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Demodex infestation and density changes remain one of the main challenges in some clinical settings. Tumour necrosis factor-α (TNF-α) inhibitors have been recommended as a first-line treatment for ankylosing spondylitis (AS). However, there have been no studies investigating the impact of TNF-α inhibitor adalimumab on changes in the Demodex density in patients with AS. The aim of this study was to investigate Demodex density changes before and after adalimumab treatment and analyse the relationship between the Demodex density and clinical characteristics in AS. It was found that the Demodex density was positively correlated with age and C-reactive protein levels and the number of Demodex mites could increase after adalimumab treatment in AS.

Here we attempted to deliver probiotics to the human gut using fruit juices as a carrier, which is less common despite the newest trend to incorporate probiotics into non-dairy food. Phenolic-rich fruit juices, including blueberry, black cherry, concord grape and pomegranate were fortified with

The retrovirus HIV‐1 integrates into the host genome and establishes a latent viral reservoir that escapes immune surveillance. Molecular mechanisms of HIV‐1 latency have been studied extensively to achieve a cure for the acquired immunodeficiency syndrome (AIDS). Latency‐reversing agents (LRAs) have been developed to reactivate and eliminate the latent reservoir by the immune system. To develop more promising LRAs, it is essential to evaluate new therapeutic targets. Here, we find that CBX4, a component of the Polycomb Repressive Complex 1 (PRC1), contributes to HIV‐1 latency in seven latency models and primary CD4(+) T cells. CBX4 forms nuclear bodies with liquid–liquid phase separation (LLPS) properties on the HIV‐1 long terminal repeat (LTR) and recruits EZH2, the catalytic subunit of PRC2. CBX4 SUMOylates EZH2 utilizing its SUMO E3 ligase activity, thereby enhancing the H3K27 methyltransferase activity of EZH2. Our results indicate that CBX4 acts as a bridge between the repressor complexes PRC1 and PRC2 that act synergistically to maintain HIV‐1 latency. Dissolution of phase‐separated CBX4 bodies could be a potential intervention to reactivate latent HIV‐1.

To identify biomarkers that reflect disease activity scores and to investigate the role of macrophage-associated chemokines in initial axial spondyloarthritis (axSpA).Patients with axSpA were enrolled. The SpondyloArthritis Research Consortium of Canada (SPARCC) method was used to score bone marrow oedema (BMO) in the inflammatory lesions on magnetic resonance imaging (MRI). Radiographic assessment of the spine was performed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Clinical variables, including inflammatory markers, serum CC chemokine ligand 2 (CCL2), CCL3, CCL7, CCL8 and C-X3-C motif ligand 1 (CX3CL1), were measured. Correlation analysis between serum levels of these macrophage-associated chemokines and clinical data was performed.There were no significant differences between the axSpA group and the healthy control group in terms of serum levels of CCL2, CCL3 or CCL8. Compared to the healthy control group, the serum levels of CCL7 and CX3CL1 were significantly higher in ankylosing spondylitis (AS) (p = 0.045, p = 0.017, respectively). In the AS subgroup, the serum level of CX3CL1 had a positive correlation with SPARCC scores.In AS, serum CCL7 and CX3CL1 levels are elevated. The serum level of CX3CL1 is associated with MRI-determined oedema in AS. CX3CL1 may be useful as a biomarker to predict active inflammation in the sacroiliac joint (SIJ) in AS. Key Points • Serum levels of CX3CL1 are associated with MRI-determined oedema in AS. • CX3CL1 may be a useful biomarker to predict active inflammation in the sacroiliac joint in AS.

