From 2011 to 2014, the BESIII experiment collected about 5 fb^-1 data at center-of-mass energies around 4 GeV for the studies of the charmonium-like and higher excited charmonium states. By analyzing the di-muon proce...From 2011 to 2014, the BESIII experiment collected about 5 fb^-1 data at center-of-mass energies around 4 GeV for the studies of the charmonium-like and higher excited charmonium states. By analyzing the di-muon process e＋e- →yma/Fsμ^＋μ^-, the center-of-mass energies of the data samples are measured with a precision of 0.8 MeV. The center-of-mass energy is found to be stable for most of the time during data taking.展开更多
Dear Editor, In plants, the transport of sugars from the site of biosynthesis to the site of utilization or storage relies on sugar transporters located in different subcellular compartments and different vascular cel...Dear Editor, In plants, the transport of sugars from the site of biosynthesis to the site of utilization or storage relies on sugar transporters located in different subcellular compartments and different vascular cell types. The SWEET sugar transporter family is one such class and is represented by 17 members in Arabidopsis. AtSWEET1 was the first plant SWEET transporter to be characterized; it acts as a glucose uniporter in multiple systems （Chen et al., 2010）.展开更多
Among the different DNA anomalies that can be present in the male gamete, DNA fragmentation is the most frequent, particularly in infertile subjects. There is now consistent evidence that a sperm containing fragmented...Among the different DNA anomalies that can be present in the male gamete, DNA fragmentation is the most frequent, particularly in infertile subjects. There is now consistent evidence that a sperm containing fragmented DNA can be alive, motile, morphologically normal and able to fertilize an oocyte. There is also evidence that the oocyte is able to repair DNA damage; however, the extent of this repair depends on the type of DNA damage present in the sperm, as well as on the quality of the oocyte. Thus, it is important to understand the possible consequences of sperm DNA fragmentation （SDF） for embryo development, implantation, pregnancy outcome and the health of progeny conceived, both naturally and by assisted reproductive technology （ART）. At present, data on the consequences of SDF for reproduction are scarce and, in many ways, inconsistent. The differences in study conclusions might result from the different methods used to detect SDF, the study design and the inclusion criteria. Consequently, it is difficult to decide whether SDF testing should be carried out in fertility assessment and ART. It is clear that there is an urgent need for the standardisation of the methods and for additional clinical studies on the impact of SDF on ART outcomes.展开更多
The C-type lectin receptors （CLRs） belong to a large family of proteins that contain a carbohydrate recognition domain （CRD） and calcium binding sites on their extracellular domains. Recent studies indicate that m...The C-type lectin receptors （CLRs） belong to a large family of proteins that contain a carbohydrate recognition domain （CRD） and calcium binding sites on their extracellular domains. Recent studies indicate that many CLRs, such as Dectin-1, Dectin-2 and Mincle, function as pattern recognition receptors （PRRs） recognizing carbohydrate ligands from infected microorganisms. Upon ligand binding, these CLRs induce multiple signal transduction cascades through their own immunoreceptor tyrosine-based activation motifs （ITAMs） or interacting with ITAM-containing adaptor proteins such as FcRy. Emerging evidence indicate that CLR-induced signaling cascades lead to the activation of nuclear factor kappaB （NF-KB） family of transcriptional factors through a Syk- and CARD9-dependent pathway（s）. The activation of NF-κB plays a critical role in the induction of innate immune and inflammatory responses following microbial infection and tissue damages. In this review, we will summarize the recent progress on the signal transduction pathways induced by CLRs. and how these CLRs activate NF-κB and contribute to innate immune and inflammatory responses.展开更多
AIM: To study the efficacy of low-dose imipramine in relieving symptoms associated with the irritable bowel syndrome (IBS). METHODS: A randomized, double-blind trial of 25 mg imipramine vs matched placebo for 12 wk wa...AIM: To study the efficacy of low-dose imipramine in relieving symptoms associated with the irritable bowel syndrome (IBS). METHODS: A randomized, double-blind trial of 25 mg imipramine vs matched placebo for 12 wk was performed. Doubling the dose was allowed once at week 2 in case of an unsatisfactory early response. Primary efficacy variables were subjective global symptom relief and quality of life (QoL) using SF-36 at week 12. RESULTS: One hundred and seven patients were enrolled by advertisement or referral by general practitioners and 56 (31 imipramine: 25 