Aerobic glycolysis,also known as the Warburg effect,and the accumulation of lactate that it causes,are increasingly recognized outside the field of oncology as triggers of chronic non-neoplastic disorders.This review ...Aerobic glycolysis,also known as the Warburg effect,and the accumulation of lactate that it causes,are increasingly recognized outside the field of oncology as triggers of chronic non-neoplastic disorders.This review integrates preclinical and clinical evidence to evaluate the ability of melatonin to reverseWarburg-effect-like metabolic reprogramming.Literature on neurodegeneration,age-related sarcopenia,type 2 diabetes,chronic kidney disease,heart failure and pulmonary arterial hypertension(PAH)has been reviewed and synthesised.In all of these conditions,hypoxia-inducible factor 1α(HIF-1α)and pyruvate dehydrogenase kinase 4(PDK4)inhibit the pyruvate dehydrogenase complex.This diverts pyruvate away fromthe tricarboxylic acid(TCA)cycle and promotes glycolysis.In cell and animal models,melatonin consistently inhibits PDK4,destabilizes HIF-1αunder normoxic conditions,activates SIRT1/3-dependentmitochondrial biogenesis andmitophagy,and eliminates reactive oxygen and nitrogen species.These actions reduce lactate production,restore oxidative phosphorylation and attenuate tissue damage.This appears to induce cognitive and synaptic improvements in Alzheimer’s and Parkinson’s disease models,increased muscle mass and function in ageing rodents,improved insulin sensitivity alongside suppression of hepatic gluconeogenesis in diabetic models,reduced fibrosis in nephropathy,and normalization of vascular remodeling in hypoxia-induced pulmonary arterial hypertension(PAH).Early-stage clinical trials corroborate a decrease in oxidative and inflammatorymarkers,improved sleep quality and modest cognitive benefits.However,they report conflicting effects on insulin sensitivity,which are largely related to the dose and timing of administration in relation to food intake.Overall,the current data suggest that melatonin is a pleiotropic metabolic modulator capable of counteracting the Warburg phenotype in multiple organs.However,human studies remain scarce,and well-designed randomised trials incorporating chronotherapy are needed before clinical adoption.展开更多
Cadmium(Cd)is a toxic trace metal that occurs naturally in agricultural soils and can accumulate in the edible parts of crops,notably in cereal grains.This study investigated the extent to which sulfur(S)fertilization...Cadmium(Cd)is a toxic trace metal that occurs naturally in agricultural soils and can accumulate in the edible parts of crops,notably in cereal grains.This study investigated the extent to which sulfur(S)fertilization increases the availability of Cd in a calcareous(Calc)and a non-calcareous(Ncalc)soil.Changes in Cd availability and speciation were monitored over a 21-d incubation period,along with changes in pH and the concentrations of sulfate,nitrate,calcium,magnesium,aluminum(Al),manganese(Mn),and nickel(Ni)in the potassium nitrate(KNO_(3))extracts,after the addition at agronomic rates of three forms of S fertilizers:elemental S(S(0)),potassium sulfate(K_(2)SO_(4)),and ammonium sulfate((NH_(4))_(2)SO_(4)).Elemental S did not increase the Cd concentration in the KNO_(3)extracts of either soil due to its too limited oxidation to sulfates.The two sulfate fertilizers had contrasting effects on Cd concentration depending on the nature of the counter cation(K^(+)or NH_(4)^(+)).While K_(2)SO_(4)caused almost no change in Cd concentration in either soil,(NH_(4))_(2)SO_(4)increased Cd concentration in both soils.The nitrification of NH_(4)^(+)reduced soil pH,thereby increasing the concentrations of Cd,Al,Mn,and Ni in the Ncalc soil over time,as evidenced by the strong negative correlations between soil pH and the concentrations of these four elements in the KNO3 extract after 21 d.In the Calc soil,the mechanism of Cd concentration increase after(NH_(4))_(2)SO_(4)addition was more difficult to understand and could result from the proton-mediated alteration of Cd-bearing phases such as carbonates,following ammonia(NH_(3))volatilization.The relevance of these results for the S fertilization of cereals in Cd-contaminated soils is discussed.展开更多
Sustainability is a leading trend in the context of food production.Additionally,consumers increasingly demand safer and less-processed products.Among the different technologies used to maintain the quality and extend...Sustainability is a leading trend in the context of food production.Additionally,consumers increasingly demand safer and less-processed products.Among the different technologies used to maintain the quality and extend the shelf-life of fresh and minimally-processed food,natural antimicrobial agents offer a promising strategy to replace conventional compounds.In this regard,phage lytic proteins or lysins,such as endolysins and virion-associated peptidoglycan hydrolases(VAPGHs),have been proposed as a viable option for the avoidance and elimination of undesirable bacteria within the food production chain.Even when applied exogenously,these proteins can degrade the bacterial cell wall maintaining their lytic activity.This feature,alongside their modular structure,which can be exploited for bioengineering,provides significant biotechnological potential.However,despite the promising properties of lysins,the main obstacle for their commercialization is the limited legal information regulating their use.This challenge underscores the need to navigate complex regulatory pathways.The primary objective of this review is to address this crucial gap and summarize the many prospective applications of endolysins during the different stages of food production.By doing so,we aim to provide clarity and insight into the regulatory challenges that must be overcome for the successful utilization of lysins.展开更多
Coffee wilt represents one of the most devastating diseases of Arabica coffee(Coffea arabica L.)plantations in the primary coffee-producing regions.In this study,coffee trees manifesting wilt symptoms accompanied by t...Coffee wilt represents one of the most devastating diseases of Arabica coffee(Coffea arabica L.)plantations in the primary coffee-producing regions.In this study,coffee trees manifesting wilt symptoms accompanied by the defoliation and drying of the whole tree were observed in the Jazan,El Baha,Najran,and Asir regions.The purpose of this investigation was to isolate and identify the Fusarium species recovered from symptomatic coffee trees.The developed fungi were initially characterized based on their morphological features followed by molecular phylogenetic multi-locus analysis of the combined sequences of ITS,TEF1-α,RPB2,and CaM.Twenty-five isolates were recovered from 28 samples.All fungal isolates were categorized morphologically under the genus Fusarium.Phylogenetic analysis positioned all the representative 15 isolates into one cluster grouping together with Neocosmospora falciformis(formerly F.falciforme)confirming their taxonomic position.Pathogenicity tests of the N.falciformis isolates were subsequently conducted on coffee seedlings,and the results revealed that all isolates induced wilt symptoms resembling those recorded in the field,and the incidence was 100%.The fungicide sensitivity test of seven investigated fungicides revealed that Maxim XL^(®) followed by Moncut^(®) exhibited the highest inhibitory effect against N.falciformis KSA 24-14,reaching 93.33%and 91.67%,respectively.To our knowledge,N.falciformis is a new causal pathogen of coffee wilt in Saudi Arabia.Remarkably,these results offer important insights for devising effective approaches to monitor and control such diseases.展开更多
The chemical characterization of phenolic extracts of salad burnet (Sanguisorba minor Scop. s.l.) and broomrape (Orobanche crenata Forsk.) was performed. Active fractions were separated and characterized and, in the c...The chemical characterization of phenolic extracts of salad burnet (Sanguisorba minor Scop. s.l.) and broomrape (Orobanche crenata Forsk.) was performed. Active fractions were separated and characterized and, in the case of O. crenata, two phenolic compounds, verbascoside and is overbascoside, were quantitatively extracted, purified and characterized. These compounds proved to be effective in reducing the growth of some important fungi responsible for the decay of fresh fruit and vegetables in postharvest. Verbascoside showed significant activity against Penicillium italicum, fairly inhibited Monilinia laxa, P. expansum, and Aspergillus carbonarius, and showed little activity against Botrytis cinerea, M. fructicola and P. digitatum. Isoverbascoside completely inhibited B. cinerea, P. digitatum, P. italicum, and P. expansum;it fairly inhibited M. laxa and A. carbonarius;while it showed to be less effective against M. fructicola. The obtained results support the possible use of some wild edible plants as a source of phenolic substances for the postharvest biological control of fresh fruit and vegetable rots.展开更多
