Proteinase 3 depletion attenuates leukemia by promoting myeloid differentiation.

Hematopoietic stem and progenitor cells (HSPCs) that have impaired differentiation can transform into leukemic blasts. However, the mechanism that controls differentiation remains elusive. Here, we show that the genetic elimination of Proteinase 3 (PRTN3) in mice led to spontaneous myeloid differentiation. Mechanistically, our findings indicate that PRTN3 interacts with the N-terminal of STAT3, serving as a negative regulator of STAT3-dependent myeloid differentiation. Specifically, PRTN3 promotes STAT3 ubiquitination and degradation, while simultaneously reducing STAT3 phosphorylation and nuclear translocation during G-CSF-stimulated myeloid differentiation. Strikingly, pharmacological inhibition of STAT3 (Stattic) partially counteracted the effects of PRTN3 deficiency on myeloid differentiation. Moreover, the deficiency of PRTN3 in primary AML blasts promotes the differentiation of those cells into functional neutrophils capable of chemotaxis and phagocytosis, ultimately resulting in improved overall survival rates for recipients. These findings indicate PRTN3 exerts an inhibitory effect on STAT3-dependent myeloid differentiation and could be a promising therapeutic target for the treatment of acute myeloid leukemia.

Localized biogenic volatile organic compound emission inventory in China: A comprehensive review.

Volatile organic compounds (VOCs) are the precursors of forming ozone (O3) and fine particulate matter (PM2.5). Accurate estimates of biogenic VOC (BVOC) emissions is essential for understanding the formation mechanism of O3 and PM2.5 pollution and precise reduction on anthropogenic emissions and thereby mitigating O3 and PM2.5 pollution. To gain comprehensive knowledge of BVOC emissions and improve the accuracy of their estimation, this study reviewed localized national, regional, and municipal emission estimations in China. From their comparisons, BVOC emission characteristics and deficiencies in the inventory compilation methodology were also investigated. The estimated BVOC emissions in China ranged between 10 and 58.9 Tg yr-1 and 10.9-18.9 Tg C yr-1, with diverse contributions for different BVOC categories. The simulated historical and future BVOC emissions exhibited an increasing trend. The uncertainty of the BVOC estimates was mainly from the applications of incomplete emission models, less localized accurate emission factors, deficient vegetation cover information, and low-resolution meteorological data in the inventory compilation. The regional and municipal BVOC emission inventories mainly focused on the Beijing-Tianjin-Hebei, Pearl River Delta, Sichuan Basin, and Yangtze River Delta regions, as well as the cities therein. For the same area, different studies reported diverse BVOC emissions by a maximum of two orders of magnitude. There is usually a lack of basic data with more detailed investigations and higher precision for estimation of BVOC emissions. By summarizing the measurements on terrestrial and marine BVOC emission fluxes, they are mainly focused on the Guangdong, Zhejiang and Jiangxi provinces, and Yellow Sea, East China Sea, and South China Sea, respectively. Expanding the temporal and spatial scales of observations is encouraged to enhance our understanding on the emissions and improve the emission estimates.

Variations in VOCs Emissions and Their O3 and SOA Formation Potential among Different Ages of Plant Foliage.

Volatile organic compounds (VOCs) emitted by plant foliage play an important role in ozone (O3) and secondary organic aerosol (SOA) formation. Their emissions can be influenced by the leaf age. We explored the VOCs emissions and their effects on the formation of O3 and SOA from plant foliage in different ages. VOCs emissions from the young, mature, and senescent leaves of Ginkgo biloba, Ligustrum lucidum, and Forsythia suspensa were measured using the dynamic enclosure system and the TD-GC-MS technique. Based on the emission rates of quantified compounds, their potential to form O3 and SOA was estimated. Results showed that there were significant differences in the VOCs emission rate and their composition among leaves in different ages. The emission rate of the total VOCs by young leaves was the highest, while the lowest by senescent leaves. Monoterpenes were the dominant VOCs category, and isoprene emission had the lowest contribution for the leaves at each age. With increasing leaf age, the proportion of monoterpenes emission increased, and the proportion of sesquiterpenes decreased. The variations of isoprene and other VOCs were different. The potentials of total VOCs, isoprene, monoterpenes, sesquiterpenes, and other VOCs to form O3 (OFP) and SOA (SOAP) varied significantly among leaves at different ages. The total OFP and SOAP were the highest by young leaves, while the lowest by senescent leaves. With increasing leaf age, the contribution of monoterpenes to OFP and SOAP also increased, while that of sesquiterpenes decreased. Our study will provide support for the more accurate parameterization of the emission model and help to understand the VOCs emissions and study the precise prevention and control of complex air pollution at different times.

