Temperature-Insensitive Nonpolar Suspensions of Polyoxyethylene Alkyl Ether-Grafted Silica Nanoparticles.

Nonpolar suspensions of organically modified particles exhibit a strong temperature sensitivity owing to the high-temperature-induced desorption/decomposition and the low-temperature-induced disorder/order conformational transition of the modifiers. This strong temperature sensitivity limits their applications, such as lubricants and oil-based drilling fluids, which require the suspensions to operate over a wide temperature range (e.g., 0-200 °C). We hypothesize that the introduction of a flexible ethylene oxide (EO) chain into the modifiers can disrupt the low-temperature-induced ordered conformation to improve the stability of the nonpolar suspensions. In this article, nonpolar suspensions with temperature insensitivity in the range of 5-160 °C were obtained via the covalent modification of silica NPs and the introduction of EO chains into the modifier molecules. Here, octadecyl-grafted silica NPs (C18-SiO2) and polyoxyethylene alkyl ether-grafted silica NPs (AEOn-SiO2) were synthesized and subsequently dispersed in mineral oil. The rheological properties of each suspension at different temperatures were evaluated, and the thermal stability of AEOn-SiO2 in mineral oil was investigated along with the conformational changes of the grafted chains. In the temperature range of 5-160 °C, the apparent viscosity and gel strength of the C18-SiO2 suspension changed dramatically, whereas the AEOn-SiO2 suspensions exhibited constant rheological properties over this temperature range. This temperature insensitivity of AEOn-SiO2 suspensions is attributed to the excellent thermal stability of AEOn-SiO2 in mineral oil and the disordered conformation of the EO chains upon cooling. This study provides a novel approach to preparing temperature-insensitive nonpolar suspensions, which have potential applications in the petroleum and lubricant industries.

Porous liquids: a novel porous medium for efficient carbon dioxide capture.

Porous liquids (PLs) are the combination of porous solid material and flowing liquid, which provides alternative options to solve difficulties in the development of porous solids. With the booming development of PLs since 2015, plenty of syntheses and applications have been reported with a specific focus on gas adsorption. Given the lack of a comprehensive review, this paper reviews the application of PLs in CO2 capture. To start with, ground-breaking case studies are reviewed to help understand the progress of PLs research. Then, as a major part of this paper, studies of PLs for CO2 capture are reviewed separately. Moreover, five basic properties of porous liquids, including stability, viscosity, selectivity, porosity, capacity, and the influencing factors are systemically reviewed respectively. Furthermore, gas storage and release mechanisms in PLs are briefly outlined, and potential processing methods of PLs used for CO2 capture are discussed.

Spontaneous Molecule Aggregation for Nearly Single-Ion Conducting Sol Electrolyte to Advance Aqueous Zinc Metal Batteries: The Case of Tetraphenylporphyrin.

Zn metal as a promising anode of aqueous batteries faces severe challenges from dendrite growth and side reactions. Here, tetraphenylporphyrin tetrasulfonic acid (TPPS) is explored as an electrolyte additive for advanced Zn anodes. It is interesting to note that TPPS spontaneously assembles into unique aggregates. As they adsorb on the Zn anode, the aggregates enhance the resistance to electrolyte percolation and dendrite growth compared to single molecules. Meanwhile, TPPS facilitates anion association in the solvation sheath of Zn2+, and boosts the transference number of Zn2+ up to 0.95. Therefore, anion-related side reactions and anion-induced electrode overpotentials are reduced accordingly. In this context, the electrolyte containing TPPS exhibits excellent electrochemical performance. Even under a high loading of MnO2 (25 mg cm-2), a limited Zn supply (N/P ratio=1.7), and a lean electrolyte (15 µL mAh-1), the full cells still represent a higher cumulative capacity compared to the reported data. The advantages of this electrolyte are also adapted to other cathode materials. The pouch cells of Zn||NaV3O8 ⋅ 1.5H2O realize a capacity of ~0.35 Ah at 0.4 C under harsh conditions.

The roles of ubiquitination in AML.

