Spinal cord injury(SCI)interrupts the flow of information between the brain and the spinal cord,thus leading to a loss of sensory information and motor paralysis of the body below the lesion.Surprisingly,most SCIs are...Spinal cord injury(SCI)interrupts the flow of information between the brain and the spinal cord,thus leading to a loss of sensory information and motor paralysis of the body below the lesion.Surprisingly,most SCIs are incomplete and spare supraspinal pathways,especially those located within the peripheral white matter of the spinal cord,which includes reticulospinal pathways originating from the medullary reticular formation.Whereas there is abundant literature about the motor cortex,its corticospinal pathway,and its capacity to modulate functional recovery after SCI,less is known about the medullary reticular formation and its reticulospinal pathway.展开更多
There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 poly...There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.展开更多
Mesenchymal stem cells(MSCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical cord.MSCs have gained significa...Mesenchymal stem cells(MSCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical cord.MSCs have gained significant attention in regenerative medicine due to their ability to modulate the immune system and favor tissue repair.MSCs enrich the medium in which they are cultivated with a broad range of bioactive molecules,including growth factors,cytokines,chemokines,enzymes,nucleic acids,and extracellular vesicles that collectively compose the MSC secretome.An increasing number of pre-clinical studies suggest that delivering in vivo an MSC-conditioned medium(i.e.,the medium collected from MSC cultures after at least 3 days of exposure)exerts neuroprotective and anti-inflammatory effects in a variety of neurological conditions.展开更多
Biodegradable implants have emerged in biomedical applications,particularly for orthopedic fixations,cardiovascular stents,and tissue engineering scaffolds.Unlike permanent implants,they are designed to degrade and be...Biodegradable implants have emerged in biomedical applications,particularly for orthopedic fixations,cardiovascular stents,and tissue engineering scaffolds.Unlike permanent implants,they are designed to degrade and be reabsorbed after implantation in the body,mitigating the need for additional surgeries and reducing associated complications.In particular,Fe-Mn-C alloys constitute a new class of promising metallic materials for medical applications due to their outstanding mechanical properties and their bio-logical performances.This study focuses on improving the degradation rates and cytotoxicity of sintered Fe-Mn-C alloys produced using the powder metallurgy process.To evaluate the impact of different pow-der preparation methods on material properties,two types of powders were used:(1)MX,prepared by mixing Fe,Mn,and C powders for 1 h;and(2)MM,obtained by mechanically milling the same powders for 10 h.Four mixtures with varying proportions of MX and MM were prepared.Two groups of samples were produced:one entirely from MX(A0),and another containing MM at 25 wt.%(A25),50 wt.%(A50),and 75 wt.%(A75).All samples exhibited a complex microstructure comprising ferrite,martensite,and residual austenite.Degradation behavior assessment in Hanks’solution over 14 days showed that adding MM increased the degradation rate,from around 0.04 mmpy for A0 to 0.12 mmpy for A25.Notably,all samples showed similar cell viability,in the range of 83%-89%for 1%extract dilution,and were non-hemolytic,with a hemolysis percentage below 1%.展开更多
Background:Although widely used,the rat model remains poorly transferable to humans for peripheral nerve regeneration studies.The rabbit is a much better choice from an anatomical perspective.However,it remains little...Background:Although widely used,the rat model remains poorly transferable to humans for peripheral nerve regeneration studies.The rabbit is a much better choice from an anatomical perspective.However,it remains little used due to the lack of available literature.The aim of this article is to demonstrate the feasibility and effectiveness of an electrophysiological protocol combined with a motor function assessment to analyze nerve repair.Methods:Ten white New Zealand rabbits underwent a 4 cm transection of the fibular nerve.Autograft regeneration over 36 weeks was compared to non-repaired controls.The compound muscle action potential(CMAP)was recorded in the tibialis anterior and the extensor digitorum brevis.An electromyogram(EMG)was obtained after needle insertion and resting muscle activity recording.The electrophysiological results were compared to the toe spread index(TSI),which assesses the motor functional recovery promoted by fibular nerve regeneration.Results:The autograft group regeneration starts between weeks 18 and 21 and normal EMG was observed around the 30th week.These electrophysiological results were compared to the well-defined toe spread reflex.This motor test showed a significant functional return of 59%at 36 weeks(p<0.05).Rabbits regain nearly 80%of their muscle mass.Conclusion:Nerve conduction allows detection of nerve regeneration of the muscle while electromyography indicates when muscle activity returns to normal.These studies are reliable and non-invasive techniques to evaluate fibular nerve regeneration in the rabbit's hindlimb.Nonetheless,it is necessary to have qualified personnel,since inter-manipulator variations have been observed.展开更多
