Corrosive effect on saturated pool boiling heat transfer characteristics of metallic surfaces with hierarchical micro/nano structures.

Surface modification is of critical interest to enhance boiling heat transfer in terms of heat transfer coefficient or critical heat flux (CHF), which is significantly affected by distinct surface morphology and wettability and it can improve the efficiency and safety of equipment. Furthermore, actual service environment may cause severe corrosion to the processed structured surfaces while its consequence on boiling heat transfer is still obscure. In this article, comprehensive researches are conducted to unravel corrosive effect on metallic samples made of stainless steel (SS) and Inconel materials with microstructures. Different constructions (i.e., microgroove, microcavity and micropillar array) and characteristic dimensions (∼20, 50 µm) of microstructure, various duration time (up to 300 days) and pH values (∼7.0-8.5) of corrosive environment are compared thoroughly. Conclusions can be drawn that not all microstructures can enhance pool boiling heat transfer characteristics, especially in terms of CHF values. More importantly, CHF value of SS microgroove sample firstly increases from 60.94 to 94.09 W·cm-2 in 50 days, then decreases to 47.77 W·cm-2 in 300 days, which can be attributed to competition result between formation of hierarchical micro/nano structure with enhancing wicking capability and chemistry condition with increasing contact angle. In addition, distinct bubble dynamics during pool boiling is also analyzed. The insights obtained from this article can be used to guide surface modification method and to reveal evolvement rule of engineered metallic surface in highly corrosive and harsh boiling heating transfer environment.

Novel Covalent Probe Selectively Targeting Glutathione Peroxidase 4 In Vivo: Potential Applications in Pancreatic Cancer Therapy.

Glutathione peroxidase 4 (GPX4) emerges as a promising target for the treatment of therapy-resistant cancer through ferroptosis. Thus, there is a broad interest in the development of GPX4 inhibitors. However, a majority of reported GPX4 inhibitors utilize chloroacetamide as a reactive electrophilic warhead, and the selectivity and pharmacokinetic properties still need to be improved. Herein, we developed a compound library based on a novel electrophilic warhead, the sulfonyl ynamide, and executed phenotypic screening against pancreatic cancer cell lines. Notably, one compound A16 exhibiting potent cell toxicity was identified. Further chemical proteomics investigations have demonstrated that A16 specifically targets GPX4 under both in situ and in vivo conditions, inducing ferroptosis. Importantly, A16 exhibited superior selectivity and potency compared to reported GPX4 inhibitors, ML210 and ML162. This provides the structural diversity of tool probes for unraveling the fundamental biology of GPX4 and exploring the therapeutic potential of pancreatic cancer via ferroptosis induction.

Simultaneous Covalent Modification of K-Ras(G12D) and K-Ras(G12C) with Tunable Oxirane Electrophiles.

Owing to their remarkable pharmaceutical properties compared to those of noncovalent inhibitors, the development of targeted covalent inhibitors (TCIs) has emerged as a powerful method for cancer treatment. The K-Ras mutant, which is prevalent in multiple cancers, has been confirmed to be a crucial drug target in the treatment of various malignancies. However, although the K-Ras(G12D) mutation is present in up to 33% of K-Ras mutations, no covalent inhibitors targeting K-Ras(G12D) have been developed to date. The relatively weak nucleophilicity of the acquired aspartic acid (12D) residue in K-Ras may be the reason for this. Herein, we present the first compound capable of covalently engaging both K-Ras(G12D) and K-Ras(G12C) mutants. Proteome profiling revealed that this compound effectively conjugates with G12C and G12D residues, modulating the protein functions in situ. These findings offer a unique pathway for the development of novel dual covalent inhibitors.

Investigation on the Composition and Extraction Mechanism of the Soluble Species from Oily Sludge by Solvent Extraction.

