Clinical significance of cyclin-dependent kinase inhibitor 2C expression in cancers: from small cell lung carcinoma to pan-cancers.

BACKGROUND: Cyclin-dependent kinase inhibitor 2C (CDKN2C) was identified to participate in the occurrence and development of multiple cancers; however, its roles in small cell lung carcinoma (SCLC) remain unclear. METHODS: Differential expression analysis of CDKN2C between SCLC and non-SCLC were performed based on 937 samples from multiple centers. The prognosis effects of CDKN2C in patients with SCLC were detected using both Kaplan-Meier curves and log-rank tests. Using receiver-operating characteristic curves, whether CDKN2C expression made it feasible to distinguish SCLC was determined. The potential mechanisms of CDKN2C in SCLC were investigated by gene ontology terms and signaling pathways (Kyoto Encyclopedia of Genes and Genomes). Based on 10,080 samples, a pan-cancer analysis was also performed to determine the roles of CDKN2C in multiple cancers. RESULTS: For the first time, upregulated CDKN2C expression was detected in SCLC samples at both the mRNA and protein levels (p of Wilcoxon rank-sum test < 0.05; standardized mean difference = 2.86 [95% CI 2.20-3.52]). Transcription factor FOXA1 expression may positively regulate CDKN2C expression levels in SCLC. High CDKN2C expression levels were related to the poor prognosis of patients with SCLC (hazard ratio > 1, p < 0.05) and showed pronounced effects for distinguishing SCLC from non-SCLC (sensitivity, specificity, and area under the curve ≥ 0.95). CDKN2C expression may play a role in the development of SCLC by affecting the cell cycle. Furthermore, the first pan-cancer analysis revealed the differential expression of CDKN2C in 16 cancers (breast invasive carcinoma, etc.) and its independent prognostic significance in nine cancers (e.g., adrenocortical carcinoma). CDKN2C expression was related to the immune microenvironment, suggesting its potential usefulness as a prognostic marker in immunotherapy. CONCLUSIONS: This study identified upregulated CDKN2C expression and its clinical significance in SCLC and other multiple cancers, suggesting its potential usefulness as a biomarker in treating and differentiating cancers.

Heterologous Expression of Pteris vittata Arsenite Antiporter PvACR3;1 Reduces Arsenic Accumulation in Plant Shoots.

Arsenic (As) is a toxic carcinogen so it is crucial to decrease As accumulation in crops to reduce its risk to human health. Arsenite (AsIII) antiporter ACR3 protein is critical for As metabolism in organisms, but it is lost in flowering plants. Here, a novel ACR3 gene from As-hyperaccumulator Pteris vittata, PvACR3;1, was cloned and expressed in Saccharomyces cerevisiae (yeast), Arabidopsis thaliana (model plant), and Nicotiana tabacum (tobacco). Yeast experiments showed that PvACR3;1 functioned as an AsIII-antiporter to mediate AsIII efflux to an external medium. At 5 µM AsIII, PvACR3;1 transgenic Arabidopsis accumulated 14-29% higher As in the roots and 55-61% lower As in the shoots compared to WT control, showing lower As translocation. Besides, transgenic tobacco under 5 µM AsIII or AsV also showed similar results, indicating that expressing PvACR3;1 gene increased As retention in plant roots. Moreover, observation of PvACR3;1-green fluorescent protein fusions in transgenic Arabidopsis showed that PvACR3;1 protein localized to the vacuolar membrane, indicating that PvACR3;1 mediated AsIII sequestration into vacuoles, consistent with increased root As. In addition, soil experiments showed ∼22% lower As in the shoots of transgenic tobacco than control. Thus, our study provides a potential strategy to limit As accumulation in plant shoots, representing the first report to decrease As translocation by sequestrating AsIII into vacuoles, shedding light on engineering low-As crops to improve food safety.

Arsenic Induced Phytate Exudation, and Promoted FeAsO4 Dissolution and Plant Growth in As-Hyperaccumulator Pteris vittata.

