Recombinant supercharged polypeptides for safe and efficient heparin neutralization.

Heparin is a widely used anticoagulant agent in the clinic. After application, its anticoagulant effect must be reversed to prevent potential side effects. Protamine sulfate (PS) is the only clinically licensed antidote that has been used for this purpose in the last 80 years, which, however, provokes severe adverse effects, such as systemic hypotension and even death. Herein, we demonstrate the potential of supercharged polypeptides as a promising alternative for protamine sulfate. A series of supercharged polypeptides with multiple positive charges was recombinantly produced, and the heparin-neutralizing performance of the polypeptides was evaluated in comparison with PS. It was found that increasing the number of charges significantly enhanced the ability to neutralize heparin and resist the screening effect induced by salt. In particular, the polypeptide bearing 72 charges (K72) exhibited an excellent heparin-neutralizing behavior that was comparable to that of PS. Further in vivo studies revealed that the heparin-triggered bleeding was almost completely alleviated by K72 while a negligible toxic effect was observed. Therefore, such recombinant supercharged polypeptides might replace protamine sulfate as heparin-reversal agents.

Intradialytic hypotension prediction using covariance matrix-driven whale optimizer with orthogonal structure-assisted extreme learning machine.

Intradialytic hypotension (IDH) is an adverse event occurred during hemodialysis (HD) sessions with high morbidity and mortality. The key to preventing IDH is predicting its pre-dialysis and administering a proper ultrafiltration prescription. For this purpose, this paper builds a prediction model (bCOWOA-KELM) to predict IDH using indices of blood routine tests. In the study, the orthogonal learning mechanism is applied to the first half of the WOA to improve the search speed and accuracy. The covariance matrix is applied to the second half of the WOA to enhance the ability to get out of local optimum and convergence accuracy. Combining the above two improvement methods, this paper proposes a novel improvement variant (COWOA) for the first time. More, the core of bCOWOA-KELM is that the binary COWOA is utilized to improve the performance of the KELM. In order to verify the comprehensive performance of the study, the paper sets four types of comparison experiments for COWOA based on 30 benchmark functions and a series of prediction experiments for bCOWOA-KELM based on six public datasets and the HD dataset. Finally, the results of the experiments are analyzed separately in this paper. The results of the comparison experiments prove fully that the COWOA is superior to other famous methods. More importantly, the bCOWOA performs better than its peers in feature selection and its accuracy is 92.41%. In addition, bCOWOA improves the accuracy by 0.32% over the second-ranked bSCA and by 3.63% over the worst-ranked bGWO. Therefore, the proposed model can be used for IDH prediction with future applications.

Low amplified spontaneous emission threshold from 2-thiophenemethylammonium quasi-2D perovskites via phase engineering.

Quasi-2D Ruddlesden-Popper perovskites attract great attention as an optical gain media in lasing applications due to their excellent optoelectronic properties. Herein, a novel quasi-2D Ruddlesden-Popper perovskite based on 2-thiophenemethylammonium (ThMA) is synthesized by a facile solution-processed method. In addition, an anti-solvent treatment method is proposed to tune the phase distribution, and preferential orientation of quasi-2D (ThMA)2Csn-1PbnBr3n+1 thin films. The large-n-dominated narrow domain distribution improves the energy transfer efficiency from small-n to large-n phases. Also, the highly oriented nanocrystals facilitate the efficient Förster energy transfer, beneficial for the carrier population transfer. Furthermore, a green amplified spontaneous emission with a low threshold of 13.92 µJ/cm2 is obtained and a single-mode vertical-cavity laser with an 0.4 nm linewidth emission is fabricated. These findings provide insights into the design of the domain distribution to realize low-threshold multicolor continuous-wave or electrically driven quasi-2D perovskites laser.

Boosted machine learning model for predicting intradialytic hypotension using serum biomarkers of nutrition.

Intradialytic hypotension (IDH) is a serious complication of hemodialysis (HD), with an incidence of more than 20%. IDH induces ischemic organ damage and even reduces the ultrafiltration and duration of HD sessions. Frequent attacks of IDH are a risk factor for death in HD patients. Malnutrition is common in HD patients and is also associated with mortality. Although the link between IDH episodes and malnutrition has been observed in practice, it has not been supported by the data. To study the relationship, we propose a promising hybrid model called BSCWJAYA_KELM, which is a wrapper feature selection method based on a variant of the JAYA optimization algorithm (SCWJAYA) and Kernel extreme learning machine (KELM). In this paper, we verify the optimization capability of the SCWJAYA algorithm in the model by comparing experiments with some state-of-the-art methods for IEEE CEC2014, IEEE CEC2017, and IEEE CEC2019 benchmark functions. The prediction accuracy of BSCWJAYA_KELM is validated by the public datasets and the HD dataset. In the experiments on the HD dataset, 1940 HD sessions of 178 HD patients are analyzed by the developed BSCWJAYA_KELM model. The key indicators selected from vast amounts of data are serum uric acid, dialysis vintage, age, diastolic pressure, and albumin. The BSCWJAYA_KELM method is a stable and excellent prediction model that can achieve a more accurate prediction of IDH.