Exercise has long been known for its active role in improving physical fitness and sustaining health.Regular moderate-intensity exercise improves all aspects of human health and is widely accepted as a preventative an...Exercise has long been known for its active role in improving physical fitness and sustaining health.Regular moderate-intensity exercise improves all aspects of human health and is widely accepted as a preventative and therapeutic strategy for various diseases.It is well-documented that exercise maintains and restores homeostasis at the organismal,tissue,cellular,and molecular levels to stimulate positive physiological adaptations that consequently protect against various pathological conditions.Here we mainly summarize how moderate-intensity exercise affects the major hallmarks of health,including the integrity of barriers,containment of local perturbations,recycling and turnover,integration of circuitries,rhythmic oscillations,homeostatic resilience,hormetic regulation,as well as repair and regeneration.Furthermore,we summarize the current understanding of the mechanisms responsible for beneficial adaptations in response to exercise.This review aimed at providing a comprehensive summary of the vital biological mechanisms through which moderate-intensity exercise maintains health and opens a window for its application in other health interventions.We hope that continuing investigation in this field will further increase our understanding of the processes involved in the positive role of moderate-intensity exercise and thus get us closer to the identification of new therapeutics that improve quality of life.展开更多
Every region around the globe has its unique climatic conditions which are set based on different orographic constant and atmospheric dynamic features. These features posses’ variability on different time scales. Det...Every region around the globe has its unique climatic conditions which are set based on different orographic constant and atmospheric dynamic features. These features posses’ variability on different time scales. Determining the local sea level change based on terrestrial non-tidal, short-term variability is complicated. Some internal mechanisms of ocean are also taking place along with the external physical ones. We show that variability at Sindh-Baluchistan coastal belt can be greatly explained via dimensional indices of the position and intensity of the atmospheric center of action (COAs). This technique has already proved its usefulness at number of location especially in Northern Atlantic. It takes into account the changes in the atmospheric pressure which is exerted on the sea surface influencing the variability in sea level on seasonal scale and on inter-annual basis. As warming causes thermal expansion of water it also causes changes in atmospheric circulation. Both of these processes affect the sea level variability on their respective time scales. Atmospheric being the quicker one of the two to pass on the effect is also more influential to explain the variability in local sea level. In this attempt the COA approach is used to assess the impact of low pressure on local sea levels.展开更多
A headspace solid-phase microextraction-gas chromatography-mass spectrometry(HS-SPME/GC-MS)method was used to study the volatile organic compounds(VOCs)associated with the differential immune response of tomato plants...A headspace solid-phase microextraction-gas chromatography-mass spectrometry(HS-SPME/GC-MS)method was used to study the volatile organic compounds(VOCs)associated with the differential immune response of tomato plants infected with the recombinant strain of potato virus Y(PVY^(C)-to),necrogenic to tomato.Analysis was carried out in UC82(UC),a virus susceptible tomato variety,comparing the same UC plants grafted or not onto a virus tolerant tomato ecotype,Manduria(Ma);the three types of samples used for the GC-MS analysis were mock-inoculated UC/Ma plants,UC/Ma+PVY^(C)-to and UC+PVY^(C)-to plants;the VOCs obtained were 111.Results from symptomatic PVY^(C)-to-infected UC plants showed a VOCs composition enriched in alcohols,fatty acid derivates,benzenoids,and salicylic acid derivatives,while in mock-inoculated UC/Ma plants VOCs were mainly characterized by methyl ester compounds.The VOC profile was in line with RNAseq data analyses,denoting that PVY^(C)-to viral RNA accumulation and disease symptoms induce the specific transcriptional activation of genes involved in VOCs biosynthesis.Furthermore,principal component analysis highlighted that VOCs of PVY^(C)-to-infected and mock-inoculated grafted plants were much closer each other than that of symptomatic PVY^(C)-to-infected non-grafted UC plants.These results suggest that VOCs profiles of tomato plants are related to the viral RNA accumulation,disease intensity and graft-derived tolerance to PVY^(C)-to infection.展开更多
1.Introduction Regular exercise induces changes in the overall diversity and in the relative abundance of certain gut microbiota phyla and families in humans1,2 and in animal models.3,4 This relationship has attracted...1.Introduction Regular exercise induces changes in the overall diversity and in the relative abundance of certain gut microbiota phyla and families in humans1,2 and in animal models.3,4 This relationship has attracted a great deal of interest because it is one of the mechanisms involved in the health benefits of regular exercise3 that could also influence performance.5 A recent publication by Scheiman et al.展开更多
It is estimated that approximately one in ten people over the age of 80 may suffer from cardiac amyloidosis(CA),a disease in which various aging-related factors,such as increased oxidative stress,can promote abnormal ...It is estimated that approximately one in ten people over the age of 80 may suffer from cardiac amyloidosis(CA),a disease in which various aging-related factors,such as increased oxidative stress,can promote abnormal protein folding and the formation of amyloid deposits in the heart.Over the long term,this tends to impair cardiac function,increasing the risk of developing cardiac conduction disorders,atrial fibrillation,thromboembolic events,heart failure(HF),and/or ventricular dysfunction.^([1,2])展开更多
Objective: Despite the fact that a restrictive use of episiotomy has proven to be beneficial, it continues to be widely used in vaginal births. Our aim was to compare women with episiotomy, to women with an intact per...Objective: Despite the fact that a restrictive use of episiotomy has proven to be beneficial, it continues to be widely used in vaginal births. Our aim was to compare women with episiotomy, to women with an intact perineum, 3 months after delivery, regarding several sexual variables, namely: sexual desire, arousal, orgasm, pain, sexual satisfaction and sexual function. Methods: An exploratory, descriptive and quantitative study using a non-probabilistic, convenience sample of 147 Portuguese women, of which 54 belonged to a control group, was performed. The groups were not significantly different regarding socio-demographic aspects. Three instruments were used: the Female Sexual Function Index, a Socio-demographic and Clinical Questionnaire and the Female Sexual Function Questionnaire. Results: Most women mentioned a moderate level of sexual interest. Women with episiotomy present higher pain intensity, less sexual satisfaction, greater changes regarding the orgasm’s duration and intensity, lower levels of sexual arousal and total sexual function, than women with intact perineum. Discussion: We found no significant differences between women with episiotomy and women with an intact perineum in most variables. However, women with episiotomy presented higher levels of pain and a lower sexual satisfaction, being these significant differences.展开更多
