Soil fungal communities show more specificity than bacteria for plant species composition in a temperate forest in China.

BACKGROUND: Soil microbiome is an important part of the forest ecosystem and participates in forest ecological restoration and reconstruction. Niche differentiation with respect to resources is a prominent hypothesis to account for the maintenance of species diversity in forest ecosystems. Resource-based niche differentiation has driven ecological specialization. Plants influence soil microbial diversity and distribution by affecting the soil environment. However, with the change in plant population type, whether the distribution of soil microbes is random or follows an ecologically specialized manner remains to be further studied. We characterized the soil microbiome (bacteria and fungi) in different plant populations to assess the effects of phytophysiognomy on the distribution patterns of soil microbial communities in a temperate forest in China. RESULTS: Our results showed that the distribution of most soil microbes in different types of plant populations is not random but specialized in these temperate forests. The distribution patterns of bacteria and fungi were related to the composition of plant communities. Fungal species (32%) showed higher specialization than bacterial species (15%) for different types of plant populations. Light was the main driving factor of the fungal community, and soil physicochemical factors were the main driving factor of the bacterial community. CONCLUSION: These findings suggest that ecological specialization is important in maintaining local diversity in soil microbial communities in this forest. Fungi are more specialized than bacteria in the face of changes in plant population types. Changes in plant community composition could have important effects on soil microbial communities by potentially influencing the stability and stress resistance of forest ecosystems.

MicroRNA-1246 suppresses the metastasis of breast cancer cells by targeting the DYRK1A/PGRN axis to prevent the epithelial-mesenchymal transition.

OBJECTIVE: Breast cancer is one of the most common malignant and highly heterogeneous tumors in women. MicroRNAs (miRNAs), such as miR-1246, play important roles in various types of malignant cancers, including triple-negative breast cancer (TNBC). However, the biological role of miR-1246 in TNBC has not yet been fully elucidated. In this study, we studied the role of miR-1246 in the occurrence and development of TNBC and its mechanism of action. METHODS: Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays were performed to observe the effects of miR-1246 on TNBC cell proliferation, migration, and invasion, respectively. The expression of epithelial-mesenchymal transition (EMT) markers was detected by western blotting. Dual luciferase reporter assays were performed to determine whether DYRK1A is a novel target of miR-1246. In addition, an immunoprecipitation experiment was performed to verify the binding of DYRK1A to PGRN. Rescue experiments were performed to determine whether DYRK1A is a novel target of miR-1246 and whether miR-1246 suppresses the metastasis of breast cancer cells by targeting the DYRK1A/PGRN axis to prevent the epithelial-mesenchymal transition. RESULTS: Our results show that miR­1246 suppresses the proliferation, migration, and invasion of TNBC cells, DYRK1A is a novel target of miR-1246 and Importin-8 mediated miR-1246 nuclear translocation. MiR­1246 plays a suppressive role in the regulation of the EMT of TNBC cells by targeting DYRK1A. DYRK1A mediates the metastasis of triple-negative breast cancer via activation of the EMT. We identified PGRN as a novel DYRK1A-interacting protein. Overexpression of PGRN and DYRK1A promoted cell proliferation and migration of TNBC, but this effect was reversed by co-expression of miR-1246 mimics.DYRK1A and PGRN act together to regulate the occurrence and development of breast cancer through miR-1246. CONCLUSION: MiR-1246 suppresses the metastasis of breast cancer cells by targeting the DYRK1A/PGRN axis and preventing the epithelial-mesenchymal transition. The MiR-1246/DYRK1A/PGRN axis regulates TNBC progression, suggesting that MiR-1246 could be promising therapeutic targets for the treatment of TNBC.

Knockdown of CENPK inhibits cell growth and facilitates apoptosis via PTEN-PI3K-AKT signalling pathway in gastric cancer.

