isocyanurates, namely, RE(H

Anoectochilus roxburghii (Wall.) Lindl. (Orchidaceae) is a rare traditional Chinese medicine. For seeking high profit, some traditional Chinese medicine sellers usually adulterated A. roxburghii with Goodyera Schlechtendaliana and Ludisia discolor or directly fake A. roxburghii using Anoectochilus formosanus. These counterfeits with similar appearance greatly influence the prescription efficacy. Therefore, there is an urgent need for an effective and fast authentication method to identify A. roxburghii and its counterfeits. In this paper, the near-infrared spectroscopy (NIRS) data of A. roxburghii and its counterfeits are mearsured. Then, an improved inception architecture based 1-dimensional convolutional neural network (Improved 1D-Inception-CNN) is designed for processing the NIRS data and identifying A. roxburghii and its counterfeits. The Improved 1D-Inception-CNN has less parameters and high calculation efficiency which makes the identification model more practical. The experimental results show that compared with traditional structured CNN models, the complexity of the Improved 1D-Inception-CNN is reduced by 40 %, the parameters are reduced by 50 % and the performances are improved by 1.01 %. Therefore, the Improved 1D-Inception-CNN model based on NIRS technology can effectively and quickly identify A. roxburghii and its counterfeits.

Silicon oxycarbide/titanium dioxide (SiOC/TiO 2 ) fibers have been prepared from tetrabutyl titanate modified polyhydromethylsiloxane through electrospinning and pyrolysis. The SiOC/TiO 2 fibers, which are hydrophobic with water contact angle of 130°, own wrinkle-like surface rising from anisotropic volume shrinkage during the pyrolysis. X-ray photoelectron spectroscopy, X-ray diffraction and transmission electron microscopy are exploited for characterization on the obtained polytitanosiloxane gel fibers and the ceramic fibers. The results indicate that the gel fibers are converted to ceramic fibers consisting of amorphous silicon and titanium oxycarbide glass by pyrolysis at 1000 °C, and further decomposed into cristobalite-SiO 2 , brookite-TiO 2 and trace of TiC nanoparticles embedded in amorphous phase at 1300 °C.

The cancer/testis antigen (CTA) lactate dehydrogenase C (LDHC) is a unique LDH isoenzyme associated with glucose and adenosine triphosphate production in mammalian germ cells. However, the role of LDHC in cancer has thus far largely remained elusive. The present study described the expression status of LDHC in human MDA‑MB‑231 breast cancer cells as well as its role in tumor invasion and migration. Immunohistochemical analysis revealed endogenous LDHC expression in the cytoplasm and nuclei of MDA‑MB‑231 cells yielded. In addition, in vitro cell invasion and migration assays revealed that when LDHC expression was blocked by its specific inhibitor, cell invasion and migration were compromised in MDA‑MB‑231 cells. Of note, inhibition of LDHC was unable to induce apoptosis in MDA‑MB‑231 cells. The present study provided evidence that the LDHC enzyme acts as a CTA in breast carcinoma and exerts an essential role in tumor invasion and migration.

A novel mixed alkali hydro-isocyanurate, KLi(HC

Additional file 1: Figure S1. All individual NMR spectra of cell and media samples. Figure S2. Representative 600Â MHz 1H NMR spectra of cell extracts and cultured media. Table S1. Assignments of metabolites from 1H NMR spectra of NPC cell extracts and cultured media. Table S2. Concentrations of characteristic metabolites derived from cultured media. Table S3. Main Raman band positions and the corresponding assignments of single living cells.

Background: Chromosomal translocations of the mixed-lineage leukemia gene (MLL; tMLL) correlate with resistance to therapy and an extremely poor prognosis for individuals with Acute Myeloid Leukemia (AML). The underlying mechanisms are still unknown. This study aims to identify the key genes and the potential molecular mechanisms involved in MLL rearrangement in AML using a bioinformatics approach. Methods: The gene expression profiles from 15 individuals with partial tandem duplication of the MLL gene (MLL-PTD)-AML and 10 tMLL-AML samples were downloaded from the Gene Expression Omnibus (GEO) database. The Differentially Expressed Genes (DEGs) were selected and functional enrichment analyses were performed. The Protein-Protein Interaction (PPI) network was established and visualized in Cytoscape. The hub genes were identified by CytoHubba and significant modules were screened out by Molecular Complex Detection (MCODE). Results: We categorized a total of 885 DEGs comprising 330 upregulated and 555 downregulated genes. The majority of DEGs were significantly enriched for calcium ion transmembrane transport, embryonic skeletal system morphogenesis and cell proliferation processes. Several pathways were enriched, including those associated with PI3K-Akt signaling and insulin resistance. We identified 32 hub genes and screened out 2 modules. Conclusion: The genes we have identified in this study may represent potential biomarkers for MLL-rearranged AML and contribute to the development of novel therapeutic strategies.

