In the Mediterranean region,despite bamboo being an alien species that can seriously alter plant and ani-mal biocoenosis,the area occupied by bamboo plantations continues to increase,especially for the purpose to sequ...In the Mediterranean region,despite bamboo being an alien species that can seriously alter plant and ani-mal biocoenosis,the area occupied by bamboo plantations continues to increase,especially for the purpose to seques-ter carbon(C).However,the C dynamics in the soil-plant system when bamboo is grown outside its native area are poorly understood.Here we investigated the C mitigation potential of the fast-growing Moso bamboo(Phyllostachys edulis)introduced in Italy for climate-change mitigation.We analyzed aboveground(AGB)and belowground(as root/shoot ratio)biomass,litter and soil organic C(SOC)at O-15-and 15-30-cm depths in a 4-year-old bamboo plantation in comparison with the former annual cropland on which the bamboo was established.To have an idea of the maximum C stored at an ecosystem level,a natural forest adjacent the two sites was also considered.In the plantation,C accumulation as AGB was stimulated,with 14.8±3.1 Mg C ha^(-1) stored in 3 years;because thinning was done to remove culms from the first year,the mean sequestration rate was 4.9 Mg C ha^(-1) a^(-1).The sequestration rates were high but comparable to other fast-growing tree species in Italy(e.g.,Pinus nigra).SOC was significantly higher in the bamboo plantation than in the cropland only at the 0-15 cm depth,but SOC stock did not differ.Possibly 4 years were not enough time for a clear increase in SOC,or the high nutrient uptake by bamboos might have depleted the soil nutrients,thus inhibiting the soil organic matter formation by bacteria.In comparison,the natural forest had significantly higher C levels in all the pools.For C dynamics at an ecosystem level,the bamboo plantation on the former annual cropland led to substantial C removal from the atmosphere(about 12 Mg C ha^(-1) a^(-1)).However,despite the promising C sequestration rates by bamboo,its introduction should be carefully considered due to potential ecological problems caused by this species in overexploited environments such as the Mediterranean area.展开更多
The neuromodulatory peptide somatostatin(somatotropin release inhibiting factor,SRIF)-14 acts at multiple levels through five SRIF receptor subtypes(sst1 to sst5).SRIF-28 is also derived from a common propeptide trans...The neuromodulatory peptide somatostatin(somatotropin release inhibiting factor,SRIF)-14 acts at multiple levels through five SRIF receptor subtypes(sst1 to sst5).SRIF-28 is also derived from a common propeptide translated from a single SRIF gene,although SRIF-14 is the predominant form in the mammalian nervous system.Due to its short half-life,synthetic SRIF analogs have been developed over the years and are available for therapeutic approaches.展开更多
Diabetic retinopathy(DR)is the most common complication of diabetes and the leading cause of visual impairment in the working-age population in the Western world(http://www.diabetesatlas.org/).One of the earliest even...Diabetic retinopathy(DR)is the most common complication of diabetes and the leading cause of visual impairment in the working-age population in the Western world(http://www.diabetesatlas.org/).One of the earliest events observed in DR is the impairment of retinal perfusion,caused by the constriction of retinal blood vessels,inducing biochemical and metabolic alterations,perycites/endothelial degeneration,and retina ischemia(Wong et al.,2016).Severe stages of DR include proliferative DR,caused by the abnormal growth of new vessels,and diabetic macular oedema in the central part of the retina.DR is strongly associated with a prolonged duration of diabetes,hypertension,and hyperglycaemia but it can persist even after replacement of normal glycaemic status(Wong et al.,2016).展开更多
We estimated water-use efficiency and potential photosyn- thetic assimilation of Holm oak (Quercus ilex L.) on slopes of NW and SW aspects in a replicated field test examining the effects of intensifying drought in ...We estimated water-use efficiency and potential photosyn- thetic assimilation of Holm oak (Quercus ilex L.) on slopes of NW and SW aspects in a replicated field test examining the effects of intensifying drought in two Mediterranean coppice forests. We used standard tech- niques for quantifying gas exchange and carbon isotopes in leaves and analyzed total chlorophyll, carotenoids and nitrogen in leaves collected from Mediterranean forests managed under the coppice system. We pos- tulated that responses to drought of coppiced trees would lead to differ- ential responses in physiological traits and that these traits could be used by foresters to adapt to predicted warming and drying in the Mediterra- nean area. We observed physiological responses of the eoppiced trees that suggested acclimation in photosynthetic potential and water-use effi- ciency: (1) a significant reduction in stomatal conductance (p〈0.01) wasrecorded as the drought increased at the SW site; (2) foliar 813C increased as drought increased at the SW site (p〈0.01); (3) variations in levels of carotenoids and foliar nitrogen, and differences in foliar morphology were recorded, and were tentatively attributed to variation in photosyn- thetic assimilation between sites. These findings increase knowledge of the capacity for acclimation of managed forests in the Mediterranean region of Europe.展开更多
Statistical analyses and descriptive characterizations are sometimes assumed to be offering information on time series forecastability.Despite the scientific interest suggested by such assumptions,the relationships be...Statistical analyses and descriptive characterizations are sometimes assumed to be offering information on time series forecastability.Despite the scientific interest suggested by such assumptions,the relationships between descriptive time series features(e.g.,temporal dependence,entropy,seasonality,trend and linearity features)and actual time series forecastability(quantified by issuing and assessing forecasts for the past)are scarcely studied and quantified in the literature.In this work,we aim to fill in this gap by investigating such relationships,and the way that they can be exploited for understanding hydroclimatic forecastability and its patterns.To this end,we follow a systematic framework bringing together a variety of–mostly new for hydrology–concepts and methods,including 57 descriptive features and nine seasonal time series forecasting methods(i.e.,one simple,five exponential smoothing,two state space and one automated autoregressive fractionally integrated moving average methods).We apply this framework to three global datasets originating from the larger Global Historical Climatology Network(GHCN)and Global Streamflow Indices and Metadata(GSIM)archives.As these datasets comprise over 13,000 monthly temperature,precipitation and river flow time series from several continents and hydroclimatic regimes,they allow us to provide trustable characterizations and