Miracle-dz/UniFAR-FTUs huggingface dataset:
Improvement of Skin Penetration, Antipollutant Activity and Skin Hydration of 7,3′,4′-Trihydroxyisoflavone Cyclodextrin Inclusion Complex

As is known, many antioxidants from plant extracts have been used as additives in skincare products to prevent skin damage following overexposure to environmental pollutants. 7,3′,4′-trihydroxyisoflavone (734THIF), an isoflavone compound, possesses various biological activities, including antioxidant, antityrosinase, photodamage protection, and anticancer effects. Unfortunately, 734THIF has poor water solubility, which limits its skin penetration and absorption, and subsequently influences its biological activity. The aim of the present study was to investigate the mechanisms for the improvement in water solubility and skin penetration of 2-hydroxypropyl-β-cyclodextrin (HPBCD) inclusion complex with 734THIF (5-7HP). We also determined its photostability, antipollutant activity in HaCaT keratinocytes, and moisturizing effect in human subjects. Our results showed that 734THIF was embedded into the lipophilic inner cavity of HPBCD and its water solubility and skin penetration were thereby improved through amorphous transformation, surface area enhancement, and hydrogen bonding formation between 734THIF and HPBCD. In addition, 5-7HP inhibited PM-induced ROS generation and then downregulated ROS-mediated COX-2 and MMP9 production and AQP-3 consumption by inhibiting the phosphorylation of MAPKs. Consequently, we suggest that 5-7HP is a safe and photostable topical ingredient to enhance the skin penetration of 734THIF and skin hydration, and therefore 5-7HP may be used as an antipollutant additive in skin care products.
Prognostic impact of alkaline phosphatase for in-hospital mortality in patients with acute coronary syndrome: a prospective cohort study in China

Objectives Alkaline phosphatase (ALP) can promote vascular calcification, but the association between ALP and in-hospital mortality in patients with acute coronary syndrome (ACS) is not well defined. Design A prospective cohort study. Setting and participants A total of 6368 patients with ACS undergoing percutaneous coronary intervention (PCI) from 1 January 2010 to 31 December 2017 were analysed. Main outcome measures In-hospital mortality was used in this study. Results ALP was analysed both as a continuous variable and according to three categories. After multivariable adjustment, in-hospital mortality was significantly higher in Tertile 3 group (ALP＞85 U/L) (OR: 2.399, 95% CI 1.080 to 5.333, p=0.032), compared with other two groups (Tertile 1: ＜66 U/L; Tertile 2: 66–85 U/L). When ALP was evaluated as a continuous variable, after multivariable adjustment, the ALP level was associated with an increased risk of in-hospital mortality (OR: 1.011, 95% CI 1.002 to 1.020, p=0.014). C-statistic of ALP for predicting in-hospital mortality was 0.630 (95% CI 0.618 to 0.642, p=0.001). The cut-off value was 72 U/L with a sensitivity of 0.764 and a speciﬁcity of 0.468. However, ALP could not significantly improve the prognostic performance of Global Registry of Acute Coronary Events (GRACE) score (GRACE score+ALP vs GRACE score: C-statistic: z=0.485, p=0.628; integrated discrimination improvement: 0.014, p=0.056; net reclassification improvement: 0.020, p=0.630). Conclusions In patients with ACS undergoing PCI, ALP was an independent predictor of in-hospital mortality. But it could not improve the prognostic performance of GRACE score.
Structural characterization of Class 2 OLD family nucleases supports a two-metal catalysis mechanism for cleavage