Previous studies have indicated that centromere protein K (CENPK) is upregulated in several cancers and related to tumorigenesis. Nevertheless, the potential function of CENPK in gastric cancer (GC) remains unknown. Here, we investigated the function of CENPK on oncogenicity and explored its underlying mechanisms in GC. Our results showed that CENPK was dramatically overexpressed in GC and was associated with poor prognosis through bioinformatics analysis. We demonstrated that CENPK is upregulated in GC tissues and cell lines. Moreover, knockdown of CENPK significantly inhibited proliferation in vitro and attenuated the growth of implanted GCs in vivo. In addition, CENPK silencing induced G1 phase cell cycle arrest and facilitated apoptosis of GC cells. KEGG pathway analysis indicated that the PI3K-AKT signalling pathway was considerably enriched. Knockdown of CENPK decreased the expression of PI3K, p-Akt (Ser437) and p-GSK3ß (Ser9) in GC cells, and increased the expression of PTEN. In conclusion, this study indicated that CENPK was overexpressed in GC and may promote gastric carcinogenesis through the PTEN-PI3K-AKT signalling pathway. Thus, CENPK may be a potential target for cancer therapeutics in GC.

Antibacterial Diphenyl Ether, Benzophenone and Xanthone Derivatives from Aspergillus flavipes.

The extract of the strain Aspergillus flavipes DL-11 exerted antibacterial activities against six Gram-positive bacteria. During the following bioassay-guided separation, ten diphenyl ethers (1-10), two benzophenones (11-12), together with two xanthones (13-14) were isolated. Among them, 4'-chloroasterric acid (1) was a new chlorinated diphenyl ether. Their structures were elucidated by extensive spectroscopic data analysis, including IR, HR-ESI-MS, NMR experiments, and by comparison with the literature data. All compounds showed moderate to strong antibacterial effects on different Gram-positive bacteria with MIC values that ranged from 3.13 to 50 µg/mL, but none of the compounds exhibited activity against Gram-negative bacteria Vibrio parahaemolyticus ATCC17802 (MIC>100 µg/mL). In particular, the MICs of some compounds are at the level of positive control.

Effects of tillage and biochar on soil physiochemical and microbial properties and its linkage with crop yield.

Vertisols are clayey soils with a high potential for improving production. Therefore, understanding the impact of tillage and fertilization on soil physicochemical properties and microbial community is essential for improving the vertisols with a high montmorillonite and smectite clay content. A 3-year field experiment was conducted to compare the effects of different tillage and fertilization practices at three depths of the vertisol under the wheat-maize cropping system in the North China Plain. The experimental treatments included rotary tillage without fertilization (R-CK), rotary tillage with chemical nitrogen (N), phosphorus (P), and potassium (K) fertilization (R-NPK), R-NPK plus biochar (R-NPKB), deep tillage without fertilization (D-CK), deep tillage with chemical N, P, and K fertilization (D-NPK), and D-NPK plus biochar (D-NPKB). The results showed that D-NPKB significantly improved winter wheat and summer maize yields by 14.4 and 3.8%, respectively, compared with R-NPK. The nitrate (NO3 --N) content of the deeper soil layer in D-NPKB was significantly higher than that in D-NPK. Meanwhile, biochar application increased the pH in the three layers. Compared with R-NPK, D-NPKB significantly increased the average content of available phosphorus (AP), soil organic carbon (SOC), and total nitrogen (TN) by 73.7, 18.5, and 19.0%, respectively. Meanwhile, Gaiellale, Sphingomonadaceae, and Nocardioidaceae were the predominant bacteria at the family level across all treatments, with a total relative proportion ranging from 14.1 to 23.6%. In addition, the abundance of Bacillaceae in deep tillage was 9.4% higher in the 20-30-cm soil layer than that in rotary tillage. Furthermore, the correlation analysis revealed a significant positive correlation between crop yield and chemical factors such as NO3 --N and the abundances of Gaiellalea, Sphingomonadaceae, and Nocardioidaceae. The findings collectively indicated that deep tillage combined with biochar application could increase the soil nutrients and modify the bacterial structure in the deeper soil layer and therefore will be beneficial for improving the productivity of the vertisols.