Arsenic hyperaccumulator Pteris vittata (PV) is efficient in taking up As and nutrients from As-contaminated soils. We evaluated the mechanisms used by PV to mobilize As and Fe by examining the impacts of As and root exudates on FeAsO4 solubilization, and As and Fe uptake in four plants: As-hyperaccumulators PV and Pteris multifida (PM), nonhyperaccumulator Pteris ensiformis (PE), and angiosperm plant tomato (Solanum lycopersicum). Phytate and oxalate were dominant in fern plants (>93%), which were 50-83, 15-42, and 0-32 mg kg(-1) phytate and 10-15, 7-26, and 4-12 mg kg(-1) oxalate for PV, PM, and PE respectively, with higher As inducing greater phytate exudation and no phytate being detected in tomato exudates. PV treated with phytate+FeAsO4 had higher As and Fe contents and larger biomass than phytate or FeAsO4 treatment, which were 340 vs 20 and 130 mg kg(-1) As in the fronds and 7900 vs 1600 and 4100 mg kg(-1) Fe in the roots. We hypothesized that As-induced phytate exudation helped PV to take up Fe and As from insoluble FeAsO4 and promoted PV growth. Our study suggests that phytate exudation may be special to fern plants, which may play an important role in enhancing As and nutrient uptake by plants, thereby increasing their efficiency in phytoremediation of As-contaminated soils.

Qualitative analysis of the helical electronic energy of inherently chiral calix[4]arenes: an approach to effectively assign their absolute configuration.

For all microhelices on aromatic rings of inherently chiral calix[4]arene, an expression was derived from one approximation and one hypothesis on the basis of the electron-on-a-helix model of Tinoco and Woody as follows: 1/E = µ(H - KΔα2), where µ = 1 for the right-handed microhelix and µ = -1 for the left-handed microhelix; and H and K are constant and greater than zero. The expression correlates microhelical electronic energy (E) with the atom polarizability difference (Δα) on both microhelix ends, which intuitively and clearly shows the impact of helical substituent polarizability on helical electronic energy. The case analysis almost entirely proves that the qualitative analysis of the helical electronic energy of inherently chiral calix[4]arenes with the expression is scientific and can be used to effectively assign their absolute configuration.

Charge-Localized Retention and Long-Term Memory Enabled by Cooperating Sterically Confined Molecular Crystallization with Spiro[fluorene-9,9'-xanthene]-Based Csp3-Hindrance.

Charge localization of memory materials plays a crucial role in the endurance and retention ability of organic nonvolatile memory, which is completely opposite from the charge delocalization of high-mobility materials. However, charge transfer of both though-space and through-bond based on molecular design principles still faces challenges. Herein, a nonplanar wide-bandgap semiconductor with Csp3-hindrance (DOCH3-DDPA-SFX) has been designed and synthesized. An effective crystallization effect of self-assembled two-dimensional nanosheets on charge trapping dynamics and kinetics is visualized by Kelvin probe force microscopy (KPFM). The trapped charges are localized completely on a single nanosheet, which has better charge trapping and retention properties than an amorphous film. Meanwhile, crystallization also greatly improves structure stability. Combining DFT theoretical calculations, the mechanisms of localization and long-term retention are discussed. The steric crystallization effects on the charge localization will guide the effective design of single-component semiconducting charge-memory materials by molecular assembly and aggregate control for high-performance organic memory.

Amine- and thiol-bifunctionalized mesoporous silica material for immobilization of Pb and Cd: Characterization, efficiency, and mechanism.

In this study, a two-step functionalizing strategy by combining co-condensation with grafting procedures was employed to synthesize well-ordered Amino- and Thiol-Bifunctionalized SBA-15 (ATBS) mesoporous silica. Its physicochemical properties, performance, and mechanisms in immobilization of toxic metals Pb and Cd in water and soil were investigated. After bi-functionalization, X-ray diffractometer, transmission electron microscope, and N2 adsorption-desorption measurements confirmed that the ATBS maintained a highly-ordered mesoporous structure, large surface area and pore volume. The elemental analysis, Fourier transform infrared spectroscopy and X-ray Photoelectron Spectroscopy (XPS) evidenced the successful incorporation of amine and thiol groups into ATBS. These structure and functional characteristics of ATBS benefited Pb and Cd sorption. Sorption isotherms of Pb and Cd were better fit with Sips and Redlich-Peterson models. Sorption kinetics suggested that Pb sorption was mainly regulated by chemical reactions, whereas both diffusion process and chemical reactions were rate-regulating steps in Cd sorption. ATBS showed the maximum sorption capacities for Pb and Cd at 120 and 38 mg g-1, respectively. The sorption mechanisms revealed by XPS measurements suggested that Cd sorption was mainly attributed to thiol groups while Pb was efficiently bond to both thiol and amino groups. High and stable sorption efficiencies were attained in the pH range of 4-6, with a higher affinity towards Pb than Cd. Furthermore, its ability to immobilize Pb and Cd in soils was examined with an incubation experiment, which showed that ATBS reduced 30-56% of MgCl2-extractable Pb and Cd in a contaminated soil. The synthesized sorbent via the two-step functionalizing strategy shows high sorption efficiency towards Pb and Cd, and thus it has potential application in remediating Pb and Cd contaminated water and soils.

