NR0B1 suppresses ferroptosis through upregulation of NRF2/c-JUN-CBS signaling pathway in lung cancer cells.

Ferroptosis has demonstrated significant potential in treating radiochemotherapy-resistant cancers, but its efficacy can be affected by recently discovered ferroptosis suppressors. In this study, we discovered that NR0B1 protects against erastin- or RSL3-induced ferroptosis in lung cancer cells. Transcriptomic analysis revealed that NR0B1 significantly interfered with the expression of 12 ferroptosis-related genes, and the expression level of NR0B1 positively correlated with that of c-JUN, NRF2, and CBS. We further revealed that NR0B1 suppression of ferroptosis depended on the activities of c-JUN, NRF2, and CBS. NR0B1 directly promoted the expression of NRF2 and c-JUN and indirectly upregulated CBS expression through enhancing NRF2 and/or c-JUN transcription. Moreover, we showed that NR0B1 depletion restrained xenograft tumor growth and facilitated RSL3-induced ferroptosis in the tumors. In conclusion, our findings uncover that NR0B1 suppresses ferroptosis by activating the c-JUN/NRF2-CBS signaling pathway in lung cancer cells, providing new evidence for the involvement of NR0B1 in drug resistance during cancer therapy.

Ultra-stable CO2-in-water foam by generating switchable Janus nanoparticles in-situ.

HYPOTHESIS: The surface of silica nanoparticles (NP) may be covalently grafted with two amino ligands to balance colloidal stability and interfacial activity via formation of in situ Janus particles. The modified NP may be combined with a like-charged diamine surfactant to create ultra-stable CO2 foam at low NP concentrations. EXPERIMENTS: The NP colloidal stability was measured up to 80 °C in 230 g/L TDS brine with dynamic light scattering. The NP surface was characterized using zeta potential, TEM, TGA, conductometric and potentiometric titrations, NMR and interfacial measurement. CO2/brine foam was generated at 60-80 °C and 15 MPa and apparent viscosity was measured vs foam quality. The foam stability was measured in-situ with an optical microscope. FINDINGS: Upon adding only 0.1 wt% NP, ultra-stable CO2 foam was observed at 60 °C with a bubble coarsening rate 3 orders of magnitude lower than with surfactant alone. Foam bubbles were spherical with NP present, but became polyhedral for the much less stable surfactant-only foams. For this novel like-charged surfactant-NP system, the limited surfactant adsorption on the NP resulted in NP stabilized CO2 foam, while maintaining NP colloidal stability at high surfactant concentrations and high salinity, providing a new perspective of NP-surfactant design.

Ultrastable N2/Water Foams Stabilized by Dilute Nanoparticles and a Surfactant at High Salinity and High Pressure.

The rapid development of unconventional oil and gas resources presents challenges for foam flooding for reservoirs with high salinity and high heterogeneity at elevated temperatures. In this study, hydrophilic anionic sulfonate-modified nanoparticles (NPs) exhibited a synergistic effect with a cationic surfactant in stabilizing N2/water foam in the presence of concentrated divalent ions from ambient temperature up to 70 °C. With low concentrations of both the sulfonated NPs (SNPs) and cationic surfactant, the foams remained stable for 4 days at 50 °C and atmospheric pressure, while the surfactant-stabilized foams collapsed completely in 1 day. This stability mechanism of foams by the SNPs and cationic surfactant is described in terms of phase behavior, bulk shear rheology of the aqueous phase, and the dilational modulus of the gas-brine interface. The high surface elastic dilational modulus E' observed upon addition of the SNP provided stability against coarsening according to the Gibbs criteria. The cryo-SEM images also showed the compact bubble structure of foams provided by the SNPs. Consequently, very minor changes in the foam bubble size were observed at 208 bar (3000 psi) and 50 °C for up to 48 h with only 0.1 wt % or 0.3 wt % SNPs and 0.01 wt % Arquad 12-50, indicating excellent foam stability. The ability of the surfactant and NPs to stabilize foams at low concentrations broadens the application of foams in subsurface reservoirs at high temperatures and salinities.

Elastic gas/water interface for highly stable foams with modified anionic silica nanoparticles and a like-charged surfactant.

HYPOTHESIS: Surface active anionic nanoparticles (NPs) with strategically designed covalent ligands may be combined with a liked-charged surfactant to form a highly elastic gas-water interface leading to highly stable gas/water foams. EXPERIMENTS: The colloidal stability of the NPs was determined by dynamic light scattering, and the surface elastic dilational modulus E' of the interface by sinusoidal oscillation of a pendant droplet at 0.1 Hz, which was superimposed on large-amplitude compression-expansion cycles. The foam stability was measured with optical microscopy of the bubble size distribution and from the macroscopic foam height. FINDINGS: The NPs played the key role the formation of a highly elastic air-water interface with a high E' despite a surfactant level well above the critical micelle concentration. Unlike the case for most previous studies, the NP amphiphilicity was essentially independent of the surfactant given the very low adsorption of the surfactant on the like-charged NP surfaces. With high E' values, both coalescence and coarsening were reduced leading to highly foam up to 80 °C. However, the surfactant facilitated foam generation at much lower shear rates than with NPs alone. The tuning of NP surfaces with ligands for colloidal stability in brine and simultaneously high amphiphilicity at the gas-water interface, over a wide range in surfactant concentration, is of broad interest for enabling the design of highly stable foams.

