Aging Mongolian pine plantations face high risks of drought-induced growth decline:evidence from both individual tree and forest stand measurements

Discerning vulnerability differences among different aged trees to drought-driven growth decline or to mortality is critical to implement age-specific countermeasures for forest management in water-limited areas.An important species for afforestation in dry environments of northern China,Mongolian pine(Pinus sylvestris var.mongolica Litv.)has recently exhibited growth decline and dieback on many sites,particularly pronounced in old-growth plantations.However,changes in response to drought stress by this species with age as well as the underlying mechanisms are poorly understood.In this study,tree-ring data and remotely sensed vegetation data were combined to investigate variations in growth at individual tree and stand scales for young(9-13 years)and aging(35-52 years)plantations of Mongolian pine in a water-limited area of northern China.A recent decline in tree-ring width in the older plantation also had lower values in satellited-derived normalized difference vegetation indices and normalized difference water indices relative to the younger plantations.In addition,all measured growth-related metrics were strongly correlated with the self-calibrating Palmer drought severity index during the growing season in the older plantation.Sensitivity of growth to drought of the older plantation might be attributed to more severe hydraulic limitations,as reflected by their lower sapwood-and leaf-specific hydraulic conductivities.Our study presents a comprehensive view on changes of growth with age by integrating multiple methods and provides an explanation from the perspective of plant hydraulics for growth decline with age.The results indicate that old-growth Mongolian pine plantations in water-limited environments may face increased growth declines under the context of climate warming and drying.

Bevacizumab biosimilar LY01008 compared with bevacizumab(Avastin)as first-line treatment for Chinese patients with unresectable,metastatic,or recurrent non-squamous non-small-cell lung cancer:A multicenter,randomized,double-blinded,phase Ⅲ trial

Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting.