Hepadnaviruses, including human hepatitis B virus （HBV）, replicate through reverse transcription of an RNA intermediate, the pregenomic RNA （pgRNA）. Despite this kinship to retroviruses, there are fundamental diff...Hepadnaviruses, including human hepatitis B virus （HBV）, replicate through reverse transcription of an RNA intermediate, the pregenomic RNA （pgRNA）. Despite this kinship to retroviruses, there are fundamental differences beyond the fact that hepadnavirions contain DNA instead of RNA. Most peculiar is the initiation of reverse transcription： it occurs by protein-priming, is strictly committed to using an RNA hairpin on the pgRNA, ε, as template, and depends on cellular chaperones; moreover, proper replication can apparently occur only in the specialized environment of intact nucleocapsids. This complexity has hampered an in-depth mechanistic understanding. The recent successful reconstitution in the test tube of active replication initiation complexes from purified components, for duck HBV （DHBV）, now allows for the analysis of the biochemistry of hepadnaviral replication at the molecular level. Here we review the current state of knowledge at all steps of the hepadnaviral genome replication cycle, with emphasis on new insights that turned up by the use of such cellfree systems. At this time, they can, unfortunately, not be complemented by three-dimensional structural information on the involved components. However, at least for the ~ RNA element such information is emerging, raising expectations that combining biophysics with biochemistry and genetics will soon provide a powerful integrated approach for solving the many outstanding questions. The ultimate, though most challenging goal, will be to visualize the hepadnaviral reverse transcriptase in the act of synthesizing DNA, which will also have strong implications for drug development.展开更多
Hypertriglyceridemia is an established cause of pancreatitis. In a case-based approach, we present a review of hypertriglyceridemJa and how it can cause pancreatitis. We outline how to investigate and manage such pati...Hypertriglyceridemia is an established cause of pancreatitis. In a case-based approach, we present a review of hypertriglyceridemJa and how it can cause pancreatitis. We outline how to investigate and manage such patients. A 35 year old man presented to the emergency department with abdominal pain and biochemical evidence of acute pancreatitis. There was no history of alcohol consumption and biliary imaging was normal. The only relevant past medical history was that of mild hyperlipidemia, treated with diet alone. Physical exam revealed epigastric tenderness, right lateral rectus palsy, lipemia retinalis, bitemporal hemianopsia and a delay in the relaxation phase of his ankle reflexes. Subsequent laboratory investigation revealed marked hypertriglyceridemia and panhypopituarism. An enhanced CT scan of the head revealed a large suprasellar mass impinging on the optic chiasm and hypothalamus. The patient was treated supportively; thyroid replacement and lipid lowering agents were started. He underwent a successful resection of a craniopharyngioma. Postoperatively, the patient did well on hormone replacement therapy. He has had no further attacks of pancreatitis. This case highlights many of the factors involved in the regulation of triglyceride metabolism. We review the common causes of hypertriglyceridemia and the proposed mechanisms resulting in pancreatitis. The incidence and management of hypertriglyceridemiainduced pancreatitis are also discussed.展开更多
We present a case of necrotizing pneumonia in an 87-year-old man without severe respiratory instability. Clinical suspicion arose due to the need for supplementary oxygen and persistent fever during treatment for comm...We present a case of necrotizing pneumonia in an 87-year-old man without severe respiratory instability. Clinical suspicion arose due to the need for supplementary oxygen and persistent fever during treatment for community-acquired pneumonia. The diagnosis was confirmed by chest computed tomography. Although necrotizing pneumonia typically requires major surgical intervention upon diagnosis, we chose conservative management with antimicrobials and chest drainage alone. The patient experienced significant improvement and resolution of pneumonia with conservative management.展开更多
The present contribution gives an overview about recent research on a TBC （thermal barrier coating） system consisted of （I） an intermetallic MCrAIY-alloy BC （bond coat） applied by VPS （vacuum plasma spraying） ...The present contribution gives an overview about recent research on a TBC （thermal barrier coating） system consisted of （I） an intermetallic MCrAIY-alloy BC （bond coat） applied by VPS （vacuum plasma spraying） and （2） an YSZ （yttria stabilised zirconia） top coat APS （air plasma sprayed） at Forschungszentrum Juelich, Institute of Energy and Climate Research （IEK-2）. The influence of high temperature dwell time, maximum and minimum temperature on crack growth kinetics during thermal cycling of such plasma sprayed TBCs is investigated using scanning electron microscopy and AE （acoustic emission） analysis. Thermocyclic life in terms of accumulated time at maximum temperature decreases with increasing high temperature dwell time and increases with increasing minimum temperature. AE analysis proves that crack growth mainly occurs during cooling at temperatures below the ductile-to-brittle transition temperature of the BC. Superimposed mechanical load cycles accelerate delamination crack growth and, in case of sufficiently high mechanical loadings, result in premature fatigue failure of the substrate. A life prediction model based on TGO growth kinetics and a fracture mechanics approach has been developed which accounts for the influence of maximum and minimum temperature as well as of high temperature dwell time with good accuracy in an extremely wide parameter range.展开更多
