Search

Objective: Bronchopulmonary dysplasia (BPD) is the most complication of premature infants, accurate identification of at-risk infants and early intervention are key to improve outcomes. The objective of this study is to explore a multifactorial model to predict the risk of BPD. Materials and methods: A total of 148 neonates with gestational age ≤ 32 weeks were recruited. Clinical data and serum samples at 1week after birth were collected. Content of serum free monosaccharides and degraded monosaccharides were analyzed by high-performance liquid chromatography (HPLC). The logistic regression analysis was drawn to build models for the early diagnosis of BPD. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of different monosaccharides for BPD, and combined with clinical data to improve the diagnostic efficiency, which was calculated using the area under the curve (AUC). Results: Of the 148 eligible infants, 42 developed BPD (28.38%), which consist of 71.43% mild (30/42) and 28.57%moderate-severe (12/42) cases. The significant risk factors for BPD in the multivariate analysis of clinical data and serum monosaccharides were gestational age, birth-weight, the duration of invasive mechanical ventilation and non-invasive ventilation, patient ductus arteriosus (PDA) and pregnancy-induced hypertension, glucose (Glc-F), mannose (Man-F), fucose (Fuc-D), galactosamine (GalN-D), galactose (Gal-D), glucose (Glc-D) and mannose (Man-D). In addition, the concentration of Glc-D and Fuc-D inmoderate-severe BPD group were significantly lower than those in mild BPD group. The combination of gestational age and Fuc-D determined the risk of developing BPD, with an AUC value of 0.9964. Conclusion: The prediction model based on the gestational age and Fuc-D predicts the development of BPD with high sensitivity (95.24%) and specificity (93.24%) and might facilitate early intervention and improve outcome.

In the context of urban stock renewal, the spatial arrangement of public cultural facilities (PCFs) should follow the principles of equity and efficiency to ensure that residents have equitable access to and quality of public cultural services. The aim of this article is to study the spatial distribution of PCFs and the coupling of supply and demand of cultural resources in Tianjin’s central area. By building a supply-demand coupling coordination model and other methods, the equalization of the spatial distribution of PCFs is measured from various perspectives, and the results suggest that more than half of the sub-districts are in a situation of supply and demand imbalance. To fulfill the purpose of meeting residents’ actual needs, balancing supply and demand for cultural resources, and coordinating the increase in stock, these sub-districts’ facilities enter the step of optimization. Depending on the circumstances, the quality and scale of these facilities are optimized, or new facility points are added based on the maximized coverage model. The optimization is shown to be beneficial in terms of updating design and coverage quantity using two real-world cases. Finally, the coverage of facilities in the study area is maximized, facility utilization is made more efficient, and residents’ needs for public cultural services are satisfied.

A rock avalanche that destroyed 23 houses and killed 35 people occurred on 28 August 2017, Nayong, SW China. Combined with the dynamic parameters from seismic signal inversion, a discrete element model, MatDEM was used to determine the rock avalanche’s kinematic behavior. Although the dynamic process obtained through inversion will be disturbed by factors, such as rockfall from the source area, by comparing the velocity of rock avalanche versus horizontal distance traveled, the best combination of parameters was selected from different values given. The dynamic process obtained by modeling was compared with the nearest seismometer frequency distribution spectrum, showing that the dynamic process is in good agreement with those parameters inverted from seismic signals. The simulation results show that the movement process lasted for nearly 40 s, with a maximum speed of 40 m/s. This model of selecting parameters contributes to explain the dynamic processes of similar rock avalanche more accurately and is of great significance to the hazard prediction in the karst area.

A crucial requirement for Software Defined Network (SDN) is that data plane forwarding behaviors should always agree with control plane policies. Such requirement cannot be met when there are forwarding anomalies , where packets deviate from the paths specified by the controller. Most anomaly detection methods for SDN install dedicated rules to collect statistics of each flow, and check whether the statistics conform to the “flow conservation principle”. We find these methods have a limited detection scope: they look at one flow each time, thus can only check a small number of flows simultaneously. In addition, dedicated rules for statistics collection can impose a large overhead on flow tables of SDN switches. To this end, this paper presents FOCES, a network-wide forwarding anomaly detection and localization method in SDN. Different from previous methods, FOCES applies a new kind of flow conservation principle at network wide, and can check forwarding behaviors of all flows in the network simultaneously, without installing any dedicated rules. Finally, FOCES applies a voting-based method to localize malicious switches when anomalies are detected. Experiments with four network topologies show that FOCES can achieve a detection precision higher than 90%, when the packet loss rate is no larger than 10%, and a localization accuracy of around 80% when the packet loss rate is no larger than 5%.