This study evaluated the effect of item inversion on the construct validity and reliability of psychometric scales and proposed a theoretical framework for the evaluation of the psychometric properties of data gathere...This study evaluated the effect of item inversion on the construct validity and reliability of psychometric scales and proposed a theoretical framework for the evaluation of the psychometric properties of data gathered with psychometric instruments. To this propose, we used the Maslach Burnout Inventory, which is the most used psychometric inventory to measure burnout in different professional context (Students, Teachers, Police, Doctors, Nurses, etc…). The version of the MBI used was the MBI-Student Survey (MBI-SS). This inventory is composed of three key dimensions: Exhaustion, Cynicism and Professional Efficacy. The two first dimensions—which have positive formulated items—are moderate to strong positive correlated, and show moderate to strong negative correlations with the 3rd dimension—which has negative formulated items. We tested the hypothesis that, in college students, formulating the 3rd dimension of burnout as Inefficacy (reverting the negatively worded items in the Efficacy dimension) improves the correlation of the 3rd dimension with the other two dimensions, improves its internal consistency, and the overall MBI-SS’ construct validity and reliability. Confirmatory factor analysis results, estimated by Maximum Likelihood, revealed adequate factorial fit for both forms of the MBI-SS (with Efficacy) vs. the MBI-SSi (with Inefficacy). Also both forms showed adequate convergent and discriminant related validity. However, reliability and convergent validity were higher for the MBI-SSi. There were also stronger (positive) correlations between the 3 factors in MBI-SSi than the ones observed in MBI-SS. Results show that positively rewording of the 3rd dimension of the MBI-SS improves its validity and reliability. We therefore propose that the 3rd dimension of the MBI-SS should be named Professional Inefficacy and its items should be positively worded.展开更多
BACKGROUNDPatients with advanced gastrointestinal cancer must cope with the negative effects of cancer and complications.AIM To evaluate psychological distress,quality of life,and coping strategies in patients with ad...BACKGROUNDPatients with advanced gastrointestinal cancer must cope with the negative effects of cancer and complications.AIM To evaluate psychological distress,quality of life,and coping strategies in patients with advanced colorectal cancer compared to non-colorectal cancer based on sex.METHODS A prospective,transversal,multicenter study was conducted in 203 patients;101(50%)had a colorectal and 102(50%)had digestive,non-colorectal advanced cancer.Participants completed questionnaires evaluating psychological distress(Brief Symptom Inventory-18),quality of life(EORTC QLQ-C30),and coping strategies(Mini-Mental Adjustment to Cancer)before starting systemic cancer treatment.RESULTS The study included 42.4%women.Women exhibited more depressive symptoms,anxiety,functional limitations,and anxious preoccupation than men.Patients with non-colorectal digestive cancer and women showed more somatization and physical symptoms than subjects with colorectal cancer and men.Men with colorectal cancer reported the best health status.CONCLUSION The degree of disease acceptance in gastrointestinal malignancies may depend on sex and location of the primary digestive neoplasm.Future interventions should specifically address sex and tumor site differences in individuals with advanced digestive cancer.展开更多
Background: Pain perception may result from orthodontic treatment and should be considered in clinical management. Its assessment should not be limited to the intensity of perceived pain but should also consider the p...Background: Pain perception may result from orthodontic treatment and should be considered in clinical management. Its assessment should not be limited to the intensity of perceived pain but should also consider the psychosocial and behavioral aspects involved. Objective: The aims of this study were to adapt and validate the Multidimensional Pain Inventory (MPI) for orthodontic patients, and present a proposal to calculate an overall score of the pain-related aspects and compare these scores with the usual methodology used. Methods: Face validity of the MPI was estimated and orthodontic version (MPI-Orthodontic) was developed. Factorial validity was evaluated by confirmatory analysis. Convergent and discriminant validity and reliability were estimated. The fit of Second-Order Hierarchical Models was estimated. Concurrent validity of MPI-Orthodontic was evaluated against the Visual Analogue Scale. Invariance of the factorial models was evaluated for independent samples and according to sex and age. Overall score was calculated using the matrix of regression weights and compared to simple arithmetic mean. Results: 507 individuals (63.3% women;age: 26.32 (SD = 11.70) years) participated. For the fit of Part I (psychosocial aspects) of the MPI-Orthodontic, it added correlation between two items and excluded one item;for Part II (behavioral aspects) two items were excluded. The models presented adequate fit to the sample. Reliability was adequate. MPI-Orthodontic presented invariance for independent samples and adequate concurrent and divergent validity. Score obtained with the simple arithmetic mean was overestimated for Part I and underestimated for Part II. Conclusion: MPI-Orthodontic was valid, reliable and invariant for the evaluation of the orthodontic pain. It is recommended to calculate overall weighted scores for pain assessment.展开更多
Background More than 90%of the carbon in grassland ecosystems is stored in the soil.Grassland land-use has been considered as a fundamental aspect altering soil carbon pool dynamics in the context of global change.How...Background More than 90%of the carbon in grassland ecosystems is stored in the soil.Grassland land-use has been considered as a fundamental aspect altering soil carbon pool dynamics in the context of global change.However,a comprehensive understanding of the effects of different land-use practices on grassland soil carbon pools is lacking.Methods Based on 2151 papers retrieved from the Web of Science database,we used bibliometric methods for the first time to summarize the research areas and trends of grassland soil carbon pools under various land uses.Results Our results showed that(1)Management,sequestration,nitrogen,land-use,and dynamics were the most frequently occurring keywords.(2)Co-occurrence network analysis classified the keywords into three thematic clusters:(i)carbon and nitrogen coupling mechanisms regulating soil organic carbon(SOC)dynamics,(ii)microbialmediated pathways linking management practices to SOC sequestration,(iii)cascading climate–vegetation–SOC.(3)Thematically,the hot topics shifted from focusing on the relationship between grassland biomass and SOC at broad geographic scales to gradually emphasizing the mechanisms of soil microbial influence on SOC,and from focusing on the effects of nitrogen deposition to focusing on the effects of global climate change on SOC.(4)We further summarize the trends of SOC pool changes under different land-use.Establishing multi-pool management to optimize soil carbon sequestration may be the key to sustainable grassland ecosystem development.Conclusions This study summarizes the research progress and future hotspots of grassland soil carbon pools under diverse land use patterns,which can help to improve the carbon sequestration potential and mitigate the effect of climate change.Better integration of molecular and ecosystem experimentation with mathematical modeling is essential for future smart management of grassland SOC pool.展开更多
Head and neck squamous cell carcinoma(HNSCC)remains a prevalent and aggressive malignancy,characterized by a lack of targeted therapies and limited clinical benefits.Here,we conducted an optimized whole-genome CRISPR ...Head and neck squamous cell carcinoma(HNSCC)remains a prevalent and aggressive malignancy,characterized by a lack of targeted therapies and limited clinical benefits.Here,we conducted an optimized whole-genome CRISPR screen across five HNSCC cell lines aimed at identifying actionable genetic vulnerabilities for rapid preclinical evaluation as novel targeted therapies.Given their critical role in cancer,cyclin-dependent kinases(CDKs)were prioritized for further investigation.Among these,CDK7 was identified as an essential and targetable gene across all five cell lines,prompting its selection for in-depth functional and molecular characterization.Genetic and pharmacological inhibition of CDK7 significantly and consistently reduced tumor cell proliferation due to generalized cell cycle arrest and apoptosis induction.Additionally,CDK7 knockout(KO)and selective inhibitors(YKL-5-124 and samuraciclib)demonstrated potent antitumor activity,effectively suppressing tumor growth in HNSCC patient-derived organoids(PDOs),as well as in both cell line-and patient-derived xenograft(PDX)mouse models with minimal toxicity.Mechanistically,CDK7 inhibition led to a broad downregulation of gene sets related to cell cycle progression and DNA repair,and significantly reduced the transcription of essential genes and untargetable vulnerabilities identified by our CRISPR screen.These findings highlight CDK7 as a promising therapeutic target for HNSCC.Our study provides strong evidence of the robust antitumor activity of CDK7-selective inhibition in disease-relevant preclinical models,strongly supporting its progression to clinical testing.展开更多