AIM To explore regional systolic strain of midwall and endocardial segments using speckle tracking echocardiography in patients with apical hypertrophic cardiomyopathy(HCM).METHODS We prospectively assessed 20 patient...AIM To explore regional systolic strain of midwall and endocardial segments using speckle tracking echocardiography in patients with apical hypertrophic cardiomyopathy(HCM).METHODS We prospectively assessed 20 patients(mean age 53 ± 16 years,range:18-81 years,10 were male),with apical HCM. We measured global longitudinal peak systolic strain(GLPSS) in the midwall and endocardium of the left ventricle. RESULTS The diastolic thickness of the 4 apical segments was 16.25 ± 2.75 mm. All patients had a normal global systolicfunction with a fractional shortening of 50% ± 8%. In spite of supernormal left ventricular(LV) systolic function,midwall GLPSS was decreased in all patients,more in the apical(-7.3% ±-8.8%) than in basal segments(-15.5% ±-6.93%),while endocardial GLPPS was significantly greater and reached normal values(apical:-22.8% ±-7.8%,basal:-17.9% ±-7.5%). CONCLUSION This study shows that two-dimensional strain was decreased mainly confined to the mesocardium,while endocardium myocardial deformation was preserved in HCM and allowed to identify subclinical LV dysfunction. This transmural heterogeneity in systolic strain had not been previously described in HCM and could be explained by the distribution of myofibrillar disarray in deep myocardial areas. The clinical application of this novel finding may help further understanding of the pathophysiology of HCM.展开更多
BACKGROUND Hypothermic machine perfusion(HMP)has demonstrated benefits in terms of early kidney transplant function compared to static cold storage.While longer preservation times have shown detrimental effects,a prev...BACKGROUND Hypothermic machine perfusion(HMP)has demonstrated benefits in terms of early kidney transplant function compared to static cold storage.While longer preservation times have shown detrimental effects,a previous paired study indicated that longer pump times(the second kidney in a pair)might lead to improved outcomes.AIM To revisit the prior paired study's somewhat unexpected results by reviewing our program's experience.METHODS A total of 61 pairs of transplant recipients who received kidneys from the same donor(2012-2021)were analyzed.Patients were divided into two groups depending on whether they were transplanted first(K1)or second(K2).Therefore,the patients in each pair had identical donor characteristics,except for time on the pump.Statistical analyses included Kaplan-Meyer analysis and paired tests,including McNemar's test,student's paired t-test,or Wilcoxon's test,as appropriate.RESULTS The two groups of recipients had similar demographics(age,body mass index,diabetes,time on dialysis,sensit-ization and retransplants).Cold ischemic times for K1 and K2 were 8.9(95%CI:7.9,9.8)and 14.7 hours(13.7,15.8)(P<0.0001),respectively.Overall,K2 had a higher rate of freedom from biopsy-proven acute rejection at 1 year(P=0.015).Delayed graft function was less common in K2,12/61(20%)than in K1,20/61(33%)(P=0.046).Finally,K2 showed a higher graft survival than K1(P=0.023).CONCLUSION Our results agree with a previous study that suggested possible advantages to longer pump times.Both studies should encourage further research into HMP's potential anti-inflammatory effect.展开更多
Au-based catalysts have been reported to be active in the cyclohexane oxidation to K-A oil, but they showed some limitiations in terms of productivity, selectivity and required reaction conditions. The possibility to ...Au-based catalysts have been reported to be active in the cyclohexane oxidation to K-A oil, but they showed some limitiations in terms of productivity, selectivity and required reaction conditions. The possibility to overcome some of these limits has been explored coupling Au with Cu, which can be suitable for undergoing the electron-switch in the initial step of the cyclohexane oxidation. Hence, a bimetallic 2 wt% Au Cu/Al_(2)O_(3) catalyst was tested in the oxidation of cyclohexane, working at mild conditions of 120 ℃ and 4 bar of O_(2). The combination of the catalyst with a very small amount of benzaldehyde used as cheaper and non-toxic radical initiator allowed to obtain a very high productivity of cyclohexanol and cyclohexanone(45 mmol*m L/mgmet*h) with a selectivity of 94%. Moreover, comparing the catalysed reaction with the non-catalysed one, the role of the catalyst has been disclosed.展开更多
1.Introduction Promoting the green and low-carbon transition of energy systems and constructing a new renewable-dominated power system is essential to achieving carbon neutrality in China[1,2].Furthermore,implementing...1.Introduction Promoting the green and low-carbon transition of energy systems and constructing a new renewable-dominated power system is essential to achieving carbon neutrality in China[1,2].Furthermore,implementing electrification and hydrogenation strategies to address energy consumption is necessary for a successful energy transition.China’s share of electricity in its total energy consumption is estimated to increase from 26%in 2021 to more than 70%by 2060.展开更多
The bones are the most common sites of breast cancer metastasis. Upon arrival within the bone microenvironment, breast cancer cells coordinate the activities of stromal cells, resulting in an increase in osteoclast ac...The bones are the most common sites of breast cancer metastasis. Upon arrival within the bone microenvironment, breast cancer cells coordinate the activities of stromal cells, resulting in an increase in osteoclast activity and bone matrix degradation. In late stages of bone metastasis, breast cancer cells induce apoptosis in osteoblasts, which further exacerbates bone loss. However, in early stages, breast cancer cells induce osteoblasts to secrete inflammatory cytokines purported to drive tumor progression. To more thoroughly evaluate the role of osteoblasts in early stages of breast cancer metastasis to the bones, we used green fluorescent protein-labeled human breast cancer cell lines MDA-MB-231 and MDA-MB-435, which both induce osteolysis after intra-femoral injection in athymic mice, and the murine pre-osteoblastic cell line MC3T3-E1 to modulate osteoblast populations at the sites of breast cancer metastasis. Breast cancer cells were injected directly into the femur with or without equal numbers of MC3T3-E1 cells. Tumors grew significantly larger when co-injected with breast cancer cells and MC3T3-E1 cells than injected with breast cancer cells alone. Osteolysis was induced in both groups, indicating that MC3T3-E1 cells did not block the ability of breast cancer cells to cause bone destruction. MC3T3-E1 cells promoted tumor growth out of the bone into the extraosseous stroma. These data suggest that breast cancer cells and osteoblasts communicate during early stages of bone metastasis and promote tumor growth.展开更多
AIM： To review all studies in the literature that have assessed Hematopoietic cell transplantation （HCT） and Crohn＇s disease （CD） with the ultimate aims of determining if this is a viable treatment option for th...AIM： To review all studies in the literature that have assessed Hematopoietic cell transplantation （HCT） and Crohn＇s disease （CD） with the ultimate aims of determining if this is a viable treatment option for those with CD. A secondary aim was to review the above literature and determine if the studies shed further light on the mechanisms involved in the pathogenesis of CD. METHODS： An extensive Medline search was performed on all articles from 1970 to 2005 using the keywords; bone marrow transplant, stem cell, hematopoietic cell, Crohn＇s disease and inflammatory bowel disease. RESULTS： We identified one case in which a patient developed CD following an allogeneic HCT from a sibling suffering with CD. Evidence for transfer of the genetic predisposition to develop CD was also identified with report of a patient that developed severe CD following an allogeneic HCT. Following HCT it was found that the donor （that had no signs or symptoms of CD） and the recipient had several haplotype mismatches in HLA class 111 genes in the IBD3 locus including a polymorphism of NOD2/CARD15 that has been associated with CD. Thirty three published cases of patients with CD who underwent either autologous or allogeneic HCT were identified. At the time of publication 29 of these 33 patients were considered to be in remission. The median follow-up time was seven years, and twenty months for allogeneic and autologous HCT respectively. For patients who underwent HCT primarily for treatment of their CD there have been no mortalities related to transplant complications. CONCLUSION： Overall these preliminary data suggest that both allogeneic and autologous HCT may be effective in inducing remission in refractory CD. This supports the hypothesis that the hematolymphatic cells play a key role in CD and that resetting of the immune system may be a critical approach in the management or cure of CD.展开更多
Bartter syndrome is a group of autosomal recessive renal tubular disorders;it has two types of presentation:antenatal and classic.The antenatal type presents as severe unexplained polyhydramnios in the second trimeste...Bartter syndrome is a group of autosomal recessive renal tubular disorders;it has two types of presentation:antenatal and classic.The antenatal type presents as severe unexplained polyhydramnios in the second trimester.This is due to fetal urinary losses of sodium,chloride,and potassium,leading to fetal polyuria.The classic type presents in the late neonatal or infancy stage,with dehydration,dyselectrolytemia,failure to thrive,and nephrocalcinosis.Antenatal scans are normal in such cases.Type I and II Bartter syndrome presents in the antenatal period,whereas type IV has a classic presentation.We describe an unusual case of type IVa Bartter syndrome presenting in the antenatal period,with severe polyhydramnios.The initial diagnosis was made based on amniotic fluid chloride levels and later confirmed by performing a genetic test.Genetic testing is important for confirming diagnosis and prognostication regarding the condition.展开更多
A new search for two-neutrino double-beta(2νββ)decay of^(136)Xe to the 0+1 excited state of 136Ba is performed with the full EXO-200 dataset.A deep learning-based convolutional neural network is used to discriminat...A new search for two-neutrino double-beta(2νββ)decay of^(136)Xe to the 0+1 excited state of 136Ba is performed with the full EXO-200 dataset.A deep learning-based convolutional neural network is used to discriminate signal from background events.Signal detection efficiency is increased relative to previous searches by EXO-200 by more than a factor of two.With the addition of the Phase II dataset taken with an upgraded detector,the median 90%confidence level half-life sensitivity of 2νββdecay to the 0+1 state of 136Ba is 2.9×10^(24)yr using a total^(136)Xe exposure of 234.1 kg yr.No statistically significant evidence for 2νββdecay to the 0^(+)_(1)state is observed,leading to a lower limit of T2ν1/2(0^(+)→0^(+)_(1))>1.4×10^(24)yr at 90%confidence level,improved by 70%relative to the current world's best constraint.展开更多
