Water-energy-vegetation nexus explain global geographical variation in surface urban heat island intensity.

Surface urban heat island (SUHI) is a key climate risk associated with urbanization. Previous case studies have suggested that precipitation (water), radiation (energy), and vegetation have important effects on urban warming, but there is a lack of research that combines these factors to explain the global geographic variation in SUHI intensity (SUHII). Here, we utilize remotely sensed and gridded datasets to propose a new water-energy-vegetation nexus concept that explains the global geographic variation of SUHII across four climate zones and seven major regions. We found that SUHII and its frequency increase from arid zones (0.36 ± 0.15 °C) to humid zones (2.28 ± 0.10 °C), but become weaker in the extreme humid zones (2.18 ± 0.15 °C). We revealed that from semi-arid/humid to humid zones, high precipitation is often coupled with high incoming solar radiation. The increased solar radiation can directly enhance the energy in the area, leading to higher SUHII and its frequency. Although solar radiation is high in arid zones (mainly in West, Central, and South Asia), water limitation leads to sparse natural vegetation, suppressing the cooling effect in rural areas and resulting in lower SUHII. In extreme humid regions (mainly in tropical areas), incoming solar radiation tends to flatten out, which, coupled with increased vegetation as hydrothermal conditions become more favorable, leads to more latent heat and reduces the intensity of SUHI. Overall, this study offers empirical evidence that the water-energy-vegetation nexus highly explains the global geographic variation of SUHII. The results can be used by urban planners seeking optimal SUHI mitigation strategies and for climate change modeling work.

miR-142-3p improves paclitaxel sensitivity in resistant breast cancer by inhibiting autophagy through the GNB2-AKT-mTOR Pathway.

Breast cancer has overtaken lung cancer as the most prevalent cancer worldwide. The development of advanced drug resistance inhibits the efficacy of paclitaxel(PTX)as a first-line chemotherapeutic agent for breast cancer. Autophagy and microRNAs (miRNAs) play a key role in chemoresistance. This study investigated the miR-142-3p effect on PTX resistance by regulating autophagy. A PTX-resistant breast cancer cell line was constructed, and miR-142-3p and G protein beta polypeptide 2 (GNB2) were filtered out using RNA sequencing and protein microarray analysis. The study revealed that miR-142-3p expression was lower in drug-resistant cells compared parental cells. Higher miR-142-3p expression inhibited the viability, migration, and autophagic flux of drug-resistant cells, while promoting apoptosis and sensitivity to PTX treatment. Mechanistically, miR-142-3p was found to amend PTX resistance by targeting GNB2, further revealing that the knockdown of GNB2 expression could activate the AKT-mTOR pathway. This study suggests that GNB2 is an essential target for miR-142-3p to restrain autophagy, providing a new reference value for improving breast cancer PTX treatment.

Solvent effect on the photophysical properties of thermally activated delayed fluorescence molecules.

As the third-generation organic electroluminescent materials, thermally activated delayed fluorescence (TADF) molecules have become the research focus recently. Significant solvent effect on TADF molecules were found experimentally, while theoretical investigations are quite limited. In this work, the solvent effect on photophysical properties of DCBPy and DTCBPy are investigated with first-principles calculations. The solvent polarity has slight influence on the molecular geometries and orbitals, while it can decrease the energy gap between the first singlet excited state (S1) and first triplet excited state (T1) significantly. Both the oscillator strength and the radiation rates of S1 increase with larger solvent polarity. The large energy gap between S1 and T1 induce negligible intersystem crossing (ISC) and reverse ISC rates between them, which also indicates higher triplet excited states are involved in the up-conversion process. Our results provide valuable information about solvent influence on the light-emitting properties of TADF molecules, which could help one better understand the light-emitting mechanism of them and favor the design of TADF molecules.

Photoluminescence properties of Ca9La(PO4)5SiO4F2:Ce3+/Tb3+/Mn2+ phosphors for applications in white light-emitting diodes and optical thermometers.

