A Small Highly Sensitive Glucose Sensor Based on a Glucose Oxidase-Modified U-Shaped Microfiber.

Diabetes patients need to monitor blood glucose all year round. In this article, a novel scheme is proposed for blood glucose detection. The proposed sensor is based on a U-shaped microfiber prepared using hydrogen-oxygen flame-heating technology, and then 3-aminopropyltriethoxysilane (APTES) and glucose oxidase (GOD) are successively coated on the surface of the U-shaped microfiber via a coating technique. The glucose reacts with the GOD of the sensor surface to produce gluconic acid, which changes the effective refractive index and then shifts the interference wavelength. The structure and morphology of the sensor were characterized via scanning electron microscope (SEM) and confocal laser microscopy (CLM). The experimental results show that the sensitivity of the sensor is as high as 5.73 nm/(mg/mL). Compared with the glucose sensor composed of the same material, the sensitivity of the sensor increased by 329%. The proposed sensor has a broad application prospect in blood glucose detection of diabetic patients due to the advantages of miniaturization, high sensitivity, and good stability.

Identification of natural compounds as SARS-CoV-2 entry inhibitors by molecular docking-based virtual screening with bio-layer interferometry.

Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which enter the host cells through the interaction between its receptor binding domain (RBD) of spike glycoprotein with angiotensin-converting enzyme 2 (ACE2) receptor on the plasma membrane of host cell. Neutralizing antibodies and peptide binders of RBD can block viral infection, however, the concern of accessibility and affordability of viral infection inhibitors has been raised. Here, we report the identification of natural compounds as potential SARS-CoV-2 entry inhibitors using the molecular docking-based virtual screening coupled with bilayer interferometry (BLI). From a library of 1871 natural compounds, epigallocatechin gallate (EGCG), 20(R)-ginsenoside Rg3 (RRg3), 20(S)-ginsenoside Rg3 (SRg3), isobavachalcone (Ibvc), isochlorogenic A (IscA) and bakuchiol (Bkc) effectively inhibited pseudovirus entry at concentrations up to 100 µM. Among these compounds, four compounds, EGCG, Ibvc, salvianolic acid A (SalA), and isoliensinine (Isl), were effective in inhibiting SARS-CoV-2-induced cytopathic effect and plaque formation in Vero E6 cells. The EGCG was further validated with no observable animal toxicity and certain antiviral effect against SARS-CoV-2 pseudovirus mutants (D614G, N501Y, N439K & Y453F). Interestingly, EGCG, Bkc and Ibvc bind to ACE2 receptor in BLI assay, suggesting a dual binding to RBD and ACE2. Current findings shed some insight into identifications and validations of SARS-CoV-2 entry inhibitors from natural compounds.

Relationship between changes in the course of COVID-19 and ratio of neutrophils-to-lymphocytes and related parameters in patients with severe vs. common disease.

To assess the relationship between the neutrophil-to-lymphocyte ratio (NLR) and related parameters to the severity of coronavirus disease 2019 (COVID-19) symptoms. Clinical data from 38 COVID-19 patients who were diagnosed, treated and discharged from the Qishan Hospital in Yantai over the period from January to February 2020 were analysed. NLR and procalcitonin (PCT) were determined in the first and fourth weeks after their admission, along with the clinical characteristics and laboratory test results of these patients. Based on results as obtained on the first and fourth weeks after admission, five indices consisting of NLR, white blood cells, neutrophils, lymphocytes (LY) and monocytes (MON) were selected to generate receiver operating characteristic curves, while optimal cutoff values, sensitivities and specificities were obtained according to the Yuden index. Statistically significant differences in neutrophils, LY and the NLR were present in the severe vs. moderate COVID-19 group from the first to the fourth week of their hospitalisation. The cut-off value of NLR for predicting the severity of COVID-19 was 4.425, with a sensitivity of 0.855 and a specificity of 0.979. A statistically significant positive correlation was present between PCT and NLR in the severe group as determined within the first week of admission. NLR can serve as a predictor of COVID-19 disease severity as patients' progress from the first to the fourth week of their hospitalisation. The statistically significant positive correlation between levels of NLR and PCT in severe patients indicated that increases in NLR were accompanied with gradual increases in PCT.