Arsenic-induced nutrient uptake in As-hyperaccumulator Pteris vittata and their potential role to enhance plant growth.

It is known that arsenic (As) promotes growth of As-hyperaccumulator Pteris vittata (PV), however, the associated mechanisms are unclear. Here we examined As-induced nutrient uptake in P. vittata and their potential role to enhance plant growth in sterile agar by excluding microbial effects. As-hyperaccumulator P. multifida (PM) and non-hyperaccumulator P. ensiformis (PE) belonging to the Pteris genus were used as comparisons. The results showed that, after 40 d of growth, As induced biomass increase in hyperaccumulators PV and PM by 5.2-9.4 fold whereas it caused 63% decline in PE. The data suggested that As played a beneficial role in promoting hyperaccumulator growth. In addition, hyperaccumulators PV and PM accumulated 7.5-13, 1.4-3.6, and 1.8-4.4 fold more As, Fe, and P than the non-hyperaccumulator PE. In addition, nutrient contents such as K and Zn were also increased while Ca, Mg, and Mn decreased or unaffected under As treatment. This study demonstrated that As promoted growth in hyperaccumulators and enhanced Fe, P, K, and Zn uptake. Different plant growth responses to As among hyperaccumulators PV and PM and non-hyperaccumulator PE may help to better understand why hyperaccumulators grow better under As-stress.

Phytate promoted arsenic uptake and growth in arsenic-hyperaccumulator Pteris vittata by upregulating phosphorus transporters.

While phosphate (P) inhibits arsenic (As) uptake by plants, phytate increases As uptake by As-hyperaccumulator Pteris vittata. Here we tried to understand the underling mechanisms by investigating the roles of phytate in soil As desorption, P transport in P. vittata, short-term As uptake, and plant growth and As accumulation from soils. Sterile soil was used to exclude microbial degradation on phytate. Results showed that inorganic P released 3.3-fold more As than that of phytate from soil. However, P. vittata accumulated 2-2.5 fold more As from soils with phytate than that in control and P treatment. In addition, different from P suppression on As uptake, solution uptake experiment showed that As uptake in phytate treatment was comparable to that of control under 0.1-7.5 µM As after 1-24 h. Moreover, responding to phytate, P. vittata P transporter PvPht1;3 increased by 3-fold while PvPht1;1 decreased by 65%. The data suggested that phytate upregulated PvPht1;3, thereby contributing to As uptake in P. vittata. Our results showed that, though with lower As release from soil compared to P, phytate induced more As uptake and better growth in P. vittata by upregulating P transporters.

Arsenic and phosphate rock impacted the abundance and diversity of bacterial arsenic oxidase and reductase genes in rhizosphere of As-hyperaccumulator Pteris vittata.

Microbially-mediated arsenic (As) transformation in soils affects As speciation and plant uptake. However, little is known about the impacts of As on bacterial communities and their functional genes in the rhizosphere of As-hyperaccumulator Pteris vittata. In this study, arsenite (AsIII) oxidase genes (aroA-like) and arsenate (AsV) reductase genes (arsC) were amplified from three soils, which were amended with 50mgkg-1 As and/or 1.5% phosphate rock (PR) and grew P. vittata for 90 d. The aroA-like genes in the rhizosphere were 50 times more abundant than arsC genes, consistent with the dominance of AsV in soils. According to functional gene alignment, most bacteria belonged to α-, ß- and γ-Proteobacteria. Moreover, aroA-like genes showed a higher biodiversity than arsC genes based on clone library analysis and could be grouped into nine clusters based on terminal restriction fragment length polymorphism (T-RFLP) analysis. Besides, AsV amendment elevated aroA-like gene diversity, but decreased arsC gene diversity. Redundancy analysis indicated that soil pH, available Ca and P, and AsV concentration were key factors driving diverse compositions in aroA-like gene community. This work identified new opportunities to screen for As-oxidizing and/or -reducing bacteria to aid phytoremediation of As-contaminated soils.

