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Cell therapy is a promising strategy for the treatment of human diseases. While the first use of cells for therapeutic purposes can be traced to the 19th century, there has been a lack of general and reliable methods to study the biodistribution and associated pharmacokinetics of transplanted cells in various animal models for preclinical evaluation. Here, we present a new platform using albumin-conjugated fluorescent nanodiamonds (FNDs) as biocompatible and photostable labels for quantitative tracking of human placenta choriodecidual membrane-derived mesenchymal stem cells (pcMSCs) in miniature pigs by magnetic modulation. With this background-free detection technique and time-gated fluorescence imaging, we have been able to precisely determine the numbers as well as positions of the transplanted FND-labeled pcMSCs in organs and tissues of the miniature pigs after intravenous administration. The method is applicable to single-cell imaging and quantitative tracking of human stem/progenitor cells in rodents and other animal models as well.

Recent evidence has shown that relations between soil moisture and precipitation at spatial and temporal aspect are contrary to each other: afternoon precipitation tends to occur at times in which conditions are overall wet and heterogeneous in the morning, but preferentially over those patches that are relatively drier than the surroundings. This study expands the notion of soil moisture‐precipitation spatial coupling by analyzing the preferred precipitation location over a range of different soil moisture patterns. Using global observations of precipitation and observationally constrained evaporative stress estimates, we confirm that relatively drier patches have more chances of receiving rain, but the preference is weakened under wetter soil conditions. During extremely wet times, wet patches have more chances of receiving rain. Moreover, the preference of precipitation to occur on drier soils is stronger when soil moisture conditions are heterogeneous. Such results indicate that the positive feedback mechanism becomes more positive as soil wetness increases and the negative feedback mechanism becomes more negative as soils become drier and more heterogeneous. The strength of these two feedback mechanisms jointly affects preferential precipitation location. Counterintuitively, analysis from 1 day after‐event soil moisture pattern shows that negative soil moisture‐precipitation coupling may in turn further heterogenize soil moisture patterns, because dry patch gets extremely wet with no or less rain in surrounding. Although results here do not necessarily imply a causal relationship, this work contributes to enhancing our understanding of soil moisture‐precipitation spatial coupling and exposes the complex nuances of these land‐atmosphere interactions.

Pulmonary hypertension is a fatal disease, however reliable prognostic tools are lacking. Heart rhythm complexity analysis is derived from non-linear heart rate variability (HRV) analysis and has shown excellent performance in predicting clinical outcomes in several cardiovascular diseases. However, heart rhythm complexity has not previously been studied in pulmonary hypertension patients. We prospectively analyzed 57 patients with pulmonary hypertension (31 with pulmonary arterial hypertension and 26 with chronic thromboembolic pulmonary hypertension) and compared them to 57 age- and sex-matched control subjects. Heart rhythm complexity including detrended fluctuation analysis (DFA) and multiscale entropy (MSE) and linear HRV parameters were analyzed. The patients with pulmonary hypertension had significantly lower mean RR, SDRR, pNN 20 , VLF, LF, LF/HF ratio, DFAα1, MSE slope 5, scale 5, area 1–5 and area 6–20 compared to the controls. Receiver operating characteristic curve analysis showed that heart rhythm complexity parameters were better than traditional HRV parameters to predict pulmonary hypertension. Among all parameters, scale 5 had the greatest power to differentiate the pulmonary hypertension patients from controls (AUC: 0.845, P < 0.001). Furthermore, adding heart rhythm complexity parameters significantly improved the discriminatory power of the traditional HRV parameters in both net reclassification improvement and integrated discrimination improvement models. In conclusion, the patients with pulmonary hypertension had worse heart rhythm complexity. MSE parameters, especially scale 5, had excellent single discriminatory power to predict whether or not patients had pulmonary hypertension.