interpretations of 12-month ahead hydroclimatic forecastability at the global scale.We first find that the exponential smoothing and state space methods for time series forecasting are rather equally efficient in identifying an upper limit of this forecastability in terms of Nash-Sutcliffe efficiency,while the simple method is shown to be mostly useful in identifying its lower limit.We then demonstrate that the assessed forecastability is strongly related to several descriptive features,including seasonality,entropy,(partial)autocorrelation,stability,(non)linearity,spikiness and heterogeneity features,among others.We further(i)show that,if such descriptive information is available for a monthly hydroclimatic time series,we can even foretell the quality of its future forecasts with a considerable degree of confidence,and(ii)rank the features according to their efficiency in explaining and foretelling forecastability.We believe that the obtained rankings are of key importance for understanding forecastability.Spatial forecastability patterns are also revealed through our experiments,with East Asia(Europe)being characterized by larger(smaller)monthly temperature time series forecastability and the Indian subcontinent(Australia)being characterized by larger(smaller)monthly precipitation time series forecastability,compared to other continental-scale regions,and less notable differences characterizing monthly river flow from continent to continent.A comprehensive interpretation of such patters through massive feature extraction and feature-based time series clustering is shown to be possible.Indeed,continental-scale regions characterized by different degrees of forecastability are also attributed to different clusters or mixtures of clusters(because of their essential differences in terms of descriptive features).展开更多
Retinal ischemia is a common clinical entity and, due to relatively ineffective treatment, remains a common cause of visual impairment and blindness. Generally, ischemic syndromes are initially characterized by low ho...Retinal ischemia is a common clinical entity and, due to relatively ineffective treatment, remains a common cause of visual impairment and blindness. Generally, ischemic syndromes are initially characterized by low homeostatic responses which, with time, induce injury to the tissue due to cell loss by apoptosis. In this re-spect, retinal ischemia is a primary cause of neuronal death. It can be considered as a sort of fnal common pathway in retinal diseases and results in irreversible morphological and functional changes. This review summarizes the recent knowledge on the effects of ischemia in retinal tissue and points out experimental strategies/models performed to gain better compre-hension of retinal ischemia diseases. In particular, the nature of the mechanisms leading to neuronal damage (i.e., excess of glutamate release, oxidative stress and infammation) will be outlined as well as the potential and most intriguing retinoprotective approaches and the possible therapeutic use of naturally occurring molecules such as neuropeptides. There is a general agreement that a better understanding of the funda-mental pathophysiology of retinal ischemia will lead tobetter management and improved clinical outcome. In this respect, to contrast this pathological state, spe-cifc pharmacological strategies need to be developed aimed at the many putative cascades generated during ischemia.展开更多
The stimulation of the human sensory receptors by compounds present in virgin olive oils (VOOs) gives rise to the sensory attributes that describe its particular aroma. The sensor panel evaluation and the molecules re...The stimulation of the human sensory receptors by compounds present in virgin olive oils (VOOs) gives rise to the sensory attributes that describe its particular aroma. The sensor panel evaluation and the molecules responsible for sensory perceptions of virgin olive oil quality are elucidated. The methodology for the evaluation of the sensory characteristics of VOOs is reported, and typical flavours and off-flavours are described. Relationships between chemical compounds and sensory characteristics are evaluated using the new sensory analyses method promoted by the International Olive Oil Council (IOOC) and included recently in EU regulation (Reg. 1348/2013 and following revisions). Oil quality may be defined in a number of ways, but the sensory perception of flavour is the ultimate determinant.展开更多
This is a review of the status of the universe as described by the standard cosmological model combined with the inflationary paradigm. Their key features and predictions, consistent with the WMAP (Wilkinson Microwave...This is a review of the status of the universe as described by the standard cosmological model combined with the inflationary paradigm. Their key features and predictions, consistent with the WMAP (Wilkinson Microwave Anisotropies Probe) and Planck Probe 2013 results, provide a significant mechanism to generate the primordial gravitational waves and the density perturbations which grow over time, and later become the large-scale structure of the universe—from the quantum fluctuations in the early era to the structure observed 13.7 billion later, our epoch. In the single field slow-roll paradigm, the primordial quantum fluctuations in the inflaton field itself translate into the curvature and density perturbations which grow over time via gravitational instability. High density regions continuously attract more matter from the surrounding space, the high density regions become more and more dense in time while depleting the low density regions. At late times the highest density regions peaks collapse into the large structure of the universe, whose gravitational instability effects are observed in the clustering features of galaxies in the sky. Thus, the origin of all structure in the universe probably comes from an early era where the universe was filled with a scalar field and nothing else.展开更多
We propose a game-theoretic model for a first-price sealed-bid auction (FPSB auction) of standing timber. A FPSB auction means that bidders simultaneously submit sealed bids so that no bidder knows the bid of any ot...We propose a game-theoretic model for a first-price sealed-bid auction (FPSB auction) of standing timber. A FPSB auction means that bidders simultaneously submit sealed bids so that no bidder knows the bid of any other participant. The highest bidder pays the submitted price. The mathematical model has been elaborated considering only two bidders. Each bidder is supposed to know only the probability distribution of the bid of the other bidder. Using ap- propriate distributions, the adversity and propensity of a bidder to risk can be described. From the view point of a bidder, the conservative solution is calculated for both types of the other bidder. If a standing timber belongs to a public owner, the market has to follow a public evidence procedure, including public auctions. The function obtained is illustrated with a numerical example of a typical standing timber auction from a forest located in central Italy. Considering average costs and prices of the local chestnut timber market, winning bids and expected gains are estimated. Their amounts are com- parable with the currently average stumpage price registered in this market.展开更多
Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brain of patients with Alzheimer’s disease (AD). In the past years considerable attention has been focu...Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brain of patients with Alzheimer’s disease (AD). In the past years considerable attention has been focused on identifying new protective substances that prevent or almost retard the appearance of amyloid beta (1-42)-related neurotoxic effects. In this study, human neuroblastoma cells (IMR-32) was used as system model to evaluate the protective role of S100b, a neurotrophic factor and neuronal survival protein, that is highly expressed by reactive astrocytes in close vicinity of beta-amyloid deposits, against amyloid beta (1-42)-dependent toxicity. Our results show that at nanomolar concentrations, S100b protects cells against Aβmediated cytotoxicity, as assessed by MTS vitality test. The protective mechanism seems to be related to the effect on bcl-2 (an anti-apoptotic gene) expression, which is highly down-regulated by amyloid beta (1-42) treatment, while resulted more expressed in the presence of S100b. On the contrary, Bax, a proapoptotic gene, resulted down-regulated by the treatment with S100 compared with the results obtained in the presence of amyloid beta (1-42) peptide. However, at micromolar doses, S100b is toxic for IMR-32 cells and its toxicity adds to that of the Aβpeptide, suggesting that additional molecular mechanisms may be involved in theneurotoxic process.展开更多
Due to the high degree of conservation of genes and mechanisms, the fruit fly Drosophila melanogaster is a powerful experimental in vivo tool to investigate complex diseases, thus complementing traditional vertebrate ...Due to the high degree of conservation of genes and mechanisms, the fruit fly Drosophila melanogaster is a powerful experimental in vivo tool to investigate complex diseases, thus complementing traditional vertebrate systems. Drosophila is also an advantageous system regarding the animal husbandry and the short generation time and lifespan.展开更多
Illegal logging is a pervasive problem of major international concern that causes many negative social, economical and environmental consequences. EUTR is a tool adopted in 2010 and entered into force in 2013 to stop ...Illegal logging is a pervasive problem of major international concern that causes many negative social, economical and environmental consequences. EUTR is a tool adopted in 2010 and entered into force in 2013 to stop the trade of timber illegally logged within the EU market. The implementation in Italy is still in progress and varies among regions. This study considers the respondents’ opinions on different EUTR characteristics, implementation processes and compliance activities. Taking Italy as an example, the questionnaire was delivered to relevant Italian foresters and timber operators in the forest-timber system. Two hypotheses are under verification: </span></span><span><span><span style="font-family:"">1</span></span></span><span><span><span style="font-family:"">) if Italian forest-wood-timber sector integrated EUTR into its activity and </span></span></span><span><span><span style="font-family:"">2</span></span></span><span><span><span style="font-family:"">) if the Italian Due Diligence system is a valid model to other countries. The questionnaire has been submitted to the wood industry stakeholders. It has been organized into six sections to collect information about the professional characteristics of respondents, their experiences on EUTR, the opinion about EUTR and FLEGT, the support received on EUTR implementation, the opinion about the checks system, and the role of EUTR in marketing timber products. Questionnaire data have been elaborated in different ways. Conclusion underlines the EUTR Italian system criticalities and some suggestions for a more effective use of EUTR in the wood market. The picture that emerges from the results collected is that the EUTR, although proposed for morally and ethically valid purposes, doesn’t have unanimous effectiveness. In particular, EUTR can generate a distortion of the market, new expenditures for importers. Various operators applaud the role of certification schemes for sustainable forest management, which indirectly makes it possible to prevent the aforementioned problem. The Italian EUTR system is working only for satisfying Regulation 995/2010 targets. This must be considered as the starting point;however, three innovative topics could be developed in the future: digitalization and computerization of EUTR certification, integration of EUTR certification with forest certifications schemes and other quality certifications, and use of EUTR in the marketing initiatives.展开更多
We report for the first time the occurrence of heteroplasmy in Grey Partridge(Perdix perdix)revealed by means of two mitochondrial fragments.The possible serious biological and management implications of this exceptio...We report for the first time the occurrence of heteroplasmy in Grey Partridge(Perdix perdix)revealed by means of two mitochondrial fragments.The possible serious biological and management implications of this exception to unilateral inheritance of mtDNA were underlined.展开更多
IBI310 is a recombinant fully human IgG1 antibody against cytotoxic T lymphocyte antigen 4.This study was conducted to evaluate IBI310 monotherapy or combination therapy with sintilimab in the patients with advanced m...IBI310 is a recombinant fully human IgG1 antibody against cytotoxic T lymphocyte antigen 4.This study was conducted to evaluate IBI310 monotherapy or combination therapy with sintilimab in the patients with advanced melanoma or urothelial carcinoma(UC).Patients in phase 1a received IBI310 at 0.3/1/2/3 mg/kg intravenously(IV)every 3 weeks(Q3W)following the accelerated titration and 3+3 escalation design.Patients in phase 1b received IBI310(1/2/3 mg/kg IV,Q3W)plus sintilimab(200 mg IV,Q3W)for four cycles,followed by sintilimab maintenance therapy.The phase 1b expansion of IBI310 plus sintilimab was performed in patients with advanced melanoma or UC.Overall,53 patients were enrolled,including 10 patients with melanoma in phase 1a,34 with melanoma,and 9 with UC in phase 1b.Overall,94.3%of patients(50/53)experienced at least one treatment-related adverse event(TRAE)with most being grade 1–2;26.4%of patients(14/53)experienced grade 3 or higher TRAEs.In phase 1a,the disease control rate(DCR)was 50.0%(95%confidence interval[CI],18.7%–81.3%).In phase 1b,the objective response rate(ORR)and DCR were 17.6%(95%CI,6.8%–34.5%)and 44.1%(95%CI,27.2%–62.1%),respectively,for melanoma,and were 22.2%(95%CI,2.8%–60.0%)and 66.7%(95%CI,29.9%–92.5%),respectively,for UC.IBI310 monotherapy or combination therapy with sintilimab was well tolerated with favorable antitumor activity across patients with advanced melanoma and UC.展开更多
