Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

One important, however, poorly understood, concept of Traditional Chinese Medicine (TCM) is that of hot, cold, and neutral nature of its bioactive principles. To advance the field, in this study, we analyzed compound-nature pairs from TCM on a large scale (>23 000 structures) via chemical space visualizations to understand its physicochemical domain and in silico target prediction to understand differences related to their modes-of-action (MoA) against proteins. We found that overall TCM natures spread into different subclusters with specific molecular patterns, as opposed to forming coherent global groups. Compounds associated with cold nature had a lower clogP and contain more aliphatic rings than the other groups and were found to control detoxification, heat-clearing, heart development processes, and have sedative function, associated with "Mental and behavioural disorders" diseases. While compounds associated with hot nature were on average of lower molecular weight, have more aromatic ring systems than other groups, frequently seemed to control body temperature, have cardio-protection function, improve fertility and sexual function, and represent excitatory or activating effects, associated with "endocrine, nutritional and metabolic diseases" and "diseases of the circulatory system". Compounds associated with neutral nature had a higher polar surface area and contain more cyclohexene moieties than other groups and seem to be related to memory function, suggesting that their nature may be a useful guide for their utility in neural degenerative diseases. We were hence able to elucidate the difference between different nature classes in TCM on the molecular level, and on a large data set, for the first time, thereby helping a better understanding of TCM nature theory and bridging the gap between traditional medicine and our current understanding of the human body.

No abstract

Forensic DNA analysis of sexual assault evidence requires unambiguous differentiation of DNA profiles in mixed samples. To investigate the feasibility of magnetic bead-based separation of sperm from cell mixtures using a monoclonal antibody against MOSPD3 (motile sperm domain-containing protein 3), 30 cell samples were prepared by mixing 10(4) female buccal epithelial cells with sperm cells of varying densities (10(3), 10(4), or 10(5) cells/mL). Western blot and immunofluorescence assays showed that MOSPD3 was detectable on the membrane of sperm cells, but not in buccal epithelial cells. After biotinylated MOSPD3 antibody was incubated successively with the prepared cell mixtures and avidin-coated magnetic beads, microscopic observation revealed that each sperm cell was bound by two or more magnetic beads, in the head, neck, mid-piece, or flagellum. A full single-source short tandem repeat profile could be obtained in 80% of mixed samples containing 10(3) sperm cells/mL and in all samples containing ≥10(4) sperm cells/mL. For dried vaginal swab specimens, the rate of successful detection was 100% in both flocked and cotton swabs preserved for 1 day, 87.5% in flocked swabs and 40% in cotton swabs preserved for 3 days, and 40% in flocked swabs and 16.67% in cotton swabs preserved for 10 days. Our findings suggest that immunomagnetic bead-based separation is potentially a promising alternative to conventional methods for isolating sperm cells from mixed forensic samples.

The objective of the present study was to determine the anticancer effects of cedrol in A549 human non-small cell lung cancer cells by examining the effects of cedrol on apoptosis induction, the phosphatidylinositol 3'-kinase (PI3K)/Akt signaling pathway, autophagy, reactive oxygen species (ROS) generation and mitochondrial transmembrane potential (MTP). The anticancer effects of cedrol were examined using A549 human lung carcinoma cells as an in vitro model. Cell viability was determined using MTT and lactate dehydrogenase (LDH) assays, and an inverted phase contrast microscope was used to examine the morphological changes in these cells. Cedrol‑triggered autophagy was confirmed by transmission electron microscopy (TEM) analysis of the cells, as well as by western blot analysis of microtubule-associated protein light-chain 3 (LC3)B expression. Intracellular ROS generation was measured by flow cytometry using 5-(6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate (CM-DCFH2-DA) staining and MTP was measured using flow cytometry. The results demonstrated that cedrol reduced cell viability and induced cell apoptosis in a dose-dependent manner. Mechanistic evaluations indicated that cedrol induced apoptosis by reducing the MTP and by decreasing the levels of phosphorylated (p-)PI3K and p-Akt. Cedrol induced autophagy, which was confirmed by TEM analysis, by increasing intracellular ROS formation in a concentration-dependent manner, which was almost completely reversed by N-acetyl-L-cysteine (NAC) and tocopherol. Taken together, these findings reveal that cedrol inhibits cell proliferation and induces apoptosis in A549 cells through mitochondrial and PI3K/Akt signaling pathways. Our findings also reveal that cedrol induced pro-death autophagy by increasing intracellular ROS production.