Background We aimed to explore associations between the presence of pets at one and 4-5 years of age with internalizing and externalizing problems at 7-8 years. Methods Participants comprised 1893 families from the IN...Background We aimed to explore associations between the presence of pets at one and 4-5 years of age with internalizing and externalizing problems at 7-8 years. Methods Participants comprised 1893 families from the INfancia y Medio Ambiente(INMA)project.Information was collected on the presence of(1)any pet,(2)dogs,(3)cats,(4)birds or(5)other animals.Pet ownership was categorized as never,always,only at age 1 and only at age 4-5.Internalizing and externalizing problems were measured at ages 7-8 years through the Strengths and Difficulties Questionnaire,a Likert questionnaire on children's behavioural and emotional symptoms.Negative binomial regression models and Tukey's multiple comparison tests were used to analyse data sets.Five sensitivity analyses were performed. Results Families that always owned a pet made up 24.4%of the sample.In addition,11.5%,4.5%,3.8%and 17.6%of the families owned a dog,cat,bird or other animal,respectively.The median(P25-P75)for internalizing problems was 3(1-5)and 5(3-8)for externalizing problems.Owning a cat only at age 4-5 increased mental health problems:relative rate ratio(RRR)[95%confidence interval(CI)]1.37(1.05-1.79)for internalizing and 1.26(1.02-1.56)for externalizing.Always having other animals was a protective factor for internalizing problems with an RRR of 0.80(0.66-0.96).These associations remained after multiple comparison testing and sensitivity analyses. Conclusion Owning a cat only at 4-5 years of age was linked to more internalizing and externalizing problems,whereas always having other animals was a protective factor against internalizing problems.展开更多
Aims Invasive species,which recently expanded,may help understand how climatic niche can shift at the time scale of the current global change.Here,we address the climatic niche shift of an invasive shrub(common gorse,...Aims Invasive species,which recently expanded,may help understand how climatic niche can shift at the time scale of the current global change.Here,we address the climatic niche shift of an invasive shrub(common gorse,Ulex europaeus)at the world and regional scales to assess how it could contribute to increasing invasibility.Methods Based on a 28187 occurrences database,we used a combination of 9 species distribution models(SDM)to assess regional climatic niche from both the native range(Western Europe)and the introduced range in different parts of the world(North-West America,South America,North Europe,Australia and New Zealand).Important Findings Despite being restricted to annual mean temperature between 4℃ and 22℃,as well as annual precipitation higher than 300 mm/year,the range of bioclimatic conditions suitable for gorse was very large.Based on a native versus introduced SDM comparison,we highlighted a niche expansion in North-West America,South America and to a lesser degree in Australia,while a niche displacement was assessed in North Europe.These niche changes induced an increase in potential occupied areas by gorse by 49,111,202 and 283%in Australia,North Europe,North-West America and South America,respectively.On the contrary,we found no evidence of niche change in New Zealand,which presents similar climatic condition to the native environment(Western Europe).This study highlights how niche expansion and displacement of gorse might increase invasibility at regional scale.The change in gorse niche toward new climatic conditions may result from adaptive plasticity or genetic evolution and may explain why it has such a high level of invasibility.Taking into account the possibility of a niche shift is crucial to improve invasive plants management and control.展开更多
Pioneering studies were carried out on red-to-black pigmented grains for brewing beers.Together with pigmented cereals,the use of pulses was also proposed for making low-alcohol,gluten-free beers with improved content...Pioneering studies were carried out on red-to-black pigmented grains for brewing beers.Together with pigmented cereals,the use of pulses was also proposed for making low-alcohol,gluten-free beers with improved contents of health-promoting compounds.So far,a new concept of beer is emerging among scientists,brewers,and consumers by expanding the assortment of conventional beer’s ingredients.Coloured(red,purple,blue,black)cereal grains and legume grains are an untapped resource of functional compounds.each denoting different and complementary beneficial effects on human health.Among others,polyphenols contribute to protect against non-communicable diseases such as hypertension,heart diseases,cancers,diabetes and obesity.In this review,we summarized the improvement in terms of phenolic compounds and antioxidant capacity of beers obtained by using pigmented cereal grains and pulses as raw ingredients versus traditional beers.We examined the influence of these alternative materials on the qualitative properties of the beers.Moreover,we reviewed the contribution of traditional and non-conventional yeasts on the flavour and quality of these new functional beers.Finally,we discussed the use of different and complementary chemical methods for monitoring the composition,organoleptic profile,safety,and authentication issues with the aim to highlight the most promising to protect and promote novel beer products.展开更多
基金supported by Government of the Principado de Asturias through the Fundacion para el Fomento en Asturias de la Investigacion Cientifica Aplicada y a la Tecnologia(FICYT)and also co-founded by the European Union,GRUPIN(IDI/2024/000719).
文摘Aerobic glycolysis,also known as the Warburg effect,and the accumulation of lactate that it causes,are increasingly recognized outside the field of oncology as triggers of chronic non-neoplastic disorders.This review integrates preclinical and clinical evidence to evaluate the ability of melatonin to reverseWarburg-effect-like metabolic reprogramming.Literature on neurodegeneration,age-related sarcopenia,type 2 diabetes,chronic kidney disease,heart failure and pulmonary arterial hypertension(PAH)has been reviewed and synthesised.In all of these conditions,hypoxia-inducible factor 1α(HIF-1α)and pyruvate dehydrogenase kinase 4(PDK4)inhibit the pyruvate dehydrogenase complex.This diverts pyruvate away fromthe tricarboxylic acid(TCA)cycle and promotes glycolysis.In cell and animal models,melatonin consistently inhibits PDK4,destabilizes HIF-1αunder normoxic conditions,activates SIRT1/3-dependentmitochondrial biogenesis andmitophagy,and eliminates reactive oxygen and nitrogen species.These actions reduce lactate production,restore oxidative phosphorylation and attenuate tissue damage.This appears to induce cognitive and synaptic improvements in Alzheimer’s and Parkinson’s disease models,increased muscle mass and function in ageing rodents,improved insulin sensitivity alongside suppression of hepatic gluconeogenesis in diabetic models,reduced fibrosis in nephropathy,and normalization of vascular remodeling in hypoxia-induced pulmonary arterial hypertension(PAH).Early-stage clinical trials corroborate a decrease in oxidative and inflammatorymarkers,improved sleep quality and modest cognitive benefits.However,they report conflicting effects on insulin sensitivity,which are largely related to the dose and timing of administration in relation to food intake.Overall,the current data suggest that melatonin is a pleiotropic metabolic modulator capable of counteracting the Warburg phenotype in multiple organs.However,human studies remain scarce,and well-designed randomised trials incorporating chronotherapy are needed before clinical adoption.
