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Targeted radionuclide therapy, in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation, has addressed unmet clinical needs and improved outcomes for patients with cancer1–4. A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue, which remains a major challenge5,6. A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution. Here we installed a sulfur (VI) fluoride exchange (SuFEx) chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance. When the engineered radiopharmaceutical binds to the tumour-specific protein, the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the ‘click’ SuFEx reaction. The application of this strategy to a fibroblast activation protein (FAP) inhibitor (FAPI) triggered more than 80% covalent binding to the protein and almost no dissociation for six days. In mice, SuFEx-engineered FAPI showed 257% greater tumour uptake than did the original FAPI, and increased tumour retention by 13-fold. The uptake in healthy tissues was rapidly cleared. In a pilot imaging study, this strategy identified more tumour lesions in patients with cancer than did other methods. SuFEx-engineered FAPI also successfully achieved targeted β- and α-radionuclide therapy, causing nearly complete tumour regression in mice. Another SuFEx-engineered radioligand that targets prostate-specific membrane antigen (PSMA) also showed enhanced therapeutic efficacy. Considering the broad scope of proteins that can potentially be ligated to SuFEx warheads, it might be possible to adapt this strategy to other cancer targets.Radiopharmaceuticals engineered with click chemistry to selectively bind to tumour-specific proteins can be used to successfully target tumour cells, boosting the pharmacokinetics of radionuclide therapy and improving tumour regression. [ABSTRACT FROM AUTHOR]

Hydroclimate reconstruction for the last millennium is essential to understand the differences in hydroclimate extremes and their causes under cold/warm conditions. In this study, the first gridded drought/flood grades (D/F grades) dataset in eastern China (EC) during the last millennium was generated. This D/F grades dataset mainly consisted of two components. The first section was created by interpolating drought/flood grades from 1500 to 2000 using the angular distance weight method. Sampling error estimates were employed to assess the effects of the interpolated dataset. The second section for the D/F grades dataset during 960–1500 was generated by constructing best subset regression models using selected tree-ring chronologies in the United States through atmospheric teleconnection. The validation parameters of the calibration equations were also derived, including the adjusted R2, predicted R2, RE, and CE. This dataset provides critical support for investigating the characteristics and causes of hydroclimate extremes in EC at various spatiotemporal scales, as well as the relationship with climate modes, such as El Niño-Southern Oscillation, Pacific Decadal Oscillation, and East Asia Summer Monsoon. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate a machine learning model based on radiomic features derived from 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) images to preoperatively predict the pathological grade in patients with pancreatic ductal adenocarcinoma (PDAC). Methods: A total of 149 patients (83 men, 66 women, mean age 61 years old) with pathologically proven PDAC and a preoperative 18F-FDG PET/CT scan between May 2009 and January 2016 were included in this retrospective study. The cohort of patients was divided into two separate groups for the training (99 patients) and validation (50 patients) in chronological order. Radiomics features were extracted from PET/CT images using Pyradiomics implemented in Python, and the XGBoost algorithm was used to build a prediction model. Conventional PET parameters, including standardized uptake value, metabolic tumor volume, and total lesion glycolysis, were also measured. The quality of the proposed model was appraised by means of receiver operating characteristics (ROC) and areas under the ROC curve (AUC). Results: The prediction model based on a twelve-feature-combined radiomics signature could stratify PDAC patients into grade 1 and grade 2/3 groups with AUC of 0.994 in the training set and 0.921 in the validation set. Conclusion: The model developed is capable of predicting pathological differentiation grade of PDAC based on preoperative 18F-FDG PET/CT radiomics features. [ABSTRACT FROM AUTHOR]

Background: 99mTc-PYP scintigraphy provides differential diagnosis of ATTR cardiomyopathy (ATTR-CM) from light chain cardiac amyloidosis and other myocardial disorders without biopsy. This study was aimed to assess the diagnostic feasibility and the operator reproducibility of 99mTc-PYP quantitative SPECT. Method: Thirty-seven consecutive patients who underwent a 99mTc-PYP thorax planar scan followed by SPECT and CT scans to diagnose suspected ATTR-CM were enrolled. For the quantitative SPECT, phantom studies were initially performed to determine the image conversion factor (ICF) and partial volume correction (PVC) factor to recover 99mTc-PYP activity concentration in the myocardium for calculating the standardized uptake value (SUV) (unit: g/ml). SUVmax was compared among groups of ATTR-CM, AL cardiac amyloidosis, and other pathogens (others) and among categories of Perugini visual scores (grades 0–3). The intra- and inter-operator reproducibility of quantitative SPECT was verified, and the corresponded repeatability coefficient (RPC) was calculated. Results: The ICF was 79,327 Bq/ml to convert count rate in pixel to 99mTc activity concentration. PVC factor as a function of the measured activity concentration ratio in the myocardium and blood-pool was [y = 1.424 × (1 − exp(− 0.759 × x)) + 0.104]. SUVmax of ATTR-CM (7.50 ± 2.68) was significantly higher than those of AL (1.96 ± 0.35) and others (2.00 ± 0.74) (all p < 0.05). SUVmax of grade 3 (8.95 ± 1.89) and grade 2 (4.71 ± 0.23) were also significantly higher than those of grade 1 (1.92 ± 0.31) and grade 0 (1.59 ± 0.39) (all p < 0.05). Correlation coefficient (R2) of SUVmax reached 0.966 to 0.978 with only small systematic difference (intra = − 0.14; inter = − 0.23) between two repeated measurements. Intra- and inter-operator RPCs were 0.688 and 0.877. Conclusions: 99mTc-PYP quantitative SPECT integrated with adjustable PVC factors is feasible to quantitatively and objectively assess the burden of cardiac amyloidosis for diagnosis of ATTR-CM. [ABSTRACT FROM AUTHOR]