Outcomes from the Use of Perioperative Extracorporeal Membrane Oxygenation in Patients Undergoing Thoracic Surgery: An 8-Year Single-Center Experience.

BACKGROUND Extracorporeal membrane oxygenation (ECMO) plays an important role in thoracic surgery. This retrospective study from a single center aimed to evaluate patient outcomes from the use of perioperative ECMO in 22 patients undergoing thoracic surgery during an 8-year period. MATERIAL AND METHODS Data were collected retrospectively from 22 patients who received ECMO (veno-arterial and veno-venous ECMO) as perioperative treatment during general thoracic surgery from January 2012 to October 2020. Patients required ECMO due to perioperative cardiopulmonary resuscitation (CPR) (2 cases), perioperative pulmonary embolism (PE) (2 cases), lung transplant (4 cases), undergoing complicated thoracic surgery (5 cases), postoperative acute respiratory distress syndrome (ARDS) (6 cases), and thoracic trauma (3 cases). RESULTS Veno-arterial ECMO was used for circulatory support in 13 cases and veno-venous ECMO was used for respiratory support in 9 cases. The average ECMO support time was 71.6±42.4 h. Twenty patients (90.9%) were successfully decannulated and 17 (77.2%) survived to discharge. Complications included severe hemorrhage (3/22 patients, 13.6%), sepsis (3/22, 13.6%), and destruction of blood cells (1/22, 4.5%). There were no significant differences in survival rates between patients receiving pre- or postoperative ECMO (P=0.135) or between veno-venous ECMO (V-V ECMO) and veno-arterial ECMO (V-A ECMO) (P=0.550). CONCLUSIONS The findings from this small retrospective study from a single center showed that perioperative ECMO improved cardiac and respiratory function in patients undergoing thoracic surgery. Optimal results require surgeons to have an understanding of the indications and ability to control the complications of ECMO.

Polarization dependent cladding modes coupling and spectral analyses of excessively tilted fiber grating.

We report on the detailed analyses of mode coupling from fiber core to cladding in excessively tilted fiber gratings (ETFGs). Cladding modes responsible for the typical dual peak pairs in the transmission spectrum of ETFGs are identified with phase matching condition, which suggests two set of dual peak pairs generated from coupling to cladding modes with even and odd azimuthal order. The polarization dependence of those dual peak pairs are also investigated by calculating the coupling coefficients of cladding modes for two orthogonal polarizations. With the calculated coupling coefficients, the measured polarization dependent spectra can be reproduced numerically.

Liu Shen capsule shows antiviral and anti-inflammatory abilities against novel coronavirus SARS-CoV-2 via suppression of NF-κB signaling pathway.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread worldwide through person-to-person contact, causing a public health emergency of international concern. At present, there is no specific antiviral treatment recommended for SARS-CoV-2 infection. Liu Shen capsule (LS), a traditional Chinese medicine, has been proven to have a wide spectrum of pharmacological properties, such as anti-inflammatory, antiviral and immunomodulatory activities. However, little is known about the antiviral effect of LS against SARS-CoV-2. Herein, the study was designed to investigate the antiviral activity of SARS-CoV-2 and its potential effect in regulating the host's immune response. The inhibitory effect of LS against SARS-CoV-2 replication in Vero E6 cells was evaluated by using the cytopathic effect (CPE) and plaque reduction assay. The number of virions of SARS-CoV-2 was observed under transmission electron microscope after treatment with LS. Proinflammatory cytokine expression levels upon SARS-CoV-2 infection in Huh-7 cells were measured by real-time quantitative PCR assays. The results showed that LS could significantly inhibit SARS-CoV-2 replication in Vero E6 cells, and reduce the number of virus particles and it could markedly reduce pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-8, CCL-2/MCP-1 and CXCL-10/IP-10) production at the mRNA levels. Moreover, the expression of the key proteins in the NF-κB/MAPK signaling pathway was detected by western blot and it was found that LS could inhibit the expression of p-NF-κB p65, p-IκBα and p-p38 MAPK, while increasing the expression of IκBα. These findings indicate that LS could inhibit SARS-CoV-2 virus infection via downregulating the expression of inflammatory cytokines induced virus and regulating the activity of NF-κB/MAPK signaling pathway in vitro, making its promising candidate treatment for controlling COVID-19 disease.

