Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication

Cell mechanics is essential to cell development and function,and its dynamics evolution reflects the physiological state of cells.Here,we investigate the dynamical mechanical properties of single cells under various drug conditions,and present two mathematical approaches to quantitatively characterizing the cell physiological state.It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate,and can be mathematically characterized by a linear timeinvariant dynamical model.It is shown that the transition matrices of dynamical cell systems significantly improve the classification accuracies of the cells under different drug actions.Furthermore,it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties,and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model.This study builds a relationship between the cellular mechanical properties and the cellular physiological state,adding information for evaluating drug efficacy.

Numerical Investigation on the Propagation Mechanism of Steady Cellular Detonations in Curved Channels

The propagation mechanism of steady cellular detonations in curved channels is investigated numerically with a detailed chemical reaction mechanism, The numerical results demonstrate that as the radius of the curvature decreases, detonation fails near the inner wall due to the strong expansion effect. As the radius of the curvature increases, the detonation front near the inner wall can sustain an underdriven detonation. In the case where deto- nation fails, a transverse detonation downstream forms and re-initiates the quenched detonation as it propagates toward the inner wall. Two kinds of propagation modes exist as the detonation is propagating in the curved channel. One is that the detonation fails first, and then a following transverse detonation initiates the quenched detonation and this process repeats itself. The other one is that without detonation failure and re-initiation, a steady detonation exists which consists of an underdriven detonation front near the inner wall subject to the diffraction and an overdriven detonation near the outer wall subject to the compression.

Cellular Mechanism of Mouse Atrial Development

During the development of mammalian heart, the left and right atria play an important role in cardiovascular circulation. The embryonic atrium is mainly formed by the differentiation of progenitor cells and the proliferation of cardiomyocytes, while the postnatal atrium is primarily shaped by the increase in the volume of cardiomyocytes. Cell proliferation and differentiation of atrial development is the basis for its functions such as “blood reservoir” and “supplementary pump”. Deep understanding the cellular mechanism of atrial development is imperative to explore the causes of common congenital arrhythmia heart diseases such as atrial fibrillation. We used genetically engineered mouse reproduction knowledge, lineage tracing method based on CreloxP system, molecular biology and immunofluorescence technology to track the cardiomyocyte lineage of Nppa-GFP mouse line with stereo fluorescence microscope and ultra-high-speed confocal microscope. Besides the atrium of Nppa-CreER;Rosa26 tdTomato mouse was examined during embryonic (E10.5 - E18.5) and postnatal (P0, P3, P5, P7, P14, P28, P8w) stage. Immunofluorescence results revealed that Nppa-positive cells labeled TNNI3-positive cardiomyocytes and protruded into the atrial cavity at the beginning of E11.5 - E12.0 and during subsequent development to form Nppa-positive myocardial trabeculae. Thick comb-shaped myocardium was observed after birth, and we suspect that this was particularly important for the normal contractile activity and pumping function of the atrium. Additionally, non-single origin of Nppa-positive trabecular myocardiocytes were revealed through Tamoxifen-induced lineage tracing experiment. Our findings reveal proliferation dynamics and non-comprehensive fate decisions of cardiomyocytes that produce the distinct architecture of the atrium chamber.

Extracellular matrix stiffness as an energy metabolism regulator drives osteogenic differentiation in mesenchymal stem cells

The biophysical factors of biomaterials such as their stiffness regulate stem cell differentiation.Energy metabolism has been revealed an essential role in stem cell lineage commitment.However,whether and how extracellular matrix(ECM)stiffness regulates energy metabolism to determine stem cell differentiation is less known.Here,the study reveals that stiff ECM promotes glycolysis,oxidative phosphorylation,and enhances antioxidant defense system during osteogenic differentiation in MSCs.Stiff ECM increases mitochondrial fusion by enhancing mitofusin 1 and 2 expression and inhibiting the dynamin-related protein 1 activity,which contributes to osteogenesis.Yes-associated protein(YAP)impacts glycolysis,glutamine metabolism,mitochondrial dynamics,and mitochondrial biosynthesis to regulate stiffness-mediated osteogenic differentiation.Furthermore,glycolysis in turn regulates YAP activity through the cytoskeletal tension-mediated deformation of nuclei.Overall,our findings suggest that YAP is an important mechanotransducer to integrate ECM mechanical cues and energy metabolic signaling to affect the fate of MSCs.This offers valuable guidance to improve the scaffold design for bone tissue engineering constructs.

