We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation r...We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.展开更多
Nowadays,the Chinese market is full of imported farming products,including products such as Thai rice,Vietnamese durian,Australian fresh meat.In the meantime,China’s special farming products also appear on the overse...Nowadays,the Chinese market is full of imported farming products,including products such as Thai rice,Vietnamese durian,Australian fresh meat.In the meantime,China’s special farming products also appear on the overseas dining table.Utilizing both the domestic and overseas markets and resources,China’s farming has展开更多
BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants signif...BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.展开更多
The author of the paper analyzes the story"Glass Coffin"in A. S. Byatt's Possession and compares it with Brothers Grimm's fairy tale with the same name. Through the study, the author identifies the q...The author of the paper analyzes the story"Glass Coffin"in A. S. Byatt's Possession and compares it with Brothers Grimm's fairy tale with the same name. Through the study, the author identifies the quest motif from our modern hero's discovery journey in Possession.展开更多
Virginia Woolf’s seventh novel,The Waves,first published by the Hogarth Press in 1931,is widely regarded as her most experimental piece of writing.The complex and elusive structure of the work,the least representatio...Virginia Woolf’s seventh novel,The Waves,first published by the Hogarth Press in 1931,is widely regarded as her most experimental piece of writing.The complex and elusive structure of the work,the least representational among Woolf’s novels,challenges the reader’s assumptions about the inner and the outer world.In the absence of a substantial story,of a convincing plot and well-defined characters,the reader is called upon to search for a deeper coherence and more profound meanings.Indeed,in The Waves the modernist writer strives for a fresh way of expressing a vision of wholeness in a broken world.The present article attempts to reread Woolf’s self-conscious novel in the double perspective of separation and reunion,of dispersal and recomposition.A close reading of selected passages will show how the poetics of fragmentation and the poetics of wholeness coexist in Woolf’s narrative,pervading the imagery and the symbols of the text.In more than one sense,the dialectic between division and unity,fragmentation and wholeness can be identified as the structuring force of the novel;most tellingly,this textual dynamism is reflected in the oscillatory motion of the waves,continuously breaking and merging.展开更多
Traditionally, silence is regarded as an absence, inaction, emptiness, or inferiority, but it figures in Woolf's novels as a presence, power, creativity, and superiority, and infused with a new psychic and narrati...Traditionally, silence is regarded as an absence, inaction, emptiness, or inferiority, but it figures in Woolf's novels as a presence, power, creativity, and superiority, and infused with a new psychic and narrative life. The present paper will examine Woolf's expression of silence in her masterpiece To the Lighthouse to reveal the power of silence.展开更多
MicroRNAs have emerged as one of the major classes of non-coding RNAs. Recent reports have placed them in high abundance in the nervous system, having key roles in development. Neurological disorders such as Parkinson...MicroRNAs have emerged as one of the major classes of non-coding RNAs. Recent reports have placed them in high abundance in the nervous system, having key roles in development. Neurological disorders such as Parkinson’s disease, Alzheimer’s disease as well as Huntington disease have also been studied and several microRNAs associated with diseases pathogenesis have been identified. Various such findings indicate differential expression levels of many of these microRNAs. Such changes in the expression levels not only indicate towards a control of the biogenesis of these microRNAs but also indicate towards critical yet unelucidated roles of regulatory proteins, which probably act in concert to control the production or maturation of these molecules. In this work, a collection of overrepresented regulatory motif signatures were identified in the DNA and RNA sequences of the precursor microRNAs. The identification of such regulatory sequence signatures promises to provide new insights into many facets of microRNA regulation and neurological disorders.展开更多
Stainless steel alloy SS-304 is widely used in many engineering applications primarily for its excellent corrosion resistance, ease of fabrication and aesthetic appeal. Many kitchen appliances are made from SS-304 all...Stainless steel alloy SS-304 is widely used in many engineering applications primarily for its excellent corrosion resistance, ease of fabrication and aesthetic appeal. Many kitchen appliances are made from SS-304 alloy because of its durability, ease of cleaning and beautiful finish. However, over the years of continuous usage and cleaning by detergent bar and abrasive clothes the initial brightness and shine of the plates and dishes undergo considerable degradation. In this work, we report the results of a thorough investigation of the physico-chemical characteristics of the surface regions of both new and old SS-304 plates of known history of continuous usage to identify the key physical and chemical factors that are responsible