Arsenic-hyperaccumulator Pteris vittata efficiently solubilized phosphate rock to sustain plant growth and As uptake.

Phosphorus (P) is one of the most important nutrients for phytoremediation of arsenic (As)-contaminated soils. In this study, we demonstrated that As-hyperaccumulator Pteris vittata was efficient in acquiring P from insoluble phosphate rock (PR). When supplemented with PR as the sole P source in hydroponic systems, P. vittata accumulated 49% and 28% higher P in the roots and fronds than the -P treatment. In contrast, non-hyperaccumulator Pteris ensiformis was unable to solubilize P from PR. To gain insights into PR solubilization by plants, organic acids in plant root exudates were analyzed by HPLC. The results showed that phytic acid was the predominant (>90%) organic acid in P. vittata root exudates whereas only oxalic acid was detected in P. ensiformis. Moreover, P. vittata secreted more phytic acid in -P and PR treatments. Compared to oxalic acid, phytic acid was more effective in solubilizing PR, suggesting that phytic acid was critical for PR utilization. Besides, secretion of phytic acid by P. vittata was not inhibited by arsenate. Our data indicated that phytic acid played an important role in efficient use of insoluble PR by P. vittata, shedding light on using insoluble PR to enhance phytoremediation of As-contaminated soils.

Phytate induced arsenic uptake and plant growth in arsenic-hyperaccumulator Pteris vittata.

Phytate is abundant in soils, which is stable and unavailable for plant uptake. However, it occurs in root exudates of As-hyperaccumulator Pteris vittata (PV). To elucidate its effect on As uptake and growth, P. vittata were grown on agar media (63 µM P) containing 50 µM As and/or 50 or 500 µM phytate with non As-hyperaccumulator Pteris ensiformis (PE) as a congeneric control for 60 d. Phytate induced efficient As and P uptake, and enhanced growth in PV, but had little effects on PE. The As concentrations in PV fronds and roots were 157 and 31 mg kg-1 in As50+phytate50, 2.2- and 3.1-fold that of As50 treatment. Phosphorus uptake by PV was reduced by 27% in As treatment than the control (P vs. P+As) but increased by 73% comparing phytate500 to phytate500+As, indicating that PV effectively took up P from phytate. Neither As nor phytate affected Fe accumulation in PV, but phytate reduced root Fe concentration in PE (46-56%). As such, the increased As and P and the unsuppressed Fe uptake in PV probably promoted PV growth. Thus, supplying phytate to As-contaminated soils may promote As uptake and growth in PV and its phytoremediation ability.

Microbial siderophores and root exudates enhanced goethite dissolution and Fe/As uptake by As-hyperaccumulator Pteris vittata.

Arsenic (As) in soils is often adsorbed on Fe-(hydro)oxides surface, rendering them more resistant to dissolution, which is undesirable for phytoremediation of As-contaminated soils. Arsenic hyperaccumulator Pteris vittata prefers to grow in calcareous soils where available Fe and As are low. To elucidate its mechanisms of acquiring Fe and As from insoluble sources in soils, we investigated dissolution of goethite with pre-adsorbed arsenate (AsV; As-goethite) in presence of four organic ligands, including two root exudates (oxalate and phytate, dominant in P. vittata) and two microbial siderophores (PG12-siderophore and desferrioxamine B). Their presence increased As solubilization from As-goethite from 0.03 to 0.27-5.33 mg L-1 compared to the control. The siderophore/phytate bi-ligand treatment released 7.42 mg L-1 soluble Fe, which was 1.2-fold that of the sum of siderophore and phytate, showing a synergy in promoting As-goethite dissolution. In the ligand-mineral-plant system, siderophore/phytate was most effective in releasing As and Fe from As-goethite. Moreover, the continuous plant uptake induced more As-goethite dissolution. The continued release of As and Fe significantly enhanced their plant uptake (from 0.01 to 0.43 mg plant-1 As and 2.7-14.8 mg plant-1 Fe) and plant growth (from 1.2 to 3.1 g plant-1 fw) in P. vittata. Since microbial siderophores and root exudates often coexist in soil rhizosphere, their synergy in enhancing dissolution of insoluble As-Fe minerals may play an important role in efficient phytoremediation of As-contaminated soils.