HOTAIR knockdown impairs metastasis of cervical cancer cells by down-regulating metastasis-related genes.

This study investigated the role of LncRNA HOTAIR knockdown in the biological impacts on cervical cancer cells. The HOTAIR gene in two human cervical cancer cell lines was silenced with small interfering (si) RNA siHOTAIR. Proliferation, apoptosis, migration and invasion of cells were assessed following the knockdown. The expressions of Notch1, EpCAM, E-cadherin, vimentin and STAT3 were assessed using qRT-PCR and Western blotting analysis. Compared with controls, HOTAIR levels were reduced significantly, the OD values of cells were significantly decreased in proliferation assays, cell apoptosis was significantly increased, cell migration and invasion were significantly reduced after HOTAIR knockdown. Molecular analysis showed that Notch1, EpCAM, vimentin and STAT3 expressions were decreased significantly, while the expression of E-cadherin was significantly increased after HOTAIR knockdown. Rescue experiments further confirmed that Notch1 and STAT3 were involved in siHOTAIR-mediated reduction of migration and invasion of cervical cancer cells.IMPACT STATEMENTWhat is already known on this subject? Long non-coding RNAs including HOTAIR, is implicated in occurrence and development of cancer and have been explored to develop new therapeutic options for cancer.What do the results of this study add? HOTAIR silencing significantly reduces the viability and migration ability of cells and induces cell apoptosis, adding experimental data supporting the potential use of HOTAIR specific-siRNA as a therapeutic avenue for the cancer.What are the implications of these findings for clinical practice and/or further research? The finding from this study would help develop clinically applicable therapeutic avenues for the cancer and identify new treatment targets in the relevant pathways leading to new drugs or treatments.

Facile construction of S-containing Co-based metal organic framework core-shell microspheres as an efficient bifunctional oxygen electrocatalyst.

A cost-effective non-noble metal bifunctional electrocatalyst towards the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) is very important for energy-related applications. Micro/nanomaterials with core-shell structures have emerged as potential non-noble metal catalyst candidates. Herein, an efficient bifunctional oxygen electrocatalyst, S-containing Co-based metal organic framework core-shell microspheres (Co-MOF-CSMSs), has been designed and constructed by using 2,2':5',2''-terthiophene-5,5''-dicarboxylic acid as a novel ligand through a facile one-step hydrothermal method. Due to the integrated favorable structural characteristics of the core-shell structure and MOFs for electrocatalysis, Co-MOF-CSMSs are revealed as a good bifunctional electrocatalyst for the ORR and OER, including an onset potential of 0.93 V vs. RHE (reversible hydrogen electrode), a half-wave potential of 0.78 V vs. RHE and an overpotential of 0.35 V at 10 mA cm-2. This work provides a low-cost and facile method to design and construct advanced micro/nanomaterials with core-shell structures to targetedly develop high-performance bifunctional oxygen electrocatalysts.

Cell-tailored calcium carbonate particles with different crystal forms from nanoparticle to nano/microsphere.

Inspired by biomineralization, the first synthesis of size-tunable calcium carbonates from nanoparticles (YC-CaCO3 NPs) to nano/microspheres (YC-CaCO3 N/MSs) with a porous structure was accomplished using a facile method under the mediation of the secretion from yeast cells (YCs). The biomolecules derived from the secretion of YCs were used as conditioning and stabilizing agents to control the biosynthesis of the YC-CaCO3 materials. The morphology and crystal forms of YC-CaCO3 materials can be affected by the biomolecules from the secretion of YCs. With increasing concentrations of biomolecules, the morphologies of the obtained CaCO3 materials changed from nanoparticles to nano/microspheres with a porous structure, while the crystal forms transformed from amorphous to calcite. Functional investigations showed that YC-CaCO3 NSs with a porous structure effectively acted as anticancer drug carriers with accurate and selective drug release in tumor tissue, which suggests that they have great potential to function as a therapeutic delivery system. These application features are mainly attributed to the satisfactory biocompatibility and biodegradability, high drug-loading capacity, and pH-dependent sustained drug release performance of the porous YC-CaCO3 NSs. The biomimetic synthesis strategy of YC-CaCO3 materials mediated by YC secretion not only helps to shed light on the biomineralization mechanism in organisms, but may also lead to a new means of biosynthesizing organic-inorganic nanocomposites.

The Role of Blood Flow in Corpus Luteum Measured by Transvaginal Two-Dimensional and Three-Dimensional Ultrasound in the Prediction of Early Intrauterine Pregnancy Outcomes.