Laser powder bed fusion (LPBF) is one of the most popular metal additive manufacturing technologies, which has found its applications in high-value sectors such as aerospace and biomedical devices. Some recent studies on the LPBF of stents have demonstrated its feasibility in the fabrication in thin strut structures including heart valve frames, as used in transcatheter aortic valve implantation (TAVI) for the treatment of severe aortic stenosis. The state of the art method of laser cutting TAVI frame limits the scope for novel concepts which are made possible by additive manufacturing. However, the surface quality and dimensional accuracy of LPBF parts are lower than that produced by laser cutting. To start the development of new TAVI concepts, the feasibility of manufacturing thin frames by LPBF has been investigated based the SAPIEN 3 frame by Edwards Lifesciences. In this study, simplified frames with strut size from 0.3 mm to 0.5 mm have been successfully manufactured. The effects of strut size, strut angle, laser power and scan speed on the dimensional accuracy and surface quality were systemically studied. In addition, a representative SAPIEN 3 frame was manufactured and assessed with high resolution X-ray scans. Good overall dimensional accuracy and low porosity was obtained for the SAPIEN 3 frame. However, inclined struts were found to have relatively low dimensional accuracy and poor surface quality.

Accurate prediction of the risk of progression of coronavirus disease (COVID-19) is needed at the time of hospitalization. Logistic regression analyses are used to interrogate clinical and laboratory co-variates from every hospital admission from an area of 2 million people with sporadic cases. From a total of 98 subjects, 3 were severe COVID-19 on admission. From the remaining subjects, 24 developed severe/critical symptoms. The predictive model includes four co-variates: age (>60 years; odds ratio [OR] = 12 [2.3, 62]); blood oxygen saturation (5.75 mg/L; OR = 9.3 [1.5, 58]); and prothrombin time (>12.3 s; OR = 6.7 [1.1, 41]). Cutoff value is two factors, and the sensitivity and specificity are 96% and 78% respectively. The area under the receiver-operator characteristic curve is 0.937. This model is suitable in predicting which unselected newly hospitalized persons are at-risk to develop severe/critical COVID-19.

Phosphorus (P) levels in eutrophic lakes with restricted external P inputs often show hysteresis resulting from sediment P diagenetic recycling. Hard water oxygenated lakes are often thought to be less susceptible to P release from sediment due to precipitation of P with calcium carbonate and P sorption on iron (Fe) oxyhydroxides in oxidized surface sediments. However, perpetuated eutrophic conditions in many hard water oxygenated lakes persist despite drastic reduction of external P inputs. What limits P sediment binding capacity and drives its release from sediments in such lakes is often less understood. Here we characterize sediment P diagenetic processes driving persistent internal loading in the Bay of Quinte, a hard water, polymictic embayment of Lake Ontario, Canada. We used a multifaceted approach, combining a comprehensive three-year study of sediment P binding forms, recent sediment stratigraphy and accumulation, high spatial resolution measurement of dissolved oxygen, redox potential and pH across the sediment-water interface and depth profiles of nutrient and metals concentrations in pore water. Despite oxygenated bottom water conditions P diffusive fluxes during summer are substantial (1–6.5 mg P/m2/day), representing as much as 50% of external P inputs. Estimated rates of benthic organic carbon degradation indicate that anaerobic organic P mineralization in anoxic sediments is the main driver of P release, which is strongly influenced by Fe reduction. Estimated rates of benthic organic carbon degradation indicate that anaerobic organic P mineralization in anoxic sediments is the main driver of P release. In surface sediment the redox sensitive P is the prevailing diagenetically reactive P phase, emphasizing strong coupling with ferric Fe. While this indicates substantial P sorption on Fe oxyhydroxides, their spare binding capacity is limited, as reducible Fe: P ratios are close to sorption limit. The calcium carbonate bound P increased with sediment depth at the expense of redox sensitive P, suggesting diagenetic sequestration into apatite with sediment burial. However, only 40% of diagenetically reactive P forms, which account for ~2/3 of the total P in surface sediment, are permanently retained during burial. Importantly, our data show that in fact significant P-flux occurs in shallow areas, with an apparent discordance with concurrent measures of long-term P release from the sediments. These results also demonstrate that short-term measures cannot be extrapolated to long-term estimates and vice versa.

