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Objective: Low-density lipoprotein receptor-related protein-1 (LRP1) regulates energy homeostasis, blood-brain barrier integrity, and metabolic signaling in the brain. Deficiency of LRP1 in inhibitory gamma-aminobutyric acid (GABA)ergic neurons causes severe obesity in mice. However, the impact of LRP1 in inhibitory neurons on memory function and cognition in the context of obesity is poorly understood., Methods: Mice lacking LRP1 in GABAergic neurons (Vgat-Cre; LRP1 loxP/loxP ) underwent behavioral tests for locomotor activity and motor coordination, short/long-term and spatial memory, and fear learning/memory. This study evaluated the relationships between behavior and metabolic risk factors and followed the mice at 16 and 32 weeks of age., Results: Deletion of LRP1 in GABAergic neurons caused a significant impairment in memory function in 32-week-old mice. In the spatial Y-maze test, Vgat-Cre; LRP1 loxP/loxP mice exhibited decreased travel distance and duration in the novel arm compared with controls (LRP1 loxP/loxP mice). In addition, GABAergic neuron-specific LRP1-deficient mice showed a diminished capacity for performing learning and memory tasks during the water T-maze test. Moreover, reduced freezing time was observed in these mice during the contextual and cued fear conditioning tests. These effects were accompanied by increased neuronal necrosis and satellitosis in the hippocampus. Importantly, the distance and duration in the novel arm, as well as the performance of the reversal water T-maze test, negatively correlated with metabolic risk parameters, including body weight, serum leptin, insulin, and apolipoprotein J. However, in 16-week-old Vgat-Cre; LRP1 loxP/loxP mice, there were no differences in the behavioral tests or correlations between metabolic parameters and cognition., Conclusions: Our findings demonstrate that LRP1 from GABAergic neurons is important in regulating normal learning and memory. Metabolically, obesity caused by GABAergic LRP1 deletion negatively regulates memory and cognitive function in an age-dependent manner. Thus, LRP1 in GABAergic neurons may play a crucial role in maintaining normal excitatory/inhibitory balance, impacting memory function, and reinforcing the potential importance of LRP1 in neural system integrity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Abstract: Acute myeloid leukemia (AML) is an aggressive hematological malignancy originating from transformed hematopoietic stem or progenitor cells. AML prognosis remains poor owing to resistance and relapse driven by leukemia stem cells (LSCs). Targeting molecules essential for LSC function is a promising therapeutic approach. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is often dysregulated in AML. We found that although PI3Kγ is highly enriched in LSCs and critical for self-renewal, it was dispensable for normal hematopoietic stem cells. Mechanistically, PI3Kγ-AKT signaling promotes nuclear factor erythroid 2-related factor 2 (NRF2) nuclear accumulation, which induces 6-phosphogluconate dehydrogenase (PGD) and the pentose phosphate pathway, thereby maintaining LSC stemness. Importantly, genetic or pharmacological inhibition of PI3Kγ impaired expansion and stemness of murine and human AML cells in vitro and in vivo. Together, our findings reveal a key role for PI3Kγ in selectively maintaining LSC function by regulating AKT-NRF2-PGD metabolic pathway. Targeting the PI3Kγ pathway may, therefore, eliminate LSCs without damaging normal hematopoiesis, providing a promising therapeutic strategy for AML., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Chemokines are cytokines with chemoattractant capacities that exert their physiological functions through the binding of chemokine receptors. Thus, chemokine and receptor complexes exert important roles in regulating development and homeostasis during routine immune surveillance and inflammation. Compared to mammals, the physiology and structure of chemokine receptors in fish have not been systematically studied. Furthermore, the salmonid-specific whole genome duplication has significantly increased the number of functional paralogs of chemokine receptors. In this context, in the current study, trout exhibited 17 cxcr genes, including 12 newly identified and 5 previously identified receptors. Interestingly, gene expression of brain cxcr1 and cxcr4 , kidney cxcr3 and cxcr4 , and spleen cxcr3 , cxcr4 , and cxcr5 subtypes were altered by bacterial infection, whereas brain cxcr1 , kidney cxcr1 and cxcr7 , and liver cxcr2 , cxcr3 , and cxcr4 subtypes were changed in response to environmental changes. Based on protein structures predicted by ColabFold, the conserved amino acids in binding pockets between trout CXCR4.1 subtypes and human CXCR4 were also analyzed. Our study is valuable from a comparative point of view, providing new insights into the identification and physiology of salmonid chemokine receptors.

