Second-line therapy for patients with steroid-refractory aGVHD: systematic review and meta-analysis of randomized controlled trials

ObjectiveSteroids-refractory (SR) acute graft-versus-host disease (aGVHD) is a life-threatening condition in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the optimal second-line therapy still has not been established. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of different second-line therapy regimens.MethodsLiterature search in MEDLINE, Embase, Cochrane Library and China Biology Medicine databases were performed to retrieve RCTs comparing the efficacy and safety of different therapy regimens for patients with SR aGVHD. Meta-analysis was conducted with Review Manager version 5.3. The primary outcome is the overall response rate (ORR) at day 28. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated with the Mantel-Haenszel method.ResultsEight eligible RCTs were included, involving 1127 patients with SR aGVHD and a broad range of second-line therapy regimens. Meta-analysis of 3 trials investigating the effects of adding mesenchymal stroma cells (MSCs) to other second-line therapy regimens suggested that the addition of MSCs is associated with significantly improvement in ORR at day 28 (RR = 1.15, 95% CI = 1.01–1.32, P = 0.04), especially in patients with severe (grade III–IV or grade C–D) aGVHD (RR = 1.26, 95% CI = 1.04–1.52, P = 0.02) and patients with multiorgan involved (RR = 1.27, 95% CI = 1.05–1.55, P = 0.01). No significant difference was observed betwwen the MSCs group and control group in consideration of overall survival and serious adverse events. Treatment outcomes of the other trials were comprehensively reviewed, ruxolitinib showed significantly higher ORR and complete response rate at day 28, higher durable overall response at day 56 and longer failure-free survival in comparison with other regimens; inolimomab shows similar 1-year therapy success rate but superior long-term overall survial in comparison with anti-thymocyte globulin, other comparisons did not show significant differences in efficacy.ConclusionsAdding MSCs to other second-line therapy regimens is associated with significantly improved ORR, ruxolitinib showed significantly better efficacy outcomes in comparison with other regimens in patients with SR aGVHD. Further well-designed RCTs and integrated studies are required to determine the optimal treatment.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022342487

Impacts of climate change and fruit tree expansion on key hydrological components at different spatial scales

Assessing how fruit tree expansion and climate variability affect hydrological components (e.g., water yield, surface runoff, underground runoff, soil water, evapotranspiration, and infiltration) at different spatial scales is crucial for the management and protection of watersheds, ecosystems, and engineering design. The Jiujushui watershed (259.32 km2), which experienced drastic forest changes over the past decades, was selected to explore the response mechanisms of hydrological components to fruit tree expansion and climate variability at different spatial scales (whole basin and subbasin scale). Specifically, we set up two change scenarios (average temperature increase of 0.5°C and fruit tree area expansion of 18.97%) in the SWAT model by analyzing historical data (1961∼2011). Results showed that climate change reduced water yield, surface runoff, and underground runoff by 6.75, 0.37, and 5.91 mm, respectively. By contrast, the expansion of fruit trees increased surface runoff and water yield by 2.81 and 4.10 mm, respectively, but decreased underground runoff by 1 mm. Interestingly, the sub-basins showed different intensities and directions of response under climate change and fruit tree expansion scenarios. However, the downstream response was overall more robust than the upstream response. These results suggest that there may be significant differences in the hydrological effects of climate change and fruit tree expansion at different spatial scales, thus any land disturbance measures should be carefully considered

Rapid and Unconditional Parametric Reset Protocol for Tunable Superconducting Qubits

Qubit initialization is a critical task in quantum computation and communication. Extensive efforts have been made to achieve this with high speed, efficiency and scalability. However, previous approaches have either been measurement-based and required fast feedback, suffered from crosstalk or required sophisticated calibration. Here, we report a fast and high-fidelity reset scheme, avoiding the issues above without any additional chip architecture. By modulating the flux through a transmon qubit, we realize a swap between the qubit and its readout resonator that suppresses the excited state population to 0.08% $\pm$ 0.08% within 34 ns (284 ns if photon depletion of the resonator is required). Furthermore, our approach (i) can achieve effective second excited state depletion, (ii) has negligible effects on neighbouring qubits, and (iii) offers a way to entangle the qubit with an itinerant single photon, useful in quantum communication applications.Comment: 38 pages, 15 figure