Oily sludge (OS) was extracted with petroleum ether (PE), methanol, carbon disulfide (CDS), acetone, and isometric CDS/acetone mixture (IMCDSAM), respectively, to obtain soluble species (E1-E5) and extraction residues (R1-R5). The soluble species were analyzed by gas chromatography/mass spectrometry (GC/MS), and the extraction residues were characterized by Fourier transform infrared spectrometry (FTIR) and thermogravimetric analysis (TGA). Results showed that the extract yield of the soluble species from OS using CDS and IMCDSAM as the solvent was 61.0 and 67.3%, respectively. GC/MS results exhibited that the compounds detected in E1-E5 are mainly hydrocarbons and oxygen-containing compounds. E1-E5 are rich in alkanes, alkenes, ketones, alcohols, and other oxygen-containing compounds. Double-bond equivalence (DBE) and carbon numbers (CNs) of the compounds detected in E1, E2, and E4 are distributed in 0-4 (DBE) and 10-20 (CNs), respectively, while the DBE and CNs of the detected compounds in E3 and E5 are concentrated in 0-6 and 15-35, respectively. Thermogravimetry-differential thermogravimetry (TG-DTG) profiles presented that pyrolysis of OS occurred mainly in the temperature range of 150-750 °C, while pyrolysis of R1-R5 took place in the range of 350-750 °C. In the temperature range of 150-550 °C, the weight losses of OS and each extraction residue differ significantly, with OS having a much higher weight loss than the extraction residues. Meanwhile, the possible mechanism of oily sludge extraction was considered. Results revealed that selecting a low-polar or nonpolar solvent capable of selectively destroying hydrogen bonds and/or aromatic interactions is critical for improving the extract yield of OS.

TMT-based quantitative proteomics analysis reveals the differential proteins between fresh and frozen-thawed sperm of yak (Bos grunniens).

Sperm cryopreservation is one of the most effective methods for the conservation of germplasm resources and used of superior sires widely. However, the motility of yak (Bos grunniens) sperm was low after thawing and the proteomics changes in sperm cryopreservation remain unknown. Therefore, the aim of this study was to explore the differences between fresh sperm and frozen sperm of yak through the proteomic analysis and thus improve the understanding of sperm cryodamage. The Tandem Mass Tags (TMT) technology was used to screen differentially expressed proteins (DEPs) before and after freezing. Then, GO and KEGG analysis were conducted to analyze the DEPs enriched signaling pathways. Finally, the DEPs, including superoxide dismutase 1 (SOD1) and NADH ubiquinone oxidoreductase core subunit S8 (NDUFS8) were verified by the immunofluorescence technique. The results showed that there were 229 DEPs between fresh and frozen-thawed yak sperm. Compared with the fresh sperm, 120 proteins were up-regulated and 109 proteins were down-regulated in frozen-thawed sperm. The GO annotation showed that the up-regulated proteins enriched in metabolic and cytoskeleton-related processes, including lipoprotein metabolic process, lipid transport, extracellular region and intermediate filament cytoskeleton organization. In contrast, the down-regulated proteins enriched in biological processes including single fertilization, sperm capacitation and response to unfolded protein. KEGG pathway analysis indicated that freezing and thawing affected the oxidative phosphorylation pathway, the fructose and mannose metabolic pathway and the glycerolipid metabolic pathway of yak sperm. Immunofluorescence results showed that the protein expression level of SOD1 protein in the frozen group was significantly lower than that in the fresh group (P < 0.01), and the protein expression level of NDUFS8 protein was significantly higher in frozen group (P < 0.01). This study revealed the DEPs between fresh and frozen-thawed sperm and provides a theoretical basis to further explore the exertion of normal biological functions of yak sperm after freezing and thawing.

Pyrolysis Kinetic Analysis of Sequential Extract Residues from Hefeng Subbituminous Coal Based on the Coats-Redfern Method.

Sequential extract residues (R i , i = 1, 2, 3, 4, and 5) were obtained from Hefeng acid-washing coal (HFAC) by petroleum ether, carbon disulfide, methanol, acetone, and isometric carbon disulfide/acetone mixture, sequentially. Pyrolysis behavior of the residues was determined using thermogravimetry analysis. The Coats-Redfern method with different reaction orders was used to analyze the pyrolysis kinetic of each sample, and the kinetic parameters, including correlation coefficient (R 2), activation energy (E), and pre-exponential factor (A), were calculated. Results showed that the weight loss of extract residues was higher than HFAC, and pyrolysis behavior varies greatly for residues, which is related to the unstable structure after extraction. From conversion-temperature (α-T) curves, the pyrolysis process was divided into three stages: low-temperature stage (150-350 °C), medium-temperature stage (350-550 °C), and high-temperature stage (550-950 °C). The medium-temperature stage made great contribution to the process of pyrolysis, which was dominated by depolymerization and decomposition reaction. The relationship between kinetic parameters and reaction order showed that the swelling effect is an important reason for the discrepancy of E for each sample in the process of pyrolysis.