This review summarizes the current knowledge on immune defence activities of the European sea bass Dicentrarchus labrax by reporting the consistent amount of work done on this economically-important species.A draft ge...This review summarizes the current knowledge on immune defence activities of the European sea bass Dicentrarchus labrax by reporting the consistent amount of work done on this economically-important species.A draft genome sequence is available for this species,together with whole transcriptomes from lymphoid and non-lymphoid tissues.Available full-length coding sequences of many immunoregulatory and immune-related genes allow for targeted quantitative PCR analysis,nowadays needed for-omics data verification,ex vivo and in vitro.The first anti-T cells monoclonal antibody teleost-wise was obtained in sea bass,followed by several monoclonal and polyclonal markers of lymphocyte populations,namely T cells(pan-T,CD3ε,TcRγ,CD45),and B cells(IgM,IgT,IgD).The combined use of molecular and biochemical tools enabled investigations on innate and acquired immune responses of sea bass in unstimulated/stimulated fish,along the development and under variable environmental conditions and food regimes.An overview of sea bass viral and bacterial pathogens and available vaccines against these microorganisms is also provided.The knowledge accumulated in the past 25 years validates the European sea bass as a reference marine model in the field of fish immunology.展开更多
FOXP3+ regulatory T (Treg) cells are critical in maintaining immune tolerance and homeostasis of the immune system. The molecular mechanisms underlying the stability, plasticity and functional activity of Treg cell...FOXP3+ regulatory T (Treg) cells are critical in maintaining immune tolerance and homeostasis of the immune system. The molecular mechanisms underlying the stability, plasticity and functional activity of Treg cells have been much studied in recent years. Here, we summarize these intriguing findings, and provide insight into their potential use or manipulation during Treg cell therapy for the treatment of autoimmune diseases, graft-versus-host disease (GVHD) and cancer.展开更多
It is widely recognized that treatment intervention in patients with rheumatoid arthritis(RA)at early stages is associated with improved outcomes.1 Hence,research efforts have been devoted to investigation of whether ...It is widely recognized that treatment intervention in patients with rheumatoid arthritis(RA)at early stages is associated with improved outcomes.1 Hence,research efforts have been devoted to investigation of whether intervention starting at the preclinical stage will prevent the clinical onset of RA.2-5 In these studies,individuals at risk for RA were identified mainly by the detection of anti-citrullinated protein antibodies(ACPAs)and/or the rheumatoid factor(RF),which may precede the clinical symptoms of RA patients.展开更多
Mediterranean forest ecosystems are characterized by various vascular plant groups with their associated mycor-rhizae and free living soil fungi with various ecological functions.Fire plays a major role in Mediterrane...Mediterranean forest ecosystems are characterized by various vascular plant groups with their associated mycor-rhizae and free living soil fungi with various ecological functions.Fire plays a major role in Mediterranean ecosystem dynamics and impacts both above-and below-ground community structure and functioning.However,studies on the effects induced by altered disturbance regimes(associated with recent land use and climate extremes)on fire ecology and especially on its below-ground impacts are few.The objectives of this study were to evaluate the effects of different wildfire regimes on soil fungal community structure using two different molecular methods.We investigated the long-term effects of wildfire on soil fungal communities associated with Pinus pinaster forests in central Portugal,by comparing the results of denaturing gradient gel electrophoresis(DGGE)-based profiling with those obtained with 454 pyrosequencing.Four forest stands with differing fire history and fire return interval,and vegetation cover(mature forest,early successional stage of pine regeneration,and forest converted to scrubland)were sampled 6 years after the last fire event.The pyrosequencing-based approach indicated ca.eight-fold higher numbers of taxa than DGGE.However,fungal community fingerprinting data obtained for the different study stands with DGGE were congruent with those obtained with pyrosequencing.Both short(7.6 years)and long(24 years)fire return intervals(indicated by the presence of ericaceous shrubs in the understorey)induced a decrease in the abun-dance ratio between basidiomycetes and ascomycetes and appeared to reduce the frequency of ectomycorrhizal fungal species and saprophytes.Wildfire significantly reduced the frequency of late stage successional taxa(e.g.Atheliaceae and Cantharellales)and known or putative saprophytes belonging to the Clavulinaceae and the Archaeorhizomycetaceae.Conversely,early successional fungal species belonging to the Thelephoraceae were favoured by both fire return inter-vals,while the abundance of Cortinarius and Hebeloma,which include several Cistus-specific species,increased with short wildfire return intervals.This last finding highlights the relationship between postfire vegetation composition and cover(vegetation successional stage),and fungal symbionts.We hypothesise that these changes could,in the long term,exhaust the resilience of Mediterranean pine forest vegetation and associated soil fungal communities by preventing pine regeneration.展开更多
This study reviews carbon stocks and carbon dynamics in diferent types of forest land in Italy:ordinary managed forests,forest plantations,old growth forests,and trees outside forests.Forest management,combined with g...This study reviews carbon stocks and carbon dynamics in diferent types of forest land in Italy:ordinary managed forests,forest plantations,old growth forests,and trees outside forests.Forest management,combined with global environmental changes,increases the capacity of carbon uptake of ordinary managed forests.Forest plantations,particularly the ones subject to short-rotation forestry systems,potentially have high soil carbon accumulation,especially in agricultural lands.Old growth forests,recently discovered as a carbon sink,cover a significant surface area in Italy.Moreover,the trees outside forests may represent a sensible carbon stock,especially in the context of urban environments.Our study points out the management actions that can be implemented in Italy to increase the carbon stocks of different forest ecosystems,such as increasing the mean annual increment in managed forests,enhancement of the national network of old growth forests,and expansion of forest plantations in suitable areas.These aspects have important implications after the recent recognition of the Land Use,Land Use Change and Forestry sector in the EU target within the 2030 Climate and Energy Policy Framework.展开更多
