We investigate the asymptotic behavior of solutions to the initial boundary value problem for the micropolar fluid model in a half line $\R_{+}:=(0,\infty).$ Inspired by the relationship between micropolar fluid and Navier-Stokes, we prove that the composite wave onsisting of the transonic boundary layer solution, the 1-rarefaction wave, the viscous 2-contact wave and the 3-rarefaction wave for the inflow problem on the micropolar fluid model is time-asymptotically stable under some smallness conditions. Meanwhile, we obtain the global existence of solutions based on the basic energy method.

By using some real analysis techniques, We study the structural characteristics of a multi-parameter Hilbert-type integral inequality with the hybrid kernel, and obtain some equivalent conditions for this inequality. We also consider the operator expression of the equivalent inequalities. The conclusions not only integrates some results of references, but also nds some new Hilbert-type integral inequalities with simple form by choosing suitable parameter values.

The present article deals with the similarity method to tackle the fractional Schrӧdinger equation where the derivative is defined in the Riesz sense. Moreover the procedure of reducing a fractional partial differential equation (FPDE) into an ordinary differential equation (ODE) has been efficiently displayed by means of suitable scaled transform to the proposed fractional equation. Furthermore the ODEs are treated effectively via the Fourier transform. The graphical solutions are also depicted for different fractional derivatives .

The purpose of this paper is to propose some coefficient conditions, characterizing the stability of periodic solutions bifurcated from zero-Hopf bifurcations of the general quadratic jerk system, and apply these theoretical results to a special jerk system in order to predict chaos. First, we characterize the zero-Hopf bifurcations of the general quadratic jerk system in $\mathbb{R}^3$. The coefficient conditions on stability of periodic solutions are obtained via the averaging theory of first order. Next, we apply the theoretical results to a two-parameter jerk system. Finally special attention is paid to a jerk system with one non-negative parameter $\epsilon$ and one non-linearity. By studying the continuation of periodic solution initiating at the zero-Hopf bifurcation, we numerically find a sequence of period doubling bifurcations which leads to the creation of chaotic attractor.

Microcephaly is a prevalent phenotype of the patients with neurodevelopmental problems, often with genetic causes. We comprehensively investigated the clinical phenotypes and genetic background of microcephaly in Korean patients. We enrolled 40 patients with microcephaly. We analyzed clinical phenotypes and radiologic images and conducted whole exome sequencing (WES) and an analysis of copy number variation (CNV). Infantile hypotonia and developmental delay were present in all patients. Thirty-four patients (85%) showed primary microcephaly. The diagnostic yield from the WES and CNV analyses was 47.5%. With WES, we detected pathogenic or likely pathogenic variants that were already known to be related to microcephaly in 12 patients (30%); nine of these were de novo variants with autosomal dominant inheritance. Two unrelated patients had mutations in the KMT2A gene. In 10 other patients, we found mutations in the GNB1, GNAO1, TCF4, ASXL1, SMC1A, VPS13B, ACTG1, EP300, and KMT2D genes. Seven patients (17.5%) were diagnosed as having pathogenic CNVs. Korean patients with microcephaly show a different genetic spectrum from that of patients with microcephaly of other ethnicities. WES with a CNV analysis represents an effective approach for diagnosing the underlying causes of microcephaly.

Aim: The aim of the present study was to evaluate the use of grosgrain and elastic stockings for the treatment of lower limb lymphedema and maintenance of the results. Method: Twenty-two consecutive patients who made use of grosgrain stockings for the treatment of lower limb lymphedema until normalization or near normalization of the limb, followed by the use of elastic stockings for the maintenance of the results. Evaluations were performed using volumetric analysis. This study involved patients with bilateral primary lower limb lymphedema located below the knee who used grosgrain stockings as monotherapy to achieve normalization or near normalization of leg volume and then began to use elastic compression stockings (30/40 mmHg) for the maintenance of the results. Results: A significant reduction in volume occurred with the use of the grosgrain stockings (p < 0.0001, paired t-test) and a significant increase occurred with the use of elastic stockings (p = 0.04). Grosgrain stockings are better than elastic stockings for the reduction in lymphedema. Conclusion: Elastic stockings are useful in maintaining the results, but must be combined with other forms of therapy for the significant mobilization of macromolecules.