A series of Ca9La(PO4)5SiO4F2:Ce3+,Tb3+,Mn2+ (CLPSF:Ce3+,Tb3+,Mn2+) phosphors were obtained by a conventional solid-state reaction method, and the luminescence properties excited by ultraviolet light were investigated in detail. The Ce3+-doped CLPSF samples show near-ultraviolet luminescence with the dominant peaks around 361 nm. Different Ce3+ emission centers were identified from the emission spectra. When the Ce3+ and Mn2+ are codoped into the host, an energy transfer (ET) from Ce3+ to Mn2+ was found, owing to which the visible emitting-light-color has been tuned from blue to light brown. The corresponding ET mechanism was studied by employing Dexter's theory. In the Ce3+-Tb3+ codoped CLPSF phosphors, the tunable emission was realized on the basis of the ET between Ce3+ and Tb3+. To further obtain the white emissions with tunable correlated color temperature, the Ce3+-Tb3+-Mn2+ tridoped CLPSF samples were designed, and the ET relationship in these phosphors were discussed. By studying the thermally luminescent properties, it was found that the Ce3+ and Mn2+ emission intensities in the CLPSF:Ce3+,Mn2+ samples showed different decrease rates with increasing temperature. The fluorescence intensity ratio (FIR) technique was used to investigate the temperature-sensing performance. On the other hand, the CLPSF:Ce3+,Tb3+ and CLPSF:Ce3+,Tb3+,Mn2+ phosphors exhibit relatively high thermally luminescent stability. The above discoveries indicate that the developed phosphors could have potential applications in LEDs and optical thermometer.

Urban Design Factors Influencing Surface Urban Heat Island in the High-Density City of Guangzhou Based on the Local Climate Zone.

Surface urban heat island (SUHI) depicts the deteriorating thermal environment in high-density cities and local climate zone (LCZ) classification provides a universal protocol for SUHI identification. In this study, taking the central urbanized area of Guangzhou in the humid subtropical region of China as the study area, the maps or images of LCZ, land surface temperature, SUHI, and urban design factors were achieved using Landsat satellite data, GIS database, and a series of retrieval and classification algorithms, and the urban design factors influencing SUHI were investigated based on 625 samples of LCZs. The results show that on the 18 September 2016 at the local time of 10:51 a.m., the land surface temperature (LST) varied greatly from 26 °C to 40 °C and the SUHI changed with a wide range of -6 °C to 8 °C in the LCZs of the study area. Seven and five urban design factors influencing the summer daytime SUHI were identified for the two dominant LCZs of LCZs 1-5 (LCZ 1 to LCZ 5) and the mixed LCZ (containing at least three types of LCZs), respectively, in which vegetation cover ratio, floor area ratio, ground emissivity, and complete surface area ratio showed negative correlations and building density showed positive correlations. The summer daytime SUHI prediction models were obtained by using the step-wise multiple linear regression, with the performance of R2 of 0.774, RMSE of 0.95 °C, and the d value of 0.91 for the model of LCZs 1-5, and the values of 0.819, 0.81 °C, and 0.94 for the model of the mixed LCZ, indicating that the models can effectively predict the changes of SUHI with LCZs. This study presents a methodology to efficiently achieve a large sample of SUHI and urban design factors of LCZs, and provides information beneficial to the urban designs and regenerations in high-density cities.

Controllable synthesis of lanthanide Yb3+ and Er3+ co-doped AWO4 (A = Ca, Sr, Ba) micro-structured materials: phase, morphology and up-conversion luminescence enhancement.

Lanthanide ion (Yb3+, Er3+) co-doped AWO4 (A = Ca, Sr, Ba) up-conversion (UC) luminescent materials have been synthesized using a hydrothermal method and characterized by various microstructural and optical techniques. The results indicate that AWO4:Yb3+,Er3+ samples have an identical body-centered tetragonal scheelite structure with different morphologies, including CaWO4:Yb3+,Er3+ microspheres, dumbbell-like SrWO4:Yb3+,Er3+ and bipyramid-like BaWO4:Yb3+,Er3+. These samples exhibit visible emissions via an UC process under near-infrared (NIR) light (980 nm) excitation. Interestingly, the UC luminescence properties of AWO4:Yb3+,Er3+ can be prominently increased after combination with fluorescent carbon dots (CDs) to form CDs@AWO4:Yb3+,Er3+ composites. Compared to the corresponding samples without combination with CDs, the UC emission intensities of CDs@CaWO4:Yb3+,Er3+, CDs@SrWO4:Yb3+,Er3+ and CDs@BaWO4:Yb3+,Er3+ composites increase about three, six and seven fold in the green emission area, and two, three and four fold in the red emission area, respectively. The mechanism of UC luminescence enhancement is probably that the loss of non-radiative transitions from the higher energy levels to the lower excited levels could be effectively reduced through the energy capture by the CD energy levels. The fluorescence enhancement for Yb3+ and Er3+ co-doped AWO4 through combination with CDs provides a simple strategy for the tungstate system and other UC luminescent host systems.