基金supported by the CNRS-INSU EC2CO program in the framework of the CADSOU project,by the Nouvelle Aquitaine Region in the framework of the ESTOCADE project,and by the French National Research Institute for Agriculture,Food and Environment(INRAE)The authors are grateful to Ms.Melike Emet(INRAE,UMR ISPA)and Ms.Sylvie Bussière(INRAE,UMR ISPA)for their help treating the samples,and to Ms.Francesca Degan(ARVALIS-Institut du végétal)and Ms.Séverine Piutti(INRAE,UMR LAE)for helpful comments.
文摘Cadmium(Cd)is a toxic trace metal that occurs naturally in agricultural soils and can accumulate in the edible parts of crops,notably in cereal grains.This study investigated the extent to which sulfur(S)fertilization increases the availability of Cd in a calcareous(Calc)and a non-calcareous(Ncalc)soil.Changes in Cd availability and speciation were monitored over a 21-d incubation period,along with changes in pH and the concentrations of sulfate,nitrate,calcium,magnesium,aluminum(Al),manganese(Mn),and nickel(Ni)in the potassium nitrate(KNO_(3))extracts,after the addition at agronomic rates of three forms of S fertilizers:elemental S(S(0)),potassium sulfate(K_(2)SO_(4)),and ammonium sulfate((NH_(4))_(2)SO_(4)).Elemental S did not increase the Cd concentration in the KNO_(3)extracts of either soil due to its too limited oxidation to sulfates.The two sulfate fertilizers had contrasting effects on Cd concentration depending on the nature of the counter cation(K^(+)or NH_(4)^(+)).While K_(2)SO_(4)caused almost no change in Cd concentration in either soil,(NH_(4))_(2)SO_(4)increased Cd concentration in both soils.The nitrification of NH_(4)^(+)reduced soil pH,thereby increasing the concentrations of Cd,Al,Mn,and Ni in the Ncalc soil over time,as evidenced by the strong negative correlations between soil pH and the concentrations of these four elements in the KNO3 extract after 21 d.In the Calc soil,the mechanism of Cd concentration increase after(NH_(4))_(2)SO_(4)addition was more difficult to understand and could result from the proton-mediated alteration of Cd-bearing phases such as carbonates,following ammonia(NH_(3))volatilization.The relevance of these results for the S fertilization of cereals in Cd-contaminated soils is discussed.
基金funded by grants PID2019-105311RB-I00(MICIU/AEI/FEDER,UE,Spain)to P.García and A.RodríguezAYUD/2021/52120(Program of Science,Technology and Innovation 2021-2023 and FEDER EU,Principado de Asturias,Spain)。
文摘Sustainability is a leading trend in the context of food production.Additionally,consumers increasingly demand safer and less-processed products.Among the different technologies used to maintain the quality and extend the shelf-life of fresh and minimally-processed food,natural antimicrobial agents offer a promising strategy to replace conventional compounds.In this regard,phage lytic proteins or lysins,such as endolysins and virion-associated peptidoglycan hydrolases(VAPGHs),have been proposed as a viable option for the avoidance and elimination of undesirable bacteria within the food production chain.Even when applied exogenously,these proteins can degrade the bacterial cell wall maintaining their lytic activity.This feature,alongside their modular structure,which can be exploited for bioengineering,provides significant biotechnological potential.However,despite the promising properties of lysins,the main obstacle for their commercialization is the limited legal information regulating their use.This challenge underscores the need to navigate complex regulatory pathways.The primary objective of this review is to address this crucial gap and summarize the many prospective applications of endolysins during the different stages of food production.By doing so,we aim to provide clarity and insight into the regulatory challenges that must be overcome for the successful utilization of lysins.
基金funded by the Deanship of Scientific Research,Vice Presidency for Graduate Studies and Scientific Research,King Faisal University,Saudi Arabia,for supporting this work for work through grant number KFU242134.
文摘Coffee wilt represents one of the most devastating diseases of Arabica coffee(Coffea arabica L.)plantations in the primary coffee-producing regions.In this study,coffee trees manifesting wilt symptoms accompanied by the defoliation and drying of the whole tree were observed in the Jazan,El Baha,Najran,and Asir regions.The purpose of this investigation was to isolate and identify the Fusarium species recovered from symptomatic coffee trees.The developed fungi were initially characterized based on their morphological features followed by molecular phylogenetic multi-locus analysis of the combined sequences of ITS,TEF1-α,RPB2,and CaM.Twenty-five isolates were recovered from 28 samples.All fungal isolates were categorized morphologically under the genus Fusarium.Phylogenetic analysis positioned all the representative 15 isolates into one cluster grouping together with Neocosmospora falciformis(formerly F.falciforme)confirming their taxonomic position.Pathogenicity tests of the N.falciformis isolates were subsequently conducted on coffee seedlings,and the results revealed that all isolates induced wilt symptoms resembling those recorded in the field,and the incidence was 100%.The fungicide sensitivity test of seven investigated fungicides revealed that Maxim XL^(®) followed by Moncut^(®) exhibited the highest inhibitory effect against N.falciformis KSA 24-14,reaching 93.33%and 91.67%,respectively.To our knowledge,N.falciformis is a new causal pathogen of coffee wilt in Saudi Arabia.Remarkably,these results offer important insights for devising effective approaches to monitor and control such diseases.
文摘The chemical characterization of phenolic extracts of salad burnet (Sanguisorba minor Scop. s.l.) and broomrape (Orobanche crenata Forsk.) was performed. Active fractions were separated and characterized and, in the case of O. crenata, two phenolic compounds, verbascoside and is overbascoside, were quantitatively extracted, purified and characterized. These compounds proved to be effective in reducing the growth of some important fungi responsible for the decay of fresh fruit and vegetables in postharvest. Verbascoside showed significant activity against Penicillium italicum, fairly inhibited Monilinia laxa, P. expansum, and Aspergillus carbonarius, and showed little activity against Botrytis cinerea, M. fructicola and P. digitatum. Isoverbascoside completely inhibited B. cinerea, P. digitatum, P. italicum, and P. expansum;it fairly inhibited M. laxa and A. carbonarius;while it showed to be less effective against M. fructicola. The obtained results support the possible use of some wild edible plants as a source of phenolic substances for the postharvest biological control of fresh fruit and vegetable rots.
基金Among these,patents were licensed to Bayer(WO2014020041-A1 and WO2014020043-A1)Bristol-Myers Squibb(WO2008057863-A1)+4 种基金Osasuna Therapeutics(WO2019057742A1)Pharmamar(WO2022049270A1 and WO2022048775-A1)Raptor Pharmaceuticals(EP2664326-A1)Samsara Therapeutics(GB202017553D0)Therafast Bio(EP3684471A1).The other authors declare that they have no competing interests.