placebo) completed the 16-wk study. Baseline characteristics were comparable. A high overall dropout rate was noted in the imipramine and placebo arms (47.5% vs 47.9%, P > 0.05), a mean of 25.0 and 37.4 d from enrollment, respectively (P < 0.05). At the end of 12 wk, there was a significant difference in global symptom relief with imipramine over placebo (per-protocol: 80.6% vs48.0%, P = 0.01) and a trend on intent-to-treat (ITT) analysis (42.4% vs 25.0%, P = 0.06). This improvement was evident early and persisted to week 16 (P = 0.024 and 0.053 by per-protocol and ITT analyses, respectively). Mean cumulative and componentspecific SF-36 scores improved in the imipramine group only (per-protocol, P < 0.01). Drug-related adverse events leading to patient dropout were more common in the imipramine group (25.4% vs 12.5%, P > 0.05). CONCLUSION: Imipramine may be effective in the treatment of IBS patients and is associated with improved QoL. Careful patient selection, initiation of a low dose with gradual escalation and monitoring for side effects may result in an improved therapeutic response.展开更多
AIM: To investigate the effect of the probiotic combination Lactibiane Tolerance<sup>®</sup> (LT) on epithelial barrier function in vitro and in vivo.
Among the different targets of administered drugs,there are membrane transporters that play also a role in drug delivery and disposition.Moreover,drug-transporter interactions are responsible for off-target effects of...Among the different targets of administered drugs,there are membrane transporters that play also a role in drug delivery and disposition.Moreover,drug-transporter interactions are responsible for off-target effects of drugs underlying their toxicity.The improvement of the drug design process is subjected to the identification of those membrane transporters mostly relevant for drug absorption,delivery and side effect production.A peculiar group of proteins with great relevance to pharmacology is constituted by the membrane transporters responsible for managing glutamine traffic in different body districts.The interest around glutamine metabolism lies in its physio-pathological role;glutamine is considered a conditionally essential amino acid because highly proliferative cells have an increased request of glutamine that cannot be satisfied only by endogenous synthesis.Then,glutamine transporters provide cells with this special nutrient.Among the glutamine transporters,SLC1A5,SLC6A14,SLC6A19,SLC7A5,SLC7A8 and some members of SLC38 family are the best characterized,so far,in both physiological and pathological conditions.Few 3D structures have been solved by CryoEM;other structural data on these transporters have been obtained by computational analysis.Interactions with drugs have been described for several transporters of this group.For some of them,the studies are at an advanced stage,for others,the studies are still in nuce and novel biochemical findings open intriguing perspectives.展开更多
Aims In this study,we examined the effects of Solidago altissima(hereafter Solidago)and two species in the genus Verbesina,Verbesina virginica and Verbesina occidentalis(hereafter Verbesina),on the structure of an old...Aims In this study,we examined the effects of Solidago altissima(hereafter Solidago)and two species in the genus Verbesina,Verbesina virginica and Verbesina occidentalis(hereafter Verbesina),on the structure of an old-field plant community and establishment by an invasive plant species,Lespedeza cuneata(hereafter Lespedeza).Methods We removed Solidago,Verbesina and both Solidago and Verbesina from 4m^(-2)plots in an intact old-field community during two growing seasons.We then quantified the effects of these removals on richness,evenness,diversity and composition of the subdominant plant community.We also measured the total aboveground biomass and the aboveground biomass of the subdominant community.To assess how these removals affected establishment by Lespedeza,we planted 20 seeds in each plot and tracked seedling emergence and survival for one growing season.Important Findings Subdominant community evenness and Shannon diversity were higher in plots from which Solidago and Verbesina were removed relative to control plots.However,there were no effects of dominant species removal on species richness or composition of the subdominant community.Total aboveground biomass was not affected by dominant species removal,suggesting that the community of subdominant species exhibited compensation.In fact,subdominant community biomass was greater when Solidago,but not Verbesina,was removed.Light availability was also greater in plots where Solidago was removed relative to control plots throughout the growing season.In addition,removal of dominant species,in particular Solidago,indirectly reduced the emergence,but not survival,of Lespedeza seedlings by directly promoting subdominant community biomass.Taken together,our results suggest that dominant old-field plant species affect subdominant community structure and indirectly promote establishment by Lespedeza.展开更多