Abstract Overcoming lysogenization defect (OLD) proteins constitute a family of uncharacterized nucleases present in bacteria, archaea, and some viruses. These enzymes contain an N-terminal ATPase domain and a C-terminal Toprim domain common amongst replication, recombination, and repair proteins. The in vivo activities of OLD proteins remain poorly understood and no definitive structural information exists. Here we identify and define two classes of OLD proteins based on differences in gene neighborhood and amino acid sequence conservation and present the crystal structures of the catalytic C-terminal regions from the Burkholderia pseudomallei and Xanthamonas campestris p.v. campestris Class 2 OLD proteins at 2.24 Å and 1.86 Å resolution respectively. The structures reveal a two-domain architecture containing a Toprim domain with altered architecture and a unique helical domain. Conserved side chains contributed by both domains coordinate two bound magnesium ions in the active site of B. pseudomallei OLD in a geometry that supports a two-metal catalysis mechanism for cleavage. The spatial organization of these domains additionally suggests a novel mode of DNA binding that is distinct from other Toprim containing proteins. Together, these findings define the fundamental structural properties of the OLD family catalytic core and the underlying mechanism controlling nuclease activity.
Emerging role of cardiac computed tomography in heart failure

Despite medical advancements, the prognosis of patients with heart failure remains poor. While echocardiography and cardiac magnetic resonance imaging remain at the forefront of diagnosing and monitoring patients with heart failure, cardiac computed tomography (CT) has largely been considered to have a limited role. With the advancements in scanner design, technology, and computer processing power, cardiac CT is now emerging as a valuable adjunct to clinicians managing patients with heart failure. In the current manuscript, we review the current applications of cardiac CT to patients with heart failure and also the emerging areas of research where its clinical utility is likely to extend into the realm of treatment, procedural planning, and advanced heart failure therapy implementation.
Vaccine or field strains: the jigsaw pattern of infectious bronchitis virus molecular epidemiology in Poland

ABSTRACT Infectious bronchitis (IB), caused by infectious bronchitis virus (IBV), account for severe economic losses in the poultry industry. The continuous emergence of a multitude of IBV variants poses many challenges for its diagnosis and control, and live attenuated vaccines, despite their routine use, still plays a significant role in driving IBV evolution, further complicating the epidemiological scenario. Unfortunately, the impact of different vaccination strategies on IB control, epidemiology, and diagnosis has rarely been investigated. This work presents the results of a large-scale diagnostic survey performed in Poland to study IBV molecular epidemiology and how vaccination may affect the viral circulation in the field. To this purpose, 589 samples were collected between May 2017 and January 2019, tested by reverse transcription-PCR for IBV and sequenced. Vaccine and field strains were discriminated based on genetic and anamnestic information. The most commonly detected lineages were 793B (79%) and variant 2 (17.4%), with sporadic detections of QX, Mass, and D274-like strains. Most of the detected strains had a vaccine origin: 46.3% matched one of the applied vaccines, while 36.5% were genetically related to vaccines not implemented in the respective protocol. Besides their practical value for the proper planning of vaccination protocols in Poland, these results suggest that only a fraction (17.2%) of the circulating strains are field ones, imposing a careful assessment of the actual IBV field menaces. Moreover, phenomena like vaccine spreading and persistence seem to occur commonly, stressing the need to further study the epidemiological consequences of the extensive use of live vaccines.
Multi-Task Deep Relative Attribute Learning for Visual Urban Perception

Visual urban perception aims to quantify perceptual attributes (e.g., safe and depressing attributes) of physical urban environment from crowd-sourced street-view images and their pairwise comparisons. It has been receiving more and more attention in computer vision for various applications, such as perceptive attribute learning and urban scene understanding. Most existing methods adopt either 1) a regression model trained using image features and ranked scores converted from pairwise comparisons for perceptual attribute prediction or 2) a pairwise ranking algorithm to independently learn each perceptual attribute. However, the former fails to directly exploit pairwise comparisons while the latter ignores the relationship among different attributes. To address them, we propose a multi-task deep relative attribute learning network (MTDRALN) to learn all the relative attributes simultaneously via multi-task Siamese networks, where each Siamese network will predict one relative attribute. Combined with deep relative attribute learning, we utilize the structured sparsity to exploit the prior from natural attribute grouping, where all the attributes are divided into different groups based on semantic relatedness in advance. As a result, MTDRALN is capable of learning all the perceptual attributes simultaneously via multi-task learning. Besides the ranking sub-network, MTDRALN further introduces the classification sub-network, and these two types of losses from two sub-networks jointly constrain parameters of the deep network to make the network learn more discriminative visual features for relative attribute learning. In addition, our network can be trained in an end-to-end way to make deep feature learning and multi-task relative attribute learning reinforces each other. Extensive experiments on the large-scale Place Pulse 2.0 dataset validate the advantage of our proposed network. Our qualitative results along with visualization of saliency maps also show that the proposed network is able to learn effective features for perceptual attributes.
Coagulation Traits of Sheep and Goat Milk