Seed germination and seedling establishment are important for the reproductive success of plants, but seeds and seedlings typically encounter constantly changing environmental conditions. By inhibiting seed germination and post-germinative growth through the PYR1/PYL/RCAR ABA receptors and PP2C co-receptors, the phytohormone abscisic acid (ABA) prevents premature germination and seedling growth under unfavorable conditions. However, little is known about how the ABA-mediated inhibition of seed germination and seedling establishment is thwarted. Here, we report that ABA Signaling Terminator (ABT), a WD40 protein, efficiently switches off ABA signaling and is critical for seed germination and seedling establishment. ABT is induced by ABA in a PYR1/PYL/RCAR-PP2C-dependent manner. Overexpression of ABT promotes seed germination and seedling greening in the presence of ABA, whereas knockout of ABT has the opposite effect. We found that ABT interacts with the PYR1/PYL/RCAR and PP2C proteins, interferes with the interaction between PYR1/PYL4 and ABI1/ABI2, and hampers the inhibition of ABI1/ABI2 by ABA-bound PYR1/PYL4, thereby terminating ABA signaling. Taken together, our results reveal a core mechanism of ABA signaling termination that is critical for seed germination and seedling establishment in Arabidopsis.

On July 23, 2019, a large catastrophic landslide occurred in Shuicheng, Guizhou, China. It was a rapid and long run-out landslide that resulted in more than 50 casualties. The displaced materials traveled an approximate distance of 1250 m, with a descending height of around 465 m. In this paper, seismic record analyses and numerical simulation were conducted to determine the run-out behavior of the Shuicheng landslide. To determine the main characteristics of the landslide, geological and climatic settings were obtained by conducting a detailed field survey. The DAN3D model was used to simulate the propagation and run-out process of the landslide. It was observed that a combined Frictional-Voellmy model provides assuring results in simulating the Shuicheng landslide. The total duration of the landslide is 60 s with an average velocity of 20 m/s. The maximum velocity is estimated to be 40 m/s along the right bank of the valley, while a high initial velocity of 24 m/s was recorded at the initiation of the landslide. Seismic records obtained from the nearby seismic stations were used to calculate the location of the event and interpret the dynamic process of the landslide. The Arias intensity, Hilbert-Huang transform, and Empirical mode decomposition were used to obtain a detailed time history of the landslide. The results of the numerical simulation and seismic record analyses are expected to portray the process of similar landslides. This will improve the accuracy of landslide hazard mapping in the region.

Objective:: Intervertebral disc degeneration (IDD) represents one of the leading causes of low back pain. Research suggests the participation of LINC01116 in IDD progression. Herein, the current study explored the underlying mechanism of LINC01116 in IDD. Methods:: The differential expression patterns of LINC01116 in IDD and normal tissues were analyzed using the GEO database. Human nucleus pulposus (NP) cells were provided and treated with IL-1β to establish IDD models in vitro. LINC01116 expression was detected and intervened. Indices such as cell proliferation, apoptosis, and extracellular matrix (ECM)-related factor expression were determined using CCK-8 assay, flow cytometry, and Western blotting. LINC01116 sublocation was identified by means of nuclear/cytosol fractionation assay. The binding relationships between LINC01116 and miR-9-5p and miR-9-5p and ZIC5 were verified by bioinformatics analysis, dual-luciferase assays, RNA immunoprecipitation (RIP) assay, and RNA-pull-down. Western blotting was conducted to measure the levels of the Wnt pathway key factors. Results and Discussion:: LINC01116 was highly expressed in the degenerative NP cells. Silencing of LINC01116 critically promoted degenerative NP cell proliferation and inhibited apoptosis and ECM loss. LINC01116 was located in the cytoplasm. In degenerative NP cell models, LINC01116 could competitively bind to miR-9-5p to elevate ZIC5 expression. LINC01116 induced NP cell apoptosis and impeded NP cell proliferation and ECM synthesis by inhibiting miR-9-5p and miR-9-5p targeted ZIC5. ZIC5 could effectively increase the levels of the Wnt pathway-related factors. Conclusion:: Silencing LINC01116 blocked its adsorption of miR-9-5p as a sponge to promote the miR-9- 5p expression and inhibit ZIC5/Wnt activation, thus impacting NP cell biological functions

