The in vivo distribution, viability, and differentiation capability of transplanted stem cells are vital for the therapeutic efficacy of stem cell–based therapy. Herein, an NIR‐II fluorescence/dual ...bioluminescence multiplexed imaging method covering the visible and the second near‐infrared window from 400 to 1700 nm is successfully developed for in vivo monitoring the location, survival, and osteogenic differentiation of transplanted human mesenchymal stem cells (hMSCs) in a calvarial defect mouse model. The exogenous Ag2S quantum dot–based fluorescence imaging in the second near‐infrared window is applied for visualizing the long‐term biodistribution of transplanted hMSCs. Endogenous red firefly luciferase (RFLuc)‐based bioluminescence imaging (BLI) and the collagen type 1 promoter–driven Gaussia luciferase (GLuc)‐based BLI are employed to report the survival and osteogenic differentiation statuses of the transplanted hMSCs. Meanwhile, by integrating the three imaging channels, multiple dynamic biological behaviors of transplanted hMSCs and the promotion effects of immunosuppression and the bone morphogenetic protein 2 on the survival and osteogenic differentiation of transplanted hMSCs are directly observed. The novel multiplexed imaging method can greatly expand the capability for multifunctional analysis of the fates and therapeutic capabilities of the transplanted stem cells, and aid in the improvement of stem cell–based regeneration therapies and their clinical translation.
An NIR‐II fluorescence/dual bioluminescence multiplexed imaging method is developed for in vivo monitoring of the location, survival, and osteogenic differentiation of transplanted human mesenchymal stem cells. The multiplexed imaging method within a broad spectral range of 400–1700 nm can greatly expand the capability for multifunctional analysis of the fates and therapeutic capabilities of the transplanted stem cells.
Although dynamic reactions of imines have been extensively studied, the dynamic behaviors manipulated by chirality remain nearly unexplored. In this work, enantioselective amine exchange reactions ...were demonstrated as a first example via the reaction of enantiomeric chiral amines such as natural amino acids with a series of innovative axially chiral 1,1′-binaphthyl-2,2′-diamine (BNDA)-based imines that were prepared from the condensation reactions between BNDA and salicylaldehyde (SA) or its derivatives. This enantioselective dynamic behavior can be directly indicated by the degree of the fluorescence response of the R-configuration of imines to the d-enantiomer of chiral amine, because the released BNDA can serve as the fluorescence signal output when the amine exchange reaction occurs, which is far higher than the response to its l-enantiomer under identical experimental conditions. For the S-configuration of chiral imines, the fluorescence response is the opposite. The enantioselective exchange reaction can be tuned by altering the electron-withdrawing or electron-donating capability of the substituent at position 4 or 5 of the SA part of chiral imines. Not only o-OH groups in SA-based imines but also protic solvents used as reaction media were found to be important to the dynamic behavior at high rates.
We show herein the phosphatase‐like catalytic activity of coordination polymers obtained after adding Ag+‐ions to thiols bearing hydrophobic alkyl chains terminated with a 1,4,7‐triazacyclononane ...(TACN) group. The subsequent addition of Zn2+ ‐ions to the self‐assembled polymers resulted in the formation of multivalent metal coordination polymers capable of catalysing the transphosphorylation of an RNA‐model compound (2‐hydroxypropyl‐4‐nitrophenyl phosphate, HPNPP) with high reactivity. Analysis of a series of metal ions showed that the highest catalytic activity was obtained when Ag+‐ions were used as the first metal ions to construct the backbone of the coordination polymer through interaction with the ‐SH group followed by Zn2+‐ions as the second metal ions complexed by the TACN‐macrocycle. Furthermore, it was demonstrated that the catalytic activity could be modulated by changing the length of the hydrophobic alkyl chain.
A series of self‐assembled multivalent Ag‐SR coordination polymers with high phosphatase‐like activity have been developed. This work represents a new alternative for the future rational design of highly efficient catalysts for hydrolysis of phosphates and carboxylates.