Background:Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer(sqNSCLC)after failure of first-line chemotherapy are limited.This study(ORIENT-3)aimed to ...Background:Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer(sqNSCLC)after failure of first-line chemotherapy are limited.This study(ORIENT-3)aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC.Methods:ORIENT-3 was an open-label,multicenter,randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy.Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m^(2) of docetaxel intravenously every 3 weeks,stratified by the Eastern Cooperative Oncology Group performance status.The primary endpoint was overall survival(OS)in the full analysis set(FAS).Secondary endpoints included progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),duration of response(DoR)and safety.Results:Between August 25,2017,and November 7,2018,290 patients were randomized.For FAS,10 patients fromthe docetaxel armwere excluded.Themedian OS was 11.79(n=145;95%confidence interval[CI],10.28-15.57)months with sintilimab versus 8.25(n=135;95%CI,6.47-9.82)months with docetaxel(hazard ratio[HR]:0.74;95%CI,0.56-0.96;P=0.025).Sintilimab treatment significantly prolonged PFS(median 4.30 vs.2.79 months;HR:0.52;95%CI,0.39-0.68;P<0.001)and showed higher ORR(25.50%vs.2.20%,P<0.001)and DCR(65.50%vs.37.80%,P<0.001)than the docetaxel arm.The median DoRwas 12.45(95%CI,4.86-25.33)months in the sintilimab arm and 4.14(95%CI,1.41-7.23)months in the docetaxel arm(P=0.045).Treatment-related adverse events of grade≥3were reported in 26(18.1%)patients in the sintilimab arm and 47(36.2%)patients in the docetaxel arm.Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors,including OVOL2(HR:0.35;P<0.001)and CTCF(HR:3.50;P<0.001),for sintilimab treatment.Conclusions:Compared with docetaxel,sintilimab significantly improved the OS,PFS,and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.展开更多
基金supported by the “Project funded by the European Union-Next Generation EU”
文摘In the Mediterranean region,despite bamboo being an alien species that can seriously alter plant and ani-mal biocoenosis,the area occupied by bamboo plantations continues to increase,especially for the purpose to seques-ter carbon(C).However,the C dynamics in the soil-plant system when bamboo is grown outside its native area are poorly understood.Here we investigated the C mitigation potential of the fast-growing Moso bamboo(Phyllostachys edulis)introduced in Italy for climate-change mitigation.We analyzed aboveground(AGB)and belowground(as root/shoot ratio)biomass,litter and soil organic C(SOC)at O-15-and 15-30-cm depths in a 4-year-old bamboo plantation in comparison with the former annual cropland on which the bamboo was established.To have an idea of the maximum C stored at an ecosystem level,a natural forest adjacent the two sites was also considered.In the plantation,C accumulation as AGB was stimulated,with 14.8±3.1 Mg C ha^(-1) stored in 3 years;because thinning was done to remove culms from the first year,the mean sequestration rate was 4.9 Mg C ha^(-1) a^(-1).The sequestration rates were high but comparable to other fast-growing tree species in Italy(e.g.,Pinus nigra).SOC was significantly higher in the bamboo plantation than in the cropland only at the 0-15 cm depth,but SOC stock did not differ.Possibly 4 years were not enough time for a clear increase in SOC,or the high nutrient uptake by bamboos might have depleted the soil nutrients,thus inhibiting the soil organic matter formation by bacteria.In comparison,the natural forest had significantly higher C levels in all the pools.For C dynamics at an ecosystem level,the bamboo plantation on the former annual cropland led to substantial C removal from the atmosphere(about 12 Mg C ha^(-1) a^(-1)).However,despite the promising C sequestration rates by bamboo,its introduction should be carefully considered due to potential ecological problems caused by this species in overexploited environments such as the Mediterranean area.
文摘The neuromodulatory peptide somatostatin(somatotropin release inhibiting factor,SRIF)-14 acts at multiple levels through five SRIF receptor subtypes(sst1 to sst5).SRIF-28 is also derived from a common propeptide translated from a single SRIF gene,although SRIF-14 is the predominant form in the mammalian nervous system.Due to its short half-life,synthetic SRIF analogs have been developed over the years and are available for therapeutic approaches.
基金supported by grants from the Italian Ministry of Education,University and Research:“PRIN2015” to DC and “Departments of Excellence-2018”Program(Dipartimenti di Eccellenza)(Department for Innovation in Biological,Agro-food and Forest systems-DIBAF-University of Tuscia,Viterbo,Italy)(Project “Landscape 4.0-food,wellbeing and environment”)
文摘Diabetic retinopathy(DR)is the most common complication of diabetes and the leading cause of visual impairment in the working-age population in the Western world(http://www.diabetesatlas.org/).One of the earliest events observed in DR is the impairment of retinal perfusion,caused by the constriction of retinal blood vessels,inducing biochemical and metabolic alterations,perycites/endothelial degeneration,and retina ischemia(Wong et al.,2016).Severe stages of DR include proliferative DR,caused by the abnormal growth of new vessels,and diabetic macular oedema in the central part of the retina.DR is strongly associated with a prolonged duration of diabetes,hypertension,and hyperglycaemia but it can persist even after replacement of normal glycaemic status(Wong et al.,2016).
基金supported by the Italian Ministry for Agricultural and Forest Policy,under the programme Ri.Selv.Italia(Research unit 3.2.1,DIBAF,University of Viterbo)
文摘We estimated water-use efficiency and potential photosyn- thetic assimilation of Holm oak (Quercus ilex L.) on slopes of NW and SW aspects in a replicated field test examining the effects of intensifying drought in two Mediterranean coppice forests. We used standard tech- niques for quantifying gas exchange and carbon isotopes in leaves and analyzed total chlorophyll, carotenoids and nitrogen in leaves collected from Mediterranean forests managed under the coppice system. We pos- tulated that responses to drought of coppiced trees would lead to differ- ential responses in physiological traits and that these traits could be used by foresters to adapt to predicted warming and drying in the Mediterra- nean area. We observed physiological responses of the eoppiced trees that suggested acclimation in photosynthetic potential and water-use effi- ciency: (1) a significant reduction in stomatal conductance (p〈0.01) wasrecorded as the drought increased at the SW site; (2) foliar 813C increased as drought increased at the SW site (p〈0.01); (3) variations in levels of carotenoids and foliar nitrogen, and differences in foliar morphology were recorded, and were tentatively attributed to variation in photosyn- thetic assimilation between sites. These findings increase knowledge of the capacity for acclimation of managed forests in the Mediterranean region of Europe.