Acute myeloid leukemia (AML) is a heterogeneously malignant disorder resulting in poor prognosis. Ubiquitination, a major post-translational modification (PTM), plays an essential role in regulating various cellular processes and determining cell fate. Despite these initial insights, the precise role of ubiquitination in AML pathogenesis and treatment remains largely unknown. In order to address this knowledge gap, we explore the relationship between ubiquitination and AML from the perspectives of signal transduction, cell differentiation, and cell cycle control; and try to find out how this relationship can be utilized to inform new therapeutic strategies for AML patients.

Measurable residual disease detected by flow cytometry independently predicts prognoses of NPM1-mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) with NPM1 mutation is a distinct genetic entity with favorable outcomes. Nevertheless, emerging evidence suggests that NPM1-mutated AML is still a highly heterogeneous disorder. In this study, 266 patients with AML with NPM1 mutations were retrospectively analyzed to evaluate the associations between variant allele frequency (VAF) of NPM1 mutations, co-mutated genes, measurable residual disease (MRD), and patient outcomes. Multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (RT-PCR) were used for monitoring MRD. Ultimately, 106 patients were included in the long-term follow-up period. Patients with high NPM1 VAF (≥ 42.43%) had poorer 2-year relapse-free survival (RFS) (55.7% vs. 70.2%, P = 0.017) and overall survival (OS) (63.7% vs. 82.0%, P = 0.027) than those with low VAF. DNMT3A mutations negatively influenced the outcomes of patients with NPM1 mutations. Patients with high DNMT3A VAF or NPM1/DNMT3A/FLT3-ITD triple mutations had shorter RFS and significantly lower OS than that in controls. After two cycles of chemotherapy, patients with positive MFC MRD results had lower RFS (MRD+ vs. MRD-:44.9% vs. 67.6%, P = 0.007) and OS (61.5% vs. 76.6%, P = 0.011) than those without positive MFC MRD results. In multivariate analysis, high NPM1 VAF (hazard ratio [HR] = 2.045; P = 0.034) and positive MRD after two cycles of chemotherapy (HR = 3.289; P = 0.003) were independent risk factors for RFS; MRD positivity after two cycles of chemotherapy (HR = 3.293; P = 0.008) independently predicted the OS of the patients. These results indicate that VAF of both NPM1 gene itself or certain co-occurring gene pre-treatment and MRD post-treatment are potential markers for restratifying the prognoses of patients AML having NPM1 mutations.

Shikonin exerts an anti-leukemia effect against FLT3-ITD mutated acute myeloid leukemia cells via targeting FLT3 tyrosine kinase and its downstream pathways.

INTRODUCTION: Acute myeloid leukemia (AML) with internal tandem duplication (ITD) mutations in Fms-like tyrosine kinase 3 (FLT3) has an unfavorable prognosis. Recently, using newly emerging inhibitors of FLT3 has led to improved outcomes of patients with FLT3-ITD mutations. However, drug resistance and relapse continue to be significant challenges in the treatment of patients with FLT3-ITD mutations. This study aimed to evaluate the anti-leukemic effects of shikonin (SHK) and its mechanisms of action against AML cells with FLT3-ITD mutations in vitro and in vivo. METHODS: The CCK-8 assay was used to analyze cell viability, and flow cytometry was used to detect cell apoptosis and differentiation. Western blotting and real-time polymerase chain reaction (RT-PCR) were used to examine the expression of certain proteins and genes. Leukemia mouse model was created to evaluate the anti-leukemia effect of SHK against FLT3-ITD mutated leukemia in vivo. RESULTS: After screening a series of leukemia cell lines, those with FLT3-ITD mutations were found to be more sensitive to SHK in terms of proliferation inhibition and apoptosis induction than those without FLT3-ITD mutations. SHK suppresses the expression and phosphorylation of FLT3 receptors and their downstream molecules. Inhibition of the NF-κB/miR-155 pathway is an important mechanism through which SHK kills FLT3-AML cells. Moreover, a low concentration of SHK promotes the differentiation of AML cells with FLT3-ITD mutations. Finally, SHK could significantly inhibit the growth of MV4-11 cells in leukemia bearing mice. CONCLUSION: The findings of this study indicate that SHK is a promising drug for the treatment of FLT3-ITD mutated AML.