Changes in the Distribution Preference of Soil Microbial Communities During Secondary Succession in a Temperate Mountain Forest.

Soil microbes play a crucial role in a forest ecosystem. However, whether the distribution of bacteria and fungi in different forest succession stages is random or following ecological specialization remains to be further studied. In the present study, we characterized soil bacterial and fungal communities to determine their distribution preference, with different succession communities in a temperate mountain forest. The Kruskal-Wallis method was used to analyze structural differences between bacterial and fungal communities in different succession processes. The specificity of soil microbial distribution in a secondary forest was studied by network analysis. The torus-translation test was used to analyze the species distribution preference of soil microbes in different succession stages. Results showed that the species composition of soil bacteria and fungi differed significantly in different succession processes. The modularity index of fungi (0.227) was higher than that of bacteria (0.080). Fungi (54.47%) had specific preferences than bacteria (49.95%) with regard to forests in different succession stages. Our work suggests that the distribution pattern of most soil microbes in a temperate mountain forest was not random but specialized in temperate mountain forests. Different microbes showed different distribution preferences. Fungi were more sensitive than bacteria during secondary succession in a temperate mountain forest. In addition, microbe-environment relations varied during secondary succession. Our results provided new insight into the mechanism through which complex soil microbial communities responded to changes in forest community succession.

Combining Clinicopathology, IVIM-DWI and Texture Parameters for a Nomogram to Predict Treatment Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients.

Objectives: This study aimed to create a nomogram for the risk prediction of neoadjuvant chemoradiotherapy (nCRT) resistance in locally advanced rectal cancer (LARC). Methods: Clinical data in this retrospective study were collected from a total of 135 LARC patients admitted to our hospital from June 2016 to December 2020. After screening by inclusion and exclusion criteria, 62 patients were included in the study. Texture analysis (TA) was performed on T2WI and DWI images. Patients were divided into response group (CR+PR) and no-response group (SD+PD) according to efficacy assessment. Multivariate analysis was performed on clinicopathology, IVIM-DWI and texture parameters for screening of independent predictors. A nomogram was created and model fit and clinical net benefit were assessed. Results: Multivariate analysis of clinicopathology parameters showed that the differentiation and T stage were independent predictors (OR values were 14.516 and 11.589, resp.; P<0.05). Multivariate analysis of IVIM-DWI and texture parameters showed that f value and Rads-score were independent predictors (OR values were 0.855, 2.790, resp.; P<0.05). In this study, clinicopathology together with IVIM-DWI and texture parameters showed the best predictive efficacy (AUC=0.979). The nomogram showed good predictive performance and stability in identifying high-risk LARC patients who are resistant to nCRT (C-index=0.979). Decision curve analyses showed that the nomogram had the best clinical net benefit. Ten-fold cross-validation results showed that the average AUC value was 0.967, and the average C-index was 0.966. Conclusions: The nomogram combining the differentiation, T stage, f value and Rads-score can effectively estimate the risk of nCRT resistance in patients with LARC.

[Characteristics of acidification and the distribution of available phosphorus along soil depths in heavy clay soils in southern Henan Province, China]. / è±«å—é»æ¿åœŸå£¤åˆ†å±‚é ¸åŒ–å’Œè€•å±‚é€Ÿæ•ˆç£·åˆ†å¸ƒç‰¹å¾.