Rationale, aims and objectives: Since the widespread implementation of electronic medical records, there have been concerns about errors, excessive copying forward, and reduced quality in resident inpatient progress notes. The goal of this study was to create and validate a tool to assess the quality of progress notes written on an inpatient neurology service. Methods: A survey assessing perceptions of resident inpatient neurology progress note quality was administered to faculty and residents, and based on these results, a four item note assessment tool (PNQIv2) was developed. The tool assessed the following attributes: (1) accuracy, (2) synthesis, (3) focus, (4) patient-centeredness, and (5) copied-forward material. 120 note reviews were completed by 4 study investigators on 30 different resident progress notes utilizing 10 out of 16 possible residents (62.5%). Mean PNQIv2 scores were calculated as well as inter-rater reliability for the overall PNQIv2 scores and their subsections using inter-class correlation coefficients and 95% confidence intervals. Results: The PNQIv2 was found to have good inter-rater reliability at 0.7 and was considered quick and simple to use. The mean total PNQIv2 score was 9.2 (SD 2) out of 12. 60% of notes were determined to be at least adequate quality by receiving a PNQIv2 score of ≥ 9, and 63% of notes contained at least 2/3 copied-forward material. Conclusions: The investigators developed a progress note assessment tool that was simple and practical to use on the wards, with good inter-rater reliability, which may be useful to formally evaluate the quality of resident inpatient progress notes.

Marine food webs are highly compartmentalized and characterizing the trophic niches among consumers is important for predicting how impact from human activities affect the structuring and functioning of marine food webs. Biomarkers such as bulk stable isotopes have proven to be powerful tools to elucidate trophic niches, but they may lack in resolution, particularly when spatio-temporal variability in a system is high. To close this gap, we investigated whether carbon isotope (δ13C) patterns of essential amino acids (EAAs), also termed δ13AA fingerprints, can characterize niche differentiation in a highly dynamic marine system. We tested the ability of δ13AA fingerprints to differentiate trophic niches among six functional groups and ten individual species in the Baltic Sea. We also tested whether fingerprints of the common zooplanktivorous fishes, herring and sprat, differ among four Baltic Sea regions with different biochemical conditions and phytoplankton assemblages. Additionally, we investigated how these results compared to bulk C and N isotope data for the same sample set. We found significantly different δ13AA fingerprints among all six functional groups. Species differentiation was in comparison less distinct, due to partial convergence of the species’ fingerprints within functional groups. Herring and sprat displayed region specific δ13AA fingerprints indicating that this approach could be used as a migratory marker. Bulk isotope data had a lower power to differentiate between trophic niches, but may provide more easily interpretable information about relative trophic position than the fingerprints. We conclude that δ13AA fingerprinting has a strong potential to advance our understanding of ecological niches, and trophic linkages from producers to higher trophic levels in dynamic marine systems. Given how management practices of marine resources and habitats are reshaping the structure and function of marine food webs, implementing new and powerful tracer methods are urgently needed to improve the knowledge base for policy makers.

Background: While opioids play a crucial role in pain’s relief, chronic exposure results in tolerance and dependence. Efforts should be made to alleviate the side effect induced by opioids. Many proteins which functionally interact with MOR can regulate the effect of opioids. Our bacterial yeast two-hybrid experiment showed ABIN-1 could bind to MOR. Here, we studied the profile and mechanism of ABIN-1 on morphine tolerance and dependence. Experimental Approach: ABIN-1 in mouse brain was interfered by AAV virus. The tolerance and dependence induced by morphine were assessed in hotplate and conditioned place preference test. The regulation of β-arrestin signalling of MOR was observed in MOR-CHO cell lines after ABIN-1 overexpression. The interaction of proteins was detected by co-immunoprecipitation and immunofluorescence. The expression of proteins was tested by western blotting and immunohistochemistry. Key Results: Morphine tolerance and dependence were attenuated by overexpression of ABIN-1 in mouse brains. ABIN-1 in the hippocampus and nucleus accumbens participated in morphine tolerance and physical dependence. MOR phosphorylation and internalization were weakened by ABIN-1 after opioids treatment. Formation of ABIN-1-β-arrestin-2 complexes promoted the translocation of β-arrestin-2 to the plasma membrane and accelerated its ubiquitination and degradation. Furthermore, attenuation of morphine tolerance by ABIN-1 was abolished in β-arrestin-2 knockout mice. Conclusions and Implications: These findings indicate that ABIN-1 co-operates with β-arrestin2 and MOR to alleviate morphine tolerance and dependence. ABIN-1 may be a target to alleviate morphine tolerance.

