Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacological evaluation of MRAP proteins on Xenopus neural melanocortin signaling

Melanocortin‐3 receptor (MC3R) and melanocortin‐4 receptor (MC4R), two neural G protein‐coupled receptors are known to be functionally critical for energy balance in vertebrates. As allosteric regulators of melanocortin receptors, melanocortin accessory proteins (MRAPs) are also involved in energy homeostasis. The interaction of MRAPs and melanocortin signaling was previously shown in mammals and zebrafish, but nothing had been reported in amphibians. As the basal class of tetrapods, amphibians occupy a phylogenetic transition between teleosts and terrestrial animals. Here we examined the evolutionary conservation of MC3R, MC4R, and MRAPs between diploid Xenopus tropicalis (xt‐) and other chordates and investigated the pharmacological regulatory properties of MRAPs on the neural MC3R and MC4R signaling. Our results showed that xtMRAP and xtMRAP2 both exerted robust potentiation effect on agonist (α‐MSH and adrenocorticotropin [ACTH]) induced activation and modulated the basal activity and cell surface translocation of xtMC3R and xtMC4R. In addition, the presence of two accessory proteins could convert xtMC3R and xtMC4R into ACTH‐preferred receptors. These findings suggest that the presence of MRAPs exhibits fine control over the pharmacological activities of the neuronal MC3R and MC4R signaling in the Xenopus tropicalis, which is physiologically relevant with the complicated transition of feeding behaviors during their life history.
Linker-Free Magnetite-Decorated Gold Nanoparticles (Fe3O4-Au): Synthesis, Characterization, and Application for Electrochemical Detection of Arsenic (III)

Linker-free magnetite nanoparticles (Fe3O4NPs)-decorated gold nanoparticles (AuNPs) were grown using a new protocol that can be used as a new platform for synthesis of other intact metal–metal oxide nanocomposites without the need for linkers. This minimizes the distance between the metal and metal oxide nanoparticles and ensures the optimum combined effects between the two material interfaces. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy confirmed the successful synthesis of the Fe3O4-Au nanocomposite, without any change in the magnetite phase. Characterization, using transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy, revealed the composite to consist of AuNPs of 70 ± 10 nm diameter decorated with tiny 10 ± 3 nm diameter Fe3O4NPs in Au:Fe mass ratio of 5:1. The prepared Fe3O4-Au nanocomposite was embedded in ionic liquid (IL) and applied for the modification of glassy carbon electrode (GCE) for the electrochemical detection of As(III) in water. By combining the excellent catalytic properties of the AuNPs with the high adsorption capacity of the tiny Fe3O4NPs towards As(III), as well as the good conductivity of IL, the Fe3O4-Au-IL nanocomposite showed excellent performance in the square wave anodic stripping voltammetry detection of As(III). Under the optimized conditions, a linear range of 1 to 100 μg/L was achieved with a detection limit of 0.22 μg/L (S/N = 3), and no interference from 100-fold higher concentrations of a wide variety of cations and anions found in water. A very low residual standard deviation of 1.16% confirmed the high precision/reproducibility of As(III) analysis and the reliability of the Fe3O4-Au-IL sensing interface. Finally, this proposed sensing interface was successfully applied to analyzing synthetic river and wastewater samples with a 95–101% recovery, demonstrating excellent accuracy, even in complex synthetic river and wastewater samples containing high concentrations of humic acid without any sample pretreatments.
Targeting IGF Perturbs Global Replication through Ribonucleotide Reductase Dysfunction

