This study presents the microwave-assisted synthesis and characterization of a series of heterometal lic coordination polymers(HMCPs)with a 4-methyl-2,6-di[(1H-1,2,4-triazol-1-yl)]phenoxo ligand with varying Eu^(Ⅲ)/T...This study presents the microwave-assisted synthesis and characterization of a series of heterometal lic coordination polymers(HMCPs)with a 4-methyl-2,6-di[(1H-1,2,4-triazol-1-yl)]phenoxo ligand with varying Eu^(Ⅲ)/Tb^(Ⅲ)ratios.Single crystal X-ray diffraction reveals a double-chain structure bridged by triazolyl groups.Powder X-ray diffraction confirms the isostructural nature of the synthesized HMCPs.The photophysical properties depend on lanthanide ion concentration and excitation wavelength,leading to a color shift from green to blue as the proportion of Tb^(Ⅲ)decreases and Eu^(Ⅲ)increases.White light generation is achieved in the 8/2 Eu^(Ⅲ)/Tb^(Ⅲ)HMCP(CIE:0.293,0.326)under 335 nm excitation.The study suggests energy transfer from Tb^(Ⅲ)to Eu^(Ⅲ),but both experimental and theoretical calculations indicate that this transfer is orders of magnitude lower than the sensitization through ligand states.展开更多
Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis...Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.展开更多
The World Health Organization （WHO） has extensively revised its manual for semen analysis, and seeks to provide reference limits for semen quality parameters. This raises the question of what is meant by ＇normal＇ ...The World Health Organization （WHO） has extensively revised its manual for semen analysis, and seeks to provide reference limits for semen quality parameters. This raises the question of what is meant by ＇normal＇ （excluding the use of this term to denote a Gaussian distribution）. It could be taken in a purely statistical sense, using a biologically arbitrary cut-off point to denote an abnormal level, typically the extreme 5 percent of the population. Alternatively, ＇normal＇ could be defined according to the biological concept of normality and abnormality, in terms of the point at which biological function becomes impaired. Either of these can be used in descriptive epidemiology, for example, to study trends, but in the case of fertility, both semen quality and functional fertility （time to pregnancy） are continuous variables with no clear threshold. The WHO manual uses the biological meaning of normal, in that it provides the semen parameter distributions for men who have recently fathered pregnancies that took 12 months or less to conceive. However, what is really needed is the same information the other way around： given a particular semen test result, what should be expected in terms of ability to conceive, and how long it is likely to take. In considering epidemiological research, the focus has been mainly on internal comparisons, rather than reference limits, but it would be beneficial if more attention were paid to the absolute levels and to what these mean in terms of function--in other words, if the data were better calibrated biologically.展开更多
Hepatitis B virus （HBV） infection is the leading causeof liver disease and hepatocellular carcinoma （HCC）worldwide, in spite of prophylactic vaccination andantiviral treatment modalities. The immunopathogenesisof ...Hepatitis B virus （HBV） infection is the leading causeof liver disease and hepatocellular carcinoma （HCC）worldwide, in spite of prophylactic vaccination andantiviral treatment modalities. The immunopathogenesisof HBV infection has been intensively studied and ispropelled by complex interactions between the virus andthe host immune system. Natural killer group 2D （NKG2D）is a well-characterized activating receptor, expressed onnatural killer （NK） cells, NK T cells and CD8＋ cytotoxic Tcells. This receptor is present in both humans and miceand binds to a diverge family of ligands that resemble theMHC-class Ⅰ molecules. Increasing evidence shows thatNKG2D-ligand interactions are critical in the establishmentof HBV persistence and the development of liver injuryand HCC. The expression of NKG2D ligands dependson the presence of several polymorphisms and is alsomodulated post-transcriptionally by HBV. While it isknown that HBV circumvents host’s innate immunityvia the NKG2D pathway but the exact mechanismsinvolved are still elusive. This letter discusses previousaccomplishments on the role of NKG2D ligand regulationin the development of chronic HBV, liver injury and HCC.Key words： Hepatitis B virus; Natural killer group 2Dreceptor; Natural killer cells; MHC class I polypeptiderelatedchain A; Hepatocellular carcinoma展开更多
Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complica...Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and noninvasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy.展开更多
Ultrasound (US) is often the first imaging modality employed in patients with suspected focal liver lesions. The role of US in the characterisation of focal liver lesions has been transformed with the introduction of ...Ultrasound (US) is often the first imaging modality employed in patients with suspected focal liver lesions. The role of US in the characterisation of focal liver lesions has been transformed with the introduction of specific contrast media and the development of specialized imaging techniques. Ultrasound now can fully characterise the enhancement pattern of hepatic lesions, similar to that achieved with contrast enhanced multiphasic computed tomography (CT) and magnetic resonance imaging (MRI). US contrast agents are safe, well-tolerated and have very few contraindications. Furthermore, real-time evaluation of the vascularity of focal liver lesions has become possible with the use of the newer microbubble contrast agents. This article reviews the enhancement pattern of the most frequent liver lesions seen, using the second generation US contrast media. The common pitfalls for each type of lesion are discussed. The recent developments in US contrast media and specific imaging techniques have been a major advance and this technique, in view of the intrinsic advantages of US, will undoubtedly gain popularity in the years to come.展开更多
This review focuses on the management of iron metabolism and iron overload experienced in the hereditary condition, human factors engineering(HFE)-associated hemochromatosis. Hemochromatosis refers to a group of genet...This review focuses on the management of iron metabolism and iron overload experienced in the hereditary condition, human factors engineering(HFE)-associated hemochromatosis. Hemochromatosis refers to a group of genetic diseases that result in iron overload; the major one globally is HFE-associated hemochromatosis. The evolution in understanding of the most common form of hereditary hemochromatosis, being the substation of cysteine to a tyrosine at position 282 in the HFE gene, has been extensively studied Novel mutations in both HFE and non-HFE genes have been indicated in this disease which hold significance in its application for the Asia-Pacific region. In conditions with iron overload, the storage of excess iron in various body tissues leads to complications and toxic damage. The most common presenting complaint for this disease is malaise, lethargy and other non-specific symptoms. In order to diagnose hereditary hemochromatosis, there are biochemical, imaging and genetic testing options. Currently, cascade screening of affected families is preferred over population-level screening. The mainstay of treatment is venesection and the appropriate approach to treatment has been consolidated over the years. Recently, the indications for venesection therapy of hemochromatosis have been challenged and are the subject of ongoing research.展开更多
Chronic liver disease has become a global health problem as a result of the increasing incidence of viral hepatitis, obesity and alcohol misuse. Over the past three decades, in the United Kingdom alone, deaths from ch...Chronic liver disease has become a global health problem as a result of the increasing incidence of viral hepatitis, obesity and alcohol misuse. Over the past three decades, in the United Kingdom alone, deaths from chronic liver disease have increased both in men and in women. Currently, 2.5% of deaths worldwide are attributed to liver disease and projected figures suggest a doubling in hospitalisation and associated mortality by 2020. Chronic liver diseases vary for clinical manifestations and natural history, with some individuals having relatively indolent disease and others with a rapidly progressive course. About 30% of patients affected by hepatitis C has a progressive disease and develop cirrhosis over a 20 years period from the infection, usually 5-10 years after initial medical presentation. The aim of the current therapeutic strategies is preventing the progression from hepatitis to fibrosis and subsequently, cirrhosis. Hepatic steatosis is a risk factor for chronic liver disease and is affecting about the half of patients who abuse alcohol. Moreover non-alcoholic fatty liver disease is part of the metabolic syndrome, associated with obesity, hypertension, type Ⅱ diabetes mellitus and dyslipidaemia, and a subgroup of patients develops non-alcoholic steatohepatitis and fibrosis with subsequent cirrhosis. The strengths and pitfalls of liver biopsy are discussed and a variety of new techniques to assess liver damage from transient elastography to experimental techniques, such as in vitro urinary nuclear magnetic resonance spectroscopy. Some of the techniques and tests described are already suitable for more widespread clinical application, as is the case with ultrasound-based liver diagnostics, but others, such as urinary metabonomics, requires a period of critical evaluation or development to take them from the research arena to clinical practice.展开更多
The intestinal epithelium possesses a remarkable ability for both proliferation and regeneration.The last two decades have generated major advances in our understanding of the stem cell populations responsible for its...The intestinal epithelium possesses a remarkable ability for both proliferation and regeneration.The last two decades have generated major advances in our understanding of the stem cell populations responsible for its maintenance during homeostasis and more recently the events that occur during injury induced regeneration.These fundamental discoveries have capitalised on the use of transgenic mouse models and in vivo lineage tracing to make their conclusions.It is evident that maintenance is driven by rapidly proliferating crypt base stem cells,but complexities associated with the technicality of mouse modelling have led to several overlapping populations being held responsible for the same behaviour.Similarly,it has been shown that essentially any population in the intestinal crypt can revert to a stem cell state given the correct stimulus during epithelial regeneration.Whilst these observations are profound it is uncertain how relevant they are to human intestinal homeostasis and pathology.Here,these recent studies are presented,in context with technical considerations of the models used,to argue that their conclusions may indeed not be applicable in understanding“homeostatic regeneration”and experimental suggestions presented for validating their results in human tissue.展开更多
AIM: To investigate whether novel, non-technical skills training for Bowel Cancer Screening (BCS) endoscopy teams enhanced patient safety knowledge and attitudes.