Mechanism of FKBP10 promoting proliferation and migration of gastric cancer cells

Objective To investigate the regulative role of FKBP10 in the progression of gastric cancer and the underlying mechanism. Methods Bioinformatics analysis was applied to detect the expression of FKBP10 in gastric cancer samples and normal samples, as well as analyze its relationship with prognosis. qRT-PCR and Western blotting were employed to measure its expression at mRNA and protein levels in gastric cancer cell lines BGC823, MGC803, SGC7901, MKN45 and AGS and human gastric epithelial cell line GES. Then colony formation and transwell assay were conducted to detect the effect of its down-regulation on the proliferation and migration of the cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to reveal the FKBP10 involved signaling pathways, which was verified by Western blotting. Results FKBP10 was up-regulated in gastric cancer cell lines than the GES cells. Knockdown of FKBP10 by siRNA restricted the proliferative and migrative abilities of gastric cancer cells. KEGG analysis indicated that FKBP10 may be involved in the process of epithelial-mesenchymal transition (EMT) and TGF-β played important role in the process. Western blotting showed that down-regulation of FKBP10 resulted in increased expression of epithelial related biomarkers while decreased expression of mesenchymal related biomarkers, then the expression of p-SMAD2/3 were reduced simultaneously. Conclusion FKBP10 promotes the proliferation and migration of gastric cancer via regulating EMT and TGF-β/SMAD signaling pathway

The essential role of Mbd5 in the regulation of somatic growth and glucose homeostasis in mice.

Methyl-CpG binding domain protein 5 (MBD5) belongs to the MBD family proteins, which play central roles in transcriptional regulation and development. The significance of MBD5 function is highlighted by recent studies implicating it as a candidate gene involved in human 2q23.1 microdeletion syndrome. To investigate the physiological role of Mbd5, we generated knockout mice. The Mbd5-deficient mice showed growth retardation, wasting and pre-weaning lethality. The observed growth retardation was associated with the impairment of GH/IGF-1 axis in Mbd5-null pups. Conditional knockout of Mbd5 in the brain resulted in the similar phenotypes as whole body deletion, indicating that Mbd5 functions in the nervous system to regulate postnatal growth. Moreover, the mutant mice also displayed enhanced glucose tolerance and elevated insulin sensitivity as a result of increased insulin signaling, ultimately resulting in disturbed glucose homeostasis and hypoglycemia. These results indicate Mbd5 as an essential factor for mouse postnatal growth and maintenance of glucose homeostasis

Spatial Pattern and Temporal Stability of Root-Zone Soil Moisture during Growing Season on a Larch Plantation Hillslope in Northwest China

Soil moisture plays a decisive role for tree growth and forest ecosystems services supply in dryland regions. Hence, it is necessary to clarify the spatio-temporal variation of soil moisture under field conditions. This study selected a hillslope in the Liupan Mountains covered by the plantation of Larix principis-rupprechtii Mayr (larch), a main afforestation tree species in north and northwest China. The volumetric soil moisture (VSM) in root zone layers was monitored with a time interval of about 15 days during the growing season (from May to October) in 2016 at 48 points on this hillslope. The aim was to evaluate the spatial pattern and temporal stability of soil moisture at slope scale. The results showed a moderate spatial variability of VSM in each soil layer, with the variation coefficients range of 17.12–22.63%. The spatial variability of VSM showed a dependence on the soil wetness and a threshold effect, it increased with rising VSM until the VSM reached a threshold of about 15%, but thereafter decreased. The mean relative difference (MRD) among the 48 points ranged from −30.56% to 27.20%, −29.89% to 39.58%, and −28.13% to 33.71% for the soil layers of 0–20, 20–40, and 40–60 cm, respectively. The associated standard deviation (SDRD) (and range) was 11.38% (5.20–26.06%), 8.28% (4.64–15.63%), and 6.51% (2.00–14.16%) for the soil layers of 0–20, 20–40, and 40–60 cm, respectively. The high Spearman’s rank coefficients (p < 0.05) among the measuring dates at each soil layer indicated that the spatial distribution of VSM in the root zone had strong temporal stability. The decrease of Spearman’ rank correlation coefficient and mean SDRD with rising soil depth indicated an increasing temporal stability of VSM with rising soil depth. The mean VSM of the three soil layers on the entire hillslope can be estimated by the direct method (using representative points determined by the index of temporal stability (ITS)) successfully, and these representative points determined by ITS were mainly located at the points with a ratio of field capacity to leaf area index (LAI) close to the slope mean. Moreover, the mean VSM of the three soil layers on the entire hillslope can also be estimated by indirect method (using the time-stable points determined by mean absolute bias error (MABE) and considering the offset between slope mean VSM and observed VSM at time-stable points), and the prediction accuracy of the indirect method was better than the direct method. Significant correlation between MRD and soil bulk density, field capacity, capillary porosity, and LAI were observed for all soil layers, indicating that both the water-retention ability in root zone soil (expressed mainly by field capacity) and water-consumption ability of trees (expressed mainly by canopy LAI) are the main factors controlling the spatial pattern of root-zone VSM on the larch plantation hillslope studied