BACKGROUND AND PURPOSE Acute lung injury (ALI) is a challenging clinical syndrome that manifests as an acute inflammatory response. The NLRP3 inflammasome is involved in the development of ALI. Yadanzigan (YDZG) is isolated from Brucea javanica (Linn.) Merr (Simaroubaceae) (Yadanzi), an anti-inflammatory herb widely used in traditional Chinese medicine. However, the anti-inflammatory effect and mechanism of YDZG on ALI have not been reported. ¬ EXPERIMENTAL APPROACH The in vitro anti-inflammatory effect and mechanism of YDZG were investigated through ELISA, qRT-PCR, Western blotting, and immunoprecipitation assay. ALI model was established by non-invasive intratracheal instillation of LPS into lung of mice. The therapeutic effect of YDZG on ALI was assessed by changes in histopathological and pro-inflammatory markers. The underlying mechanisms were investigated by Western blotting on lung tissue. KEY RESULTS YDZG specifically inhibits NLRP3 inflammasome activation. In cultured macrophages, YDZG attenuated the NF-κB pathway and mitochondrial reactive oxygen species production and enhanced TRIM31 expression to inhibit NLRP3 inflammasome activation. YDZG also ameliorated LPS-induced acute lung injury in mice by inhibiting the expression of NLRP3. CONCLUSIONS AND IMPLICATIONS This study uncovers the underlying mechanism and the anti-inflammatory activity of YDZG in ALI, suggesting that NLRP3 inflammasome may be an effective target of the treatment with ALI.

Whether a female honey bee (Apis mellifera) develops into a worker or a queen depends on her nutrition during development, which changes the epigenome to alter the developmental trajectory. Beekeepers typically exploit this developmental plasticity to produce queen bees by transplanting worker larvae into queen cells to be reared as queens, thus redirecting a worker developmental pathway to a queen developmental pathway. We studied the consequences of this manipulation for the queen phenotype and methylome over four generations. Queens reared from worker larvae consistently had fewer ovarioles than queens reared from eggs. Over four generations the methylomes of lines of queens reared from eggs and worker larvae diverged, accumulating increasing differences in exons of genes related to caste differentiation, growth and immunity. We discuss the consequences of these cryptic changes to the honey bee epigenome for the health and viability of honey bee stocks.

Abstract As flatfish, turbot undergo metamorphosis as part of their life cycle. In the larval stage, turbot live at the ocean surface, but after metamorphosis they move to deeper water and turn to benthic life. Thus, the light environment differs greatly between life stages. The vision system plays a great role in organic evolution, but reports of the relationship between the visual system and benthic life are rare. In this study, branch- and branch-site models were implemented in the CODEML program within PAML4.9i to compare the selective constraints acting on the visual opsin genes of five flatfish species, including turbot and four freshwater species. Based on synteny and spectral tuning sites analyses, we demonstrated that RH2C may be an important subtype of green opsin gene that was retained by turbot and possibly other flatfish species during evolution. Moreover, E122Q and M207L substitutions in RH2C, which were found to be under positive selection, may contribute to the survival of turbot in the bluish colored ocean. Real-time PCR results suggested that heterochronic shifts in opsin expression may be an important strategy for turbot to adapt to benthic life. Finally, turbot exhibited a bounded plasticity of opsin expression in response to different photic environments, which seems to be a mechanism for rapid adaption to changing environmental light. Keywords: turbot, benthic life, adaption, opsin, heterochronic shift, plasticity