This study identifies regulation of ribonucleotide reductase function and dNTP supply by IGFs and demonstrates that IGF axis blockade induces replication stress and reciprocal co-dependence on ATM. Inhibition of IGF receptor (IGF1R) delays repair of radiation-induced DNA double-strand breaks (DSB), prompting us to investigate whether IGF1R influences endogenous DNA damage. Here we demonstrate that IGF1R inhibition generates endogenous DNA lesions protected by 53BP1 bodies, indicating under-replicated DNA. In cancer cells, inhibition or depletion of IGF1R delayed replication fork progression accompanied by activation of ATR–CHK1 signaling and the intra-S-phase checkpoint. This phenotype reflected unanticipated regulation of global replication by IGF1 mediated via AKT, MEK/ERK, and JUN to influence expression of ribonucleotide reductase (RNR) subunit RRM2. Consequently, inhibition or depletion of IGF1R downregulated RRM2, compromising RNR function and perturbing dNTP supply. The resulting delay in fork progression and hallmarks of replication stress were rescued by RRM2 overexpression, confirming RRM2 as the critical factor through which IGF1 regulates replication. Suspecting existence of a backup pathway protecting from toxic sequelae of replication stress, targeted compound screens in breast cancer cells identified synergy between IGF inhibition and ATM loss. Reciprocal screens of ATM-proficient/deficient fibroblasts identified an IGF1R inhibitor as the top hit. IGF inhibition selectively compromised growth of ATM-null cells and spheroids and caused regression of ATM-null xenografts. This synthetic-lethal effect reflected conversion of single-stranded lesions in IGF-inhibited cells into toxic DSBs upon ATM inhibition. Overall, these data implicate IGF1R in alleviating replication stress, and the reciprocal IGF:ATM codependence we identify provides an approach to exploit this effect in ATM-deficient cancers. Significance: This study identifies regulation of ribonucleotide reductase function and dNTP supply by IGFs and demonstrates that IGF axis blockade induces replication stress and reciprocal codependence on ATM. Graphical Abstract: http://cancerres.aacrjournals. org/content/canres/81/8/2128/F1.large. jpg. Graphical Abstract
Clinical application values of neutrophil-to-lymphocyte ratio in intracranial aneurysms

Inflammation plays an important role in the pathogenesis and growth of intracranial aneurysms (IAs). We investigated the clinical value of the neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic subclinical inflammation in patients with IAs. Consecutive patients with IAs who underwent endovascular treatment (EVT) were enrolled in the study. The evaluation indicators were aneurysm size and rupture, a poor outcome at 3 to 6 months, and delayed cerebral ischemia (DCI) during hospitalization. In total, 532 patients with IAs underwent EVT (mean age, 54.0 years; 62.4% female). Among patients with ruptured IAs, those with a higher NLR had an increased risk of a poor outcome at 3 to 6 months and DCI during hospitalization than those with a lower NLR. A higher NLR was significantly more strongly associated with the size of unruptured aneurysms and aneurysm rupture than a lower NLR. The NLR and C-reactive protein concentration showed similar predictive ability for aneurysm size and treatment prognosis. The NLR was lower at discharge than admission for patients with ruptured IAs and DCI. An elevated NLR was significantly associated with the size of unruptured IAs, an increased risk of a poor outcome, and DCI in patients with ruptured IAs.
Epidemiology of United States Inpatient Open Globe Injuries from 2009-2015

ABSTRACT Purpose To study the epidemiology of inpatient open globe injuries (OGI) in the United States (US). Methods This was a retrospective cohort study of patients with a primary diagnosis of OGI in the National Inpatient Sample (NIS) from 2009 to 2015. Sociodemographic characteristics, including age, gender, race, ethnicity, insurance, and income were stratified for comparison. Annual prevalence rates were calculated using 2010 US Census data. Statistical analysis included Chi-square tests, ANCOVA, and Tukey tests. Results A total of 6,821 US inpatient hospital discharge records met inclusion/exclusion criteria. The estimated national prevalence of OGI during the 5-year period from 2009 to 2015 was 34,061 (95% confidence interval [CI] 31,445–36,677). The overall annual prevalence rate was 1.58 per 100,000 per year (CI 1.56–1.59). Overall, average annual prevalence rates were highest among patients 85 years or older (7.72, CI 6.95–8.49), on Medicare (3.92, CI 3.84–4.00), males (2.28, CI 2.25–2.30), African Americans (2.38, CI 2.32–2.44), and Native Americans (1.80, CI 1.62–2.00). OGI rates were lowest among Whites (1.21, CI 1.19–1.22), females (0.89, CI 0.87–0.91), those with private insurance (0.84, CI 0.82–0.86), and Asians (0.69, CI 0.64–0.74). Being in the lowest income quartile was a risk factor for OGI (p < .05). Conclusions Inpatient OGIs disproportionately affected those over 85, young males, elderly females, patients of African-American descent, on Medicare, and in the lowest income quartile. Additionally, children and young children had lower rates of OGI compared to adolescents. Further studies should delineate causes for socioeconomic differences in OGI rates to guide future public health measures.
Conformational Landscape of Cytochrome P450 Reductase Interactions

