Mortality from hepatitis B virus (HBV)–related acute‐on‐chronic liver failure (ACLF) is high due to limited treatment options. Preclinical and clinical investigations have proved that treatment with ...mesenchymal stromal cells (MSCs) is beneficial for recovery from liver injury. We hypothesized that the outcome of HBV‐related ACLF would be improved by MSC treatment. From 2010 to 2013, 110 patients with HBV‐related ACLF were enrolled in this open‐label, nonblinded randomized controlled study. The control group (n = 54) was treated with standard medical therapy (SMT) only. The experimental group (n = 56) was infused weekly for 4 weeks with 1.0 to 10 × 105 cells/kg allogeneic bone marrow–derived MSCs and then followed for 24 weeks. The cumulated survival rate of the MSC group was 73.2% (95% confidence interval 61.6%‐84.8%) versus 55.6% (95% confidence interval 42.3%‐68.9%) for the SMT group (P = 0.03). There were no infusion‐related side effects, but fever was more frequent in MSC compared to SMT patients during weeks 5‐24 of follow‐up. No carcinoma occurred in any trial patient in either group. Compared with the control group, allogeneic bone marrow–derived MSC treatment markedly improved clinical laboratory measurements, including serum total bilirubin and Model for End‐Stage Liver Disease scores. The incidence of severe infection in the MSC group was much lower than that in the SMT group (16.1% versus 33.3%, P = 0.04). Mortality from multiple organ failure and severe infection was higher in the SMT group than in the MSC group (37.0% versus 17.9%, P = 0.02). Conclusion: Peripheral infusion of allogeneic bone marrow–derived MSCs is safe and convenient for patients with HBV‐related ACLF and significantly increases the 24‐week survival rate by improving liver function and decreasing the incidence of severe infections. (Hepatology 2017;66:209–219).
The laurel family within the Magnoliids has attracted attentions owing to its scents, variable inflorescences, and controversial phylogenetic position. Here, we present a chromosome-level assembly of ...the Litsea cubeba genome, together with low-coverage genomic and transcriptomic data for many other Lauraceae. Phylogenomic analyses show phylogenetic discordance at the position of Magnoliids, suggesting incomplete lineage sorting during the divergence of monocots, eudicots, and Magnoliids. An ancient whole-genome duplication (WGD) event occurred just before the divergence of Laurales and Magnoliales; subsequently, independent WGDs occurred almost simultaneously in the three Lauralean lineages. The phylogenetic relationships within Lauraceae correspond to the divergence of inflorescences, as evidenced by the phylogeny of FUWA, a conserved gene involved in determining panicle architecture in Lauraceae. Monoterpene synthases responsible for production of specific volatile compounds in Lauraceae are functionally verified. Our work sheds light on the evolution of the Lauraceae, the genetic basis for floral evolution and specific scents.
•A magnetically coupled two-degree-of-freedom harvester for rotation is proposed.•The electromechanical coupling model is developed and validated experimentally.•The harvester can generate high ...voltage at low rotating speeds.•The harvester can harvest vibration energy in multiple frequency bands.
Energy can be harvested from rotational motion for powering wireless autonomous electronic devices. The paper presents a magnetically coupled two-degree-of-freedom vibration energy harvester for rotary motion applications. The design consists of two inverted piezoelectric cantilever beams whose free ends point to the rotating shaft. The centrifugal force of the inverted cantilever beam is beneficial to producing large amplitude in a low speed range. The electromechanical coupling dynamical model is developed by the energy method from Hamilton’s principle and validated experimentally. The experimental results indicate that the presented harvester is suitable for low speed rotation and can harvest vibration energy in multiple frequency bands. The first and second resonant behaviors of voltage can be obtained at 420 r/min and 550 r/min, and the average output powers are 564μW and 535.3μW, respectively.
Conventional oxygen‐dependent photodynamic therapy (PDT) has faced severe challenges because of the non‐specificity of most available photosensitizers (PSs) and the hypoxic nature of tumor tissues. ...Here, an O2 self‐sufficient cell‐like biomimetic nanoplatform (CAT‐PS‐ZIF@Mem) consisting of the cancer cell membrane (Mem) and a cytoskeleton‐like porous zeolitic imidazolate framework (ZIF‐8) with the embedded catalase (CAT) protein molecules and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4, defined as PS) is developed. Because of the immunological response and homologous targeting abilities of the cancer cell membrane, CAT‐PS‐ZIF@Mem is selectively accumulated at the tumor site and taken up effectively by tumor cells after intravenous injection. After the intracellular H2O2 penetration into the framework, it is catalyzed by CAT to produce O2 at the hypoxic tumor site, facilitating the generation of toxic 1O2 for highly effective PDT in vivo under near‐infrared irradiation. By integrating the immune escape, cell homologous recognition, and O2 self‐sufficiency, this cell‐like biomimetic nanoplatform demonstrates highly specific and efficient PDT against hypoxic tumor cells with much reduced side‐effect on normal tissues.