A 7-Day Decitabine-Included Conditioning Regimen Accelerated Donor Hematopoietic Engraftment while Reduced the Occurrence of Mucositis without Interfering with Prognosis.

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the standard and curative treatment strategy for patients with hematologic malignancies. Recently, decitabine-included regimens have been investigated by several studies including ours, which may prevent relapse of primary malignant diseases. METHODS: This study was to retrospectively evaluate a 7-day decitabine-included regimen with reduced dose of idarubicin for patients with hematologic malignancies who underwent allo-HSCT. RESULTS: A total of 84 patients were enrolled, including 24 cases in 7-day and 60 cases in 5-day decitabine groups, respectively. Patients conditioned with 7-day decitabine regimen showed accelerated neutrophil (12.05 ± 1.97 vs. 13.86 ± 3.15; u = 9.309, p < 0.001) and platelet (16.32 ± 6.27 vs. 21.37 ± 8.57; u = 8.887, p < 0.001) engraftment compared with those treated with 5-day decitabine regimen. Patients in the 7-day decitabine group showed a significantly lower incidence rate of total (50.00% [12/24] versus 78.33% [47/60]; χ2 = 6.583, p = 0.010) and grade III or above (4.17% [1/24] vs. 31.67% [19/60]; χ2 = 7.147, p = 0.008) oral mucositis compared to those in the 5-day decitabine group. However, the occurrence of other major complications post-allo-HSCT and outcomes of patients in these two groups were comparable. CONCLUSION: These results demonstrate that this 7-day decitabine-contained new conditioning regimen seems to be feasible and safe for patients with myeloid neoplasms who receive allo-HSCT, and a large-scale prospective study is needed to confirm the findings of this study.

Tissue oxygen saturation is predictive of lactate clearance in patients with circulatory shock.

BACKGROUND: Tissue oxygen saturation (StO2) decrease could appear earlier than lactate alteration. However, the correlation between StO2 and lactate clearance was unknown. METHODS: This was a prospective observational study. All consecutive patients with circulatory shock and lactate over 3 mmol/L were included. Based on the rule of nines, a BSA (body surface area) weighted StO2 was calculated from four sites of StO2 (masseter, deltoid, thenar and knee). The formulation was as follows: masseter StO2 × 9% + (deltoid StO2 + thenar StO2) × (18% + 27%)/ 2 + knee StO2 × 46%. Vital signs, blood lactate, arterial and central venous blood gas were measured simultaneously within 48 h of ICU admission. The predictive value of BSA-weighted StO2 on 6-hour lactate clearance > 10% since StO2 initially monitored was assessed. RESULTS: A total of 34 patients were included, of whom 19 (55.9%) had a lactate clearance higher than 10%. The mean SOFA score was lower in cLac ≥ 10% group compared with cLac < 10% group (11 ± 3 vs. 15 ± 4, p = 0.007). Other baseline characteristics were comparable between groups. Compared to non-clearance group, StO2 in deltoid, thenar and knee were significantly higher in clearance group. The area under the receiver operating curves (AUROC) of BSA-weighted StO2 for prediction of lactate clearance (0.92, 95% CI [Confidence Interval] 0.82-1.00) was significantly higher than StO2 of masseter (0.65, 95% CI 0.45-0.84; p < 0.01), deltoid (0.77, 95% CI 0.60-0.94; p = 0.04), thenar (0.72, 95% CI 0.55-0.90; p = 0.01), and similar to knee (0.87, 0.73-1.00; p = 0.40), mean StO2 (0.85, 0.73-0.98; p = 0.09). Additionally, BSA-weighted StO2 model had continuous net reclassification improvement (NRI) over the knee StO2 and mean StO2 model (continuous NRI 48.1% and 90.2%, respectively). The AUROC of BSA-weighted StO2 was 0.91(95% CI 0.75-1.0) adjusted by mean arterial pressure and norepinephrine dose. CONCLUSIONS: Our results suggested that BSA-weighted StO2 was a strong predictor of 6-hour lactate clearance in patients with shock.

Comparative 4D Label-Free Quantitative Proteomic Analysis of Bombus terrestris Provides Insights into Proteins and Processes Associated with Diapause.

