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Abstract To tackle the clinical challenge of noninvasively assessing immunotherapy efficacy in patients, here we used positron emission tomography (PET) with 68Ga-grazytracer, which targets granzyme B, a crucial effector molecule secreted by activated CD8+ T cells. In this phase 1/2 clinical trial (NCT05000372) involving a diverse cohort of 24 patients with solid tumors and lymphomas who received immunotherapies, including immune checkpoint inhibitors (either alone or with chemotherapies) and chimeric antigen receptor-T cell therapy, we examined the in vivo behaviors of 68Ga-grazytracer. Primary endpoints were safety, biodistribution, granzyme B specificity, and the predictive utility of 68Ga-grazytracer, while secondary endpoint was the relationship between 68Ga-grazytracer uptake and tumor immune phenotype. 68Ga-grazytracer exhibited a safe profile and specifically targeted granzyme B in patients. 68Ga-grazytracer PET showed superior predictive value for short-term prognosis and progression-free survival than those of conventional assessment criteria, including RECIST 1.1 and PERCIST. Moreover, the uptake of 68Ga-grazytracer in tumors was significantly higher in those with a “non-desert” immune phenotype than those with an immune “desert” phenotype, thereby meeting the primary and secondary endpoints of this trial. Collectively, we successfully visualized CD8+ T cell effector function in humans using 68Ga-grazytracer PET, offering insights for enhancing immunotherapy assessment, patient stratification and treatment planning.

Abstract Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main body This selection of highlights provides commentary on 19 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals. Conclusion Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field in many aspects.

Active fault zones are critical pathways for the migration of deep fluids to the Earth’s surface, carrying gases such as He, Rn, and CO2 that provide evidence for the physical and chemical dynamics of the Earth’s interior. This review examines the geochemical characteristics of fault zone gases and their implications for understanding fault activity and seismic events. Fault zones with high activity levels exhibit significant gas release, and variations in soil and hot spring gas concentrations can serve as indicators of seismic activity. Changes in gas concentrations and isotopic ratios, particularly before and after earthquakes, reflect the dynamic interplay between deep-sourced and shallow-sourced fluids. Seismic-induced stress alterations enhance gas release along fault zones, leading to observable anomalies that can aid in earthquake monitoring and prediction. The study underscores the importance of isotope tracing in deciphering fluid sources, migration pathways, and the evolution of fault zones, providing valuable information for assessing tectonic activity and mitigating seismic risks.

This study focused on the chemical composition of the rivers in the middle and upper reaches of the Yarlung Tsangpo River system. Samples were collected in April 2015 to analyze spatiotemporal variation characteristics and determine weathering processes and CO2 consumption using principal component analysis (PCA) and a modified forward model. The TDS on the southern bank of the upper and middle reaches of the Yarlung Tsangpo basin was found to be higher than that on the northern bank because of the difference in stratigraphic structure. The results show that the chemical facies of the rivers all belonged to Ca-HCO3, and the rate of sulfuric acid-dominated chemical weathering was extremely high in the sub-watershed by TZ+⁎/HCO3−⁎. Four major reservoirs (precipitation, silicates, carbonates, and evaporites) produce ions. The results of the chemical budget show that their contribution rates were 7.80% vs. 5.09% (PCA vs. modified forward model, the same below): 21.8% vs. 24.7%, 42.80% vs. 50.22%, and 10.30% vs. 21.59%, respectively. The ionic components from carbonate weathering in the study area were dominant, which is the main reason why the calculated results of the carbonate weathering rate (CWR) were higher than the silicate weathering rate (SWR). The CWR reached its maximum value during the monsoon period, whereas the SWR showed the opposite trend. Moreover, CO2 sequestration by chemical weathering of rivers might be the main carbon sink in Tibet, which contributes to the realization of carbon neutrality in Tibet.

Abstract During the ongoing uplift and expansion of the southeastern margin of the Tibetan Plateau, the front edge of the Sichuan‐Yunnan rhombic block (SYB) has experienced intense tectonic activity and frequent seismicity. In this study, the fluid geochemistry in the primary active faults at the front edge of the SYB was investigated, with the aim of understanding the tectonic activity and intersection relationship between the Xiaojiang fault (XJF) and the Red River fault (RRF). Thermal spring water and gases exhibit a coupled spatial distribution relationship; relatively high ion concentrations and 3He/4He ratios (Rc/Ra ratios of 0.21 to 0.62Ra) are observed along the RRF, Qujiang fault (QJF), and Shiping‐Jianshui fault (SJF). Multidisciplinary research results have indicated that mantle‐derived intrusion has been detected in the crust beneath the QJF and SJF. The current tectonic activity in the front edge of the SYB remains intense, with compressive stresses shifting toward the western side of the XJF and accumulating on the QJF and SJF. This has led to the development of fractures, enhancing the water–rock interaction and deep‐derived gas degassing along the faults. The unmixing characteristics of fluids at the intersection area of these two faults suggest the absence of conduits for fluid migration between the faults. Owing to the lower gas 3He/4He ratios, lower shear strain rates, stable reservoir temperature field, and extremely low historical seismicity in the Indo‐Chinese block, it is speculated that the current movement of the XJF may not cut through the RRF and continue southward.