for the loss of shine. Several analytical techniques viz. SEM/EDX, AFM, XPS, XRD, Reflectance FTIR, Profilometry and Reflectance spectrometry in the visible region have been used for experimental investigation of surface structure, morphology, roughness profile, chemical composition and appearance measurements of several steel samples. In addition, glossmeter has been used to measure the gloss of the samples at certain specific angles. It seems that surface roughness is one of the key physical parameters that play an important role in the reduction of brightness and shine. The other parameter is the presence of a thin surface film on the steel surface. In order to analyze the experimental data and to predict the shine and brightness phenomena quantitatively, we have used Fresnel’s theory to compute first the reflectance from each component of SS-304 alloy assuming it to be a smooth surface and then extended it to compute the reflectance of the alloy surface (SS-304). In order to interpret the reflectance from old and used plates, we have further used Beckmann’s theory of light scattering from random rough surface to analyze and predict the appearance aspects of the alloy surface quantitatively. Both the experimental and computed results show good agreement, thus validating the reflectance model used for computing the reflectance from SS-304 alloy surface and the appropriateness of Beckmann’s model of random rough surface.展开更多
The primary assumption of Neuroscience is that all experiences are strongly correlated with or caused by the specifics of brain structures and their particular dynamics. The profound experiences attributed to the “se...The primary assumption of Neuroscience is that all experiences are strongly correlated with or caused by the specifics of brain structures and their particular dynamics. The profound experiences attributed to the “sensed presence” and their cultural anthropomorphisms such as deities and gods are persistent reports in human populations that are frequently associated with permanent changes in behavior, reduced depression and alleviation of pain. The majority of traditional clinical observations and modern imaging techniques have emphasized the central role of right temporal lobe structures and their directly related networks. The experimental simulation of sensed presences which can result in attributions to spiritual, deity-based or mystical sources within the clinical laboratory by the application of physiologically-patterned magnetic fields across the temporal lobes through our God Helmet requires the same precision of technology that is essential for synthesizing molecular treatments for modifying anomalous behavior, depression and pain. Despite the clinical utility of these simulated conditions within Neuroscience and Medicine, misinformation concerning the bases and efficacy of this new technology persist. Here we present detailed technical clarifications and rebuttals to refute these misconceptions. A Hegelian approach to this delay of development and impedance provides a context through which the ultimate synthesis and application of this technology may be accommodated in the near future.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82271327(to ZW),82072535(to ZW),81873768(to ZW),and 82001253(to TL).
文摘We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.
文摘Nowadays,the Chinese market is full of imported farming products,including products such as Thai rice,Vietnamese durian,Australian fresh meat.In the meantime,China’s special farming products also appear on the overseas dining table.Utilizing both the domestic and overseas markets and resources,China’s farming has
基金Supported by the National Natural Science Foundation of China,No.81573507,No.81473283,No.81173131,and No.81320108027Guangdong Provincial Key Laboratory Construction Foundation,No.2017B030314030+1 种基金The National Key Research and Development Program,No.2016YFC0905003the 111 Project,No.B16047
文摘BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.
文摘The author of the paper analyzes the story"Glass Coffin"in A. S. Byatt's Possession and compares it with Brothers Grimm's fairy tale with the same name. Through the study, the author identifies the quest motif from our modern hero's discovery journey in Possession.
文摘Virginia Woolf’s seventh novel,The Waves,first published by the Hogarth Press in 1931,is widely regarded as her most experimental piece of writing.The complex and elusive structure of the work,the least representational among Woolf’s novels,challenges the reader’s assumptions about the inner and the outer world.In the absence of a substantial story,of a convincing plot and well-defined characters,the reader is called upon to search for a deeper coherence and more profound meanings.Indeed,in The Waves the modernist writer strives for a fresh way of expressing a vision of wholeness in a broken world.The present article attempts to reread Woolf’s self-conscious novel in the double perspective of separation and reunion,of dispersal and recomposition.A close reading of selected passages will show how the poetics of fragmentation and the poetics of wholeness coexist in Woolf’s narrative,pervading the imagery and the symbols of the text.In more than one sense,the dialectic between division and unity,fragmentation and wholeness can be identified as the structuring force of the novel;most tellingly,this textual dynamism is reflected in the oscillatory motion of the waves,continuously breaking and merging.