基金Funding from the Italian Ministry of Environment, Land and Sea Protection (MATTM) for the Sim PRO project (2020–2021) is acknowledged by (in alphabetical order): S. Grimaldi, G. Papacharalampous and E. Volpifunding from the Italian Ministry of Education, University and Research (MIUR), in the frame of the Departments of Excellence Initiative 2018–2022, attributed to the Department of Engineering of Roma Tre Universityfunding from the EU Horizon 2020 project CLINT (Climate Intelligence: Extreme events detection, attribution and adaptation design using machine learning) under Grant Agreement 101003876
文摘Statistical analyses and descriptive characterizations are sometimes assumed to be offering information on time series forecastability.Despite the scientific interest suggested by such assumptions,the relationships between descriptive time series features(e.g.,temporal dependence,entropy,seasonality,trend and linearity features)and actual time series forecastability(quantified by issuing and assessing forecasts for the past)are scarcely studied and quantified in the literature.In this work,we aim to fill in this gap by investigating such relationships,and the way that they can be exploited for understanding hydroclimatic forecastability and its patterns.To this end,we follow a systematic framework bringing together a variety of–mostly new for hydrology–concepts and methods,including 57 descriptive features and nine seasonal time series forecasting methods(i.e.,one simple,five exponential smoothing,two state space and one automated autoregressive fractionally integrated moving average methods).We apply this framework to three global datasets originating from the larger Global Historical Climatology Network(GHCN)and Global Streamflow Indices and Metadata(GSIM)archives.As these datasets comprise over 13,000 monthly temperature,precipitation and river flow time series from several continents and hydroclimatic regimes,they allow us to provide trustable characterizations and interpretations of 12-month ahead hydroclimatic forecastability at the global scale.We first find that the exponential smoothing and state space methods for time series forecasting are rather equally efficient in identifying an upper limit of this forecastability in terms of Nash-Sutcliffe efficiency,while the simple method is shown to be mostly useful in identifying its lower limit.We then demonstrate that the assessed forecastability is strongly related to several descriptive features,including seasonality,entropy,(partial)autocorrelation,stability,(non)linearity,spikiness and heterogeneity features,among others.We further(i)show that,if such descriptive information is available for a monthly hydroclimatic time series,we can even foretell the quality of its future forecasts with a considerable degree of confidence,and(ii)rank the features according to their efficiency in explaining and foretelling forecastability.We believe that the obtained rankings are of key importance for understanding forecastability.Spatial forecastability patterns are also revealed through our experiments,with East Asia(Europe)being characterized by larger(smaller)monthly temperature time series forecastability and the Indian subcontinent(Australia)being characterized by larger(smaller)monthly precipitation time series forecastability,compared to other continental-scale regions,and less notable differences characterizing monthly river flow from continent to continent.A comprehensive interpretation of such patters through massive feature extraction and feature-based time series clustering is shown to be possible.Indeed,continental-scale regions characterized by different degrees of forecastability are also attributed to different clusters or mixtures of clusters(because of their essential differences in terms of descriptive features).
基金Supported by Italian Ministry of Education,University and Research(PRIN2005,grant No.2005052312)and University of Tuscia
文摘Retinal ischemia is a common clinical entity and, due to relatively ineffective treatment, remains a common cause of visual impairment and blindness. Generally, ischemic syndromes are initially characterized by low homeostatic responses which, with time, induce injury to the tissue due to cell loss by apoptosis. In this re-spect, retinal ischemia is a primary cause of neuronal death. It can be considered as a sort of fnal common pathway in retinal diseases and results in irreversible morphological and functional changes. This review summarizes the recent knowledge on the effects of ischemia in retinal tissue and points out experimental strategies/models performed to gain better compre-hension of retinal ischemia diseases. In particular, the nature of the mechanisms leading to neuronal damage (i.e., excess of glutamate release, oxidative stress and infammation) will be outlined as well as the potential and most intriguing retinoprotective approaches and the possible therapeutic use of naturally occurring molecules such as neuropeptides. There is a general agreement that a better understanding of the funda-mental pathophysiology of retinal ischemia will lead tobetter management and improved clinical outcome. In this respect, to contrast this pathological state, spe-cifc pharmacological strategies need to be developed aimed at the many putative cascades generated during ischemia.
文摘The stimulation of the human sensory receptors by compounds present in virgin olive oils (VOOs) gives rise to the sensory attributes that describe its particular aroma. The sensor panel evaluation and the molecules responsible for sensory perceptions of virgin olive oil quality are elucidated. The methodology for the evaluation of the sensory characteristics of VOOs is reported, and typical flavours and off-flavours are described. Relationships between chemical compounds and sensory characteristics are evaluated using the new sensory analyses method promoted by the International Olive Oil Council (IOOC) and included recently in EU regulation (Reg. 1348/2013 and following revisions). Oil quality may be defined in a number of ways, but the sensory perception of flavour is the ultimate determinant.
文摘This is a review of the status of the universe as described by the standard cosmological model combined with the inflationary paradigm. Their key features and predictions, consistent with the WMAP (Wilkinson Microwave Anisotropies Probe) and Planck Probe 2013 results, provide a significant mechanism to generate the primordial gravitational waves and the density perturbations which grow over time, and later become the large-scale structure of the universe—from the quantum fluctuations in the early era to the structure observed 13.7 billion later, our epoch. In the single field slow-roll paradigm, the primordial quantum fluctuations in the inflaton field itself translate into the curvature and density perturbations which grow over time via gravitational instability. High density regions continuously attract more matter from the surrounding space, the high density regions become more and more dense in time while depleting the low density regions. At late times the highest density regions peaks collapse into the large structure of the universe, whose gravitational instability effects are observed in the clustering features of galaxies in the sky. Thus, the origin of all structure in the universe probably comes from an early era where the universe was filled with a scalar field and nothing else.
文摘We propose a game-theoretic model for a first-price sealed-bid auction (FPSB auction) of standing timber. A FPSB auction means that bidders simultaneously submit sealed bids so that no bidder knows the bid of any other participant. The highest bidder pays the submitted price. The mathematical model has been elaborated considering only two bidders. Each bidder is supposed to know only the probability distribution of the bid of the other bidder. Using ap- propriate distributions, the adversity and propensity of a bidder to risk can be described. From the view point of a bidder, the conservative solution is calculated for both types of the other bidder. If a standing timber belongs to a public owner, the market has to follow a public evidence procedure, including public auctions. The function obtained is illustrated with a numerical example of a typical standing timber auction from a forest located in central Italy. Considering average costs and prices of the local chestnut timber market, winning bids and expected gains are estimated. Their amounts are com- parable with the currently average stumpage price registered in this market.
文摘Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brain of patients with Alzheimer’s disease (AD). In the past years considerable attention has been focused on identifying new protective substances that prevent or almost retard the appearance of amyloid beta (1-42)-related neurotoxic effects. In this study, human neuroblastoma cells (IMR-32) was used as system model to evaluate the protective role of S100b, a neurotrophic factor and neuronal survival protein, that is highly expressed by reactive astrocytes in close vicinity of beta-amyloid deposits, against amyloid beta (1-42)-dependent toxicity. Our results show that at nanomolar concentrations, S100b protects cells against Aβmediated cytotoxicity, as assessed by MTS vitality test. The protective mechanism seems to be related to the effect on bcl-2 (an anti-apoptotic gene) expression, which is highly down-regulated by amyloid beta (1-42) treatment, while resulted more expressed in the presence of S100b. On the contrary, Bax, a proapoptotic gene, resulted down-regulated by the treatment with S100 compared with the results obtained in the presence of amyloid beta (1-42) peptide. However, at micromolar doses, S100b is toxic for IMR-32 cells and its toxicity adds to that of the Aβpeptide, suggesting that additional molecular mechanisms may be involved in theneurotoxic process.