A first search for the Ξ_(bc)^(+)J/ψΞ_(c)^(+) decay is performed by the LHCb experiment with a data sample of proton-proton collisions, corresponding to an integrated luminosity of 9 fb−1 recorded at centre-of-mass...A first search for the Ξ_(bc)^(+)J/ψΞ_(c)^(+) decay is performed by the LHCb experiment with a data sample of proton-proton collisions, corresponding to an integrated luminosity of 9 fb−1 recorded at centre-of-mass energies of 7, 8, and 13 TeV. Two peaking structures are seen with a local (global) significance of 4.3(2.8) and 4.1(2.4) standard deviations at masses of 6571 and 6694 MeV/c2, respectively. Upper limits are set on the Ξ+bc baryon production cross-section times the branching fraction relative to that of the B+c→J/ψD+s decay at centre-of-mass energies of 8 and 13 TeV, in the Ξ+bc and in the B+c rapidity and transverse-momentum ranges from 2.0 to 4.5 and 0 to 20GeV/c, respectively. Upper limits are presented as a function of the Ξ+bc mass and lifetime.展开更多
A search for the rare decays W^(+)→D_(s)^(+)γ and Z→D0γis performed using proton-proton collision data collected by the LHCb experiment at a centre-of-mass energy of 13TeV,corresponding to an integrated luminosity...A search for the rare decays W^(+)→D_(s)^(+)γ and Z→D0γis performed using proton-proton collision data collected by the LHCb experiment at a centre-of-mass energy of 13TeV,corresponding to an integrated luminosity of 2.0fb−1.No significant signal is observed for either decay mode and upper limits on their branching fractions are set using W^(+)→D_(s)^(+)γ and Z→μ+μ−decays as normalization channels.The upper limits are 6.5×10^(−4) and 2.1×10^(−3) at 95% confidence level for the W^(+)→D_(s)^(+)γ and Z→D^(0)γ decay modes,respectively.This is the first reported search for the Z→D^(0)γ decay,while the upper limit on the W+→D+sγbranching fraction improves upon the previous best limit.展开更多
Collagen-based biomaterials are used widely as tissue engineering scaffolds because of their excellent bioactivity and their similarity to the natural ECM.The regeneration of healthy bone tissue requires simultaneous ...Collagen-based biomaterials are used widely as tissue engineering scaffolds because of their excellent bioactivity and their similarity to the natural ECM.The regeneration of healthy bone tissue requires simultaneous support for both osteoblasts and,where angiogenesis is intended,endothelial cells.Hence it is important to tailor carefully the biochemical and structural characteristics of the scaffold to suit the needs of each cell type.This work describes for the first time a systematic study to gain insight into the cell type-specific response of primary human osteoblast(hOBs)and human dermal microvascular endothelial cells(HDMECs)to insoluble collagen-based biomaterials.The behaviour was evaluated on both 2D films and 3D scaffolds,produced using freeze-drying.The collagen was cross-linked at various EDC/NHS concentrations and mono-cultured with hOBs and HDMECs to assess the effect of architectural features and scaffold stabilization on cell behaviour.It was observed that 3D scaffolds cross-linked at 30%of the standard conditions in literature offered an optimal combination of mechanical stiffness and cellular response for both cell types,although endothelial cells were more sensitive to the degree of cross-linking than hOBs.Architectural features have a time-dependent impact on the cell migration profile,with alignment being the most influential parameter overall.展开更多
文摘Hepadnaviruses, including human hepatitis B virus （HBV）, replicate through reverse transcription of an RNA intermediate, the pregenomic RNA （pgRNA）. Despite this kinship to retroviruses, there are fundamental differences beyond the fact that hepadnavirions contain DNA instead of RNA. Most peculiar is the initiation of reverse transcription： it occurs by protein-priming, is strictly committed to using an RNA hairpin on the pgRNA, ε, as template, and depends on cellular chaperones; moreover, proper replication can apparently occur only in the specialized environment of intact nucleocapsids. This complexity has hampered an in-depth mechanistic understanding. The recent successful reconstitution in the test tube of active replication initiation complexes from purified components, for duck HBV （DHBV）, now allows for the analysis of the biochemistry of hepadnaviral replication at the molecular level. Here we review the current state of knowledge at all steps of the hepadnaviral genome replication cycle, with emphasis on new insights that turned up by the use of such cellfree systems. At this time, they can, unfortunately, not be complemented by three-dimensional structural information on the involved components. However, at least for the ~ RNA element such information is emerging, raising expectations that combining biophysics with biochemistry and genetics will soon provide a powerful integrated approach for solving the many outstanding questions. The ultimate, though most challenging goal, will be to visualize the hepadnaviral reverse transcriptase in the act of synthesizing DNA, which will also have strong implications for drug development.