Cellular and mitochondrial membrane phospholipids provide the substrate for synthesis and release of prostaglandins in response to certain chemical,mechanical,noxious and other stimuli.Prostaglandin D_(2),prostaglandi...Cellular and mitochondrial membrane phospholipids provide the substrate for synthesis and release of prostaglandins in response to certain chemical,mechanical,noxious and other stimuli.Prostaglandin D_(2),prostaglandin E_(2),prostaglandin F_(2)α,prostaglandin I_(2)and thromboxane-A_(2)interact with five major receptors(and their sub-types)to elicit specific downstream cellular and tissue actions.In general,prostaglandins have been associated with pain,inflammation,and edema when they are present at high local concentrations and involved on a chronic basis.However,in acute settings,certain endogenous and exogenous prostaglandins have beneficial effects ranging from mediating muscle contraction/relaxation,providing cellular protection,regulating sleep,and enhancing blood flow,to lowering intraocular pressure to prevent the development of glaucoma,a blinding disease.Several classes of prostaglandins are implicated(or are considered beneficial)in certain central nervous system dysfunctions(e.g.,Alzheimer’s,Parkinson’s,and Huntington’s diseases;amyotrophic lateral sclerosis and multiple sclerosis;stroke,traumatic brain injuries and pain)and in ocular disorders(e.g.,ocular hypertension and glaucoma;allergy and inflammation;edematous retinal disorders).This review endeavors to address the physiological/pathological roles of prostaglandins in the central nervous system and ocular function in health and disease,and provides insights towards the therapeutic utility of some prostaglandin agonists and antagonists,polyunsaturated fatty acids,and cyclooxygenase inhibitors.展开更多
The malfeasant role of the hypoxic tumour microenvironment(TME)in cancer progression was recognized decades ago but the exact mechanisms that augment the hallmarks of cancer and promote treatment resistance continue t...The malfeasant role of the hypoxic tumour microenvironment(TME)in cancer progression was recognized decades ago but the exact mechanisms that augment the hallmarks of cancer and promote treatment resistance continue to be elucidated.Gastroesophageal cancers(GOCs)represent a major burden of worldwide disease,responsible for the deaths of over 1 million people annually.Disentangling the impact of hypoxia in GOCs enables a better overall understanding of the disease pathogenesis while shining a light on novel therapeutic strategies and facilitating precision treatment approaches with the ultimate goal of improving outcomes for patients with these diseases.This review discusses the underlying principles and processes of the hypoxic response and the effect of hypoxia in promoting the hallmarks of cancer in the context of GOCs.We focus on its bidirectional influence on inflammation and how it drives angiogenesis,innate and adaptive immune evasion,metastasis,and the reprogramming of cellular bioenergetics.The contribution of the hypoxic GOC TME to treatment resistance is examined and a brief overview of the pharmacodynamics of hypoxiatargeted therapeutics is given.The principal methods that are used in measuring hypoxia and how they may enhance prognostication or provide rationale for individually tailored management in the case of tumours with significant hypoxic regions are also discussed.展开更多
The incidence of hepatocellular carcinoma(HCC) isknown to be high in West Africa with an approximateyearly mortality rate of 200000. Several factors are responsible for this. Early acquisition of risk factors; with ve...The incidence of hepatocellular carcinoma(HCC) isknown to be high in West Africa with an approximateyearly mortality rate of 200000. Several factors are responsible for this. Early acquisition of risk factors; with vertical or horizontal transmission of hepatitis B(HBV), environmental food contaminants(aflatoxins), poor management of predisposing risk factors and poorlymanaged strategies for health delivery. There has been a low uptake of childhood immunisation for hepatitis B in many West African countries. Owing to late presentations, most sufferers of HCC die within weeks of their diagnosis. Highlighted reasons for the specific disease pattern of HCC in West Africa include:(1) high rate of risk factors;(2) failure to identify at risk populations;(3) lack of effective treatment; and(4) scarce resources for timely diagnosis. This is contrasted to the developed world, which generally has sufficient resources to detect cases early for curative treatment. Provision of palliative care for HCC patients is limited by availability and affordability of potent analgesics. Regional efforts, as well as collaborative networking activities hold promise that could change the epidemiology of HCC in West Africa.展开更多
Over the past few years,rapid advancements in the internet and communication technologies have led to increasingly intricate and diverse networking systems.As a result,greater intelligence is necessary to effectively ...Over the past few years,rapid advancements in the internet and communication technologies have led to increasingly intricate and diverse networking systems.As a result,greater intelligence is necessary to effectively manage,optimize,and maintain these systems.Due to their distributed nature,machine learning models are challenging to deploy in traditional networks.However,Software-Defined Networking(SDN)presents an opportunity to integrate intelligence into networks by offering a programmable architecture that separates data and control planes.SDN provides a centralized network view and allows for dynamic updates of flow rules and softwarebased traffic analysis.While the programmable nature of SDN makes it easier to deploy machine learning techniques,the centralized control logic also makes it vulnerable to cyberattacks.To address these issues,recent research has focused on developing powerful machine-learning methods for detecting and mitigating attacks in SDN environments.This paper highlighted the countermeasures for cyberattacks on SDN and how current machine learningbased solutions can overcome these emerging issues.We also discuss the pros and cons of using machine learning algorithms for detecting and mitigating these attacks.Finally,we highlighted research issues,gaps,and challenges in developing machine learning-based solutions to secure the SDN controller,to help the research and network community to develop more robust and reliable solutions.展开更多