文摘Exercise has long been known for its active role in improving physical fitness and sustaining health.Regular moderate-intensity exercise improves all aspects of human health and is widely accepted as a preventative and therapeutic strategy for various diseases.It is well-documented that exercise maintains and restores homeostasis at the organismal,tissue,cellular,and molecular levels to stimulate positive physiological adaptations that consequently protect against various pathological conditions.Here we mainly summarize how moderate-intensity exercise affects the major hallmarks of health,including the integrity of barriers,containment of local perturbations,recycling and turnover,integration of circuitries,rhythmic oscillations,homeostatic resilience,hormetic regulation,as well as repair and regeneration.Furthermore,we summarize the current understanding of the mechanisms responsible for beneficial adaptations in response to exercise.This review aimed at providing a comprehensive summary of the vital biological mechanisms through which moderate-intensity exercise maintains health and opens a window for its application in other health interventions.We hope that continuing investigation in this field will further increase our understanding of the processes involved in the positive role of moderate-intensity exercise and thus get us closer to the identification of new therapeutics that improve quality of life.
文摘Every region around the globe has its unique climatic conditions which are set based on different orographic constant and atmospheric dynamic features. These features posses’ variability on different time scales. Determining the local sea level change based on terrestrial non-tidal, short-term variability is complicated. Some internal mechanisms of ocean are also taking place along with the external physical ones. We show that variability at Sindh-Baluchistan coastal belt can be greatly explained via dimensional indices of the position and intensity of the atmospheric center of action (COAs). This technique has already proved its usefulness at number of location especially in Northern Atlantic. It takes into account the changes in the atmospheric pressure which is exerted on the sea surface influencing the variability in sea level on seasonal scale and on inter-annual basis. As warming causes thermal expansion of water it also causes changes in atmospheric circulation. Both of these processes affect the sea level variability on their respective time scales. Atmospheric being the quicker one of the two to pass on the effect is also more influential to explain the variability in local sea level. In this attempt the COA approach is used to assess the impact of low pressure on local sea levels.
基金funding from the European Union Next Generation EU(PIANO NAZIONALE DI RIPRESA E RESILIENZA(PNRR)–MISSIONE 4 COMPONENTE 2,INVESTIMENTO 1.4–D.D.103217/06/2022,CN00000022)。
文摘A headspace solid-phase microextraction-gas chromatography-mass spectrometry(HS-SPME/GC-MS)method was used to study the volatile organic compounds(VOCs)associated with the differential immune response of tomato plants infected with the recombinant strain of potato virus Y(PVY^(C)-to),necrogenic to tomato.Analysis was carried out in UC82(UC),a virus susceptible tomato variety,comparing the same UC plants grafted or not onto a virus tolerant tomato ecotype,Manduria(Ma);the three types of samples used for the GC-MS analysis were mock-inoculated UC/Ma plants,UC/Ma+PVY^(C)-to and UC+PVY^(C)-to plants;the VOCs obtained were 111.Results from symptomatic PVY^(C)-to-infected UC plants showed a VOCs composition enriched in alcohols,fatty acid derivates,benzenoids,and salicylic acid derivatives,while in mock-inoculated UC/Ma plants VOCs were mainly characterized by methyl ester compounds.The VOC profile was in line with RNAseq data analyses,denoting that PVY^(C)-to viral RNA accumulation and disease symptoms induce the specific transcriptional activation of genes involved in VOCs biosynthesis.Furthermore,principal component analysis highlighted that VOCs of PVY^(C)-to-infected and mock-inoculated grafted plants were much closer each other than that of symptomatic PVY^(C)-to-infected non-grafted UC plants.These results suggest that VOCs profiles of tomato plants are related to the viral RNA accumulation,disease intensity and graft-derived tolerance to PVY^(C)-to infection.
基金supported by Ministerio de Economíay Competitividad under Grant DEP2015-69980-P to BFGPrograma de Ayudas a Grupos de Investigación del Principado de Asturias to FLB(FC-GRUPIN-IDI/2018/000120)。
文摘1.Introduction Regular exercise induces changes in the overall diversity and in the relative abundance of certain gut microbiota phyla and families in humans1,2 and in animal models.3,4 This relationship has attracted a great deal of interest because it is one of the mechanisms involved in the health benefits of regular exercise3 that could also influence performance.5 A recent publication by Scheiman et al.
文摘It is estimated that approximately one in ten people over the age of 80 may suffer from cardiac amyloidosis(CA),a disease in which various aging-related factors,such as increased oxidative stress,can promote abnormal protein folding and the formation of amyloid deposits in the heart.Over the long term,this tends to impair cardiac function,increasing the risk of developing cardiac conduction disorders,atrial fibrillation,thromboembolic events,heart failure(HF),and/or ventricular dysfunction.^([1,2])
文摘Objective: Despite the fact that a restrictive use of episiotomy has proven to be beneficial, it continues to be widely used in vaginal births. Our aim was to compare women with episiotomy, to women with an intact perineum, 3 months after delivery, regarding several sexual variables, namely: sexual desire, arousal, orgasm, pain, sexual satisfaction and sexual function. Methods: An exploratory, descriptive and quantitative study using a non-probabilistic, convenience sample of 147 Portuguese women, of which 54 belonged to a control group, was performed. The groups were not significantly different regarding socio-demographic aspects. Three instruments were used: the Female Sexual Function Index, a Socio-demographic and Clinical Questionnaire and the Female Sexual Function Questionnaire. Results: Most women mentioned a moderate level of sexual interest. Women with episiotomy present higher pain intensity, less sexual satisfaction, greater changes regarding the orgasm’s duration and intensity, lower levels of sexual arousal and total sexual function, than women with intact perineum. Discussion: We found no significant differences between women with episiotomy and women with an intact perineum in most variables. However, women with episiotomy presented higher levels of pain and a lower sexual satisfaction, being these significant differences.
文摘This study evaluated the effect of item inversion on the construct validity and reliability of psychometric scales and proposed a theoretical framework for the evaluation of the psychometric properties of data gathered with psychometric instruments. To this propose, we used the Maslach Burnout Inventory, which is the most used psychometric inventory to measure burnout in different professional context (Students, Teachers, Police, Doctors, Nurses, etc…). The version of the MBI used was the MBI-Student Survey (MBI-SS). This inventory is composed of three key dimensions: Exhaustion, Cynicism and Professional Efficacy. The two first dimensions—which have positive formulated items—are moderate to strong positive correlated, and show moderate to strong negative correlations with the 3rd dimension—which has negative formulated items. We tested the hypothesis that, in college students, formulating the 3rd dimension of burnout as Inefficacy (reverting the negatively worded items in the Efficacy dimension) improves the correlation of the 3rd dimension with the other two dimensions, improves its internal consistency, and the overall MBI-SS’ construct validity and reliability. Confirmatory factor analysis results, estimated by Maximum Likelihood, revealed adequate factorial fit for both forms of the MBI-SS (with Efficacy) vs. the MBI-SSi (with Inefficacy). Also both forms showed adequate convergent and discriminant related validity. However, reliability and convergent validity were higher for the MBI-SSi. There were also stronger (positive) correlations between the 3 factors in MBI-SSi than the ones observed in MBI-SS. Results show that positively rewording of the 3rd dimension of the MBI-SS improves its validity and reliability. We therefore propose that the 3rd dimension of the MBI-SS should be named Professional Inefficacy and its items should be positively worded.
基金Supported by The FSEOM(Spanish Society of Medical Oncology Foundation)grant for Projects of the Collaborative Groups in 2018 and by an Astra Zeneca grant,No.ES2020-1939.