AIMS: We tested the responses of soil respiration to irrigation, at different proportions of field capacity, in constructed grasslands in the Inner Mongolia Autonomous Region of northern China, and ...tried to identify the underlying physiological mechanisms. METHODS: The experiment included a legume (Medicago sativa) and a forage grass (Elymus nutans) in sole-crops and a mixed sowing, with four water treatments: a control and three levels of irrigation (low, medium, and high) at three application times: during the regreening, elongation, and heading stages. RESULTS: The soil respiration rate (R ₛ) responded strongly to water addition. Irrigation increased the cumulative growing season R ₛ, which ranged from 257 g C m⁻² years⁻¹ to 500 g C m⁻² years⁻¹ for M. sativa, from 299 to 391 g C m⁻² years⁻¹ for E. nutans + M. sativa, and from 209 to 296 g C m⁻² years⁻¹ for E. nutans. Irrigation increased the cumulative R ₛ by 7 to 49 %. R ₛ of the grass–legume mixture was 1.2 to 1.4 times the corresponding values in the E. nutans plots. In addition to the effects of soil temperature and moisture content, R ₛ was explained by differences in the net photosynthetic rate and in microbial biomass. Water addition increased Q ₁₀, which was strongly and positively correlated with the total C, C/N ratio, and cellulose content of the plants. CONCLUSIONS: R ₛ responded strongly to irrigation, although the response differed between the two species. The grass–legume mixtures showed increased R ₛ compared to values in the grass sole-crop. R ₛ appears to be determined by moisture and temperature, but also by the net photosynthetic rate and by microbial properties such as microbial biomass.
Proximal humerus fractures (PHFs) are common. With the development of locking plates, open reduction and internal fixation (ORIF) of the proximal humerus can provide excellent clinical outcomes. The ...quality of fracture reduction is crucial in the locking plate fixation of proximal humeral fractures. The purpose of this study was to determine the impact of 3-dimensional (3D) printing technology and computer virtual technology assisted preoperative simulation on the reduction quality and clinical outcomes of 3-part and 4-part proximal humeral fractures.
A retrospective comparative analysis of 3-part and 4-part PHFs undergoing open reduction internal fixation was performed. Patients were divided into 2 groups according to whether computer virtual technology and 3D printed technology were used for preoperative simulation: the simulation group and the conventional group. Operative time, intraoperative bleeding, hospital stay, quality of fracture reduction, Constant scores, American Society for Shoulder and Elbow Surgery (ASES) scores, shoulder range of motion, complications, and revision surgeries were assessed.
This study included 67 patients (58.3%) in the conventional group and 48 patients (41.7%) in the simulation group. The patient demographics and fracture characteristics were comparable in these groups. Compared with the conventional group, the simulation group had shorter operation time and less intraoperative bleeding (P < 0.001, both). Immediate postoperative assessment of fracture reduction showed a higher incidence of greater tuberosity cranialization of < 5 mm, neck-shaft angle of 120° to 150°, and head shaft displacement of < 5 mm in the simulation group. The incidence of good reduction was 2.6 times higher in the simulation group than in the conventional group (95% CI, 1.2-5.8). At the final follow-up, the chance of forward flexion > 120° (OR 5.8, 95% CI 1.8-18.0) and mean constant score of > 65 (OR 3.4, 95% CI 1.5-7.4) was higher in the simulation group than the conventional group, as well as a lower incidence of complications in the simulation group was obtained (OR 0.2, 95% CI 0.1-0.6).
This study identified that preoperative simulation assisted by computer virtual technology and 3D printed technology can improve reduction quality and clinical outcomes in treatment of 3-part and 4-part PHFs.
A number of uracil amides cleave poly (ADP-ribose) polymerase and therefore novel thiouracil amide compounds were synthesized and screened for the loss of cell viability in a ...human-estrogen-receptor-positive breast cancer cell line. The synthesized compounds exhibited moderate to significant efficacy against human breast cancer cells, where the compound
IC
value was found to be 18 μM. Thouracil amide compounds
and
inhibited the catalytical activity of PARP1, enhanced cleavage of PARP1, enhanced phosphorylation of H2AX, and increased CASPASE 3/7 activity. Finally, in silico analysis demonstrated that compound
interacted with PARP1. Hence, specific thiouracil amides may serve as new drug-seeds for the development of PARP inhibitors for use in oncology.
Introduction/Aims
Lymphatic vessels are responsible for the removal of metabolic waste from body tissues. They also play a crucial role in skeletal muscle functioning thorough their high‐energy ...metabolism. In this study we investigated whether disuse muscle atrophy induced by hindlimb unloading is associated with an alteration in the number of lymphatic vessels and differential expression of lymphangiogenic factors in the soleus muscle.
Methods
Male C57BL/6 mice were subjected to tail suspension (TS) for 2 or 4 weeks to induce soleus muscle atrophy. After TS, lymphatic and blood capillaries in the soleus muscle were visualized and counted by double staining with LYVE‐1 and CD31. The protein and mRNA levels of vascular endothelial growth factor (VEGF)‐C, VEGF‐D, and vascular endothelial growth factor receptor‐3 were measured by Western blotting and real‐time reverse transcript polymerase chain reaction, respectively.