Objectives To identify disease activity scores and biomarkers that reflect magnetic resonance imaging (MRI)-determined sacroiliac joint (SIJ) inflammation in ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). Methods Patients who had AS and nr-axSpA were enrolled. All the patients underwent SIJ MRI. SpondyloArthritis Research Consortium of Canada (SPARCC) method was used to score bone marrow edema in the inflammatory lesions on MRI. Radiographic assessment of the spine was performed using modified Stoke Ankylosing Spondylitis Spine Score. Clinical variables, inflammatory markers, serum alkaline phosphatase, osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX-I), and procollagen I N-terminal peptide (PINP) were measured. Correlation analysis between MRI-determined SIJ inflammation scores and disease activity scores and laboratory variables was performed. Results Thirty-five patients had AS and 36had nr-axSpA. Significant differences were noted between the AS group and the nr-axSpA group in terms of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Ankylosing Spondylitis Disease Activity Score (ASDAS)-ESR, ASDAS-CRP, PINP, and SPARCC (p Conclusions In AS, PINP and age independently correlated with active inflammation on SIJ MRI. PINP may be useful as a marker of objective inflammation in AS.

Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanism and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the clinic to treat bacterial infection, significantly restrained the cell entry of Ebola virus, SARS-CoV and MERS-CoV by specifically inhibiting the activity of cathepsin L (CTSL). Here, we found that the cleavage sites of CTSL on the Spike of SARS-CoV-2 were highly conserved among all the variants. The treatment with teicoplanin suppressed the proteolytic activity of CTSL on Spike and prevented the cellular infection of different pseudotyped SARS-CoV-2 viruses. Teicoplanin potently prevented the entry of authentic SARS-CoV-2 into the cellular cytoplasm with an IC50 of 2.038 μM for the Wuhan-Hu-1 reference strain and an IC50 of 2.116 μM for the SARS-CoV-2 (D614G) variant. The pre-treatment of teicoplanin also prevented SARS-CoV-2 infection in hACE2 mice. In summary, our data reveal that CTSL is required for both SARS-CoV-2 and SARS-CoV infection and demonstrate the therapeutic potential of teicoplanin for universal anti-CoVs intervention.ImportanceDisease prevention and treatment are two important countermeasures to end the coronavirus disease 2019 (COVID-19). However, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, evolves all the time, resulting in the emerging of many epidemic SARS-CoV-2 mutants, which significantly impairs the effectiveness of early strain-based vaccines and antibodies. Developing universal vaccines and broad-spectrum antiviral drugs are essential to confront SARS-CoV-2 mutants including those may emerge in the future. Our study reported here showed that the cleavage sites of cellular cathepsin L (CTSL) are highly conserved among all the SARS-CoV-2 mutants and SARS-CoV. The CTSL inhibitor teicoplanin not only inhibited the cell entry of two live SARS-CoV-2 strains and various pseudotyped viruses but also prevented live virus infection in animal models. Based on our previous finding that teicoplanin also inhibited SARS-CoV and MERS-CoV infection, we believe that teicoplanin possesses the potential to become a universal anti-CoVs drug.

Distribution network planning is the basis to guarantee reliable operation of ‘Coal to Electricity’ (‘C2E’) distribution network. While, as a kind of incremental load, there is no standard about transformer capacity for each ‘C2E’ consumer. As a result, ‘C2E’ distribution network planning and design lacks basic rules. Aimed at this problem, a method named ‘Heat load to Electricity load’ for calculating ‘C2E’ incremental load and average transformer capacity per consumer is proposed in this paper, which provides basis to ‘C2E’ distribution network and electrical equipment selection. With this method, ‘C2E’ electrical load and average transformer capacity is determined by heating load of building in demand side. An example with typical residential building in Beijing is taken in this paper. Heating load of building is calculated using DeST (Designer’s Simulation Toolkits) firstly. Then, with the kind of electrical heating equipment, average transformer capacity for each ‘C2E’ consumer in Beijing rural area is given.