Principally the basis of ISE is selecting of a support solid matrix and a nonsoluble compound or complexes of insighted cation, mixed with this solid. For preparing the ISE membranes there are some materials such PVC,...Principally the basis of ISE is selecting of a support solid matrix and a nonsoluble compound or complexes of insighted cation, mixed with this solid. For preparing the ISE membranes there are some materials such PVC, PE, organic polyelectrolytes, conducting polymers and inorganic compounds. The black white microscope photos are included, too. Detailed schemes and pictures of the electrodes and correlations were shown in the following article. Results are seen compatible for construction of the versatile ISE electrodes.展开更多
Today with certainty, the petroleum industry is fostering sanguinely the fields’ development programs for the optimization of reservoir characterization through worth-full appliances of computer analysis techniques. ...Today with certainty, the petroleum industry is fostering sanguinely the fields’ development programs for the optimization of reservoir characterization through worth-full appliances of computer analysis techniques. The time element is of prime importance for optimistic petroleum development projects. Therefore, the frontline of “Real-time Analysis” is added into the applications of computer solving techniques for achieving and sketching up the real-time cost effectiveness in analyzing field development programs. It focuses on the phases of real-time well test data acquisition system, real-time secure access to the well test data either on field or in office and real-time data interpretation unit. This interface will yield the productive results for the field of reservoir’s pressure transient analysis and wells’ systems analysis by following the up-to-date preferred, accurate and effective well test analytical principles with modern real-time computer applications and techniques. It also lays emphasis for the comfort and reliability of data in creating best interpersonal working modes within a reputable and esteemed petroleum development organization.展开更多
Flow through a channel bounded by a porous layer is considered when a transition layer exists between the channel and the medium. The variable permeability in the transition layer is chosen such that Brinkman’s equat...Flow through a channel bounded by a porous layer is considered when a transition layer exists between the channel and the medium. The variable permeability in the transition layer is chosen such that Brinkman’s equation governing the flow reduces to a generalized inhomogeneous Airy’s differential equation. Solution to the resulting generalized Airy’s equation is obtained in this work and solution to the flow through the transition layer, of the same configuration, reported in the literature, is recovered from the current solution.展开更多
This paper analyzes the influence of fatigue loading on the residual stress profile in high strength steel wires. To this end, different sinusoidal loads with diverse values of maximum loading level and number of cycl...This paper analyzes the influence of fatigue loading on the residual stress profile in high strength steel wires. To this end, different sinusoidal loads with diverse values of maximum loading level and number of cycles were simulated on wires in which several residual stress profiles had been previously introduced, some of them with a tensile state and others with a compressive state. An analysis was made of the evolution with time of such residual stress laws by comparing them at key instants of loading, that is, at initial instant, at maximum load, at minimum load and at final instant. Numerical results show only a minor influence of fatigue loading on the residual stress profile.展开更多
Soybean is the most produced oil crop in the world, with great increase in its annual production as well as great generation of waste from its industrialization. The soybean hulls can be used for the elaboration of pr...Soybean is the most produced oil crop in the world, with great increase in its annual production as well as great generation of waste from its industrialization. The soybean hulls can be used for the elaboration of products such as carboxymethyl cellulose (CMC), adding high value to this residue and it can be used as a coating polymer in seeds. The objective of this work was to analyze the physiological quality of soybean seeds treated with CMC and fungicide, recording images to verify the effectiveness of the coating in the seeds. The experiment was randomized into factorial scheme 2 × 4 with four replicates, two soybean cultivars M-7110 and M-7739 and four types of coating: without (control), CMC, fungicide and fungicide/CMC. The variables analyzed were: vigor (first count), germination test, accelerated aging, length and dry mass of the radicle and hypocotyl length. The images were made with a scanning electron microscope (SEM) with zoom of 50 and 200 times. The CMC used alone or with fungicide, provided good physiological quality of soybean seeds. In some analyzes there was difference between the cultivars M 7110 and M 7739. The combination of CMC and fungicide provided a better coating on the seeds.展开更多
基金Project supported by Fondo Nacional de Desarrollo Científico y Tecnologico,FONDECYT(1200033)the National Doctoral Scholarship(21192195)+2 种基金Chile,Conselho Nacional de Desenvolvimento Científico e Tecnologico(CNPq,427164/2018-4 and 310307/2021-0)Funda?āo de AmparoàPesquisa do Estado de Goiás(FAPEG),Brazil,developed within the scope of the project CICECO-Aveiro Institute of Materials(UIDB/50011/2020,UIDP/50011/2020,LA/P/0006/2020)LogicALL(PTDC/CTMCTM/0340/2021)financed through the FCT-Foundation for Science and Technology/Ministry of Education(PIDDAC-Central Government Investment and Development Expenditure Program),Portugal。
文摘This study presents the microwave-assisted synthesis and characterization of a series of heterometal lic coordination polymers(HMCPs)with a 4-methyl-2,6-di[(1H-1,2,4-triazol-1-yl)]phenoxo ligand with varying Eu^(Ⅲ)/Tb^(Ⅲ)ratios.Single crystal X-ray diffraction reveals a double-chain structure bridged by triazolyl groups.Powder X-ray diffraction confirms the isostructural nature of the synthesized HMCPs.The photophysical properties depend on lanthanide ion concentration and excitation wavelength,leading to a color shift from green to blue as the proportion of Tb^(Ⅲ)decreases and Eu^(Ⅲ)increases.White light generation is achieved in the 8/2 Eu^(Ⅲ)/Tb^(Ⅲ)HMCP(CIE:0.293,0.326)under 335 nm excitation.The study suggests energy transfer from Tb^(Ⅲ)to Eu^(Ⅲ),but both experimental and theoretical calculations indicate that this transfer is orders of magnitude lower than the sensitization through ligand states.
基金The NIHR Biomedical Research Centre funding scheme and the following for authors’ funding and support: AIG is funded by a scholarship from the Egyptian Government SAK is supported by a grant from the Higher Education Funding Council for England (HEFCE)+5 种基金 SDTR is funded by grants from the British Medical Research Council (MRC), London, United Kingdomthe British Engineering, Physics and Science Research Council (EPSRC), Swindon, United Kingdomthe Alan Morement Memorial Fund AMMF, Essex, UK Broad Foundation, Los Angeles, United StatesPfizer Global Research and Development Inc, Sandwich, United Kingdom GlaxoSmithKline, Ware, United Kingdom
文摘Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.
文摘The World Health Organization （WHO） has extensively revised its manual for semen analysis, and seeks to provide reference limits for semen quality parameters. This raises the question of what is meant by ＇normal＇ （excluding the use of this term to denote a Gaussian distribution）. It could be taken in a purely statistical sense, using a biologically arbitrary cut-off point to denote an abnormal level, typically the extreme 5 percent of the population. Alternatively, ＇normal＇ could be defined according to the biological concept of normality and abnormality, in terms of the point at which biological function becomes impaired. Either of these can be used in descriptive epidemiology, for example, to study trends, but in the case of fertility, both semen quality and functional fertility （time to pregnancy） are continuous variables with no clear threshold. The WHO manual uses the biological meaning of normal, in that it provides the semen parameter distributions for men who have recently fathered pregnancies that took 12 months or less to conceive. However, what is really needed is the same information the other way around： given a particular semen test result, what should be expected in terms of ability to conceive, and how long it is likely to take. In considering epidemiological research, the focus has been mainly on internal comparisons, rather than reference limits, but it would be beneficial if more attention were paid to the absolute levels and to what these mean in terms of function--in other words, if the data were better calibrated biologically.
文摘Hepatitis B virus （HBV） infection is the leading causeof liver disease and hepatocellular carcinoma （HCC）worldwide, in spite of prophylactic vaccination andantiviral treatment modalities. The immunopathogenesisof HBV infection has been intensively studied and ispropelled by complex interactions between the virus andthe host immune system. Natural killer group 2D （NKG2D）is a well-characterized activating receptor, expressed onnatural killer （NK） cells, NK T cells and CD8＋ cytotoxic Tcells. This receptor is present in both humans and miceand binds to a diverge family of ligands that resemble theMHC-class Ⅰ molecules. Increasing evidence shows thatNKG2D-ligand interactions are critical in the establishmentof HBV persistence and the development of liver injuryand HCC. The expression of NKG2D ligands dependson the presence of several polymorphisms and is alsomodulated post-transcriptionally by HBV. While it isknown that HBV circumvents host’s innate immunityvia the NKG2D pathway but the exact mechanismsinvolved are still elusive. This letter discusses previousaccomplishments on the role of NKG2D ligand regulationin the development of chronic HBV, liver injury and HCC.Key words： Hepatitis B virus; Natural killer group 2Dreceptor; Natural killer cells; MHC class I polypeptiderelatedchain A; Hepatocellular carcinoma
基金MMEC is supported by a Fellowship from the Sir Halley Stewart Trust (Cambridge, United Kingdom)SDT-R, MMEC, HKSF and RN have been participant workers in the PROLIFICA project in West Africafunded by the European Union Framework 7
文摘Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and noninvasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy.