基金Supported by Alberta Heritage Foundation for Medical Research and Canadian Institute of Health Research
文摘Hypertriglyceridemia is an established cause of pancreatitis. In a case-based approach, we present a review of hypertriglyceridemJa and how it can cause pancreatitis. We outline how to investigate and manage such patients. A 35 year old man presented to the emergency department with abdominal pain and biochemical evidence of acute pancreatitis. There was no history of alcohol consumption and biliary imaging was normal. The only relevant past medical history was that of mild hyperlipidemia, treated with diet alone. Physical exam revealed epigastric tenderness, right lateral rectus palsy, lipemia retinalis, bitemporal hemianopsia and a delay in the relaxation phase of his ankle reflexes. Subsequent laboratory investigation revealed marked hypertriglyceridemia and panhypopituarism. An enhanced CT scan of the head revealed a large suprasellar mass impinging on the optic chiasm and hypothalamus. The patient was treated supportively; thyroid replacement and lipid lowering agents were started. He underwent a successful resection of a craniopharyngioma. Postoperatively, the patient did well on hormone replacement therapy. He has had no further attacks of pancreatitis. This case highlights many of the factors involved in the regulation of triglyceride metabolism. We review the common causes of hypertriglyceridemia and the proposed mechanisms resulting in pancreatitis. The incidence and management of hypertriglyceridemiainduced pancreatitis are also discussed.
文摘We present a case of necrotizing pneumonia in an 87-year-old man without severe respiratory instability. Clinical suspicion arose due to the need for supplementary oxygen and persistent fever during treatment for community-acquired pneumonia. The diagnosis was confirmed by chest computed tomography. Although necrotizing pneumonia typically requires major surgical intervention upon diagnosis, we chose conservative management with antimicrobials and chest drainage alone. The patient experienced significant improvement and resolution of pneumonia with conservative management.
文摘The present contribution gives an overview about recent research on a TBC （thermal barrier coating） system consisted of （I） an intermetallic MCrAIY-alloy BC （bond coat） applied by VPS （vacuum plasma spraying） and （2） an YSZ （yttria stabilised zirconia） top coat APS （air plasma sprayed） at Forschungszentrum Juelich, Institute of Energy and Climate Research （IEK-2）. The influence of high temperature dwell time, maximum and minimum temperature on crack growth kinetics during thermal cycling of such plasma sprayed TBCs is investigated using scanning electron microscopy and AE （acoustic emission） analysis. Thermocyclic life in terms of accumulated time at maximum temperature decreases with increasing high temperature dwell time and increases with increasing minimum temperature. AE analysis proves that crack growth mainly occurs during cooling at temperatures below the ductile-to-brittle transition temperature of the BC. Superimposed mechanical load cycles accelerate delamination crack growth and, in case of sufficiently high mechanical loadings, result in premature fatigue failure of the substrate. A life prediction model based on TGO growth kinetics and a fracture mechanics approach has been developed which accounts for the influence of maximum and minimum temperature as well as of high temperature dwell time with good accuracy in an extremely wide parameter range.
