From creep to flow: Granular materials under cyclic shear.

When unperturbed, granular materials form stable structures that resemble the ones of other amorphous solids like metallic or colloidal glasses. Whether or not granular materials under shear have an elastic response is not known, and also the influence of particle surface roughness on the yielding transition has so far remained elusive. Here we use X-ray tomography to determine the three-dimensional microscopic dynamics of two granular systems that have different roughness and that are driven by cyclic shear. Both systems, and for all shear amplitudes Γ considered, show a cross-over from creep to diffusive dynamics, indicating that rough granular materials have no elastic response and always yield, in stark contrast to simple glasses. For the system with small roughness, we observe a clear dynamic change at Γ ≈ 0.1, accompanied by a pronounced slowing down and dynamical heterogeneity. For the large roughness system, the dynamics evolves instead continuously as a function of Γ. We rationalize this roughness dependence using the potential energy landscape of the systems: The roughness induces to this landscape a micro-corrugation with a new length scale, whose ratio over the particle size is the relevant parameter. Our results reveal the unexpected richness in relaxation mechanisms for real granular materials.

The clinical outcome of COVID-19 is strongly associated with microbiome dynamics in the upper respiratory tract.

OBJECTIVES: The respiratory tract is the portal of entry for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a variety of respiratory pathogens other than SARS-CoV-2 have been associated with severe cases of COVID-19 disease, the dynamics of the upper respiratory microbiota during disease the course of disease, and how they impact disease manifestation, remain uncertain. METHODS: We collected 349 longitudinal upper respiratory samples from a cohort of 65 COVID-19 patients (cohort 1), 28 samples from 28 recovered COVID-19 patients (cohort 2), and 59 samples from 59 healthy controls (cohort 3). All COVID-19 patients originated from the earliest stage of the epidemic in Wuhan. Based on a modified clinical scale, the disease course was divided into five clinical disease phases (pseudotimes): "Healthy" (pseudotime 0), "Incremental" (pseudotime 1), "Critical" (pseudotime 2), "Complicated" (pseudotime 3), "Convalescent" (pseudotime 4), and "Long-term follow-up" (pseudotime 5). Using meta-transcriptomics, we investigated the features and dynamics of transcriptionally active microbes in the upper respiratory tract (URT) over the course of COVID-19 disease, as well as its association with disease progression and clinical outcomes. RESULTS: Our results revealed that the URT microbiome exhibits substantial heterogeneity during disease course. Two clusters of microbial communities characterized by low alpha diversity and enrichment for multiple pathogens or potential pathobionts (including Acinetobacter and Candida) were associated with disease progression and a worse clinical outcome. We also identified a series of microbial indicators that classified disease progression into more severe stages. Longitudinal analysis revealed that although the microbiome exhibited complex and changing patterns during COVID-19, a restoration of URT microbiomes from early dysbiosis toward more diverse status in later disease stages was observed in most patients. In addition, a group of potential pathobionts were strongly associated with the concentration of inflammatory indicators and mortality. CONCLUSION: This study revealed strong links between URT microbiome dynamics and disease progression and clinical outcomes in COVID-19, implying that the treatment of severe disease should consider the full spectrum of microbial pathogens present.

Highly sensitive and specific graphene oxide-based FRET aptasensor for quantitative detection of human soluble growth stimulating gene protein 2.

Soluble growth stimulation expressed gene 2 (sST2) is a new generation biomarker in the diagnosis and prognosis of heart failure (HF). Here, the sST2-specific aptamers were selected from a random ssDNA library with the full length of 88 nucleotides (nt) via target-immobilized magnetic beads (MB)-based systematic evolution of ligands by exponential enrichment (SELEX) technology. After eight rounds of selection, six aptamers with the most enrichment were selected. Among, the aptamer L1 showed the high-affinity binding to sST2 with the lowest Kd value (77.3 ± 0.05 nM), which was chosen as the optimal aptamer for further molecular docking. Then, the aptamer L1 was used to construct a graphene oxide (GO) - based fluorescence resonance energy transfer (FRET) biosensor for sST2, which exhibits a linear detection range of 0.1-100 µg/ml and a detection limit of 3.7 ng/ml. The aptasensor was applied to detect sST2 in real samples, with a good correlation and agreement with the traditional enzyme-linked immunosorbent assay (ELISA) when quantitative analyzing the sST2 concentration in serum samples from HF patients. The results show that not only an efficient strategy for screening the practicable aptamer, but also a rapid and sensitive detection platform for sST2 were established.

Long-term, real-time and label-free live cell image processing and analysis based on a combined algorithm of CellPose and watershed segmentation.