Identification of Alzheimer's Disease Progression Stages Using Topological Measures of Resting-State Functional Connectivity Networks: A Comparative Study.

Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely employed to examine brain functional connectivity (FC) alterations in various neurological disorders. At present, various computational methods have been proposed to estimate connectivity strength between different brain regions, as the edge weight of FC networks. However, little is known about which model is more sensitive to Alzheimer's disease (AD) progression. This study comparatively characterized topological properties of rs-FC networks constructed with Pearson correlation (PC), dynamic time warping (DTW), and group information guided independent component analysis (GIG-ICA), aimed at investigating the sensitivity and effectivity of these methods in differentiating AD stages. A total of 54 subjects from Alzheimer's Disease Neuroimaging Initiative (ANDI) database, divided into healthy control (HC), mild cognition impairment (MCI), and AD groups, were included in this study. Network-level (global efficiency and characteristic path length) and nodal (clustering coefficient) metrics were used to capture groupwise difference across HC, MCI, and AD groups. The results showed that almost no significant differences were found according to global efficiency and characteristic path length. However, in terms of clustering coefficient, 52 brain parcels sensitive to AD progression were identified in rs-FC networks built with GIG-ICA, much more than PC (6 parcels) and DTW (3 parcels). This indicates that GIG-ICA is more sensitive to AD progression than PC and DTW. The findings also confirmed that the AD-linked FC alterations mostly appeared in temporal, cingulate, and angular areas, which might contribute to clinical diagnosis of AD. Overall, this study provides insights into the topological properties of rs-FC networks over AD progression, suggesting that FC strength estimation of FC networks cannot be neglected in AD-related graph analysis.

An optimized machine learning framework for predicting intradialytic hypotension using indexes of chronic kidney disease-mineral and bone disorders.

Intradialytic hypotension (IDH) is the most common acute complication in hemodialysis (HD) sessions and is associated with increased morbidity and mortality in HD patients. To prevent the episode of IDH, it is critical to predict its occurrence. Chronic kidney disease-mineral and bone disorders (CKD-MBD) induce cardiac and vascular calcification, which impairs the compensatory mechanisms of blood pressure during HD. In this study, we proposed a feature selection framework called BSWEGWO_KELM to analyze 1940 records from 178 HD patients, which was based on an enhanced grey wolf optimization (GWO) algorithm and the kernel extreme learning machine (KELM). Then, global optimization experiments, together with feature selection experiments on public data sets and HD dataset, were performed to verify the effectiveness of the BSWEGWO_KELM method. The experimental results showed that the established BSWEGWO_KELM had the capability of screening out the key indicators such as dialysis vintage, mean arterial pressure (MAP), alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH). Consequently, BSWEGWO_KELM can be applied as a practical and accurate method to predict IDH.

Effect of sex on the association between arterial partial pressure of oxygen and in-hospital mortality in ICU patients with cardiogenic shock: a retrospective cohort study.

Background: Maintaining tissue perfusion and oxygen supply are essential for cardiogenic shock (CS) treatment. Sex has been reported to be associated with mortality and oxygen use in patients with CS. Males and females respond differently to hypoxia. We designed this cohort study to evaluate the effects of sex on the association between the arterial partial pressure of oxygen (PaO2) and in-hospital mortality. Methods: We used the Medical Information Mart for Intensive Care (MIMIC) IV database for this cohort study. The outcome was in-hospital mortality. The relationship between the PaO2 and in-hospital mortality was compared with sex (via an interaction test) using multivariable Cox regression models. Presence of interaction between PaO2 and sex was tested by using inter interaction terms. Results: A total of 1,772 patients with CS were enrolled in this study. The association between PaO2 and in-hospital mortality appeared to differ between males and females [hazard ratio (HR): 0.997, 95% confidence interval (CI): 0.995-0.999 vs. HR: 1.002, 95% CI: 0.999-1.003, P for interaction =0.002]. We repeated the analyses, based on different PaO2 category (PaO2 <60 mmHg; PaO2 60-100 mmHg; PaO2 >100 mmHg) and the results remained stable, P for interaction =0.008. Conclusions: Sex affects the relationship between PaO2 and in-hospital mortality in CS patients. Our findings may lead to the development of individualized therapies that focus on the use of different target oxygen partial pressures in different sexes to treat patients with CS.