文摘AIM To explore regional systolic strain of midwall and endocardial segments using speckle tracking echocardiography in patients with apical hypertrophic cardiomyopathy(HCM).METHODS We prospectively assessed 20 patients(mean age 53 ± 16 years,range:18-81 years,10 were male),with apical HCM. We measured global longitudinal peak systolic strain(GLPSS) in the midwall and endocardium of the left ventricle. RESULTS The diastolic thickness of the 4 apical segments was 16.25 ± 2.75 mm. All patients had a normal global systolicfunction with a fractional shortening of 50% ± 8%. In spite of supernormal left ventricular(LV) systolic function,midwall GLPSS was decreased in all patients,more in the apical(-7.3% ±-8.8%) than in basal segments(-15.5% ±-6.93%),while endocardial GLPPS was significantly greater and reached normal values(apical:-22.8% ±-7.8%,basal:-17.9% ±-7.5%). CONCLUSION This study shows that two-dimensional strain was decreased mainly confined to the mesocardium,while endocardium myocardial deformation was preserved in HCM and allowed to identify subclinical LV dysfunction. This transmural heterogeneity in systolic strain had not been previously described in HCM and could be explained by the distribution of myofibrillar disarray in deep myocardial areas. The clinical application of this novel finding may help further understanding of the pathophysiology of HCM.
基金This study was reviewed and approved by our local Research Ethics Board(Bio-REB#1894).
文摘BACKGROUND Hypothermic machine perfusion(HMP)has demonstrated benefits in terms of early kidney transplant function compared to static cold storage.While longer preservation times have shown detrimental effects,a previous paired study indicated that longer pump times(the second kidney in a pair)might lead to improved outcomes.AIM To revisit the prior paired study's somewhat unexpected results by reviewing our program's experience.METHODS A total of 61 pairs of transplant recipients who received kidneys from the same donor(2012-2021)were analyzed.Patients were divided into two groups depending on whether they were transplanted first(K1)or second(K2).Therefore,the patients in each pair had identical donor characteristics,except for time on the pump.Statistical analyses included Kaplan-Meyer analysis and paired tests,including McNemar's test,student's paired t-test,or Wilcoxon's test,as appropriate.RESULTS The two groups of recipients had similar demographics(age,body mass index,diabetes,time on dialysis,sensit-ization and retransplants).Cold ischemic times for K1 and K2 were 8.9(95%CI:7.9,9.8)and 14.7 hours(13.7,15.8)(P<0.0001),respectively.Overall,K2 had a higher rate of freedom from biopsy-proven acute rejection at 1 year(P=0.015).Delayed graft function was less common in K2,12/61(20%)than in K1,20/61(33%)(P=0.046).Finally,K2 showed a higher graft survival than K1(P=0.023).CONCLUSION Our results agree with a previous study that suggested possible advantages to longer pump times.Both studies should encourage further research into HMP's potential anti-inflammatory effect.
基金The Authors gratefully acknowledge the supportof bilateral project CNR-HAS(MTA)SAC.AD002.037.
文摘Au-based catalysts have been reported to be active in the cyclohexane oxidation to K-A oil, but they showed some limitiations in terms of productivity, selectivity and required reaction conditions. The possibility to overcome some of these limits has been explored coupling Au with Cu, which can be suitable for undergoing the electron-switch in the initial step of the cyclohexane oxidation. Hence, a bimetallic 2 wt% Au Cu/Al_(2)O_(3) catalyst was tested in the oxidation of cyclohexane, working at mild conditions of 120 ℃ and 4 bar of O_(2). The combination of the catalyst with a very small amount of benzaldehyde used as cheaper and non-toxic radical initiator allowed to obtain a very high productivity of cyclohexanol and cyclohexanone(45 mmol*m L/mgmet*h) with a selectivity of 94%. Moreover, comparing the catalysed reaction with the non-catalysed one, the role of the catalyst has been disclosed.
基金funded by the Henan Institute for Chinese Development Strategy of Engineering and Technology(2022HENZDA02)the Science and Technology Department of Sichuan Province(2021YFH0010)the High-End Foreign Experts Program of the Yunnan Revitalization Talents Support Plan of Yunnan Province。
文摘1.Introduction Promoting the green and low-carbon transition of energy systems and constructing a new renewable-dominated power system is essential to achieving carbon neutrality in China[1,2].Furthermore,implementing electrification and hydrogenation strategies to address energy consumption is necessary for a successful energy transition.China’s share of electricity in its total energy consumption is estimated to increase from 26%in 2021 to more than 70%by 2060.