Due to the development of drug resistance, the outcome for the majority of patients with acute myeloid leukemia (acute myelogenous leukemia; AML) remains poor. To prevent drug resistance and increase the therapeutic efficacy of treating AML, the development of new combinatory drug therapies is necessary. Sonic hedgehog (Shh) is expressed in AML biopsies and is essential for the drug resistance of cancer stem cells of AML. AML patients are frequently infected by bacteria and exposed to lipopolysaccharide (LPS). LPS itself, its derivatives, and its downstream effectors, such as tumor necrosis factor-α (TNF-α) and interferons (IFNs), have been shown to provoke anti-tumor effects. The application of a Shh inhibitor against AML cells in the presence of LPS/TNF-α/IFNs has not been investigated. We found that the Shh inhibitor cyclopamine in combination with LPS treatment synergistically induced massive cell apoptosis in THP-1 and U937 cells. The cytotoxic effects of this combined drug treatment were confirmed in 5 additional AML cell lines, in primary AML cells, and in an AML mouse model. Replacing cyclopamine with another Shh inhibitor, Sant-1, had the same effect. LPS could be substituted by TNF-α or IFNs to induce AML cell death in combination with cyclopamine. Our results suggest a potential strategy for the development of new therapies employing Shh antagonists in the presence of LPS/TNF-α/IFNs for the treatment of AML patients.

When soil moisture content (SM) falls within a transitional regime between dry and wet, it controls evaporation rates, affecting atmospheric heat and humidity. Accordingly, different SM regimes correspond to different gears of land-atmosphere coupling, affecting climate. Determining patterns of SM regimes and their future changes is imperative. Global distributions of shifts between SM regimes from eight climate models are examined. Under increasing CO2, the range of SM extends into unprecedented coupling regimes in many locations. SM in many arid regions migrates from the transitional toward the dry regime, while an opposite migration appears in semiarid regions. Transitional regimes also emerge in currently humid areas of the tropics and high latitudes. These changes imply that a larger fraction of the world will evolve to experience more than one gear of land-atmosphere coupling, with the strongly coupled transitional regime growing the most. Furthermore, the locally predominant gear may change under global warming.

When soil moisture (SM) content falls within a transitional regime between dry and wet conditions, it controls evaporation, affecting atmospheric heat and humidity. Accordingly, different SM regimes correspond to different gears of land-atmosphere coupling, affecting climate. Determining patterns of SM regimes and their future evolution is imperative. Here, we examine global SM regime distributions from ten climate models. Under increasing CO2, the range of SM extends into unprecedented coupling regimes in many locations. Solely wet regime areas decline globally by 15.9%, while transitional regimes emerge in currently humid areas of the tropics and high latitudes. Many semiarid regions spend more days in the transitional regime and fewer in the dry regime. These imply that a larger fraction of the world will evolve to experience multiple gears of land-atmosphere coupling, with the strongly coupled transitional regime expanding the most. This could amplify future climate sensitivity to land-atmosphere feedbacks and land management.

Pulmonary hypertension (PH) is a fatal disease—even with state-of-the-art medical treatment. Non-invasive clinical tools for risk stratification are still lacking. The aim of this study was to investigate the clinical utility of heart rhythm complexity in risk stratification for PH patients. We prospectively enrolled 54 PH patients, including 20 high-risk patients (group A; defined as WHO functional class IV or class III with severely compromised hemodynamics), and 34 low-risk patients (group B). Both linear and non-linear heart rate variability (HRV) variables, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE), were analyzed. In linear and non-linear HRV analysis, low frequency and high frequency ratio, DFAα1, MSE slope 5, scale 5, and area 6–20 were significantly lower in group A. Among all HRV variables, MSE scale 5 (AUC: 0.758) had the best predictive power to discriminate the two groups. In multivariable analysis, MSE scale 5 (p = 0.010) was the only significantly predictor of severe PH in all HRV variables. In conclusion, the patients with severe PH had worse heart rhythm complexity. MSE parameters, especially scale 5, can help to identify high-risk PH patients.