A large-scale spanwise and wall-normal array of sonic anemometers in the atmospheric surface layer is used to acquire all three components of instantaneous fluctuating velocity as well as temperature in a range of stability conditions. These data permit investigation of the three-dimensional statistical structure of turbulence structures. Based on a similar dataset, Krug et al. (Boundary-Layer Meteorol., vol. 172, 2019, pp. 199–214) reported a self-similar range of wall-attached turbulence structures under both unstable and near-neutral stability conditions. They considered only a wall-normal array and thus assessed statistical structure in the wall-normal direction, in relation to the streamwise wavelength. The present work extends the view of a self-similar range of turbulence structures, by including the statistical structure in the spanwise direction. Moreover, by analysing the phase shift between synchronized measurements in the spectral domain, it is inferred how a scale-dependent inclination angle in the streamwise/wall-normal plane varies with stability. Results suggest that the self-similar wall-attached structures have similar aspect ratios between streamwise/wall-normal scales and streamwise/spanwise scales such that $\lambda _x/\Delta z : \lambda _x/\Delta y \approx 1$ for both near-neutral and unstable conditions. Under the most unstable conditions, coherent structures with $\lambda _x/\delta = 1$ are inclined at angles as high as $65^{\circ }$ relative to the solid boundary, while larger scales $\lambda _x/\delta = 6$ exhibit inclination angles of approximately $35^{\circ }$ . For near-neutral stability conditions, the angle tends towards $12^{\circ }$ for all scales. It is noted that in the near-neutral condition, the structure inclination angle and the aspect ratio – and thus the statistical modelling of coherent structures in the atmospheric surface layer – are highly sensitive to the value of the stability parameter.

Variation in the type of tissue that larvae feed on can produce marked differences in developmental rate and body size, which can compromise predictions of minimum postmortem interval. A series of experiments were conducted to investigate the effect of fat content in the diet on larval growth in Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae), an important forensic blowfly species in China. Bionomical parameters such as body size, development time, mortality, and sex ratio were observed. The results indicated that fat content in the diet has a dramatic effect on the body size and larval development. More dietary fat content was beneficial for development of larvae in first and early second instar. But it was adverse in the later third instar. Significantly, a high-fat diet resulted in increased development rates and the production of undersized larvae and adults. Overall mortality of larvae and pupa was higher when more fat was added to the diet, but sex ratio of adults was not negatively affected. This study highlights that the fat content in the diet should be considered in the entomological research and forensic application when estimating minimum postmortem interval on the basis of larval body size and developmental stage.

BackgroundPleckstrin homology‐like domain family A, member 3 (PHLDA3), a crucial member of the PHLDA family, is involved in tumor suppression, kidney injury, liver injury, and glucose metabolism. However, the role of PHLDA3 in pathological cardiac hypertrophy and heart failure remains unclear.Methods and ResultsIn the present study, PHLDA3 expression was downregulated in hypertrophic murine hearts and angiotensin II‐treated cardiomyocytes. Next, an in vitro study suggested, by using gain‐ and loss‐of‐function approaches, that PHLDA3 attenuates Ang II exposure‐induced cardiomyocyte hypertrophy. Consistent with the cell phenotype, disruption of PHLDA3 aggravated the effects of pressure overload‐induced pathological cardiac hypertrophy, fibrosis, and dysfunction. In contrast, PHLDA3 overexpression resulted in an attenuated hypertrophic phenotype. Molecular analysis revealed that PHLDA3 suppressed the activation of AKT‐mTOR‐GSK3β‐P70S6K signaling in response to hypertrophic stress, and the blockage of AKT activation rescued these adverse pathological effects of PHLDA3 deficiency‐induced by AB and Ang II, respectively, in vivo and in vitro.ConclusionsCollectively, our data indicated that PHLDA3 could ameliorate pressure overload‐induced cardiac remodeling mainly by blocking the AKT signaling pathway, suggesting that PHLDA3 may represent a therapeutic target for the treatment of pathological cardiac hypertrophy and heart failure.