Abstract Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main Body This commentary of highlights has resulted in 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals. Conclusion Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field in various topics including new PET-labelling methods, FAPI-tracers and imaging, and radionuclide therapy being the scope of EJNMMI Radiopharmacy and Chemistry.

Abstract In the search for precursors to earthquakes, correlation has been found between geochemical characteristics of soil gases and seismic activity. In this paper we present evidence that seismic waves can trigger emission of soil radon (Rn) and carbon dioxide (CO2). An active experiment was performed in two fault zones in China, the Annighe fault in Sichuan province and the Xiadian fault in Heibei province. An active seismic source was used to generate seismic waves at 10 m depth in wells within bedrock. Rn and CO2 detectors were placed around the wells at a distance of ∼1 m for observing the effects of the seismic waves on the emission of the gases. The observations confirm that the seismic waves have a significant and direct effect on the concentration and flux of soil radon and carbon dioxide. When the seismic events were triggered, the observed concentrations of Rn and CO2 immediately increased and reached peak values within 5–50 min and 30–60 min, with corresponding increases of Rn and CO2 concentrations by 10.5%–238.7% and 3.1%–54.1%, respectively. The measured concentrations and flux of CO2 and Rn after the passage of the seismic waves showed strong correlation, confirming the suggestion that CO2 is the carrier gas for Rn. To the best of our knowledge this is the first direct, in‐situ measurement of gas emission caused by the passage of seismic waves and provides important constraints for better understanding of geochemical earthquake precursors.

Study region: Inner Tibetan Plateau (ITP) is the largest plateau in the world, with only four national basic stations covering an area of 5.76 × 105 km2. Study focus: Satellite precipitation products (SPPs) have widely been evaluated on a regional scale. However, a comprehensive quantitative evaluation of SPPs using multiple indices has not been reported. Here, 16 SPPs were quantitatively and comprehensively evaluated for precipitation occurrence and time series using an improved rank score (RS) method. The new observation network, which had more than the number of national stations, was applied for evaluating SPPs to increase the reliability of results. New hydrological insights for the region: Integrated Multi-satellite Retrievals for the Global Precipitation Measurement (IMERG)-Early and IMERG-Late runs showed the best overall performance, with an RS value of 0.91. The optimal SPPs varied according to the evaluation indices but mostly belonged to IMERG-Early, IMERG-Late, Multi-Source Weighted-Ensemble Precipitation (MSWEP), Global Satellite Mapping of Precipitation near-real-time (GSMaP-NRT), and Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks (PERSIANN) Dynamic Infrared Rain Rate near-real-time (PDIR-Now). Overall, most SPPs detected precipitation; however, the SPPs poorly measured the precipitation time series but adequately detected precipitation in the range of 10–25 mm in terms of the three indices of precipitation occurrence. The proposed improved RS method can be used to comprehensively evaluate other products and models.

Abstract Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Results This commentary of highlights has resulted in 23 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals and also a contribution in relation to MRI-agents is included. Conclusion Trends in (radio)chemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry.

Accurately identifying patients who respond to immunotherapy remains clinically challenging. A noninvasive method that can longitudinally capture information about immune cell function and assist in the early assessment of tumor responses is highly desirable for precision immunotherapy. Here, we show that PET imaging using a granzyme B–targeted radiotracer named 68Ga-grazytracer, could noninvasively and effectively predict tumor responses to immune checkpoint inhibitors and adoptive T cell transfer therapy in multiple tumor models. 68Ga-grazytracer was designed and selected from several radiotracers based on non-aldehyde peptidomimetics, and exhibited excellent in vivo metabolic stability and favorable targeting efficiency to granzyme B secreted by effector CD8+ T cells during immune responses. 68Ga-grazytracer permitted more sensitive discrimination of responders and nonresponders than did 18F-fluorodeoxyglucose, distinguishing between tumor pseudoprogression and true progression upon immune checkpoint blockade therapy in mouse models with varying immunogenicity. In a preliminary clinical trial with 5 patients, no adverse events were observed after 68Ga-grazytracer injection, and clinical responses in cancer patients undergoing immunotherapy were favorably correlated with 68Ga-grazytracer PET results. These results highlight the potential of 68Ga-grazytracer PET to enhance the clinical effectiveness of granzyme B secretion–related immunotherapies by supporting early response assessment and precise patient stratification in a noninvasive and longitudinal manner.

