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Radiotherapy is a powerful tool in the treatment of cancer that has the advantage of preserving normal tissues. However, tumor radioresistance currently remains a major impediment to effective RT. Thus, exploring effective radiation sensitizers is urgently needed. In this study, we have shown that diosmetin, the aglycone of the lavonoid glycoside from olive leaves, citrus fruits and some medicinal herbs, has a promising effect on radiotherapy sensitization. In our results, DIO could induce G1 phase arrest and thus enhance the radiosensitivity of radioresistant A549/IR lung cancer cells. Furthermore, DIO also restrains the IR-induced DNA damage repair by inhibiting the activated Akt signaling pathway. The combination of Akt inhibition (DIO, LY294002 or MK-2206) and radiation potently blocked A549/IR cancer cell proliferation. In summary, these observations suggest that the natural compound DIO could act as a potential drug for the treatment of radioresistant lung cancer cells.

In reality, nanoindentation test is an efficient technique for probing the mechanical properties of biological tissue that soaked in the liquid media to keep the bioactivity. However, the effects of flotage imposed on the indenter will lead to inaccuracy when calculating mechanical properties (for instance, elastic modulus and hardness) by using depth-sensing nanoindentation. In this paper, the effects of flotage on the nanoindentation results of cortical bone were investigated by finite element analysis (FEA) simulation. Comparisons of nanoindentation simulation results of bone samples with and without being soaked in the liquid media were carried out. Conclusions show that the difference of load-displacement curves in the case of soaking sample and without soaking sample conditions varies widely based on the change of indentation depth. In other words, the nanoindentation measurements in liquid media will cause significant error in the calculated Young’s modules and hardness due to the flotage. By taking into account the effect of flotage, these errors are particularly important to the accurate biomechanics characterization of biological samples.

Domestication has altered a variety of traits within the Eurasian perch (Perca fluviatilis), including phenotypic, physiological and behavioral traits of Eurasian perch (Perca fluviatilis). Little is known, however, about the genetic changes between domesticated and wild Eurasian perch. In this study, we assembled a high-quality de novo reference transcriptome and identified differentially expressed genes between wild and domesticated Eurasian perch. A total of 113,709 transcripts were assembled, and 58,380 transcripts were annotated. Transcriptomic comparison revealed 630 differentially expressed genes between domesticated and wild Eurasian perch. Within domesticated Eurasian perch there were 412 genes that were up-regulated including MHCI, MHCII, chia, ighm within immune system development. There were 218 genes including try1, ctrl, ctrb, cela3b, cpa1 and cpb1, which were down-regulated that were associated with digestive processes. Our results indicated domestication drives the changes of immune and digestive system of Eurasian perch. Our study not only provide valuable genetic resources for further studies in Eurasian perch, but also provide novel insights into the genetic basis of physiological changes in Eurasian perch during domestication process.

Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity.

Tigecycline (TIG), the first member of glycylcycline bacteriostatic agents, has been approved to treat complicated infections in the clinic because of its expanded-spectrum antibiotic potential. Recently, an increasing number of studies have emphasized the anti-tumor effects of TIG. The inhibitory effects of TIG on cancer depend on several activating signaling pathways and abnormal mitochondrial function in cancer cells. The aim of this review is to summarize the cumulative anti-tumor evidence supporting TIG activity against different cancer types, including acute myeloid leukemia (AML), glioma, non-small cell lung cancer (NSCLC), among others. In addition, future clinical trials are discussed that will evaluate the security and validate the underlying the tumor-killing properties of TIG.

SiCp/6061Al composites have been developed and widely applied in many fields, such as automobile, aerospace, shipping, and so on. Considering heat treatment, service environment, and strength of composites, this paper comprehensively studies the mechanical properties of SiCp/6061Al composites with a large range of SiC mass fractions under T6 treatments and different tensile temperatures. SiCp/6061Al composites were successfully prepared by hot press sintering at various SiC mass fractions (0–30%), and the influences of SiC concentration and T6 treatment on the mechanical properties of composites were characterized via tensile tests at room temperature, 100, and 200 °C. Microstructure and fracture surfaces of composites with various SiC concentrations were further analyzed by optical microscope and SEM. The formula for the biggest critical reinforcement concentration for the saturated distribution of SiC is proposed to reveal the strengthening rule of different SiC concentrations. Results show that the effect of T6 treatment on the mechanical properties of composites is a marked increase in tensile strength and an obvious decrease in elongation. The increase in the SiC mass fraction, except at 30%, is able to bring an increase in tensile strength and a decrease in elongation, and the change of the elongation is insignification in T6-treated specimens. The tensile strength of T6-treated specimens decreases as temperature increases, and the composite has a maximum elongation at 100 °C.

In this research, the mechanical behavior of undoped n-type GaAs was investigated by nanoindentation experiments using two types of indenters—Berkovich and flat-tip—with force applied up to 1000 mN. From the measured force-depth curves, an obvious pop-in phenomenon occurred at force of 150 mN with the flat-tip indenter representing elastic–plastic transition. The Young’s modulus and hardness of GaAs were calculated to be 60–115 GPa and 6–10 GPa, respectively, under Berkovich indenter. Based on the observation of indent imprints, the fracture characteristics of GaAs were also discussed. A recovery of crack by the next indentation was observed at 1000 mN with Berkovich indenter. In the case of flat-tip indentation, however, surface material sank into a wing shape from 400 mN. In this sinking region, a density of fork-shaped sinking, slip lines, and crossed pits contributed to the slip bands, and converging crossed twinning deformations inside the GaAs material were generated. Since cracks and destructions on GaAs surface took place more easily under the flat-tip indentation than that of Berkovich, a machining tool with a sharp tip is recommended for the mechanical machining of brittle materials like GaAs.