Research Progress of the Antiviral Bioactivities of Natural Flavonoids

Flavonoids are now considered as an indispensable component in a variety of nutraceutical and pharmaceutical applications.Most recent researches have focused on the health aspects of flavonoids for humans.Especially,different flavonoids have been investigated for their potential antiviral activities,and several natural flavonoids exhibited significant antiviral properties both in vitro and in vivo.This review provides a survey of the literature regarding the evidence for antiviral bioactivities of natural flavonoids,highlights the cellular and molecular mechanisms of natural flavonoids on viruses,and presents the details of most reported flavonoids.Meanwhile,future perspectives on therapeutic applications of flavonoids against viral infections were discussed.

Antibacterial and anti-parasitic activities of Terfezia claveryi methanolic extract against some common pathogenic agents of infectious diarrhea

Objective:To assess the antidiarrheal effects of Terfezia claveryi methanolic extract against Escherichia coli,Salmonella typhimurium,Shigella flexneri,and Giardia lamblia.Methods:Antibacterial effects of the Terfezia claveryi methanolic extract were carried out by determining the minimum inhibitory concentration(MIC)and minimum bactericidal concentration through micro broth dilution technique.Furthermore,reactive oxygen species production and protein leakage were evaluated.To evaluate the in vitro anti-giardial effects of Terfezia claveryi methanolic extract,Giardia lamblia WB(ATCC®30957)trophozoites were treated with various concentrations of Terfezia claveryi methanolic extract for 10-360 min.In addition,the plasma membrane permeability of trophozoites treated with Terfezia claveryi methanolic extract was determined.The cytotoxicity effects of Terfezia claveryi methanolic extract against normal(HEK293T)and cancer(MCF-7)cells were also assessed using the MTT assay.Results:The MIC and minimum bactericidal concentration of Terfezia claveryi methanolic extract against bacterial strains were in the range of 0.52-1.04 and 1.04-2.08 mg/mL,respectively.The results revealed that reactive oxygen species production and protein leakage were significantly increased after the bacteria were treated with the Terfezia claveryi methanolic extract,especially at 1/3 and 1/2 MICs(P<0.001).Furthermore,Terfezia claveryi methanolic extract decreased the viability of Giardia lamblia trophozoites in a dose-dependent manner.Terfezia claveryi methanolic extract at 1,2,and 4 mg/mL resulted in 100%mortality in Giardia lamblia trophozoites after 360,240,and 120 min,respectively.Moreover,Terfezia claveryi methanolic extract altered the permeability of plasma membrane of Giardia lamblia trophozoites by increasing the concentration.MTT assay revealed that the 50%cytotoxic concentrations values for HEK293T and MCF-7 cells were 4.32 mg/mL and 6.40 mg/mL,respectively,indicating that Terfezia claveryi methanolic extract had greater cytotoxicity against cancer cells than normal cells.Conclusions:Terfezia claveryi methanolic extract had potent in vitro antibacterial and anti-parasitic effects on Escherichia coli,Salmonella typhimurium,Shigella flexneri,and Giardia lamblia by affecting cell membrane permeability and reactive oxygen species generation with no significant cytotoxicity on normal cells.

Applications of atomic force microscopy in immunology

Cellular mechanics,a major regulating factor of cellular architecture and biological functions,responds to intrinsic stresses and extrinsic forces exerted by other cells and the extracellular matrix in the microenvironment.Cellular mechanics also acts as a fundamental mediator in complicated immune responses,such as cell migration,immune cell activation,and pathogen clearance.The principle of atomic force microscopy(AFM)and its three running modes are introduced for the mechanical characterization of living cells.The peak force tapping mode provides the most delicate and desirable virtues to collect high-resolution images of morphology and force curves.For a concrete description of AFM capabilities,three AFM applications are discussed.These applications include the dynamic progress of a neutrophil-extracellular-trap release by neutrophils,the immunological functions of macrophages,and the membrane pore formation mediated by perforin,streptolysin O,gasdermin D,or membrane attack complex.

Archaeal viruses-novel,diverse and enigmatic

Recent research has revealed a remarkable diversity of viruses in archaeal-rich environments where spindles, spheres, fila- ments and rods are common, together with other exceptional morphotypes never recorded previously. Moreover, their dou- ble-stranded DNA genomes carry very few genes exhibiting homology to those of bacterial and eukaryal viruses. Studies on viral life cycles are still at a preliminary stage but important insights are being gained especially from microarray analyses of viral transcripts for a few model virus-host systems. Recently, evidence has been presented for some exceptional archaeal- nspecific mechanisms for extra-cellular morphological development of virions and for their cellular extrusion. Here we sum- marise some of the recent developments in this rapidly developing and exciting research area.