The Chinese inland basins (CIBs) are vulnerable to global warming and human activities due to low precipitation and high potential evaporation. Terrestrial water storage (TWS) is an important component of the hydrological cycle and essential for evaluating the water resource security of the CIBs. Although some studies have focused on water storage trends in sub-basins of the CIBs, only few studies have analyzed water storage trends in the CIBs as a whole. In this study, trends and magnitudes of precipitation, TWS, and actual evapotranspiration (AET) were detected by the rank-based non-parametric Mann–Kendall test and trend magnitude method. Based on the hydrological budget of the closed inland basin, the monthly series of AET were simulated and the main factors affecting TWS changes in the CIBs and each closed basin were identified. Results showed that both precipitation and AET significantly increased in the CIBs. Precipitation decreased from the northwest and southeast regions to the central region in the CIBs. Moreover, the annual TWS in the CIBs significantly decreased mainly due to the increased AET. Approximately 60% AET increase was attributed to increased irrigation diversions. At the basin scale, similar to the CIBs, changes in AET were the predominant factor influencing changes in TWS in the Tarim basin (TRB), Turpan basin (TPB), and Hexi Corridor basin (HCB). Qiangtang Plateau basin (QPB) Qaidam basin (QDB) the increase in precipitation contributed more than 60% increase in TWS glacier melting and irrigation diversion.

Satellite precipitation products (SPPs) have been widely evaluated at regional scales. However, there have been few quantitative comprehensive evaluations of SPPs using multiple indices. Ten high-resolution SPPs were quantitatively and comprehensively evaluated from precipitation occurrence and series indices using an improved rank score (RS) method in the data-scarce Qinghai–Tibetan Plateau (QTP). The new observation network, along with a number of national basic stations, was applied for SPP evaluation to obtain more reliable results. The results showed that the GPM and MSWEP showed the strongest overall performance, with an RS value of 0.75. CHIRPS and GPM had the strongest performance at measuring precipitation occurrence (RS = 0.92) and series (RS = 0.75), respectively. The optimal SPPs varied in evaluation indices, but also concentrated in the MSWEP, GPM, and CHIRPS. The bias of SPPs was markedly in the QTP, with relative error generally between −80% and 80%. In general, most SPPs showed the ability to detect precipitation occurrence. However, the SPPs showed relatively weak performance at measuring precipitation series. The mean Kling–Gupta efficiency of all stations was

Abstract Background Adoptive T cell transfer-based immunotherapy yields unsatisfactory results in the treatment of solid tumors, partially owing to limited tumor infiltration and the immunosuppressive microenvironment in solid tumors. Therefore, strategies for the noninvasive tracking of adoptive T cells are critical for monitoring tumor infiltration and for guiding the development of novel combination therapies. Methods We developed a radiolabeling method for cytotoxic T lymphocytes (CTLs) that comprises metabolically labeling the cell surface glycans with azidosugars and then covalently conjugating them with 64Cu-1,4,7-triazacyclononanetriacetic acid-dibenzo-cyclooctyne (64Cu-NOTA-DBCO) using bioorthogonal chemistry. 64Cu-labeled control-CTLs and ovalbumin-specific CTLs (OVA-CTLs) were tracked using positron emission tomography (PET) in B16-OVA tumor-bearing mice. We also investigated the effects of focal adhesion kinase (FAK) inhibition on the antitumor efficacy of OVA-CTLs using a poly(lactic-co-glycolic) acid (PLGA)-encapsulated nanodrug (PLGA-FAKi). Results CTLs can be stably radiolabeled with 64Cu with a minimal effect on cell viability. PET imaging of 64Cu-OVA-CTLs enables noninvasive mapping of their in vivo behavior. Moreover, 64Cu-OVA-CTLs PET imaging revealed that PLGA-FAKi induced a significant increase in OVA-CTL infiltration into tumors, suggesting the potential for a combined therapy comprising OVA-CTLs and PLGA-FAKi. Further combination therapy studies confirmed that the PLGA-FAKi nanodrug markedly improved the antitumor effects of adoptive OVA-CTLs transfer by multiple mechanisms. Conclusion These findings demonstrated that metabolic radiolabeling followed by PET imaging can be used to sensitively profile the early-stage migration and tumor-targeting efficiency of adoptive T cells in vivo. This strategy presents opportunities for predicting the efficacy of cell-based adoptive therapies and for guiding combination regimens. Graphic Abstract

Abstract Rapid progress has been made to identify and study the causative agent leading to coronavirus disease 2019 (COVID‐19) but many questions including who is most susceptible and what determines severity remain unanswered. Angiotensin‐converting enzyme 2 (ACE2) is a key factor in the infection process of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). In this study, molecularly specific positron emission tomography imaging agents for targeting ACE2 are first developed, and these novel agents are evaluated in vitro, in preclinical model systems, and in a first‐in‐human translational ACE2 imaging of healthy volunteers and a SARS‐CoV‐2 recovered patient (NCT04422457). ACE2 expression levels in different organs in live subjects are quantitatively delineated and observable differences are measured in the patient recovered from COVID‐19. Surprising sites of uptake in the breast, reproductive system and very low uptake in pulmonary tissues are reported. This novel method can add a unique tool to facilitate SARS‐CoV‐2 related research and improve understanding of this enigmatic disease. Molecular imaging provides quantitative annotation of ACE2, the SARS‐CoV‐2 entry receptor, to noninvasively monitor organs impacted by the COVID‐19.