Effective forest regeneration is essential for sustainable forestry practices.In Sweden,mechanical site preparation and manual planting is the dominating method,but sourcing labour for the physically demanding work is...Effective forest regeneration is essential for sustainable forestry practices.In Sweden,mechanical site preparation and manual planting is the dominating method,but sourcing labour for the physically demanding work is difficult.An autonomous scarifying and planting system(Autoplant)could meet the requirements of the forest industry and,for this,a tool for regeneration planning and routing is needed.The tool,Pathfinder,plans the regeneration and routes based on the harvested production(hpr)files,soil moisture and parent material maps,no-go areas(for culture or nature conservation),digital elevation models(DEM),and machine data(e.g.,working width,critical slope,time taken for different turn angles).The overall planting solution is either a set of capacity constrained routes or a continuous route and could be used for any planting machine as well as for traditional scarifiers as disc trenchers or mounders pulled by forwarders.Pathfinder was tested on eleven regeneration areas throughout Sweden,both with continuous routes and routes based on a carrying capacity of 1500 seedlings.The net operation area,species and seedling density suggestions were deemed relevant by expert judgement in the field.The routes provided by Pathfinder were compared with solutions given by two experienced drivers and a third solution based on the actual soil scarification at the site.Total driving distance did not differ significantly between the suggestions,but Pathfinder included less side-slope driving on steep slopes(≥27%or 15°)and medium slopes(15–27%).The chosen threshold value for steep slopes(where side-slope driving should be avoided)affects the routing,and a lower threshold means more turning and longer driving distance.Pathfinder is not only a tool for routing of planting machines,but also helps in planning of traditional regeneration by providing a more correct net area and tree species suggestions based on the growth of the previous stand.It also diminishes the risk of severe soil disturbance by excluding the wettest area in the planning.展开更多
Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.Ho...Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.However,determining the optimal dosage and route of administration to minimize toxicity while maintaining efficacy remains challenging.Methods:In this study,we investigated the effect of orally administered tacrolimus in rabbits,with an aim to achieve a whole blood target trough level of 3-10 ng/m L,and looked at signs of tissue rejection after the transplantation of a human nerve conduit to repair a severed fibular nerve.An oral dosage range of 0.25-1.5 mg/kg/d was studied for up to 1 year in 63 New Zealand rabbits.Results:We demonstrated the feasibility of long-term grafting in rabbits while maintaining safe immunosuppression,with side effects mainly limited to diarrhea.Customizing the administered dose proved crucial for graft efficacy and low toxicity,which translated into 100%individual survival.We suggest an oral tacrolimus dose of 1.0-1.5 mg/kg depending on individual heterogeneity and recommend to implement a close therapeutic drug monitoring in the rabbits to maintain a whole blood tacrolimus trough level within the range of 5-12 ng/m L,as levels below 5 ng/m L showed signs of inflammation in the graft.Conclusion:The oral administration of tacrolimus enabled efficient immunosuppression of rabbits over a 1-year period without significant side effects or loss of animals.展开更多
Febrile infants are at greater risk of invasive bacterial infections (IBI),which include bacterial meningitis and bacteremia.Although bacterial meningitis is uncommon,^([1-2])it remains a concern for clinicians treati...Febrile infants are at greater risk of invasive bacterial infections (IBI),which include bacterial meningitis and bacteremia.Although bacterial meningitis is uncommon,^([1-2])it remains a concern for clinicians treating infants younger than 90 d.Guidelines for investigating fever without a source(meaning without an apparent source of infection,or of nonobvious origin) are numerous around the world but remain conflicting,particularly on whether to perform a lumbar puncture for cerebrospinal fluid (CSF) analysis in infants older than 22 d and hence at lower risk than younger infants.展开更多