Serotonergic system is involved in the regulation of physiological functions and behavioral traits including cognition, memory, aggression, stress coping, appetite and immunomodulation. Serotonin exerts its functions via binding distinct serotonin receptors which are classified into 7 groups. Salmonid exhibits expanded functional gene copies due to salmonid-specific whole genome duplication. However, serotonin receptor (htr) repertoire is not fully identified in rainbow trout (Oncorhynchus mykiss). In this study, we identified 39 htr genes, including 14 htr1, 4 htr2, 4 htr2 like, 3 htr3, 4 htr4, 2 htr5, 2 htr6, and 6 htr7 subtypes. We investigated physiological functions of serotonin receptors in response to bacterial pathogens exposure and salinity changes. We showed htr1, htr2, htr4 and htr7 subtypes were associated with immunomodulation in response to Vibrio anguillarum or Aeromonas salmonicida infection. Saltwater (salinity of 15) transfer significantly altered htr1, htr2, htr4, and htr7 subtypes, suggesting trout Htr was associated with osmoregulation. We further showed residues interacted with inverse agonist (methiothepin) and serotonin analogue (5-Carboxamidotryptamine) were conserved between trout and human, suggesting exogenous ligands targeting human HTRs might have a role in aquaculture. This study showed duplicated trout Htrs might be physiologically neofunctionalized and potentially exhibit pleiotropic effects in regulating immunomodulation and osmoregulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Human activities can cause zinc (Zn) contamination of aquatic environments. Zn is an essential trace metal, but effects of environmentally relevant Zn exposure on the brain-intestine axis in fish are poorly understood. Here, six-month-old female zebrafish (Danio rerio) were exposed to environmentally relevant Zn concentrations for six weeks. Zn significantly accumulated in the brain and intestine, causing anxiety-like behaviors and altered social behaviors. Zn accumulation altered levels of neurotransmitters, including serotonin, glutamate, and γ-aminobutyric acid, in the brain and intestine, and these changes were directly associated with changes in behavior. Zn caused oxidative damage and mitochondrial dysfunction, and impaired NADH dehydrogenase, thereby dysregulating the energy supply in brain. Zn exposure resulted in nucleotide imbalance and dysregulation of DNA replication and the cell cycle, potentially impairing the self-renewal of intestinal cells. Zn also disturbed carbohydrate and peptide metabolism in the intestine. These results indicate that chronic exposure to Zn at environmentally relevant concentrations dysregulates the bidirectional interaction of the brain-intestine axis with respect to neurotransmitters, nutrients, and nucleotide metabolites, thereby causing neurological disorder-like behaviors. Our study highlights the necessity to evaluate the negative impacts of chronic environmentally relevant Zn exposure on the health of humans and aquatic animals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The melanocortin-4 receptor (MC4R) is essential for the modulation of energy balance and reproduction in both fish and mammals. Rainbow trout ( Oncorhynchus mykiss ) has been extensively studied in various fields and provides a unique opportunity to investigate divergent physiological roles of paralogues. Herein we identified four trout mc4r ( mc4ra1 , mc4ra2 , mc4rb1 , and mc4rb2 ) genes. Four trout Mc4rs (omMc4rs) were homologous to those of teleost and mammalian MC4Rs. Multiple sequence alignments, a phylogenetic tree, chromosomal synteny analyses, and pharmacological studies showed that trout mc4r genes may have undergone different evolutionary processes. All four trout Mc4rs bound to two peptide agonists and elevated intracellular cAMP levels dose-dependently. High basal cAMP levels were observed at two omMc4rs, which were decreased by Agouti-related peptide. Only omMc4rb2 was constitutively active in the ERK1/2 signaling pathway. Ipsen 5i, ML00253764, and MCL0020 were biased allosteric modulators of omMc4rb1 with selective activation upon ERK1/2 signaling. ML00253764 behaved as an allosteric agonist in Gs-cAMP signaling of omMc4rb2. This study will lay the foundation for future physiological studies of various mc4r paralogs and reveal the evolution of MC4R in vertebrates.

Rainbow trout (Oncorhynchus mykiss), an important economic cold-water fish worldwide, is severely threatened by viruses and bacteria in the farming industry. The vibriosis outbreak has caused a significant setback to aquaculture. Vibrio anguillarum, one of the common disease-causing vibriosis associated with severe lethal vibriosis in aquaculture, infects fish mainly by adsorption and invasion of the skin, gills, lateral line and intestine. To investigate the defense mechanism of rainbow trout against the pathogen after infection with Vibrio anguillarum, trout were intraperitoneally injected by Vibrio anguillarum and divided into symptomatic group (SG) and asymptomatic group (AG) according to the phenotype. RNA-Seq technology was used to evaluate the transcriptional signatures of liver, gill and intestine of trout injected with Vibrio anguillarum (SG and AG) and corresponding control groups (CG(A) and CG(B)). The GO and KEGG enrichment analyses were used to investigate the mechanisms underlying the differences in susceptibility to Vibrio anguillarum. Results showed that in SG, immunomodulatory genes in the cytokine network were activated and tissue function-related genes were down-regulated, while apoptosis mechanisms were activated. However, AG responded to Vibrio anguillarum infection by activating complement related immune defenses, while metabolism and function related genes were up-regulated. Conclusively, a rapid and effective immune and inflammatory response can successfully defend Vibrio anguillarum infection. However, a sustained inflammatory response can lead to tissue and organ damage and cause death. Our results may provide a theoretical basis for breeding rainbow trout for disease resistance., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Zinc is an essential nutrient for life, but over-accumulation can result in toxicity. Anthropogenic activities can increase zinc concentrations in aquatic environments (e.g., to ∼0.46-1.00 mg/L), which are above the safe level of 0.1 mg/L. We investigated the behavior and physiology of zebrafish (Danio rerio) in response to environment-related exposure to zinc chloride at 0.0 (Ctrl), 1.0 (ZnCl 2 -low) and 1.5 (ZnCl 2 -high) mg/L for 6 weeks (the zinc conversion ratio of zinc chloride is ∼0.48 and the nominal (measured) values were: Ctrl, 0 (∼0.01); ZnCl 2 -low, 0.48 (∼0.51); ZnCl 2 -high, 0.72 (∼0.69) mg/L). Low-zinc exposure resulted in significantly increased locomotion and fast moving behaviors, while high-zinc exposure resulted in significantly increased aggression and freezing frequency. Single cell RNA-seq of neurons, astrocytes, and oligodendrocytes of the brain revealed expression of genes related to ion transport, neuron generation, and immunomodulation that were heterogeneously regulated by zinc exposure. Astrocyte-induced central nervous system inflammation potentially integrated neurotoxicity and behavior. Integrated analyses of brain and hepatic transcriptional signatures showed that genes (and pathways) dysregulated by zinc were associated with sensory functions, circadian rhythm, glucose and lipid metabolism, and amyloid β-protein clearance. Our results showed that environment-related zinc contamination can be heterogeneously toxic to brain cells and can disturb coordination of brain-liver physiology. This may disrupt neurobehavior and cause a neurodegeneration-like syndrome in adult zebrafish., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Anthropogenic activities discharge zinc into aquatic ecosystems, and the effects of long-term and low-concentration zinc exposure on fish behavior are unclear. We evaluated the behavior and physiology of male zebrafish (Danio rerio) after a 6-week exposure to 1.0 or 1.5 ppm (mg/L) zinc chloride. The exposure caused anxiety-like behaviors and altered the social preferences in both exposure groups. Analysis of transcriptional changes suggested that in the brain, zinc exerted heterogenetic effects on immune and neurotransmitter functions. Exposure to 1.0 ppm zinc chloride resulted in constitutive immune dyshomeostasis, while exposure to 1.5 ppm zinc chloride impaired the neurotransmitter glutamate. In the intestine, zinc dysregulated self-renewal of intestinal cells, a potential loss of defense function. Moreover, exposure to 1.5 ppm zinc chloride suppressed intestinal immune functions and dysregulated tyrosine metabolism. These behavioral alterations suggested that the underlying mechanisms were distinct and concentration-specific. Overall, environmental levels of zinc can alter male zebrafish behaviors by dysregulating neurotransmitter and immunomodulation signatures., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Mitogen-activated protein kinase kinases (MKKs) are intermediate kinases of mitogen-activated protein kinases (MAPKs) signaling pathways. MKKs are activated by mitogen-activated protein kinase kinase kinase (MKKK) and then the activated MKKs trigger the activation of downstream MAPKs. MAPK signaling pathways play an important role in regulating immune functions including apoptosis and inflammation. However, studies on identification and characterization of mkk repertoire in rainbow trout (Oncorhynchus mykiss) are still limited. Trout experienced 4 rounds (4R) of whole genome duplication (WGD), thus exhibiting increased paralogs of mkks with potentially functional diversity. In this study, we identified 17 mkk genes in trout and the following bacterial challenge (Vibrio anguillarum) studies showed functional diversity of different mkk subtypes. Vibrio anguillarum infection resulted in significantly up-regulated mkk2 subtypes in spleen and liver, and mkk4b3 in spleen, suggesting immunomodulation was regulated by activation of ERK, p38 and JNK pathways. Compared to other mkk subtypes, mkk6s were down-regulated in symptomatic group, rather than asymptomatic group. The organisms present negative feedback on MAPK activation, thus reducing extra damage to cells. We observed down-regulated mkk6s with up-regulated genes (dusp1 & dusp2) involved in negative feedback of MAPK activation. Based on these results, we might propose the distinct expression patterns of genes associated with MAPK pathways resulted in different phenotypes and symptoms of trout in response to bacterial challenge., (Copyright © 2021. Published by Elsevier Ltd.)