Simple Summary The suitability of milk for cheese production is usually predicted at dairy plants using mathematical formulas, which are based on milk protein and fat content. In addition, several methods, which use a small volume of milk to simulate the cheesemaking processes and stages, are currently available at the laboratory level. Those methods have been developed and improved for cow milk. In the present review, the author reports the available literature and current methods to analyze coagulation traits from sheep and goat milk. Abstract Milk production from sheep and goat species is continuously growing worldwide, and its main use is for cheesemaking. Given that the final quality of cheese is linked to the traits of raw milk cheese yield at dairy plants, it is often calculated by using predictive formulas based on fat and protein content. Predictive formulas have been studied for bovine milk and are very effective but not appropriate for sheep and goat milk. Several methods, which simulate the actual coagulation processes, are available at the laboratories. This article reviews the available literature about rennet coagulation and cheese yield traits from sheep and goat milk and the methods used at the laboratory level. In general, if compared to cow milk, sheep and goat milk are characterized by shorter rennet coagulation times and a very limited amount of non-coagulating samples. Curd firmness of sheep milk is almost independent from the rennet coagulation time, and some coagulation traits can be predicted by infrared spectra. In addition, coagulation traits are characterized by appropriate values of heritability to be considered in selective breeding plans. With regard to goat milk, rennet coagulation time and cheese yield are strongly influenced by the breed effect.
A Hormone That Lost Its Receptor: Anti-Müllerian Hormone (AMH) in Zebrafish Gonad Development and Sex Determination

Anti-Mullerian hormone (Amh) inhibits female reproductive duct development, signals oocyte reserve, and marks polycystic ovarian syndrome. Zebrafish lacks Mullerian ducts and the typical Amh receptor, questioning evolving roles of Amh. Yan et al. made knockout mutations in zebrafish. Fetal mammalian testes secrete Anti-Müllerian hormone (Amh), which inhibits female reproductive tract (Müllerian duct) development. Amh also derives from mature mammalian ovarian follicles, which marks oocyte reserve and characterizes polycystic ovarian syndrome. Zebrafish (Danio rerio) lacks Müllerian ducts and the Amh receptor gene amhr2 but, curiously, retains amh. To discover the roles of Amh in the absence of Müllerian ducts and the ancestral receptor gene, we made amh null alleles in zebrafish. Results showed that normal amh prevents female-biased sex ratios. Adult male amh mutants had enormous testes, half of which contained immature oocytes, demonstrating that Amh regulates male germ cell accumulation and inhibits oocyte development or survival. Mutant males formed sperm ducts and some produced a few offspring. Young female mutants laid a few fertile eggs, so they also had functional sex ducts. Older amh mutants accumulated nonvitellogenic follicles in exceedingly large but sterile ovaries, showing that Amh helps control ovarian follicle maturation and proliferation. RNA-sequencing data partitioned juveniles at 21 days postfertilization (dpf) into two groups that each contained mutant and wild-type fish. Group21-1 upregulated ovary genes compared to Group21-2, which were likely developing as males. By 35 dpf, transcriptomes distinguished males from females and, within each sex, mutants from wild types. In adult mutants, ovaries greatly underexpressed granulosa and theca genes, and testes underexpressed Leydig cell genes. These results show that ancestral Amh functions included development of the gonadal soma in ovaries and testes and regulation of gamete proliferation and maturation. A major gap in our understanding is the identity of the gene encoding a zebrafish Amh receptor; we show here that the loss of amhr2 is associated with the breakpoint of a chromosome rearrangement shared among cyprinid fishes.
Contribution of prostaglandins to exercise hyperaemia: workload, ethnicity and sex matter!