Objectives:Glioblastoma(GB)is a grade IV glial tumor characterized by high malignancy and dismal prognosis,primarily due to high recurrence rates and therapeutic resistance.The epidermal growth factor receptor(EGFR),a...Objectives:Glioblastoma(GB)is a grade IV glial tumor characterized by high malignancy and dismal prognosis,primarily due to high recurrence rates and therapeutic resistance.The epidermal growth factor receptor(EGFR),a receptor tyrosine kinase(RTK),regulates signaling pathways,including cell growth,proliferation,survival,migration,and cell death.Many cancers utilize immune checkpoints(ICs)to attenuate immune responses.CD73 is an enzyme that functions as an IC by hydrolyzing AMP to adenosine,suppressing immune cells in the tumor microenvironment.However,the role of CD73 in resistance to EGFR inhibitors is poorly understood.This study aims to elucidate the resistance mechanisms induced by anti-EGFR treatment and to evaluate an anti-CD73 approach to overcome resistance mediated by anti-EGFR monotherapy.Methods:The U251 GB cell line was treated with AG1478,an EGFR inhibitor,and the resistance markers MRP-1,PD-L1,and CD73 were evaluated using flow cytometry.Additionally,we assessed the combination effects of AG1478 and APCP(an EGFR and a CD73 inhibitor,respectively)on cell cycle progression,proliferation,apoptosis,and migration in vitro.Results:We observed high EGFR,PD-L1,and CD73 expression in human GB cells.The treatment with AG1478 increased the expression of resistance markers MRP-1,PD-L1,and CD73,whereas it decreased CTLA-4.The combination of AG1478 and APCP did not alter proliferation or apoptosis but interfered with cell cycling,arresting the cells in the G1 phase,decreasing cell motility and partially reversing MRP-1 overexpression.Conclusion:In summary,our findings indicate that CD73 inhibition has a modest effect in overcoming resistance to EGFR monotherapy in vitro.Thus,further in vivo studies are needed,as the inhibition of both EGFR and CD73 affects cells in the tumor microenvironment and could potentially enhance anti-tumor immunity.展开更多
The application of different coatings on solar photovoltaic(PV)panels can be an efficient solution to increase performance and further mitigate the emission of greenhouse gases.This study uses the Life Cycle Assessmen...The application of different coatings on solar photovoltaic(PV)panels can be an efficient solution to increase performance and further mitigate the emission of greenhouse gases.This study uses the Life Cycle Assessment(LCA)methodology and the environmental payback concept to analyze the effects of the application of a nano-silica coating on a solar PV system installed in the Brazilian Northeast.Firstly,an uncoated reference 16.4 MW PV system is designed,and the detailed inventory is presented(PV panels,supporting structure,inverters,junction boxes,cables,transportation,maintenance and operation-including the replacement of equipment).The results of the LCA quantify the greenhouse gas emissions associated with the PV system.Electricity production is estimated by technical and local climate data.Subsequently,the environmental payback time of the system is calculated,which is the time required for the PV system to offset the emissions associated with system manufacturing,operation,and disposal.This is the first Brazilian study to verify the effects of a self-cleaning coating on a solar PV system throughout its lifetime,compared to the uncoated(reference system).The original photovoltaic system emitted 22,534,773 kg CO_(2)-eq,with an environmental payback of 5 years and 1 day.When the self-cleaning coating is applied,the emissions are 21,511,317 kg CO_(2)-eq(almost 5%lower)with a payback of 4 years,1 month and 26 days.The application of self-cleaning coatings reduces the required area for installation(due to increased efficiency),and not only reduces emissions but is also aligned with global sustainability targets and contributes to the concept of sustainable and intelligent cities.展开更多
There are limited biosecurity measures directed at preventing airborne transmission of viruses in swine.The effectiveness of dust mitigation strategies such as oil sprinkling,to decrease risk of airborne virus transmi...There are limited biosecurity measures directed at preventing airborne transmission of viruses in swine.The effectiveness of dust mitigation strategies such as oil sprinkling,to decrease risk of airborne virus transmission are unknown.Metagenomics and qPCR for common fecal viruses were used to hunt for a ubiquitous virus to serve as a proxy when evaluating the efficiency of mitigation strategies against airborne viral infectious agents.Air particles were collected from swine buildings using high-volume air samplers.Extracted DNA and RNA were used to perform specific RT-qPCR and qPCR and analyzed by highthroughput sequencing.Porcine astroviruses group 2 were common(from 102 to 105 genomic copies per cubic meter of air or gc/m^(3),93%positivity)while no norovirus genogroup II was recovered from air samples.Porcine torque teno sus virus were detected by qPCR in low concentrations(from 101 to 102 gc/m^(3),47%positivity).Among the identified viral families by metagenomics analysis,Herelleviridae,Microviridae,Myoviridae,Podoviridae,and Siphoviridae were dominant.The phage vB_AviM_AVP of Aerococcus was present in all air samples and a newly designed qPCR revealed between 101 and 105 gc/m^(3) among the samples taken for the present study(97%positivity)and banked samples from5-and 15-year old studies(89%positivity).According to the present study,both the porcine astrovirus group 2 and the phage vB_AviM_AVP of Aerococcus could be proxy for airborne viruses of swine buildings.展开更多