Discovery of Hexahydrofuro[3,2-b]furans as New Kinase-Selective and Orally Bioavailable JAK3 Inhibitors for the Treatment of Leukemia Harboring a JAK3 Activating Mutant.

Janus kinase 3 (JAK3) is a potential target for the treatment of hematological malignancies. Herein, we report the discovery of a series of new orally bioavailable irreversible JAK3 kinase inhibitors. The representative compound 12n potently inhibited JAK3 kinase activity with an IC50 value of 1.2 nM and was more than 900-fold selective over JAK1, JAK2, and Tyk2. Cell-based assays revealed that 12n significantly suppressed phosphorylation of JAK3 and the downstream effectors STAT3/5 and also robustly restrained proliferation of BaF3 cells transfected with JAK3M511I activating mutation and human leukemia U937 cells harboring JAK3M511I with IC50 values of 22.9 and 20.2 nM, respectively. More importantly, 12n showed reasonable pharmacokinetic (PK) properties, and oral administration of 12n at a dose of 50 mg/kg twice daily led to tumor regression in a U937 cell inoculated xenograft mouse model. Thus, 12n represents a promising lead compound for further optimization to discover new therapeutic agents for hematological malignancies.

Effect of the Nickel Source on the Structure, Performance, and Carbon Deposition of the Ni/Al2O3 Catalyst for CO2-CH4 Reforming.

Ni/Al2O3 catalysts were prepared with Ni(NO3)2·6H2O, NiSO4·6H2O, NiCl2·6H2O, and NiC4H6O4·4H2O as nickel sources by the solution combustion method. The catalysts were characterized by X-ray diffraction, H2 temperature-programmed hydrogenation, TG-DTG, TPH, and transmission electron microscopy methods, and the effect of the nickel source on performance of the Ni/Al2O3 catalyst was investigated via the CO2-CH4 reforming experiment. Results showed that Ni dispersion, Ni size, and the metal-support interaction between active component Ni and the support were influenced significantly by anion in nickel sources, resulting in that the performance of each catalyst was different. Highly dispersed Ni species, small Ni crystallite size, and strong metal-support interaction were presented in the Ni/Al2O3 catalysts with Ni(NO3)2·6H2O and NiSO4·6H2O as nickel sources. Evaluation results showed that the catalyst prepared with Ni(NO3)2·6H2O exhibited higher activity and stability, with CH4 and CO2 conversions of 31.21 and 48.97%. Carbon deposition analysis demonstrated that the catalyst prepared with NiSO4·6H2O contained more graphite carbon.

Functional Group Characteristics and Pyrolysis/Combustion Performance of Karamay OS Based on FT-IR and TG-DTG Analyses.

Proximate analysis, ultimate analysis, Fourier-transform infrared spectroscopy (FT-IR), and thermogravimetry-differential thermal analysis characterization were carried out on oily sludge (OS) samples OS1-OS5, from Karamay, Xinjiang, China. The Coast-Redfern model (CRm) was used to simulate the pyrolysis and combustion kinetics of oily samples. The results showed that the peak area percentage of benzene ring trisubstitution of OS5, in the range of 700-900 cm-1, is close to 75%, corresponding to its high volatile content. Based on the kinetic analysis by the CRm, it is found that the fitting degree of the five samples is better when the reaction order is selected as n = 2, with R 2 close to 1.00 and 2RT/E to 0. Among them, the S N and D W of OS5 are 17.8 × 10-10%2 min-2 °C-3 and 0.10899 × 10-5% min-1 °C-2, respectively, higher than those of other samples, indicating a good combustion performance.

Effects of Promoters on the Structure, Performance, and Carbon Deposition of Ni-Al2O3 Catalysts for CO2-CH4 Reforming.