Effects of street canyon design on pedestrian thermal comfort in the hot-humid area of China.

The design characteristics of street canyons were investigated in Guangzhou in the hot-humid area of China, and the effects of the design factors and their interactions on pedestrian thermal comfort were studied by numerical simulations. The ENVI-met V4.0 (BASIC) model was validated by field observations and used to simulate the micrometeorological conditions and the standard effective temperature (SET) at pedestrian level of the street canyons for a typical summer day of Guangzhou. The results show that the micrometeorological parameters of mean radiant temperature (MRT) and wind speed play key roles in pedestrian thermal comfort. Street orientation has the largest contribution on SET at pedestrian level, followed by aspect ratio and greenery, while surface albedo and interactions between factors have small contributions. The street canyons oriented southeast-northwest or with a higher aspect ratio provide more shade, higher wind speed, and better thermal comfort conditions for pedestrians. Compared with the east-west-oriented street canyons, the north-south-oriented street canyons have higher MRTs and worse pedestrian thermal comfort due to their wider building spacing along the street. The effects of greenery change with the road width and the time of the day. Street canyon design is recommended to improve pedestrian thermal comfort. This study provides a better understanding of the effects of street canyon design on pedestrian thermal comfort and is a useful guide on urban design for the hot-humid area of China.

Construction of pH-responsive and up-conversion luminescent NaYF4:Yb³âº/Er³âº@SiO2@PMAA nanocomposite for colon targeted drug delivery.

Colon-targeted drug delivery system has attracted much interest because it can improve therapeutic efficacy and reduce the side effect in practical clinic. Herein, we constructed a multifunctional drug delivery system with colonic targeting and tracking by up-conversion (UC) luminescence based on core-shell structured NaYF4:Yb(3+)/Er(3+)@SiO2@PMAA nanocomposite. The resultant materials exhibited bright UC luminescence, pH-responsive property and excellent biocompatibility. The drug release behaviors in different pH environment were investigated using 5-aminosalicylic acid (5-ASA) as a model drug. The 5-ASA molecules release from NaYF4:Yb(3+)/Er(3+)@SiO2@PMAA nanocomposite exhibit a significant pH-responsive colon targeted property, i.e., a little amount of drug release in simulated gastric fluid (SGF, pH = 1.2) but a large amount of drug release in simulated colonic fluid (SCF, pH = 7.4) Moreover, the drug release process could be monitored by the change of UC emission intensity. These results implied that the multifunctional nanocomposite is a promising drug carrier for targeted release of 5-ASA in the colon.

[Mechanism Research of Gambogenic Acid on Proliferation,Apoptosis and Invasion of Cervical Carcinoma He La Cells].

Objective: To investigate the effects of gambogenic acid on proliferation,apoptosis and invasion of human cervical carcinoma HeLa cells. Methods: HeLa cells were given different concentrations of gambogenic acid( 0. 00,0. 63,1. 25,2. 50,5. 00 and 10. 00 mg / L) for 72 h,MTT assay was used to measure the cells proliferation. Flow cytometry was used to measure cell cycle. Fluorescence microscopy and DNA ladder analysis were used to measure the apoptosis of HeLa cells. Transwell chambers was adopted to detect the cells invasion. The expression levels of mRNA and protein of BCL-2,BAX,NF-κB and E-cadherin were detected by RT-PCR and Western blot. Results: After treatment with different concetrations of gambogenic acid for 72 h, the proliferation of HeLa cells was significantly inhibited, and in a concentration dependent manner. The ability of invasion was decreased with the concentration of gambogenic acid increased, which was detected by Transwell chamber assays in vitro. RT PCR and Western blot demonstrated that gambogenic acid up-regulated the expressions of BAX and E-cadherin and down-regulated the expression of mRNA and protein of BCL-2 and NF-κB. Conclusion: Gambogenic acid can inhibite the proliferation and invasion of HeLa cells,and promote the cells apoptosis in a concentration dependent manner.