The acidification of agricultural soil in the southern part of the North China Plain has become more obvious, which is particularly true for the heavy clay soil types, such as yellow-cinnamon and lime concretion black soils. To understand the spatial variability of the pH value and nutrients on the vertical agricultural soil profile of heavy clay soils in this area, we measured pH values and available phosphorus (AP) in 63 farmland sample points from Xiping County in the southern Henan Province. Geostatistical methods and ArcGIS technology were used to map soil pH values along three soil depths (0-10, 10-20, and 20-30 cm) and the spatial distribution of soil AP in the tillage layer (0-20 cm). Furthermore, the correlation between pH and AP was analyzed. The results showed that mean pH values of typical yellow-cinnamon and typical fluvo-aquic soils from three soil layers were 4.98, 4.93, 5.31, and 5.46, 5.81, 6.26, respectively, which gradually increased with soil depths. However, there was no significant difference among the three soil layers. Mean pH values of typical lime concretion black soil from the three soil layers were 5.23, 5.43 and 6.03, respectively, and that of the 20-30 cm soil layer was significantly higher than that of the 0-10 cm (by 0.8-1 pH unit) and the 10-20 cm layers. The pH of the 20-30 cm soil layer of the calcareous lime concretion black and moist soils were also significantly higher than that of the 0-10 and 10-20 cm soil layers. The AP contents of the typical yellow-cinnamon, typical lime concretion black, moist, typical fluvo-aquic and calcareous lime concretion black soils in 0-20 cm soil layer were 8.85-54.75, 4.27-37.49, 8.22-51.80, 6.07-34.82, and 13.22-22.85 mg·kg-1, respectively. The results of the map indicated that the areas with low AP were distributed in the middle of the study area in blocks, and the areas with high AP were distributed around the study area in dots and flakes. The pH values of the typical yellow-cinnamon, typical lime concretion black, and moist soils positively correlated with the content of AP in the 0-20 cm soil layer. In conclusion, the heavy clay soil in southern Henan Province became stratified acidification, which slowed down along the soil depth. Soil AP contents in the tillage layer were distributed unevenly in the study area, and were affected by soil types and soil pH. These results would be useful for the improvement of heavy clay soil acidification in the southern part of the North China Plain.

Serological and Molecular Characterization of Hepatitis B Virus Infection in Gastric Cancer.

Hepatitis B virus (HBV) infection has been reported to be associated with gastric cancer (GC). Nonetheless, no study has revealed the role of HBV infection in the survival of patients with GC, and the mutation profiles of HBV-infected patients with GC have never been documented. Here, we performed an updated meta-analysis and found a significantly increased risk of GC in HBV-infected individuals (sOR, 1.29; 95% CI, 1.22-1.37). Furthermore, we observed that in the Anhui area, the rate of serum HBsAg positivity (OR, 1.62; 95% CI, 1.03-2.55) was significantly higher in GC patients than in controls. Moreover, our results showed that HBV-positive patients had significantly worse disease-free survival (HR, 1.98; 95% CI, 1.39-2.82) and overall survival (HR, 1.84; 95% CI, 1.19-2.85) than HBV-negative patients. The results of Cox proportional hazards regression proved that HBV infection was an independent adverse prognostic factor in GC. Furthermore, by performing targeted-NGS, we found unique mutation profiles in HBV-infected GC samples, including five frequently mutated protein-coding genes (KMT2B, KMT2D, SOX1, FGF12, and TUBB2B). Expression and survival analyses of these genes identified three novel candidate genes that may have potential roles in GC development. Gene Ontology enrichment analysis showed that the recurrent mutations in HBV-positive GC samples were related to cell proliferation, cell migration, and transcription. Taking together, our study proved that HBV infection is an independent prognostic factor in GC patients. The unique mutation profiles of HBV-infected patients with GC open a new research direction toward the underling mechanism between HBV infection and GC.

Efficacy and safety of intermittent versus continuous dose apatinib plus docetaxel as second-line therapy in patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma: a randomized controlled study.