Oxidative reactions catalyzed by Cytochrome P450 enzymes (CYPs), which constitute the most relevant group of drug-metabolizing enzymes, are enabled by their redox partner Cytochrome P450 reductase (CPR). Both proteins are anchored to the membrane of the endoplasmic reticulum and the CPR undergoes a conformational change in order to interact with the respective CYP and transfer electrons. Here, we conducted over 22 microseconds of molecular dynamics (MD) simulations in combination with protein–protein docking to investigate the conformational changes necessary for the formation of the CPR–CYP complex. While some structural features of the CPR and the CPR–CYP2D6 complex that we highlighted confirmed previous observations, our simulations revealed additional mechanisms for the conformational transition of the CPR. Unbiased simulations exposed a movement of the whole protein relative to the membrane, potentially to facilitate interactions with its diverse set of redox partners. Further, we present a structural mechanism for the susceptibility of the CPR to different redox states based on the flip of a glycine residue disrupting the local interaction network that maintains inter-domain proximity. Simulations of the CPR–CYP2D6 complex pointed toward an additional interaction surface of the FAD domain and the proximal side of CYP2D6. Altogether, this study provides novel structural insight into the mechanism of CPR–CYP interactions and underlying conformational changes, improving our understanding of this complex machinery relevant for drug metabolism.
Hall resistivity in the heavy Fermion normal state of up to 26 T

The Hall resistivity has been measured in single crystal at low temperatures (0.1-4.2 K) for magnetic field -axis up to 26 T. For temperatures , the Hall coefficient goes asymptotically to zero, indicating a compensated-metal ground state. Since the Hall resistivity does not show an anomaly at the metamagnetic crossover of 20 T in the Fermi-liquid state below 0.8 K, a drastic change of the Fermi surface is unlikely at the crossover. A change of the skew scattering contribution to the Hall effect has been observed around 6 and 2 K, i.e. near respectively the magnetic ordering temperature and the temperature below which the Fermi-liquid state appears.
Functionality of bovine milk proteins and other factors in foaming properties of milk: a review

Abstract For many dairy products such as cappuccino-style beverages, the top foam layer determines the overall product quality (e.g. their appearance, texture, mouthfeel and coffee aroma release rate) and the consumer acceptance. Proteins in milk are excellent foaming agents, but the foaming properties of milk are greatly affected by several factors such as the protein content, ratio of caseins to whey proteins, casein micelle size, pH, minerals, proteolysis, presence of low molecular weight compounds (lipids and their hydrolyzed products) and high molecular weight compounds (polysaccharides); milk processing conditions (e.g. homogenization, heat treatment and aging); and foaming method and temperature. These factors either induce changes in the molecular structure, charge and surface activity of the milk proteins; or interfere and/or compete with milk proteins in the formation of highly viscoelastic film to stabilize the foam. Some factors affect the foamability while others determine the foam stability. In this review, functionality of milk proteins in the production and stabilization of liquid foam, under effects of these factors is comprehensively discussed. This will help to control the foaming process of milk on demand for a particular application, which still is difficult and challenging for researchers and the dairy industry.
A Pathophysiology of Type 2 Diabetes Unrelated to Metabolic Syndrome.

