Macleanfanning4788

The surface of pulmonary alveolar subphase is covered with a mixture of lipids and proteins. This lung surfactant plays a crucial role in lung functioning. It shows a complex phase behavior which can be altered by the interaction with third molecules such as drugs or pollutants. For studying multicomponent biological systems, it is of interest to couple experimental approach with computational modelling yielding atomic-scale information. Simple two, three, or four-component model systems showed to be useful for getting more insight in the interaction between lipids, lipids and proteins or lipids and proteins with drugs and impurities. These systems were studied theoretically using molecular dynamic simulations and experimentally by means of the Langmuir technique. A better understanding of the structure and behavior of lung surfactants obtained from this research is relevant for developing new synthetic surfactants for efficient therapies, and may contribute to public health protection.Concentrations of 127I and 129I in rainwater samples from several stations across Argentina (latitudes between 25° S and 55° S) were measured and analyzed for the assessment of distribution patterns and potential sources of 129I in the Southern Hemisphere. Measured 129I levels, clearly above those explainable by natural background and atmospheric nuclear weapons tests, can be understood by the injection into the Southern Hemisphere of 129I that had been discharged from nuclear fuel reprocessing plants in the Northern Hemisphere.In clinical practice, a large number of patients have failed to receive chemotherapy or combination therapy because of drug resistance, recurrence and metastasis of specific sites. Therefore, how to choose the initial chemotherapy individually and reduce the occurrence of drug resistance is the key to cure high-risk GTN. This study investigated the efficacy of chemotherapy based on 5-fluorouracil (5-FU) regimen and EMA/CO regimen as the initial chemotherapy regimen in the treatment of high-risk gestational trophoblastic neoplasms (high-risk GTN). The treatment status of high-risk GTN patients who received primary chemotherapy using 5-Fu regimens (FAV and FA regimens) or EMA/CO regimens at Cancer Hospital of China Medical University from 2002 to 2019 was retrospective analyzed. Regular follow-up was conducted to evaluate its efficacy and to analyze prognostic factors. There were a total of 87 high-risk patients, 75 in the 5-FU-based group and 12 in the EMA/CO group. The clinical characteristics of patients in ognosis of high-risk GTN (P = 0.003). Conclusion Both 5-FU regimen and EMA / CO regimen can be used as the first-line treatment for high-risk GTN patients, and their effects are similar. For high-risk GTN patients with drug resistance, EMA / CO, FAEV and PEB can be used as second-line salvage chemotherapy.Osteoarthritis occurs when the number of senescent chondrocytes in the joints reaches an intolerable level. The purpose of our study was to explore the therapeutic effect and mechanism of action of A-1331852 in osteoarthritis. Doxorubicin and etoposide were used to induce cell senescence as determined by the cessation of cell proliferation, augmented senescence-associated beta-galactosidase (SA-β-Gal) staining, and increased p53 expression levels. The CCK-8 cytotoxicity assay and SA-β-Gal staining demonstrated that Bcl-xL inhibitors could selectively remove senescent chondrocytes without damaging healthy chondrocytes. A-1331852 induced caspase-dependent death of senescent chondrocytes with decreased mitochondrial membrane potential, nuclear concentration, plasma membrane rupture, and PARP cleavage. Most importantly, A-1331852 upregulated BAK expression levels, indicating that BAK plays a key role in the A-1331852-induced apoptosis of senescent chondrocytes. Live-cell fluorescence resonance energy transfer showed that A-1331852 detached the binding of Bcl-xL to BAK and promoted the oligomerization of BAK on the mitochondrial membrane. In conclusion, this study provides the first evidence that A-1331852 selectively promotes apoptosis in senescent chondrocytes by interfering with the interaction between Bcl-xL and BAK.Autophagy is a double-edged sword that affects tumor progression by promoting cell survival or death depending on different living contexts. The concrete mechanism by which autophagy modulates the efficacy of radiotherapy for prostate cancer (PC) remains unclear. We exposed RM-1 PC cells to X-ray and explored the role of autophagy in radiation injury. Our results showed increased apoptosis and autophagy levels in RM-1 cells after radiation. Pharmacological inhibition of autophagy by chloroquine significantly mitigated radiation-induced apoptosis, while the enhancement of autophagy by rapamycin aggravated apoptosis. this website Sirt1, a member of sirtuin family, deacetylates various transcription factors to trigger cell survival in response to radiation injury. We found that radiation led to Sirt1 downregulation, which was reversed by the inhibition of autophagy. On the contrary, enhanced autophagy further diminished protein level of Sirt1. Notably, overexpression of Sirt1 by plasmid significantly alleviated radiation-induced apoptosis, but silenced Sirt1 by siRNA further induced apoptosis, indicating the radioprotective effect of Sirt1 on RM-1 cells. In summary, our findings suggested that autophagy-mediated Sirt1 downregulation might be a promising therapeutic target for PC.The present study was to identify abnormal methylation genes implicated in esophageal squamous cell carcinoma (ESCC). Genomic methylation alterations in ESCC tissues were analyzed using laser-microdissection and whole-genome bisulfite sequencing. CXCL14 promoter was frequently hypermethylated in ESCC tissues. The correlation of CXCL14 hypermethylation status and the mRNA and protein expression levels were validated using nested methylation-specific PCR (nMS-PCR), RNAscope in situ hybridization (RISH) and Western blot. RISH results showed completely negative CXCL14 expression in 34.3% (34/99) ESCC, compared with those in the basal layer cells of normal epithelia. Low expression of CXCL14 was more present in patients with lower differentiation. The anticancer role of CXCL14 has been commonly associated with immune regulation in the literature. Here, we observed by functional analysis that CXCL14 can also act as a tumor suppressor in ESCC cells. 