Modified Ni-Al2O3 catalysts with Ca, Co, and Ce species as promoters were prepared by the combustion method, and the structure, morphology, reduction characteristic, and CO2-CH4 reforming of the catalysts were discussed by X-ray diffraction (XRD), H2-temperature-programmed reduction (H2-TPR), energy-dispersive X-ray (EDX) mapping, NH3-temperature-programmed desorption (NH3-TPD), N2 adsorption-desorption, thermogravimetric-differential thermal analysis (TG-DTG), and temperature-programmed hydrogenation (TPH) methods. The crystal size of Ni on Ca-Ni-Al2O3 was 16.97 nm, and the active component and additive were distributed well in the catalyst. Co-Ni-Al2O3 presented a surface area of 65.70 m2·g-1 and a pore diameter of 161.60 nm. Ce-Ni-Al2O3 showed relatively stable nickel-aluminum spinel (NiAl2O4), which could not be easily reduced to the active component Ni. Evaluation results demonstrated that the performance of the catalysts followed the order Co-Ni-Al2O3 > Ca-Ni-Al2O3 > Ni-Al2O3 > Ce-Ni-Al2O3. Carbon deposition analysis showed that the carbon resistance of Ca-Ni-Al2O3 was poor and graphitic carbon was generated on the catalyst. However, Ce-Ni-Al2O3 showed less carbon deposition, which might have resulted from the lower activity of the catalyst.

Effect of Ca Promoter on the Structure, Performance, and Carbon Deposition of Ni-Al2O3 Catalyst for CO2-CH4 Reforming.

Ni-Al2O3 catalyst with different Ca abundance for CO2-CH4 reforming was prepared by the solution combustion method. By some mature characterization methods, such as XRD, H2-TPR, EDX mapping, TEM, TPH and TG-DTG technologies, and the reforming experiment, the effect of Ca content on the structure, reforming performance, and carbon deposition of Ni-Al2O3 catalyst was investigated. Results showed that the grain size of active component Ni on the 4 wt % Ca-modified catalyst (Ni-Ca-4) was small (13.67 nm), presenting good dispersion, and that Ni and Ca elements were well distributed on the support, which was more conducive to the CO2-CH4 reforming. Evaluation results showed that activity of Ni-Ca-4 was higher than the others, with CH4 and CO2 conversions of 52.0 and 96.7%, respectively, and H2/CO ratio close to unit. Carbon deposition proposed that the amount of carbon deposited on the surface of Ni-Ca-4 was lower (18%), and the type of carbon was attributed to amorphous carbon, indicating that 4 wt % Ca-promoted catalyst presented better anticarbon deposition performance.

Outcome after a new porous tantalum rod implantation for treatment of early-stage femoral head osteonecrosis.

BACKGROUND: Tantalum rods have been used in osteonecrosis of the femoral head (ONFH) for several years, while Zimmer trabecular metal implants have been proposed as the best choice. The aim of this study was to evaluate the effect of a new porous tantalum rod on the treatment of early ONFH. METHODS: From July 2014 to December 2015, 19 patients (21 hips) were treated with Runze tantalum rod, and 20 patients (20 hips) received Zimmer tantalum prosthesis. All patients were followed up for at least 3 years. RESULTS: There was no significant difference in demographic characteristics and the Harris Hip Score (HHS) improvement between the two groups. Kaplan-Meier analysis did not show any statistically significant difference in survival rates. One case in the Runze group had persistent pain and required conversion to total hip arthroplasty (THA) 8 months post-surgery. Histological evaluations revealed the presence of abundant new bone ingrowth into pores of the tantalum. The osteonecrosis observed in other patients was almost unchanged. At final follow-up, progressive collapse of the femoral head or the apparent joint space narrowing had not occurred. CONCLUSIONS: Compared with the traditional implants, implantation of the Chinese tantalum rod in the treatment of Association Research Circulation Osseous (ARCO) stages I, and II ONFH demonstrated highly encouraging clinical results.

Efficacy of novel nano-hydroxyapatite/polyurethane composite scaffolds with silver phosphate particles in chronic osteomyelitis.