[Expression of Micro-RNA 218 in Cervical Cancer and Its Effect on Proliferation, Apoptosis and Invasion of HeLa Cells].

OBJECTIVES: To investigate the expression and clinical significance of microRNA-218(miR-218)in human cervical cancer and the effects ofmiR-218 on proliferation, cell apoptosis and invasion of HeLa cells. METHODS: QRT-PCR was used to detect the expression ofmiR-218 in 23 cases of normal cervical tissues and 114 cases of cervical cancer, and the relationship between the expression and the clinicopathological features was analyzed; HeLa cells were devided into three groups: non transfection (control group), transfected with empty liposomes negative control goup (NC group), transfected with miR-218 mimic (miR-218M group). The cell growth inhibiting ratio of HeLa cells was assessed by MTT assay. Fluorescence activated cell sorting was used to measure cell apoptosis. Changes of cell migration ability were detected by wound healing test and Transwell assay. QRT-PCR and Western blot were used to detect the expression of Bcl-2, Bax, NF-κB and E-cadherin, respectively. RESULTS: The expression ofmiR-218 in cervical cancer was down regulated, and there were significant differences in the different pathological types, stages, lymph node metastasis and interstitial infiltration in cervical cancer tissues ( P<0.01); After being transfected with miR-218 mimic, the proliferation of HeLa cells was significantly inhibited. The ability of invasion was decreased. QRT-PCR and Western blot showed that after being transfected with miR-218 mimic, the expression levels of Bcl-2 mRNA and protein were down-regulated and Bax mRNA and protein expression levels were increased, E-cadherin mRNA and protein expression were up-regulated, but NF -κB mRNA and protein expression were down-regulated. CONCLUSIONS: he low-expression of miR-218 is correlated with the poor clinicopathological features in human cervical cancer. MiR-218 overexpression reduces cancer cell proliferation and induces apoptosis and inhibits cell migration, suggesting that miR-218 may play a key role in the progression of human cervical cancer.

A novel Ce³âº activated Lu3MgAl3SiO12 garnet phosphor for blue chip light-emitting diodes with excellent performance.

A novel Ce(3+) activated Lu3MgAl3SiO12:Ce phosphor was synthesized and found to crystallize in the garnet structure. The crystal structure of the synthesized phosphor has been characterised by X-ray diffraction and Rietveld refinement. Both room and high temperature photoluminescence spectra are utilized to investigate the luminescence properties and crystal field splitting. The high temperature quenching of these phosphors and their quantum efficiency (QE) are also studied using both the prepared YAG:Ce and the commercial YAG:Ce phosphor named P46-y3 as the reference. Upon excitation with blue light, the composition-optimized Lu3MgAl3SiO12:Ce phosphor exhibited strong yellow light with a high QE of 81.2% and better thermal stability than that of the commercial phosphor. The results indicate that the Lu3MgAl3SiO12:Ce phosphor can serve as a candidate for blue chip LEDs.

A single-component white-emitting CaSr2Al2O6:Ce3+, Li+, Mn2+ phosphor via energy transfer.

A series of single-component Ce(3+), Li(+), Mn(2+) ions codoped color-tunable CaSr2Al2O6 phosphors were synthesized by a high-temperature solid-state reaction, and the photoluminescence properties as well as the energy transfer mechanism from Ce(3+) to Mn(2+) ions have been investigated in detail. The Ce(3+) activated phosphors have strong absorption in the range of 250-420 nm and can give a blue emission centered at about 460 nm. When Mn(2+) ions are codoped, the emission of CaSr2Al2O6:Ce(3+), Li(+), Mn(2+) phosphors can be tuned from blue to red through adjusting the doping concentration of the Mn(2+) ions, under the irradiation of 358 nm. When the concentration of Mn(2+) is increased to 0.02, a warm-white light can be obtained with good CIE coordinates of (0.388, 0.323) and a low CCT of 3284 K. The energy transfer mechanism from the Ce(3+) to Mn(2+) ions is demonstrated to be a quadrupole-quadrupole interaction based on the analysis of the decay curves of the phosphors. The thermal quenching stability was also investigated. The results indicate that CaSr2Al2O6:Ce(3+), Li(+), Mn(2+) samples might have potential applications in w-LEDs.