Background: Prematurely-born individuals tend to exhibit higher resting oxidative stress, although evidence suggests they may be more resistant to acute hypoxia-induced redox balance alterations. We aimed to investiga...Background: Prematurely-born individuals tend to exhibit higher resting oxidative stress, although evidence suggests they may be more resistant to acute hypoxia-induced redox balance alterations. We aimed to investigate the redox balance changes across a 3-day hypobaric hypoxic exposure at 3375 m in healthy adults born preterm(gestational age ≤ 32 weeks) and their term-born(gestational age ≥ 38 weeks)counterparts.Methods: Resting venous blood was obtained in normoxia(prior to altitude exposure), immediately upon arrival to altitude, and the following 3mornings. Antioxidant(superoxide dismutase(SOD), catalase, glutathione peroxidase(GPx), and ferric reducing antioxidant power(FRAP)),pro-oxidant(xanthine oxidase(XO) and myeloperoxidase(MPO)) enzyme activity, oxidative stress markers(advanced oxidation protein product(AOPP) and malondialdehyde(MDA)), nitric oxide(NO) metabolites(nitrites, nitrates, and total nitrite and nitrate(NOx)), and nitrotyrosine were measured in plasma.Results: SOD increased only in the preterm group(p < 0.05). Catalase increased at arrival in preterm group(p < 0.05). XO activity increased at Day 3 for the preterm group, while it increased acutely(arrival and Day 1) in control group. MPO increased in both groups throughout the3 days(p < 0.05). AOPP only increased at arrival in the preterm(p < 0.05) whereas it decreased at arrival up to Day 3(p < 0.05) for control.MDA decreased in control group from arrival onward. Nitrotyrosine decreased in both groups(p < 0.05). Nitrites increased on Day 3(p < 0.05)in control group and decreased on Day 1(p < 0.05) in preterm group.Conclusion: These data indicate that antioxidant enzymes seem to increase immediately upon hypoxic exposure in preterm adults. Conversely, the blunted pro-oxidant enzyme response to prolonged hypoxia exposure suggests that these enzymes may be less sensitive in preterm individuals.These findings lend further support to the potential hypoxic preconditioning effect of preterm birth.展开更多
The presence of heterozygous individuals in a population is crucial for maintaining genetic diversity,which can positively affect fitness and adaptability to environmental changes.While inbreeding generally reduces th...The presence of heterozygous individuals in a population is crucial for maintaining genetic diversity,which can positively affect fitness and adaptability to environmental changes.While inbreeding generally reduces the proportion of heterozygous individuals in a population,polyploidy tends to increase the proportion.North American Populus tremuloides is one of the most widely distributed and ecologically important tree species in the Northern Hemisphere.However,genetic variation in Mexican populations of P.tremuloides,including the genetic signatures of their adaptation to a variety of environments,remains largely uncharacterized.The aim of this study was to analyze how inbreeding coefficient(FIS)and ploidy are associated with clonal richness,population cover,climate and soil traits in 91 marginal to small,isolated populations of this tree species throughout its entire distribution in Mexico.Genetic variables were determined using 36,810 filtered SNPs derived from genome re-sequencing.We found that FIS was approximately between 0 and e1,indicating an extreme heterozygosity excess.One key contributor to the observed extreme heterozygosity excess was asexual reproduction,although ploidy levels cannot explain this excess.Analysis of all neutral SNPs showed that asexual reproduction was positively correlated with observed heterozygosity(Ho)but negatively correlated with expected heterozygosity(He).Analysis of outlier SNPs also showed that asexual reproductionwas positively correlated with Ho and negatively correlated with He,although this latter correlation was not significant.These findings support the presence of a Meselson effect.展开更多
基金supported by Craig H.Neilsen Foundation,Wings for Life Foundation,Canadian Institutes of Health Research,and Fonds de Recherche Québec-Santé(to FB).
文摘Spinal cord injury(SCI)interrupts the flow of information between the brain and the spinal cord,thus leading to a loss of sensory information and motor paralysis of the body below the lesion.Surprisingly,most SCIs are incomplete and spare supraspinal pathways,especially those located within the peripheral white matter of the spinal cord,which includes reticulospinal pathways originating from the medullary reticular formation.Whereas there is abundant literature about the motor cortex,its corticospinal pathway,and its capacity to modulate functional recovery after SCI,less is known about the medullary reticular formation and its reticulospinal pathway.
基金supported by funding from Parkinson Canadafunded by a scholarship from Parkinson Canadaa scholarship from Fonds d’Enseignement et de Recherche (FER) (Faculty of Pharmacy, Université Laval)
文摘There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.