Results
TS for 2 weeks resulted in a significant decrease in the number of blood capillaries compared with controls. However, there was no significant change in the number of lymphatic capillaries. By contrast, TS for 4 weeks resulted in a significant decrease in the number of lymphatic and blood capillaries. We observed a significant decrease in the mRNA levels of VEGF‐C and VEGF‐D in mice subjected to TS for 4 weeks.
Discussion
The decrease of intramuscular lymphatic vessels may a crucial role in the process of muscle atrophy.
Purpose
Ipilimumab, a fully human monoclonal antibody specific to CTLA-4, has been shown to improve overall survival in metastatic melanoma patients. As a consequence of CTLA-4 blockade, ipilimumab ...treatment is associated with proliferation and activation of peripheral T cells. To better understand various tumor-associated components that may influence the clinical outcome of ipilimumab treatment, gene expression profiles of tumors from patients treated with ipilimumab were characterized.
Experimental design
Gene expression profiling was performed on tumor biopsies collected from 45 melanoma patients before and 3 weeks after the start of treatment in a phase II clinical trial.
Results
Analysis of pre-treatment tumors indicated that patients with high baseline expression levels of immune-related genes were more likely to respond favorably to ipilimumab. Furthermore, ipilimumab appeared to induce two major changes in tumors from patients who exhibited clinical activity: genes involved in immune response showed increased expression, whereas expression of genes for melanoma-specific antigens and genes involved in cell proliferation decreased. These changes were associated with the total lymphocyte infiltrate in tumors, and there was a suggestion of association with prolonged overall survival in these patients. Many IFN-γ-inducible genes and Th1-associated markers showed increased expression after ipilimumab treatment, suggesting an accumulation of this particular type of T cell at the tumor sites, which might play an important role in mediating the antitumor activity of ipilimumab.
Conclusions
These results support the proposed mechanism of action of ipilimumab, suggesting that cell-mediated immune responses play an important role in the antitumor activity of ipilimumab.
•Rs differed greatly among the land-use types of the semi-arid temperate grassland.•Soil water availability is a primary constraint on grass ecosystem C processes.•The contribution of Rr to Rs ranged ...from 13 to 62% among the land-use type.•Rs were correlated with aboveground biomass, soil organic matter and root biomass.•Litter decomposition and litter quality also appear to be important biotic factors.
Land use change has greatly affected ecosystem C processes and C exchanges in grassland ecosystems. The aim of this study was to determine the effects of land use (mowing, grazing exclusion, and grazing) on soil respiration (Rs) of a semi-arid temperate grassland during two growing seasons in Inner Mongolia, northern China, and to identify the main factors that affected Rs. During the growing season, Rs for the mowing, grazing exclusion, and grazing land-use types averaged 129, 150, and 194gCm−2yr−1, respectively, in 2011 (a dry year), versus 309, 272, and 262gCm−2yr−1, respectively, in 2012 (a wet year). Root respiration (Rr) accounted for 13–55% of Rs in 2011, versus 10–62% in 2012. Rs was strongly positively correlated with soil moisture for all three land uses, but weakly correlated with soil temperature (R2<0.4 in all cases). Rs was significantly positively correlated with aboveground biomass (R2=0.834), soil organic matter (R2=0.765), root biomass (R2=0.704), lignin mass loss rate (R2=0.422), and the cellulose mass loss rate (R2=0.849) and significantly negatively correlated with the litter C/N (R2=0.609). The temperature sensitivity (Q10) exhibited large monthly changes, and ranged from 0.52 to 2.12. Rainfall plays a dominant role in soil respiration: precipitation increased soil respiration, but the response differed among the land-use types. Thus, soil water availability is a primary constraint on plant growth and ecosystem C processes. Soil temperature plays a secondary role. Litter decomposition rates and litter quality also appear to be important.
Role of microRNA (miRNA) has been highlighted in pathogen-host interactions recently. At present, their role in active pulmonary tuberculosis is unknown. The aim of the study was to delineate miRNA ...expression in sputum supernatant of patients with active pulmonary tuberculosis. Expression of miRNAs was evaluated by microarray analysis and differentially expressed miRNAs were validated by RT-qPCR. Secreted cytokines TNF-α and IL-6 were measured by ELISA. We found that 95 miRNAs were differentially expressed between tuberculosis group and controls. More miRNAs (52 out of 95 miRNAs) were underexpressed than overexpressed during tuberculosis infection. Overexpression of miR-3179, miR-147 and underexpression of miR-19b-2* in TB group compared with controls were confirmed in the validation cohort. TNF-α and IL-6 levels were not significantly altered between TB group and controls. For the first time, differential expression of miRNAs in sputum was found in active pulmonary tuberculosis. The study provides rationale for identifying the role of miRNAs in the pathogenesis of pulmonary tuberculosis and indicates potential for miRNA-based therapeutic strategies.
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