Reconstructed hydroclimatic spatial patterns from historical documents, the chronology of El Niño events since 1525, Meiyu (a unique rainy season dominated by the East Asian summer monsoon in eastern China) series since 1736, and a 1000-year control simulation using the Community Earth System Model were used to analyze the occurrence of anomalous summer precipitation patterns over eastern China with El Niño events. The results show that the frequency of the south-flood north-drought during 1525–2005 was significantly higher during El Niño episodes. Specifically, the occurrences of the triple pattern with floods in the Yangtze River Valley but droughts in its north and south (FYRDNS) as well as the dipole pattern with floods in the south but droughts in the north (FSDN) divided by the Yangtze River both increased in El Niño developing years, while the occurrence of FSDN increased in El Niño decaying years. Among 44 severe and extreme Meiyu events over the middle and lower reaches of the Yangtze River in 1736–2016, 75% of events occurred during El Niño episodes. Especially, 80% of extreme Meiyu events occurred in El Niño decaying years. The 1000-year control simulation captured well the reconstructed triple pattern of FYRDNS in developing years and the dipole pattern of FSDN in decaying years, with more noticeable precipitation anomalies for developing years of very strong and extremely strong El Niño events. These results implicated that the El Niño is likely an early signal for the occurrence of the south-flood north-drought over eastern China. [ABSTRACT FROM AUTHOR]

To synthesize zeolites in a safe and cost-saving manner is the first and the most important task for zeolite application in industry. In the present work, FeAPO-5 aluminophosphate molecular sieve with high iron content was ionothermally synthesized by microwave irradiation at ambient pressure using low dosage of eutectic mixture as the solvent. The influences of seed crystals and mechanochemical pretreatment on the synthesis of FeAPO-5 were investigated in detail. The resultant relatively pure FeAPO-5 molecular sieves were characterized by XRD, ICP-AES, SEM, N2 physisorption and UV-Vis diffuse reflectance spectrometer, and their catalytic performances were studied using phenol hydroxylation as a probe reaction. The XRD results revealed that pure FeAPO-5 can be readily obtained from mechanochemically pretreated reactants, regardless of whether or not the seed crystals were added. The ICP-AES measurements suggested that only by using specific seed crystals can pure FeAPO-5 molecular sieve with high iron content be synthesized. The SEM analysis implied that seed crystals may play a role of morphology-directing agent in these syntheses. The catalytic results demonstrated that longer pronounced induction period were only observed over those FeAPO-5 catalysts with sole framework iron species. The different catalytic activity among five selected catalysts was largely determined by their different densities of framework iron species, while the selectivity towards dihydroxybenzene was mainly controlled by the diffusion path length. Under given reaction conditions, FeAPO-5 catalyst with up to 6.79 wt% of iron content gave 42.0% dihydroxybenzene yield with a selectivity of 94.1%. [ABSTRACT FROM AUTHOR]

Copyright of Advances in Atmospheric Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Advances in Atmospheric Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Based on reconstructions of precipitation events from the rain and snowfall archives of the Qing Dynasty (1736–1911), the drought/flood index data mainly derived from Chinese local gazettes from 1736–2000, and the observational data gathered since 1951, the spatial patterns of monsoon rainbands are analyzed at different time scales. Findings indicate that monsoon rainfall in northern China and the middle-lower reaches of the Yangtze River have significant inter-annual (e.g., 5–7-yr and 2–4-yr) as well as inter-decadal (e.g., 20–30-yr and quasi-10-yr) fluctuation signals. The spatial patterns in these areas also show significant cycles, such as on a 60–80-yr time scale, a reversal phase predominates the entire period from 1736–2000; on a quasi-30-yr time scale, a consistent phase was prevalent from 1736 to 2000; and on a 20-yr time scale, the summer monsoon rains show different spatial patterns before and after 1870. [ABSTRACT FROM AUTHOR]

We review here proxy records of temperature and precipitation in China during the Holocene, especially the last two millennia. The quality of proxy data, methodology of reconstruction, and uncertainties in reconstruction were emphasized in comparing different temperature and precipitation reconstruction and clarifying temporal and spatial patterns of temperature and precipitation during the Holocene. The Holocene climate was generally warm and wet. The warmest period occurred in 9.6–6.2 cal ka BP, whereas a period of maximum monsoon precipitation started at about 11.0 cal ka BP and lasted until about 8.0–5.0 cal ka BP. There were a series of millennial-scale cold or dry events superimposed on the general trend of climate changes. During past two millennia, a warming trend in the 20th century was clearly detected, but the warming magnitude was smaller than the maximum level of the Medieval Warm Period and the Middle Holocene. Cold conditions occurred over the whole of China during the Little Ice Age (AD 1400–AD 1900), but the warming of the Medieval Warm Period (AD 900–AD 1300) was not distinct in China, especially west China. The spatial pattern of precipitation showed significant regional differences in China, especially east China. The modern warm period has lasted 20 years from 1987 to 2006. Bi-decadal oscillation in precipitation variability was apparent over China during the 20th century. Solar activity and volcanic eruptions both were major forcings governing the climate variability during the last millennium. [ABSTRACT FROM AUTHOR]