Enhanced photoluminescence and thermal properties of size mismatch in Sr(2.97-x-y)Eu0.03Mg(x)Ba(y)SiO5 for high-power white light-emitting diodes.

In this Study, Mg(2+) and Ba(2+) act to enhance the maximum emission of Sr2.97SiO5:0.03Eu(2+) significantly and redshift the emission band to the orange-red region in Sr(2.97-x-y)Mg(x)Ba(y)SiO5:0.03Eu(2+). Size mismatch between the host and the doped cations tunes the photoluminescence spectra shift systematically. A slight blue shift when increasing the amount of Mg(2+) occurs in the Sr(2.97-x)Eu0.03Mg(x)SiO5 lattices, and a rapid red shift occurs when Ba(2+) is codoped in the Sr(2.57-y)Eu0.03Mg0.4Ba(y)SiO5 lattices. The emission spectra were tuned from 585 to 601 nm by changing the concentration of Ba(2+). Accordingly, we propose the underlying mechanisms of the changes in the photoluminescence properties by adjusting the cation composition of phosphors. The influence of the size mismatch on the thermal quenching is also observed. This mechanism could be widely applied to oxide materials and could be useful in tuning the photoluminescence properties, which are sensitive to local coordination environment. The emission bands of Sr(2.97-x-y)Eu0.03Mg(x)Ba(y)SiO5 show the blue shift with increasing temperature, which could be described in terms of back tunneling of the excited electrons from the low-energy excited state to the high-energy excited state. Thus, the Sr(2.97-x-y)Eu0.03Mg(x)Ba(y)SiO5 phosphors could have potential applications in the daylight LEDs or warm white LEDs.

Structure, photoluminescent and cathodoluminescent properties of a rare-earth free red emitting ß-Zn3B2O6:Mn2+ phosphor.

A rare-earth free red emitting ß-Zn3B2O6:Mn(2+) phosphor was prepared by a solid-state reaction method. The crystal structure, photoluminescent and cathodoluminescent properties of ß-Zn3B2O6:Mn(2+) were systematically investigated. The absorption and photoluminescence excitation spectra confirm that ß-Zn3B2O6:Mn(2+) matches the UV LED chip. Under UV light and low-voltage electron beam excitations, an interesting orange-red emission band centered at ∼600 nm of Mn(2+) at the tetrahedral Zn(2+) sites is observed. Besides, the unusual red shift with increasing Mn(2+) content is also found and contributed to an exchange interaction between Mn(2+). In addition, under low-voltage excitation, ß-Zn3B2O6:Mn(2+) exhibits higher color purity of 98.1% than that of the commercial ZnS:Ag,Cd yellow phosphor and reported ZnGeN2:Mn(2+) orange phosphor, which indicated the ß-Zn3B2O6:Mn(2+) has a patenting application in FEDs.

Tunable luminescence Y3Al5O12:0.06Ce³âº, xMn²âº phosphors with different charge compensators for warm white light emitting diodes.

Y3Al5O12:0.06Ce³âº, xMn²âº (YAG:0.06Ce,xMn) phosphors have been synthesized and the effect of different charge compensators on the color adjustment has been investigated for the first time. The luminescence properties of Mn2+ singly doped and co-doped with Ce3+ into YAG host have been discussed. It is observed that in singly doped sample, Mn2+ ions not only occupy two kinds of Al3+ sites to generate a yellow and a deep red emission bands, but also occupy Y3+ sites to obtain a green emission band in YAG host. Considering Mn2+ substitution for Al3+, quadrivalence ions including Zr4+, Ge4+ and Si4+ ions are introduced to balance the charge difference. The results show that Si4+ as charge compensator exhibits the best tunable effect on controlling the Mn2+ emissions in YAG:0.06Ce, xMn. In Si4+-Mn2+ co-doped samples, the emission color can be tuned from greenish-yellow to red with increasing the content of Mn2+. The Commission International de L'Eclairage (CIE) chromaticity coordinates are also investigated.

[In vitro interaction of human pancreatic cancer cells and rat dorsal root ganglia: a co-culture model].