Background: Previous studies of the second-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma (GC/GEJAC) had reported that apatinib combined with chemotherapy improved the treatment outcomes. However, the benefits were sometimes limited due to the tolerance of continuous dose regimen. This randomized controlled study aimed to investigate the efficacy and safety of intermittent or continuous dose apatinib plus docetaxel as a second-line therapy in patients with advanced GC/GEJAC. Methods: Advanced GC/GEJAC patients who failed first-line chemotherapy were recruited (enrollment time: from September 15, 2017 to July 21, 2019), and randomly assigned to either the intermittent dose group (IG group) or the continuous dose group (CG group) (1:1 ratio) using the block randomization method. In the IG group, patients received apatinib 500 mg/d for 5 consecutive days then held for 2 days plus docetaxel 60 mg/m2 q3w, in a 3-week cycle. In the CG group, patients received apatinib 500 mg daily plus docetaxel 60 mg/m2 q3w, in a 3-week cycle. The progression free survival (PFS) was evaluated every two cycles and follow-ups were performed monthly. The primary endpoint was PFS, and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: In total, 76 eligible patients were enrolled and randomly assigned (1:1 ratio). The IG group exhibited similar PFS compared to the CG group [median PFS: 3.88 (95% CI: 1.72-6.03) months vs. 3.98 (95% CI: 1.06-6.90) months, P=0.546] and OS [median OS: 9.00 (95% CI: 5.31-12.70) months vs. 9.40 (95% CI: 5.20-13.59) months, P=0.310]. ORR (21.1% vs. 18.4%, P=0.773) and DCR (60.5% vs. 60.5%, P=1.000) were of not statistically different between the IG and CG groups. As for safety, the IG group exhibited less frequent hypoproteinemia (31.6% vs. 55.3%, P=0.037) and lactate dehydrogenase increased (18.4% vs. 44.7%, P=0.014), while no differences in other adverse events were observed between the two groups. Conclusions: Intermittent dose apatinib plus docetaxel was equally effective and more tolerable than continuous dose apatinib plus docetaxel as a second-line therapy in patients with advanced GC/GEJAC. Trial Registration: ClinicalTrials.gov NCT03334591.

PH-sensitive Dioctadecylamine-501 polymeric micelles for delivery of insulin.

In this work, fluorescently labeled smart micelle copolymers which consist of Dioctadecylamine-501 (DODA-501) as the hydrophobic segment, N-isopropylacrylamide (NIPAAm) as well as acrylic acid (AAc) as the hydrophilic segments were prepared. These micelles showed both thermo- and pH-sensitive properties due to the nature properties of NIPAAm and AAc, respectively. The particle size of the prepared micelles ranged from 94 approximately 200 nm and was found to increase with DODA-501 concentration. The size of particles varied in different pH mediums or different temperatures suggesting these micelles were pH- and thermo-sensitive. The image of confocal laser scanning microscopy (CLSM) illustrates these micelles had the ability to encapsulate rhodamine solution. From CLSM observation, fluorescein isothiocyanate (FITC) expression was found on the surface of micelles indicating the target detecting ability of these micelles. In drug loading and release studies, these micelles had the ability to encapsulate insulin and its release was pH sensitive, being more rapid under intestinal fluid environment, but resisting the drug release at gastric fluid environment. Stability test indicates these micelles had good stability during storage. These results suggest the pH-sensitivity of the DODA-501 polymeric micelles may be an interesting candidate for oral drug delivery system.

[Spectral properties of 2-(2'-hydroxyphenyl) benzimidazole].

2-(2'-hydroxyphenyl) benzimidazole (HBI) is one kind of organic molecule with excited-state proton transfer (ESPT) effect. The absorption spectra of HBI were observed in toluene, the mixture of toluene and ethanol, and ethanol, respectively. It was found that the absorption spectra in the three solvents are similar. The fluorescence of HBI was observed under the excitation of 317 nm light. Only one fluorescence band with a peak wavelength of 470 nm was observed in the toluene. There appeared two fluorescence bands in the mixed solvents and ethanol, of which the peak wavelength was 370 and 450 nm, respectively. Based on the ESPT theory, the fluorescence band with a peak at 370 nm is attributed to the emission from enol form of HBI molecule, while the band with a peak at 470 nm is attributed to the emission from tautomer form (i. e. keto form) via ESPT process. Because of the strong polarity of ethanol, the intermolecular H-bond can be formed between the HBI molecules and the ethanol and HBI molecules tend to exist in the solvated form. When HBI molecules in solvated form were excited, the zwitterionic form of HBI was formed via ESPT and returned to the ground state accompanied with fluorescence emission, so the fluorescence band with a peak at 450 nm is attributed to the zwitterionic emission of HBI. When the HBI in the three kinds of solvents was excited by the picosecond laser pulse at 532 nm, the two-photon induced fluorescence was not observed in the nonpolar solvents but observed in the polar solvents, which indicate that two-photon effect occurred in solvated form.