Intra-Annual Variation of Stem Radius of Larix principis-rupprechtii and Its Response to Environmental Factors in Liupan Mountains of Northwest China

Fine-resolution studies on the stem radius variation at short timescale can provide useful information about the tree growth process and the major environmental variables that trigger and drive stem radius variation. This study investigated the stem radius variation of Larix principis-rupprechtii Mayr growing in the semi-humid Liupan Mountains of Northwest China at daily and seasonal scales using high-resolution automatic band dendrometers from May to October in 2015. The results showed that the stem radius variation of Larix principis-rupprechtii has a clear diurnal pattern which can be divided into contraction, recovery, and increment phases; and also a seasonal pattern which can be divided into three stages: (1) the rapid growth stage in spring (stage 1) with the radius increment of 94.0% of the total in the entire growing period; (2) the persistent shrinkage stage in the dry summer (stage 2) with a negative diurnal radius increment for most days, and a significantly larger amplitude of stem contraction and recovery than other stages; (3) the minimal growth stage in autumn (stage 3), mainly caused by the lowering temperature and leaf area. The amplitude of stem contraction was significantly correlated with air temperature (both the mean and highest value) in all three stages: vapor pressure deficit (VPD) in stage 1; relative humidity (RH), VPD and soil moisture (Ms) in stage 2; and soil temperature (Ts) in stage 3. This indicates that the stem radius contraction was mainly controlled by the factors influencing tree transpiration rate in spring and autumn stages, but jointly controlled by the factors influencing both the tree transpiration rate and the soil moisture availability in the dry summer stage. The factors controlling the stem radius recovery was similar to the stem contraction. The amplitude of stem increment was significantly correlated with the rainfall amount and air temperature (both the mean and highest value) in stage 1 and 3, Ms in stage 2, and the lowest air temperature and Ts in stage 3. This indicates that temperature and precipitation were the key factors controlling the stem radius increment in the spring and autumn stages, and soil moisture was the main factor limiting the stem radius increment in the dry summer stage at the study site with semi-humid climate in Northwest China

Enhancing Role of Guiding Signs Setting in Metro Stations with Incorporation of Microscopic Behavior of Pedestrians

In the metro operation environment, guiding signs provide direction and route conversion instructions to pedestrians. In metro stations with massive passenger flow, the rationality of sign setting would exert distinct effects on the efficiency of passenger flow. Currently, most studies on guiding signs focus on architecture, aesthetics and simulation. However, perspectives from humanization of pedestrian guidance signs such as pedestrian behavior needs and pedestrian cognition were seldom proposed. In this paper, the microscopic behavior characteristics data of pedestrians at different positions in typical metro stations were collected through pedestrian tracking experiments. After analyzing the characteristics of pedestrians’ microscopic behavior in metro stations, otherness of walking speed was found out among pedestrians in different types of passageways. The walking speed of pedestrians in closed-type passageways is higher than other types. Moreover, pedestrian speed at the stairs adjacent to the platform is higher than that at the stairs not adjacent to the platform. With the increase of crowd density, the change of walking speed of pedestrians can be represented by a unimodal curve. Finally, the key points of optimal setting of guiding signs in different regions and different periods were obtained according to the result analysis of the experiment. The research results of this paper can provide theoretical support and technical guidance for the optimal establishment of pedestrian guiding signs in metro stations with massive passenger flow