Diapause, an adaptative strategy for survival under harsh conditions, is a dynamic multi-stage process. Bombus terrestris, an important agricultural pollinator, is declining in the wild, but artificial breeding is possible by imitating natural conditions. Mated queen bees enter reproductive diapause in winter and recover in spring, but the regulatory mechanisms remain unclear. Herein, we conducted a comparative 4D label-free proteomic analysis of queen bees during artificial breeding at seven timepoints, including pre-diapause, diapause, and post-diapause stages. Through bioinformatics analysis of proteomic and detection of substance content changes, our results found that, during pre-diapause stages, queen bees had active mitochondria with high levels of oxidative phosphorylation, high body weight, and glycogen and TAG content, all of which support energy consumption during subsequent diapause. During diapause stages, body weight and water content were decreased but glycerol increased, contributing to cold resistance. Dopamine content, immune defense, and protein phosphorylation were elevated, while fat metabolism, protein export, cell communication, signal transduction, and hydrolase activity decreased. Following diapause termination, JH titer, water, fatty acid, and pyruvate levels increased, catabolism, synaptic transmission, and insulin signaling were stimulated, ribosome and cell cycle proteins were upregulated, and cell proliferation was accelerated. Meanwhile, TAG and glycogen content decreased, and ovaries gradually developed. These findings illuminate changes occurring in queen bees at different diapause stages during commercial production.

Genome-wide identification and expression analysis of the ftsH protein family and its response to abiotic stress in Nicotiana tabacum L.

BACKGROUND: The filamentous temperature-sensitive H protease (ftsH) gene family plays an important role in plant growth and development. FtsH proteins belong to the AAA protease family. Studies have shown that it is a key gene for plant chloroplast development and photosynthesis regulation. In addition, the ftsH gene is also involved in plant response to stress. At present, the research and analysis of the ftsH gene family are conducted in microorganisms such as Escherichia coli and Oenococcus and various plants such as Arabidopsis, pear, rice, and corn. However, analysis reports on ftsH genes from tobacco (Nicotiana tabacum L.), an important model plant, are still lacking. Since ftsH genes regulate plant growth and development, it has become necessary to systematically study this gene in an economically important plant like tobacco. RESULTS: This is the first study to analyze the ftsH gene from Nicotiana tabacum L. K326 (NtftsH). We identified 20 ftsH genes from the whole genome sequence, renamed them according to their chromosomal locations, and divided them into eight subfamilies. These 20 NtftsH genes were unevenly distributed across the 24 chromosomes. We found four pairs of fragment duplications. We further investigated the collinearity between these genes and related genes in five other species. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis identified differential expression patterns of NtftsH in different tissues and under various abiotic stress conditions. CONCLUSIONS: This study provides a comprehensive analysis of the NtftsH gene family. The exon-intron structure and motif composition are highly similar in NtftsH genes that belong to the same evolutionary tree branch. Homology analysis and phylogenetic comparison of ftsH genes from several different plants provide valuable clues for studying the evolutionary characteristics of NtftsH genes. The NtftsH genes play important roles in plant growth and development, revealed by their expression levels in different tissues as well as under different stress conditions. Gene expression and phylogenetic analyses will provide the basis for the functional analysis of NtftsH genes. These results provide a valuable resource for a better understanding of the biological role of the ftsH genes in the tobacco plant.

Genus-Wide Characterization of Bumblebee Genomes Provides Insights into Their Evolution and Variation in Ecological and Behavioral Traits.

Bumblebees are a diverse group of globally important pollinators in natural ecosystems and for agricultural food production. With both eusocial and solitary life-cycle phases, and some social parasite species, they are especially interesting models to understand social evolution, behavior, and ecology. Reports of many species in decline point to pathogen transmission, habitat loss, pesticide usage, and global climate change, as interconnected causes. These threats to bumblebee diversity make our reliance on a handful of well-studied species for agricultural pollination particularly precarious. To broadly sample bumblebee genomic and phenotypic diversity, we de novo sequenced and assembled the genomes of 17 species, representing all 15 subgenera, producing the first genus-wide quantification of genetic and genomic variation potentially underlying key ecological and behavioral traits. The species phylogeny resolves subgenera relationships, whereas incomplete lineage sorting likely drives high levels of gene tree discordance. Five chromosome-level assemblies show a stable 18-chromosome karyotype, with major rearrangements creating 25 chromosomes in social parasites. Differential transposable element activity drives changes in genome sizes, with putative domestications of repetitive sequences influencing gene coding and regulatory potential. Dynamically evolving gene families and signatures of positive selection point to genus-wide variation in processes linked to foraging, diet and metabolism, immunity and detoxification, as well as adaptations for life at high altitudes. Our study reveals how bumblebee genes and genomes have evolved across the Bombus phylogeny and identifies variations potentially linked to key ecological and behavioral traits of these important pollinators.