Limb-bud and heart as a novel biomarker for gastric intestinal type adenocarcinoma.

The present study compared the expression levels of limb-bud and heart (LBH) between gastric intestinal-type adenocarcinoma (GITA) and healthy gastric tissues; with the aim of investigating the possible effect of LBH on the prognosis of patients with GITA and to analyze the associated signaling pathways in GITA. Three Oncomine gastric datasets were utilized for the preliminary prediction of the expression levels of LBH mRNA in GITA and healthy gastric tissues. Gene expression and corresponding clinical data of 163 patients with GITA were downloaded from The Cancer Genome Atlas. Wilcoxon signed rank-sum test was used to distinguish the clinical value of LBH expression in the various clinicopathological features. Subsequently, Kaplan-Meier univariate and Cox multivariate survival analyses were performed to determine the prognostic significance of LBH expression in patients with GITA. Function enrichment analysis was conducted for the co-expression gene of LBH, defined as correlation coefficient r>0.06 and P<0.05 using Pearson's χ2 test. Bioinformatics data demonstrated that compared with that in the normal gastric mucosa, LBH mRNA expression was dramatically higher in GITA tissues (P<0.05). There were significant relationships between the differential expression levels of LBH and clinicopathological parameters in GITA patients (all p<0.05), including pathological stage T (T3-4 vs. T1-2), lymph node metastasis (no vs. yes), distant metastasis (no vs. yes), histological grade (grade 3 vs. grades 1-2) and tumor stage (stages 3-4 vs. stages 1-2). Additionally, the overall survival and disease-free survival (DFS) of patients in the high expression group were poorer compared with those in the low expression group (P<0.05). Cox multivariate survival analysis indicated that increased LBH expression was an independent predictor of poor DFS prognosis in patients with GITA (P=0.045). In summary, LBH is highly expressed in GITA, which can be used as an independent predictor of poor prognosis in patients with GITA. LBH co-expressed genes are closely associated with GITA tumor migration and metastasis.

[Spectroscopic investigation of 3-hydroxyflavone in different polarity and pH values solutions].

The absorption and fluorescence spectra of 3-hydroxyflavone (3-HF) in different polar solvents were observed with UV-Vis spectrometer and fluorescence spectrometer, respectively. There are three absorption bands in the absorption spectra, wherein two absorption bands with absorption peak at 300 and 345 nm, respectively, are strong, and the other one with absorption peak at 415 nm is weak When the samples in different polar solvents were excited by 345 nm light, there appeared two new fluorescence bands peaked at 400 and 526 nm, respectively. The fluorescence band at 400 nm is attributable to the emission from enol structure and its intensity increases with increasing the polarity of protic solvents; that at 526 nm is attributable to the emission from the isomer structure and its intensity decreases with increasing the polarity of protic solvents. The results show that the increase in the polarity of protic solvents prevents the formation of isomer. When the samples in different polar solvents were excited by 415 nm light, three new fluorescence bands peaked at 440, 471 and 515 nm have not been reported so far. In order to identify the three new fluorescence bands, we prepared the samples with pH value of 5.0, 4.0 and 3.0 through incorporating the different amounts of acetic acid into 3-HF solution. The fluorescence spectra in different pH value solution were observed under excitation of 415 nm light, and it was found that the intensity of two fluorescence bands in the region of shorter wavelength changes with pH values changing. For identifying the fluorescence band of 515 nm peak wavelength, we put sodium hydroxide into 3-HF in ethanol solution and prepared 3-HF samples with pH values of 8.0, 8.5, 9.0, and 10.0. When the samples were excited by the 415 nm light, it was found that two fluorescence bands in the region of shorter wavelength disappeared and the intensity of the fluorescence band of 515 nm was enhanced. Since in sodium hydroxide solution 3-HF forms anion easily, we ascribed the fluorescence band with 515 nm peak wavelength to the emission from the 3-HF anion.