Objective: The purpose of this study was to explore the application of transvaginal two-dimensional and three-dimensional power Doppler ultrasound in pregnancy corpus luteum to predict the final outcome of early intrauterine pregnancy. Methods: This is a prospective observational cohort study. Six hundred early intrauterine pregnant women in Shanghai Changning Maternity and Infant Health Hospital were selected as the research objects from January 2015 to December 2015. According to the follow-up of 12 weeks, these pregnant women were divided into the normal pregnancy group (group A, n = 512) and the terminational pregnancy group (group B, n = 88). They all underwent both transvaginal two-dimensional ultrasound and three-dimensional power Doppler ultrasound to obtain relevant parameters of corpus luteum, namely, the average diameter of the corpus luteum (D), resistance index (RI), pulsatility index (PI), corpus luteum volume (V), vascularization index (VI), blood flow index (FI), and vascularized blood flow index (VFI). Among them, V, VI, FI, and VFI were calculated with the virtual organ computer-aided analysis method. Receiver operator characteristic (ROC) curves were drawn. The corresponding diagnostic cut-off, sensitivity, and specificity were calculated and compared. Results: Compared with group A, the D, V, VI, FI, and VFI of corpus luteum in group B were statistically significant lower while RI and PI were statistically significant higher (P < 0.05). The diagnostic cut-off values in the prediction of early intrauterine pregnancy outcomes were D: 14.48, RI: 0.56, PI: 0.81, V: 3.89, VI: 21.48, FI: 38.99, and VFI: 10.21 respectively, and the sensitivity and specificity were D (99.2%, 67.0%), RI (98.9%, 65.0%), PI (78.4%, 89.1%), V (95.1%, 78.4%), VI (74.%, 90.9%), FI (91.8%, 90.9%), and VFI (93.9%, 87.5%) respectively. The area under the ROC curve of the combined index (RI + FI) was 0.963, which was not significantly higher compared with any single index, and both the sensitivity and specificity were 94.3%. Conclusion: Both transvaginal two-dimensional and three-dimensional ultrasonography are of high diagnostic value in predicting the early intrauterine pregnancy outcomes.

A descriptive analysis of injury triage, surge of medical demand, and resource use in an university hospital after 8.12 Tianjin Port Explosion, China.

OBJECTIVE: The 8.12 Tianjin Port Explosion in 2015 caused heavy casualties. Pingjin Hospital, an affiliated college hospital in Tianjin, China participated in the rescue activities. This study aims to analyze the emergency medical response to this event and share experience with trauma physicians to optimize the use of medical resource and reduce mortality of critical patients. METHODS: As a trauma centre at the accident city, our hospital treated 298 patients. We retrospectively analyzed the data of emergency medical response, including injury triage, injury type, ICU patient flow, and medical resource use. RESULTS: There were totally 165 deaths, 8 missing, and 797 non-fatal injuries in this explosion. Our hospital treated 298 casualties in two surges of medical demand. The first one appeared at 1 h after explosion when 147 wounded were received and the second one at 4 h when 31 seriously injured patients were received, among whom 29 were transferred from Tianjin Emergency Center which was responsible for the scene injury triage. After reexamination and triage, only 11 cases were defined as critical ill patients. The over-triage rate reached as high as 62.07%. Seventeen patients underwent surgery and 17 patients were admitted to the intensive care unit. CONCLUSIONS: The present pre-hospital system is incomplete and may induce two surges of medical demand. The first one has a much larger number of casualties than predicted but the injury level is mild; while the second one has less wounded but almost all of them are critical patients. The over-triage rate is high. The hospital emergency response can be improved by an effective re-triage and implementation of a hospital-wide damage control.

Effect of picric acid and enzymatic creatinine on the efficiency of the glomerular filtration rate predicator formula.

BACKGROUND: To investigate the impact of serum creatinine measurement on the applicability of glomerular filtration rate (GFR) evaluation equations. METHODS: 99mTc-DTPA plasma clearance rate was used as GFR reference (rGFR) in patients with chronic kidney disease (CKD). Serum creatinine was measureded using enzymatic or picric acid creatinine reagent. The GFR of the patients were estimated using the Cockcroft-Gault equation corrected for body surface area, simplified Modification of Diet in Renal Disease (MDRD) equation, simplified MDRD equation corrected to isotopes dilution mass spectrometry, the CKD epidemiology collaborative research equation, and two Chinese simplified MDRD equations. RESULTS: Significant differences in the eGFR results estimated through enzymatic and picric acid methods were observed for the same evaluation equation. The intraclass correlation coefficient (ICC) of eGFR when the creatinine was measured by the picric acid method was significantly lower than that of the enzymatic method. The assessment accuracy of every equation using the enzymatic method to measure creatinine was significantly higher than that measured by the picric acid method when rGFR was > or = 60 mL/min/1.73m2. CONCLUSIONS: A significant difference was demonstrated in the same GFR evaluation equation using the picric acid and enzymatic methods. The enzymatic creatinine method was better than the picric acid method.