OBJECTIVE: To establish an in vitro model of perineural invasion (PNI) with co-culture of human pancreatic cancer cells and rat root ganglion, to observe the neurite outgrowth and pancreatic cancer cell proliferation and migration, and to explore the molecular basis of perineural invasion (PNI) of pancreatic cancer. METHODS: Human pancreatic cancer cell line (MIA PaCa-2) and rat dorsal root ganglion (DRG) were co-cultured in Matrigel matrix to generate the PNI model. The neurite outgrowth, pancreatic cancer cell colony formation, neurite-colony contact and retrograde migration were observed under an inverted microscope. The data were analyzed with the Image-Pro Plus 5.0 system. The proliferative index (PI) was measured by immunohistochemical staining with the Ki-67 antibody. In order to determine the absorbance (A) of the pancreatic cancer cells, MTT assay was used. The apoptotic index (AI) was evaluated by flow cytometry. RESULTS: Neurite outgrowth was stimulated in the presence of pancreatic cancer cells. After 72 hours of the co-culture, MIA PaCa colonies co-cultured with DRG exhibited a significantly larger colony area (242.83 ± 4.92) than that of the control (182.50 ± 5.39, P < 0.001). In the MIA PaCa-2/DRG co-culture system, the neurites exhibited a trend of growing towards the pancreatic cancer cell colony. However, the pancreatic cancer cells showed a trend of retrogradely migrating to the DRG along the neurite outgrowth, when MIA PaCa-2 colonies touched the DRG. The positive rate of Ki-67 nuclear antigen was significantly higher than in the co-culture group. The PI value was higher in the experimental group (12.80%) than that in the control group (6.81%, P < 0.01). The MTT assay showed that proliferation of the pancreatic cancer cells was more active than that in the control group. Flow cytometry analysis showed that the apoptosis rate of the pancreatic cancer cell was 2.46%, significantly lower than that of the control group (4.89%, P < 0.001). CONCLUSIONS: An in vitro co-culture model of rat dorsal root ganglion and human pancreatic cancer cell line is successfully established in this study. This MIA PaCa-2/DRG co-culture system demonstrates that the neural-pancreatic carcinoma cell interaction is a mutually beneficial process for the growth of neurites and pancreatic carcinoma cells. The pancreatic cancer cells show a trend of migrating to the DRG along the neurite outgrowth.

A facile one-step solvothermal synthesis of graphene/rod-shaped TiO2 nanocomposite and its improved photocatalytic activity.

Graphene sheets were obtained through solvothermal reduction of colloidal dispersion of graphene oxide in benzyl alcohol. The graphene/rod-shaped TiO(2) nanocomposite was synthesized by this novel and facile solvothermal method. During the solvothermal reaction, both the reduction of graphene oxide and the growth of rod-shaped TiO(2) nanocrystals as well as its deposition on graphene occur simultaneously. The photocatalytic activity of graphene/rod-shaped TiO(2) and graphene/spherical TiO(2) nanocomposites was compared. In the photocatalytic degradation of methyl orange (MO), the graphene/rod-shaped TiO(2) nanocomposite with the optimized graphene content of 0.48 wt% shows good stability and exhibits a significant enhancement of photocatalytic activity compared to the bare commercial TiO(2) (P25) and graphene/spherical TiO(2) nanocomposite with the same graphene content. Photocurrent experiments were performed, which demonstrate that the photocurrent of the graphene/rod-shaped TiO(2) nanocomposite electrode is about 1.2 times as high as that of the graphene/spherical TiO(2) nanocomposite electrode. The photocatalytic mechanism of graphene/rod-shaped TiO(2) nanocomposite was also discussed on the basis of the experimental results. This work is anticipated to open a possibility in the integration of graphene and TiO(2) with various morphologies for obtaining high-performance photocatalysts in addressing environmental protection issues.

MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and LASP1 in human triple-negative breast cancer cells.