ß-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling.

ß-Sitosterol (24-ethyl-5-cholestene-3-ol) is a common phytosterol Chinese medical plants that has been shown to possess antioxidant and anti-inflammatory activity. In this study we investigated the effects of ß-sitosterol on influenza virus-induced inflammation and acute lung injury and the molecular mechanisms. We demonstrate that ß-sitosterol (150-450 µg/mL) dose-dependently suppresses inflammatory response through NF-κB and p38 mitogen-activated protein kinase (MAPK) signaling in influenza A virus (IAV)-infected cells, which was accompanied by decreased induction of interferons (IFNs) (including Type I and III IFN). Furthermore, we revealed that the anti-inflammatory effect of ß-sitosterol resulted from its inhibitory effect on retinoic acid-inducible gene I (RIG-I) signaling, led to decreased STAT1 signaling, thus affecting the transcriptional activity of ISGF3 (interferon-stimulated gene factor 3) complexes and resulting in abrogation of the IAV-induced proinflammatory amplification effect in IFN-sensitized cells. Moreover, ß-sitosterol treatment attenuated RIG-I-mediated apoptotic injury of alveolar epithelial cells (AEC) via downregulation of pro-apoptotic factors. In a mouse model of influenza, pre-administration of ß-sitosterol (50, 200 mg·kg-1·d-1, i.g., for 2 days) dose-dependently ameliorated IAV-mediated recruitment of pathogenic cytotoxic T cells and immune dysregulation. In addition, pre-administration of ß-sitosterol protected mice from lethal IAV infection. Our data suggest that ß-sitosterol blocks the immune response mediated by RIG-I signaling and deleterious IFN production, providing a potential benefit for the treatment of influenza.

Extracorporeal membrane oxygenation in patients with heart transplantation : A clinical prognosis analysis.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is indicated for bridging to heart transplantation, graft failure, and right heart failure after heart transplantation. This study explored risk factors affecting the clinical prognosis of cardiac transplantation patients treated with ECMO during the perioperative period. METHODS: Data on 28 heart transplantation patients with ECMO obtained from January 2012 to January 2018 in the People's Hospital of Zhongshan City were retrospectively analyzed. RESULTS: A total of 25 patients (20 male and 5 female) were finally included. Heart transplantation was performed mainly due to cardiomyopathy (77.8%). Of the treated patients, 18 (72%) survived and were discharged, 4 were treated with cardiopulmonary resuscitation (CPR) before ECMO, and 3 died in hospital. There were no differences between the surviving and death group donors (N-terminal pro b­type natriuretic peptide [NT-proBNP], creatine kinase-muscle/brain [CK-MB], warm ischemia time of donated heart, cold ischemia time of donated heart, total ischemia time of donated heart, and donor type). In univariate analysis, body mass index (BMI), length of stay in the intensive care unit (ICU), and CPR were relevant prognostic factors for heart transplantation patients with ECMO. Multi-factor logistic regression showed that CPR before ECMO (odds ratio, OR, 49.45; 95% confidence interval, CI, [1.37, 1781.6]; P = 0.033) is an independent risk factor influencing prognosis. CONCLUSION: ECMO is an important life support method for patients before and after heart transplantation surgery. Obesity, poor preoperative cardiac function, and considerable intraoperative red blood cell transfusion may influence prognosis. Extracardiac compression before ECMO is an independent risk factor for prognosis.