Many carcinomas feature hypoxia, a condition has long been associated with tumor progression and poor prognosis, as well as resistance to chemoradiotherapy. Here, we report that the F-box protein JFK promotes mammary tumor initiation and progression in MMTV-PyMT murine model of spontaneous breast cancer. We find that JFK is inducible under hypoxic conditions, in which hypoxia-inducible factor HIF-1α binds to and transcriptionally activates JFK in breast cancer cells. Consistently, analysis of public clinical datasets reveals that the mRNA level of JFK is positively correlated with that of HIF-1α in breast cancer. We show that JFK deficiency leads to a decrease in HIF-1α-induced glycolysis in breast cancer and sensitizes hypoxic breast cancer cells to ionizing radiation and chemotherapeutic treatment. These results indicate that JFK is an important player in hypoxic response, supporting the pursuit of JFK as a potential therapeutic target for breast cancer intervention.

The deubiquitylase OTUD3 can function as a tumour-suppressor by stabilizing PTEN. Here, the authors show that OTUD3 also has an oncogenic role in lung cancer by stabilizing the glucose-regulated protein GRP78.

Rainfall is the main factor that induces debris flow. Satellite rainfall products provide a new source of data in terms of debris flow-triggering conditions to overcome the lack of rainfall data coverage from ground-based rainfall gauges in large-scale mountainous regions. In this study, the applicability of four satellite rainfall products (CMORPH, GPM, MSWEP, and PERSIANN) in the Hengduan Mountain region (HMR) was evaluated with reference to ground observation data from 2000 to 2020. The critical rainfall and rainfall thresholds under different rainfall patterns and warning levels that trigger debris flows were analyzed according to the empirical cumulative distribution function (ECDF) and cumulative probability. The results showed that CMORPH (comprehensive indicator score (CI = 0.72) and GPM (CI = 0.70) performed better in the simulation of daily rainfall sequence consistency and extreme rainfall conditions in the study area. CMORPH also had the highest reconstruction rate for correctly capturing rainfall events that triggered debris flows, with a value of 89%. Approximately half of the rainfall patterns that cause debris flows are antecedent-effective-rainfall-dominated. Both intraday-rainfall-dominated and intraday-antecedent-rainfall-balanced patterns were below 30%. There were evident differences in the critical rainfall for different rainfall patterns under the same warning level. By comparing the results of previous studies on rainfall thresholds, it is believed that the results of this study confirm the application of satellite rainfall products; in addition, the calculated rainfall thresholds can provide a reference for the early warning of debris flows in the HMR. In general, this work is of great significance to the prediction and early warning of debris flow hazards.

There are currently no effective therapies available for acute kidney injury (AKI). Here the authors generate molybdenum-based polyoxometalate nanoclusters and show that these have preferential renal uptake and can ameliorate AKI pathology in mice by scavenging reactive oxygen species.

The side effects of cancer drugs limit their utility. Here, the authors developed a method in which an inactive (prodrug) version of the cancer drug doxorubicin enters tumour cells and then gets activated inside the cells upon a trigger facilitated by enzyme-instructed supramolecular self-assembly.

Objectives Strategies to improve the responsiveness of programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint blockade therapy remain an essential topic in cancer immunotherapy. In this study, we developed a new radiolabeled nanobody-based imaging probe 99mTc-MY1523 targeting PD-L1 for the enhanced therapeutic efficacy of PD-L1 blockade immunotherapy by the guidance of 99mTc-MY1523 SPECT/CT imaging.Methods The binding affinity and specificity of nanobody MY1523 were measured in vitro. MY1523 was radiolabeled with 99mTc by a site-specific transpeptidation of Sortase-A, and the biodistribution and single photon emission CT (SPECT)/CT were performed in mice bearing different tumors. We used interferon-γ (IFN-γ) as an intervention means to establish animal models with different levels of PD-L1 expression, then investigated the ability of 99mTc-MY1523 SPECT/CT for the in vivo non-invasive measurement of PD-L1 expression in tumors. Finally, the PD-L1 blockade immunotherapies guided by 99mTc-MY1523 SPECT/CT were carried out in MC-38, A20, and 4T1 tumor-bearing mouse models, followed by the testing of tumor infiltration T cells.Results MY1523 exhibited a high binding affinity and specificity to PD-L1 and had no competitive binding with the therapeutic antibody. 99mTc-MY1523 was prepared with high specific activity and radiochemical purity. It was found that tumor PD-L1 expression was dynamically upregulated by IFN-γ intervention in MC-38, A20, and 4T1 tumor-bearing mouse models, as indicated by 99mTc-MY1523 SPECT/CT. The PD-L1 blockade therapy initiated during the therapeutic time window determined by 99mTc-MY1523 SPECT/CT imaging significantly enhanced the therapeutic efficacy in all animal models, while the tumor growth was effectively suppressed, and the survival time of mice was evidently prolonged. A correlation between dynamically upregulated PD-L1 expression and improved PD-L1 blockade therapy effectiveness was revealed, and the markedly increased infiltration of effector T cells into tumors was verified after the imaging-guided therapy.Conclusion Our results demonstrated that 99mTc-MY1523 SPECT/CT allowed a real-time, quantitative and dynamic mapping of PD-L1 expression in vivo, and the imaging-guided PD-L1 blockade immunotherapy significantly enhanced the therapeutic efficacy. This strategy merits translation into clinical practice for the better management of combination therapies with radiotherapy or chemotherapy.

