Earlier spring leaf unfolding is a frequently observed response of plants to climate warming. Many deciduous tree species require chilling for dormancy release, and warming-related reductions in ...chilling may counteract the advance of leaf unfolding in response to warming. Empirical evidence for this, however, is limited to saplings or twigs in climate-controlled chambers. Using long-term in situ observations of leaf unfolding for seven dominant European tree species at 1,245 sites, here we show that the apparent response of leaf unfolding to climate warming (ST, expressed in days advance of leaf unfolding per °C warming) has significantly decreased from 1980 to 2013 in all monitored tree species. Averaged across all species and sites, ST decreased by 40% from 4.0 ± 1.8 days °C(-1) during 1980-1994 to 2.3 ± 1.6 days °C(-1) during 1999-2013. The declining ST was also simulated by chilling-based phenology models, albeit with a weaker decline (24-30%) than observed in situ. The reduction in ST is likely to be partly attributable to reduced chilling. Nonetheless, other mechanisms may also have a role, such as 'photoperiod limitation' mechanisms that may become ultimately limiting when leaf unfolding dates occur too early in the season. Our results provide empirical evidence for a declining ST, but also suggest that the predicted strong winter warming in the future may further reduce ST and therefore result in a slowdown in the advance of tree spring phenology.
AIM: Although numerous studies have reported advanced Northern Hemisphere spring phenology since the 1980s, recent studies based on remote sensing have reported a reversal or deceleration of this ...trend. This study aimed (1) to fully understand recent spring phenology shifts using both in situ observations and satellite‐based normalized difference vegetation index (NDVI) datasets, and (2) to test whether the NDVI methods capture the trends observed in situ. LOCATION: Western Central Europe. METHODS: Temporal spring phenology trends (leaf unfolding dates) were examined using 1,001,678 in situ observations of 31 plant species at 3984 stations, as well as NDVI‐based start‐of‐season dates, obtained using five different methods, across the pixels that included the phenology stations. RESULTS: In situ and NDVI observations both indicated that spring phenology significantly advanced during the period 1982–2011 at an average rate of −0.45 days yr⁻¹. This trend was not uniform across the period and significantly weakened over the period 2000–2011. Furthermore, opposite trends were found between in situ and NDVI observations over the period 2000–2011. Averaged over all species, the in situ observations indicated a slower but still advancing trend for leaf unfolding, whereas the NDVI series showed a delayed spring phenology. MAIN CONCLUSIONS: The recent trend reversal in the advancement of spring phenology in western Central Europe is likely to be related to the response of early spring species to the cooling trend in late winter. In contrast, late spring species continued to exhibit advanced leaf unfolding, which is consistent with the warming trend during spring months. Because remote sensing does not distinguish between species, the signal of growing‐season onset may only reflect the phenological dynamics of these earliest species in the pixel, even though most species still exhibit advancing trends.
Recent studies have revealed large unexplained variation in heat requirement‐based phenology models, resulting in large uncertainty when predicting ecosystem carbon and water balance responses to ...climate variability. Improving our understanding of the heat requirement for spring phenology is thus urgently needed. In this study, we estimated the species‐specific heat requirement for leaf flushing of 13 temperate woody species using long‐term phenological observations from Europe and North America. The species were defined as early and late flushing species according to the mean date of leaf flushing across all sites. Partial correlation analyses were applied to determine the temporal correlations between heat requirement and chilling accumulation, precipitation and insolation sum during dormancy. We found that the heat requirement for leaf flushing increased by almost 50% over the study period 1980–2012, with an average of 30 heat units per decade. This temporal increase in heat requirement was observed in all species, but was much larger for late than for early flushing species. Consistent with previous studies, we found that the heat requirement negatively correlates with chilling accumulation. Interestingly, after removing the variation induced by chilling accumulation, a predominantly positive partial correlation exists between heat requirement and precipitation sum, and a predominantly negative correlation between heat requirement and insolation sum. This suggests that besides the well‐known effect of chilling, the heat requirement for leaf flushing is also influenced by precipitation and insolation sum during dormancy. However, we hypothesize that the observed precipitation and insolation effects might be artefacts attributable to the inappropriate use of air temperature in the heat requirement quantification. Rather than air temperature, meristem temperature is probably the prominent driver of the leaf flushing process, but these data are not available. Further experimental research is thus needed to verify whether insolation and precipitation sums directly affect the heat requirement for leaf flushing.
Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. Due to the rise in the incidence rate of RA and the limitations of existing therapies, the search for new treatment strategies ...for RA has become a global focus. Ferroptosis is a novel programmed cell death characterized by iron-dependent lipid peroxidation, with distinct differences from apoptosis, autophagy, and necrosis. Under the conditions of iron accumulation and the glutathione peroxidase 4 (GPX4) activity loss, the lethal accumulation of lipid peroxide is the direct cause of ferroptosis. Ferroptosis mediates inflammation, oxidative stress, and lipid oxidative damage processes, and also participates in the occurrence and pathological progression of inflammatory joint diseases including RA. This review provides insight into the role and mechanism of ferroptosis in RA and discusses the potential and challenges of ferroptosis as a new therapeutic strategy for RA, with an effort to provide new targets for RA prevention and treatment.
Heat requirement, expressed in growing degree days (GDD), is a widely used method to assess and predict the effect of temperature on plant development. Until recently, the analysis of spatial ...patterns of GDD requirement for spring vegetation green‐up onset was limited to local and regional scales, mainly because of the sparse and aggregated spatial availability of ground phenology data. Taking advantage of the large temporal and spatial scales of remote sensing‐based green‐up onset data, we studied the spatial patterns of GDD requirement for vegetation green‐up at northern middle and high latitudes. We further explored the correlations between GDD requirement for vegetation green‐up and previous winter season chilling temperatures and precipitation, using spatial partial correlations. We showed that GDD requirement for vegetation green‐up onset declines towards the north at a mean rate of 18.8 °C‐days per degree latitude between 35°N and 70°N, and vary significantly among different vegetation types. Our results confirmed that the GDD requirement for vegetation green‐up is negatively correlated with previous winter chilling, which was defined as the number of chilling days from the day when the land surface froze in the previous autumn to the day of green‐up onset. This negative correlation is a well‐known phenomenon from local studies. Interestingly, irrespective of the vegetation type, we also found a positive correlation between the GDD requirement and previous winter season precipitation, which was defined as the sum of the precipitation of the month when green‐up onset occur and the precipitation that occurred during the previous 2 months. Our study suggests that GDD requirement, chilling and precipitation may have complex interactions in their effects on spring vegetation green‐up phenology. These findings have important implications for improving phenology models and could therefore advance our understanding of the interplay between spring phenology and carbon fluxes.
Circulating tumor cells (CTCs) could serve as a predictive biomarker in breast cancer (BC). Due to its high heterogeneity, the diagnostic and prognostic values of CTC are challenging.
We searched ...published studies from the databases of PubMed, Cochrane Library, Embase, and MEDLINE. The detection capability and hazard ratios (HRs) of CTCs were extracted as the clinical diagnosis and prognosis evaluation. Subgroup analyses were divided according to the detection methods, continents, treatment periods, therapeutic plans, and cancer stages.
In this study, 35 publications had been retrieved with 8,935 patients enrolled. The diagnostic efficacy of CTC detection has 74% sensitivity and 98% specificity. The positive CTC detection (CTC
) would predict worse OS and PFS/DFS in both mid-therapy and post-therapy (HR
, 3.09; 95% CI, 2.17-4.39; HR
, 2.06; 95% CI, 1.72-2.47). Moreover, CTC
indicated poor survival irrespective of the treatment phases and sampling times (HR
, 2.43; 95% CI, 1.85-3.19; HR
, 1.82; 95% CI, 1.66-1.99). The CTC
was associated with poor survival regardless of the continents of patients (HR
= 2.43; 95% CI, 1.85-3.19).
Our study suggested that CTC
was associated with a worse OS and PFS/DFS in the Asian population. The detection method, the threshold level of CTC
, therapeutic approaches, and sampling times would not affect its diagnostic and prognostic values.
Virus-induced IFN-α secretion by plasmacytoid dendritic cells (pDCs) is negatively impacted by IgE and has been linked to asthma exacerbations. Eosinophils, another contributor to type 2 ...inflammation, are also associated with asthma severity.
We sought to investigate the impact of eosinophils on pDC antiviral interferon responses and determine whether anti–IL-5/5Rα therapy enhances pDC antiviral function.
Blood pDCs purified from anonymous donors were stimulated in vitro with rhinovirus (RV)-16 in the presence or absence of eosinophils/eosinophil supernatants. IFN-α was measured in supernatants and RNA collected for bulk RNA-sequencing. Next, purified pDCs from 8 individuals with moderate to severe asthma, treated or not treated with anti–IL-5/5Rα therapy, were cultured ex vivo with or without RV; IFN-α secretion and differential gene expression analysis were compared between groups.
Exposure to either eosinophils or eosinophil supernatants inhibited RV-induced pDC IFN-α secretion in a dose-dependent manner and did not impact pDC viability. Eosinophil-derived neurotoxin and TGF-β partially recapitulated pDC IFN-α inhibition. Transcriptome analysis revealed global repression of pDC interferon response patterns by eosinophils, most notably in basal expression of interferon-stimulated genes. Increased RV-induced IFN-α secretion and transcription as well as increased basal interferon-stimulated gene expression was detected in pDCs from participants treated with anti–IL-5/5Rα therapy.