The excessive apoptosis of nucleus pulposus (NP) cells is a major risk factor in the progress of cervical intervertebral disc degeneration (IVDD). In this study, we investigated the impact of miR-98 on apoptosis of NP cells and the potential molecular mechanisms. Lipopolysaccharide (LPS) was used to establish an NP cell IVDD model. The sponging effect of miR-98 on TRAIL 3′UTR was predicted by ENCORI and assessed by the dual-luciferase reporter gene system. The expression levels of miR-98, TRAIL, and TRAIL pathway-related genes were tested by qRT-PCR, Western blot, and immunofluorescence analysis. Cell apoptosis was analyzed by Hoechst 33258 staining and flow cytometry. Cell viability was analyzed by MTT assay. It was found that the expression level of miR-98 was downregulated, while the level of TRAIL was upregulated in IVDD tissues, and their levels were negatively and positively associated with the clinical MRI grade, respectively. The LPS treatment resulted in a significant decrease of the miR-98 expression level and an increase of the TRAIL expression level in NP cells. miR-98 reduced NP cell apoptosis under LPS treatment in vitro. miR-98 directly targeted TRAIL. Moreover, the mRNA and protein levels of DR5, FADD, cleaved caspase8, cleaved caspase3, and cleaved PARP were downregulated by miR-98 overexpression. Overexpression of TRAIL partially reversed the suppressive roles of miR-98 on cell apoptosis and activation of the TRAIL pathway. We concluded that miR-98 inhibited apoptosis of NP cells by inactivating the TRAIL pathway via targeting TRAIL in IVDD NP cells. These results indicated that miR-98 might be a therapeutic target for IVDD.

Summary Background Calcium ion (Ca2+) is essential for human physiology by regulating various signal transduction pathways inside all cells and in the blood circulation. Aim We compared circulating Ca2+ levels in the healthy control against 48 different types of human diseases. Design A total of 144 201 independent test results of Ca2+ levels from 48 clinically defined diseases and 141 679 independent test results of Ca2+ from healthy individuals who came to the hospital for annual physical examination were retrieved during the past 5 years. Methods Ca2+ was determined by the standard ‘Arsenazo III method’ in the clinical laboratory of Affiliated Hospital of Qingdao University. We analyzed all data using RStudio V.1.3.1073 and python libraries 3.8. Results All 48 types of diseases had decreased Ca2+ levels than the healthy control based on either mean or median values. Patients suffering from preeclampsia had the lowest Ca2+ levels among all 48 diseases. The perfect area under the curve, sensitivity, and specificity values of 1.0, 0.96 and 0.96 indicated that Ca2+ was an excellent biomarker for diagnosing preeclampsia. Extremely low Ca2+ was present in patients suffering kidney-related diseases. Since the correlation between each disease on the statistical features is proportional to their vector distance, the two-component analysis revealed that preeclampsia, sepsis and chronic obstructive pulmonary disease were closely related among 48 diseases. Conclusions All human diseases were associated with reduced circulating Ca2+ levels, where the decreased Ca2+ was a perfect biomarker for preeclampsia. Kidney-related conditions were related to over-down-regulation of Ca2+ levels. The resemblance of preeclampsia to sepsis and chronic obstructive pulmonary disease based on two-component analysis suggested that the three unrelated diseases might share a similar mechanism of the circulating Ca2+ regulation.