Background and Purpose: Although β1-blockers impressively reduce mortality in chronic heart failure (CHF), there are concerns about negative inotropic effects and worsening of hemodynamics in acute decompensated heart failure. May receptor theory dispel these concerns and confirm clinical practice to use β1-blockers? Experimental Approach: In CHF, concentrations of catecholamines at the β1-adrenoceptors usually exceed their dissociation constants (KDs). The homodimeric β1-adrenoceptors have a receptor reserve and display negative cooperativity. We considered the binomial distribution of occupied receptor dimers with respect to the interaction of an exogenous β1-blocker and elevated endogenous agonist concentrations > [KDs], corresponding to an elevated sympathetic tone. Key Results: Modeling based on binomial distribution suggests that in the presence of a low concentration of the antagonist, the activation of the dimer receptors is higher than that in its absence. This leads to increased positive inotropic effects of endogenous catecholamines due to a β1-blocker. Conclusion and Implications: To understand the positive inotropic sequels of β1-blockers in CHF is clinically relevant. This article may help to eliminate the scepticism of clinicians about the use of β1-blockers because of their supposed negative inotropic effect, since on the contrary a positive inotropic effect can be expected for receptor-theoretical reasons.

Corals show spatial acclimatization to local environment conditions. The various cellular mechanisms involved in local acclimatization and variable bleaching patterns in corals remain to be thoroughly investigated. In this study, the modulation of a protein involved in cellular heat stress tolerance, the Heat shock protein 70 (Hsp70), was compared at both gene expression and protein level in Acropora muricata colonies from two contrasting environments, in the lagoonal system of Belle Mare (Mauritius), having differential bleaching susceptibilities. The relative Hsp70 levels varied significantly between colonies from the different environments, colonies having different health status and the year of collection. Before the bleaching event of 2016, near-coast colonies had higher basal levels of Hsp70 gene and protein compared to back reef colonies. During the bleaching event, the near-coast colonies did not bleach and had significantly higher relative levels of Hsp70 compared to bleached back reef colonies. The A. muricata colonies investigated had genetically identical host genotype and were hosting the same Symbiodiniaceae genus (Symbiodinium) irrespective of habitat and sampling year. These findings provide further evidence of the involvement of Hsp70 in conferring bleaching resistance to corals. Understanding of these processes is paramount for improvement of conservation efforts, where Hsps could potentially be used as proactive biomarkers for heat stress in corals.

Background: HSG4112 is a clinical-stage drug candidate for the treatment of obesity. Here, we report its discovery and preclinical efficacy.  Methods: In high-fat diet (HFD)-induced obese male C57BL/6J mice, we tested the weight loss effect of synthetic compounds derived from a structure-activity relationship (SAR) study of glabridin, a natural compound known to reduce body weight and influence energy homeostasis. After selecting HSG4112 as our optimized compound from this discovery method, we characterized its pharmacological effects on parameters related to obesity through in vivo metabolic and biochemical measurements, histology and gene expression analysis, and indirect calorimetry.Results: Through the SAR study, we identified four novel components of glabridin pertinent for its anti-obesity activity, and found that HSG4112, an optimized structural analog of glabridin, markedly supersedes glabridin in weight reduction efficacy and chemical stability. 6-week administration of HSG4112 to HFD-induced obese mice led to dose-dependent normalization of obesity-related parameters, including body weight, muscle and adipose tissue weight, adipocyte size, and serum leptin/insulin/glucose levels. The weight reduction induced by HSG4112 was partially mediated by decreased food intake and mainly mediated by increased energy expenditure, with no change in physical activity. Accordingly, the pattern of transcriptional changes was aligned with increased energy expenditure in the liver and muscles. Following significant body weight reduction, robust amelioration of histopathology and blood markers of fatty liver were also observed.  Conclusions: Our study demonstrates the key chemical components of glabridin pertinent to its weight loss effects and suggests HSG4112 as a promising novel drug candidate for the pharmacological treatment of obesity.

Aluminum (Al) toxicity in acid soils significantly affects plant growth, agricultural productivity and ecosystem health. Here we investigated plant Al tolerance from evolutionary physiological, molecular, and ecological perspectives. Genetic similarity and phylogenetic analysis of Al tolerance-associated gene families showed that many of these were conserved from streptophyte algae to angiosperms, indicating land plants have evolved gradually in adaptation to Al-rich acid soil during plant terrestrialization. In particular, vacuolar phosphate transporter SPX-major facility superfamily (SPX-MFS) and inorganic phosphate (Pi) transporter 1 subfamily (PHT1s) of streptophyte algae showed higher genetic similarity to land plants than chlorophyte algae. PHT1 subfamily exhibited a significant expand during the evolution from streptophyte algae to liverworts and then to eudicots. Moreover, we identified an Al-tolerant Tibetan wild barley accession XZ29, showing high levels of Phosphorus(P)-containing glycolytic intermediates under Al stress. We found a new Al-tolerance mechanism that Al-induced Pi efflux from root elongation zone to chelate rhizosphere Al3+ and immobilization of Al with P reduce Al accumulation in barley root cells. These results indicated that Tibetan wild barley has evolved unique P transport and metabolism for the adaptation to harsh conditions in eastern and southeastern Tibet where acid soils contain high P.