Vascular Complications of Lower Limb Ischemia in Patients with Femoral Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Lower limb ischemia in patients with extracorporeal membrane oxygenation (ECMO) via femoral artery catheterization negatively affects patient mortality and survivors' quality of life [Gulkarov 2020]. In this study, ECMO was established via femoral artery catheterization. This study aimed to identify the risk factors of lower limb ischemia to provide sufficient evidence for its prevention. METHODS: All patients with venoarterial (VA) ECMO via femoral artery catheterization in Zhongshan People's Hospital from January 2008 to November 2019 retrospectively were analyzed. Patients' general information and ECMO-related information were obtained, and the main outcome variables were survival and discharge and intubation-related adverse events (limb ischemia and incision bleeding). Logistic regression analysis was used to determine the independent risk factors of limb ischemia in patients with VA ECMO. RESULTS: A total of 179 (98 [54.7%] men and 81 [45.3%] women) eligible patients were included in this study. Moreover, a total of 90 patients (48.9%) had low cardiac output, 41 (22.3%) had acute myocardial infarction, and 33 (17.9%) had fulminant myocarditis. Eighty-six (48.04%) patients survived to hospital discharge, 36 (20.11%) had limb ischemia, and 42 (23.46%) had incision bleeding. Furthermore, the ECMO-assisted time was 114.23 ± 67.88 hours. There was no significant difference in age, sex, and Sequential Organ Failure Assessment score between the limb ischemia group and the non-limb ischemia group. Multivariate logistic regression analysis showed that peripheral artery disease (odds ratio, 27.12; 95% confidence interval, 5.614-130.96) was an independent risk factor of limb ischemia in patients with ECMO. CONCLUSION: Limb ischemia is a common complication in patients with VA ECMO, and peripheral artery disease is an independent risk factor of limb ischemia in patients with VA ECMO via femoral artery catheterization.

Peptidomimetic inhibitors of APC-Asef interaction block colorectal cancer migration.

The binding of adenomatous polyposis coli (APC) to its receptor Asef relieves the negative intramolecular regulation of Asef and leads to aberrant cell migration in human colorectal cancer. Because of its crucial role in metastatic dissemination, the interaction between APC and Asef is an attractive target for anti-colorectal-cancer therapy. We rationally designed a series of peptidomimetics that act as potent inhibitors of the APC interface. Crystal structures and biochemical and cellular assays showed that the peptidomimetics in the APC pocket inhibited the migration of colorectal cells by disrupting APC-Asef interaction. By using the peptidomimetic inhibitor as a chemical probe, we found that CDC42 was the downstream GTPase involved in APC-stimulated Asef activation in colorectal cancer cells. Our work demonstrates the feasibility of exploiting APC-Asef interaction to regulate the migration of colorectal cancer cells, and provides what to our knowledge is the first class of protein-protein interaction inhibitors available for the development of cancer therapeutics targeting APC-Asef signaling.

The phyllosphere indigenous microbiota of Brassica campestris L. change its diversity in responding to di-n-butyl phthalate pollution.

In this study, the effects of di-n-butyl phthalate (DBP) on the phyllosphere bacterial community of field mustard (Brassica campestris L.) at the five-leaf stage were investigated. The indigenous alpha-diversity of the phyllosphere bacteria was altered after spraying with different concentrations of DBP. Shannon diversity indices were significantly changed on day 5 after treatment at DBP concentrations > 400 mg L-1 (P > 0.05). Nevertheless, the difference between treatment and control was not significant on day 9 after DBP treatment (P > 0.05). Exposure to DBP resulted in a decrease in Proteobacteria and Firmicutes, and an increase in Actinobacteria at all sampling intervals. These changes included significant increases in the relative abundance of Paracoccus and Rhodococcus, and significant decreases in that of Pseudomonas, Exiguobacterium, an unclassified genus of Pseudomonadaceae, and an unclassified genus of Enterobacteriaceae. This study provides new evidence for the possibility of using phyllosphere microbiota to remediate DBP contamination.

Experimental observation of wave localization at the Dirac frequency in a two-dimensional photonic crystal microcavity.