Regio- and enantioselective umpolung gem-difluoroallylation of hydrazones via palladium catalysis enabled by N-heterocyclic carbene ligand.

The enantioselective construction of C-CF2R (R: alkyl or fluoroalkyl) bonds has attracted the attention of synthetic chemists because of the importance of chiral fluorinated compounds in life and materials sciences. Catalytic asymmetric fluoroalkylation has mainly been realized under organocatalysis and Lewis acid catalysis, with substrates limited to carbonyl compounds. Few examples using transition-metal catalysis exist, owing to side reactions including decomposition and isomerization of fluoroalkylating reagents. Herein we report umpolung asymmetric difluoroallylation of hydrazones with 3-bromo-3,3-difluoropropene (BDFP) under palladium catalysis. Difluoroallylation products having quaternary chiral carbon centers are afforded in good yields with high α/γ- and enantioselectivities. The usefulness of the reaction products is demonstrated and an inner-sphere mechanism of the reaction is proposed. The use of chiral N-heterocyclic carbene as ligand is the key for the selectivities as well as the productivity of the reaction.

Discovery of a naturally occurring broad-spectrum inhibitor against gut bacterial ß-glucuronidases from Ginkgo biloba.

Gut bacterial ß-glucuronidases (GUS) play an important role in deconjugation of various O-glucuronides, which are tightly linked with the drug-induced intestinal toxicity. Increasing evidence has indicated that inhibition of bacterial GUS could alleviate GUS-associated intestinal toxicity, but the potent and broad-spectrum inhibitors against multiple bacterial GUS have been rarely reported. This study aimed to find potent and broad-spectrum GUS inhibitors from Ginkgo biloba. It was found that amentoflavone displayed relatively strong inhibition on three GUS including CpGUS, SpasGUS and EcGUS. Further investigations demonstrated that amentoflavone could inhibit GUS-mediated PNPG hydrolysis in a dose-dependent manner with IC50 values of 2.36 µM, 2.88 µM and 3.43 µM for CpGUS, SpasGUS and EcGUS, respectively. Inhibition kinetic studies showed that amentoflavone functioned as a non-competitive inhibitor against all tested GUS with Ki values of less than 2 µM. Docking simulations indicated that amentoflavone could tightly bind on allosteric sites of three GUS mainly via hydrogen bonding interactions, and the number of hydroxyl groups of amentoflavone played crucial roles in these interactions. Collectively, our findings suggested that amentoflavone was a potent broad-spectrum inhibitor against bacterial GUS, which can be used as a promising lead compound for developing novel agents to alleviate GUS-associated intestinal toxicity.

Tuning Surface Chemistry and Ionic Strength to Control Nanoparticle Adsorption and Elastic Dilational Modulus at Air-Brine Interface.

The relationship between the interfacial rheology of nanoparticle (NP) laden air-brine interfaces and NP adsorption and interparticle interactions is not well understood, particularly as a function of the surface chemistry and salinity. Herein, a nonionic ether diol on the surface of silica NPs provides steric stabilization in bulk brine and at the air-brine interface, whereas a second smaller underlying hydrophobic ligand raises the hydrophobicity to promote NP adsorption. The level of NPs adsorption at steady state is sufficient to produce an interface with a relatively strong elastic dilational modulus E' = dγ/d ln A. However, the interface is ductile with a relatively slow change in E' as the interfacial area is varied over a wide range during compression and expansion. In contrast, for silica NPs stabilized with only a single hydrophobic ligand, the interfaces are often more fragile and may fracture with small changes in area. The presence of concentrated divalent cations improves E' and ductility by screening electrostatic dipolar repulsion and strengthening the attractive forces between nanoparticles. The ability to tune the interfacial rheology with NP surface chemistry is of great interest for designing more stable gas/brine foams.

Tuning Nanoparticle Surface Chemistry and Interfacial Properties for Highly Stable Nitrogen-In-Brine Foams.