基金supported by grants from“Departments of Excellence-2018”Program(Dipartimenti di Eccellenza)to DIBAF(University of Tuscia,Viterbo,Italy)(Project“Landscape 4.0-food,wellbeing and environment”)(to DC)。
文摘Due to the high degree of conservation of genes and mechanisms, the fruit fly Drosophila melanogaster is a powerful experimental in vivo tool to investigate complex diseases, thus complementing traditional vertebrate systems. Drosophila is also an advantageous system regarding the animal husbandry and the short generation time and lifespan.
文摘Illegal logging is a pervasive problem of major international concern that causes many negative social, economical and environmental consequences. EUTR is a tool adopted in 2010 and entered into force in 2013 to stop the trade of timber illegally logged within the EU market. The implementation in Italy is still in progress and varies among regions. This study considers the respondents’ opinions on different EUTR characteristics, implementation processes and compliance activities. Taking Italy as an example, the questionnaire was delivered to relevant Italian foresters and timber operators in the forest-timber system. Two hypotheses are under verification: </span></span><span><span><span style="font-family:"">1</span></span></span><span><span><span style="font-family:"">) if Italian forest-wood-timber sector integrated EUTR into its activity and </span></span></span><span><span><span style="font-family:"">2</span></span></span><span><span><span style="font-family:"">) if the Italian Due Diligence system is a valid model to other countries. The questionnaire has been submitted to the wood industry stakeholders. It has been organized into six sections to collect information about the professional characteristics of respondents, their experiences on EUTR, the opinion about EUTR and FLEGT, the support received on EUTR implementation, the opinion about the checks system, and the role of EUTR in marketing timber products. Questionnaire data have been elaborated in different ways. Conclusion underlines the EUTR Italian system criticalities and some suggestions for a more effective use of EUTR in the wood market. The picture that emerges from the results collected is that the EUTR, although proposed for morally and ethically valid purposes, doesn’t have unanimous effectiveness. In particular, EUTR can generate a distortion of the market, new expenditures for importers. Various operators applaud the role of certification schemes for sustainable forest management, which indirectly makes it possible to prevent the aforementioned problem. The Italian EUTR system is working only for satisfying Regulation 995/2010 targets. This must be considered as the starting point;however, three innovative topics could be developed in the future: digitalization and computerization of EUTR certification, integration of EUTR certification with forest certifications schemes and other quality certifications, and use of EUTR in the marketing initiatives.
文摘We report for the first time the occurrence of heteroplasmy in Grey Partridge(Perdix perdix)revealed by means of two mitochondrial fragments.The possible serious biological and management implications of this exception to unilateral inheritance of mtDNA were underlined.
基金supported by grants from Beijing Health Technologies Promotion Program(BHTPP2022041)Peking University Clinical Scientist Training Program,the Fundamental Research Funds for the Central Universities(BMU2024PYJH010)+2 种基金Beijing Municipal Administration of Hospitals Incubating Program(PX2021046)Science Foundation of Peking University Cancer Hospital(PY202333)Innovent Biologics,Inc.,Suzhou,China.The funder,Innovent Biologics,was involved in the study design,data collection,data analysis,and data interpretation.
文摘IBI310 is a recombinant fully human IgG1 antibody against cytotoxic T lymphocyte antigen 4.This study was conducted to evaluate IBI310 monotherapy or combination therapy with sintilimab in the patients with advanced melanoma or urothelial carcinoma(UC).Patients in phase 1a received IBI310 at 0.3/1/2/3 mg/kg intravenously(IV)every 3 weeks(Q3W)following the accelerated titration and 3+3 escalation design.Patients in phase 1b received IBI310(1/2/3 mg/kg IV,Q3W)plus sintilimab(200 mg IV,Q3W)for four cycles,followed by sintilimab maintenance therapy.The phase 1b expansion of IBI310 plus sintilimab was performed in patients with advanced melanoma or UC.Overall,53 patients were enrolled,including 10 patients with melanoma in phase 1a,34 with melanoma,and 9 with UC in phase 1b.Overall,94.3%of patients(50/53)experienced at least one treatment-related adverse event(TRAE)with most being grade 1–2;26.4%of patients(14/53)experienced grade 3 or higher TRAEs.In phase 1a,the disease control rate(DCR)was 50.0%(95%confidence interval[CI],18.7%–81.3%).In phase 1b,the objective response rate(ORR)and DCR were 17.6%(95%CI,6.8%–34.5%)and 44.1%(95%CI,27.2%–62.1%),respectively,for melanoma,and were 22.2%(95%CI,2.8%–60.0%)and 66.7%(95%CI,29.9%–92.5%),respectively,for UC.IBI310 monotherapy or combination therapy with sintilimab was well tolerated with favorable antitumor activity across patients with advanced melanoma and UC.
基金supported by the“Department of Excellence-2018”Program(Dipartimenti di Eccellenza)of the Italian Ministry of Education,University and Research,DIBAF-Department for Innovation in Biological,Agro-food and Forest Systems,University of Tuscia,Project“Landscape 4.0-food,wellbeing and environment”.
文摘This review summarizes the current knowledge on immune defence activities of the European sea bass Dicentrarchus labrax by reporting the consistent amount of work done on this economically-important species.A draft genome sequence is available for this species,together with whole transcriptomes from lymphoid and non-lymphoid tissues.Available full-length coding sequences of many immunoregulatory and immune-related genes allow for targeted quantitative PCR analysis,nowadays needed for-omics data verification,ex vivo and in vitro.The first anti-T cells monoclonal antibody teleost-wise was obtained in sea bass,followed by several monoclonal and polyclonal markers of lymphocyte populations,namely T cells(pan-T,CD3ε,TcRγ,CD45),and B cells(IgM,IgT,IgD).The combined use of molecular and biochemical tools enabled investigations on innate and acquired immune responses of sea bass in unstimulated/stimulated fish,along the development and under variable environmental conditions and food regimes.An overview of sea bass viral and bacterial pathogens and available vaccines against these microorganisms is also provided.The knowledge accumulated in the past 25 years validates the European sea bass as a reference marine model in the field of fish immunology.