AIM:To evaluate the overlap of autoimmune hepatitis in hepatitis C virus(HCV)-infected patients with intense interface hepatitis.METHODS:Among 1759 patients with hepatitis C submitted to liver biopsy,92(5.2%) presente...AIM:To evaluate the overlap of autoimmune hepatitis in hepatitis C virus(HCV)-infected patients with intense interface hepatitis.METHODS:Among 1759 patients with hepatitis C submitted to liver biopsy,92(5.2%) presented intense interface hepatitis.These patients were evaluated regarding the presence of antinuclear antibody(ANA),anti-smooth muscle antibody(SMA) and anti-liver/kidney microsomal antibody(LKM-1),levels of γ-globulin and histological findings related to autoimmune hepatitis(plasma cell infiltrate and presence of rosettes).RESULTS:Among patients with hepatitis C and intense interface hepatitis there was a low prevalence of autoantibodies(ANA=12%,SMA=5%,LKM-1=0%) and the median γ-globulin level was within the normal range.Typical histological findings of autoimmune disease were observed in only two cases(2%).After applying the score for diagnosis of autoimmune hepatitis,only one patient was classified with a definitive diagnosis of autoimmune hepatitis.Since overlap with autoimmune hepatitis was not the explanation for the intense necroinflammatory activity in patients with chronic hepatitis C we sought to identify the variables associated with this finding.The presence of intense interface hepatitis was associated with more advanced age,both at the time of infection and at the time of the biopsy,and higher prevalence of blood transfusion and alcohol abuse.CONCLUSION:Although possible,overlap with autoimmune hepatitis is a very rare association in HCV-infected patients with intense interface hepatitis,an unusual presentation which seems to be related to other host variables.展开更多
The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced （stage M and selected stage 11） colorectal ca...The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced （stage M and selected stage 11） colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage 11 disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.展开更多
The clinical management of metastatic （stage IV） colorectal cancer （CRC） is a common challenge faced by surgeons and physicians. The last decade has seen exciting developments in the management of CRC, with signif...The clinical management of metastatic （stage IV） colorectal cancer （CRC） is a common challenge faced by surgeons and physicians. The last decade has seen exciting developments in the management of CRC, with significant improvements in prognosis for patients diagnosed with stage IV disease. Treatment options have expanded from 5-fluorouracil alone to a range of pharmaceutical and interventional therapies, improving survival, and providing a cure in selected cases. Enhanced understanding of the biologic pathways most important in colorectal carcinogenesis has led to a new generation of drugs showing promise in advanced disease. It is hoped that in the near future the treatment paradigm of metastatic CRC will be analogous to that of a chronic illness, rather than a rapidly terminal condition. This overview discusses the epidemiology of advanced CRC and currently available therapeutic options including medical, surgical, ablative and novel modalities in the management of metastatic colorectal cancer.展开更多
As non-photosynthesizing organs, roots are dependent on diffusion of oxygen from the external environment and, in some in stances, from the shoot for their aerobic metabolism . Establishment of hypoxic niches in the d...As non-photosynthesizing organs, roots are dependent on diffusion of oxygen from the external environment and, in some in stances, from the shoot for their aerobic metabolism . Establishment of hypoxic niches in the developing tissues of plants has been postulated as a consequence of insufficient diffusion of oxygen to satisfy the demands throughout development. Here, we report that such niches are established at specific stages of lateral root primordia development in Arabidopsis thaliana grown under aerobic conditions. Using gain- and loss-of-function mutants, we show that ERF-Ⅶ transcription factors, which mediate hypoxic responses, control root architecture by acting in cells with a high level of auxin signaling. ERF-Ⅶs repress the expression of the auxin-induced genes LBD16, LBD18, and PUCHI, which are essential for lateral root development, by binding to their promoters. Our results support a model in which the establishment of hypoxic n iches in the developing lateral root primordia con tributes to the shutting down of key auxin-induced genes and regulates the production of lateral roots.展开更多