Optical systems provide a new and practical platform for studying Bloch oscillations. This study investigates the fundamental-mode propagation of polarization-dependent Bloch oscillations. By using the three-dimensional properties of femtosecond laser direct writing, we fabricate a polymer-based gradient waveguide array and determine the Bloch oscillations under different polarization inputs by using the birefringence gradient and the equivalent refractive index, thus exhibiting a polarization-dependent Bloch period. Our results provide a new, to the best of our knowledge, paradigm for two-dimensional optical Bloch modes and highlight the influence of optical polarization in the same system, which provides a possibility to observe richer physics related to Bloch oscillations in one structure.

Energy homeostasis, which refers to the physiological processes that the energy intake is exquisitely coordinated with energy expenditure, is critical for survival. Therefore, multiple and complex mechanisms have been involved in the regulation of energy homeostasis. The central melanocortin system plays an important role in modulating energy homeostasis. This system includes the orexigenic neurons, expressing neuropeptide Y/Agouti-related protein (NPY/AgRP), and the anorexigenic neurons expressing proopiomelanocortin (POMC). The downstream receptors of NPY, AgRP and post-translational products of POMC are G protein-coupled receptors (GPCRs). This review summarizes the compelling evidence demonstrating that NPY and melanocortin receptors are involved in energy homeostasis. Subsequently, the comparative studies on physiology and pharmacology of NPY and melanocortin receptors in humans, rodents and teleosts are summarized. Also, we provide a strategy demonstrating the potential application of the new ligands and/or specific variants of melanocortin system in aquaculture., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Ocean University of China 2021.)

Caspases are highly conserved cysteine-dependent aspartyl-specific proteases that play an important role in regulating cell death and inflammation. However, the caspase genes have not been systematically studied in rainbow trout (Oncorhynchus mykiss). Rainbow trout experienced 4 rounds (4R) of genome duplication in the evolutionary history. Thereby an increased numbers of paralogs are observed in trout, probably with more complicated gene functions. We identified 18 caspase genes in rainbow trout, including two inflammatory caspases (casp1a, casp1b), six apoptosis executioner caspases (casp3, casp3a1, casp3a2, casp3b, casp6, and casp7), nine apoptosis initiator caspases (casp2a, casp2b, casp8, casp9a, casp9b, casp10a, casp10b, casp20a, and casp20b) and one uncategorized caspase gene (casp17). To investigate the potentially physiological functions of caspase genes, we challenged the rainbow trout with Aeromonas salmonicida (A. salmonicida) and Vibrio anguillarum (V. anguillarum). Results showed that the CASP3-regulated intrinsic apoptosis was activated after A. salmonicida infection, while the CASP8 and CASP6-regulated extrinsic apoptosis exerted the greatest effect on trout challenged with V. anguillarum. In response to V. anguillarum infection, the data of RNA-Seq further showed the casp8 was tightly integrated with the significantly enriched Gene Ontology terms and functional pathways, including apoptosis regulation, pathogen detection and immunomodulation. Our study provides a foundation for the physiological functions and regulatory network of the caspase genes in teleosts., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rainbow trout ( Oncorhynchus mykiss ) is one of the most common aquaculture fish species worldwide. Vibriosis disease outbreaks cause significant setbacks to aquaculture. The stress and immune responses are bidirectionally modulated in response to the health challenges. Therefore, an investigation into the regulatory mechanisms of the stress and immune responses in trout is invaluable for identifying potential vibriosis treatments. We investigated the transcriptional profiles of genes associated with stress and trout immune functions after Vibrio anguillarum infection. We compared the control trout (CT, 0.9% saline injection), asymptomatic trout (AT, surviving trout with minor or no symptoms after bacteria injection), and symptomatic trout (ST, moribund trout with severe symptoms after bacteria injection). Our results showed activated immunomodulatory genes in the cytokine network and downregulated glucocorticoid and mineralocorticoid receptors in both AT and ST, indicating activation of the proinflammatory cytokine cascade as a common response in AT and ST. Moreover, the AT specifically activated the complement- and TNF-associated immune defenses in response to V. anguillarum infection. However, the complement and coagulation cascades, as well as steroid hormone homeostasis in ST, were disturbed by V. anguillarum . Our studies provide new insights toward understanding regulatory mechanisms in stress and immune functions in response to diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hou, Xin, Yang, Zeng, Zhao, Liu, Zhang, Daniel, Li and Wen.)