Recently, chronic osteomyelitis is still a challenging surgical problem. Unfortunately, the traditional clinical method using bone cement loaded antibiotics is restricted due to its non-biodegradability and limited release of antibiotics. Hydroxyapatite is a good adsorbent with good biocompatibility, an ideal bone repair material, and can avert the requirement for the secondary surgical procedure of removal. In this study, nano-hydroxyapatite combined with a polyurethane containing 3% silver (Ag/n-HA/PU) was synthesized, and investigated for its efficacy of treating chronic bone infection with bone defects. To clarify its silver ions release characteristics, the concentration of the Ag+ in the elution was analyzed every day after in vitro deionized water immersion. A chronic osteomyelitis of tibia in rabbit model was established, and 70 New Zealand rabbits were divided into 4 groups, including the blank control group, nano-hydroxyapatite combined with polyurethane (n-HA/PU) implant group, 3% Ag/n-HA/PU group and 10% Ag/n-HA/PU group after debridement. Routine blood tests, radiography, Micro-CT, and histological staining were conducted at 4 days, 3, 6 and 12 weeks post-treatment. The results showed that the released silver from the 3% Ag/n-HA/PU and 10% Ag/n-HA/PU exhibited an initial burst release and followed by a slow controlled release up to 39 days and 42 days respectively. A good repair of bone defects, an appropriate rate of degradation of scaffolds and no significant toxicity were observed in the 3% Ag/n-HA/PU group, indicating the advantages of this novel synthetic scaffold to be a potential option for the treatment of chronic osteomyelitis. A novel nano-composite, nano-hydroxyapatite combined with a polyurethane containing 3% silver (Ag/n-HA/PU) provide controlled release of Ag+, illustrated by its abilities of biodegradation, antimicrobial activity, and favorable repair of bone defects in the treatment of chronic osteomyelitis.

[Novel nano-hydroxyapatite/polyurethane composite scaffold in the treatment of chronic osteomyelitis].

Objective: To evaluate the bone repair efficacy of the new nano-hydroxyapatite (n-HA)/polyurethane (PU) composite scaffold in the treatment of chronic osteomyelitis in tibia. Methods: A novel levofloxacin@mesoporous silica microspheres (Lev@MSNs)/n-HA/PU was successfully synthesized. Its surface structure was observed by scanning electron microscopy (SEM). Fifty adult female New Zealand rabbits were randomly selected, and osteomyelitis was induced in the right tibia of the rabbit by injecting bacterial suspension ( Staphylococcus aureus; 3×10 7 CFU/mL), which of the method was described by Norden. A total of 45 animals with the evidence of osteomyelitis were randomly divided into 4 groups, and the right medullary cavity of each animal was exposed. Animals in the blank control group (group A, n=9) were treated with exhaustive debridement only. The remaining animals were first treated by exhaustive debridement, and received implantations of 5 mg Lev@PMMA (group B, n=12), 1 mg Lev@MSNs/n-HA/PU (group C, n=12), and 5 mg Lev@MSNs/n-HA/PU (group D, n=12), respectively. At 12 weeks postoperatively, the right tibia of rabbits were observed by X-ray film, and then gross observation, methylene blue/acid fuchsin staining, and SEM observation of implant-bone interface, as well as biomechanical test (measuring the maximal compression force) were performed. Results: X-ray films showed that the infection were severer than those of preoperation in group A, while the control of inflammation and bone healing of rabbits in group D were obviously better than those at preoperation. The gross observation showed extensive bone destruction in group A, a significant gap between bone tissue and the material in groups B and C, and close combination between bone tissue and the material in group D. The histology of the resected specimens showed that there was no obvious new bone formation around the materials in groups B and C, and there was abundant new bone formation around the periphery and along the voids of the materials and active bone remodeling in group D. The SEM observation of the bone-implant interface demonstrated that no new bone formation was observed at the bone-implant interface in groups B and C. However, bony connections and blurred boundaries were observed between the material and host bone tissue in group D. The biomechanical test showed the maximal compression force of groups B and D were significantly higher than that of groups A and C ( P<0.05), but there was no significant difference between groups B and D ( P>0.05). Conclusion: The novel synthetic composite Lev@MSNs/n-HA/PU exhibit good antibacterial activities, osteoconductivity, and biomechanical properties, and show great potential in the treatment of chronic osteomyelitis of rabbits.