Long noncoding RNA NEAT1 is an unfavorable prognostic factor and regulates migration and invasion in gastric cancer.

BACKGROUND: Long noncoding RNAs (LncRNAs) have been demonstrated as playing important roles in diverse biological processes including tumorigenesis. However, the clinical significance and biological function of LncRNA nuclear-enriched abundant transcript 1 (NEAT1) in gastric cancer are still unknown. The aim of this study was to identify the role of LncRNA NEAT1 in gastric cancer. METHODS: The expression of LncRNA NEAT1 was detected in gastric cancer samples and cell lines by real-time PCR. The clinical and prognostic significance of LncRNA NEAT1 in gastric cancer patients was analyzed. Furthermore, the biological function of LncRNA NEAT1 on tumor cell growth and mobility were explored through MTT, colony formation, transwell migration, and invasion assays in vitro. The potential mechanism of LncRNA NEAT1 was identified by Western blot. RESULTS: LncRNA NEAT1 was overexpressed in gastric cancer tissues and cell lines and corrected with clinical stage, histological type, lymph node metastasis, and distant metastasis. Furthermore, patients with high levels of LncRNA NEAT1 had poorer survival than those with lower levels of LncRNA NEAT1. Univariate and multivariate Cox regression analyses showed that LncRNA NEAT1 overexpression was a poor independent prognostic factor for gastric cancer patients. Moreover, knocking down LncRNA NEAT1 expression significantly suppressed the gastric cancer cell migration and invasion in vitro and regulated EMT-associated proteins expression. CONCLUSION: LncRNA NEAT1 plays an important role on gastric cancer tumorigenesis and progression and may act as a potential biomarker for therapeutic strategy and prognostic prediction.

Arsenic uptake, arsenite efflux and plant growth in hyperaccumulator Pteris vittata: Role of arsenic-resistant bacteria.

Bacteria-mediated arsenic (As) transformation and their impacts on As and P uptake and plant growth in As-hyperaccumulator Pteris vittata (PV) were investigated under sterile condition. All As-resistant bacteria (9 endophytic and 6 rhizospheric) were As-reducers except one As-oxidizer. After growing two months in media with 37.5 mg kg(-1) AsV, As concentrations in the fronds and roots were 3655-5389 (89-91% AsIII) and 971-1467 mg kg(-1) (41-73% AsIII), corresponding to 22-52% decrease in the As in the media. Bacterial inoculation enhanced As and P uptake by up to 47 and 69%, and PV growth by 20-74%, which may be related to elevated As and P in plants (r = 0.88-0.97, p < 0.05). Though AsV was supplied, 95% of the As in the bacteria-free media was AsIII, suggesting efficient efflux of AsIII by PV roots (120 µg g(-1) root fw). This was supported by the fact that no AsV was detected in media inoculated with As-reducers while 95% of AsV was detected with As-oxidizer. Our data showed that, under As-stress, PV reduced As toxicity by efficient AsIII efflux into media and AsIII translocation to the fronds, and bacteria benefited PV growth probably via enhanced As and P uptake.

High As exposure induced substantial arsenite efflux in As-hyperaccumulator Pteris vittata.

Arsenite (AsIII) efflux is an important mechanism for arsenic (As) detoxification in plants. Low AsIII efflux has been observed in As-hyperaccumulator Pteris vittata, which may contribute to its highly efficient As translocation and accumulation; however, the results may be compromised by microbial AsIII oxidation, relatively low As concentration in the medium and short-term As exposure. Here, sterile P. vittata sporophytes were cultivated in sterile medium containing 10, 200 and 500 µM arsenate (AsV) for 28 d. Arsenite efflux to the growth medium and As speciation in P. vittata was investigated. Low AsIII efflux at 12% of AsV uptake was observed at 10 µM AsV, but high AsIII efflux (36-76%) was observed at 200 and 500 µM AsV, with 1987-2397 mg kg(-1) As being accumulated in the fronds. This is the first report to show efficient AsIII efflux in P. vittata. This study showed that P. vittata may use high AsIII efflux to cope with As toxicity under high As exposure, which may be necessary to sustain growth while accumulating As.