BackgroundAbscisic acid (ABA) plays an important role in plant growth and adaptation through the ABA signaling pathway. The ABA-responsive element binding (AREB/ABF) family transcriptional factors are central regulators that integrate ABA signaling with various signaling pathways. It has long been known that ABA inhibits rhizobial infection and nodule formation in legumes, but the underlying molecular mechanisms remain elusive.ResultsHere, we show that nodulation is very sensitive to ABA and exogenous ABA dramatically inhibits rhizobial infection and nodule formation in soybean. In addition, we proved that GmbZIP1, an AREB/ABF transcription factor, is a major regulator in both nodulation and plant response to ABA in soybean.GmbZIP1was specifically expressed during nodule formation and development. Overexpression ofGmbZIP1resulted in reduced rhizobial infection and decreased nodule number. Furthermore,GmbZIP1is responsive to ABA, and ectopic overexpression ofGmbZIP1increased sensitivity of Arabidopsis plants to ABA during seed germination and postgerminative growth, and conferred enhanced drought tolerance of plants. Remarkably, we found that GmbZIP1 directly binds to the promoter ofGmENOD40–1, a marker gene for nodule formation, to repress its expression.ConclusionOur results identified GmbZIP1 as a node regulator that integrates ABA signaling with nodulation signaling to negatively regulate nodule formation.

Additional file 1:. Supplementary information contains Supplementary Fig. S1-S3.

A rock avalanche that destroyed 23 houses and killed 35 people occurred on 28 August 2017, Nayong, SW China. Combined with the dynamic parameters from seismic signal inversion, a discrete element model, MatDEM was used to determine the kinematic behaviour of the rock avalanche. By comparing the velocity evolution process of numerical simulation with that of seismic signal inversion, we are able to find the best fitting parameters. The dynamic process obtained by modelling was compared with the frequency distribution spectrum of the nearest seismometer, showing that the dynamic process is in good agreement with those parameters inverted from seismic signals. The simulation results show that the movement process lasted for nearly 40 s, with a maximum speed of 40 m/s. The selected models and parameters contribute to explain the dynamic processes of similar rock avalanche more accurately and are of considerable significance to the hazard prediction in karst area.

DELLA (GAI/RGA/RGL1/RGL2/RGL3) proteins are key negative regulators in GA (gibberellin) signaling and are involved in regulating plant growth as a response to environmental stresses. It has been shown that the DELLA protein PROCERA (PRO) in tomato promotes drought tolerance, but its molecular mechanism remains unknown. Here, we showed that the gai-1 (gibberellin insensitive 1) mutant (generated from the gai-1 (Ler) allele (with a 17 amino acid deletion within the DELLA domain of GAI) by backcrossing gai-1 (Ler) with Col-0 three times), the gain-of-function mutant of GAI (GA INSENSITIVE) in Arabidopsis, increases drought tolerance. The stomatal density of the gai-1 mutant was increased but its stomatal aperture was decreased under abscisic acid (ABA) treatment conditions, suggesting that the drought tolerance of the gai-1 mutant is a complex trait. We further tested the interactions between DELLA proteins and ABF2 (abscisic acid (ABA)-responsive element (ABRE)-binding transcription factors) and found that there was a strong interaction between DELLA proteins and ABF2. Our results provide new insight into DELLA proteins and their role in drought stress tolerance.

A focused SAR study was conducted on a series of N1-substituted pyrazolopyrimidinone PDE2 inhibitors to reveal compounds with excellent potency and selectivity. The series was derived from previously identified internal leads and designed to enhance steric interactions with key amino acids in the PDE2 binding pocket. Compound 26 was identified as a lead compound with excellent PDE2 selectivity and good physicochemical properties.

A rock avalanche that destroyed 23 houses and killed 35 people occurred on August 28, 2017 in Nayong, southwest China. A discrete element model, MatDEM, was combined with the dynamic parameters of seismic signal inversion to determine the kinematic behavior of rock avalanches. The best fitting parameters were identified by comparing the velocity evolution process of numerical simulation with that of seismic signal inversion. The dynamic process obtained by modeling was compared with the frequency distribution spectrum of the nearest seismometer, with results revealing that the dynamic process agrees with the parameters inverted from the seismic signals. The simulation results further indicate that the movement process lasted for nearly 40 s, with a maximum speed of 40 m/s. The selected models and parameters can help provide a more accurate explanation of the dynamic processes of similar rock avalanches and are significant to hazard prediction in karst areas.

