Metabolic remodeling is a key feature of cancer development.Knowledge of cancer metabolism has greatly expanded since the first observation of abnormal metabolism in cancer cells,the so-called Warburg effect.Malignant...Metabolic remodeling is a key feature of cancer development.Knowledge of cancer metabolism has greatly expanded since the first observation of abnormal metabolism in cancer cells,the so-called Warburg effect.Malignant cells tend to modify cellular metabolism to favor specialized fermentation over the aerobic respiration usually used by most normal cells.Thus,targeted cancer therapies based on reprogramming nutrient or metabolite metabolism have received substantial attention both conceptually and in clinical practice.In particular,the management of nutrient availability is becoming more attractive in cancer treatment.In this review,we discuss recent findings on tumor metabolism and potential dietary interventions based on the specific characteristics of tumor metabolism.First,we present a comprehensive overview of changes in macronutrient metabolism.Carbohydrates,amino acids,and lipids,are rewired in the cancer microenvironment individually or systematically.Second,we summarize recent progress in cancer interventions applying different types of diets and specific nutrient restrictions in pre-clinical research or clinical trials.展开更多
The effects of brassinosteroid signaling on shoot and root development have been characterized in great detail but a simple consistent positive or negative impact on a basic cellular parameter was not identified.In th...The effects of brassinosteroid signaling on shoot and root development have been characterized in great detail but a simple consistent positive or negative impact on a basic cellular parameter was not identified.In this study,we combined digital 3D single-cell shape analysis and single-cell mRNA sequencing to charac-terize root meristems and mature root segments of brassinosteroid-blind mutants and wild type.The resul-tant datasets demonstrate that brassinosteroid signaling affects neither cell volume nor cell proliferation capacity.Instead,brassinosteroid signaling is essential for the precise orientation of cell division planes and the extent and timing of anisotropic cell expansion.Moreover,we found that the cell-aligning effects of brassinosteroid signaling can propagate to normalize the anatomy of both adjacent and distant brassinosteroid-blind cells through non-cell-autonomous functions,which are sufficient to restore growth vigor.Finally,single-cell transcriptome data discern directly brassinosteroid-responsive genes from genes that can react non-cell-autonomously and highlight arabinogalactans as sentinels of brassinosteroid-dependent anisotropic cell expansion.展开更多
An increasing number of patients are being killed by coronavirus disease 2019(COVID-19),however,risk factors for the fatality of COVID-19 remain unclear.A total of 21,392 COVID-19 cases were recruited in the Hubei Pro...An increasing number of patients are being killed by coronavirus disease 2019(COVID-19),however,risk factors for the fatality of COVID-19 remain unclear.A total of 21,392 COVID-19 cases were recruited in the Hubei Province of China between December 2019 and February 2020,and followed up until March 18,2020.We adopted Cox regression models to investigate the risk factors for case fatality and predicted the death probability under specific combinations of key predictors.Among the 21,392 patients,1,020(4.77%)died of COVID-19.Multivariable analyses showed that factors,including age(R60 versus<45 years,hazard ratio[HR]=7.32;95%confidence interval[CI],5.42,9.89),sex(male versus female,HR=1.31;95%CI,1.15,1.50),severity of the disease(critical versus mild,HR=39.98;95%CI,29.52,48.86),comorbidity(HR=1.40;95%CI,1.23,1.60),highest body temperature(>39C versus<39C,HR=1.28;95%CI,1.09,1.49),white blood cell counts(>103109/L versus(4–10)3109/L,HR=1.69;95%CI,1.35,2.13),and lymphocyte counts(<0.83109/L versus(0.8–4)3109/L,HR=1.26;95%CI,1.06,1.50)were significantly associated with case fatality of COVID-19 patients.Individuals of an older age,who were male,with comorbidities,and had a critical illness had the highest death probability,with 21%,36%,46%,and 54%within 1–4 weeks after the symptom onset.Risk factors,including demographic characteristics,clinical symptoms,and laboratory factors were confirmed to be important determinants of fatality of COVID-19.Our predictive model can provide scientific evidence for a more rational,evidence-driven allocation of scarce medical resources to reduce the fatality of COVID-19.展开更多
基金This work was supported by the National Key R&D Program of China(Grant Nos.2020YFA0803402 and 2019YFA0801703)the Natural Science Foundation of China(Grant Nos.81790250/81790253,91959202,82121004,and 81872240)the Innovation Program of Shanghai Municipal Education Commission(Grant No.N173606).