Arsenic-induced plant growth of arsenic-hyperaccumulator Pteris vittata: Impact of arsenic and phosphate rock.

Phosphate rock (PR) has been shown to promote plant growth and arsenic (As) uptake by As-hyperaccumulator Pteris vittata (PV). However, little is known about its behaviors in agricultural soils. In this study, impact of 50 mg kg(-1) As and/or 1.5% PR amendment on plant As accumulation and growth was investigated by growing PV for 90 d in three agricultural soils. While As amendment significantly increased plant As uptake and substantially promoted PV growth, the opposite was observed with PR amendment. Arsenic amendment increased plant frond As from 16.9-265 to 961-6017 mg kg(-1),whereas PR amendment lowered frond As to 10.2-216 mg kg(-1). The As-induced plant growth stimulation was 69-71%. While PR amendment increased plant Ca and P uptake, As amendment showed opposite results. The PV biomass was highly correlated with plant As at r = 0.82, but with weak correlations with plant Ca or P at r < 0.30. This study confirmed that 1) As significantly promoted PV growth, probably independent of Ca or P uptake, 2) PR amendment didn't enhance plant growth or As uptake by PV in agricultural soils with adequate available P, and 3) PV effluxed arsenite (AsIII) growing in agricultural soils.

Identification of Novel PPARα/γ Dual Agonists by Virtual Screening of Specs Database.

Rosiglitazone was restricted clinically due to the side effects such as edema, weight gain and cardiac failure mainly attributing to the single and selective PPARγ activation. Nowadays, multi-targeted PPARs agonists remained to be a hot topic in the antidiabetic medicinal chemistry field. In this paper, the cooperative PPARα/γ dual agonists were screened from Specs database via the flow chart of docking, ADMET prediction and molecular dynamics (MD) simulations. Representative compounds ZINC36517927 and ZINC13573581 displayed higher binding scores, better pharmacokinetic profiles and were predicted to display the best binding affinity with PPARα/γ. Complex-based pharmacophore (CBP) models showed the key interactions in the PPARα/γ active sites. 20 ns simulations performed to the PPAR-ligand complexes indicated a stable binding conformation. This work provided an approach to identify novel high-efficiency PPARα/γ dual agonists for the treatment of type 2 diabetes mellitus (T2DM).

Association between cadherin-17 expression and pathological characteristics of gastric cancer: a meta-analysis.

AIM: To construct a meta-analysis in order to examine the relationship between cadherin-17 (CDH17) and gastric cancer (GC). METHODS: Related articles were selected by searching the following English or Chinese electronic databases: CINAHL, MEDLINE, Science Citation Index, the Chinese Journal Full-Text, and the Weipu Journal. Newcastle-Ottawa Scale (NOS) criteria were used to ensure consistency in reviewing and reporting results. Statistical analyses were conducted with Version 12.0 STATA statistical software. RESULTS: Ultimately, 11 articles, with a total of 2,120 GC patients, were found to be eligible for study inclusion. In comparisons of GC patients by TNM stage (III-IV vs I-II: OR = 2.35, 95%CI: 1.15-4.825, P = 0.019), histologic grade (3-4 vs 1-2: OR = 3.48, 95%CI: 1.36-8.92, P = 0.009), invasion grade (T3-4 vs T1-2: OR = 2.86; 95%CI: 1.69-4.83; P = 0.000), and lymph node metastasis (positive vs negative: OR = 2.64; 95%CI: 1.33-5.27; P = 0.006), it was found that CDH17 showed more positive expressions in each of the more severe cases. Country-stratified analyses from all four experimental subgroups showed that high CDH17 expression levels may be related to GC among Chinese and Korean populations (all P < 0.05), with the exception of the invasion grade T3-4 vs T1-2 comparison, where the relation only held among the Chinese population (OR = 2.86, 95%CI: 1.69-4.83, P = 0.000). CONCLUSION: Collectively, the data reflects the capacity of CDH17 in tumor proliferation and metastasis among GC patients.