Background: The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD., Methods: A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency., Results: In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio = 0.80; 95% confidence interval: 0.45-1.07; P  = 0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P = 0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P = 0.8785)., Conclusions: As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD., Trial Registration: chictr.org.cn, No. ChiCTR-TRC-12003513., (Copyright © 2020 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

G protein-coupled receptors (GPCRs) play critical roles in transmitting a variety of extracellular signals into the cells and regulate diverse physiological functions. Naturally occurring mutations that result in dysfunctions of GPCRs have been known as the causes of numerous diseases. Significant progresses have been made in elucidating the pathophysiology of diseases caused by mutations. The multiple intracellular signaling pathways, such as G protein-dependent and β-arrestin-dependent signaling, in conjunction with recent advances on biased agonism, have broadened the view on the molecular mechanism of disease pathogenesis. This review aims to briefly discuss biased agonism of GPCRs (biased ligands and biased receptors), summarize the naturally occurring GPCR mutations that cause biased signaling, and propose the potential pathophysiological relevance of biased mutant GPCRs associated with various endocrine diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

An energy trade-off is existed between immunological competence and growth. The axis of growth hormone releasing hormone, somatostatin, growth hormone, insulin-like growth factor (GHRH-SST-GH-IGF axis) regulates growth performances and immune competences in rainbow trout (Oncorhynchus mykiss). The salmonid-specific whole genome duplication event is known to result in duplicated copies of several key genes in GHRH-SST-GH-IGF axis. In this study, we evaluated the physiological functions of GHRH-SST-GH-IGF axis in regulating crosstalk between growth and immunity. Based on principal components analysis (PCA), we observed the overall expression profiles of GHRH-SST-GH-IGF axis were significantly altered by Vibrio anguillarum infection. Trout challenged with Vibrio anguillarum showed down-regulated igf1s subtypes and up-regulated igfbp1a1. The brain sst genes (sst1a, sst1b, sst3b and sst5) and igfpbs genes (igfbp4s and igfbp5b2) were significantly affected by V. anguillarum infection, while the igfbp4s, igfbp5s, igfbp6s and igf2bps genes showed significant changes in peripheral immune tissues in response to V. anguillarum infection. Gene enrichment analyses showed functional and signaling pathways associated with apoptosis (such as p53, HIF-1 or FoxO signaling) were activated. We further proposed a possible model that describes the IGF and IGFBPs-regulated interaction between cell growth and programmed death. Our study provided new insights into the physiological functions and potentially regulatory mechanisms of the GHRH-SST-GH-IGF axis, indicating the pleiotropic effects of GHRH-SST-GH-IGF axis in regulating crosstalk between growth and immunity in trout., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Stimulus-responsive optical polymers, especially gels, are enabling new-concept energy-transducing "smart" optics. Full exploitation of their molecule-derived tuning and integration with traditional micro/nano-optics/optoelectronics rely on the implementation of devices by advanced "intelligent" micro/nano-manufacturing technologies, especially photolithographies with wide compatibility. In light of the increasing need for an organic combination of smart optical materials and digital micro/nano-manufacturing, novel "smart" optical micro-switches, namely, stimulus-actuated Mach-Zehnder interferometers as a proof-of-concept demonstration, were prototyped with protein-based hydrogels via aqueous multiphoton femtosecond laser direct writing (FsLDW). Protein-based Mach-Zehnder-interferometric smart optical devices here display a morphological quality sufficient for optical applications (average surface roughness ≤∼20 nm), nano-precision three-dimensional (3D) geometry of these millimeter-scale devices and purposely structured distribution of photo-crosslinking degree. Moreover, the device configuration was customized with unbalanced branches in which meticulous stimulus-responsive ability can be realized by simply tuning the surrounding chemical stimuli (i.e., Na 2 SO 4 concentration here). The "heterogeneous" configuration with unbalanced branches (i.e., different optical and stimulus-responsive features) exhibits as-designed "smart" switching of propagated near-infrared light (∼808 nm). These capabilities, along with total biodegradation, indicate the application promise of this gel-based optic construction strategy towards novel "intelligent", bio/eco-friendly, self-tuning or sensing photonic integrated systems like optofluidics.

We propose UV-IR femtosecond laser hybrid lithography for the efficient printing of complex on-chip waveguides, which offers good performance in terms of processing efficiency and accuracy. With this three-dimensional printing technology, waveguides with complex cross-section shapes, such as owls and kittens, can be easily fabricated with an efficiency increased by 1500% (for ${6}\;\unicode{x00B5} {\rm m}\; \times \;{6}\;\unicode{x00B5} {\rm m}$6µm×6µm). In addition, a circular cross-section waveguide with an extremely low birefringence and complex ${8} \times {8}$8×8 random walk networks were quickly customized, which implies that in the design and preparation of the large-scale optical chips, the proposed maskless method allows for the preparation of highly customized devices.

Natural compound eyes provide the inspiration for developing artificial optical devices that feature a large field of view (FOV). However, the imaging ability of artificial compound eyes is generally based on the large number of ommatidia. The lack of a tunable imaging mechanism significantly limits the practical applications of artificial compound eyes, for instance, distinguishing targets at different distances. Herein, we reported zoom compound eyes that enable variable-focus imaging by integrating a deformable poly(dimethylsiloxane) (PDMS) microlens array (MLA) with a microfluidic chamber. The thin and soft PDMS MLA was fabricated by soft lithography using a hard template prepared by a combined technology of femtosecond laser processing and wet etching. As compared with other mechanical machining strategies, our combined technology features high flexibility, efficiency, and uniformity, as well as designable processing capability, since the size, distribution, and arrangement of the ommatidia can be well controlled during femtosecond laser processing. By tuning the volume of water injected into the chamber, the PDMS MLA can deform from a planar structure to a hemispherical shape, evolving into a tunable compound eye of variable FOV up to 180°. More importantly, the tunable chamber can functionalize as the main zoom lens for tunable imaging, which endows the compound eye with the additional capability of distinguishing targets at different distances. Its focal length can be turned from 3.03 mm to infinity with an angular resolution of 3.86 × 10 -4 rad. This zoom compound eye combines the advantages of monocular eyes and compound eyes together, holding great promise for developing advanced micro-optical devices that enable large FOV and variable-focus imaging.