文摘Metabolic remodeling is a key feature of cancer development.Knowledge of cancer metabolism has greatly expanded since the first observation of abnormal metabolism in cancer cells,the so-called Warburg effect.Malignant cells tend to modify cellular metabolism to favor specialized fermentation over the aerobic respiration usually used by most normal cells.Thus,targeted cancer therapies based on reprogramming nutrient or metabolite metabolism have received substantial attention both conceptually and in clinical practice.In particular,the management of nutrient availability is becoming more attractive in cancer treatment.In this review,we discuss recent findings on tumor metabolism and potential dietary interventions based on the specific characteristics of tumor metabolism.First,we present a comprehensive overview of changes in macronutrient metabolism.Carbohydrates,amino acids,and lipids,are rewired in the cancer microenvironment individually or systematically.Second,we summarize recent progress in cancer interventions applying different types of diets and specific nutrient restrictions in pre-clinical research or clinical trials.
基金funded by core funding from the University of Lausanne,the Swiss National Science Foundation(grant 310030B_185379,awarded to C.S.H.)The Research Foundation-Flanders(FWO,post-doc fellowship 1215820N,awarded to T.E.)+2 种基金the European Research Council(ERC Start ing Grant TORPEDO,714055,awarded to B.D.R.)the BBSRC(grant BB/S002804/1 to G.W.B.)the Deutsche Forschungsgemeinschaft(DFG,post-doctoral fellowship GR 5009/1-1,awarded to M.G.).
文摘The effects of brassinosteroid signaling on shoot and root development have been characterized in great detail but a simple consistent positive or negative impact on a basic cellular parameter was not identified.In this study,we combined digital 3D single-cell shape analysis and single-cell mRNA sequencing to charac-terize root meristems and mature root segments of brassinosteroid-blind mutants and wild type.The resul-tant datasets demonstrate that brassinosteroid signaling affects neither cell volume nor cell proliferation capacity.Instead,brassinosteroid signaling is essential for the precise orientation of cell division planes and the extent and timing of anisotropic cell expansion.Moreover,we found that the cell-aligning effects of brassinosteroid signaling can propagate to normalize the anatomy of both adjacent and distant brassinosteroid-blind cells through non-cell-autonomous functions,which are sufficient to restore growth vigor.Finally,single-cell transcriptome data discern directly brassinosteroid-responsive genes from genes that can react non-cell-autonomously and highlight arabinogalactans as sentinels of brassinosteroid-dependent anisotropic cell expansion.
基金We thank all the staff involved in the field survey and the anonymous reviewers for the valuable comments.We appreciate the support provided by the National Natural Science Foundation of China(82041021).
文摘An increasing number of patients are being killed by coronavirus disease 2019(COVID-19),however,risk factors for the fatality of COVID-19 remain unclear.A total of 21,392 COVID-19 cases were recruited in the Hubei Province of China between December 2019 and February 2020,and followed up until March 18,2020.We adopted Cox regression models to investigate the risk factors for case fatality and predicted the death probability under specific combinations of key predictors.Among the 21,392 patients,1,020(4.77%)died of COVID-19.Multivariable analyses showed that factors,including age(R60 versus<45 years,hazard ratio[HR]=7.32;95%confidence interval[CI],5.42,9.89),sex(male versus female,HR=1.31;95%CI,1.15,1.50),severity of the disease(critical versus mild,HR=39.98;95%CI,29.52,48.86),comorbidity(HR=1.40;95%CI,1.23,1.60),highest body temperature(>39C versus<39C,HR=1.28;95%CI,1.09,1.49),white blood cell counts(>103109/L versus(4–10)3109/L,HR=1.69;95%CI,1.35,2.13),and lymphocyte counts(<0.83109/L versus(0.8–4)3109/L,HR=1.26;95%CI,1.06,1.50)were significantly associated with case fatality of COVID-19 patients.Individuals of an older age,who were male,with comorbidities,and had a critical illness had the highest death probability,with 21%,36%,46%,and 54%within 1–4 weeks after the symptom onset.Risk factors,including demographic characteristics,clinical symptoms,and laboratory factors were confirmed to be important determinants of fatality of COVID-19.Our predictive model can provide scientific evidence for a more rational,evidence-driven allocation of scarce medical resources to reduce the fatality of COVID-19.