Diagenetic sediment phosphorus (P) recycling is a widespread phenomenon, which causes degradation of water quality and promotes harmful algal blooms in lakes worldwide. Strong P coupling with iron (Fe) in some lakes is thought to inhibit diagenetic P efflux, despite elevated P concentrations in the sediment. In these sediments, the high Fe content leads to P scavenging on ferric Fe near the sediment surface, which increases the overall P retention. Reduced external Fe inputs in such lakes due to industrial pollution control may lead to unintended consequences for sediment P retention. Here, we study sediment geochemistry and sediment-water interactions in the historically polluted Hamilton Harbour (Lake Ontario, Canada) which has undergone 30 years of restoration efforts. We investigate processes controlling diagenetic P recycling, which has previously been considered minor due to historically high Fe loading. Our results demonstrate that present sediment P release is substantial, despite sediment Fe content reaching 6.5% (dry weight). We conclude that the recent improvement of wastewater treatment and industrial waste management practices has reduced Fe pollution, causing a decrease in diagenetically reactive Fe phases, resulting in the reduction of the ratio of redox-sensitive P and Fe, and the suppression of P scavenging on Fe oxyhydroxides.

Aiming at the integrated energy optimization problem of residential buildings including production energy, energy storage and energy use objects, such as photovoltaic power generation, solar heat, electric heating, heat storage, battery, household power load and so on, this paper formulate the energy scheduling policy under the current running state referring to the scheduling policy of similar running state in history from the point of view of data mining. Firstly, a random matrix of basic status of residential buildings energy is constructed. Based on this, a similarity search method based on standardized Euclidean distance measure is proposed. This method forms four standardized Euclidean distances that are the solar irradiance vector, outdoor temperature vector, residential buildings’ electric load vector and heat load vector by the similarity measure calculation based on the standardized Euclidean distance model. The weight analysis method is used to uniformly process a standardized European distance comprehensive index as a measure of similarity. Then, the paper analyses the threshold setting principle of similarity measure. Finally, the optimization process of scheduling strategy of residential buildings energy based on similarity search method is given. A simulation example of an actual residential buildings under a typical scenario of sunny day in winter shows that the proposed similarity search method based on the standardized Euclidean distance measure can make full use of a large amount of historical operating data and speed up the optimization efficiency of optimal scheduling strategy for integrated buildings energy. The scheduling strategy can guide energy storage to play the role of energy transfer, and guide the electric heating equipment and the time-shifting electric load to work in the valley period through the peak and valley electricity prices, thereby the user’s bill is effectively reduced.

Magnetic resonance imaging (MRI) has been proven to reliably assess regional perfusion and left ventricular (LV) function of microembolized myocardium. The visibility of microinfarct on delayed enhancement MRI (DE-MRI) is limited and dependent on technical and biological issues. Furthermore, MRI underestimates total microinfarct size compared with microscopy. MRI studies revealed that the presence of microemboli in pre-existing acute infarct delays infarct healing and magnifies LV remodeling. Discrimination of acute from chronic microinfarct is based on presence of inflammatory cells, edema and scar tissue, respectively. These noninvasive findings highlight the importance of prognostic utility of MRI and warrant larger clinical studies or registries to evaluate the significance of presence of focal microinfarct. Serial microscopic studies revealed that intravascular microemboli migrate into the extravascular space and this migration process is a function of time. This phenomenon may limit the use of microemboli therapy in occluding hemorrhagic blood vessels or treating tumors. Despite current standard of care, existing methods and therapies do not prevent coronary embolization nor reverse their deleterious effects.

Distributed electric heating have become the main way to surrounding area user in winter, so it is very important to forecast short-term electric heating distribution load quickly and accurately. A novel method is proposed, in which the Back Propagation (BP) neural network algorithm is intelligently combined with ensemble empirical mode decomposition (EEMD), and it can deal with different weather type and temperature change on the residents' heating behavior. The daily load sequence is decomposed into four series of low-to-high frequency sub-sequences and a remnant sub-sequence by EEMD method. And then, each sub-sequence, temperature data and meteorological data are input into the BP neural network to predict. Finally, the predicted components are sum up to obtain the final prediction result. EEMD-BP is applied in Coal-to-Electricity Project in beijing and the distribution network load with a large proportion of electric heating is forecast. The simulation results show that EEMD-BP method can effectively reduce the prediction error.