An effective model for predicting serum albumin level in hemodialysis patients.

Patients on hemodialysis (HD) are known to be at an increased risk of mortality. Hypoalbuminemia is one of the most important risk factors of death in HD patients, and is an independent risk factor for all-cause mortality that is associated with cardiac death, infection, and Protein-Energy Wasting (PEW). It is a clinical challenge to elevate serum albumin level. In addition, predicting trends in serum albumin level is effective for personalized treatment of hypoalbuminemia. In this study, we analyzed a total of 3069 records collected from 314 HD patients using a machine learning method that is based on an improved binary mutant quantum grey wolf optimizer (MQGWO) combined with Fuzzy K-Nearest Neighbor (FKNN). The performance of the proposed MQGWO method was evaluated using a series of experiments including global optimization experiments, feature selection experiments on open data sets, and prediction experiments on an HD dataset. The experimental results showed that the most critical relevant indicators such as age, presence or absence of diabetes, dialysis vintage, and baseline albumin can be identified by feature selection. Remarkably, the accuracy and the specificity of the method were 98.39% and 96.77%, respectively, demonstrating that this model has great potential to be used for detecting serum albumin level trends in HD patients.

Target Controllability of Two-Layer Multiplex Networks Based on Network Flow Theory.

In this paper, we consider the target controllability of two-layer multiplex networks, which is an outstanding challenge faced in various real-world applications. We focus on a fundamental issue regarding how to allocate a minimum number of control sources to guarantee the controllability of each given target subset in each layer, where the external control sources are limited to interact with only one layer. It is shown that this issue is essentially a path cover problem, which is to locate a set of directed paths denoted as P and cycles denoted as C to cover the target sets under the constraint that the nodes in the second layer cannot be the starting node of any element in P , and the number of elements in P attains its minimum. In addition, the formulated path cover problem can be further converted into a maximum network flow problem, which can be efficiently solved by an algorithm called maximum flow-based target path-cover (MFTP). We rigorously prove that MFTP provides the minimum number of control sources for guaranteeing the target controllability of two-layer multiplex networks. It is anticipated that this paper would serve wide applications in target control of real-life networks.

Improved rice cooking approach to maximise arsenic removal while preserving nutrient elements.

Inorganic arsenic (iAs) is a group 1 carcinogen, and consumption of rice can be a significant pathway of iAs exposure in the food chain. Although there are regulations in place to control iAs for marketed rice in some countries, additional measures are explored to remove arsenic from rice. Due to the surface-bound and soluble nature of iAs, previous studies have shown that it can be removed to a significant extent using different cooking methods. Towards this goal we modified and tested the absorption method in combination with four home-friendly cooking treatments (UA = unwashed and absorbed, WA = washed and absorbed, PSA = pre-soaked and absorbed, and PBA = parboiled and absorbed) using both brown and white rice (3 types each). The nutrient elements were measured using ICP-MS and arsenic speciation was carried out using LC-ICP-MS. Overall, our results show that PBA was the optimum approach assessed, removing 54% and 73% of inorganic arsenic (iAs) for brown and white rice respectively, raising the margin of exposure (MOE) by 3.7 for white rice and 2.2 times for brown rice, thus allowing the consumption of rice more safely for infants, children and adults. Other cooking treatments were effective in reducing the iAs concentration from white rice only. Here we also report changes in selected nutrient elements (P, K, Mg, Zn and Mn) which are relatively abundant in rice. In general, the treatments retained more nutrients in brown rice than white rice. No significant loss of Zn was observed from both rice types and the loss of other nutrients was similar or less than in comparison to reported losses from rice cooked in excess water in the literature. We conclude that PBA is a promising technique and further research is needed by including different regional rice types and water quality levels.

Effects of long-term cadmium exposure on trehalose metabolism, growth, and development of Aedes albopictus (Diptera: Culicidae).