Hypoxia generally refers to a dissolved oxygen (DO) level that is less than 2-3 mg/L. With ongoing global warming and environment pollution, environmental or geological studies showed hypoxia frequently occurs in global aquatic systems including ocean, river, estuaries and coasts. A preliminary study was performed to evaluate hypoxia tolerant of rainbow trout (Oncorhynchus mykiss) with parameters of mortality, behavior, endocrine and metabolite, identifying three DO levels including normoxia (Ctrl, 7.0 mg/L), non-lethal hypoxia (NH, 4.5 mg/L) and lethal hypoxia (LH, 3.0 mg/L). Furthermore, trout was treated by Ctrl, NH and LH for six hours to mimic the acute hypoxia in wild and/or farming conditions. A significantly higher mortality was observed in LH group. Trout of NH and LH showed stressful responses with unnormal swimming, increased serum cortisol and up-regulated gill hif1α transcription. Despite trout of NH and LH increased the oxygen delivery abilities by increasing the serum hemoglobin levels, the anerobic metabolism were inevitably observed with increased lactate. This study also showed a prolonged influence of NH and LH on growth after 30-days' recovery. Based on RNA-Seq data, different expression genes (DEGs) associated with stress, apoptosis, antioxidant, chaperone, growth, calcium and vitamin D metabolism were identified. Enrichment analysis showed DEGs were clustered in osteoclast differentiation, apoptosis and intracellular signaling transduction pathways. Results further showed NH and LH significantly decreased bone calcium content and disrupted the growth hormone-insulin-like growth factor (GH-IGF) axis. Our study might contribute to a better understanding of the effects of hypoxia on rainbow trout., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Low levels of stresses cause eustress while high stressful situations result in distress. Female rainbow trout (Oncorhynchus mykiss) was reared under crowded conditions to mimic the stressful environment of intensive fishery production. Trout was stocked for 300 days with initial densities of 4.6 ± 0.02 (final: 31.1 ± 0.62), 6.6 ± 0.03 (final: 40.6 ± 0.77), and 8.6 ± 0.04 (final: 49.3 ± 1.09) kg/m 3 as SD1, SD2 and SD3. We assessed molecular, cellular and organismal parameters to understand the flexibility of neuro-endocrine-immune network during stress. Trout with higher initial density (SD3) displayed the slightly activated hypothalamus-pituitary-interrenal (HPI) axis with positively increased antioxidant enzyme activities and anti-inflammatory cytokine transcriptions on day 60 or 120. These results indicated that low level of stress was capable of exerting eustress by activating neuro-endocrine-immune network with beneficial adaptation. Transition from eustress to distress was induced by the increased intensity and duration of crowding stress on day 240 and 300. The prolonged activation of HPI axis resulted in suppressed growth hormone-insulin-like growth factor (GH-IGF) axis, up-regulated cytokine transcriptions and severe reactive oxygen species stress. Stress means reset of neuro-endocrine-immune network with energy expenditure and redistribution. Digestive ability of trout with distress was also inhibited on day 240 and 300, indicating a decreased total energy supplement and energy distribution for functions are not necessary for surviving such as growth and reproduction. Consequently, we observed the dyshomeostasis of energy balance and neuro-endocrine-immune network of trout during long-term crowding conditions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Melanocortin-4 receptor (MC4R) plays important roles in regulation of multiple physiological processes including energy homeostasis, reproduction, sexual function, and other functions in mammals. Recent studies suggested that teleost MC4Rs have different physiological functions and pharmacological characteristics when compared to mammalian MC4Rs. In this study, we investigated spotted sea bass ( Lateolabrax maculatus ) MC4R ( Lm MC4R) physiology and pharmacology. Spotted sea bass mc4r consisted of a 984 bp open reading frame encoding a protein of 327 amino acids. Lm MC4R was homologous to those of several teleost MC4Rs and human MC4R (hMC4R). qRT-PCR and in situ hybridization revealed that mc4r transcripts were highly expressed in the brain, followed by pituitary and liver. Brain mc4r transcripts were down-regulated in long-term and short-term fasting challenges. Lm MC4R was a functional receptor with lower maximal binding and higher basal activity than hMC4R. THIQ was not able to displace 125 I-NDP-MSH but could affect intracellular cAMP accumulation, suggesting that it was an allosteric ligand for Lm MC4R. In vitro studies with spotted sea bass brain cells indicated that mRNA levels of neuropeptide Y and Agouti-related peptide were down-regulated by α-MSH. In summary, we cloned spotted sea bass MC4R, and showed that it had different pharmacological properties compared to hMC4R, and potentially different functions., (Copyright © 2019 Zhang, Hou, Wen, Li, Qi, Li and Tao.)

X-linked acrogigantism (XLAG) is a recently described early-onset gigantism due to GPR101 duplication that induces growth hormone (GH) oversecretion. GPR101, which belongs to Family A rhodopsin-like family of G protein-coupled receptors, is predominantly expressed in hypothalamus and pituitary, suggesting that GPR101 might be important in regulating diverse functions such as energy balance and reproduction. Most mammalian GPR101s have extremely long third intracellular loops (ICL3); however, zebrafish GPR101 has a much shorter ICL3, but a longer C-terminus. GnRH-(1-5), a GnRH metabolite, can modulate the hypothalamus-pituitary-gonad axis and cancer cell migration via activating GPR101. GPR101 couples to both Gα s and Gα i proteins. GPR101 duplication has a causative role in XLAG, while GPR101 variants, especially c.924G>C (E308D), located at ICL3, are attributed to acromegaly. Some GPR101 mutations that are associated with a small proportion of pituitary tumors without GH oversecretion have also been identified recently. This chapter will summarize studies on GPR101, including its molecular cloning and tissue distribution, physiology, pharmacology, and pathophysiology., (© 2019 Elsevier Inc. All rights reserved.)