基金Supported by Research Grant from the British Medical Research Council, Pfizer Global Research (Sandwich, UK) and the United Kingdom Department of Health Research and Development Fund. SM is funded by a clinical and research fellowship from the Société des Radiologistes de l’Hpital St-Franois d’Assise, Québec, Canada
文摘Ultrasound (US) is often the first imaging modality employed in patients with suspected focal liver lesions. The role of US in the characterisation of focal liver lesions has been transformed with the introduction of specific contrast media and the development of specialized imaging techniques. Ultrasound now can fully characterise the enhancement pattern of hepatic lesions, similar to that achieved with contrast enhanced multiphasic computed tomography (CT) and magnetic resonance imaging (MRI). US contrast agents are safe, well-tolerated and have very few contraindications. Furthermore, real-time evaluation of the vascularity of focal liver lesions has become possible with the use of the newer microbubble contrast agents. This article reviews the enhancement pattern of the most frequent liver lesions seen, using the second generation US contrast media. The common pitfalls for each type of lesion are discussed. The recent developments in US contrast media and specific imaging techniques have been a major advance and this technique, in view of the intrinsic advantages of US, will undoubtedly gain popularity in the years to come.
文摘This review focuses on the management of iron metabolism and iron overload experienced in the hereditary condition, human factors engineering(HFE)-associated hemochromatosis. Hemochromatosis refers to a group of genetic diseases that result in iron overload; the major one globally is HFE-associated hemochromatosis. The evolution in understanding of the most common form of hereditary hemochromatosis, being the substation of cysteine to a tyrosine at position 282 in the HFE gene, has been extensively studied Novel mutations in both HFE and non-HFE genes have been indicated in this disease which hold significance in its application for the Asia-Pacific region. In conditions with iron overload, the storage of excess iron in various body tissues leads to complications and toxic damage. The most common presenting complaint for this disease is malaise, lethargy and other non-specific symptoms. In order to diagnose hereditary hemochromatosis, there are biochemical, imaging and genetic testing options. Currently, cascade screening of affected families is preferred over population-level screening. The mainstay of treatment is venesection and the appropriate approach to treatment has been consolidated over the years. Recently, the indications for venesection therapy of hemochromatosis have been challenged and are the subject of ongoing research.
基金Mary ME Crossey is supported by a Fellowship grant from the Sir Halley Stewart Foundation (Cambridge, United Kingdom)
文摘Chronic liver disease has become a global health problem as a result of the increasing incidence of viral hepatitis, obesity and alcohol misuse. Over the past three decades, in the United Kingdom alone, deaths from chronic liver disease have increased both in men and in women. Currently, 2.5% of deaths worldwide are attributed to liver disease and projected figures suggest a doubling in hospitalisation and associated mortality by 2020. Chronic liver diseases vary for clinical manifestations and natural history, with some individuals having relatively indolent disease and others with a rapidly progressive course. About 30% of patients affected by hepatitis C has a progressive disease and develop cirrhosis over a 20 years period from the infection, usually 5-10 years after initial medical presentation. The aim of the current therapeutic strategies is preventing the progression from hepatitis to fibrosis and subsequently, cirrhosis. Hepatic steatosis is a risk factor for chronic liver disease and is affecting about the half of patients who abuse alcohol. Moreover non-alcoholic fatty liver disease is part of the metabolic syndrome, associated with obesity, hypertension, type Ⅱ diabetes mellitus and dyslipidaemia, and a subgroup of patients develops non-alcoholic steatohepatitis and fibrosis with subsequent cirrhosis. The strengths and pitfalls of liver biopsy are discussed and a variety of new techniques to assess liver damage from transient elastography to experimental techniques, such as in vitro urinary nuclear magnetic resonance spectroscopy. Some of the techniques and tests described are already suitable for more widespread clinical application, as is the case with ultrasound-based liver diagnostics, but others, such as urinary metabonomics, requires a period of critical evaluation or development to take them from the research arena to clinical practice.