An O2 self‐sufficient cell‐like biomimetic nanoplatform based on zeolitic imidazolate framework (ZIF‐8) is developed for effective photodynamic therapy (PDT). In vitro and in vivo investigations confirm that this cell‐like PDT agent possesses immune escape, homologous targeting, and O2 self‐sufficient capabilities for highly specific PDT against hypoxic tumor cells.
Quercetin is a potent cancer therapeutic agent and dietary antioxidant present in fruit and vegetables. Quercetin prevents tumor proliferation by inducing cell cycle arrest and is a well known cancer ...therapeutic agent and autophagy mediator. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, gold-quercetin into poly(DL-lactide-co-glycolide) nanoparticles was examined. In this study, we explored the role and possible underlying mechanisms of quercetin nanoparticle in regulation of antitumor activity in liver cancer cells. Treatment with quercetin nanoparticle effectively inhibited the liver cancer cell proliferation, cell migration and colony formation, thus suppressing liver cancer progression. Quercetin nanoparticle also upregulated apoptosis markedly. Further study suggested that quercetin nanoparticle accelerated the cleavage of caspase-9, caspase-3, and induced the up-releasing of cytochrome c (Cyto-c), contributing to apoptosis in liver cancer cells. Quercetin nanoparticles also promoted telomerase reverse transcriptase (hTERT) inhibition through reducing AP-2β expression and decreasing its binding to hTERT promoter. In addition, quercetin nanoparticle had an inhibitory role in cyclooxygenase 2 (COX-2) via suppressing the NF-κB nuclear translocation and its binding to COX-2 promoter. Quercetin nanoparticle also inactivated Akt and ERK1/2 signaling pathway. Taken together, our results suggested that quercetin nanoparticle had an antitumor effect by inactivating caspase/Cyto-c pathway, suppressing AP-2β/hTERT, inhibiting NF-κB/COX-2 and impeding Akt/ERK1/2 signaling pathways. Our results provided new mechanistic basis for further investigation of quercetin nanoparticles to find potential therapeutic strategies and possible targets for liver cancer inhibition.
This experiment explored the effects of single application of seven types of slow- and controlled-release fertilizers on rice yield and various population characteristics. Based on a study of the ...nitrogen (N) release characteristics of these fertilizers, pot experiments were conducted in 2018 and 2019 with split fertilization (CK, urea applied split equally at basal and panicle initiation stages, respectively) as control, which assessed the effects on SPAD value, yield and yield components, dynamic changes of rice tillers and dry matter accumulation. The results showed that the N release characteristics of different types of slow- and controlled-release fertilizers were significantly different. Polymer-coated urea (PCU) showed a controlled-release mode and provided sustained release throughout the whole growth stages. Sulfur-coated urea (SCU) exhibited a slow-release mode, providing insufficient release at the middle and late stages. Urease inhibitor urea (AHA) and urea-formaldehyde (UF) yielded a rapid-release mode, with an explosive N release at the early stage and no release at the middle and late stages. These results showed that PCU delayed the peak seedling stage. Compared with CK, dry matter accumulation and SPAD showed no significant differences, and due to the continuous release of N throughout the growth stages, rice yield, spikelets per panicle, seed setting rate, and 1 000-grain weight were all increased. Owing to the lack of N supply at the late stage and the low number of spikelets, SCU led to a reduction of rice yield, which is nevertheless not statistically significant. AHA and UF were susceptible to environmental factors and had varying effects on rice yield. The results of this experiment indicated that given a fixed amount of N applied in a pot, the stronger the N supply capacity and the longer the effective duration time of the fertilizer, the higher the dry matter accumulation at the late growth stage, and the higher the rice yield.