The surface temperature and vegetation index (Ts/VI) method is a remote sensing-based quantitative approach. It is widely used for estimating the evapotranspiration, evaporative fraction, and surface soil moisture (SSM). However, this method can only be used in flat regions. In this study, we investigated the effect of altitude when using the Ts/VI method for estimating the SSM in heterogeneous regions. The results showed that the temperature vegetation dryness index (TVDI) method performed poorly at estimating the SSM in the source region of the Yangtze River; there was a weak correlation with the observed SSM, and R2 was only 0.167. However, the performance of the method improved considerably when the effects of both altitude and frozen soil were considered; the TVDI had a strong correlation with the observed SSM, and R2 improved to 0.617. In the study area, the effects of altitude on the TVDI values were greater than those of the frozen soil. In general, the Ts/VI method can obtain satisfactory results in mountainous regions if the effects of both the altitude and frozen soil are considered.

Evapotranspiration (ET) is essential for connecting ecosystems and directly affects the water consumption of forests, grasslands, and farmlands. Eight global remote sensing-based ET (RS_ET) datasets generated using satellite imagery and ground-based observations were comprehensively assessed using monthly ET time series simulated by the water balance (WB) method at the catchment scale in the Hengduan Mountain (HDM) region, including the Nu River, Lancang River, and Jinsha River basins. The complementary relationship (CR) model, which derives ET from meteorological data, was also evaluated against WB-based ET (WB_ET). In addition, WB_ET, RS_ET, and CR-based ET (CR_ET) data were used to investigate ET spatial and temporal variations at the catchment, grid, and site scale, respectively. Most RS_ET datasets accurately simulated monthly ET with an average index of agreement ranging from 0.71–0.91. The Operational Simplified Surface Energy Balance dataset outperformed other RS_ET datasets, with Nash–Sutcliffe efficiency coefficient (NSE) and Kling–Gupta efficiency values of 0.80 and 0.90, respectively. RS_ET datasets generally performed better in northern semiarid areas than in humid southern areas. The monthly ET simulation by the CR model was consistent with that of the WB_ET in the HDM region, with mean values of correlation coefficient (cc) and NSE at each site of 0.89 and 0.68, respectively. The model showed better performance in simulating monthly ET in the Lancang River Basin than in the Nu River and Lancang River basins, with mean cc and NSE of 0.92 and 0.83, respectively. Generally, annual ET trends were consistent at the catchment, grid, and site scale, as estimated by the WB method, RS_ET datasets, and CR model. It showed a significant decreasing trend in the northern semiarid region of the HDM while exhibiting an increasing trend in the humid southern region.

The sources of soil gases in the Tangshan fault zone, North China, were discussed, based on the soil gas compositions and isotopic ratios obtained by measurement in the field and sample analysis in the laboratory. Soil gas compositions and isotopic ratios indicate that air (A) end-member, limestone (L) end-member, and sediment (S) end-member are the major end-member components contributing to the soil gas in our study area, with fractional contributions in the range of 2-15 vol.%, 23-36 vol.%, and 62-65 vol.%, respectively, to CO2 from the gas wells. According to the relationship among the 3He/4He, average CO2 concentration, and He concentration of soil gas, the deepest depth the fault cut downward and the most developed fractures in the segment where the Heibeiligong (HBLG) well located were inferred, and the shallower depth the fault cut downward and the more developed fractures in the fault segments where the Weifengshan (WFS), Siwangzhuang (SWZ), Tianjingyice (TJYC), and Douhetai (DHT) wells located were inferred. Significant variations in CO2 concentration were observed in soil gases sampled in DHT, HBLG, and WFS soil gas wells in concomitance with a local seismic sequence by 2018 confirming for the first time a possible source of carbon dioxide generated in underlying limestones.