Introduction: Conformational diseases are caused by structurally abnormal proteins that cannot fold properly and achieve their native conformation. Misfolded proteins frequently originate from genetic mutations that may lead to loss-of-function diseases involving a variety of structurally diverse proteins including enzymes, ion channels, and membrane receptors. Pharmacoperones are small molecules that cross the cell surface plasma membrane and reach their target proteins within the cell, serving as molecular scaffolds to stabilize the native conformation of misfolded or well-folded but destabilized proteins, to prevent their degradation and promote correct trafficking to their functional site of action. Because of their high specificity toward the target protein, pharmacoperones are currently the focus of intense investigation as therapy for several conformational diseases. Areas covered: This review summarizes data on the mechanisms leading to protein misfolding and the use of pharmacoperone drugs as an experimental approach to rescue function of distinct misfolded/misrouted proteins associated with a variety of diseases, such as lysosomal storage diseases, channelopathies, and G protein-coupled receptor misfolding diseases. Expert commentary: The fact that many misfolded proteins may retain function, offers a unique therapeutic opportunity to cure disease by directly correcting misrouting through administering pharmacoperone drugs thereby rescuing function of disease-causing, conformationally abnormal proteins.

To study the expression of four estrogen receptor genes (erα1, erα2, erβ1, erβ2) of female rainbow trout (Oncorhynchus mykiss) during first ovarian development, trouts were sampled from different ovarian stages. Serum E 2 (estradiol) was measured by ELISA and estrogen receptors mRNA expression were examined by qRT-PCR. Our results showed a close association between increased erα1 and vitellogenin mRNA expression during ovarian maturation and increased erα2 mRNA expression in mature ovarian stages. Correlation analysis revealed that a negative relationship between serum E 2 and ovarian erβ1 (or hepatic erβ2), but ovarian erβ2 mRNA expression was relatively unchanged during first ovarian development. Trout were also reared in different densities as stocking density 1, 2 and 3 (SD1, 4.6-31.1 kg/m 3 ; SD2, 6.6-40.6 kg/m 3 ; SD3, 8.6-49.3 kg/m 3 ) to elucidate effects of high density on estrogen receptor expression. Histology observation showed ovarian development of trout in higher densities were retard with a relatively early stage and fewer vitellogenin accumulation. Trout in high densities showed significantly decreased serum E 2 , erα mRNA expression and increasing trends of erβ mRNA expression. A noticeable increase of ovarian erβ2 mRNA expression was seen in trout when density is approaching to 50 kg/m 3 . In conclusion, we may hypothesize that increased erβ mRNA expression triggered by high density result in decreased erα mRNA expression and vitellogenesis. As a result, ovarian development in higher densities was retard., (Copyright © 2017. Published by Elsevier Inc.)

This study describes the preparation and properties of a novel aliphatic cost-effective segmented polyurethanes (SPUs) based on poly(ether ester) (poly-(ε-caprolactone-co-l-lactide)-poly(ethylene glycol)-poly-(ε-caprolactone-co-l-lactide), PECLA) and uniform-size diurethane diisocyanates (HDI-BDO-HDI). PECLA was synthesized via bulk ring-opening polymerization with poly(ethylene glycol) (PEG) as an initiator and ε-caprolactone, l-lactide as monomers. By chain extension of PECLA diol with HDI-BDO-HDI, three SPUs with different hydrophilic segments content and hard segments content were obtained. The chemical structures of the chain extender, PECLA and SPUs were confirmed by 1 H NMR, 13 C NMR, FT-IR, HR-TOF-MS and GPC. The influences of PEG content and uniform-size hard segments on in vitro degradability and mechanical properties of SPU films were researched. Similar thermostability observed in TGA curves of SPU films indicated that the hard segments and PEG content had little influence on the thermostability. The formation of microsphase-separated morphologies, which were demonstrated by the results of DSC and XRD, and physical-linking (H-bonds) network structures led to better mechanical properties of SPU films (ultimate stress: 23.1-17.9 MPa; elongation at break: 840-1130%). The results of water absorption and water contact angle showed that the bulk and surface hydrophilicity were closely related with the hydrophilic PEG content in SPU backbone. And the water absorption being less than 10 wt% indicated that the SPU films had low swelling property. In vitro hydrolytic degradation studies showed that the time of the SPU films becoming fragments was 34-19 days and the degradation rate increased with the increasing content of hydrophilic segments in SPUs, indicating that the degradation rate of SPU films could be controlled by adjusting PEG content. Cytotoxicity test of film extracts were conducted using L929 cells, and the relative growth rate exceeded 90% after incubation for 24, 48 and 72 h, showing excellent cytocompatibility. The acceptable mechanical properties, controllable biodegradability and excellent cytocompatibility of the polyurethanes can make them good candidates for further biomedical applications.

The objective of this study was to determine the hypothalamus-pituitary-gonad (HPG) axis of female rainbow trout (Oncorhynchus mykiss) during early ovarian development and under high rearing density. Trouts were sampled from 240 (ovarian stage II) to 540 (ovarian stage IV) days following hatching (DFH) as control group (Ctrl, 4.6-31.1kg/m(3)) to determine HPG axis during early ovarian development. Trouts from the same batch of fertilized eggs were reared in two higher densities during 240-540 DFH as stocking density 1 and 2 (SD1, 6.6-40.6kg/m(3); SD2, 8.6-49.3kg/m(3)) to elucidate effects of high density on reproductive parameters. Dopamine, E2 (estradiol), 17α,20β-P (17α,20β-dihydroxy4-pregnen-3-one) and P4 (progesterone) were evaluated by radioimmunoassay or ELISA. mRNA expression of hypothalamic gnrh-1, -2 (gonadotropin-releasing hormone-1, -2), pituitary gonadotropins (fsh/lh, follicle-stimulating hormone/luteinizing hormone) and their cognate receptors (fshr/lhr) in ovaries were examined by qRT-PCR. Our findings demonstrated mRNA expression of hypothalamic sgnrh-1, pituitary fsh and ovarian fshr increased in early ovarian development (360 DFH). Serum 17α,20β-P and pituitary lh mRNA expression first increased when trouts were in ovarian stage III (420 DFH). Ovaries were at different stages when reared in different densities. Long-term high density treatment (over 31.7kg/m(3)) resulted in decreased hypothalamic sgnrh-1, pituitary fsh, ovarian fshr, serum E2, and increased hypothalamus gnrh-2 and serum dopamine during vitellogenin synthesis, suggesting HPG of rainbow trout might be retarded under dense rearing condition., (Copyright © 2016 Elsevier Inc. All rights reserved.)