In a recent article, Chen et aL [Electrochimica Acta, 2014, 130： 279] presented their fabrication and characterization results on a graphene/n-Si solar cell where the Au nanoparticles were inserted in graphene to inc...In a recent article, Chen et aL [Electrochimica Acta, 2014, 130： 279] presented their fabrication and characterization results on a graphene/n-Si solar cell where the Au nanoparticles were inserted in graphene to increase its optical and electrical properties. The higher efficiency of the device was attributed to increased conductivity of graphene after doping with Au nanoparticles. However, the knowledge in the field of Schottky diode solar cells relates this to increased band bending at the junction. Also, to explain the instability behaviour, they concluded that the growth of silicon oxide on the Si surface or oxygen adsorption on the window layer resulted in the device performance increasing initially and decreasing in the end. However, this instability seems to be due to variation in series resistance reduced at the beginning because of slightly lowered Fermi level and increased at the end by the self-compensation by deep in-diffusion ofAu nanoparticles into n-Si layer. We also propose that inserting a very thin p-type layer at the junction will enhance the carrier collection and performance of this device.展开更多
The Rosoideae is a subfamily of the Rosaceae that contains a number of species of economic importance,including the soft fruit species strawberry(Fragaria 3ananassa),red(Rubus idaeus)and black(Rubus occidentalis)raspb...The Rosoideae is a subfamily of the Rosaceae that contains a number of species of economic importance,including the soft fruit species strawberry(Fragaria 3ananassa),red(Rubus idaeus)and black(Rubus occidentalis)raspberries,blackberries(Rubus spp.)and one of the most economically important cut flower genera,the roses(Rosa spp.).Molecular genetics and genomics resources for the Rosoideae have developed rapidly over the past two decades,beginning with the development and application of a number of molecular marker types including restriction fragment length polymorphisms,amplified fragment length polymorphisms and microsatellites,and culminating in the recent publication of the genome sequence of the woodland strawberry,Fragaria vesca,and the development of high throughput single nucleotide polymorphism(SNP)-genotyping resources for Fragaria,Rosa and Rubus.These tools have been used to identify genes and other functional elements that control traits of economic importance,to study the evolution of plant genome structure within the subfamily,and are beginning to facilitate genomic-assisted breeding through the development and deployment of markers linked to traits such as aspects of fruit quality,disease resistance and the timing of flowering.In this review,we report on the developments that have been made over the last 20 years in the field of molecular genetics and structural genomics within the Rosoideae,comment on how the knowledge gained will improve the efficiency of cultivar development and discuss how these advances will enhance our understanding of the biological processes determining agronomically important traits in all Rosoideae species.展开更多
Assaying parathyroid hormone(PTH) in the washing liquid after fine-needle aspiration biopsy(FNAB) seems to be a valid approach to locate parathyroid tissue.PTH-FNAB was evaluated in 47 patients with a clinical picture...Assaying parathyroid hormone(PTH) in the washing liquid after fine-needle aspiration biopsy(FNAB) seems to be a valid approach to locate parathyroid tissue.PTH-FNAB was evaluated in 47 patients with a clinical picture of primary hyper-parathyroidism(PHP) and ultrasonography(US) suggestive of parathyroid lesion.The patients were subdivided into two groups on the basis of the absence or presence of US thyroid alterations.The result of PTH-FNAB was compared with those of cytology,scintigraphy and,in 24 patients,surgical outcome.PTH-FNAB samples with a value higher than that recorded in the serum and higher than our institutional cut-off were deemed to be probable samples of parathyroid tissue.Cytology proved diagnostic for benign thyroid lesions,non-diagnostic for thyroid lesions,hyperplastic parathyroid tissue,undetermined or malignant thyroid lesions and other lesions in 45%,30%,17%,4%,and 4% of cases,respectively.In 47% of cases,PTH-FNAB indicated that the sample had been taken in parathyroid tissue.In patients without US alterations,the diagnostic accuracy of PTH-FNAB was greater than that of scintigraphy.After surgery,comparison between the results of PTH-FNAB and scintigraphy,in terms of positive predictive value(PPV),revealed the superiority of PTH-FNAB;PPV was 94% for FNAB and 71% for scintigraphy,while sensitivity was 83% and 69%,respectively.PTH-FNAB evaluation after FNAB appears to be more diagnostic than cytology and scintigraphy.Of all the procedures used,PTH-FNAB appears to be the method of choice when the target is US suggestive and reachable.PTH-FNAB appears to be a useful method of guiding surgical intervention.展开更多
Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and function.This cellular process is evolutionarily highly conserved to quality control of many pr...Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and function.This cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino acids.This process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein markers.Some of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).展开更多
Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid compositi...Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).展开更多
基金Supported by National Key Basic Research Program of China(2015CB856700)National Natural Science Foundation of China(11125525,11235011.11322544,11335008,11425524,Y61137005C)+7 种基金Chinese Academy of Sciences(CAS)Large-Scale Scientific Facility Program,CAS Center for Excellence in Particle Physics(CCEPP),Collaborative Innovation Center for Particles and Interactions(CICPI),Joint Large-Scale Scientific Facility Funds of NSFC and CAS(11179007,U1232201,U1332201),CAS(KJCX2-YW-N29,KJCX2-YWN45),100 Talents Program of CASNational 1000 Talents Program of China,INPACShanghai Key Laboratory for Particle Physics and Cosmology,German Research Foundation DFG(Collaborative Research Center CRC-1044)Istituto Nazionale di Fisica Nucleare,Italy,Ministry of Development of Turkey(DPT2006K-120470)Russian Foundation for Basic Research(14-07-91152)Swedish Research Council,U.S.Department of Energy(DE-FG02-04ER41291,DE-FG02-05ER41374,DE-FG02-94ER40823,DESC0010118)U.S.National Science Foundation,University of Groningen(RuG)and Helniholtzzentrum fuer Schwerionenforschung GmbH(GSI),DarmstadtWCU Program of National Research Foundation of Korea(R32-2008-000-10155-0)
文摘From 2011 to 2014, the BESIII experiment collected about 5 fb^-1 data at center-of-mass energies around 4 GeV for the studies of the charmonium-like and higher excited charmonium states. By analyzing the di-muon process e＋e- →yma/Fsμ^＋μ^-, the center-of-mass energies of the data samples are measured with a precision of 0.8 MeV. The center-of-mass energy is found to be stable for most of the time during data taking.
文摘Dear Editor, In plants, the transport of sugars from the site of biosynthesis to the site of utilization or storage relies on sugar transporters located in different subcellular compartments and different vascular cell types. The SWEET sugar transporter family is one such class and is represented by 17 members in Arabidopsis. AtSWEET1 was the first plant SWEET transporter to be characterized; it acts as a glucose uniporter in multiple systems （Chen et al., 2010）.
文摘Among the different DNA anomalies that can be present in the male gamete, DNA fragmentation is the most frequent, particularly in infertile subjects. There is now consistent evidence that a sperm containing fragmented DNA can be alive, motile, morphologically normal and able to fertilize an oocyte. There is also evidence that the oocyte is able to repair DNA damage; however, the extent of this repair depends on the type of DNA damage present in the sperm, as well as on the quality of the oocyte. Thus, it is important to understand the possible consequences of sperm DNA fragmentation （SDF） for embryo development, implantation, pregnancy outcome and the health of progeny conceived, both naturally and by assisted reproductive technology （ART）. At present, data on the consequences of SDF for reproduction are scarce and, in many ways, inconsistent. The differences in study conclusions might result from the different methods used to detect SDF, the study design and the inclusion criteria. Consequently, it is difficult to decide whether SDF testing should be carried out in fertility assessment and ART. It is clear that there is an urgent need for the standardisation of the methods and for additional clinical studies on the impact of SDF on ART outcomes.
文摘The C-type lectin receptors （CLRs） belong to a large family of proteins that contain a carbohydrate recognition domain （CRD） and calcium binding sites on their extracellular domains. Recent studies indicate that many CLRs, such as Dectin-1, Dectin-2 and Mincle, function as pattern recognition receptors （PRRs） recognizing carbohydrate ligands from infected microorganisms. Upon ligand binding, these CLRs induce multiple signal transduction cascades through their own immunoreceptor tyrosine-based activation motifs （ITAMs） or interacting with ITAM-containing adaptor proteins such as FcRy. Emerging evidence indicate that CLR-induced signaling cascades lead to the activation of nuclear factor kappaB （NF-KB） family of transcriptional factors through a Syk- and CARD9-dependent pathway（s）. The activation of NF-κB plays a critical role in the induction of innate immune and inflammatory responses following microbial infection and tissue damages. In this review, we will summarize the recent progress on the signal transduction pathways induced by CLRs. and how these CLRs activate NF-κB and contribute to innate immune and inflammatory responses.