Cytoplasmic ERß1 expression is associated with survival of patients with Stage IV lung adenocarcinoma and an EGFR mutation at exon 21 L858R subsequent to treatment with EGFR-TKIs.

The present study assessed whether estrogen receptor (ER)ß1 is associated with the survival of patients with advanced lung adenocarcinoma, with or without mutations of the epidermal growth factor receptor (EGFR) following treatment with EGFR-tyrosine kinase inhibitors (TKIs). Pathologically confirmed stage IV lung adenocarcinomas were assessed for EGFR mutations and ERß1 expression. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and the log-rank test. A total of 122 out of the 201 (60.7%) patients had EGFR mutations, 64 (31.8%) of which were EGFR Del19 and 58 mutations (28.9%) were EGFR exon 21 L858R mutation. The presence of EGFR mutations was significantly increased in female patients compared with male patients (P<0.001) and in non-smokers compared with smokers (P<0.001). Patients with EGFR mutations had a significantly improved PFS and OS compared with patients without EGFR mutations treated with EGFR-TKIs. Furthermore, ERß1 expression was significantly increased in patients with EGFR mutations compared with patients without EGFR mutations (P=0.001). However, the median PFS (P=0.005) and OS (P=0.002) of patients carrying the EGFR exon 21 L858R mutation was significantly decreased in patients with tumors where ERß1 cytoplasmic expression was high. The multivariate analysis demonstrated that ERß1 expression was the only independent predictor of PFS (P=0.002) and OS (P=0.003) in patients carrying the EGFR exon 21 L858R mutation. The data demonstrated that ERß1 expression may predict outcomes of patients with lung adenocarcinoma treated with EGFR-TKI.

Effect of Apatinib on Serum CD4+CD25+ T cells, NK Cells, and T Cells Subgroup in Malignant Tumor.

OBJECTIVE: The immune makers including CD4+CD25+ T cells, natural killer cells, and T cells subgroup were retrospectively analyzed to find the relationship between apatinib and the immune system in the patients treated with apatinib. METHOD: Forty-two patients with advanced malignant tumors orally took apatinib as treatment and 16 patients with the same situation did not take apatinib as a control group. These patients were all included in the study, and they orally received apatinib 500 mg daily as monotherapy or combination. The treatment was continued until disease progression or intolerable toxicity. CD4+CD25+ T cells, natural killer cells, and T cells subgroup were detected before and 1 month after therapy for all the patients. The relationship between the changing number of immune cells and progression-free survival was analyzed in this study. RESULT: For the apatinib group, the rate of CD4+CD25+ T cells significantly increased (P = .048). The median progression-free survival was 3.25 months for the 42 patients. The median progression-free survival in the patients with the rate of CD4+CD25+ T cells increased and decreased was 5.8 months and 2.9 months, respectively (P = .012). Multivariate analysis found the increased rate of CD4+CD25+ T cells was an independent prognostic factor for a longer progression-free survival. The rate of natural killer cells and T cells subgroup did not change much after apatinib therapy, and they were not independent prognostic factors for progression-free survival. CONCLUSION: The rate of CD4+CD25+ T cells is very important in patients with apatinib treatment. The changing number of CD4+CD25+ T cells may be a good indicator for apatinib prognosis. Natural killer cells and T cells subgroup did not change much after apatinib, and they were not independent prognostic factors for progression-free survival.

Early detection of enamel demineralization by optical coherence tomography.