To determine whether the potential effects on liver and kidney caused by dental alloys could be reduced or terminated by the removal of nickel-chromium (Ni-Cr) alloy, cobalt-chromium (Co-Cr) alloy, and commercially pure titanium (CP-Ti), they were placed in the cheek pouches of Syrian hamsters according to ISO 10993-10. Then, the peak/plateau and end times of trace metals in the blood were determined with or without the removal of the dental alloys. Based on these time points, the trace metals and their effects on liver and kidney were examined. We found that trace metals released from these dental alloys and titanium were accumulated transiently in the blood, liver, and kidney but had no effect on the histopathology of the liver or kidney. Although the functions of the liver and kidney were compromised, the function of these tissues seemed to be clinically acceptable compared to those in control Syrian hamsters. In addition, the apoptotic effect on renal cells was terminated by removing the Ni-Cr and Co-Cr alloys, and that on hepatocytes was also eliminated by removing the Ni-Cr alloy. In contrast, the effect of the Co-Cr alloy on hepatocytes was temporary and recovered by itself. Taken together, Ni- and Co-based dental alloys and titanium have no effect on the histopathology or function of liver and kidney. Moreover, Ni-Cr and Co-Cr alloys induce transient trace metal accumulation and apoptotic effects in liver and kidney, which can be reduced or terminated by the removal of the alloys, while CP-Ti shows favorable biocompatibility.

Background/Aims: Acute myeloid leukemia (AML) remains a hematologic malignancy with poor survival and a high risk of relapse, which is mainly caused by the emergence of multidrug resistance (MDR). The identification of novel agents to improve therapeutic strategies becomes important priority for AML treatment. It has been shown that emodin has therapeutic effects on many kinds of human malignant tumors. In this study, we investigated the anti-leukemia effects of emodin alone or in combination with cytarabine (Ara-C) on multidrug-resistant AML HL-60/ADR cells and in a mouse xenograft model of human highly tumorigenic AML HL-60/H3 cells. The underlying mechanism was also addressed. Methods: Cell viability after treatment was measured by MTT assay. The DNA fragmentation assay, Annexin V-PE/7-AAD, AO/EB staining, and electron microscopy were introduced to assess the apoptotic induction effects. Changes in protein expression in the Akt and ERK signaling pathways were determined by western blotting. In vivo antileukemia effects on HL-60/H3 xenograft model and overall mouse survival outcomes were further analyzed in this study. Results: Emodin dose-dependently induced growth inhibition and apoptotic effects in resistant HL-60/ADR cells in vitro as well as in the HL-60/H3 xenograft models in vivo. Moreover, emodin significantly enhanced chemosensitivity of AML cells to Ara-C, inhibited leukemic cell growth, and improved survival in the mouse xenograft model of AML. Dual targeting of Akt and ERK signaling pathways might contribute to the anti-leukemia effects on AML cells in vitro and in vivo. Conclusion: Emodin and its combination with Ara-C may be considered a promising therapeutic approach in AML and worthy of further investigation.

Suppressor of activator protein-1, regulated by interferon (SARI), is a novel basic leucine zipper containing type I IFN-inducible early response protein that plays an important regulatory role in a wide variety of tumors, including leukemia. However, the functional role of SARI in myeloid leukemia is not thoroughly understood. In this study, we discovered that knock-down of SARI expression suppressed cell growth and colony formation, inhibited invasion, enhanced imatinib (STI571)-mediated apoptosis, and induced G0/G1 and G2/M arrest in human K562 myeloid leukemia cells. Moreover, using immunoblotting, we provide evidence that silencing of SARI resulted in declined expression of cyclinD1 and cyclinA2, as well as down-regulation of mTOR, c-myc p-mTOR, p-PI3K (p85), p-Akt, p70-S6K, p-p70-S6K and NF-κB (p65) that involved in the PI3K/Akt/mTOR and NF-κB signaling pathways. Taken together, our results demonstrate that SARI functions as an oncogenic role in K562 myeloid leukemia cells through regulating the PI3K/Akt/mTOR and NF-κB signaling pathways.

The WWOX gene is considered to be a tumor-suppressor gene which encodes a protein (Wwox) implicated in various types of solid human cancers. It has been shown that overexpression of WWOX in human tumors promotes apoptosis in vitro and suppresses tumor growth in vivo. Recently, we investigated the effects of WWOX overexpression in vitro and observed marked growth arrest in human leukemia cells; however, the underlying mechanism(s) for this effect is unknown. The present study aimed to elucidate the primary mechanism(s) underlying WWOX-mediated apoptosis in human leukemia. We traced the interactions between WWOX and its associated factors p73 and p53 after WWOX overexpression was induced in Jurkat and K562 cells. Our data revealed that p73 participates in WWOX-mediated apoptosis in Jurkat and K562 cells through binding with Wwox in the cytoplasm without a nuclear-cytoplasmic translocation.