Prevalence of hyperuricemia and its related risk factors in healthy adults from Northern and Northeastern Chinese provinces.

BACKGROUND: Hyperuricemia (HUA) is a potential risk factor for developing insulin resistance, hypertension, dyslipidemia and cardiovascular disease. Therefore, we studied the prevalence of HUA and associated risk factors in the population of two provinces in northern China. METHODS: Based on the research of Chinese Physiological Constant and Health Conditions conducted in 2008-2010, we enrolled 29,639 subjects in a randomized, stratified study in four sampling areas in Heilongjiang Province and the Inner Mongolia Autonomous Region. We collected 13,140 serum samples to determine biochemical indicators including uric acid(UA), glucose, blood lipids, liver function, and renal function, and finally a representative sample of 8439 aged 18 years and older was determined. We also defined and stratified HUA, hypertension, diabetes, obesity and lipid abnormalities according to international guidelines. RESULTS: There were significant differences in the UA levels between different genders and regions. The total prevalence of HUA is 13.7%. Men had a higher prevalence of HUA than women (21% vs. 7.9%; P < 0.0001). As age increased, HUA prevalence decreased in men but rose in women. The suburbs of big cities had the highest HUA prevalence (18.7%), and in high-prevalence areas the proportion of women with HUA also increased. A stepwise logistic regression model was used to filter out twelve HUA risk factors, including age, gender, residence, hypercholesterolemia, hypertriglyceridemia, impaired fasting glucose, hypertension, obesity, abdominal obesity, CKD, drinking and sleeping. After adjusting for these factors, the odds ratio of HUA was 1.92 times higher in men than in women. Compared with agricultural and pastoral areas, the odds ratio of having HUA was 2.14 for participants in the suburbs of big cities and 1.57 in the center of big cities. CONCLUSIONS: The prevalence of HUA is high in northern China. The differences in HUA prevalence by geographic region suggested that unbalanced economic development and health education, therefore HUA prevention measures should be strengthened to improve quality of life and reduce health care costs.

[NVP-BEZ235 inhibits proliferation and colony-forming capability of CD34(+)CD38(-) human acute myeloid leukemia stem cells].

This study was aimed to explore the effect of NVP-BEZ235, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, on proliferation, cell cycle and colony forming capability of CD34(+)CD38(-) human acute myeloid leukemia (AML) KG1a cells. Flow cytometry was used to detect expression of CD34 and CD38 on the surface of human AML KG1a cells; Trypan blue assay was used to analyze the effect of NVP-BEZ235 at various concentrations on proliferation of KG1a cells; flow cytometry was performed to examine the cell cycle of KG1a cells after NVP-BEZ235 treatment; Soft agar colony-forming experiment was used to detect the colony forming ability of KG1a cells treated with NVP-BEZ235 at various concentrations. The results indicated that the percentage of CD34(+)CD38(-) AML KG1a cells was (98.02 ± 0.72)%. NVP-BEZ235 (0.125 - 1 µmol/L) inhibited the proliferation of KG1a cells in a time-and dose-dependent manner (P < 0.05) and the 50% inhibition concentrations (IC50) at 24 h and 48 h were 0.597 µmol/L and 0.102 µmol/L, respectively. KG1a cells were arrested at G0/G1 phase after treating with 0.5 µmol/L NVP-BEZ235 for 24 h, it was significantly higher than that of control group (83.2 ± 3.80)% vs (43.47 ± 9.60)% (P < 0.05). KG1a cells treated with NVP-BEZ235 (0 - 1 µmol/L) for 14 d and 21 d, the number of colony decreased respectively from (375.67 ± 21.46) per 2500 KG1a cells and (706.33 ± 87.31) per 2500 KG1a cells to 0, with statistical significance (P < 0.05). It is concluded that NVP-BEZ235 can inhibit proliferation and colony-forming capability of CD34(+)CD38(-) human AML KG1a cells.

Serum γ-glutamyltransferase and uric acid levels are associated with impaired fasting glucose in adults from Inner Mongolia, China.