Trapping light within cavities or waveguides in photonic crystals is an effective technology in modern integrated optics. Traditionally, cavities rely on total internal reflection or a photonic bandgap to achieve field confinement. Recent investigations have examined new localized modes that occur at a Dirac frequency that is beyond any complete photonic bandgap. We design Al2O3 dielectric cylinders placed on a triangular lattice in air, and change the central rod size to form a photonic crystal microcavity. It is predicted that waves can be localized at the Dirac frequency in this device without photonic bandgaps or total internal reflections. We perform a theoretical analysis of this new wave localization and verify it experimentally. This work paves the way for exploring localized defect modes at the Dirac point in the visible and infrared bands, with potential applicability to new optical devices.

Impact of Heavy Metal Pollution on Ammonia Oxidizers in Soils in the Vicinity of a Tailings Dam, Baotou, China.

Soil heavy metal pollution has received increasing attention due to their toxicity to soil microorganisms. We have analyzed the effects of heavy metal pollution on ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in soils in the vicinity of a tailings dam of Baotou region, China. Results showed that AOB were dominated with Nitrosomonas-like clusters, while AOA was dominated by group1.1b (Nitrososphaera cluster). Single Cd and Cr contents, as well as compound heavy metal pollution levels, had a significant negative impact on soil potential nitrification rate and both diversities of AOA and AOB. No clear relationship was found between any single heavy metal and abundance of AOA or AOB. But compound pollution could significantly decrease AOA abundance. The results indicated that heavy metal pollution had an obviously deleterious effect on the abundance, diversity, activity and composition of ammonia oxidizers in natural soils.

Tunable random polymer fiber laser.

We have demonstrated the realization of on-line temperature-controlled random lasers (RLs) in the polyhedral oligomeric silsesquioxanes (POSS) nanoparticles (NPs) as well as Pyrromethene 597 (PM597) laser dye, Fe3O4/SiO2 NPs as well as PM597, and only PM597 doped polymer optical fibers (POFs), respectively. The RLs can be obtained from the gained POFs system caused by multiple scattering of emitted light. The refractive index of the fiber core materials can be easily tuned via temperature due to the polymer with large thermo-optic coefficient. Meanwhile, the scattering mean free path of core in the POFs, which is the key role for the emission wavelength of RLs, is strongly dependent on the matrix refractive index. Thus emission wavelength of RLs in the POF temperature can be controlled through changing the temperature. With the increasing the temperature, the RL emission wavelength has occurred red-shift effect for the POFs.

Spatial algebraic solitons at the Dirac point in optically induced nonlinear photonic lattices.

The discovery of a new type of soliton occurring in periodic systems is reported. This type of nonlinear excitation exists at a Dirac point of a photonic band structure, and features an oscillating tail that damps algebraically. Solitons in periodic systems are localized states traditionally supported by photonic bandgaps. Here, it is found that besides photonic bandgaps, a Dirac point in the band structure of triangular optical lattices can also sustain solitons. Apart from their theoretical impact within the soliton theory, they have many potential uses because such solitons are possible in both Kerr material and photorefractive crystals that possess self-focusing and self-defocusing nonlinearities. The findings enrich the soliton family and provide information for studies of nonlinear waves in many branches of physics.

A novel allosteric site in casein kinase 2α discovered using combining bioinformatics and biochemistry methods.