基金supported by the National Centre for the Replacement Refinement & Reduction of Animals in Research Crack It solution “Neuroinflammation and nociception in a dish”(https://nc3rs.org.uk/crackit/news/new-solutionneuroinflammation-and-nociception-dish) fund(to AM)。
文摘Mesenchymal stem cells(MSCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical cord.MSCs have gained significant attention in regenerative medicine due to their ability to modulate the immune system and favor tissue repair.MSCs enrich the medium in which they are cultivated with a broad range of bioactive molecules,including growth factors,cytokines,chemokines,enzymes,nucleic acids,and extracellular vesicles that collectively compose the MSC secretome.An increasing number of pre-clinical studies suggest that delivering in vivo an MSC-conditioned medium(i.e.,the medium collected from MSC cultures after at least 3 days of exposure)exerts neuroprotective and anti-inflammatory effects in a variety of neurological conditions.
基金supported by the Natural Science and En-gineering Research Council of Canada(Discovery and Alliance),and PRIMA(Quebec Ministry for Economy and Innovation).
文摘Biodegradable implants have emerged in biomedical applications,particularly for orthopedic fixations,cardiovascular stents,and tissue engineering scaffolds.Unlike permanent implants,they are designed to degrade and be reabsorbed after implantation in the body,mitigating the need for additional surgeries and reducing associated complications.In particular,Fe-Mn-C alloys constitute a new class of promising metallic materials for medical applications due to their outstanding mechanical properties and their bio-logical performances.This study focuses on improving the degradation rates and cytotoxicity of sintered Fe-Mn-C alloys produced using the powder metallurgy process.To evaluate the impact of different pow-der preparation methods on material properties,two types of powders were used:(1)MX,prepared by mixing Fe,Mn,and C powders for 1 h;and(2)MM,obtained by mechanically milling the same powders for 10 h.Four mixtures with varying proportions of MX and MM were prepared.Two groups of samples were produced:one entirely from MX(A0),and another containing MM at 25 wt.%(A25),50 wt.%(A50),and 75 wt.%(A75).All samples exhibited a complex microstructure comprising ferrite,martensite,and residual austenite.Degradation behavior assessment in Hanks’solution over 14 days showed that adding MM increased the degradation rate,from around 0.04 mmpy for A0 to 0.12 mmpy for A25.Notably,all samples showed similar cell viability,in the range of 83%-89%for 1%extract dilution,and were non-hemolytic,with a hemolysis percentage below 1%.
基金The Quebec Cell,Tissue and Gene Therapy Network–ThéCell,a thematic network supported by the FRQCanadian Institutes of Health Research,Grant/Award Number:PJT-175015+1 种基金the Fonds de recherche du Québec(FRQ)through the research centre grant for the CHU de Québec-UniversitéLaval Research Center,Grant/Award Number:30641the FRQ,the Fondation du CHU de Québec-UniversitéLaval and from Neuro Québec。
文摘Background:Although widely used,the rat model remains poorly transferable to humans for peripheral nerve regeneration studies.The rabbit is a much better choice from an anatomical perspective.However,it remains little used due to the lack of available literature.The aim of this article is to demonstrate the feasibility and effectiveness of an electrophysiological protocol combined with a motor function assessment to analyze nerve repair.Methods:Ten white New Zealand rabbits underwent a 4 cm transection of the fibular nerve.Autograft regeneration over 36 weeks was compared to non-repaired controls.The compound muscle action potential(CMAP)was recorded in the tibialis anterior and the extensor digitorum brevis.An electromyogram(EMG)was obtained after needle insertion and resting muscle activity recording.The electrophysiological results were compared to the toe spread index(TSI),which assesses the motor functional recovery promoted by fibular nerve regeneration.Results:The autograft group regeneration starts between weeks 18 and 21 and normal EMG was observed around the 30th week.These electrophysiological results were compared to the well-defined toe spread reflex.This motor test showed a significant functional return of 59%at 36 weeks(p<0.05).Rabbits regain nearly 80%of their muscle mass.Conclusion:Nerve conduction allows detection of nerve regeneration of the muscle while electromyography indicates when muscle activity returns to normal.These studies are reliable and non-invasive techniques to evaluate fibular nerve regeneration in the rabbit's hindlimb.Nonetheless,it is necessary to have qualified personnel,since inter-manipulator variations have been observed.
基金funded by Vinnova,the Swedish Innovation Agency as a part of the Autoplant project(Dnr 2020-04202 and 2023-02747).
