Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer.

Recent genomic analyses have revealed substantial tumor heterogeneity across various cancers. However, it remains unclear whether and how genomic heterogeneity is constrained during tumor evolution. Here, we sequence a unique cohort of multiple synchronous lung cancers (MSLCs) to determine the relative diversity and uniformity of genetic drivers upon identical germline and environmental background. We find that each multicentric primary tumor harbors distinct oncogenic alterations, including novel mutations that are experimentally demonstrated to be functional and therapeutically targetable. However, functional studies show a strikingly constrained tumorigenic pathway underlying heterogeneous genetic variants. These results suggest that although the mutation-specific routes that cells take during oncogenesis are stochastic, genetic trajectories may be constrained by selection for functional convergence on key signaling pathways. Our findings highlight the robust evolutionary pressures that simultaneously shape the expansion and constraint of genomic diversity, a principle that holds important implications for understanding tumor evolution and optimizing therapeutic strategies.Across cancer types tumor heterogeneity has been observed, but how this relates to tumor evolution is unclear. Here, the authors sequence multiple synchronous lung cancers, highlighting the evolutionary pressures that simultaneously shape the expansion and constraint of genomic heterogeneity

Antimicrobial and molecular interaction studies on derivatives of curcumin against Streptococcus pneumoniae which caused pneumonia

Background: The antimicrobial properties and molecular interaction analysis of curcumin and its derivatives against three different strains of Streptococcus pneumoniae (Penicillin-susceptible, Penicillin-intermediate and Penicillin-resistant) are studied. Results: These properties were analyzed based on the measurement of the inhibition zone, minimum inhibitory concentration (MIC), and rate of kill revealed that curcumin monoglucoside, curcumin diglucoside and curcumin possessed strong antimicrobial properties even on the Penicillin-resistant strains. Additionally, the molecular docking simulation analyses against Penicillin Binding Protein of S. pneumoniae also confirm that these compounds docked at the active site of the enzyme. Further, the molecular dynamics simulation validates the conformational stability of the docked ligand\u2013protein complexes in the dynamic environment. Conclusion: curcumin monoglucoside, curcumin diglucoside and curcumin can be prescribed for treatment against Penicillin-resistant S. pneumoniae

Pharmacokinetics and bioequivalence evaluation of acamprosate calcium tablets in healthy Chinese volunteers

AbstractBackgroundFew pharmacokinetic data of acamprosate were available in Chinese population and no medication is approved for alcohol dependence in China.Purpose1. Investigate the pharmacokinetic properties of acamprosate calcium in healthy Chinese male volunteers on single- and multiple-dose administration. 2. Compare the bioequivalence of two formulations of acamprosate calcium tablets both under fasting and fed conditions.MethodsThis open-label, randomized study included 3 stages. In each stage, a 2-way crossover bioequivalence study was conducted to study the pharmacokinetic properties and bioequivalence of acamprosate calcium tablets on multiple dosing after standardized meals, single dosing under fasting conditions and fed conditions, respectively. The washout period between each treatment in a stage and between each stage was 1week. Plasma acamprosate calcium was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG, and laboratory tests.ResultsTotally, 36 male subjects were enrolled in the study and all of them completed the whole 3 study stages. Main pharmacokinetic parameters of test and reference formulations were as follows: multiple dosing, Tmax 9.94±6.59 and 9.47±5.47h, Cmax 435.74±348.10 and 346.54±155.66ng·mL−1, AUC0-t 8600.52±5264.77 and 9315.10±6820.03ng·mL−1·h, AUC0–∞ 8845.38±5838.18 and 9669.24±7326.53ng·mL−1·h, t1/2 10.06±8.83 and 9.87±10.35h; single dosing under fasting conditions, Tmax 7.29±4.87 and 6.57±1.85h, Cmax 247.85±110.05 and 244.64±132.43ng·mL−1, AUC0-t 3385.41±1418.92 and 3496.24±1767.29ng·mL−1·h, AUC0–∞ 3781.53±1556.96 and 3829.56±1981.25ng·mL−1·h, t1/2 13.07±17.24 and 10.26±7.78h; single dosing under fed conditions, Tmax 17.72±9.42 and 19.50±9.84h, Cmax 183.90±74.52 and 168.14±60.67ng·mL−1, AUC0-t 3181.71±1368.24 and 3575.11±1416.39ng·mL−1·h, AUC0–∞3442.39±2002.53 and 3624.44±1418.12ng·mL−1·h, t1/2 8.76±12.28 and 6.67±4.84h, respectively. In all three stages, 90% CIs for the test/reference ratio of AUC0–t and AUC0–∞ were located within 80%–125%, 90% CI for Cmax was within 70%–143%.ConclusionsSimilar pharmacokinetic results of acamprosate calcium tablets in healthy Chinese volunteers were found as those in Caucasic population. In all three stages, the two formulations met the regulatory criteria for bioequivalence.Chictr.org identifier: ChiCTR-TTRCC-14004853