基金Supported by A Private Research Fund From the Division of Gastroenterology at the American University of Beirut Medical Center, Beirut, Lebanon
文摘AIM: To study the efficacy of low-dose imipramine in relieving symptoms associated with the irritable bowel syndrome (IBS). METHODS: A randomized, double-blind trial of 25 mg imipramine vs matched placebo for 12 wk was performed. Doubling the dose was allowed once at week 2 in case of an unsatisfactory early response. Primary efficacy variables were subjective global symptom relief and quality of life (QoL) using SF-36 at week 12. RESULTS: One hundred and seven patients were enrolled by advertisement or referral by general practitioners and 56 (31 imipramine: 25 placebo) completed the 16-wk study. Baseline characteristics were comparable. A high overall dropout rate was noted in the imipramine and placebo arms (47.5% vs 47.9%, P > 0.05), a mean of 25.0 and 37.4 d from enrollment, respectively (P < 0.05). At the end of 12 wk, there was a significant difference in global symptom relief with imipramine over placebo (per-protocol: 80.6% vs48.0%, P = 0.01) and a trend on intent-to-treat (ITT) analysis (42.4% vs 25.0%, P = 0.06). This improvement was evident early and persisted to week 16 (P = 0.024 and 0.053 by per-protocol and ITT analyses, respectively). Mean cumulative and componentspecific SF-36 scores improved in the imipramine group only (per-protocol, P < 0.01). Drug-related adverse events leading to patient dropout were more common in the imipramine group (25.4% vs 12.5%, P > 0.05). CONCLUSION: Imipramine may be effective in the treatment of IBS patients and is associated with improved QoL. Careful patient selection, initiation of a low dose with gradual escalation and monitoring for side effects may result in an improved therapeutic response.
基金Supported by PiLeJe,37,quai-de-Grenelle,batiment Pollux,75738 Paris cedex 15
文摘AIM: To investigate the effect of the probiotic combination Lactibiane Tolerance<sup>®</sup> (LT) on epithelial barrier function in vitro and in vivo.
基金This work was supported by PON(Programma Operativo Nazionale)Project No.01_00937PRIN(Progetti di Ricerca di Rilevante Interesse Nazionale)Project No 2017PAB8EM to CI granted by MIUR(Ministry of Education,University and Research)ItalyPRIN(Progetti di Ricerca di Rilevante Interesse Nazionale)Project No 2017PAB8EM.
文摘Among the different targets of administered drugs,there are membrane transporters that play also a role in drug delivery and disposition.Moreover,drug-transporter interactions are responsible for off-target effects of drugs underlying their toxicity.The improvement of the drug design process is subjected to the identification of those membrane transporters mostly relevant for drug absorption,delivery and side effect production.A peculiar group of proteins with great relevance to pharmacology is constituted by the membrane transporters responsible for managing glutamine traffic in different body districts.The interest around glutamine metabolism lies in its physio-pathological role;glutamine is considered a conditionally essential amino acid because highly proliferative cells have an increased request of glutamine that cannot be satisfied only by endogenous synthesis.Then,glutamine transporters provide cells with this special nutrient.Among the glutamine transporters,SLC1A5,SLC6A14,SLC6A19,SLC7A5,SLC7A8 and some members of SLC38 family are the best characterized,so far,in both physiological and pathological conditions.Few 3D structures have been solved by CryoEM;other structural data on these transporters have been obtained by computational analysis.Interactions with drugs have been described for several transporters of this group.For some of them,the studies are at an advanced stage,for others,the studies are still in nuce and novel biochemical findings open intriguing perspectives.
文摘Aims In this study,we examined the effects of Solidago altissima(hereafter Solidago)and two species in the genus Verbesina,Verbesina virginica and Verbesina occidentalis(hereafter Verbesina),on the structure of an old-field plant community and establishment by an invasive plant species,Lespedeza cuneata(hereafter Lespedeza).Methods We removed Solidago,Verbesina and both Solidago and Verbesina from 4m^(-2)plots in an intact old-field community during two growing seasons.We then quantified the effects of these removals on richness,evenness,diversity and composition of the subdominant plant community.We also measured the total aboveground biomass and the aboveground biomass of the subdominant community.To assess how these removals affected establishment by Lespedeza,we planted 20 seeds in each plot and tracked seedling emergence and survival for one growing season.Important Findings Subdominant community evenness and Shannon diversity were higher in plots from which Solidago and Verbesina were removed relative to control plots.However,there were no effects of dominant species removal on species richness or composition of the subdominant community.Total aboveground biomass was not affected by dominant species removal,suggesting that the community of subdominant species exhibited compensation.In fact,subdominant community biomass was greater when Solidago,but not Verbesina,was removed.Light availability was also greater in plots where Solidago was removed relative to control plots throughout the growing season.In addition,removal of dominant species,in particular Solidago,indirectly reduced the emergence,but not survival,of Lespedeza seedlings by directly promoting subdominant community biomass.Taken together,our results suggest that dominant old-field plant species affect subdominant community structure and indirectly promote establishment by Lespedeza.