文摘Effective forest regeneration is essential for sustainable forestry practices.In Sweden,mechanical site preparation and manual planting is the dominating method,but sourcing labour for the physically demanding work is difficult.An autonomous scarifying and planting system(Autoplant)could meet the requirements of the forest industry and,for this,a tool for regeneration planning and routing is needed.The tool,Pathfinder,plans the regeneration and routes based on the harvested production(hpr)files,soil moisture and parent material maps,no-go areas(for culture or nature conservation),digital elevation models(DEM),and machine data(e.g.,working width,critical slope,time taken for different turn angles).The overall planting solution is either a set of capacity constrained routes or a continuous route and could be used for any planting machine as well as for traditional scarifiers as disc trenchers or mounders pulled by forwarders.Pathfinder was tested on eleven regeneration areas throughout Sweden,both with continuous routes and routes based on a carrying capacity of 1500 seedlings.The net operation area,species and seedling density suggestions were deemed relevant by expert judgement in the field.The routes provided by Pathfinder were compared with solutions given by two experienced drivers and a third solution based on the actual soil scarification at the site.Total driving distance did not differ significantly between the suggestions,but Pathfinder included less side-slope driving on steep slopes(≥27%or 15°)and medium slopes(15–27%).The chosen threshold value for steep slopes(where side-slope driving should be avoided)affects the routing,and a lower threshold means more turning and longer driving distance.Pathfinder is not only a tool for routing of planting machines,but also helps in planning of traditional regeneration by providing a more correct net area and tree species suggestions based on the growth of the previous stand.It also diminishes the risk of severe soil disturbance by excluding the wettest area in the planning.
基金the Canadian Institutes of Health Research(CIHR),Grant/Award Number:PJT-175016the Fonds de recherche du Québec(FRQ)through the research centre grant for the CHU de Québec-UniversitéLaval Research Center,Grant/Award Number:30641+2 种基金the Quebec Cell,Tissue and Gene Therapy Network—ThéCellthe FRQS,the Fondation du CHU de Québec-UniversitéLavalNeuro Québec。
文摘Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.However,determining the optimal dosage and route of administration to minimize toxicity while maintaining efficacy remains challenging.Methods:In this study,we investigated the effect of orally administered tacrolimus in rabbits,with an aim to achieve a whole blood target trough level of 3-10 ng/m L,and looked at signs of tissue rejection after the transplantation of a human nerve conduit to repair a severed fibular nerve.An oral dosage range of 0.25-1.5 mg/kg/d was studied for up to 1 year in 63 New Zealand rabbits.Results:We demonstrated the feasibility of long-term grafting in rabbits while maintaining safe immunosuppression,with side effects mainly limited to diarrhea.Customizing the administered dose proved crucial for graft efficacy and low toxicity,which translated into 100%individual survival.We suggest an oral tacrolimus dose of 1.0-1.5 mg/kg depending on individual heterogeneity and recommend to implement a close therapeutic drug monitoring in the rabbits to maintain a whole blood tacrolimus trough level within the range of 5-12 ng/m L,as levels below 5 ng/m L showed signs of inflammation in the graft.Conclusion:The oral administration of tacrolimus enabled efficient immunosuppression of rabbits over a 1-year period without significant side effects or loss of animals.
基金the financial contribution of the Groupe de Recherche En Médecine d’Urgence du CHUL (GREMUC)which is the local emergency department research group。
文摘Febrile infants are at greater risk of invasive bacterial infections (IBI),which include bacterial meningitis and bacteremia.Although bacterial meningitis is uncommon,^([1-2])it remains a concern for clinicians treating infants younger than 90 d.Guidelines for investigating fever without a source(meaning without an apparent source of infection,or of nonobvious origin) are numerous around the world but remain conflicting,particularly on whether to perform a lumbar puncture for cerebrospinal fluid (CSF) analysis in infants older than 22 d and hence at lower risk than younger infants.
基金supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq,n°406035/2021-0 and PQ n°311580/2021-1,FigueiróF)Instituto Nacional de Ciência e Tecnologia-INCT/CNPq/CAPES/FAPERGS Grant no.465671/2014-4Jean Sévigny received support from the Natural Sciences and Engineering Research Council of Canada(NSERC,RGPIN-2023-05498).