文摘BACKGROUNDPatients with advanced gastrointestinal cancer must cope with the negative effects of cancer and complications.AIM To evaluate psychological distress,quality of life,and coping strategies in patients with advanced colorectal cancer compared to non-colorectal cancer based on sex.METHODS A prospective,transversal,multicenter study was conducted in 203 patients;101(50%)had a colorectal and 102(50%)had digestive,non-colorectal advanced cancer.Participants completed questionnaires evaluating psychological distress(Brief Symptom Inventory-18),quality of life(EORTC QLQ-C30),and coping strategies(Mini-Mental Adjustment to Cancer)before starting systemic cancer treatment.RESULTS The study included 42.4%women.Women exhibited more depressive symptoms,anxiety,functional limitations,and anxious preoccupation than men.Patients with non-colorectal digestive cancer and women showed more somatization and physical symptoms than subjects with colorectal cancer and men.Men with colorectal cancer reported the best health status.CONCLUSION The degree of disease acceptance in gastrointestinal malignancies may depend on sex and location of the primary digestive neoplasm.Future interventions should specifically address sex and tumor site differences in individuals with advanced digestive cancer.
文摘Background: Pain perception may result from orthodontic treatment and should be considered in clinical management. Its assessment should not be limited to the intensity of perceived pain but should also consider the psychosocial and behavioral aspects involved. Objective: The aims of this study were to adapt and validate the Multidimensional Pain Inventory (MPI) for orthodontic patients, and present a proposal to calculate an overall score of the pain-related aspects and compare these scores with the usual methodology used. Methods: Face validity of the MPI was estimated and orthodontic version (MPI-Orthodontic) was developed. Factorial validity was evaluated by confirmatory analysis. Convergent and discriminant validity and reliability were estimated. The fit of Second-Order Hierarchical Models was estimated. Concurrent validity of MPI-Orthodontic was evaluated against the Visual Analogue Scale. Invariance of the factorial models was evaluated for independent samples and according to sex and age. Overall score was calculated using the matrix of regression weights and compared to simple arithmetic mean. Results: 507 individuals (63.3% women;age: 26.32 (SD = 11.70) years) participated. For the fit of Part I (psychosocial aspects) of the MPI-Orthodontic, it added correlation between two items and excluded one item;for Part II (behavioral aspects) two items were excluded. The models presented adequate fit to the sample. Reliability was adequate. MPI-Orthodontic presented invariance for independent samples and adequate concurrent and divergent validity. Score obtained with the simple arithmetic mean was overestimated for Part I and underestimated for Part II. Conclusion: MPI-Orthodontic was valid, reliable and invariant for the evaluation of the orthodontic pain. It is recommended to calculate overall weighted scores for pain assessment.
基金supported by the Joint Found of the National Natural Science Foundation of China(U23A2004)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA28110300)+3 种基金the national key research and development program(2022YFF1300601)the key research and development program of Jilin Province(20220203023SF)the Innovation Team Project of Northeast Institute of Geography and Agroecology,Chinese Academy of Sciences(2023CXTD02)supported by the Joachim Herz Foundation(850035)
文摘Background More than 90%of the carbon in grassland ecosystems is stored in the soil.Grassland land-use has been considered as a fundamental aspect altering soil carbon pool dynamics in the context of global change.However,a comprehensive understanding of the effects of different land-use practices on grassland soil carbon pools is lacking.Methods Based on 2151 papers retrieved from the Web of Science database,we used bibliometric methods for the first time to summarize the research areas and trends of grassland soil carbon pools under various land uses.Results Our results showed that(1)Management,sequestration,nitrogen,land-use,and dynamics were the most frequently occurring keywords.(2)Co-occurrence network analysis classified the keywords into three thematic clusters:(i)carbon and nitrogen coupling mechanisms regulating soil organic carbon(SOC)dynamics,(ii)microbialmediated pathways linking management practices to SOC sequestration,(iii)cascading climate–vegetation–SOC.(3)Thematically,the hot topics shifted from focusing on the relationship between grassland biomass and SOC at broad geographic scales to gradually emphasizing the mechanisms of soil microbial influence on SOC,and from focusing on the effects of nitrogen deposition to focusing on the effects of global climate change on SOC.(4)We further summarize the trends of SOC pool changes under different land-use.Establishing multi-pool management to optimize soil carbon sequestration may be the key to sustainable grassland ecosystem development.Conclusions This study summarizes the research progress and future hotspots of grassland soil carbon pools under diverse land use patterns,which can help to improve the carbon sequestration potential and mitigate the effect of climate change.Better integration of molecular and ecosystem experimentation with mathematical modeling is essential for future smart management of grassland SOC pool.
基金supported by the Instituto de Salud Carlos III(ISCIII)through the project grants PI19/00560,PI21/00208,PI22/00167,PI24/00398,PMPTA22/00167 and CIBERONC(CB16/12/00390,CB16/12/00228,and CB16/12/00442)co-funded by the European Union,the Instituto de Investigación Sanitaria del Principado de Asturias(ISPA),Fundación Bancaria CajasturIUOPA,and Universidad de Oviedo.Additional funding was provided through grants PID2020-117236RB-I00 and CNS2023-1444-73+15 种基金funded by MCIU/AEI/10.13039/501100011033 and“European Union Next Generation EU/PRTR”the Scientific Foundation of the Spanish Association against Cancer(LABAE235202ALVA)also funded by the Government of the Principality of Asturias through the Agency for Science,Business Competitiveness and Innovation of the Principality of Asturias and co-financed by the European Union,through the Grants“Subvenciones para Grupos de Investigación de Organismos del Principado de Asturias para el Ejercicio 2024”(IDE/2024/000778)M.O.-R.,I.P.,and E.P.-A are recipients of a PFIS predoctoral fellowship from ISCIII(FI23/00037,FI24/00083 and FI20/00064)S.D.M.is supported by a grant from the Programa de Formación de Profesorado Universitario from the Spanish Ministry of Universities(FPU21/05639)S.A.-T.is a recipient of a Miguel Servet fellowship from ISCIII(CP23/00101)co-funded by the European UnionK.T.is supported by Wellcome Trust(grants RG83195,G106133 and G127005)UKRI Medical Research Council(grant RG83195)Leukaemia UK(grants G108148 and G117699)I.F.is a recipient of a Miguel Servet fellowship from ISCIII(CP21/00052)M.A.F.was supported by the Asociación Española contra el Cáncer(AECC2019/INVES19001ALVA)M.A.G.is a recipient of a Severo Ochoa predoctoral fellowship from the Principado de Asturias(BP21-205)F.H.-P.is a recipient of a Miguel Servet fellowship from ISCIII(CP24/00064)funded by Fundación Alimerka and recipient of a Maria Zambrano postdoctoral fellowship at the University of Oviedo(2022-2024).
文摘Head and neck squamous cell carcinoma(HNSCC)remains a prevalent and aggressive malignancy,characterized by a lack of targeted therapies and limited clinical benefits.Here,we conducted an optimized whole-genome CRISPR screen across five HNSCC cell lines aimed at identifying actionable genetic vulnerabilities for rapid preclinical evaluation as novel targeted therapies.Given their critical role in cancer,cyclin-dependent kinases(CDKs)were prioritized for further investigation.Among these,CDK7 was identified as an essential and targetable gene across all five cell lines,prompting its selection for in-depth functional and molecular characterization.Genetic and pharmacological inhibition of CDK7 significantly and consistently reduced tumor cell proliferation due to generalized cell cycle arrest and apoptosis induction.Additionally,CDK7 knockout(KO)and selective inhibitors(YKL-5-124 and samuraciclib)demonstrated potent antitumor activity,effectively suppressing tumor growth in HNSCC patient-derived organoids(PDOs),as well as in both cell line-and patient-derived xenograft(PDX)mouse models with minimal toxicity.Mechanistically,CDK7 inhibition led to a broad downregulation of gene sets related to cell cycle progression and DNA repair,and significantly reduced the transcription of essential genes and untargetable vulnerabilities identified by our CRISPR screen.These findings highlight CDK7 as a promising therapeutic target for HNSCC.Our study provides strong evidence of the robust antitumor activity of CDK7-selective inhibition in disease-relevant preclinical models,strongly supporting its progression to clinical testing.