Snowmelt water is essential to the water resources management over the Three-River Headwater Region (TRHR), where hydrological processes are influenced by snowmelt runoff and sensitive to climate change. The objectives of this study were to analyse the contribution of snowmelt water to the total streamflow (fQ,snow) in the TRHR by applying a snowmelt tracking algorithm and Variable Infiltration Capacity (VIC) model. The ratio of snowfall to precipitation, and the variation of the April 1 snow water equivalent (SWE) associated with fQ,snow, were identified to analyse the role of snowpack in the hydrological cycle. Prior to the simulation, the VIC model was validated based on the observed streamflow data to recognize its adequacy in the region. In order to improve the VIC model in snow hydrology simulation, Advanced Scanning Microwave Radiometer E (ASMR-E) SWE product data was used to compare with VIC output SWE to adjust the snow parameters. From 1971 to 2007, the averaged fQ,snow was 19.9% with a significant decreasing trend over entire TRHR (p < 0.05).The influence factor resulted in the rate of change in fQ,snow which were different for each sub-basin TRHR. The decreasing rate of fQ,snow was highest of 0.24%/year for S_Lantsang, which should be due to the increasing streamflow and the decreasing snowmelt water. For the S_Yangtze, the increasing streamflow contributed more than the stable change of snowmelt water to the decreasing fQ,snow with a rate of 0.1%/year. The April 1 SWE with the minimum value appearing after 2000 and the decreased ratio of snowfall to precipitation during the study period, suggested the snow solid water resource over the TRHR was shrinking. Our results imply that the role of snow in the snow-hydrological regime is weakening in the TRHR in terms of water supplement and runoff regulation due to the decreased fQ,snow and snowfall.

Understanding the geochemistry of natural waters is helpful for grasping how the water environment responds to climate and environment changes. The basin of the Yarlung Tsangpo River, the most important river in the Tibetan Plateau, was selected as the study area. Based on our field sampling data and the previously published data of major ions in the river, we distinguished the different sources of the riverine ionic budget. Subsequently, the changes in their contributions were determined over the past four decades. The results indicate that carbonate weathering was the main source of the dissolved ions in the Yarlung Tsangpo River. Consequently, an increasing trend was found in the Ca2+, Mg2+, and HCO3− concentrations in the river water. Conversely, silicate weathering, the secondary source of ions, declined after 2000. More notably, the sulfide oxidation process was considerably enhanced over the study period, which resulted in a two-fold increase in SO42− in the riverine water.

Based on the precipitation δ18O values from the datasets of the Global Network of Isotopes in Precipitation (GNIP), the National Centers for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) Reanalysis data, and previous researches, we explored the temporal and spatial variations of precipitation δ18O in a typical monsoon climate zone, the Pearl River basin (PRB), and adjacent regions. The results showed that the temporal variations of precipitation δ18O for stations should be correlated with water vapor sources, the distance of water vapor transport, the changes in location, and intensity of the intertropical convergence zone (ITCZ) rather than “amount effect.” Meanwhile, local meteorological and geographical factors showed close correlations with mean weighted precipitation δ18O values, suggesting that “altitude effect” and local meteorological conditions were significant for the spatial variations of precipitation δ18O. Moreover, we established linear regression models for estimating the mean weighted precipitation δ18O values, which could better estimate variations in precipitation δ18O than the Bowen and Wilkinson model in the PRB and adjacent regions.

Two statistical downscaling models, the non-homogeneous hidden Markov model (NHMM) and the Statistical Down–Scaling Model (SDSM) were used to generate future scenarios of both mean and extremes in the Tarim River basin,which were based on nine combined scenarios including three general circulation models (GCMs) (CSIRO30, ECHAM5,and GFDL21) predictor sets and three special report on emission scenarios (SRES) (SRES A1B, SRES A2, and SRESB1). Local climate change scenarios generated from statistical downscaling models was also compared with thatprojected by raw GCMs outputs. The results showed that the magnitude of changes for annual precipitation projected byraw GCMs outputs was greater than that generated by using statistical downscaling model. The difference betweenchanges of annual maximum air temperature projected by statistical downscaling model and raw GCMs outputs was notas significant as that for annual precipitation. In total, the magnitude of these increasing trends projected by bothstatistical downscaling models and raw GCMs outputs was the greatest under SRES A2 scenario and the smallest underB1 scenario, with A1B scenario in–between. Generally, the magnitude of these increasing trends in the period of 2081 to2100 was greater than that in the period of 2046 to 2065. The magnitude of standard deviation changes for dailyprecipitation projected by raw GCMs outputs was greater than that generated by statistical downscaling model undermost of combined scenarios in both periods.

CryoSat-2 altimetry has become a valuable tool for monitoring the water level of lakes. In this study, a concentrated probability density function (PDF) method was proposed for preprocessing CryoSat-2 Geophysical Data Record (GDR) data. CryoSat-2 altimetry water levels were preprocessed and evaluated by in situ gauge data from 12 lakes in China. Results showed that the accuracy of the raw GDR data was limited due to outliers in most of the along-track segments. The outliers were generally significantly lower than the in situ values by several meters, and some by more than 30 m. Outlier detection, therefore, improves upon the accuracy of CryoSat-2 measurements. The concentrated PDF method was able to greatly improve the accuracy of CryoSat-2 measurements. The preprocessed CryoSat-2 measurements were able to observe lake levels with a high accuracy at nine of the twelve lakes, with an absolute mean difference of 0.09 m, an absolute standard deviation difference of 0.04 m, a mean root mean square error of 0.27 m, and a mean correlation coefficient of 0.84. Overall, the accuracy of CryoSat-2-derived lake levels was validated in China. In addition, the accuracy of Database for Hydrological Time Series of Inland Waters (DAHITI) and HYDROWEB water level products was also validated by in situ gauge data.