Trehalose is the major blood sugar in insects; it not only serves as an energy source but also plays important roles in physiological responses to adverse conditions. However, only a few studies have explored the effects of heavy metal exposure stress on trehalose metabolism in insects. Therefore, in this study, we examined the effects of cadmium stress on changes in trehalose metabolism in Aedes albopictus. Three concentrations of cadmium (0.005, 0.01, and 0.1 mg/L) were selected for evaluation of long-term stress in Ae. albopictus (from eggs to adults); Ae. albopictus in double-distilled water was used as the control group. The trehalose and glucose contents, trehalase activity, and trehalose metabolism-related gene expression were determined. The effects of long-term cadmium exposure on growth, development, and reproduction were also assessed. Trehalose contents were increased, whereas glucose contents and trehalase activity were decreased in Ae. albopictus following long-term exposure to low concentrations of cadmium compared with those in untreated individuals. Moreover, the expression of trehalose-6-phosphate synthase was upregulated, and that of trehalase was downregulated, indicating that Ae. albopictus may enhance trehalose synthesis to resist cadmium stress. Cadmium exposure also caused Ae. albopictus individuals to become smaller with a longer developmental duration, whereas both reproduction and hatching rates of the offspring were decreased compared with those in the control group. Our findings demonstrated that cadmium exposure affected the morphology, physiology, and biochemistry of Ae. albopictus. These findings also confirmed the role of trehalose in the response of Ae. albopictus to cadmium stress, providing insights into the effects of heavy metal stress on trehalose metabolism in an insect model.

Clinical experience with tigecycline in the treatment of hospital-acquired pneumonia caused by multidrug resistant Acinetobacter baumannii.

BACKGROUND: Tigecycline, with broad in vitro antibacterial activity, has been widely used off-label for nosocomial pneumonia caused by multi-drug resistant Acinetobacter baumannii (MDRAB). However, many concerns have been raised about the efficacy of tigecycline treatment as the inconsistent results from previous clinical studies. METHODS: This retrospective study evaluated the outcome of adult patients with monomicrobial MDRAB nosocomial pneumonia treated with tigecycline between 2015 and 2017. RESULTS: A total of 77 patients was eligible for this study, and the overall clinical success and 30-day survival rates were 70.03 and 70.13%, respectively, however, the microbiological eradication rate was relatively low (48%). Multivariate analysis indicated that shorter duration of tigecycline use associated with increased clinical failure, whereas higher CURB65 scores, mechanical ventilation and tigecycline resistant to MDRAB have significant association with 30-day mortality. CONCLUSIONS: Our results suggest that tigecycline is one of the potential choices for the treatment of hospital-acquired pneumonia caused by MDRAB, especially with a MIC≤2 mg/L. In addition, a longer duration of tigecycline treatment may be required to insure better clinical outcomes.

Protective effects of lncRNA H19 silence against hypoxia-induced injury in PC-12 cells by regulating miR-28.

LncRNA H19 has been widely reported to be up-regulated upon hypoxia. We aimed to uncover the function and mechanism of lncRNA H19 in hypoxic PC-12 cells. Neural-like PC-12 cells were exposed to hypoxia to stimulating an in vitro model of hypoxic brain damage. The expression levels of lncRNA H19 in PC-12 cells were altered by transfection, then cell viability, migration and apoptosis were assessed respectively. Moreover, the cross-regulation between lncRNA H19, miR-28 and SP1 was studied to reveal one of the possible mechanisms of lncRNA H19's function. We found that hypoxia induced remarkable decreases in cell viability and migration, and induced a notable increase in cell apoptosis. Hypoxia-induced cell damage was aggravated by lncRNA H19 overexpression, while was alleviated by lncRNA H19 silence. miR-28 was negatively regulated by lncRNA H19, and SP1 was a target gene of miR-28. Furthermore, lncRNA H19 down-regulated miR-28 expression, which in turn preventing SP1 from degradation by miR-28, and ultimately deactivated PDK/AKT and JAK/STAT signaling pathways. In conclusion, our research demonstrated a protective role of lncRNA H19 silence in hypoxic PC-12 cells. A possible mechanism of which lncRNA H19 functioned to PC-12 cells was that lncRNA H19 down-regulated miR-28 expression, preventing SP1 exhausted by miR-28.

Reduction of Intrinsic Electron Emittance from Photocathodes Using Ordered Crystalline Surfaces.

The generation of intense electron beams with low emittance is key to both the production of coherent x rays from free electron lasers, and electron pulses with large transverse coherence length used in ultrafast electron diffraction. These beams are generated today by photoemission from disordered polycrystalline surfaces. We show that the use of single crystal surfaces with appropriate electronic structures allows us to effectively utilize the physics of photoemission to generate highly directed electron emission, thus reducing the emittance of the electron beam being generated.