A crucial requirement for Software Defined Network (SDN) is that data plane forwarding behaviors should always agree with control plane policies. Such requirement cannot be met when there are forwarding anomalies, where packets deviate from the paths specified by the controller. Most anomaly detection methods for SDN install dedicated rules to collect statistics of each flow, and check whether the statistics conform to the flow conservation principle. Such per-flow detection methods have a limited detection scope: they look at one flow each time, thus can only check a limited number of flows simultaneously. In addition, dedicated rules for statistics collection can impose a large overhead on flow tables of SDN switches. To this end, this paper presents FOCES, a network-wide forwarding anomaly detection method in SDN. Different from previous methods, FOCES applies a new kind of flow conservation principle at network wide, and can check forwarding behaviors of all flows in the network simultaneously, without installing any dedicated rules. Experiments show FOCES can achieve a detection precision higher than 90% for four network topologies, even when packet loss rates are as high as 10%.

An efficient microwave-assisted extraction technique was used to extract wedelolactone from Eclipta alba. To optimize the effects of the microwave-assisted extraction (MAE) processing parameters on the yield of wedelolactone, a response surface methodology with a central composite rotatable design was employed. Four independent variables were investigated: microwave power, ethanol concentration, extraction time and the solvent-to-solid ratio. The optimum conditions were: microwave power, 208W; ethanol concentration, 90%; extraction time, 26.5min; and solvent-tosolid ratio, 33mL·g−1. Under the optimal conditions, the extraction yield of wedelolactone was (82.67±0.16)%, which is in close agreement with the value predicted by the statistical model. MAE was also compared to other conventional methods, including ultrasonic assisted extraction, extraction at room temperature and heat reflux extraction. MAE has distinct advantages for the extraction of wedelolactone in terms of both time and efficiency. Therefore, MAE is a reliable method for the extraction of wedelolactone from Eclipta alba.

On 28th August 2017, a disastrous rock avalanche occurred in Nayong, Guizhou, China. This catastrophic event killed 35 people and destroyed 23 houses. In this study, the failure process of the avalanche was analyzed using UAV video footage and seismic signal recordings obtained for the pre- and post-failure stages of the landslide. To better understand the possible mechanism of the avalanche and its dynamic characteristics, a numerical simulation was conducted using a dynamic model (DAN3D) to simulate the runout behaviour of the displaced materials. Simulated results indicate that the failure process of the Nayong rock avalanche lasted approximately 30 s; the duration of the failure process is close to that from the UAV video footage and seismic signal recordings (35 s). The duration of movement during the landslide process is estimated to be approximately 90 s with a maximum velocity of 40 m/s. The combined frictional-Voellmy model delivered the most accurate results when simulating this event. The selected models and parameters are expected to aid in clarifying the propagation processes of similar rock avalanches and thus improve the accuracy of hazard prediction in mountainous karst areas.

Efficient and applicable approach to macrolactonizations, with ready availability of starting materials and simple operation, remains a challenging task for the organic community. We developed a ‘freshman-can-do’ protocol to medium- and large-sized lactones, not depending on high-dilution or slow addition techniques. Application of this method for the synthesis of natural lactones or potentially pharmaceutical compounds might be useful for organic chemists and pharmacists.

Isobaric vapor–liquid equilibrium (VLE) data for the system (ethyl myristate + ethyl palmitate) were measured at 0.5, 1.0 and 1.5 kPa with a VLE modified Othmer still. The esters used in this study are the major components of biodiesel. Thermodynamic consistency of the experimental data was checked both with the Herington consistency test and point consistency test of Van Ness Test, which ensure the reliability of experimental data. Furthermore, the experimental VLE data were regressed with Nonrandom Two-Liquid (NRTL) activity coefficient model and predicted by UNIFAC and Dortmund (modified UNIFAC) models. The results show that the calculated values of the vapor-phase mole fraction and boiling temperature by NRTL, UNIFAC models and Dortmund model agree well with the experimental data.

Quinoline derivatives are important heterocyclic compounds because of their natural occurrence and applications in pharmaceutical fields. In this paper, a sequence of propargyl-allenyl isomerization and aza-electrocyclization for the synthesis of polyfunctionalized quinolines are described.