文摘Traditionally, silence is regarded as an absence, inaction, emptiness, or inferiority, but it figures in Woolf's novels as a presence, power, creativity, and superiority, and infused with a new psychic and narrative life. The present paper will examine Woolf's expression of silence in her masterpiece To the Lighthouse to reveal the power of silence.
文摘MicroRNAs have emerged as one of the major classes of non-coding RNAs. Recent reports have placed them in high abundance in the nervous system, having key roles in development. Neurological disorders such as Parkinson’s disease, Alzheimer’s disease as well as Huntington disease have also been studied and several microRNAs associated with diseases pathogenesis have been identified. Various such findings indicate differential expression levels of many of these microRNAs. Such changes in the expression levels not only indicate towards a control of the biogenesis of these microRNAs but also indicate towards critical yet unelucidated roles of regulatory proteins, which probably act in concert to control the production or maturation of these molecules. In this work, a collection of overrepresented regulatory motif signatures were identified in the DNA and RNA sequences of the precursor microRNAs. The identification of such regulatory sequence signatures promises to provide new insights into many facets of microRNA regulation and neurological disorders.
文摘Stainless steel alloy SS-304 is widely used in many engineering applications primarily for its excellent corrosion resistance, ease of fabrication and aesthetic appeal. Many kitchen appliances are made from SS-304 alloy because of its durability, ease of cleaning and beautiful finish. However, over the years of continuous usage and cleaning by detergent bar and abrasive clothes the initial brightness and shine of the plates and dishes undergo considerable degradation. In this work, we report the results of a thorough investigation of the physico-chemical characteristics of the surface regions of both new and old SS-304 plates of known history of continuous usage to identify the key physical and chemical factors that are responsible for the loss of shine. Several analytical techniques viz. SEM/EDX, AFM, XPS, XRD, Reflectance FTIR, Profilometry and Reflectance spectrometry in the visible region have been used for experimental investigation of surface structure, morphology, roughness profile, chemical composition and appearance measurements of several steel samples. In addition, glossmeter has been used to measure the gloss of the samples at certain specific angles. It seems that surface roughness is one of the key physical parameters that play an important role in the reduction of brightness and shine. The other parameter is the presence of a thin surface film on the steel surface. In order to analyze the experimental data and to predict the shine and brightness phenomena quantitatively, we have used Fresnel’s theory to compute first the reflectance from each component of SS-304 alloy assuming it to be a smooth surface and then extended it to compute the reflectance of the alloy surface (SS-304). In order to interpret the reflectance from old and used plates, we have further used Beckmann’s theory of light scattering from random rough surface to analyze and predict the appearance aspects of the alloy surface quantitatively. Both the experimental and computed results show good agreement, thus validating the reflectance model used for computing the reflectance from SS-304 alloy surface and the appropriateness of Beckmann’s model of random rough surface.
文摘The primary assumption of Neuroscience is that all experiences are strongly correlated with or caused by the specifics of brain structures and their particular dynamics. The profound experiences attributed to the “sensed presence” and their cultural anthropomorphisms such as deities and gods are persistent reports in human populations that are frequently associated with permanent changes in behavior, reduced depression and alleviation of pain. The majority of traditional clinical observations and modern imaging techniques have emphasized the central role of right temporal lobe structures and their directly related networks. The experimental simulation of sensed presences which can result in attributions to spiritual, deity-based or mystical sources within the clinical laboratory by the application of physiologically-patterned magnetic fields across the temporal lobes through our God Helmet requires the same precision of technology that is essential for synthesizing molecular treatments for modifying anomalous behavior, depression and pain. Despite the clinical utility of these simulated conditions within Neuroscience and Medicine, misinformation concerning the bases and efficacy of this new technology persist. Here we present detailed technical clarifications and rebuttals to refute these misconceptions. A Hegelian approach to this delay of development and impedance provides a context through which the ultimate synthesis and application of this technology may be accommodated in the near future.