基金Supported by a Fellowship grant from Cancer Research UK C14094/A27178core funding from Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute
文摘The intestinal epithelium possesses a remarkable ability for both proliferation and regeneration.The last two decades have generated major advances in our understanding of the stem cell populations responsible for its maintenance during homeostasis and more recently the events that occur during injury induced regeneration.These fundamental discoveries have capitalised on the use of transgenic mouse models and in vivo lineage tracing to make their conclusions.It is evident that maintenance is driven by rapidly proliferating crypt base stem cells,but complexities associated with the technicality of mouse modelling have led to several overlapping populations being held responsible for the same behaviour.Similarly,it has been shown that essentially any population in the intestinal crypt can revert to a stem cell state given the correct stimulus during epithelial regeneration.Whilst these observations are profound it is uncertain how relevant they are to human intestinal homeostasis and pathology.Here,these recent studies are presented,in context with technical considerations of the models used,to argue that their conclusions may indeed not be applicable in understanding“homeostatic regeneration”and experimental suggestions presented for validating their results in human tissue.
基金Supported by NHS Bowel Cancer Screening ProgrammeDrs.Matharoo and Sevdalis are affiliated with the Imperial Centre for Patient Safety and Service Quality(www.cpssq.org),affiliated with the Imperial Patient Safety Translational Research Centre,which is funded by the National Institute for Health Research
文摘AIM: To investigate whether novel, non-technical skills training for Bowel Cancer Screening (BCS) endoscopy teams enhanced patient safety knowledge and attitudes.
文摘Cellular and mitochondrial membrane phospholipids provide the substrate for synthesis and release of prostaglandins in response to certain chemical,mechanical,noxious and other stimuli.Prostaglandin D_(2),prostaglandin E_(2),prostaglandin F_(2)α,prostaglandin I_(2)and thromboxane-A_(2)interact with five major receptors(and their sub-types)to elicit specific downstream cellular and tissue actions.In general,prostaglandins have been associated with pain,inflammation,and edema when they are present at high local concentrations and involved on a chronic basis.However,in acute settings,certain endogenous and exogenous prostaglandins have beneficial effects ranging from mediating muscle contraction/relaxation,providing cellular protection,regulating sleep,and enhancing blood flow,to lowering intraocular pressure to prevent the development of glaucoma,a blinding disease.Several classes of prostaglandins are implicated(or are considered beneficial)in certain central nervous system dysfunctions(e.g.,Alzheimer’s,Parkinson’s,and Huntington’s diseases;amyotrophic lateral sclerosis and multiple sclerosis;stroke,traumatic brain injuries and pain)and in ocular disorders(e.g.,ocular hypertension and glaucoma;allergy and inflammation;edematous retinal disorders).This review endeavors to address the physiological/pathological roles of prostaglandins in the central nervous system and ocular function in health and disease,and provides insights towards the therapeutic utility of some prostaglandin agonists and antagonists,polyunsaturated fatty acids,and cyclooxygenase inhibitors.
文摘The malfeasant role of the hypoxic tumour microenvironment(TME)in cancer progression was recognized decades ago but the exact mechanisms that augment the hallmarks of cancer and promote treatment resistance continue to be elucidated.Gastroesophageal cancers(GOCs)represent a major burden of worldwide disease,responsible for the deaths of over 1 million people annually.Disentangling the impact of hypoxia in GOCs enables a better overall understanding of the disease pathogenesis while shining a light on novel therapeutic strategies and facilitating precision treatment approaches with the ultimate goal of improving outcomes for patients with these diseases.This review discusses the underlying principles and processes of the hypoxic response and the effect of hypoxia in promoting the hallmarks of cancer in the context of GOCs.We focus on its bidirectional influence on inflammation and how it drives angiogenesis,innate and adaptive immune evasion,metastasis,and the reprogramming of cellular bioenergetics.The contribution of the hypoxic GOC TME to treatment resistance is examined and a brief overview of the pharmacodynamics of hypoxiatargeted therapeutics is given.The principal methods that are used in measuring hypoxia and how they may enhance prognostication or provide rationale for individually tailored management in the case of tumours with significant hypoxic regions are also discussed.
基金Supported by Fellowships from The London Clinic,London,United Kingdom(to Dr.Ladep)the Halley Stewart Foun-dation,Cambridge,United Kingdom(to Mary ME Crossey)
文摘The incidence of hepatocellular carcinoma(HCC) isknown to be high in West Africa with an approximateyearly mortality rate of 200000. Several factors are responsible for this. Early acquisition of risk factors; with vertical or horizontal transmission of hepatitis B(HBV), environmental food contaminants(aflatoxins), poor management of predisposing risk factors and poorlymanaged strategies for health delivery. There has been a low uptake of childhood immunisation for hepatitis B in many West African countries. Owing to late presentations, most sufferers of HCC die within weeks of their diagnosis. Highlighted reasons for the specific disease pattern of HCC in West Africa include:(1) high rate of risk factors;(2) failure to identify at risk populations;(3) lack of effective treatment; and(4) scarce resources for timely diagnosis. This is contrasted to the developed world, which generally has sufficient resources to detect cases early for curative treatment. Provision of palliative care for HCC patients is limited by availability and affordability of potent analgesics. Regional efforts, as well as collaborative networking activities hold promise that could change the epidemiology of HCC in West Africa.