BACKGROUND: Serum γ-glutamyltransferase (GGT) and uric acid (UA) levels are elevated in patients with diabetes or cardiovascular disease. Prediabetes, characterized by impaired glucose tolerance, is an important risk factor for overt diabetes as well as cardiovascular disease. Therefore, the aim of this study was to explore the relationship between GGT, UA and prediabetes in a Chinese population, and provide a scientific basis for the early prevention and treatment of diabetes. METHODS: We performed a cross-sectional population-based study in a cohort of 2694 subjects (1211 men and 1483 women, aged 35-86 years). Questionnaires and physical examinations were performed using standardized procedures. Fasting blood was collected to measure glucose and other biochemical parameters. The subjects were divided into two groups with either normal fasting glucose (NFG) or impaired fasting glucose (IFG), according to international diagnostic criteria. Logistic regression analysis was performed to estimate odds ratios (OR) and 95% confidence intervals. RESULTS: Compared with the NFG group, the IFG group had significantly higher blood pressure but lower high-density lipoprotein-cholesterol in women. Body mass index, waist circumference, triglyceride, glucose, GGT, and UA levels were significantly higher in males and females in the IFG group than those in the NFG group. Logistic regression analysis revealed that the OR for prediabetes increased with increasing serum GGT quartiles and UA quartiles. GGT and UA were positively associated with prediabetes in men and women, independent of age, ethnicity, smoking, alcohol consumption, blood pressure, physical labor, and other confounders. CONCLUSIONS: We found that serum GGT and UA levels were positively associated with prediabetes in men and women living in areas inhabited by Chinese ethnic minorities. As elevated GGT and UA levels were associated with significantly increased risk of prediabetes, they may be used as sensitive biological markers of prediabetes.

Effectiveness of a nurse-led intensive educational programme on chronic kidney failure patients with hyperphosphataemia: randomised controlled trial.

AIMS AND OBJECTIVES: To prospectively evaluate the effects of a nurse-led educational intervention on the management of hyperphosphataemia as well as knowledge of phosphate among patients with end-stage renal disease. BACKGROUND: Haemodialysis and phosphate binder therapy are the major methods used to reduce the phosphate level in dialysis patients. However, patient education related to hyperphosphataemia, diet and phosphate binders may be another important factor associated with the success of the control of the hyperphosphataemia. DESIGN: This prospective randomised controlled trial was conducted during the period from June 2009-March 2011 at the HD units of two hospitals in Tianjin, China. METHODS: A total of 80 participants were randomly assigned to experimental group (n=40) and control group (n=40). Participants in the experimental group received the nurse-led intensive educational programme, including individualised education and educational session about diet and medicine regimes, etc., while participants in the control group received the routine guidance. RESULTS: There were statistically significant differences between the study groups in decline in serum phosphorus and calcium-phosphorus product levels and improvement in patients' general knowledge three months postintervention, and these differences sustained until the end of the study. Increased serum calcium level was observed both in the experimental group and in the control group, but there was no significant difference between groups. No statistical significance was found regarding serum albumin level between the groups. No significant difference in the serum parathyroid hormone level was found between the groups by month 6. CONCLUSIONS: Nurse-led intensive educational programme plays an important role in the control of hyperphosphataemia among patients with end-stage renal disease. RELEVANCE TO CLINICAL PRACTICE: Chronic kidney failure patients with hyperphosphataemia are more likely to benefit from nurse-led intensive educational programmes.

Electrophoretic deposition of HA/MWNTs composite coating for biomaterial applications.

A composite coating of hydroxyapatite (HA)/multi-walled carbon nanotubes (MWNTs) has been fabricated by electrophoretic deposition (EPD). The nano powders of HA and MWNTs were dispersed in ethanol with total concentration of 0.005 g/mL and MWNTs 20% and 30% contents (wt). And the pH value of suspension was adjusted in a range from 4 to 5. After stabilization the mixture was ultrasonically treated for 3 h to form a stable suspension. Prior to the electrophoretic deposition, the titanium substrate was hydrothermally treated at 140 in NaOH (10 mol/L) solution for 6 h. A titanium sheet and circinal net of stainless steel were used as a cathode and an anode respectively, and a constant deposition voltage of 30 V was applied for 50-60 s in the EPD process. The thickness of the coatings was controlled from 10 microm to 20 microm. The samples of composite coating were then sintered in a resistance tube furnace in flowing argon at 700 for 2 h. The structure of the as prepared coating was characterized by SEM and XRD, and the bonding force of the coating/substrate was measured by an interfacial shear strength test. It is shown that the bonding strengths between the coating and the titanium substrate is as high as 35 MPa. The cell culture experiments indicate that the prepared composite coating of HA/MWNTs possesses good biocompatibility.