In this study, we assessed the performance of 34 Coupled Model Intercomparison Project Phase 5 (CMIP5) general climate models (GCMs) for simulating the observed temperature over the Lower Mekong Basin (LMB) in 1961⁻2004. An improved score-based method was used to rank the performance of the GCMs over the LMB. Two methods of multi-model ensemble (MME), sub-ensemble from the top 25% ranked GCMs and full ensemble from the entire GCMs, were calculated using arithmetic mean (AM) method and downscaled using the Delta method to project future temperature change during two future time periods, the near future (2006⁻2049) and the far future (2050⁻2093), under representative concentration pathways (RCP2.6, RCP4.5, and RCP8.5 scenarios) over the LMB. The improved score-based method combining multiple criteria showed a robust assessment of the GCMs performance over the LMB, which can provide good information for projecting future temperature change. The results showed a significant increase in temperature over the LMB under the two ensembles. However, there were differences in the magnitudes of the future temperature increase between the two ensemble methods, with a higher mean annual temperature increase from full ensemble and sub-ensemble at 1.26 °C (1.09 °C), 1.90 °C (1.70 °C), and 2.97 °C (2.78 °C) during 2050⁻2093 under the RCP2.6, RCP4.5, and RCP8.5 scenarios compared to the values at 0.93 °C (0.87 °C), 0.99 °C (0.95 °C), and 1.09 °C (1.06 °C) during 2006⁻2049, respectively, relative to the reference time period of 1961⁻2004. In the future (2006⁻2093), the temperature is likely to increase at 0.06 °C, 0.18 °C, and 0.39 °C decade−1 under the RCP2.6, RCP4.5, and RCP8.5 scenarios by the sub-ensemble, while a higher temperature increase at 0.08 °C, 0.20 °C, and 0.42 °C was found by the full ensemble over the LMB, relative to the reference time period of 1961⁻2004. On the whole, the higher warming mainly occurred in the northern and central areas over the LMB, while the lower warming mainly occurred in the southeast and the southwest, especially under the RCP4.5 and RCP8.5 scenarios, with the warming increased with increasing RCP for both ensembles. Moreover, in order to reduce the uncertainty of temperature projection in further studies in the LMB, multiple methods of GCMs ensemble should be considered and compared.

This study assessed the performances of 34 Coupled Model Intercomparison Project Phase 5 (CMIP5) general circulation models (GCMs) in reproducing observed precipitation over the Lower Mekong Basin (LMB). Observations from gauge-based data of the Asian Precipitation-Highly Resolved Observational Data Integration Towards Evaluation of Water Resources (APHRODITE) precipitation data were obtained from 1975 to 2004. An improved score-based method was used to rank the performance of the GCMs in reproducing the observed precipitation over the LMB. The results revealed that most GCMs effectively reproduced precipitation patterns for the mean annual cycle, but they generally overestimated the observed precipitation. The GCMs showed good ability in reproducing the time series characteristics of precipitation for the annual period compared to those for the wet and dry seasons. Meanwhile, the GCMs obviously reproduced the spatial characteristics of precipitation for the dry season better than those for annual time and the wet season. More than 50% of the GCMs failed to reproduce the positive trend of the observed precipitation for the wet season and the dry season (approximately 52.9% and 64.7%, respectively), and approximately 44.1% of the GCMs failed to reproduce positive trend for annual time over the LMB. Furthermore, it was also revealed that there existed different robust criteria for assessing the GCMs’ performances at a seasonal scale, and using multiple criteria was superior to a single criterion in assessing the GCMs’ performances. Overall, the better-performed GCMs were obtained, which can provide useful information for future precipitation projection and policy-making over the LMB.

Targeted radionuclide therapy, which is based on the selective delivery of a sufficient radiation dose to tumors without significantly affecting normal tissues, is a promising therapeutic approach for the treatment of a wide variety of malignancies. Integrins, a family of cell adhesion molecules, play key roles during tumor angiogenesis and metastasis. Among all the integrins, αvβ3 seems to be the most important in the process of tumor angiogenesis. Integrin αvβ3 is highly expressed on activated endothelial cells, new-born vessels as well as some tumor cells, but is not present in resting endothelial cells and most normal organ systems, making it a suitable target for anti-tumor therapy. In this review, we summarize the current development and applications of antibody-, peptide-, and other ligand-based integrin targeted radiotherapeutics for tumor radiation therapy.