文摘Over the past few years,rapid advancements in the internet and communication technologies have led to increasingly intricate and diverse networking systems.As a result,greater intelligence is necessary to effectively manage,optimize,and maintain these systems.Due to their distributed nature,machine learning models are challenging to deploy in traditional networks.However,Software-Defined Networking(SDN)presents an opportunity to integrate intelligence into networks by offering a programmable architecture that separates data and control planes.SDN provides a centralized network view and allows for dynamic updates of flow rules and softwarebased traffic analysis.While the programmable nature of SDN makes it easier to deploy machine learning techniques,the centralized control logic also makes it vulnerable to cyberattacks.To address these issues,recent research has focused on developing powerful machine-learning methods for detecting and mitigating attacks in SDN environments.This paper highlighted the countermeasures for cyberattacks on SDN and how current machine learningbased solutions can overcome these emerging issues.We also discuss the pros and cons of using machine learning algorithms for detecting and mitigating these attacks.Finally,we highlighted research issues,gaps,and challenges in developing machine learning-based solutions to secure the SDN controller,to help the research and network community to develop more robust and reliable solutions.
文摘Principally the basis of ISE is selecting of a support solid matrix and a nonsoluble compound or complexes of insighted cation, mixed with this solid. For preparing the ISE membranes there are some materials such PVC, PE, organic polyelectrolytes, conducting polymers and inorganic compounds. The black white microscope photos are included, too. Detailed schemes and pictures of the electrodes and correlations were shown in the following article. Results are seen compatible for construction of the versatile ISE electrodes.
文摘Today with certainty, the petroleum industry is fostering sanguinely the fields’ development programs for the optimization of reservoir characterization through worth-full appliances of computer analysis techniques. The time element is of prime importance for optimistic petroleum development projects. Therefore, the frontline of “Real-time Analysis” is added into the applications of computer solving techniques for achieving and sketching up the real-time cost effectiveness in analyzing field development programs. It focuses on the phases of real-time well test data acquisition system, real-time secure access to the well test data either on field or in office and real-time data interpretation unit. This interface will yield the productive results for the field of reservoir’s pressure transient analysis and wells’ systems analysis by following the up-to-date preferred, accurate and effective well test analytical principles with modern real-time computer applications and techniques. It also lays emphasis for the comfort and reliability of data in creating best interpersonal working modes within a reputable and esteemed petroleum development organization.
文摘Flow through a channel bounded by a porous layer is considered when a transition layer exists between the channel and the medium. The variable permeability in the transition layer is chosen such that Brinkman’s equation governing the flow reduces to a generalized inhomogeneous Airy’s differential equation. Solution to the resulting generalized Airy’s equation is obtained in this work and solution to the flow through the transition layer, of the same configuration, reported in the literature, is recovered from the current solution.
文摘This paper analyzes the influence of fatigue loading on the residual stress profile in high strength steel wires. To this end, different sinusoidal loads with diverse values of maximum loading level and number of cycles were simulated on wires in which several residual stress profiles had been previously introduced, some of them with a tensile state and others with a compressive state. An analysis was made of the evolution with time of such residual stress laws by comparing them at key instants of loading, that is, at initial instant, at maximum load, at minimum load and at final instant. Numerical results show only a minor influence of fatigue loading on the residual stress profile.
文摘Soybean is the most produced oil crop in the world, with great increase in its annual production as well as great generation of waste from its industrialization. The soybean hulls can be used for the elaboration of products such as carboxymethyl cellulose (CMC), adding high value to this residue and it can be used as a coating polymer in seeds. The objective of this work was to analyze the physiological quality of soybean seeds treated with CMC and fungicide, recording images to verify the effectiveness of the coating in the seeds. The experiment was randomized into factorial scheme 2 × 4 with four replicates, two soybean cultivars M-7110 and M-7739 and four types of coating: without (control), CMC, fungicide and fungicide/CMC. The variables analyzed were: vigor (first count), germination test, accelerated aging, length and dry mass of the radicle and hypocotyl length. The images were made with a scanning electron microscope (SEM) with zoom of 50 and 200 times. The CMC used alone or with fungicide, provided good physiological quality of soybean seeds. In some analyzes there was difference between the cultivars M 7110 and M 7739. The combination of CMC and fungicide provided a better coating on the seeds.