Casein kinase 2 (CK2) is a highly pleiotropic serine-threonine kinase, which catalyzed phosphorylation of more than 300 proteins that are implicated in regulation of many cellular functions, such as signal transduction, transcriptional control, apoptosis and the cell cycle. On the other hand, CK2 is abnormally elevated in a variety of tumors, and is considered as a promising therapeutic target. The currently available ATP-competitive CK2 inhibitors, however, lack selectivity, which has impeded their development in cancer therapy. Because allosteric inhibitors can avoid the shortcomings of conventional kinase inhibitors, this study was aimed to discover a new allosteric site in CK2α and to investigate the effects of mutations in this site on the activity of CK2α. Using Allosite based on protein dynamics and structural alignment, we predicted a new allosteric site that was partly located in the αC helix of CK2α. Five residues exposed on the surface of this site were mutated to validate the prediction. Kinetic analyses were performed using a luminescent ADP detection assay by varying the concentrations of a peptide substrate, and the results showed that the mutations I78C and I78W decreased CK2α activity, whereas V31R, K75E, I82C and P109C increased CK2α activity. Potential allosteric pathways were identified using the Monte Carlo path generation approach, and the results of these predicted allosteric pathways were consistent with the mutation analysis. Multiple sequence alignments of CK2α with the other kinases in the family were conducted using the ClustalX method, which revealed the diversity of the residues in the site. In conclusion, we identified a new allosteric site in CK2α that can be altered to modulate the activity of the kinase. Because of the high diversity of the residues in the site, the site can be targeted using rational drug design of specific CK2α inhibitors for biological relevance.

Pinanamine Is a Promising Lead Compound against Influenza A Virus: Evidence from in Vitro and in Vivo Efficacy Compared to Amantadine.

Influenza A viruses with the presence of mutations in M2 still circulate and threaten to avian species and human in China. A novel M2 inhibitor pinanamine was previously identified as an antiviral agent by an in vitro assay. In this study, we monitored the activity of pinanamine against influenza A/FM1/47 (H1N1) virus infection in cell culture and mice. Pinanamine showed more potent antiviral effect than ribavirin, and was as effective as oseltamivir carboxylate and amantadine in Madin-Darby canine kidney (MDCK) cells. Pinanamine at dose of 50 mg/kg/d administrated once a day for 6 d starting 24 h prior to virus exposure promoted survival rate of infected mice to 100% (p<0.001) and produced significant reduction (p<0.001) in lung virus yields and lung index. Even lower the dose of 3.1 mg/kg/d, pinanamine was 60% protective (p<0.05), which was equivalent to treatment with amantadine at 50 mg/kg/d. Our finding highlights the potential of pinanamine as a promising lead compound for influenza A virus.

Polarized random laser emission from an oriented disorder polymer optical fiber.

We demonstrate the realization of a polarized random polymer fiber laser (RPFL) in the different disordered gain media doped polymer optical fibers (POFs). Multiple scattering of disordered media in the orientated POF was experimentally verified to account for polarized lasing observed in our RPFL system. This Letter presents a new avenue for fabricating polarized RPFLs in a large scale. Meanwhile, the polarization-maintaining property of random lasing for different disorder POF are researched, which will open a window to designing a polarization-maintaining random fiber laser.

Modulation of large absolute photonic bandgaps in two-dimensional plasma photonic crystal containing anisotropic material.

The large absolute photonic bandgaps of two-dimensional (2D) anisotropic magnetic plasma photonic crystals with hexagonal and square lattices are obtained by introducing tellurium dielectric rods using the modified plane wave expansion method. Equations for calculating the band structures in the irreducible part of the first Brillouin zone are theoretically deduced. The modulation properties indicate that the location and bandwidth of the absolute photonic bandgaps (PBGs) could be tuned by filling factor, plasma frequency, and magnetic field. The effective tunable ranges and critical values of these parameters are found. These results could be helpful in designing 2D anisotropic PPCs with large absolute PBGs.

Light trapping at Dirac point in 2D triangular Archimedean-like lattice photonic crystal.

Optical cavities and waveguides are critical parts of modern optical devices. Traditionally, optical cavities and waveguides rely on photonic bandgaps, or total internal reflection, to achieve light trapping. It has been reported that a novel light trapping, which exists in triangular and honeycomb lattices, is attributed to the so-called Dirac point. Our analysis reveals that 2D triangular Archimedean-like lattice photonic crystals also can support this Dirac mode with similar characteristics. This is a new type of localized mode with a different algebraic field profile at a different specified Dirac frequency, which is also beyond any complete photonic bandgap. The new wave localization has different features and can be applied to the design of new optical devices.