Levofloxacin loaded mesoporous silica microspheres/nano-hydroxyapatite/polyurethane composite scaffold for the treatment of chronic osteomyelitis with bone defects.

Chronic osteomyelitis is a prolonged persistent disease accompanied by bone destruction and sequestrum formation, it is very difficult to treat. Antibiotic loaded polymethyl methacrylate (PMMA) has been used in clinical. However, when PMMA was implanted in the body, the deficiencies is that it is non-biodegradable and a second operation is needed. Here, we synthesize a novel levofloxacin loaded mesoporous silica microspheres/nano-hydroxyapatite/polyurethane composite scaffolds, and evaluated the therapeutic effect in treating chronic osteomyelitis with bone defects in rabbit model compared with bulk PMMA. X-ray, Micro CT, gross pathology as well as immunohistochemical staining were performed at predesignated time points (1, 3, 6 and 12 weeks). Our results demonstrated that the efficiency of mesoporous silica microspheres/nano-hydroxyapatite/polyurethane composite scaffolds loaded with 5 mg levofloxacin was much better at treating bone defects than the other groups. This novel synthetic scaffold may provide a solution for the treatment of chronic osteomyelitis.

Benzyl-triphenyl-phospho-nium perchlorate.

The asymmetric unit of the title compound, C(25)H(22)P(+)·ClO(4) (-), contains two independent cations and two independent anions. The closest inter-molecular contact is a weak inter-molecular C-H⋯π(arene) inter-action.

Natural products-based insecticidal agents 6. Design, semisynthesis, and insecticidal activity of novel monomethyl phthalate derivatives of podophyllotoxin against Mythimna separata Walker in vivo.

To discover the more potent analogs, 12 novel monomethyl phthalate derivatives of podophyllotoxin were synthesized and preliminarily tested against the pre-third-instar larvae of Mythimna separata Walker in vivo at the concentration of 1mg/mL. Compounds 8e-i showed the higher insecticidal activity than podophyllotoxin. Especially 8g exhibited the most potent insecticidal activity compared with toosendanin, a commercially available insecticide derived from Melia azedarach. The structure-activity relationships demonstrated that trans-lactone, 4beta-substitution, 2beta-chlorine substitution, and 4'-methoxy group were the important structural properties of podophyllotoxins for good insecticidal activity.

(11,13-Dimethyl-1,4,7,10-tetra-azacyclo-trideca-10,13-dienato)copper(II) per-chlorate.

The title complex, [Cu(C(11)H(21)N(4))]ClO(4), comprises [Cu(II)(L)](+) (L = 11,13-dimethyl-1,4,7,10-tetra-azacyclo-trideca-10,12-dien-ate) cations and a perchlorate anion. The Cu atom is located on a twofold crystallographic symmetry axis and is coordinated by four N atoms in a slightly distorted square-planar geometry. Inter-molecular N-H⋯O hydrogen bonds are present.

[Expression of human nerve growth factor gene in E. coli].

OBJECTIVE: To investigate the structure and function of human nerve growth factor (beta-NGF) and the gene encoding beta-NGF. METHODS: A pair of specific primers (29 mer) for the sequence encoding human beta-NGF was designed and synthesized. A 380 bp fragment was amplified from human blood genomic DNA by polymerase chain reaction, and cloned into pGEM-T Easy vector. The identified insert fragment from the recombinant pGEM-T-NGF was directionally ligated with linearized pGEX-5T with the compatible termini. E. coli JM 109 was transformed with the expression recombinant p5TNGF and induced by IPTG. RESULTS: The cloned DNA fragment was identified as the full-length sequence encoding human beta-NGF by restriction analysis and DNA sequencing. SDS-PAGE and Western blot revealed the cloned NGF gene expressed as a fusion protein (40.5 x 10(3) u) in the cells transformed by p5TNGF. The soluble fusion protein was determined to be 503.2 mg/L, accounting for 6.8% of the total soluble protein (7.4 g/L) of bacterial cells. This fusion protein was found to have antigenic activities of NGF. CONCLUSION: The clone containing the full-length sequence encoding human beta-NGF is obtained and successfully expressed in E. coli to be of use for studying the biological functions of human beta-NGF gene.