5-Aza-dC treatment suppressed CXCL14 methylation and up-regulated the expression of CXCL14. Ectopic expression of CXCL14 suppressed the proliferation, invasion, tumor growth, and lung metastasis of ESCC cells. Both ectopic expression and induction of CXCL14 with 5-Aza-dC inhibited the activity of SRC, MEK1/2 and STAT3 in ESCC cells, while activated EGFR. Importantly, a combination of CXCL14 expression and SRC or EGFR inhibitor dramatically repressed the proliferation of ESCC cells and the growth of xenografts. Our findings revealed a direct tumor suppressor role of CXCL14, but not through the immune system. The data suggest that for ESCC patients with low level CXCL14, increasing CXCL14 expression combined with inhibition of SRC or EGFR might be a promising therapeutic strategy.Cancer-derived exosomes carry a variety of important biomarkers specific to the formation, invasion and metastasis of tumor tissue. Dynamic monitoring of exosomes originated from cancer cells has clinical significance. Here we proposed a novel method to employ zirconium-metal-organic frameworks (Zr-MOFs) for extracting and identifying exosomes from blood. At first UiO-66 was magnetically modified as the adsorbent to anchor exosomes by forming Zr-O-P bonds. Then UiO-66-NH2 modified with anti-EpCAM was used to construct the fluorescent probe to recognize the extracted EpCAM-positive exosomes by forming a "MOF-exosome-MOF" structure. The proposed fluorescence detection method was evaluated by quantifying MCF-7 cell-derived exosomes at the concentration as low as 16.72 particles/μl. This method was successfully applied to analyze exosomes in the plasma samples from healthy donors and breast cancer patients, demonstrating that our method might have a great potential in assisting the early diagnosis and in dynamically monitoring the efficacy of cancer treatment. We believe that the method could be extended to the detection of other biomarkers in exosomes derived from cancer cell.Understanding the processes that create inhibitory demands is central to understanding the role of inhibitory control in all aspects of development. The processes that create inhibitory demands on most developmental tasks seem clear and well understood. However, there is one inhibitory task that appears substantially easier than the others the Reverse Categorization task, in which children are asked to "reverse sort" items (e.g., put large items in a small box and put small items in a large box). This finding is both surprising and problematic because it cannot be explained by any existing account of inhibitory development. Four experiments with 3- and 4-year-olds sought to explain why the Reverse Categorization task is easy. Two experiments (N = 64) investigated the hypothesis that children conceptualize the task in a way that reduces its inhibitory demands; and two experiments (N = 56) tested the hypothesis that the task is easier because children sort items slowly. The data indicate that children spontaneously respond more slowly on the Reverse Categorization task than on other inhibitory tasks and that this slowing reduces the task's cognitive demands. The way in which slowed responding works, and its relation to other inhibition-reducing interventions, is discussed.Recent research revealed that infants attend to agents' intentions when they evaluate helping actions. The current study investigated whether infants also consider agents' intentions when they evaluate distributive actions. In Experiment 1, 9-month-old infants were first shown two failed attempts to perform a distribution. In the "failed equal distribution," the distributor first tried to reach one of the recipients to deliver an apple, failed, and then attempted to reach the other possible recipient to deliver a different apple and also failed. In the "failed unequal distribution," a different distributor always tried unsuccessfully to reach the same beneficiary. Then, in the test phase, infants were presented with the two distributors side by side, and infants' spontaneous preferential looking and reaching actions were recorded. We found a reliable preference for the equal distributor in both the visual and manual responses. Experiments 2 and 3 helped to rule out alternative explanations based on perceptual cues and affiliative biases. Overall, these findings suggest that infants' ability to evaluate distributive actions relies not only on the outcomes but also on the distributors' intentions.In three studies, it was tested whether children (N = 184; aged 6-10 years, White, mid- to high income) from a U.S. midwestern city used other individuals' gender and race to predict who is in charge and the means by which power is gained (Study 1) and whether children's own gender predicted their assignments of positions of authority (Study 2A) and pursuits of positions of authority (Study 2B). When asked to predict who was in charge at different workplaces, with age White children decreased their race-based, power-related favoritism; children were increasingly likely with age to link White adults to rather questionable routes to power as well as Black adults with meritorious reasons for gaining power (Study 1). In addition, boys (but not girls) systematically associated power with adult workers of their own gender and did so regardless of whether or not power had been obtained meritoriously (Study 1). Nonetheless, when given the option to assign an authority role (Study 2A) or assume an authority role (Study 2B), boys and girls exhibited comparable levels of in-group and self-biases.