OBJECTIVE Clinically, type 2 diabetes mellitus (T2DM) is heterogeneous, but the prevailing pathophysiologic hypothesis nevertheless contends that components of metabolic syndrome are central to all cases of T2DM. Here, we reevaluated this hypothesis. RESEARCH DESIGN AND METHODS We conducted a cross-sectional analysis of 138 women from the monocenter, post gestational diabetes study PPSDiab, 73 of which had incident prediabetes or T2DM. Additionally, we examined all the 412 incident cases of T2DM in phases 3-9 of the Whitehall II Study in comparison to healthy controls. Our analysis included a medical history, anthropometrics, oral glucose tolerance testing, and laboratory chemistry in both studies. Additional analyses from the PPSDiab Study consisted of cardiopulmonary exercise testing, magnetic resonance imaging, auto-antibody testing, and the exclusion of glucokinase maturity-onset diabetes of the young. RESULTS We found that 33 (45%) of the women with prediabetes or T2DM in the PPSDiab Study displayed no components of metabolic syndrome. They reached no point for metabolic syndrome in the NCEP ATP3 score other than hyperglycemia and, moreover, had levels of liver fat content, plasma triglycerides, hdl cholesterol, c-reactive protein, and blood pressure that were comparable to healthy controls. In the Whitehall II Study, 62 (15%) of the incident T2DM cases fulfilled the same criteria. In both studies, these cases without metabolic syndrome revealed insulin resistance and inadequately low insulin secretion. CONCLUSIONS Our results contradict the hypothesis that components of metabolic syndrome are central to all cases of T2DM. Instead, they suggest the common occurrence of a second, unrelated pathophysiology.
Effects of trace elements on phosphatase activity in soils

Studies to evaluate the effects on the activity of acid and alkaline phosphatases of 20 trace elements showed that all trace elements inhibit the activity of phosphatases in soils. Results showed that the relative effectiveness of the trace elements in inhibition of phosphatase activity depends on the soil. When the trace elements were compared by using 25 . mu.mole/g soil, the average inhibition of acid phosphatase in three soils showed that Hg(II), As(V), W(VI), and Mo(VI) were the most effective (average inhibition >50%) and that Ba(II), Co(II), and As(III) were the least effective (average inhibition <10%) inhibitors. Other elements that inhibited acid phosphatase activity in soils were: Cu(I), Ag(I), Cd(II), Cu(II), Zn(II), Mn(II), Sn(II), Ni(II), Pb(II), Fe(II), Cr(III), Fe(III), B(III), Al(III), V(IV), and Se(IV); their degrees of effectiveness varied in the three soils used. The most effective inhibitors of alkaline phosphatase activity in soils were Ag(I), Cd(II), V(IV), and As(V). All the trace elements that inhibited acid phosphatase activity also inhibited alkaline phosphatase activity. The order of effectiveness of the trace elements in inhibition of acid phosphatase activity was different from that of inhibition of alkaline phosphatase activity. Generally, the inhibitory effect of trace elements was less in the presence ofmore » 2.5 . mu.mole/g soil than in the presence of 25 . mu.mole/g soil. In addition to the effect of trace elements, phosphate ion inhibited acid and alkaline phosphatase activities in soils. Related anions such as NO/sub 2//sup -/, NO/sub 3//sup -/, Cl/sup -/, and SO/sup 2 -//sub 4/ were not inhibitory in the presence and absence of buffer. « less
WeChat as a Platform for Baduanjin Intervention in Patients With Stable Chronic Obstructive Pulmonary Disease in China: Retrospective Randomized Controlled Trial