Enamel is the outermost layer of the tooth that protects it from invasion. In general, an acidic environment accelerates tooth demineralization, leading to the formation of cavities. Scanning electron microscopy (SEM) is conventionally used as an in vitro tool for the observation of tooth morphology changes with acid attacks. Yet, SEM has intrinsic limitations for the potential application of in vivo detection in the early demineralization process. In this study, a high-resolution optical coherence tomography (OCT) system with the axial and transverse resolutions of 2.0 and 2.7 µm in teeth has been utilized for characterizing the effect of the acidic environment (simulated by phosphoric acid) on the enamel topology. The scattering coefficient and the surface roughness of enamel can be directly derived from the OCT results, enabling a quantitative evaluation of the topology changes with demineralization. The dynamic process induced by the acid application is also recorded and analyzed with OCT, depicting the evolution of the demineralization process on enamel. Notably, the estimated enamel scattering coefficient and surface roughness significantly increase with the application time of acid and the results illustrate that the values of both parameters after demineralization are significantly larger than those obtained before the demineralization, illustrating both parameters could be effective to differentiate the healthy and demineralized teeth and determine the severity. The obtained results unambiguously illustrate that demineralization of the tooth surface can be successfully detected by OCT and further used as an indicator of early-stage cavity formation.

Cytotoxic abietane and kaurane diterpenoids from Celastrus orbiculatus.

Celastrus orbiculatus is a medicinal plant belonging to the Celastraceae family. In this survey on the secondary metabolites of plants for obtaining antitumor substances, the chemical constituents of the stems of C. orbiculatus were investigated. Nortriptonoterpene (1), a new C19-norabietane diterpenoid, together with six other known abietane-type diterpenoids (2-7) and five known kaurane-type diterpenoids (8-12) were isolated and identified from the EtOAc extract of C. orbiculatus. Their structures were elucidated on the basis of extensive spectroscopic methods, including UV, IR, HR-ESI-MS, ECD, and NMR experiments, and by comparison with literature data. Compound 1 is a new C19-norabietane diterpenoid with 19 carbons. All compounds except for 10 and 11 were isolated from C. orbiculatus for the first time. The NMR data of 9 were reported for the first time. Compounds 1, 7 and 11 showed cytotoxicities against SGC-7901 with IC50 values of 63.2, 80.9 and 56.7 µM, respectively.

[The spectra properties of 2-(2'-hydroxyphenyl)benzothiazole in different solvents].

2-(2 -hydroxyphenyl)benzothiazole (HBT) is a typical compound with excited--state intramolecular proton transfer (ESIPT) effect. The mechanism of the influence of the solvent polarity on the ESIPT effect of HBT was investigated by means of absorption and fluorescence spectra in different polar solvents. The absorption spectra of HBT molecule in all solvents have the similar configuration and are mainly situated in the UV region from 260 to 370 nm. The absorption peaks are located at 287 and 335 nm and have the decline trend with the increase in the solvent polarity. In addition, there is a very weak absorption band at 400 nm and it is attributable to the absorption from the keto form of HBT. Under UV excitation at 335 nm, the fluorescence spectra in all the solvents were obtained. All the fluorescence spectra exhibit dual fluorescence peaks, which are located at 385 and 512 nm respectively. The former is attributed to the emission from the HBT enol forms, named the normal fluorescence, and the latter the emission from the keto tautomer emission, named ESIPT fluorescence. The fluorescence spectra of HBT show that the intensity of the normal fluorescence is obviously increased and the intensity of the ESIPT fluorescence is decreased with enhancing the polarity of the solvents. This indicates that the strong polar solvents are not favorable to the ESIPT of HBT. Because the solvated enols in the polar solvent prevent the ESIPT from happening, the ESIPT efficiency of HBT in cyclohexane is the largest and that of HBT in ethanol is the smallest. The three fluorescence bands of HBT in different polarity solvents were observed with 400 nm excitation. One fluorescence band at ca. 510 nm is referred to as the ESIPT fluorescence. This confirms that the weak absorption at 400 nm results from the keto tautomer and the enol and keto forms can coexist under the normal condition, but the enol form is the absolutely predominant. In addition, the other two unknown fluorescent emission bands appear at 436 and 456 nm respectively. Their possible origin is the emission from the deprotonated anion of HBT keto tautomer.