Rare earth elements are known to alleviate heavy metal stress. However, the potential mechanisms of alleviation remain unclear. This study compared the effects of La(NO3)3 and La(NO3)3-amino acid chelates (La(Ⅲ)-AA) on growth, oxidative stress, ultrastructure, bioaccumulation and gene expression in rice. Results demonstrated that 20 mg/L La(Ⅲ)-AA can effectively ameliorate CuSO4 (50 mg/L) stress in rice by reducing oxidative stress and increasing chlorophyll content, thus promoting growth. ICP and TEM revealed an antagonistic effect between La(Ⅲ) and Cu(Ⅱ). Exogenous La(Ⅲ)-AA decreased Cu(Ⅱ) content in rice leaves, stems and roots by 55.56%, 59.46% and 26.29%, and ameliorated Cu(Ⅱ) damage by maintaining the ultrastructure of mesophyll cells. RNA sequencing identified 7020 differentially expressed genes, and 8 were validated by qRT-PCR. Indole-3-acetic acid (IAA) concentration was detected by HPLC. Correlation analysis between OsGH3.4-IAA-Expansin revealed that IAA content is negatively correlated with OsGH3.4 (r=-0.82, P <0.05), and positively correlated with Expansin (r = 0.78, P <0.05). It’s assumed that La(Ⅲ)-induced OsGH3.4 could inhibit IAA-dependent Expansin expression, thereby conferring resistance to Cu stress. This work provides novel insights into the molecular basis underlying La-induced Cu tolerance in rice.

Letter to the Editor, BJOG Exchange

In habitats with low water availability, a fundamental challenge for plants will be to maximize photosynthetic C-gain whilst minimizing transpirational water-loss. This tradeoff between C-gain and water-loss can in part be achieved through the coordination of leaf-level photosynthetic and hydraulic traits. To test the relationship of photosynthetic C-gain and transpirational water-loss we grew under common growth conditions 18 C4 grasses adapted to habitats with different mean annual precipitation (MAP) and measured leaf-level structural and anatomical traits associated with mesophyll conductance (gm) and leaf hydraulic conductance (Kleaf). The C4 grasses adapted to lower MAP showed greater mesophyll surface area exposed to intercellular air spaces (Smes) and adaxial stomatal density (SDada) which supported greater gm. These grasses also showed greater leaf thickness and vein-to-epidermis distance which may lead to lower Kleaf. Collectively, these leaf traits associated with gm and Kleaf scaled positively with photosynthetic rates (Anet) and leaf-level water-use efficiency (WUE) with low MAP adapted grasses exhibiting greater Anet and WUE. In summary, we identify a suite of leaf-level traits that appear important for adaptation of C4 grasses to habitats with low MAP and may be useful to identify C4 species showing greater Anet and WUE in drier conditions.

Large amount of algae has been significantly increased due to eutrophication of water bodies. However, algae is rich in bio-active compounds, such as vitamins, proteins, polysaccharides, unsaturated fatty acids, nucleic acids, minerals and pigments. In the study, spirulina was proved to be an novel and appropriate co-metabolic substance in enhancing the anaerobic degradation of quinoline and indole. When the dosage of Spirulina powder was 1.0 mg/L, reactor showed the highest degradation efficiency, with ratios of 99.77% and 99.57%, respectively. Further, the addition of Spirulina powder led to the increase of MLSS, MLVSS, proteins, and polysaccharides concentration of sludge. Finally, the addition of Spirulina powder resulted in the decrease of Acinetobacter and the enrichment of Aminicenantes, Levilinea, and Longilinea. The reactor with Spirulina powder had richer and more diverse archaea community.