Isobaric vapor–liquid equilibrium (VLE) data of the mixture of methyl palmitate and methyl stearate at 0.1 kPa, 1 kPa, 5 kPa, and 10 kPa were measured with a modified Othmer still. Methyl palmitate and methyl stearate were the major components of the biodiesel. The experimental results were correlated with Wilson and nonrandom two-liquid (NRTL) activity coefficient models and were compared with a group contribution model (UNIFAC). The binary interaction parameters of the Wilson and NRTL models were fitted into the experimental data which were obtained at different pressures. The UNIFAC model did not predict the VLE for methyl palmitate and methyl stearate at reduced pressures well. The Wilson and NRTL models could well correlate with the experimental data at 1 kPa, 5 kPa, and 10 kPa. However, for the lower pressure 0.1 kPa, the Wilson model and NRTL model had worse correlatations with our experimental data than the higher pressures. These models could develop VLE calculations of the mixtures and provide g...

Serine/threonine protein kinases Aurora A, B, and C play essential roles in cell mitosis and cytokinesis. Currently a number of Aurora kinase inhibitors with different isoform selectivities are being evaluated in the clinic. Herein we report the discovery and characterization of 21c (AC014) and 21i (AC081), two structurally novel, potent, kinome-selective pan-Aurora inhibitors. In the human colon cancer cell line HCT-116, both compounds potently inhibit histone H3 phosphorylation and cell proliferation while inducing 8N polyploidy. Both compounds administered intravenously on intermittent schedules displayed potent and durable antitumor activity in a nude rat HCT-116 tumor xenograft model and exhibited good in vivo tolerability. Taken together, these data support further development of both 21c and 21i as potential therapeutic agents for the treatment of solid tumors and hematological malignancies.

Herein we report the synthesis of graphitic carbon nitride (g-C 3 N 4 ) by directly heating sulfuric acid treated melamine precursor. Thermoanalytical methods (TG-DSC) in combination with XRD, XPS and elemental analysis were used to characterize the condensation steps of the precursor. The TG-DSC curves clearly show significant difference in thermal behavior between the treated and untreated melamine. The sublimation of melamine during condensation was significantly suppressed by treating melamine with sulfuric acid. The decomposition of melamine sulfuric acid and the condensation of melamine occur simultaneously. The N/C ratio of the prepared carbon nitride (1.53) is slight higher than that of the ideal crystal g-C 3 N 4 (1.33), indicating the incomplete condensation of amino groups in the material. The XPS and elemental analysis show that there is no sulfur residue in the final product. The sample synthesized from sulfuric acid treated melamine shows relatively higher BET surface area. The photocatalytic performance of the as prepared carbon nitride was evaluated under visible light irradiation ( λ > 420 nm). The photocatalytic H 2 production rate on sample synthesized from sulfuric acid treated melamine is 2 times higher than that on sample synthesized from untreated melamine.

The problem of designing a crude distillation unit (CDU) is not only a distillation design. It has the added complexity that the properties of crudes are different around the world, sometimes from heavy to light. In this work, we focused our attention on designing a predistillation scheme suitable for heavy crude oils by thermodynamic analysis. The exergy efficiencies and losses were analyzed to evaluate available schemes indicating that the two-preflash-drums case, with the highest exergy efficiencies, lowest exergy losses, and lowest furnace duty, is the best choice for heavy crude oils. In addition, the method of selecting the optimum process for energy saving may benefit the process optimization of other distillation units.

The synthesis of polysubstituted oxazolines is of great interest due to the synthetic and pharmaceutical importance. We developed a sequence of Pummerer/Michael reactions for the stereoselective synthesis of 5-(1-(arylthio)vinyl)-oxazolines.

A process of depolymerization of a new fucosylated chondroitin sulphate from Thelenata ananas by free-radicals was developed. The fractions with different molecular weights and a narrow molecular weight distribution was obtained. The products were characterised by physicochemical properties, FT-IR spectra and NMR spectra. The results confirm the retention of primary structure of the fractions after the depolymerization. Furthermore, the anticoagulant activity of the fractions was evaluated by the activated partial thromboplastin time (APTT). The APTT activity decreases in proportion to the molecular weight following a logarithmic-like function, and the potentiating of prolongation of APTT activity requires at least an oligosaccharide chain of about 6–8 units (6000–7000 Da). Compared to high doses of low molecular weight heparin (LMWH), a more desirable molecular weight fraction (13,950 Da) demonstrates significantly lower anticoagulant activity. Thus, the fraction has more potential as an antithrombotic agent with reduced bleeding risk relative to LMWH.