文摘Objectives:Glioblastoma(GB)is a grade IV glial tumor characterized by high malignancy and dismal prognosis,primarily due to high recurrence rates and therapeutic resistance.The epidermal growth factor receptor(EGFR),a receptor tyrosine kinase(RTK),regulates signaling pathways,including cell growth,proliferation,survival,migration,and cell death.Many cancers utilize immune checkpoints(ICs)to attenuate immune responses.CD73 is an enzyme that functions as an IC by hydrolyzing AMP to adenosine,suppressing immune cells in the tumor microenvironment.However,the role of CD73 in resistance to EGFR inhibitors is poorly understood.This study aims to elucidate the resistance mechanisms induced by anti-EGFR treatment and to evaluate an anti-CD73 approach to overcome resistance mediated by anti-EGFR monotherapy.Methods:The U251 GB cell line was treated with AG1478,an EGFR inhibitor,and the resistance markers MRP-1,PD-L1,and CD73 were evaluated using flow cytometry.Additionally,we assessed the combination effects of AG1478 and APCP(an EGFR and a CD73 inhibitor,respectively)on cell cycle progression,proliferation,apoptosis,and migration in vitro.Results:We observed high EGFR,PD-L1,and CD73 expression in human GB cells.The treatment with AG1478 increased the expression of resistance markers MRP-1,PD-L1,and CD73,whereas it decreased CTLA-4.The combination of AG1478 and APCP did not alter proliferation or apoptosis but interfered with cell cycling,arresting the cells in the G1 phase,decreasing cell motility and partially reversing MRP-1 overexpression.Conclusion:In summary,our findings indicate that CD73 inhibition has a modest effect in overcoming resistance to EGFR monotherapy in vitro.Thus,further in vivo studies are needed,as the inhibition of both EGFR and CD73 affects cells in the tumor microenvironment and could potentially enhance anti-tumor immunity.
基金support of the Paraíba State Research Foundation(FAPESQ)(call No.09/2021)National Council for Scientific and Technological Development(CNPq Productivity Grants 309452/2021-0,308753/2021-6)+1 种基金Scientific Initiation Scholarships(PIBIC)within the Federal University of Paraíba(UFPB)Silvia Guillén Lambea thanks Grant RYC2021-034265-I funded by MCIN/AEI/10.13039/501100011033 and by“European Union Next Generation EU/PRTR”。
文摘The application of different coatings on solar photovoltaic(PV)panels can be an efficient solution to increase performance and further mitigate the emission of greenhouse gases.This study uses the Life Cycle Assessment(LCA)methodology and the environmental payback concept to analyze the effects of the application of a nano-silica coating on a solar PV system installed in the Brazilian Northeast.Firstly,an uncoated reference 16.4 MW PV system is designed,and the detailed inventory is presented(PV panels,supporting structure,inverters,junction boxes,cables,transportation,maintenance and operation-including the replacement of equipment).The results of the LCA quantify the greenhouse gas emissions associated with the PV system.Electricity production is estimated by technical and local climate data.Subsequently,the environmental payback time of the system is calculated,which is the time required for the PV system to offset the emissions associated with system manufacturing,operation,and disposal.This is the first Brazilian study to verify the effects of a self-cleaning coating on a solar PV system throughout its lifetime,compared to the uncoated(reference system).The original photovoltaic system emitted 22,534,773 kg CO_(2)-eq,with an environmental payback of 5 years and 1 day.When the self-cleaning coating is applied,the emissions are 21,511,317 kg CO_(2)-eq(almost 5%lower)with a payback of 4 years,1 month and 26 days.The application of self-cleaning coatings reduces the required area for installation(due to increased efficiency),and not only reduces emissions but is also aligned with global sustainability targets and contributes to the concept of sustainable and intelligent cities.
文摘There are limited biosecurity measures directed at preventing airborne transmission of viruses in swine.The effectiveness of dust mitigation strategies such as oil sprinkling,to decrease risk of airborne virus transmission are unknown.Metagenomics and qPCR for common fecal viruses were used to hunt for a ubiquitous virus to serve as a proxy when evaluating the efficiency of mitigation strategies against airborne viral infectious agents.Air particles were collected from swine buildings using high-volume air samplers.Extracted DNA and RNA were used to perform specific RT-qPCR and qPCR and analyzed by highthroughput sequencing.Porcine astroviruses group 2 were common(from 102 to 105 genomic copies per cubic meter of air or gc/m^(3),93%positivity)while no norovirus genogroup II was recovered from air samples.Porcine torque teno sus virus were detected by qPCR in low concentrations(from 101 to 102 gc/m^(3),47%positivity).Among the identified viral families by metagenomics analysis,Herelleviridae,Microviridae,Myoviridae,Podoviridae,and Siphoviridae were dominant.The phage vB_AviM_AVP of Aerococcus was present in all air samples and a newly designed qPCR revealed between 101 and 105 gc/m^(3) among the samples taken for the present study(97%positivity)and banked samples from5-and 15-year old studies(89%positivity).According to the present study,both the porcine astrovirus group 2 and the phage vB_AviM_AVP of Aerococcus could be proxy for airborne viruses of swine buildings.