基金supported by U.S. Army Medical Research and Materiel Command grants W81-XWH-07-1-0399 (to D.R. Welch) and W81-XWH-08-1-0779 (to T.M. Bodenstine)partial support from NIH-CA134981 and CA-87728 (D.R. Welch)the National Foundation for Cancer Research Center for Metastasis Research (D.R. Welch) and Susan G. Komen for the Cure (D.R. Welch)
文摘The bones are the most common sites of breast cancer metastasis. Upon arrival within the bone microenvironment, breast cancer cells coordinate the activities of stromal cells, resulting in an increase in osteoclast activity and bone matrix degradation. In late stages of bone metastasis, breast cancer cells induce apoptosis in osteoblasts, which further exacerbates bone loss. However, in early stages, breast cancer cells induce osteoblasts to secrete inflammatory cytokines purported to drive tumor progression. To more thoroughly evaluate the role of osteoblasts in early stages of breast cancer metastasis to the bones, we used green fluorescent protein-labeled human breast cancer cell lines MDA-MB-231 and MDA-MB-435, which both induce osteolysis after intra-femoral injection in athymic mice, and the murine pre-osteoblastic cell line MC3T3-E1 to modulate osteoblast populations at the sites of breast cancer metastasis. Breast cancer cells were injected directly into the femur with or without equal numbers of MC3T3-E1 cells. Tumors grew significantly larger when co-injected with breast cancer cells and MC3T3-E1 cells than injected with breast cancer cells alone. Osteolysis was induced in both groups, indicating that MC3T3-E1 cells did not block the ability of breast cancer cells to cause bone destruction. MC3T3-E1 cells promoted tumor growth out of the bone into the extraosseous stroma. These data suggest that breast cancer cells and osteoblasts communicate during early stages of bone metastasis and promote tumor growth.
基金Alberta Heritage Foundation for Medical Research and the Canadian Institute of Health Research
文摘AIM： To review all studies in the literature that have assessed Hematopoietic cell transplantation （HCT） and Crohn＇s disease （CD） with the ultimate aims of determining if this is a viable treatment option for those with CD. A secondary aim was to review the above literature and determine if the studies shed further light on the mechanisms involved in the pathogenesis of CD. METHODS： An extensive Medline search was performed on all articles from 1970 to 2005 using the keywords; bone marrow transplant, stem cell, hematopoietic cell, Crohn＇s disease and inflammatory bowel disease. RESULTS： We identified one case in which a patient developed CD following an allogeneic HCT from a sibling suffering with CD. Evidence for transfer of the genetic predisposition to develop CD was also identified with report of a patient that developed severe CD following an allogeneic HCT. Following HCT it was found that the donor （that had no signs or symptoms of CD） and the recipient had several haplotype mismatches in HLA class 111 genes in the IBD3 locus including a polymorphism of NOD2/CARD15 that has been associated with CD. Thirty three published cases of patients with CD who underwent either autologous or allogeneic HCT were identified. At the time of publication 29 of these 33 patients were considered to be in remission. The median follow-up time was seven years, and twenty months for allogeneic and autologous HCT respectively. For patients who underwent HCT primarily for treatment of their CD there have been no mortalities related to transplant complications. CONCLUSION： Overall these preliminary data suggest that both allogeneic and autologous HCT may be effective in inducing remission in refractory CD. This supports the hypothesis that the hematolymphatic cells play a key role in CD and that resetting of the immune system may be a critical approach in the management or cure of CD.
文摘Bartter syndrome is a group of autosomal recessive renal tubular disorders;it has two types of presentation:antenatal and classic.The antenatal type presents as severe unexplained polyhydramnios in the second trimester.This is due to fetal urinary losses of sodium,chloride,and potassium,leading to fetal polyuria.The classic type presents in the late neonatal or infancy stage,with dehydration,dyselectrolytemia,failure to thrive,and nephrocalcinosis.Antenatal scans are normal in such cases.Type I and II Bartter syndrome presents in the antenatal period,whereas type IV has a classic presentation.We describe an unusual case of type IVa Bartter syndrome presenting in the antenatal period,with severe polyhydramnios.The initial diagnosis was made based on amniotic fluid chloride levels and later confirmed by performing a genetic test.Genetic testing is important for confirming diagnosis and prognostication regarding the condition.
文摘A new search for two-neutrino double-beta(2νββ)decay of^(136)Xe to the 0+1 excited state of 136Ba is performed with the full EXO-200 dataset.A deep learning-based convolutional neural network is used to discriminate signal from background events.Signal detection efficiency is increased relative to previous searches by EXO-200 by more than a factor of two.With the addition of the Phase II dataset taken with an upgraded detector,the median 90%confidence level half-life sensitivity of 2νββdecay to the 0+1 state of 136Ba is 2.9×10^(24)yr using a total^(136)Xe exposure of 234.1 kg yr.No statistically significant evidence for 2νββdecay to the 0^(+)_(1)state is observed,leading to a lower limit of T2ν1/2(0^(+)→0^(+)_(1))>1.4×10^(24)yr at 90%confidence level,improved by 70%relative to the current world's best constraint.