A functional chromogen gene C from wild rice is involved in a different anthocyanin biosynthesis pathway in indica and japonica.

KEY MESSAGE: we identified a functional chromogen gene C from wild rice, providing a new insight of anthocyanin biosynthesis pathway in indica and japonica. Accumulation of anthocyanin is a desirable trait to be selected in rice domestication, but the molecular mechanism of anthocyanin biosynthesis in rice remains largely unknown. In this study, a novel allele of chromogen gene C, OrC1, from Oryza rufipongon was cloned and identified as a determinant regulator of anthocyanin biosynthesis. Although OrC1 functions in purple apiculus, leaf sheath and stigma in indica background, it only promotes purple apiculus in japonica. Transcriptome analysis revealed that OrC1 regulates flavonoid biosynthesis pathway and activates a few bHLH and WD40 genes of ternary MYB-bHLH-WD40 complex in indica. Differentially expressed genes and metabolites were found in the indica and japonica backgrounds, indicating that OrC1 activated the anthocyanin biosynthetic genes OsCHI, OsF3H and OsANS and produced six metabolites independently. Artificial selection and domestication of C1 gene in rice occurred on the coding region in the two subspecies independently. Our results reveal the regulatory system and domestication of C1, provide new insights into MYB transcript factor involved in anthocyanin biosynthesis, and show the potential of engineering anthocyanin biosynthesis in rice.

Mesenchymal stem/stromal cell-based therapy: mechanism, systemic safety and biodistribution for precision clinical applications.

Mesenchymal stem/stromal cells (MSCs) are a promising resource for cell-based therapy because of their high immunomodulation ability, tropism towards inflamed and injured tissues, and their easy access and isolation. Currently, there are more than 1200 registered MSC clinical trials globally. However, a lack of standardized methods to characterize cell safety, efficacy, and biodistribution dramatically hinders the progress of MSC utility in clinical practice. In this review, we summarize the current state of MSC-based cell therapy, focusing on the systemic safety and biodistribution of MSCs. MSC-associated risks of tumor initiation and promotion and the underlying mechanisms of these risks are discussed. In addition, MSC biodistribution methodology and the pharmacokinetics and pharmacodynamics of cell therapies are addressed. Better understanding of the systemic safety and biodistribution of MSCs will facilitate future clinical applications of precision medicine using stem cells.

Activated biochar derived from spent Auricularia auricula substrate for the efficient adsorption of cationic azo dyes from single and binary adsorptive systems.

In this study, spent Auricularia auricula substrate (AS)-derived biochar (ASBCs) and activated biochar with NaOH (A-ASBC) were evaluated for the adsorption of cationic azo dyes, including methylene blue (MB), rhodamine B (RB), and crystal violet (CV), from single and binary adsorptive systems. A-ASBC showed a higher maximum adsorption capacity for these dyes (MB: 53.62 mg·g-1, RB: 32.33 mg·g-1, CV: 735.73 mg·g-1) than ASBCs in a single system because it had a greater specific surface area and more oxygen containing-functional groups on the surface. The adsorption process of the three dyes onto the adsorbents was in good agreement with the Freundlich adsorption isotherm and fit the pseudo-second-order kinetic model, which revealed sorbate polymolecular layer formation over the adsorbent surface and the involvement of chemisorption. The adsorption mechanism showed that the adsorption of three dyes on adsorbents could be postulated as a multistep process with extraordinary affinity-induced adsorption in terms of both physisorption and chemisorption. In the binary adsorptive system, the results showed that all MB, RB, and CV had antagonistic/competitive effects on each other's adsorption (QBinary/QSingle < 1). Furthermore, a phytotoxic assay affirmed the effectiveness of the adsorbent in adsorbing dye species from aqueous solutions using Brassica pekinensis L. seeds as the model. Therefore, activated biochar prepared from AS can be used as a potentially economical and effective adsorbent for treating printing and dyeing wastewater.