For the first time, proteins, a promising biocompatible and functionality-designable biomacromolecule material, acted as the host material to construct three-dimensional (3D) whispering-gallery-mode (WGM) microlasers by multiphoton femtosecond laser direct writing (FsLDW). Protein/Rhodamine B (RhB) composite biopolymer was used as optical gain medium innovatively. By adopting high-viscosity aqueous protein ink and optimized scanning mode, protein-based WGM microlasers were customized with exquisite true 3D geometry and smooth morphology. Comparable to previously reported artificial polymers, protein-based WGM microlasers here were endowed with valuable performances including steady operation in air and even in aqueous environments, and a higher quality value (Q) of several thousands (without annealing). Due to the "smart" feature of protein hydrogel, lasing spectrum was responsively adjusted by step of ~0.4 nm blueshift per 0.83-mmol/L Na2SO4 concentration change (0 ~ 5-mmol/L in total leading to ~2.59-nm blueshift). Importantly, other performances including Q, FWHM, FSR, peak intensities, exhibited good stability during adjustments. So, these protein-based 3D WGM microlasers might have potential in applications like optical biosensing and tunable "smart" biolasers, useful in novel photonic biosystems and bioengineering.

Objective: To establish the fingerprint analysis method of Ganershu intermediate by HPLC., Methods: An analysis was performed on a sunFire C18 (4. 6 mm x 250 mm, 5 microm) column with acetonitrile-0.1% phosphate aqueous as the mobile phase by gradient elution. The flow rate was 1.0 mL/min, the detection wavelength was 320 nm and detection time was 80 min. The column temperature was 35 degrees C. In the recorded chromatogram of Ganershu intermediate, neohesperidin was used as reference substance, and RSD of the relative retention time and the relative peak areas of all peaks compared with its peak were measured. The similarity of 10 batches of Ganershu intermediate was appraised by the similarity evaluation system. Using the external standard method, the contents of chlorogenic acid, neohesperidin and naringin were determined in 10 batches of intermediate., Results: Tweenty-three peaks were separated on HPLC fingerprint in Ganershu intermediate, degree of similarity of fingerprint for ten batches of Ganershu intermediate were greater than 0.90. Three compounds' contents were almost the same in each batch of intermediate sample., Conclusion: The method is stable, accurate, reliable and can be used as a quality control for Ganershu intermediate and sustained-release capsules.

Although previous studies showed that transthoracic echocardiography (TTE) can be used to guide transcatheter closure of atrial septal defect (ASD), whether TTE can be used to guide transcatheter closure of secundum ASD with a deficient superior-anterior rim is unknown and this critical issue was addressed in the present study. A total of 280 patients with secundum ASD who underwent transcatheter ASD closure were recruited and divided into groups A and B depending on ASD superior-anterior rim>4 mm (n = 118) or ≤4 mm (n = 162). TTE was used to guide Amplatzer-type septal occluder (ASO) positioning and assess residual shunt. Procedure success was defined as no, trivial and small residual shunt immediately after the procedure as assessed by color Doppler flow imaging. Group A and group B did not differ in complication rate (8.55% vs.7.55%), procedure success rate (98.3% vs. 95.0%) or complete closure rate immediately after the procedure (89.7% vs. 89.3%) or at 6-month follow-up (98.3% vs. 96.8%). The mean procedure and fluoroscopy time in group B were much longer than those in group A. In conclusion, the absence of a sufficient superior-anterior rim in patients undergoing percutaneous closure of secundum-type ASDs using fluoroscopic and TTE guidance is associated with slightly greater device malposition and migration as well as increased procedural and fluoroscopic times, but the overall complication rate did not differ with TTE guidance when compared to historical controls that used TEE guidance.

Objective: To evaluate the efficacy and safety of Chinese medicinal shensongyangxin capsules in the treatment of paroxysmal atrial fibrillation., Methods: From August 2007 to July 2008, Beijing Chaoyang Hospital conducted a multicenter study, select the eleven hospital's outpatient subjects, aged 18 to 75 years old, male or female, paroxysmal atrial fibrillation (at least one electrocardiogram diagnosis) seizure frequency ≥ 2 times/month, according to the ratio 1:1:1, subjects were randomly divided into three groups: a. shensongyangxin group, taking shensongyangxin capsule 4 + propafenone analogues 150 mg, 3 times a day; b. propafenone group, taking propafenone tablets 150 mg + 4 shensongyangxin analogues, 3 times a day; shensongyangxin capsule + propafenone group, taking shensongyangxin capsule 4 + propafenone 150 mg, 3 times a day. The treatment course is 8 weeks, with 3 times of follow-up., Results: Total of 349 cases of paroxysmal atrial fibrillation, which 117 cases in shensongyangxin group, 115 cases in propafenone group; 117 cases in shensongyangxin + propafenone group. The baseline data analysis showed that there were no significantly difference (P > 0.05) among the three groups of atrial fibrillation seizure frequency, vital signs, general condition, medical history, 24-hour ambulatory ECG, 12-lead normal electrocardiogram, cardiac ultrasound and symptoms. The comparison before and after (8 weeks) treatment showed that the frequency (from 6 times/m to 2 times/m in each group, P < 0.01), number of cases [from 46 (43.3%) to 22 (20.8%), 43 (43.4%) to 25 (25.3%), and 40 (40.6%) to 31 (29.2%), respectively P < 0.01] and duration time of attack of atrial fibrillation (from 4 h to 0.5 h, 4 h to 0.5 h, and 4.25 h to 0.5 h, respectively P < 0.01) all decreased in three groups. No significant difference among the three groups comparing the overall effect (62.3%, 58.6%, and 58.5%, respectively, P > 0.05), while the efficacy of TCM symptoms in shensongyangxin group (80.2%) was better than that of propafenone group (67.7%) (P < 0.05). Safety evaluation showed that adverse reaction rate was 1.8% in shensongyangxin group, and 8.2% and 5.4% in propafenone group and shensongyangxin + propafenone group., Conclusion: Shensongyangxin capsules and propafenone have comparable efficacies in the treatment of PAF. The efficacy of TCM symptoms is better than propafenone. Shensongyangxin capsules have an excellent profile of safety.