Viscosity of Polar-Nonpolar Gas Mixtures Empirical method

The adequacy of the familiar Sutherland expression for tho viscosity of gas mixtures is tested successfully for binary mixtures involving one component as polar. The limited calculations of this paper also reveal that the co-efficients of the Sutherland expression may be treated as approximately temperature independent. This interesting result may find great use in predicting values at high temperatures where no direct measurements are available

Geometric bionics: Lotus effect helps polystyrene nanotube films get good blood compatibility

Various biomaterials have been widely used for manufacturing biomedical applications including artificial organs, medical devices and disposable clinical apparatus, such as vascular prostheses, blood pumps, artificial kidney, artificial hearts, dialyzers and plasma separators, which could be used in contact with blood^1^. However, the research tasks of improving hemocompatibility of biomaterials have been carrying out with the development of biomedical requirements^2^. Since the interactions that lead to surface-induced thrombosis occurring at the blood-biomaterial interface become a reason of familiar current complications with grafts therapy, improvement of the blood compatibility of artificial polymer surfaces is, therefore a major issue in biomaterials science^3^. After decades of focused research, various approaches of modifying biomaterial surfaces through chemical or biochemical methods to improve their hemocompatibility were obtained^1^. In this article, we report that polystyrene nanotube films with morphology similar to the papilla on lotus leaf can be used as blood-contacted biomaterials by virtue of Lotus effect^4^. Clearly, this idea, resulting from geometric bionics that mimicking the structure design of lotus leaf, is very novel technique for preparation of hemocompatible biomaterials

Woody species have stronger facilitative effects on soil biota than on plants along an aridity gradient

Questions: Woody shrub encroachment affects community structure and composition. However, most studies focus on their effects on understorey plant communities, and the relative importance of shrubs in affecting plants vs. soil biota communities is poorly known. Location: Inner Mongolian Steppe, China. Methods: We examined the effect of shrubs on multiple community attributes, including plants, soil biota (bacteria, fungi and nematodes), and soil fertility, and quantified how these effects changed from semi‐arid to hyper‐arid conditions (from 281 to 110 mm of mean annual precipitation). In addition, we assessed whether the effects of shrubs on plant communities were directly mediated by biotic filtering in seed germination and establishment, or indirectly mediated by plant biomass or soil fertility in the case of soil organisms. Results: The effect of shrubs on soil biota was generally more positive than on plants, and it increased with aridity. We found that a larger proportion of belowground taxa depended on shrub presence (36%) than plants (20%). Soil nematodes and soil bacteria were directly influenced by shrub presence whereas soil fungi were indirectly influenced by enhanced soil fertility. Shrubs also increased plant biomass under all conditions but only increased plant species richness in the most arid conditions. Despite the generally positive effect of shrubs, and the fact that they weakened the filtering effects of aridity on seed germination, aridity was a stronger predictor of changes in species composition than shrub presence was, particularly for plants. Conclusions: Our results illustrate the variety of positive effects of shrubs and show that they are particularly important in supporting biodiversity in the most arid conditions. These strong and positive effects could partially buffer the impacts of increasing aridity on dryland soil biodiversity, but our study suggests that facilitative interactions may not be able to completely mitigate the impacts of increasing aridity on drylands.This research was funded by National Natural Science Foundation of China [31901140, 31570453] and China Scholarship Council. SS was supported by the Spanish Government under a Ramón y Cajal contract (RYC-2016- 20604)