文摘FOXP3+ regulatory T (Treg) cells are critical in maintaining immune tolerance and homeostasis of the immune system. The molecular mechanisms underlying the stability, plasticity and functional activity of Treg cells have been much studied in recent years. Here, we summarize these intriguing findings, and provide insight into their potential use or manipulation during Treg cell therapy for the treatment of autoimmune diseases, graft-versus-host disease (GVHD) and cancer.
基金supported by an Innovative Research Award by Rheumatology Research Foundation and by VA Merit Review grant(I01BX005195).
文摘It is widely recognized that treatment intervention in patients with rheumatoid arthritis(RA)at early stages is associated with improved outcomes.1 Hence,research efforts have been devoted to investigation of whether intervention starting at the preclinical stage will prevent the clinical onset of RA.2-5 In these studies,individuals at risk for RA were identified mainly by the detection of anti-citrullinated protein antibodies(ACPAs)and/or the rheumatoid factor(RF),which may precede the clinical symptoms of RA patients.
基金supported by the Portuguese Foundation for Science and Technology(FCT)through a Ph.D.grant for E.B.(SFRH/BD/21730/2005).
文摘Mediterranean forest ecosystems are characterized by various vascular plant groups with their associated mycor-rhizae and free living soil fungi with various ecological functions.Fire plays a major role in Mediterranean ecosystem dynamics and impacts both above-and below-ground community structure and functioning.However,studies on the effects induced by altered disturbance regimes(associated with recent land use and climate extremes)on fire ecology and especially on its below-ground impacts are few.The objectives of this study were to evaluate the effects of different wildfire regimes on soil fungal community structure using two different molecular methods.We investigated the long-term effects of wildfire on soil fungal communities associated with Pinus pinaster forests in central Portugal,by comparing the results of denaturing gradient gel electrophoresis(DGGE)-based profiling with those obtained with 454 pyrosequencing.Four forest stands with differing fire history and fire return interval,and vegetation cover(mature forest,early successional stage of pine regeneration,and forest converted to scrubland)were sampled 6 years after the last fire event.The pyrosequencing-based approach indicated ca.eight-fold higher numbers of taxa than DGGE.However,fungal community fingerprinting data obtained for the different study stands with DGGE were congruent with those obtained with pyrosequencing.Both short(7.6 years)and long(24 years)fire return intervals(indicated by the presence of ericaceous shrubs in the understorey)induced a decrease in the abun-dance ratio between basidiomycetes and ascomycetes and appeared to reduce the frequency of ectomycorrhizal fungal species and saprophytes.Wildfire significantly reduced the frequency of late stage successional taxa(e.g.Atheliaceae and Cantharellales)and known or putative saprophytes belonging to the Clavulinaceae and the Archaeorhizomycetaceae.Conversely,early successional fungal species belonging to the Thelephoraceae were favoured by both fire return inter-vals,while the abundance of Cortinarius and Hebeloma,which include several Cistus-specific species,increased with short wildfire return intervals.This last finding highlights the relationship between postfire vegetation composition and cover(vegetation successional stage),and fungal symbionts.We hypothesise that these changes could,in the long term,exhaust the resilience of Mediterranean pine forest vegetation and associated soil fungal communities by preventing pine regeneration.
文摘This study reviews carbon stocks and carbon dynamics in diferent types of forest land in Italy:ordinary managed forests,forest plantations,old growth forests,and trees outside forests.Forest management,combined with global environmental changes,increases the capacity of carbon uptake of ordinary managed forests.Forest plantations,particularly the ones subject to short-rotation forestry systems,potentially have high soil carbon accumulation,especially in agricultural lands.Old growth forests,recently discovered as a carbon sink,cover a significant surface area in Italy.Moreover,the trees outside forests may represent a sensible carbon stock,especially in the context of urban environments.Our study points out the management actions that can be implemented in Italy to increase the carbon stocks of different forest ecosystems,such as increasing the mean annual increment in managed forests,enhancement of the national network of old growth forests,and expansion of forest plantations in suitable areas.These aspects have important implications after the recent recognition of the Land Use,Land Use Change and Forestry sector in the EU target within the 2030 Climate and Energy Policy Framework.
基金funded by Innovent biologics,Inc.Eli Lilly and Companypartly supported by China National Major Project for New Drug Innovation(2017ZX09304015).
文摘Background:Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer(sqNSCLC)after failure of first-line chemotherapy are limited.This study(ORIENT-3)aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC.Methods:ORIENT-3 was an open-label,multicenter,randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy.Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m^(2) of docetaxel intravenously every 3 weeks,stratified by the Eastern Cooperative Oncology Group performance status.The primary endpoint was overall survival(OS)in the full analysis set(FAS).Secondary endpoints included progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),duration of response(DoR)and safety.Results:Between August 25,2017,and November 7,2018,290 patients were randomized.For FAS,10 patients fromthe docetaxel armwere excluded.Themedian OS was 11.79(n=145;95%confidence interval[CI],10.28-15.57)months with sintilimab versus 8.25(n=135;95%CI,6.47-9.82)months with docetaxel(hazard ratio[HR]:0.74;95%CI,0.56-0.96;P=0.025).Sintilimab treatment significantly prolonged PFS(median 4.30 vs.2.79 months;HR:0.52;95%CI,0.39-0.68;P<0.001)and showed higher ORR(25.50%vs.2.20%,P<0.001)and DCR(65.50%vs.37.80%,P<0.001)than the docetaxel arm.The median DoRwas 12.45(95%CI,4.86-25.33)months in the sintilimab arm and 4.14(95%CI,1.41-7.23)months in the docetaxel arm(P=0.045).Treatment-related adverse events of grade≥3were reported in 26(18.1%)patients in the sintilimab arm and 47(36.2%)patients in the docetaxel arm.Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors,including OVOL2(HR:0.35;P<0.001)and CTCF(HR:3.50;P<0.001),for sintilimab treatment.Conclusions:Compared with docetaxel,sintilimab significantly improved the OS,PFS,and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.