基金funded by grants from the EU(FP7-ENV-2011 cod 282957,HEALTH.2010.2.4.5-1,cod 874583and cod 101136566)+14 种基金Spain:ISCIII(Red INMA G03/176 G03/176,FIS-FEDER:PI03/1615,PI04/1509,PI04/1436,FIS-PI04/2018,PI06/1213,CB06/02/0041,PI06/0867,PI08/1151,PI09/02311,PI09/00090,PI11/01007,PI11/02591,PI11/02038,PI12/00610,PI13/1944,PI13/2032,PI13/02429,PI13/02187,PI14/00891,PI14/01687,PI16/1288,PI17/00663,PI18/00909,PI18/01142,PI18/01237,PI19/1338,P23/1578,incl.FEDER funds)Miguel Servet-FEDER(MS11/00178,MS15/00025,MSII16/00051,MS20/0006)Spanish Ministry of Universities(Margarita Salas Grant MS21-133)Sara Borrell(CD23/00090,co-financed by the European Union)Grant CEX2023-0001290-S funded by MCIN/AEI/10.13039/501100011033 CIBERESPConsejo General de Enfermería(PNI22_CGE45)the Alicia Koplowitz Foundation 2017Generalitat Valenciana(CIAICO/2021/132,BEST/2020/059,AICO 2020/285,AICO/2021/182,and CIDEGENT/2019/064)FISABIO(UGP-15-230,UGP-15-244,UGP-15-249)Generalitat de Catalunya-CIRIT 1999SGR 00241Generalitat de Catalunya-AGAUR 2009 SGR 501,EU Commission(261357)Generalitat de Catalunya through the CERCA ProgramObra Social Cajastur/Fundación Liberbank and UNIVERSIDAD DE OVIEDODepartment of Health of the Basque Government(2005111093,2009111069,2013111089,2015111065,and 2018111086)the Provincial Government of Gipuzkoa(DFG06/002,DFG08/001,DFG15/221,and DFG 89/17).
文摘Background We aimed to explore associations between the presence of pets at one and 4-5 years of age with internalizing and externalizing problems at 7-8 years. Methods Participants comprised 1893 families from the INfancia y Medio Ambiente(INMA)project.Information was collected on the presence of(1)any pet,(2)dogs,(3)cats,(4)birds or(5)other animals.Pet ownership was categorized as never,always,only at age 1 and only at age 4-5.Internalizing and externalizing problems were measured at ages 7-8 years through the Strengths and Difficulties Questionnaire,a Likert questionnaire on children's behavioural and emotional symptoms.Negative binomial regression models and Tukey's multiple comparison tests were used to analyse data sets.Five sensitivity analyses were performed. Results Families that always owned a pet made up 24.4%of the sample.In addition,11.5%,4.5%,3.8%and 17.6%of the families owned a dog,cat,bird or other animal,respectively.The median(P25-P75)for internalizing problems was 3(1-5)and 5(3-8)for externalizing problems.Owning a cat only at age 4-5 increased mental health problems:relative rate ratio(RRR)[95%confidence interval(CI)]1.37(1.05-1.79)for internalizing and 1.26(1.02-1.56)for externalizing.Always having other animals was a protective factor for internalizing problems with an RRR of 0.80(0.66-0.96).These associations remained after multiple comparison testing and sensitivity analyses. Conclusion Owning a cat only at 4-5 years of age was linked to more internalizing and externalizing problems,whereas always having other animals was a protective factor against internalizing problems.
基金supported by the Centre Nationale de la Recherche Scientifique(CNRS)the MARIS Agence Nationale de la Recherche project(ANR grant ANR-14-CE03-0007-01)Institut National de la Recherche Agronomique(INRA Institute).
文摘Aims Invasive species,which recently expanded,may help understand how climatic niche can shift at the time scale of the current global change.Here,we address the climatic niche shift of an invasive shrub(common gorse,Ulex europaeus)at the world and regional scales to assess how it could contribute to increasing invasibility.Methods Based on a 28187 occurrences database,we used a combination of 9 species distribution models(SDM)to assess regional climatic niche from both the native range(Western Europe)and the introduced range in different parts of the world(North-West America,South America,North Europe,Australia and New Zealand).Important Findings Despite being restricted to annual mean temperature between 4℃ and 22℃,as well as annual precipitation higher than 300 mm/year,the range of bioclimatic conditions suitable for gorse was very large.Based on a native versus introduced SDM comparison,we highlighted a niche expansion in North-West America,South America and to a lesser degree in Australia,while a niche displacement was assessed in North Europe.These niche changes induced an increase in potential occupied areas by gorse by 49,111,202 and 283%in Australia,North Europe,North-West America and South America,respectively.On the contrary,we found no evidence of niche change in New Zealand,which presents similar climatic condition to the native environment(Western Europe).This study highlights how niche expansion and displacement of gorse might increase invasibility at regional scale.The change in gorse niche toward new climatic conditions may result from adaptive plasticity or genetic evolution and may explain why it has such a high level of invasibility.Taking into account the possibility of a niche shift is crucial to improve invasive plants management and control.
文摘Pioneering studies were carried out on red-to-black pigmented grains for brewing beers.Together with pigmented cereals,the use of pulses was also proposed for making low-alcohol,gluten-free beers with improved contents of health-promoting compounds.So far,a new concept of beer is emerging among scientists,brewers,and consumers by expanding the assortment of conventional beer’s ingredients.Coloured(red,purple,blue,black)cereal grains and legume grains are an untapped resource of functional compounds.each denoting different and complementary beneficial effects on human health.Among others,polyphenols contribute to protect against non-communicable diseases such as hypertension,heart diseases,cancers,diabetes and obesity.In this review,we summarized the improvement in terms of phenolic compounds and antioxidant capacity of beers obtained by using pigmented cereal grains and pulses as raw ingredients versus traditional beers.We examined the influence of these alternative materials on the qualitative properties of the beers.Moreover,we reviewed the contribution of traditional and non-conventional yeasts on the flavour and quality of these new functional beers.Finally,we discussed the use of different and complementary chemical methods for monitoring the composition,organoleptic profile,safety,and authentication issues with the aim to highlight the most promising to protect and promote novel beer products.
基金supported by the French Agence Nationale de la Recherche(project MARIS ANR-14-CE03-0007-01andprojectSWATCHANR-18-PRIM-0006)by the'Institut national de recherche pour I'agriculture,I'alimentation et I'environnement'(INRAE)supported by the Conseil Regional de La Réunion,the French Ministry of Agriculture and Food,the European Union(Feader program,grant n°AG/974/DAAF/2016-00096 and Feder program,grant n°GURTDI20151501-0000735).