Background Pulmonary rehabilitation is a crucial part of the nonpharmacological treatment of stable chronic obstructive pulmonary disease (COPD), but management remains problematic. WeChat could serve as a useful tool in patient management. Baduanjin is a popular exercise in China that is usually applied in pulmonary rehabilitation, which has been confirmed to be effective in improving lung function and life quality. Objective This study aimed to explore the efficiency of WeChat in the management of Baduanjin exercise in COPD patients. Methods A total of 200 patients from the respiratory department of Putuo Hospital participated in the Baduanjin rehabilitation project from September 2018 to October 2019, and were randomly assigned to the WeChat and control groups and followed up using the WeChat platform or telephone for 12 weeks. The frequency of Baduanjin exercise, lung function (percentage of forced expiratory volume in 1 second predicted, FEV1% predicted), and COPD assessment test (CAT) scores were collected and compared between the two groups. The number of message exchanges and a satisfaction survey on the WeChat platform were used to assess the feasibility of WeChat management outside the hospital. Results The Baduanjin exercise frequency significantly differed between the control group and WeChat group (F=33.82, P<.001) and across various time points (F=214.87, P<.001). After the follow-up on WeChat, there were fewer patients not performing Baduanjin exercise. The FEV1% predicted value significantly differed before and after Baduanjin exercise in the control group (Z=−3.686, P<.001) and the WeChat group (Z=−6.985, P<.001). A significant difference in the FEV1% predicted value was observed after Baduanjin exercise between the two groups (Z=−3.679, P<.001). The CAT score significantly differed before and after Baduanjin exercise in the control group (Z=−4.937, P<.001) and the WeChat group (Z=−5.246, P<.001). A significant difference in the CAT score was observed after Baduanjin exercise between the two groups (Z=−5.246, P<.001). The number of completed Baduanjin exercises, lung function, and CAT scores in active patients were higher than those in nonactive patients. All satisfaction survey items were scored with more than 4 points. Among the items, the highest score (mean 4.54, SD 0.77) was for continued WeChat management, followed by the effective management of Baduanjin exercise (mean 4.46, SD 0.87). The patients in the WeChat group showed much higher enthusiasm for and compliance with Baduanjin exercise, resulting in better life quality and lung function. The patients were very satisfied with the WeChat management because of the obvious curative effect and home feeling. Conclusions The WeChat platform provided a feasible, effective, and sustainable management plan for Baduanjin rehabilitation. Trial Registration Chinese Clinical Trial Registry ChiCTR1900028248; http://www.chictr. org.cn/showprojen.aspx? proj=46995
Diagnostic features of SARS‐COVID‐2‐positive patients: A rapid review and meta‐analysis

Abstract Aims To identify the main diagnostic features of SARS‐CoV‐2‐positive patients at the time of hospitalisation and their prevalence. Background Since the COVID‐19 outbreak in China in December of 2019, several studies attempted to identify the epidemiological, viral and clinical characteristics of SARS‐CoV‐2. Given the rapid widespread transmission of the COVID‐19 disease worldwide, a more comprehensive and up‐to‐date understanding of its features is needed to better inform nurses, clinicians and public health policy makers. Methods A rapid review and meta‐analysis were carried out to identify the main diagnostic features of SARS‐CoV‐2‐positive patients at the time of hospitalisation. All case series, cross‐sectional, case–control and cohort studies published from 01/01/2020 till 30/06/2020 in English and Chinese that stated all or at least two of the outcomes of interest (clinical features, laboratory and radiological findings) were included. We performed a random‐effects model meta‐analysis to calculate pooled prevalence and 95% confidence intervals. Conduction of the review adheres to the PRISMA checklist. Results 21 studies involving 8837 patients were included in the quantitative synthesis. Fever, cough and fatigue were the most common clinical features, while the most relevant laboratory abnormalities at the time of hospitalisation were lymphopenia, elevated C‐reactive protein and lactate dehydrogenase. CT images showed a bilateral lung involvement, with ground glass infiltrates and patchy shadows on most patients. Conclusion This review provides an up‐to‐date synthesis of main diagnostic features of SARS‐CoV‐2‐positive patients at the time of hospitalisation. Relevance to Clinical Practice Our findings could provide guidance for nurses and clinicians to early identification of positive patients at the time of the hospitalisation through a complete definition of main clinical features, laboratory and CT findings.
Modulation of Electroosmotic Flow Strength with End-Grafted Polymer Chains

We report on coarse-grained molecular dynamics simulations of the electroosmotic flow (EOF) of an electrolyte confined in a cylindrical, nanoscopic pore. We present results for the equilibrium distribution of fluid particles and ions in the electrolyte, and we show that our computational model reproduces the well-known characteristics of EOF in the steady-state regime, in particular the well-known pluglike character of this type of flow when the Debye length is small compared to the characteristic channel size. Upon adding a number of neutral, grafted polymer chains on the interior capillary surface, we find a significant reduction of the magnitude of the EOF. We characterize the polymer coatings and further show that the observed reduction in flow strength, as a function of polymer surface coverage, is in quantitative agreement with recent theoretical scaling predictions regarding the coupling of EOF and polymer coatings in small Debye length systems. As far as we know, our results constitute the first i.