BACKGROUND: This study was performed to investigate the effect of microRNA-203 (miR-203) on cell proliferation and migration in triple-negative breast cancer (TNBC). METHODS: Real-time PCR was performed to detect the expression of miR-203 in TNBC cell lines. miR-203 precursor and control microRNA (miRNA) were transfected into triple-negative breast cancer (TNBC) cell lines and the effects of miR-203 up-regulation on the proliferation and migration of cells were investigated. Meanwhile, the mRNA and protein levels of baculoviral IAP repeat-containing protein 5 (BIRC5) and Lim and SH3 domain protein 1 (LASP1) were measured. Luciferase assays were also performed to validate BIRC5 and LASP1 as miR-203 targets. RESULTS: Both miR-203 and BIRC5 siRNA signicantly inhibited cell proliferation in TNBC cells. Both miR-203 and LASP1 siRNA signicantly inhibited cell migration in TNBC cells, also. Moreover, up-regulated of BIRC5 and LASP1 was able to abrogate the effects induced by transfection with the miR-203 precursor. CONCLUSIONS: These data suggest that miR-203 may function as a tumor suppressor in TNBC cells. Thus, miR-203 could be a potential therapeutic target for this disease.

Mitochondrial DNA depletion promotes impaired oxidative status and adaptive resistance to apoptosis in T47D breast cancer cells.

The mutation and reduction of mitochondrial DNA (mtDNA) have been extensively detected in human cancers. The effects of mitochondrial dysfunction are particularly important in breast cancer, because estrogen-mediated metabolites generate large quantities of local reactive oxygen species in the breast, which directly bind to mtDNA and facilitate neoplastic transformation. To further elucidate the molecular roles of mtDNA in breast cancer, we determined the oxidative status of a breast tumor cell line lacking mtDNA (T47D ρ°) and analyzed its susceptibility after exposure to various anticancer drugs as well as different proapoptotic signals. Our data showed that T47D ρ° cells generated significantly increased levels of lactate with concomitantly reduced oxygen consumption and ATP production compared with the wild-type (WT). The amount of reactive oxygen species generation in ρ cells was lowered to approximately 12% that of parental cells, as evidenced by the oxidation of redox-sensitive probes. Although mtDNA depletion did not affect the expression of superoxide dismutase or its activity, the activities of antioxidant enzymes, catalase and glutathione peroxidase, were significantly higher in ρ° cells compared with WT cells. In addition, mtDNA-depleted cells displayed a decreased sensitivity and accumulation of chemotherapeutic drugs (doxorubicin, vincristine, and paclitaxel), potentially because of the upregulated expression of multidrug resistance 1 (MDR1) gene and its product P-glycoprotein. When compared with their WT counterparts, T47D ρ° cells were also more resistant to apoptosis induced by varying concentrations of staurosporine and anti-Fas antibody. Altogether, our results indicate the importance of intact mtDNA for maintaining the proper intracellular oxidative status. These data provide evidence for a possible role of mtDNA content reduction in acquiring an apoptosis-resistant phenotype during breast tumor progression and might contribute to effective therapeutic strategies for this common malignancy.

[Relationship between mutation of BRCA1 and susceptibility to early onset of breast cancer].

OBJECTIVE: To detect the prevalence of Breast Cancer Susceptibility Gene 1 (BRCA1) mutations and single nucleotide polymorphism (SNP) among young patients with breast cancer and to study the relationship between BRCA1 gene mutation and susceptibility to breast cancer. METHODS: 30 samples of breast cancer tissue were collected from female patients with breast cancer diagnosed when they were aged < or = 35 5 of which had at least one first-degree relative affected with breast cancer. Genomic DNA was extracted from the breast cancer tissues. The PCR products were amplified in the coding sequence of exon 2, 11C, 11F, 11L, 11I, 16, and 20 by using polymerase chain reaction. Then the PCR products were analyzed using DNA direct sequencing. The sequence was compared with the DNA Star-MagAlign software. RESULTS: A total of 14 sequence variations in BRCA1 gene were identified, including 3 frameshift mutations (cDNA2639, 2640delTA, 3343 delG, and 3398delT) and 11 spot mutations (cDNA 2570 C > T, cDNA 2620 A > T, 1473 A > G, 1561 C > T, 1594G > A, 2206 A > G, 2227 T > C, 2659 C > A, 2806T > C, 3307 A > G, and 3375 G > A). Three patients with these mutations had a family history of breast cancer. The mutation frequency of BRCA1 was 10% (3/30). No mutation was found in the exons 16 and 20. CONCLUSION: Patients with breast cancer aged < or = 35 have BRCA1 mutations located in the exon 11 mainly. The mutation frequency of the breast cancer patients aged < or = 35 with breast cancer family history is higher than those without family history. Three frameshift mutation sites may be related to early onset of breast cancer.