Our findings highlight a novel mechanism through which type 2 inflammation regulates pDC IFN-α responses relevant to RV respiratory infections in the context of eosinophilic airway disease, suggesting a potential mechanism through which eosinophil-depleting therapies may reduce severity of RV illnesses.
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As a terpenoids natural product isolated from the plant Thunder God Vine, Celastrol is widely studied for its pharmacological activities, including anti-tumor activities. The clinical application of ...Celastrol is strictly limited due to its severe side effects, whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural optimization. Target identification has a far-reaching influence on the development of innovative drugs, and omics data has been widely used for unbiased target prediction. However, it is difficult to enrich target of specific phenotype from thousands of genes or proteins, especially for natural products with broad promising activities. Here, we developed a text-mining-based web-server tool to enrich targets from omics data of inquired compounds. Then peroxiredoxin 1 (PRDX1) was identified as the ROS-manipulating target protein of Celastrol in colorectal cancer. Our solved high-resolution crystal structure revealed the unique covalent binding mode of Celastrol with PRDX1. New derivative compound 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized based on crystal structure analysis. Both Celastrol and 19-048 effectively suppressed the proliferation of colorectal cancer cells. The anti-tumor efficacy of Celastrol and 19-048 was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer cells. Several downstream genes of p53 signaling pathway were dramatically up-regulated with Celastrol or 19-048 treatment. Our findings reveal that the side effects of Celastrol could be reduced via structural modification, and PRDX1 inhibition is promising for the treatment of colorectal cancer.
•A process-based model (ORCHIDEE-crop) is calibrated efficiently with particle filter.•LGP of different rice types show varied response to change in climate and management.•Change in managements have ...larger impacts than climate change for early & single rice.•Regional modelling should consider multiple rice types & changing management practices.•Improved records on management & observation error are vital for reducing uncertainty.
Whether crop phenology changes are caused by change in managements or by climate change belongs to the category of problems known as detection-attribution. Three type of rice (early, late and single rice) in China show an average increase in Length of Growing Period (LGP) during 1991–2012: 1.0±4.8day/decade (±standard deviation across sites) for early rice, 0.2±4.5day/decade for late rice and 2.0±6.0day/decade for single rice, based on observations from 141 long-term monitoring stations. Positive LGP trends are widespread, but only significant (P<0.05) at 25% of early rice, 22% of late rice and 38% of single rice sites. We developed a Bayes-based optimization algorithm, and optimized five parameters controlling phenological development in a process-based crop model (ORCHIDEE-crop) for discriminating effects of managements from those of climate change on rice LGP. The results from the optimized ORCHIDEE-crop model suggest that climate change has an effect on LGP trends dependent on rice types. Climate trends have shortened LGP of early rice (−2.0±5.0day/decade), lengthened LGP of late rice (1.1±5.4day/decade) and have little impacts on LGP of single rice (−0.4±5.4day/decade). ORCHIDEE-crop simulations further show that change in transplanting date caused widespread LGP change only for early rice sites, offsetting 65% of climate change induced LGP shortening. The primary drivers of LGP change are thus different among the three types of rice. Management are predominant driver of LGP change for early and single rice. This study shows that complex regional variations of LGP can be reproduced with an optimized crop model. We further suggest that better documenting observational error and management practices can help reduce large uncertainties existed in attribution of LGP change, and future rice crop modelling in global/regional scales should consider different types of rice and variable transplanting dates in order to better account impacts of management and climate change.
Quantifying the coupled cycles of carbon and water is essential for exploring the response mechanisms of arid zone terrestrial ecosystems and for formulating a sustainable and practical solution to ...issues caused by climate change. Water use efficiency (WUE), one of the comprehensive indicators for assessing plant growth suitability, can accurately reflect vegetation’s dynamic response to changing climate patterns. This study assesses the spatio-temporal changes in WUE (ecosystem water use efficiency, soil water use efficiency, and precipitation water use efficiency) from 2000 to 2018 and quantifies their relationship with meteorological elements (precipitation, temperature, drought) and the vegetation index (NDVI). The study finds that the sensitivity of NDVI to WUE is highly consistent with the spatial law of precipitation. The εPre threshold range of different types of WUE is about 200 mm or 1600 mm (low-value valley point) and 300 mm or 1500 mm (high-value peak point), and the εTem threshold value is 3~6 °C (high-value peak point) and 9~12 °C (low-value valley point). The degree to which vegetation WUE is influenced by precipitation is positively correlated with its time lag, whereas the degree to which temperature influences vegetation is negatively correlated. The WUE time lag is very long in hilly regions and is less impacted by drought; it is quite short in plains and deserts, where it is substantially affected by drought. These findings may be of great significance in responding to the severe situation of increasingly scarce water resources and the deterioration of the ecological environment across Central Asia.
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