基金funded by the Swiss National Science Foundation(SNSF Grant No.320030L_192073 to GM)the Slovenian Research Agency(ARRS Grant No.N5-0152 to TD).
文摘Background: Prematurely-born individuals tend to exhibit higher resting oxidative stress, although evidence suggests they may be more resistant to acute hypoxia-induced redox balance alterations. We aimed to investigate the redox balance changes across a 3-day hypobaric hypoxic exposure at 3375 m in healthy adults born preterm(gestational age ≤ 32 weeks) and their term-born(gestational age ≥ 38 weeks)counterparts.Methods: Resting venous blood was obtained in normoxia(prior to altitude exposure), immediately upon arrival to altitude, and the following 3mornings. Antioxidant(superoxide dismutase(SOD), catalase, glutathione peroxidase(GPx), and ferric reducing antioxidant power(FRAP)),pro-oxidant(xanthine oxidase(XO) and myeloperoxidase(MPO)) enzyme activity, oxidative stress markers(advanced oxidation protein product(AOPP) and malondialdehyde(MDA)), nitric oxide(NO) metabolites(nitrites, nitrates, and total nitrite and nitrate(NOx)), and nitrotyrosine were measured in plasma.Results: SOD increased only in the preterm group(p < 0.05). Catalase increased at arrival in preterm group(p < 0.05). XO activity increased at Day 3 for the preterm group, while it increased acutely(arrival and Day 1) in control group. MPO increased in both groups throughout the3 days(p < 0.05). AOPP only increased at arrival in the preterm(p < 0.05) whereas it decreased at arrival up to Day 3(p < 0.05) for control.MDA decreased in control group from arrival onward. Nitrotyrosine decreased in both groups(p < 0.05). Nitrites increased on Day 3(p < 0.05)in control group and decreased on Day 1(p < 0.05) in preterm group.Conclusion: These data indicate that antioxidant enzymes seem to increase immediately upon hypoxic exposure in preterm adults. Conversely, the blunted pro-oxidant enzyme response to prolonged hypoxia exposure suggests that these enzymes may be less sensitive in preterm individuals.These findings lend further support to the potential hypoxic preconditioning effect of preterm birth.
基金We thank the Mexican Consejo Nacional de Humanidades,Ciencias y Tecnologías(CONAHCYT)for the financial support provided to the first author to carry out his training in the Institutional Doctoral Program in Agricultural and Forestry Sciences(PIDCAFUJED)with Scholarship No.334852financial support with agreement number CONACYT-FRQ-2016:279459 for the project“Genome-wide scans for detecting adaptation to climate and soil in Populus tremuloides as the most widely distributed tree species in North America”Dr.Jesús M.Olivas-García assisted in the sampling in the state of Chihuahua,Mexico,and Katrin Groppe,Thünen Institute of Forest Genetics,Germany,provided excellent lab work.The Emerging Leaders of the Americas Program(ELAP)of the Government of Canada awarded a scholarship and the Institute of Integrative and Systems Biology(IBIS)of Laval University allowed the use of its campus and contributed to the training of the first author.
文摘The presence of heterozygous individuals in a population is crucial for maintaining genetic diversity,which can positively affect fitness and adaptability to environmental changes.While inbreeding generally reduces the proportion of heterozygous individuals in a population,polyploidy tends to increase the proportion.North American Populus tremuloides is one of the most widely distributed and ecologically important tree species in the Northern Hemisphere.However,genetic variation in Mexican populations of P.tremuloides,including the genetic signatures of their adaptation to a variety of environments,remains largely uncharacterized.The aim of this study was to analyze how inbreeding coefficient(FIS)and ploidy are associated with clonal richness,population cover,climate and soil traits in 91 marginal to small,isolated populations of this tree species throughout its entire distribution in Mexico.Genetic variables were determined using 36,810 filtered SNPs derived from genome re-sequencing.We found that FIS was approximately between 0 and e1,indicating an extreme heterozygosity excess.One key contributor to the observed extreme heterozygosity excess was asexual reproduction,although ploidy levels cannot explain this excess.Analysis of all neutral SNPs showed that asexual reproduction was positively correlated with observed heterozygosity(Ho)but negatively correlated with expected heterozygosity(He).Analysis of outlier SNPs also showed that asexual reproductionwas positively correlated with Ho and negatively correlated with He,although this latter correlation was not significant.These findings support the presence of a Meselson effect.
