Driscollpeacock1064

Sphingosine kinase 1 (SPHK1) regulates cell proliferation and survival by converting sphingosine to the signaling mediator sphingosine 1-phosphate (S1P). SPHK1 is widely overexpressed in most cancers, promoting tumor progression and is associated with clinical prognosis. Numerous studies have explored SPHK1 as a promising target for cancer therapy. However, due to insufficient knowledge of SPHK1 oncogenic mechanisms, its inhibitors' therapeutic potential in preventing and treating cancer still needs further investigation. In this review, we summarized the metabolic balance regulated by the SPHK1/S1P signaling pathway and highlighted the oncogenic mechanisms of SPHK1 via the upregulation of autophagy, proliferation, and survival, migration, angiogenesis and inflammation, and inhibition of apoptosis. Drug candidates targeting SPHK1 were also discussed at the end. This review provides new insights into the oncogenic effect of SPHK1 and sheds light on the future direction for targeting SPHK1 as cancer therapy.The contamination risks of microorganisms and mycotoxins in low-moisture foods have heightened public concern. Developing novel decontamination technologies to improve the safety of low-moisture foods is of great interest in both economics and public health. This review summarizes the working principles and applications of novel thermal decontamination technologies such as superheated steam, infrared, microwave, and radio-frequency heating as well as extrusion cooking. These methods of decontamination can effectively reduce the microbial load on products andmoderately destruct the mycotoxins. Meanwhile, several integrated technologies have been developed that take advantage of synergistic effects to achieve the maximum destruction of contaminants and minimize the deterioration of products.Lactobacillus and Bifidobacterium spp. are best understood for their applications as probiotics, which are often transient, but as commensals it is probable that stable colonization in the gut is important for their beneficial roles. Recent research suggests that the establishment and persistence of strains of Lactobacillus and Bifidobacterium in the gut are species- and strain-specific and affected by natural history, genomic adaptability, and metabolic interactions of the bacteria and the microbiome and immune aspects of the host but also regulated by diet. This provides new perspectives on the underlying molecular mechanisms. With an emphasis on host-microbe interaction, this review outlines how the characteristics of individual Lactobacillus and Bifidobacterium bacteria, the host genotype and microbiome structure,diet, and host-microbe coadaptation during bacterial gut transition determine and influence the colonization process. The diet-tuned and personally tailored colonization can be achieved via a machine learning prediction model proposed here.Rising health concerns and increasing obesity levels in human society have led some consumers to cut back on animal protein consumption and switch to plant-based proteins as an alternative. Soy protein is a versatile protein supplement and contains well-balanced amino acids, making it comparable to animal protein. With sufficient processing and modification, the quality of soy protein can be improved above that of animal-derived proteins, if desired. The modern food industry is undergoing a dynamic change, with advanced processing technologies that can produce a multitude of foods and ingredients with functional properties from soy proteins, providing consumers with a wide variety of foods. This review highlights recent progress in soy protein processing technologies. Using the current literature, the processing-induced structural changes in soy protein are also explored. Furthermore, the molecular structure of soy protein, particularly the crystal structures of β-conglycinin and glycinin, is comprehensively revisited.

Fibrinolysis (lysis) has been extensively studied in trauma patients. Many studies on the distribution of lysis phenotype have been conducted in setting with short prehospital time. This study aimed to evaluate the distribution of lysis phenotypes in a population with prolonged prehospital times in a rural environment.

A retrospective study was performed at an American College of Surgeons-verified level 1 trauma center, serving a large rural population. Full trauma team activations from January 1, 2017 to August 31, 2018 were evaluated, and all patients with an ISS>15 analyzed. Thromboelastography was routinely performed on all participants on arrival. C381 Lysis phenotypes were classified based on LY30 results shutdown (≤.8%), physiologic (.9-2.9%), and hyper (>2.9%).

259 patients were evaluated, 134 (52%) presented direct from the scene. For scene patients, lysis distribution was 24% physiologic, 49% shutdown, and 27% hyper. Transferred patients demonstrated a reduction in physiologic lysis to 14% (

= .03), shutdown present in 66%, and hyper in 20%. Empiric prehospital tranexamic acid was given to 18 patients, physiologic lysis was present in 6%, shutdown 72%, and hyper 22%; this increase was not statistically significant (

= .5).

Fibrinolysis phenotypes are not consistent across all trauma populations. This study showed rural trauma patients had a significantly increased rate of pathologic lysis. This was consistent for scene and transfer patients who received care at another facility prior to arrival for definitive care. Future studies to evaluate the factors influencing these differences are warranted.