Nanoindentation techniques, with high spatial resolution and force sensitivity, have recently been moved into the center of the spotlight for measuring the mechanical properties of biomaterials, especially bridging the scales from the molecular via the cellular and tissue all the way to the organ level, whereas characterizing soft biomaterials, especially down to biomolecules, is fraught with more pitfalls compared with the hard biomaterials. In this review we detail the constitutive behavior of soft biomaterials under nanoindentation (including AFM) and present the characteristics of experimental aspects in detail, such as the adaption of instrumentation and indentation response of soft biomaterials. We further show some applications, and discuss the challenges and perspectives related to nanoindentation of soft biomaterials, a technique that can pinpoint the mechanical properties of soft biomaterials for the scale-span is far-reaching for understanding biomechanics and mechanobiology.

The northern pike (Esox lucius L.), an important predatory freshwater species, is undergoing significant population decline. In this study, 18 novel polymorphic microsatellite loci were isolated and used for assessing genetic variation in the Chinese Ulungur and Hungarian Balaton populations of the species. The number of alleles ranged from 2 to 13, observed heterozygosity from 0.154 to 0.920 and expected heterozygosity from 0.145 to 0.921, thereby indicating the specific usefulness of these suites of markers for investigating genetic variability.

Effects of temperature and strain rate on the fracture behaviors of an Al-Zn-Mg-Cu alloy are investigated by isothermal uniaxial tensile experiments at a wide range of temperatures and strain rates, from room temperature (RT) to 400 °C and from 10−4 s−1 to 10−1 s–1, respectively. Generally, the elevation of temperature leads to the increasing of elongation to fracture and the reduction of peak stress, while higher strain rate results in the decreasing of elongation to fracture and the increasing of peak stress. Interestingly, we found that the coefficient of strain rate sensitivity (m-value) considerably rises at 200 °C and work of fracture (Wf) fluctuates drastically with the increase of strain rate at RT and 100 °C, both of which signify a non-uniform and unstable deformation state below 200 °C. A competition of work hardening (WH) and dynamic recrystallization (DRX) exists at 200 °C, making it serve as a transitional temperature. Below 200 °C, WH is the main deformation mechanism of flow stress, and DRX dominates the flow stress above 200 °C. It has been found that from RT to 200 °C, the main feature of microstructure is the generation of dimples and microvoids. Above 200 °C, the coalescence of dimples and microvoids mainly leads to the failure of specimen, while the phenomenon of typically equiaxed dimples and nucleation appear at 400 °C. The observations of microstructure are perfectly consistent with the related macroscopic results. The present work is able to provide a comprehensive understanding of flow stress of an Al-Zn-Mg-Cu alloy at a wide range of temperatures and strain rates, which will offer valuable information to the optimization of the hot forming process and structural design of the studied alloy.

The topological organization underlying brain networks has been extensively investigated using resting-state fMRI, focusing on the low frequency band from 0.01 to 0.1 Hz. However, the frequency specificities regarding the corresponding brain networks remain largely unclear. In the current study, a data-driven method named complementary ensemble empirical mode decomposition (CEEMD) was introduced to separate the time series of each voxel into several intrinsic oscillation rhythms with distinct frequency bands. Our data indicated that the whole brain BOLD signals could be automatically divided into five specific frequency bands. After applying the CEEMD method, the topological patterns of these five temporally correlated networks were analyzed. The results showed that global topological properties, including the network weighted degree, network efficiency, mean characteristic path length and clustering coefficient, were observed to be most prominent in the ultra-low frequency bands from 0 to 0.015 Hz. Moreover, the saliency of small-world architecture demonstrated frequency-density dependency. Compared to the empirical mode decomposition method (EMD), CEEMD could effectively eliminate the mode-mixing effects. Additionally, the robustness of CEEMD was validated by the similar results derived from a split-half analysis and a conventional frequency division method using the rectangular window band-pass filter. Our findings suggest that CEEMD is a more effective method for extracting the intrinsic oscillation rhythms embedded in the BOLD signals than EMD. The application of CEEMD in fMRI data analysis will provide in-depth insight in investigations of frequency specific topological patterns of the dynamic brain networks.

The composition of a genome with respect to all possible short DNA motifs impacts the ability of DNA binding proteins to locate and bind their target sites. Since nonfunctional DNA binding can be detrimental to cellular functions and ultimately to organismal fitness, organisms could benefit from reducing the number of nonfunctional DNA binding sites genome wide. Using in vitro measurements of binding affinities for a large collection of DNA binding proteins, in multiple species, we detect a significant global avoidance of weak binding sites in genomes. We demonstrate that the underlying evolutionary process leaves a distinct genomic hallmark in that similar words have correlated frequencies, a signal that we detect in all species across domains of life. We consider the possibility that natural selection against weak binding sites contributes to this process, and using an evolutionary model we show that the strength of selection needed to maintain global word compositions is on the order of point mutation rates. Likewise, we show that evolutionary mechanisms based on interference of protein-DNA binding with replication and mutational repair processes could yield similar results and operate with similar rates. On the basis of these modeling and bioinformatic results, we conclude that genome-wide word compositions have been molded by DNA binding proteins acting through tiny evolutionary steps over time scales spanning millions of generations.