Hepatitis B Virus Infection Rate and Distribution in Chinese Systemic Lupus Erythematosus Patients.

BACKGROUND: The aim of this study was to investigate the hepatitis B virus (HBV) infection rate in systemic lupus erythematosus (SLE) patients in China, and to determine the age and sex distribution. MATERIAL AND METHODS: A total of 3981 SLE patients diagnosed in The First Affiliated Hospital of Sun Yat-sen University from January 1996 to December 2011 were retrospectively investigated for evaluation of the HBV infection rate. The HBV infection rate and the positive rate of hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) were standardized to national census data in 2000 and compared with the prevalence found in the 2006 national survey. RESULTS: The age and sex standardized HBV infection rate in Chinese SLE patients was 3.3%. The age and sex standardized positive rate of HBsAb and HBcAb were 58.1% and 26.1%, respectively. As compared with the prevalence from the 2006 national survey, the HBV infection rate and the positive rate of HBcAb were lower and the positive rate of HBsAb was higher in SLE patients aged 15-49 years old compared to peers in the general population. There was no difference in HBV infection rate between males and females (4.2% vs. 2.8%, p=0.088) in SLE patients. CONCLUSIONS: The HBV infection rate was relatively lower in SLE patients compared with the general population, but there was no difference in pediatric patients or patients aged above 50 years old. Unlike in the general population, the HBV infection rate had no statistical differences between males and females in SLE patients.

A stigmatic ultraviolet-visible monochromator for use with a high brightness laser driven plasma light source.

Laser driven plasma light sources offer highly intense output in the UV-visible region combined with a source size as small as 100 µm. In order to effectively use the small source size in high brightness applications, a stigmatic monochromator and focusing system must be used. Here we describe a simple brightness preserving optical system that should be useful across a broad range of applications. The output flux of this system is between 6 × 10(11) ph∕s and 4 × 10(12) ph∕s with a spectra resolution of 1.7 nm and field spot size of 0.1 mm from the UV to the VIS spectra range.

Magnetic phases of cobalt atomic clusters on tungsten.

First-principle calculations are employed to show that the magnetic structure of small atomic clusters of Co, formed on a crystalline W(110) surface and containing 3-12 atoms, strongly deviates from the usual stable ferromagnetism of Co in other systems. The clusters are ferri-, ferro- or non-magnetic, depending on cluster size and geometry. We determine the atomic Co moments and their relative alignment, and show that antiferromagnetic spin alignment in the Co clusters is caused by hybridization with the tungsten substrate and band filling. This is in contrast with the typical strong ferromagnetism of bulk Co alloys, and ferromagnetic coupling in Fe/W(110) clusters.

Surface state engineering of molecule-molecule interactions.

Engineering the electronic structure of organics through interface manipulation, particularly the interface dipole and the barriers to charge carrier injection, is of essential importance to improve organic devices. This requires the meticulous fabrication of desired organic structures by precisely controlling the interactions between molecules. The well-known principles of organic coordination chemistry cannot be applied without proper consideration of extra molecular hybridization, charge transfer and dipole formation at the interfaces. Here we identify the interplay between energy level alignment, charge transfer, surface dipole and charge pillow effect and show how these effects collectively determine the net force between adsorbed porphyrin 2H-TPP on Cu(111). We show that the forces between supported porphyrins can be altered by controlling the amount of charge transferred across the interface accurately through the relative alignment of molecular electronic levels with respect to the Shockley surface state of the metal substrate, and hence govern the self-assembly of the molecules.

Temperature dependence of metal-organic heteroepitaxy.

The nucleation and growth of 2D layers of tetraphenyl porphyrin molecules on Ag(111) are studied with variable-temperature scanning tunneling microscopy. The organic/metal heteroepitaxy occurs by strict analogy to established principles for metal heteroepitaxy. A hierarchy of energy barriers for diffusion on terraces and along edges and around corners of adislands is established. The temperature is key to activating these barriers selectively, thus determining the shape of the organic aggregates, from a fractal shape at lower temperatures to a compact shape at higher temperatures. The energy barriers for the terrace diffusion of porpyrins and the molecule-molecule binding energy were determined to be 30 meV < E(terrace) < 60 and 130 meV < E(diss) < 160 meV, respectively, from measurements of island sizes as a function of temperature. This study provides an experimental verification of the validity of current models of epitaxy for the heteroepitaxy of organics and is thus expected to help establish design principles for complex metal-organic hybrid structures.