Developing a rapid and quantitative method to accurately evaluate the physiological abilities of living cells is critical for tumor control. Many experiments have been conducted in the field of biology in an attempt to measure the proliferation and movement abilities of cells, but existing methods cannot provide real-time and objective data for label-free cells. The quantitative imaging technique, including an automatic segmentation algorithm for individual label-free cells, has been a breakthrough in this regard. In this study, we develop a combined automatic image processing algorithm of CellPose and watershed segmentation for the long-term and real-time imaging of label-free cells. This method shows strong reliability in cell identification regardless of cell densities, allowing us to obtain accurate information about the number and proliferation ability of the target cells. Additionally, our results also suggest that this method is a reliable way to assess real-time data on drug cytotoxicity, cell morphology, and cell movement ability.

Modulation of Neuroinflammation: Advances in Roles and Mechanisms of the IL-33/ST2 Axis Involved in Ischemic Stroke.

Interleukin (IL)-33 was initially recognized as a constituent of the IL-1 cytokine family in 2005. It exerts pleiotropic effects by regulating immune responses via its binding to the receptor ST2 (IL-33R). The IL-33/ST2 pathway has been linked to several inflammatory disorders. In human and rodents, the broad expression of IL-33 in spinal cord tissues and brain indicates its central nervous system-specific functions. Growing evidence supports the protective effects of the IL-33/ST2 pathway in ischemic stroke, along with a better understanding of the underlying mechanisms. IL-33 plays a crucial role in the regulation of the release of inflammatory molecules from glial cells in response to neuropathological lesions. Moreover, IL-33/ST2-mediated neuroprotection following cerebral ischemia may be linked to T-cell function, specifically regulatory T cells. Soluble ST2 (sST2) acts as a decoy receptor in the IL-33/ST2 axis, blocking IL-33 signaling through the membrane ST2 receptor. sST2 has also been identified as a potential inflammatory biomarker of ischemic stroke. Targeting sST2 specifically to eliminate its inhibition of the protective IL-33/ST2 pathway in ischemic brain tissues is a promising approach for the treatment of ischemic stroke.

Equivalence of Fluctuation-Dissipation and Edwards' Temperature in Cyclically Sheared Granular Systems.

Using particle trajectory data obtained from x-ray tomography, we determine two kinds of effective temperatures in a cyclically sheared granular system. The first one is obtained from the fluctuation-dissipation theorem which relates the diffusion and mobility of lighter tracer particles immersed in the system. The second is the Edwards compactivity defined via the packing volume fluctuations. We find robust agreement between these two temperatures, independent of the type of the tracers, cyclic shear amplitudes, and particle surface roughness, giving therefore the first experimental evidence that the concept of effective temperature is valid in driven frictional granular systems.

The Potential Role of Leucine-rich Repeat-containing Protein 8A in Central Nervous System: Current Situation and Prospect.

Cell swelling usually initiates the regulatory volume decrease (RVD) process mediated mainly by volume-regulated anion channels (VRACs), which are formed by multiple different leucine-rich repeat-containing protein 8 (LRRC8) family members. VRAC currents have been widely recorded in astrocytes, neurons and microglia in the brain, and VRACs have been suggested to be involved in the important pathogenesis of cell swelling-related central nervous system (CNS) diseases, such as ischemic stroke, epilepsy and epileptogenesis, glioblastoma (GBM), and so on. Recently, the increasing studies started to focus on LRRC8A (SWELL1), an obligatory subunit of VRAC indentified in 2014, which may be the key target to regulate the VRAC functions. After cerebral ischemia, the swollen astrocytes, neurons and microglia can activate LRRC8A-dependent VRACs, which may respectively promote the release of excitatory amino acids (EAA), interaction with ionotropic glutamate receptors, and regulating inflammation, suggesting the pleiotropic roles of LRRC8A in swollen brain cells. For the treatment of cell swelling-related CNS diseases, specific targeting LRRC8A may be a superior strategy to inhibit swollen-induced VRAC hyperactivity without blocking the normal VRAC function.

Experimental Test of the Edwards Volume Ensemble for Tapped Granular Packings.

Using x-ray tomography, we experimentally investigate granular packings subject to mechanical tapping for three types of beads with different friction coefficients. We validate the Edwards volume ensemble in these three-dimensional granular systems and establish a granular version of thermodynamic zeroth law. Within the Edwards framework, we also explicitly clarify how friction influences granular statistical mechanics by modifying the density of states, which allows us to determine the entropy as a function of packing fraction and friction. Additionally, we obtain a granular jamming phase diagram based on geometric coordination number and packing fraction.

Microscopic structure and dynamics study of granular segregation mechanism by cyclic shear.