There is a critical need to develop diagnostic procedures enabling early detection of tumors while at a curable stage. Technetium 99m ( 99m Tc)-labeled VQ peptide ( 99m Tc-HYNIC-VQ) identified through screening phage display peptide libraries against fresh human colonic adenomas was prepared and evaluated for tumor detection. 99m Tc-HYNIC-VQ was prepared by a non-SnCl 2 method with more than 99% radiochemical purity. The biodistribution in the HT-29 tumor model showed that although the absolute tumor uptake values were relatively low (0.60 ± 0.09, 0.41 ± 0.09, 0.36 ± 0.18, and 0.19 ± 0.08 %ID/g at 0.5, 1, 2, and 4 hours postinjection, respectively), the tumor uptake was higher than that of any of the other organs except for the kidneys at any time point examined, which led to the high tumor to nontarget ratios. The tumors and inflammation were clearly visualized with high contrast. Although the mechanism of accumulation of radiolabeled VQ peptide in tumors and inflammation needs to be further investigated, 99m Tc-HYNIC-VQ is a promising imaging agent for the early detection of tumors or premalignancies, at least for screening patients with a high risk of developing cancers.

The purpose of this study was to noninvasively monitor the therapeutic efficacy of cyclophosphamide (CTX) in a mouse model by dual-modality molecular imaging: positron emission tomography (PET) and bioluminescence imaging (BLI). Firefly luciferase (fLuc) transfected HCC-LM3-fLuc human hepatocellular carcinoma cells were injected subcutaneously into BALB/c nude mice to establish the experimental tumor model. Two groups of HCC-LM3-fLuc tumor-bearing mice ( n = 7 per group) were treated with saline or CTX (100 mg/kg on days 0, 2, 5, and 7). BLI and 18 F-fluorodeoxyglucose ( 18 F-FDG) PET scans were done to evaluate the treatment efficacy. CTX induced a 25.25 ± 13.13% and 35.91 ± 25.85% tumor growth inhibition rate on days 9 and 12 posttreatment, respectively, as determined by BLI. A good linear correlation was found between the tumor sizes measured by caliper and the BLI signals determined by optical imaging ( R 2 = .9216). 18 F-FDG imaging revealed a significant uptake reduction in the tumors of the CTX-treated group compared to that in the saline control group (5.30 ± 1.97 vs 3.00 ± 2.11% ID/g) on day 16 after CTX treatment. Dual-modality molecular imaging using BLI and small-animal PET can play important roles in the process of chemotherapy and will provide noninvasive and reliable monitoring of the therapeutic response.

Integrin α v β 3 plays great roles in tumor angiogenesis, invasion, and metastasis. We report here the noninvasive visualization of tumor integrin α v β 3 expression by using near-infrared fluorescence (NIRF) imaging of an IRDye800-labeled new cyclic RGD (arginine-glycine-aspartic acid) dimer with tetra(ethylene glycol) (PEG 4 ) linkers (ie, E[PEG 4 -c(RGDfK)] 2 , PEG 4 = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) in a U87MG tumor model. Fluorescent dye–labeled E[PEG 4 -c(RGDfK)] 2 were subjected to in vitro cell staining, in vivo NIRF imaging, ex vivo NIRF imaging, and histologic studies. The in vitro and in vivo characterization of dye-labeled E[PEG 4 -c(RGDfK)] 2 were compared with dye-labeled RGD dimer without PEG 4 linkers (namely, E[c(RGDfK)] 2 ). Both Cy5.5-E[PEG 4 -c(RGDfK)] 2 and Cy5.5-E[c(RGDfK)] 2 exhibited integrin α v β 3 binding specificity in a cell-staining experiment. In vivo NIRF imaging showed higher tumor accumulation and tumor to background contrast of IRDye800-E[PEG 4 -c(RGDfK)] 2 over IRDye800-E[c(RGDfK)] 2. The tumor integrin α v β 3 specificity of IRDye800-E[PEG 4 -c(RGDfK)] 2 was confirmed by successful inhibition of tumor uptake in the presence of an excess dose of c(RGDfK). Histologic examination revealed both tumor vasculature and tumor cell integrin α v β 3 binding of IRDye800-E[PEG 4 -c(RGDfK)] 2 in vivo. In summary, NIRF imaging with IRDye800-E[PEG 4 -c(RGDfK)] 2 offers an easy, fast, and low-cost way to detect and semiquantify tumor integrin α v β 3 expression in living subjects.

Large earthquakes can cause both casualties and economic losses, but they also provide invaluable opportunities for earthquake scientific research. Geofluids, due to their wide distribution, sensitive response to underground conditions, and ease of observation, are widely applied in field investigations after earthquakes. Analyzing the origin of fluids, energy transfer processes, temperature/pressure conditions, and the spatial-temporal evolution of geofluids can provide valuable information concerning the mechanism of earthquake precursor anomalies, short-term prediction methods, identification of the seismogenic faults, determination of earthquake risk, and the environmental impact of post-earthquake fluids. This article details post-earthquake scientific expeditions and research on fluid geochemistry in China and abroad, aimed at providing ideas and guidance for future scientific expedition work and geochemistry-related earthquake studies. [ABSTRACT FROM AUTHOR]