Association Between Caliber of Retinal Vessels and Cardiovascular Disease: a Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: The aim of this study to is report the findings of a systemic review and meta-analysis of the literature on the association between retinal vascular caliber and cardiovascular diseases. RECENT FINDINGS: The caliber of retinal vessels has been recognized as an important biomarker for risk stratification in various cardiovascular diseases, such as coronary artery disease, heart failure, stroke, and mortality. Non-invasively quantifying retinal vasculature may be useful in screening individuals who are at risk of cardiovascular disease. Further evaluating the role of retinal vessel anatomy and incorporating it into a scoring system on risk of cardiovascular diseases are needed in future studies.

Cross-sectional study for the clinical application of extracorporeal membrane oxygenation in Mainland China, 2018.

BACKGROUND: To investigate the epidemiology and in-hospital mortality of veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) in Mainland China throughout 2018. METHODS: Patients supported by ECMO from 1700 tertiary hospitals in 31 provinces from January 1 to December 31, 2018, were selected from the National Clinical Improvement System database. RESULTS: The 1700 included hospitals had 2073 cases of ECMO in 2018, including 714 VV and 1359 VA ECMOs. The average patient age was 50 years (IQR 31-63), and 1346 were male. The average hospital stay was 17 days (IQR 7-30), and the average costs per case was $36,334 (IQR 22,547-56,714). The three provinces with the highest number of ECMO cases were Guangdong, Beijing, and Zhejiang; the southeast coastal areas and regions with higher GDP levels had more cases. Overall in-hospital mortality was 29.6%. Mortality was higher among patients who were male, over 70 years old, living in underdeveloped areas, and who were treated during the summer. Mortality in provinces with more ECMO cases was relatively low. The co-existence of congenital malformations, blood system abnormalities, or nervous system abnormalities increased in-hospital mortality. CONCLUSIONS: Mortality and medical expenses of ECMO among patients in China were relatively low, but large regional and seasonal differences were present. Risk factors for higher in-hospital mortality were older age, male sex, in underdeveloped areas, and treatment during the summer. Additionally, congenital malformations and blood system and nervous system abnormalities were associated with in-hospital mortality.

Analysis of factors associated with vision after cataract surgery in chronic renal failure patients on dialysis.

BACKGROUND: To analyze the related factors of visual acuity after phacoemulsification and intraocular lens implantation in chronic renal failure (CRF) patients. METHODS: We retrospectively analyzed 42 patients (51 eyes) with CRF (failure, uremia) on hemodialysis or peritoneal dialysis and 40 patients (50 eyes) without CRF as a control group. Each individual underwent physical and laboratory examinations including best corrected visual acuity (BCVA), slit lamp examination, intraocular pressure, corneal endothelial cell count, fundus examination and optical coherence tomography (OCT) for macular examination. The patients with abnormal platelet, liver and kidney function, coagulation function received treatment accordingly to reduce the perioperative risk. All patients underwent phacoemulsification with IOL implantation. Follow-up examinations were performed at 1 week, 1 month and 3 months after surgery and included BCVA, slit lamp examination, noncontact IOP, dilated fundus examination and OCT of the macula. RESULTS: In control group the preoperative RBC, HB, Cr, and urea values were not associated with the pre- or postoperative BCVA. The RBC, HB, Cr, urea, SBP, DBP, preoperative BCVA and postoperative BCVA values were all significantly different between CRF and control group(P < 0.05). CONCLUSION: In CRF patients, the RBC, HB, Cr and Urea indexes should be monitored before the cataract operation for guarded visual outcome. The pre-existing ocular comorbidities could significantly compromise the vision. The CRF patients could achieve relatively good visual outcome after cataract surgery when the underlaying diseases are effectively managed.

Pancreatic kallikrein protects against diabetic retinopathy in KK Cg-Ay/J and high-fat diet/streptozotocin-induced mouse models of type 2 diabetes.