Granular mixtures with size difference can segregate upon shaking or shear. However, the quantitative study of this process remains difficult because it can be influenced by many mechanisms. Conflicting results on similar experimental systems are frequently obtained when the experimental conditions are not well controlled, which is mainly due to the fact that many mechanisms can be at work simultaneously. Moreover, it is often that macroscopic or empirical measures, which lack microscopic physical bases, are used to explain the experimental findings and therefore cannot provide an accurate and complete depiction of the overall process. Here, we carry out a detailed and systematic microscopic structure and dynamics study of a cyclically sheared granular system with rigorously controlled experimental conditions. We find that both convection and arching effect play important roles in the segregation process in our system, and we can quantitatively identify their respective contributions.

Collective dynamics of gastric cancer cells in fluid.

Gastric cancer (GC) is the most common digestive system malignant cancer, and gastric cancer cells (GCC) can migrate in normal solid tissue and lymphatic fluid. Previously, much research has focused on the migration process when the cells are in the solid condition, such as migration through tissue, adhesion, and invasion processes, while little is known about the migration process of GCC in lymphatic fluid. In the current study, we investigate the migration of GCC in a fluid condition in an in vitro environment. We find that the cells diffuse mainly because of their cell viability. Therefore, despite the fact that lymph fluid is almost quiescent, GCCs can migrate around easily. The dynamics of cells also demonstrate a collective glassy dynamic similar to ordinary inactive glassy materials. As density of the cells increases, the movement of the cells becomes slower, and the collective dynamic becomes heterogeneous, which is similar to the dynamically heterogeneous behavior in glassy materials. The results will help us gain a better knowledge of the characteristics of GCC dynamics in the liquid phase which is crucial for the understanding of the mechanism for lymphatic metastasis. This can also potentially help early diagnosis of lymph node metastasis in GC and provide new insights for future clinical treatment.

Serum-soluble ST2 as a novel biomarker reflecting inflammatory status and illness severity in patients with COVID-19.

Aim: The authors studied the role of soluble ST2 (sST2) in COVID-19 and its relationship with inflammatory status and disease severity. Materials & methods: Serum levels of sST2 and interleukin (IL)-33, C-reactive protein (CRP), serum amyloid protein (SAA), IL-6 and procalcitonin (PCT), and T lymphocyte subsets from 80 subjects diagnosed with COVID-19 including 36 mild, 41 severe and three asymptomatic cases were tested. Results: Serum sST2 levels were significantly increased in COVID-19 patients, which were positively correlated with CRP, but negatively correlated with CD4+ and CD8+ T lymphocyte counts. Serum sST2 levels in nonsurviving severe cases were persistently high during disease progression. Conclusion: Serum sST2 level test is helpful for reflecting inflammatory status and illness severity of COVID-19.

Environmental contamination of SARS-CoV-2 in healthcare premises.

OBJECTIVES: A large number of healthcare workers (HCWs) were infected by SARS-CoV-2 during the ongoing outbreak of COVID-19 in Wuhan, China. Hospitals are significant epicenters for the human-to-human transmission of the SARS-CoV-2 for HCWs, patients, and visitors. No data has been reported on the details of hospital environmental contamination status in the epicenter of Wuhan. METHODS: We collected 626 surface swabs within the Zhongnan Medical Center in Wuhan in the mist of the COVID-19 outbreak between February 7 - February 27, 2020. Dacron swabs were aseptically collected from the surfaces of 13 hospital function zones, five major objects, and three major PPE. The SARS-CoV-2 RNAs were detected by reverse transcription-PCR. RESULTS: The most contaminated zones were the intensive care unit specialized for taking care of novel coronavirus pneumonia (NCP) (31.9%), Obstetric Isolation Ward specialized for pregnant women with NCP (28.1%), and Isolation Ward for NCP (19.6%). We classified the 13 zones into four contamination levels. The most contaminated objects were self-service printers (20.0%), desktop/keyboard (16.8%), and doorknob (16.0%). Both hand sanitizer dispensers (20.3%) and gloves (15.4%) were the most contaminated PPE. CONCLUSION: Our findings emphasize the urgent need to ensure adequate environmental cleaning, strengthen infection prevention training, and improve infection prevention among HCWs during the outbreak of COVID-19.

Asymptomatic SARS-CoV-2 Infection in Household Contacts of a Healthcare Provider, Wuhan, China.

We found that all 5 asymptomatic household contacts of a Wuhan, China, physician with coronavirus disease had severe acute respiratory syndrome coronavirus 2 detected by PCR. The index patient and 2 contacts also had abnormal chest computed tomography scans. Asymptomatic infected household contacts of healthcare workers with coronavirus disease might be underrecognized.