Perovskite solar cells (PSCs) may offer huge potential in photovoltaic conversion, yet their practical applications face one major obstacle: their low stability, or quick degradation of their initial ...efficiencies. Here, a new design scheme is presented to enhance the PSC stability by using low‐temperature hydrothermally grown hierarchical nano‐SnO2 electron transport layers (ETLs). The ETL contains a thin compact SnO2 layer underneath a mesoporous layer of SnO2 nanosheets. The mesoporous layer plays multiple roles of enhancing photon collection, preventing moisture penetration and improving the long‐term stability. Through such simple approaches, PSCs with power conversion efficiencies of ≈13% can be readily obtained, with the highest efficiency to be 16.17%. A prototypical PSC preserves 90% of its initial efficiency even after storage in air at room temperature for 130 d without encapsulation. This study demonstrates that hierarchical SnO2 is a potential ETL for fabricating low‐cost and efficient PSCs with long‐term stability.
Low‐temperature hydrothermally grown hierarchical SnO2
, a mesoporous layer of nanosheet arrays on a compact nanoparticle layer, is used as the electron transporting layer to enhance the long‐term stability of perovskite solar cells. A mesoporous device preserves 90% of its initial efficiency, even after storage in air for 130 d without encapsulation.
Tumor microenvironment (TME) plays a crucial role in the initiation and progression of lung adenocarcinoma (LUAD); however, there is still a challenge in understanding the dynamic modulation of the ...immune and stromal components in TME. In the presented study, we applied CIBERSORT and ESTIMATE computational methods to calculate the proportion of tumor-infiltrating immune cell (TIC) and the amount of immune and stromal components in 551 LUAD cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were analyzed by COX regression analysis and protein-protein interaction (PPI) network construction. Then, Bruton tyrosine kinase (BTK) was determined as a predictive factor by the intersection analysis of univariate COX and PPI. Further analysis revealed that BTK expression was negatively correlated with the clinical pathologic characteristics (clinical stage, distant metastasis) and positively correlated with the survival of LUAD patients. Gene Set Enrichment Analysis (GSEA) showed that the genes in the high-expression BTK group were mainly enriched in immune-related activities. In the low-expression BTK group, the genes were enriched in metabolic pathways. CIBERSORT analysis for the proportion of TICs revealed that B-cell memory and CD8+ T cells were positively correlated with BTK expression, suggesting that BTK might be responsible for the preservation of immune-dominant status for TME. Thus, the levels of BTK might be useful for outlining the prognosis of LUAD patients and especially be a clue that the status of TME transition from immune-dominant to metabolic activity, which offered an extra insight for therapeutics of LUAD.
Early hematoma growth is a devastating neurological complication after intracerebral hemorrhage. We aim to report and evaluate the usefulness of computed tomography (CT) black hole sign in predicting ...hematoma growth in patients with intracerebral hemorrhage.
Patients with intracerebral hemorrhage were screened for the presence of CT black hole sign on admission head CT performed within 6 hours after onset of symptoms. The black hole sign was defined as hypoattenuatting area encapsulated within the hyperattenuating hematoma with a clearly defined border. The sensitivity, specificity, and positive and negative predictive values of CT black hole sign in predicting hematoma expansion were calculated. Logistic regression analyses were used to assess the presence of the black hole sign and early hematoma growth.
A total of 206 patients were enrolled. Black hole sign was found in 30 (14.6%) of 206 patients on the baseline CT scan. The black hole sign was more common in patients with hematoma growth (31.9%) than those without hematoma growth (5.8%; P<0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of back hole sign in predicting early hematoma growth were 31.9%, 94.1%, 73.3%, and 73.2%, respectively. The time-to-admission CT scan, baseline hematoma volume, and the presence of black hole sign on admission CT independently predict hematoma growth in multivariate model.
The CT black hole sign could be used as a simple and easy-to-use predictor for early hematoma growth in patients with intracerebral hemorrhage.
A percutaneous ventricular assist device (pVAD) is an effective method to treat heart failure, but its complications, mainly hemolysis and thrombus formation, cannot be ignored. Accurate evaluation ...of hemolysis and thrombus formation in pVAD is essential to guide the development of pVAD and reduce the incidence of complications.
This study optimized the numerical model to predict hemolysis and thrombus formation in pVAD. The hemolysis model is based on the power law function, and the multi-component thrombus prediction model is improved by introducing the von Willebrand factor.
The error between the numerical simulation and the hydraulic performance experiment is within 5%. The numerical results of hemolysis are in good agreement with those of in vitro experiments. Meanwhile, the thrombus location predicted by the numerical model is the same as that found in the in vivo experiment.
The numerical model suggested in this study may therefore accurately assess the possible hemolytic and thrombotic dangers in pVAD, making it an effective tool to support the development of pVAD.
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