基金Supported by CAPES research support agency, Brazil
文摘AIM:To evaluate the overlap of autoimmune hepatitis in hepatitis C virus(HCV)-infected patients with intense interface hepatitis.METHODS:Among 1759 patients with hepatitis C submitted to liver biopsy,92(5.2%) presented intense interface hepatitis.These patients were evaluated regarding the presence of antinuclear antibody(ANA),anti-smooth muscle antibody(SMA) and anti-liver/kidney microsomal antibody(LKM-1),levels of γ-globulin and histological findings related to autoimmune hepatitis(plasma cell infiltrate and presence of rosettes).RESULTS:Among patients with hepatitis C and intense interface hepatitis there was a low prevalence of autoantibodies(ANA=12%,SMA=5%,LKM-1=0%) and the median γ-globulin level was within the normal range.Typical histological findings of autoimmune disease were observed in only two cases(2%).After applying the score for diagnosis of autoimmune hepatitis,only one patient was classified with a definitive diagnosis of autoimmune hepatitis.Since overlap with autoimmune hepatitis was not the explanation for the intense necroinflammatory activity in patients with chronic hepatitis C we sought to identify the variables associated with this finding.The presence of intense interface hepatitis was associated with more advanced age,both at the time of infection and at the time of the biopsy,and higher prevalence of blood transfusion and alcohol abuse.CONCLUSION:Although possible,overlap with autoimmune hepatitis is a very rare association in HCV-infected patients with intense interface hepatitis,an unusual presentation which seems to be related to other host variables.
文摘The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced （stage M and selected stage 11） colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage 11 disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.
文摘The clinical management of metastatic （stage IV） colorectal cancer （CRC） is a common challenge faced by surgeons and physicians. The last decade has seen exciting developments in the management of CRC, with significant improvements in prognosis for patients diagnosed with stage IV disease. Treatment options have expanded from 5-fluorouracil alone to a range of pharmaceutical and interventional therapies, improving survival, and providing a cure in selected cases. Enhanced understanding of the biologic pathways most important in colorectal carcinogenesis has led to a new generation of drugs showing promise in advanced disease. It is hoped that in the near future the treatment paradigm of metastatic CRC will be analogous to that of a chronic illness, rather than a rapidly terminal condition. This overview discusses the epidemiology of advanced CRC and currently available therapeutic options including medical, surgical, ablative and novel modalities in the management of metastatic colorectal cancer.
文摘As non-photosynthesizing organs, roots are dependent on diffusion of oxygen from the external environment and, in some in stances, from the shoot for their aerobic metabolism . Establishment of hypoxic niches in the developing tissues of plants has been postulated as a consequence of insufficient diffusion of oxygen to satisfy the demands throughout development. Here, we report that such niches are established at specific stages of lateral root primordia development in Arabidopsis thaliana grown under aerobic conditions. Using gain- and loss-of-function mutants, we show that ERF-Ⅶ transcription factors, which mediate hypoxic responses, control root architecture by acting in cells with a high level of auxin signaling. ERF-Ⅶs repress the expression of the auxin-induced genes LBD16, LBD18, and PUCHI, which are essential for lateral root development, by binding to their promoters. Our results support a model in which the establishment of hypoxic n iches in the developing lateral root primordia con tributes to the shutting down of key auxin-induced genes and regulates the production of lateral roots.