基金The project support from CERN and from the national agencies:CAPES,CNPq,FAPERJ and FINEP(Brazil)MOST and NSFC(China)+18 种基金CNRS/IN2P3(France)BMBF,DFG and MPG(Germany)INFN(Italy)NWO(Netherlands)MNiSW and NCN(Poland)MEN/IFA(Romania)MICINN(Spain)SNSF and SER(Switzerland)NASU(Ukraine)STFC(United Kingdom)DOE NP and NSF(USA).We acknowledge the computing resources that are provided by CERN,IN2P3(France),KIT and DESY(Germany),INFN(Italy),SURF(Netherlands),PIC(Spain),GridPP(United Kingdom),CSCS(Switzerland),IFIN-HH(Romania),CBPF(Brazil),Polish WLCG(Poland)and NERSC(USA).Individual groups or members have received support from ARC and ARDC(Australia)Minciencias(Colombia)AvH Foundation(Germany)EPLANET,Marie Sklodowska-Curie Actions and ERC(European Union)A*MIDEX,ANR,IPhU and Labex P2IO,and Région Auvergne-RhôneAlpes(France)Key Research Program of Frontier Sciences of CAS,CAS PIFI,CAS CCEPP,Fundamental Research Funds for the Central Universities,and Sci.&Tech.Program of Guangzhou(China)GVA,XuntaGal,GENCAT and Prog.Atracción Talento,CM(Spain)SRC(Sweden)the Leverhulme Trust,the Royal Society and UKRI(United Kingdom).
文摘A first search for the Ξ_(bc)^(+)J/ψΞ_(c)^(+) decay is performed by the LHCb experiment with a data sample of proton-proton collisions, corresponding to an integrated luminosity of 9 fb−1 recorded at centre-of-mass energies of 7, 8, and 13 TeV. Two peaking structures are seen with a local (global) significance of 4.3(2.8) and 4.1(2.4) standard deviations at masses of 6571 and 6694 MeV/c2, respectively. Upper limits are set on the Ξ+bc baryon production cross-section times the branching fraction relative to that of the B+c→J/ψD+s decay at centre-of-mass energies of 8 and 13 TeV, in the Ξ+bc and in the B+c rapidity and transverse-momentum ranges from 2.0 to 4.5 and 0 to 20GeV/c, respectively. Upper limits are presented as a function of the Ξ+bc mass and lifetime.
文摘A search for the rare decays W^(+)→D_(s)^(+)γ and Z→D0γis performed using proton-proton collision data collected by the LHCb experiment at a centre-of-mass energy of 13TeV,corresponding to an integrated luminosity of 2.0fb−1.No significant signal is observed for either decay mode and upper limits on their branching fractions are set using W^(+)→D_(s)^(+)γ and Z→μ+μ−decays as normalization channels.The upper limits are 6.5×10^(−4) and 2.1×10^(−3) at 95% confidence level for the W^(+)→D_(s)^(+)γ and Z→D^(0)γ decay modes,respectively.This is the first reported search for the Z→D^(0)γ decay,while the upper limit on the W+→D+sγbranching fraction improves upon the previous best limit.
基金supported by the Engineering and Physical Sciences Research Council(EPSRC)and Geistlich Pharma AG.R.E.C.and S.M.B.acknowledge funding from an EPSRC Professorial Fellowship(EP/N019938/1)which also supported the research undertaken by D.V.B.D.V.B.would like to thank the Cambridge Royce facilities grant EP/P024947/1 and Sir Henry Royce Institute-recurrent grant EP/R00661X/1.
文摘Collagen-based biomaterials are used widely as tissue engineering scaffolds because of their excellent bioactivity and their similarity to the natural ECM.The regeneration of healthy bone tissue requires simultaneous support for both osteoblasts and,where angiogenesis is intended,endothelial cells.Hence it is important to tailor carefully the biochemical and structural characteristics of the scaffold to suit the needs of each cell type.This work describes for the first time a systematic study to gain insight into the cell type-specific response of primary human osteoblast(hOBs)and human dermal microvascular endothelial cells(HDMECs)to insoluble collagen-based biomaterials.The behaviour was evaluated on both 2D films and 3D scaffolds,produced using freeze-drying.The collagen was cross-linked at various EDC/NHS concentrations and mono-cultured with hOBs and HDMECs to assess the effect of architectural features and scaffold stabilization on cell behaviour.It was observed that 3D scaffolds cross-linked at 30%of the standard conditions in literature offered an optimal combination of mechanical stiffness and cellular response for both cell types,although endothelial cells were more sensitive to the degree of cross-linking than hOBs.Architectural features have a time-dependent impact on the cell migration profile,with alignment being the most influential parameter overall.