The contribution of prostaglandins (PGs) to exercise hyperaemia is controversial. In this review, we argue this is partly explained by differences in exercise intensity between studies. The effects of cyclooxygenase (COX) inhibition and PG assays indicate that PGs contribute more at moderate to heavy than at light workloads and are mainly released by low tissue O2. But, the release and actions of PGs also depend on other O2‐dependent dilators including ATP, adenosine and NO. K+ may inhibit the action of PGs and other mediators by causing hyperpolarization, but contributes to the hyperaemia. Thus, at lighter loads, the influence of PGs may be blunted by K+, while COX inhibition leads to compensatory increases in other O2‐dependent dilators. In addition, we show that other sources of variability are sex and ethnicity. Our findings indicate that exercise hyperaemia following rhythmic contractions at 60% maximum voluntary contraction, is smaller in young black African (BA) men and women than in their white European (WE) counterparts, but larger in men than in women of both ethnicities. We propose the larger absolute force in men causes greater vascular occlusion and accumulation of dilators, while blunted hyperaemia in BAs may reflect lower oxidative capacity and O2 requirement. Nevertheless, COX inhibition attenuated peak hyperaemia by ∼30% in WE, BA men and WE women, indicating PGs make a substantial contribution in all three groups. There was no effect in BA women. Lack of PG involvement may provide early evidence of endothelial dysfunction, consistent in BA women with their greater risk of cardiovascular disease.
A new mouse model of GLUT1 deficiency syndrome exhibits abnormal sleep-wake patterns and alterations of glucose kinetics in the brain

ABSTRACT Dysfunction of glucose transporter 1 (GLUT1) proteins causes infantile epilepsy, which is designated as a GLUT1 deficiency syndrome (GLUT1DS; OMIM #606777). Patients with GLUT1DS display varied clinical phenotypes, such as infantile seizures, ataxia, severe mental retardation with learning disabilities, delayed development, hypoglycorrhachia, and other varied symptoms. Glut1Rgsc200 mutant mice mutagenized with N-ethyl-N-nitrosourea (ENU) carry a missense mutation in the Glut1 gene that results in amino acid substitution at the 324th residue of the GLUT1 protein. In this study, these mutants exhibited various phenotypes, including embryonic lethality of homozygotes, a decreased cerebrospinal-fluid glucose value, deficits in contextual learning, a reduction in body size, seizure-like behavior and abnormal electroencephalogram (EEG) patterns. During EEG recording, the abnormality occurred spontaneously, whereas the seizure-like phenotypes were not observed at the same time. In sleep-wake analysis using EEG recording, heterozygotes exhibited a longer duration of wake times and shorter duration of non-rapid eye movement (NREM) sleep time. The shortened period of NREM sleep and prolonged duration of the wake period may resemble the sleep disturbances commonly observed in patients with GLUT1DS and other epilepsy disorders. Interestingly, an in vivo kinetic analysis of glucose utilization by positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose imaging revealed that glucose transportation was reduced, whereas hexokinase activity and glucose metabolism were enhanced. These results indicate that a Glut1Rgsc200 mutant is a useful tool for elucidating the molecular mechanisms of GLUT1DS. This article has an associated First Person interview with the joint first authors of the paper. Summary: New phenotypes are revealed by a GLUT1 deficiency mutant mouse model carrying a missense mutation in Glut1.
Cutaneous pharmacologic cAMP induction induces melanization of the skin and improves recovery from ultraviolet injury in melanocortin 1 receptor‐intact or heterozygous skin