文摘In a recent article, Chen et aL [Electrochimica Acta, 2014, 130： 279] presented their fabrication and characterization results on a graphene/n-Si solar cell where the Au nanoparticles were inserted in graphene to increase its optical and electrical properties. The higher efficiency of the device was attributed to increased conductivity of graphene after doping with Au nanoparticles. However, the knowledge in the field of Schottky diode solar cells relates this to increased band bending at the junction. Also, to explain the instability behaviour, they concluded that the growth of silicon oxide on the Si surface or oxygen adsorption on the window layer resulted in the device performance increasing initially and decreasing in the end. However, this instability seems to be due to variation in series resistance reduced at the beginning because of slightly lowered Fermi level and increased at the end by the self-compensation by deep in-diffusion ofAu nanoparticles into n-Si layer. We also propose that inserting a very thin p-type layer at the junction will enhance the carrier collection and performance of this device.
基金Rosoideae genome research and comparative genomics at FEM are supported by the research office of the Provincia autonoma di Trento
文摘The Rosoideae is a subfamily of the Rosaceae that contains a number of species of economic importance,including the soft fruit species strawberry(Fragaria 3ananassa),red(Rubus idaeus)and black(Rubus occidentalis)raspberries,blackberries(Rubus spp.)and one of the most economically important cut flower genera,the roses(Rosa spp.).Molecular genetics and genomics resources for the Rosoideae have developed rapidly over the past two decades,beginning with the development and application of a number of molecular marker types including restriction fragment length polymorphisms,amplified fragment length polymorphisms and microsatellites,and culminating in the recent publication of the genome sequence of the woodland strawberry,Fragaria vesca,and the development of high throughput single nucleotide polymorphism(SNP)-genotyping resources for Fragaria,Rosa and Rubus.These tools have been used to identify genes and other functional elements that control traits of economic importance,to study the evolution of plant genome structure within the subfamily,and are beginning to facilitate genomic-assisted breeding through the development and deployment of markers linked to traits such as aspects of fruit quality,disease resistance and the timing of flowering.In this review,we report on the developments that have been made over the last 20 years in the field of molecular genetics and structural genomics within the Rosoideae,comment on how the knowledge gained will improve the efficiency of cultivar development and discuss how these advances will enhance our understanding of the biological processes determining agronomically important traits in all Rosoideae species.
文摘Assaying parathyroid hormone(PTH) in the washing liquid after fine-needle aspiration biopsy(FNAB) seems to be a valid approach to locate parathyroid tissue.PTH-FNAB was evaluated in 47 patients with a clinical picture of primary hyper-parathyroidism(PHP) and ultrasonography(US) suggestive of parathyroid lesion.The patients were subdivided into two groups on the basis of the absence or presence of US thyroid alterations.The result of PTH-FNAB was compared with those of cytology,scintigraphy and,in 24 patients,surgical outcome.PTH-FNAB samples with a value higher than that recorded in the serum and higher than our institutional cut-off were deemed to be probable samples of parathyroid tissue.Cytology proved diagnostic for benign thyroid lesions,non-diagnostic for thyroid lesions,hyperplastic parathyroid tissue,undetermined or malignant thyroid lesions and other lesions in 45%,30%,17%,4%,and 4% of cases,respectively.In 47% of cases,PTH-FNAB indicated that the sample had been taken in parathyroid tissue.In patients without US alterations,the diagnostic accuracy of PTH-FNAB was greater than that of scintigraphy.After surgery,comparison between the results of PTH-FNAB and scintigraphy,in terms of positive predictive value(PPV),revealed the superiority of PTH-FNAB;PPV was 94% for FNAB and 71% for scintigraphy,while sensitivity was 83% and 69%,respectively.PTH-FNAB evaluation after FNAB appears to be more diagnostic than cytology and scintigraphy.Of all the procedures used,PTH-FNAB appears to be the method of choice when the target is US suggestive and reachable.PTH-FNAB appears to be a useful method of guiding surgical intervention.
基金supported by Grants from Spanish FEDER/Science and Innovation Ministry I+D+i-RETOS-PID2021-124801NB-100Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas(CIBERN ED+1 种基金an initiative of the ISCIII)[PI2016/01]the Fundocion Ramon Areces and Banco Santander to the CBMSO(to FW)。
文摘Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and function.This cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino acids.This process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein markers.Some of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).
基金supported by PTDC-01778/2022-NeuroDev3D,iNOVA4Health(UIDB/04462/2020 and UIDP/04462/2020)LS4FUTURE(LA/P/0087/2020)。
文摘Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).