The p38α mitogen-activated protein (MAP) kinase is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1β and tumor necrosis factor α. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, and Crohn’s disease, as well as other diseases where aberrant cytokine signaling is the driver of disease. In this communication, we describe a novel class of 7-alkyl-1,5-bis-aryl-pyrazolopyridinone-based p38α inhibitors. In particular, compound 3f is highly potent in the enzyme and cell-based assays, selective in an Ambit kinase screen, and efficacious (ED50 ≤ 0.01 mg/kg) in the rat collagen induced arthritis (CIA) model.

The p38 mitogen-activated protein kinase (MAPK) is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1beta and tumor necrosis factor alpha. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, osteoporosis, and many other diseases where aberrant cytokine signaling is the driver of disease. Herein, we describe a novel class of 3-amino-7-phthalazinylbenzoisoxazole-based inhibitors. With relatively low molecular weight, these compounds are highly potent in enzyme and cell-based assays, with minimal protein shift in 50% human whole blood. Compound 3c was efficacious (ED 50 = 0.05 mg/kg) in the rat collagen induced arthritis (CIA) model.

c-Met is a receptor tyrosine kinase that plays a key role in several cellular processes but has also been found to be overexpressed and mutated in different human cancers. Consequently, targeting this enzyme has become an area of intense research in drug discovery. Our studies began with the design and synthesis of novel pyrimidone 7, which was found to be a potent c-Met inhibitor. Subsequent SAR studies identified 22 as a more potent analog, whereas an X-ray crystal structure of 7 bound to c-Met revealed an unexpected binding conformation. This latter finding led to the development of a new series that featured compounds that were more potent both in vitro and in vivo than 22 and also exhibited different binding conformations to c-Met. Novel c-Met inhibitors have been designed, developed, and found to be potent in vitro and in vivo.

In this study, the feasibility of applying a magnetotactic bacterial isolate (MTB), Stenotrophomonas sp. to the removal of Au(III) was investigated. Biosorption experiments showed that Au(III) biosorption capacity exhibited no significant difference in the initial pH range of 1.0-5.5, while decreased more significantly in the initial pH range of 5.5-13.0. Langmuir isotherm indicated that the maximum Au(III) biosorption capacity of Stenotrophomonas sp. were 506, 369 and 308 mg g(-1) dry weight biomass at the initial pH values of 2.0, 7.0 and 12.0, respectively. Thiourea was proved to be an effective desorbent to recover Au from the MTB biomass and 91% Au adsorbed on the biomass could be recovered at equilibrium when the thiourea concentration was 0.8M. The magnetic separator developed by our research team used for separating Au loaded MTB biomass showed high separation efficiency, with 100% biomass removed at the magnetic intensity of 1200 Gs in 180 min. The analyses from FTIR and XRD further confirmed that the reduction of Au(III) to Au(0) by the reductants on the MTB biomass occurred, and the deposition of nano-crystal Au(0) particles, ranging from 24.7 to 31.4 nm, could be estimated on the biomass surface.

The separation and purification of linoleic acid (LA) from sunflower seed oil by urea complex fractionation was studied. Crystallization reaction conditions of urea inclusion were optimized using the response surface method, and the optimal model was developed. Using the linear weighting method of the fitting model for optimization, the optimal balance between the purity and the recovery of LA was obtained. Under optimal conditions, the purity of LA was 87.8%, and the recovery was 83.4% at a urea-to-fatty acids ratio (w/w) of 0.94, 95% ethanol-to-urea (v/w) of 5.00, a crystallization temperature of 18.0 °C, and a crystallization time of 5.0 h. Verification results revealed that the predicted values from these models were reasonably close to the experimentally observed values.

This paper proposes a modified operation mode of batch extractive distillation with two reboilers. The separation of ethanol and water using as ethylene glycol is well done to validate the feasibility of this mode. The pilot-plant experimental data under the identical operational conditions between the regular mode and the modified mode are in particular discussed. The studied results prove more practical advantages of the modified mode over the regular mode such as easier operation control, more flexibility and higher separation efficiency etc. So it supplies certain guidance for the industrial application of batch extractive distillation process.