The pdf document that contains the application and comparison of the methods to the data from patients with non-small cell lung cancer, all supplementary notes and figures. Figure S1 shows the median connectivity criterion of the pathway based distance score when the scoring matrix is treated as original data matrix instead of a distance matrix. Figure S2 shows the standard deviation of the connectivity criteria of all the methods across the 100 simulated low dimension data. Figure S3 shows the Dunn Index of all four methods as an alternative to the connectivity criterion using the low dimension simulation model. Figure S4 shows the comparison across all the methods using low dimensional simulation model with 40% of genes in the chosen pathways to be perturbed. Figure S5 shows the median and the standard deviation of the connectivity criterion of all four methods using the low dimension simulation model with a high background noise level (B = 3). Figure S6 shows the Dunn Index of all four methods as an alternative to the connectivity criterion using the low dimension simulation model with a high background noise level (B = 3). Figure S7 shows the performance comparison across the four methods using the low dimension simulation model with a high background noise (B = 3) and 40% of genes in the chosen pathways to be perturbed. Figure S8 shows the performance comparison across the four methods using the high dimension simulation model with a lower percentage of genes in the chosen pathways to be perturbed (20% and 40%). Figure S9 plots the purity of the clustering result by each pathway versus the number of genes in the corresponding pathway. Figure S10 shows the visualization of the distance matrices calculated by the four methods and their corresponding connectivity criteria for the real gene expression data from patients with non-small cell lung cancer. (PDF 5361 kb)

In the present paper, the impact of freshwater (ARC21 and LS0519) and marine (PCC8806) Synechococcus cyanobacteria on calcium carbonate (CaCO 3 ) precipitation has been examined in respect of the formation rates and morphology of crystals. Acid–base potentiometric titrations were employed to study surface functional groups, while CaCO 3 experiments have been carried out in presence and absence of cells at low to near-equilibrium conditions in respect to CaCO 3 . During these experiments, the pH values have been monitored, Ca and alkalinity were measured and precipitates have been investigated by Raman spectroscopy and Atomic Force and Scanning Electron microscopy. Our results showed that the Synechococcus strains exhibited different surface reactivity with total concentration of surface functional groups of 0.342 and 0.350 mM g −1 of dry bact. for freshwater strains, and 0.662 mM g −1 of dry bact. for the marine strain, which are on the same order of magnitude as that reported for bacterial cell surfaces. The marine strain showed the highest CaCO 3 formation rate with Ca 2+ removal of 18 mM g −1 dry bact. compared to 6–7 mM g −1 dry bact. for freshwater strains. The morphological diversity in crystals has been linked to presence of specific functional groups. The linking cell surface properties to crystal morphologies and precipitation rates propose that bacterial surfaces may modulate CaCO 3 formation. Results of this work should allow better understanding of biominiralization in marine and freshwater systems as they define the precipiatation rates in typical range of pH necessary for estimation of CaCO 3 formation by cyanobacterial communities.

The utility of a simple, low-cost detection platform for label-free electrochemical characterization of acetylcholinesterase (AChE) inhibition is demonstrated as a potential tool for screening of small-molecule therapeutic agents for Alzheimer's disease (AD). Technique validation was performed against the standard Ellman's colorimetric assay using the clinically established cholinesterase inhibitor (ChEI), Donepezil (Aricept®). Electrochemical measurements were obtained by differential pulse voltammetry (DPV) performed using a portable potentiostat system for detection of the enzymatic product, thiocholine (TCh), by direct oxidation on unmodified gold screen-printed electrodes. The IC50 profiles for Donepezil measured in vitro were found to be comparable between both colorimetric and electrochemical detection methods for the analysis of purified human erythrocyte-derived AChE (28 ± 7 nM by DPV; 26 ± 8 nM by Ellman's method). The selectivity of this unmodified electrode system was compared to a range of biological sulfur-containing compounds including cysteine, homocysteine, glutathione and methionine as well as ascorbic acid. Preliminary studies also demonstrated the potential applicability of this electrochemical technique for the analysis of Donepezil in crude cholinesterase samples from anterior cortex homogenates of C57BL/6J mice.