Objectives: To investigate the prevalence of pathogenic and likely-pathogenic variants detected by chromosomal microarray analysis (CMA), among pregnancies with fetal short long bones diagnosed by ultrasound. Design: A retrospective study. Setting: The study was based on national records from the Israeli Ministry of Health. Sample: Chromosomal microarray analyses performed nationwide, during January 2016 to March 2018, for the indication of prenatal diagnosis of short long bones (n=66). Methods: Clinical data was retrieved from genetic counselling summary letters and from patients’ medical records. The CMA yield was compared to two cohorts that reported the background risk. Main outcome measure: Pathogenic/likely pathogenic CMA. Results: There were 4 cases with a pathogenic/likely pathogenic result (6%). The rate of chromosomal abnormalities was significantly higher compared to the background risk for copy number variations (CNVs) [P<0.001], [odds ratio (OR) 4.5, 95% CI 1.6-12.7], [OR 5.8, 95% CI 2-16.2], for both isolated [OR 6.1, 95% CI 1.4-26], [OR 7.8, 95% CI 1.8-33.5], and non-isolated cases[OR 10, 95% CI 2.2-44], [OR 12.8, 95% CI 2.9-57], , and for cases in which the lowest estimated bone length percentile was above the 3rd percentile (below 5th percentile) [OR 23, 95% CI 6.2-87], [OR 29.9, 95% CI 8-111], . Conclusion: The yield of CMA in cases with short long bones (both isolated and non-isolated) is significantly higher than the background risk for chromosomal anomalies in pregnancies with no sonographic anomalies. This suggests that CMA should be offered in pregnancies with a diagnosis of fetal short long bones.

Objectives: This meta-analysis aims to investigate the association between I131 treatment and pregnancy outcomes. Methods: Electronic database PubMed, Embase and the Cochrane Library were throughly searched until December 2017. Databases were searched for studies that reported the incidence of pregnancy outcomes (spontaneous abortion, induce abortion, premature birth, stillbirth) in DTC participants with I131 treatment or not. Meta-analysis was performed in Stata/SE12. A random or fixed effects model was adopted according to the result of heterogeneity test. Results: A total of 6 observational studies were eligible, involving 14132 participants and 2969 pregnancies. It showed that postoperative I131 treatment for DTC had no significant effect on spontaneous abortion (OR = 1.05, P = 0.701), induced abortion (OR = 1.06, P = 0.859), abortion (OR = 1.07, P = 0.597), premature birth (OR = 1.49, P = 0.073) and stillbirth (OR = 1.58, P = 0.364). The group in which interval time between last I131 treatment and pregnancy >1 year had significantly lower risk of abortion than with interval <1 year (OR = 0.50, P = 0.000. Conclusions: I131 treatment for DTC had no significant effect on pregnancy outcomes. Pregnancy is not recommended for DTC patients within 1 year after 131I treatment.

Utilizing phosphate more efficiently is crucial for sustainable crop production. Highly efficient rice (Oryza sativa) cultivars have been identified and this study aims to identify metabolic markers associated with P utilization efficiency. P deficiency generally reduced leaf P concentrations and CO2 assimilation rates but efficient cultivars were reducing leaf P concentrations further than inefficient ones while maintaining similar CO2 assimilation rates. Adaptive changes in carbon metabolism were detected but equally in efficient and inefficient cultivar groups. Groups furthermore did not differ with respect to partial substitutions of phospholipids by sulfo- and galactolipids. Metabolites significantly more abundant in the efficient group, such as sinapate, benzoate and glucoronate, were related to antioxidant defense and may help alleviating oxidative stress caused by P deficiency. Sugar alcohols ribitol and threitol were another marker metabolite for higher phosphate efficiency as were several amino acids, especially threonine. Since these metabolites are not known to be associated with P deficiency, they may provide novel clues for the selection of more P efficient genotypes. In conclusion, metabolite signatures detected here were not related to phosphate metabolism but rather helped P efficient lines to keep vital processes functional under the adverse conditions of P starvation.

This paper presents a new method for the optimization of the allocation of spectral resources. It is based on the variations of the PAPR as a function of the sub-bands allocations for transmission in the context of a MPSoC based on RF interconnections. The method shows that a specific distribution of the frequency sub-bands leads to a diminution of the PAPR which is an important criterion in signal transmission.