Fibrinolysis phenotypes are not consistent across all trauma populations. This study showed rural trauma patients had a significantly increased rate of pathologic lysis. This was consistent for scene and transfer patients who received care at another facility prior to arrival for definitive care. Future studies to evaluate the factors influencing these differences are warranted.The health benefits of green space are well known, but the health effects of green infrastructure less so. Green infrastructure goes well beyond the presence of green space and refers more to a strategically planned network of natural and seminatural areas, with other environmental features designed and managed to deliver a wide range of ecosystem services and possibly to improve human health. In this narrative review, we found that small green infrastructure, such as green roofs and walls, has the potential to mitigate urban flooding, attenuate indoor temperatures and heat islands, improve air quality, and muffle noise, among other benefits, but these effects have not been linked directly to health. Larger green infrastructure has been associated with reduced temperatures, air pollution, and crimes and violence, but less so with health, although some evidence suggests that it may be beneficial for health (e.g., good health, decreased mortality). Finally, parks and street trees show many health benefits, but it is not clear if they can always be considered green infrastructure.We have performed shadowgraphy experiments on a dilute polymer solution subjected to a temperature gradient in order to investigate simultaneous thermal and solutal non-equilibrium fluctuations (NEFs). The gravitational quenching of the NEFs at small q-vectors defines the thermal and solutal roll-off wavevectors, which can be extracted from both the static structure function and the time correlation functions. Both methods yield good agreement, and the ∼10% larger static solutal roll-off wavevector coincides with a similar observation reported in the literature. The thermal diffusivity of the solution and the diffusion, thermodiffusion, and Soret coefficients of the polymer can be obtained from the q-dependence of the relaxation times and from the thermal and solutal roll-off wavevectors without explicit knowledge of the optical contrast factors. This provides an alternative route for the measurement of diffusive transport coefficients, albeit with an unfavorable error propagation.HN3 is a unique liquid energetic material that exhibits ultrafast detonation chemistry and a transition to metallic states during detonation. We combine the Chebyshev interaction model for efficient simulation (ChIMES) many-body reactive force field and the extended-Lagrangian multiscale shock technique molecular dynamics method to calculate the detonation properties of HN3 with the accuracy of Kohn-Sham density-functional theory. ChIMES is based on a Chebyshev polynomial expansion and can accurately reproduce density-functional theory molecular dynamics (DFT-MD) simulations for a wide range of unreactive and decomposition conditions of liquid HN3. We show that addition of random displacement configurations and the energies of gas-phase equilibrium products in the training set allows ChIMES to efficiently explore the complex potential energy surface. Schemes for selecting force field parameters and the inclusion of stress tensor and energy data in the training set are examined. Structural and dynamical properties and chemistry predictions for the resulting models are benchmarked against DFT-MD. We demonstrate that the inclusion of explicit four-body energy terms is necessary to capture the potential energy surface across a wide range of conditions. Our results generally retain the accuracy of DFT-MD while yielding a high degree of computational efficiency, allowing simulations to approach orders of magnitude larger time and spatial scales. The techniques and recipes for MD model creation we present allow for direct simulation of nanosecond shock compression experiments and calculation of the detonation properties of materials with the accuracy of Kohn-Sham density-functional theory.To advance our quest to understand the role of low energy electrons in biomolecular systems, we performed investigations on dissociative electron attachment (DEA) to gas-phase N-ethylformamide (NEF) and N-ethylacetamide (NEA) molecules. Both molecules contain the amide bond, which is the linkage between two consecutive amino acid residues in proteins. Thus, their electron-induced dissociation can imitate the resonant behavior of the DEA process in more complex biostructures. Our experimental results indicate that in these two molecules, the dissociation of the amide bond results in a double resonant structure with peaks at ∼5 eV and 9 eV. We also determined the energy position of resonant states for several negative ions, i.e., the other dissociation products from NEF and NEA. Our predictions of dissociation channels were supported by density functional theory calculations of the corresponding threshold energies. Our results and those previously reported for small amides and peptides imply the fundamental nature for breakage of the amide bond through the DEA process.Phonon contributions to organic crystal structures and thermochemical properties can be significant, but computing a well-converged phonon density of states with lattice dynamics and periodic density functional theory (DFT) is often computationally expensive due to the need for large supercells. Using semi-empirical methods like density functional tight binding (DFTB) instead of DFT can reduce the computational costs dramatically, albeit with noticeable reductions in accuracy. This work proposes approximating the phonon density of states via a relatively inexpensive DFTB supercell treatment of the phonon dispersion that is then corrected by shifting the individual phonon modes according to the difference between the DFT and DFTB phonon frequencies at the Γ-point. The acoustic modes are then computed at the DFT level from the elastic constants. In several small-molecule crystal test cases, this combined approach reproduces DFT thermochemistry with kJ/mol accuracy and 1-2 orders of magnitude less computational effort.