Objective: To evaluate malaria situation in areas of Yunnan Province bordering with Myanmar, Laos and Vietnam., Methods: Blood samples on filter paper were collected from the entry people in March to December of 2007 involving 19 national and provincial ports of entry. Indirect fluorescent antibody test (IFAT) was carried out by using the blood samples collected before June 30 as the first half year and after July 1 as the second half year. Analysis was made on the relationship of IFAT positive rate and GMRT to malaria incidence in the province reported by the China information system for disease control and prevention., Results: IFAT positive rate in the first half year (5.6%) was 20.9% higher than that of second half year (4.4%) (chi2=12.95%, P<0.05). There was a positive correlation between IFAT positive rate and the number of malaria cases reported in 2007 from the 8 bordering prefectures (r=0.8124, P<.05). The highest IFAT positive rate was found in Dehong (8.7%), Baoshan (7.1%), and Lingcang (65%). Among the 19 entry ports, the highest IFAT positive rate was found in 5 entry ports: Lvliang, Laying, Jiegao, Houqiao, and Qingshuihe, all in China-Myanmar border. The IFAT positive rate in the Chinese entry people increased with their days of staying outside the border. Among the entry people, the highest antibody positive rate was from those of Myanmar nationality (11.7%) followed by those from Yunnan (3.7%)., Conclusion: To certain extent, higher malaria incidence outside the border impacts that of Yunnan Province.

Objective: To observe the outcome of percutaneous balloon mitral valvuloplasty (PBMV) in patients with rheumatic mitral valve stenosis., Methods: From April 1992 to November 2008, 1768 patients underwent PBMV in our hospital.Clinical and echocardiographic follow up data were analyzed in 426 patients from April 1992 to August 1998. Left atrial pressure and the mitral valve gradient (MVG) were measured before and immediately after PBMV in all patients., Results: PBMV was successful in 1748 out of 1768 patients (98.86%). Left atrial pressure decreased from (38 +/- 7) mm Hg (1 mm Hg = 0.133 kPa) to (12 +/- 4) mm Hg (P < 0.001), MVG decreased from (28 +/- 6) mm Hg to (8 +/- 3) mm Hg (P < 0.001) and the area of the mitral valve increased from (0.98 +/- 0.26) cm(2) to (1.97 +/- 0.39) cm(2) (P < 0.001) post PBMV. The main complications included death (n = 2), acute pericardial effusion (n = 1), severe mitral regurgitation (n = 12), cerebral embolism (n = 2) and pulmonary edema (n = 1). Ten years follow up was finished in 426 patients and 288 patients (67.6%) were still in NYHA class Ior II without mitral valve replace operation or repeated PBMV, restenosis was evidenced in 140 patients (33.3%) and 31 patients dead (7.5%)., Conclusion: PBMV was an effective therapy option for patients with rheumatic mitral valve stenosis.

Water-soluble porphyrins can be phase transferred by the hyperbranched multiarm copolymer PEI-PZLys; good catalytic activities and recyclabilities were observed for oxidation catalyzed by the encapsulated porphyrins.

Objective: To discuss the feasibility of the operation of minimal invasive with gallbladder preserved via choledochoscopy., Methods: From February 1992 to June 2006, there were 760 patients who underwent cholecystolithiasis treated with the minimal invasive operation with gallbladder preserved via choledochoscopy, among which there were 428 males and 332 females, aged from 18 to 81 years old. All cases were diagnosed by ultrasonography and their gallbladder functions were proved normal by the examination of oral cholecystography or ECT before operation. In the operation gallstones were removed from gallbladder completely., Results: There were 612 cases who were followed up for 1-15 years and the follow-up rate was 80.5%. All patients recovered well after operation. The post-operation rate of recurrence of gallstone was 0.49%, 4.39%, 5.83%, 6.60%, 7.21% and 8.38% within the first year, the second year, the third year, the fifth year, the seventh year and the ninth year respectively, rate of recurrence of gallstone were 10.11% within both the tenth and the fifteenth year., Conclusions: The minimal invasive operation with gallbladder preserved via choledochoscopy is effective to cholecystolithiasis patients whose gallbladder function is normal. It is a feasible operation that preserves the normal functional gallbladder and improves the patients' life quality.

Background: Warfarin is a commonly prescribed anticoagulant drug for the prevention of thromboses. To address the association of genetic factors and warfarin dosage for ethnic Han Chinese, we genotyped six candidate genes involved in the warfarin interactive pathway with focus on SNPs with reported association with warfarin dose., Methods: We recruited a study population consisted of 318 patients receiving warfarin treatment and 995 healthy controls. PCR and direct sequencing were used to identify the sequence polymorphisms., Results: In our study population, SNP rs1799853 of CYP2C9, rs1687390 of ORM1-2, and rs2069919 of PROC showed no variation. SNPs rs12714145 of GGCX and rs1799809 of PROC showed no significant correlation with warfarin dose. The associations of SNPs rs9934438 and rs9923231 of VKORC1, the 3 (rs1057910) and C(-65) (rs9332127) alleles of CYP2C9, and SNP rs4653436 of EPHXI with the dose of warfarin were significant., Conclusion: A multiple regression model based on the genetic polymorphisms of VKORC1, CYP2C9, EPHX1 and the non-genetic factors of age and body weight can explain 40.2% of the variance in warfarin dose in Han Chinese patients. Translation of this knowledge into clinical guidelines for warfarin prescription may improve the safety and efficacy of warfarin treatment among Han Chinese.

During the acquisition of a magnetic resonance images (MRI), blurring and ghosting artifacts caused by the patient's motion can seriously affect the result of diagnosis. A novel automatic post-processing strategy, inverse iterative correction (IIC), has been developed to suppress MRI artifacts due to the object's in-plane rigid-body motion. By means of the proposed histogram-based entropy function, IIC method uses two successive steps to reduce the simulated motion artifacts: first, the inverse phase errors are added to all possible simulated patient's motion directions, and in the second step, the actual directions and displacement from the patient's motion are estimated to properly correct the phase, hence remove the artifacts after searching all the trial directions. To verify its feasibility, the proposed method was used to reduce rigid-motion artifacts due to simulated motion in MRI images. The experimental results showed that the new algorithm significantly outperforms over the entropy auto-focus compensation algorithm on the quality of corrections for the motion artifacts and computational cost.