Homozygous loss of function of the melanocortin 1 receptor (MC1R) is associated with a pheomelanotic pigment phenotype and increased melanoma risk. MC1R heterozygosity is less well studied, although individuals inheriting one loss‐of‐function MC1R allele are also melanoma‐prone. Using the K14‐Scf C57BL/6J animal model whose skin is characterized by lifelong retention of interfollicular epidermal melanocytes like that of the human, we studied pigmentary, UV responses, and DNA repair capacity in the skin of variant Mc1r background. Topical application of forskolin, a skin‐permeable pharmacologic activator of cAMP induction to mimic native Mc1r signaling, increased epidermal eumelanin levels, increased the capacity of Mc1r‐heterozygous skin to resist UV‐mediated inflammation, and enhanced the skin's ability to clear UV photolesions from DNA. Interestingly, topical cAMP induction also promoted melanin accumulation, UV resistance, and accelerated clearance in Mc1r fully intact skin. Together, our findings suggest that heterozygous Mc1r loss is associated with an intermediately melanized and DNA repair‐proficient epidermal phenotype and that topical cAMP induction enhances UV resistance in Mc1r‐heterozygous or Mc1r‐wild‐type individuals by increasing eumelanin deposition and by improving nucleotide excision repair.
Urban Design Factors Influencing Surface Urban Heat Island in the High-Density City of Guangzhou Based on the Local Climate Zone

Surface urban heat island (SUHI) depicts the deteriorating thermal environment in high-density cities and local climate zone (LCZ) classification provides a universal protocol for SUHI identification. In this study, taking the central urbanized area of Guangzhou in the humid subtropical region of China as the study area, the maps or images of LCZ, land surface temperature, SUHI, and urban design factors were achieved using Landsat satellite data, GIS database, and a series of retrieval and classification algorithms, and the urban design factors influencing SUHI were investigated based on 625 samples of LCZs. The results show that on the 18 September 2016 at the local time of 10:51 a.m., the land surface temperature (LST) varied greatly from 26 °C to 40 °C and the SUHI changed with a wide range of −6 °C to 8 °C in the LCZs of the study area. Seven and five urban design factors influencing the summer daytime SUHI were identified for the two dominant LCZs of LCZs 1–5 (LCZ 1 to LCZ 5) and the mixed LCZ (containing at least three types of LCZs), respectively, in which vegetation cover ratio, floor area ratio, ground emissivity, and complete surface area ratio showed negative correlations and building density showed positive correlations. The summer daytime SUHI prediction models were obtained by using the step-wise multiple linear regression, with the performance of R2 of 0.774, RMSE of 0.95 °C, and the d value of 0.91 for the model of LCZs 1–5, and the values of 0.819, 0.81 °C, and 0.94 for the model of the mixed LCZ, indicating that the models can effectively predict the changes of SUHI with LCZs. This study presents a methodology to efficiently achieve a large sample of SUHI and urban design factors of LCZs, and provides information beneficial to the urban designs and regenerations in high-density cities.
Effects of Portulaca Oleracea Extract on Acute Alcoholic Liver Injury of Rats

The present study was envisaged to investigate the chemical constituents and the intervention effects of Portulaca oleracea extract (POE) on acute alcoholic liver injury of rats. The chemical composition of POE was detected by high performance liquid chromatography (HPLC). Sixty male Wistar rats were divided into 6 groups: Normal control (NC) group, acute alcoholic liver injury model group (ALI), low, medium and high dose of POE (25, 50, 100 mg/kg) groups and bifendate (BF, 3.75 mg/kg) group. Each group was given by intragastrical administration for 7 days. Alcoholic liver injury was induced in the experimental model by administering 50% ethanol at 8 mL/kg and repeated administration after 6 h, for a period of 7 days. The results showed that pretreatment with POE significantly reduced the ethanol-elevated serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and triglyceride (TG). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver were enhanced followed by administration of POE, while the content of nitric oxide (NO) and malondialdehyde (MDA) was found to decrease. Hepatic content of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was also reduced by POE treatment. These results indicated that POE could increase the antioxidant capacity and relieve the inflammatory injury of the liver cells induced by ethanol. Meanwhile, in our study, POE reduced the expression of miR-122, acetyl coenzyme A carboxylase (ACC) 1 mRNA and protein and increased the expression of lipoprotein lipase (LPL) mRNA and protein in liver, which indicated that POE could improve the lipid metabolism disorder induced by ethanol. Our findings suggested that POE had protective effects on acute alcoholic liver injury of rats.