AIMS/HYPOTHESIS: Many studies have shown that tissue kallikrein has effects on diabetic vascular complications such as nephropathy, cardiomyopathy and neuropathy, but its effects on diabetic retinopathy are not fully understood. Here, we investigated the retinoprotective role of exogenous pancreatic kallikrein and studied potential mechanisms of action. METHODS: We used KK Cg-Ay/J (KKAy) mice (a mouse model of spontaneous type 2 diabetes) and mice with high-fat diet/streptozotocin (STZ)-induced type 2 diabetes as our models. After the onset of diabetes, both types of mice were injected intraperitoneally with either pancreatic kallikrein (KKAy + pancreatic kallikrein and STZ + pancreatic kallikrein groups) or saline (KKAy + saline and STZ + saline groups) for 12 weeks. C57BL/6J mice were used as non-diabetic controls for both models. We analysed pathological changes in the retina; evaluated the effects of pancreatic kallikrein on retinal oxidative stress, inflammation and apoptosis; and measured the levels of bradykinin and B1 and B2 receptors in both models. RESULTS: In both models, pancreatic kallikrein improved pathological structural features of the retina, increasing the thickness of retinal layers, and attenuated retinal acellular capillary formation and vascular leakage (p < 0.05). Furthermore, pancreatic kallikrein ameliorated retinal oxidative stress, inflammation and apoptosis in both models (p < 0.05). We also found that the levels of bradykinin and B1 and B2 receptors were increased after pancreatic kallikrein in both models (p < 0.05). CONCLUSIONS/INTERPRETATION: Pancreatic kallikrein can protect against diabetic retinopathy by activating B1 and B2 receptors and inhibiting oxidative stress, inflammation and apoptosis. Thus, pancreatic kallikrein may represent a new therapeutic agent for diabetic retinopathy.

Intracellular Delivery of Luciferase with Fluorescent Nanodiamonds for Dual-Modality Imaging of Human Stem Cells.

Delivering functional proteins (such as enzymes) into cells is important in various biological studies and is often accomplished indirectly by transfection with DNA or mRNA encoding recombinant proteins. However, the transfection efficiency of conventional plasmid methods is low for primary cells, which are crucial sources of cell therapy. Here, we present a new platform based on the use of fluorescent nanodiamond (FND) as a biocompatible nanocarrier to enable rapid, effective, and homogeneous labeling of human mesenchymal stem cells (MSCs) with luciferase for multiplex assays and ultrasensitive detection. More than 100 pg of FND and 100 million copies of firefly luciferase can be delivered into each MSC through endocytosis. Moreover, these endocytic luciferase molecules are catalytically active for hours, allowing the cells to be imaged and tracked in vitro as well as in vivo by both fluorescence and bioluminescence imaging. Our results demonstrate that luciferase-conjugated FNDs are useful as multifunctional labels of human stem cells for diverse theranostic applications.

CSF3R mutations were associated with an unfavorable prognosis in patients with acute myeloid leukemia with CEBPA double mutations.

The aim of this study was to explore the clinical features and prognostic significance of CSF3R mutations in AML patients with CEBPA double mutations (CEBPAdm). One hundred one AML patients with CEBPAdm were retrospectively analyzed in this study. Mutation status of CSF3R gene, clinical features, and long-term outcomes were analyzed. The frequency of CSF3R mutations in patients with CEBPAdm was 19.80% (20/101). Patients with CSF3R mutations were associated with a lower platelet (u = 2.728, P = 0.006) and higher leukocytes (u = 3.178, P = 0.001) compared with those with wide-type CSF3R gene. The 5-year relapse-free survival (RFS) was 18.7% in patients with CSF3R mutations, which was significantly lower than those with wide-type CSF3R (31.8%) (P = 0.015). The 5-year overall survival (OS) was also significantly different between patients with and without CSF3R mutations (17.5% versus 57.4%, P = 0.019). The prevalence of CSF3R mutations was high in AML patients with CEBPAdm, which indicated a poor prognosis, and CSF3R mutations may be a new potential candidate for prognostically re-stratifying AML patients with CEBPAdm.