The design of surface chemistries on nanoparticles (NPs) to stabilize gas/brine foams with concentrated electrolytes, especially with divalent ions, has been elusive. Herein, we tune the surface of 20 nm silica NPs by grafting a hydrophilic and a hydrophobic ligand to achieve two seemingly contradictory goals of colloidal stability in brine and high NP adsorption to yield a viscoelastic gas-brine interface. Highly stable nitrogen/water (N2/brine) foams are formed with CaCl2 concentrations up to 2% from 25 to 90 °C. The viscoelastic gas-brine interface retards drainage of the lamellae, and the high dilational elasticity arrests coarsening (Ostwald ripening) with no observable change in foam bubble size over 48 h. The ability to design NP-laden viscoelastic interfaces for highly stable foams, even with high divalent ion concentrations, is of fundamental mechanistic interest for a broad range of foam applications and in particular foams for CO2 sequestration and enhanced oil recovery.

Effect of surface chemistry of silica nanoparticles on contact angle of oil on calcite surfaces in concentrated brine with divalent ions.

HYPOTHESIS: For an oil droplet on calcite with an intervening brine film, the water contact angle θw may be reduced markedly (greater water wetness) with surface modified silica nanoparticles (NP). Modification with cationic, anionic, and nonionic ligands may be used to control the nanoparticle adsorption and interactions at the oil-brine and brine-calcite interfaces to influence the rate and degree of reduction in θw. EXPERIMENTS: The colloidal stability at 25 °C was determined in concentrated divalent brine (8 wt% NaCl and 2 wt% CaCl2) with dynamic light scattering, and the NP adsorption was determined on calcite. The NP adsorption at the oil-brine interface was characterized with the elastic dilational modulus. θw was measured for model decane-stearic acid droplets and crude oil droplets on calcite from 25 to 80 °C. FINDINGS: The fastest rate and greatest extent of reduction in θw for grafted ligands followed the order: cationic quaternary trimethylamine > sulfonate > methyl phosphonate > gluconamide. New mechanisms for reduction in θw were demonstrated on the basis of changes in interactions from NP adsorption at each interface. The greatest efficacy for the cationic NPs results from the weakest adsorption on calcite, steric repulsion at the three-phase contact line and the greatest desorption of carboxylate surfactants from the calcite.

A review on the recent development of cyclodextrin-based materials used in oilfield applications.

Cyclodextrin has been studied for more than 120 years. Due to the special structure and selectivity of the cyclodextrin cavity, native cyclodextrins, cyclodextrin derivatives and inclusion complexes have received extensive attention and are widely used in medicine, food, the environment, cosmetics, chemical analysis, separation technology, catalysts and other fields. Cyclodextrin-based materials have been applied to oilfields since the early 1980s and performed well in enhancing the performance of petroleum chemicals and improving the efficiency of oil exploration. This review introduces the characteristics of cyclodextrin-based materials, including cyclodextrin polymers, inclusion complexes and new cyclodextrin nanocomposites, and summarizes their applications in oilfields for the first time, such as retarded acid solution, enhanced oil recovery, clay stabilizers, corrosion and scale inhibitors, wastewater treatment, etc. Meanwhile, the action mechanisms, major challenges and development tendencies of cyclodextrin-based materials in oilfields are also comprehensively discussed.

Pancreatic lipase inhibitory constituents from Fructus Psoraleae.

Pancreatic lipase (PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae (FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL (IC50 < 10 µmol·L-1). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate (4-MUO) hydrolysis, with the Ki values of 1.61, 3.77 and 10.16 µmol·L-1, respectively. Furthermore, docking simulations indicated that two chalcones (isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors.

Pancreatic lipase inhibitory constituents from Fructus Psoraleae / 中国天然药物

Pancreatic lipase (PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae (FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL (IC < 10 μmol·L). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate (4-MUO) hydrolysis, with the K values of 1.61, 3.77 and 10.16 μmol·L, respectively. Furthermore, docking simulations indicated that two chalcones (isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors.

CLOCK and BMAL1 stabilize and activate RHOA to promote F-actin formation in cancer cells.

Circadian genes control most of the physiological functions in cancer cells, including cell proliferation, migration, and invasion. The CLOCK and BMAL1 complex plays a central role in circadian rhythms. Previous studies have shown that circadian genes may act as oncogenes or tumor-suppressor genes. In addition, F-actin, regulated by RHOA, has been shown to participate in tumor progression. However, the roles of the CLOCK and BMAL1 genes in the regulation of tumor progression via the RHOA-ROCK-CFL pathway remain largely unclear. Here we first indicate that the rearrangement of F-actin is regulated by CLOCK and BMAL1. We found that CLOCK and BMAL1 can upregulate RHOA expression by inhibiting CUL3-mediated ubiquitination and activate RHOA by reducing the interaction between RHOA and RhoGDI. Consequently, CLOCK and BMAL1 control the expression of the components of the RHOA-ROCK-CFL pathway, which alters the dynamics of F-actin/G-actin turnover and promotes cancer cell proliferation, migration, and invasion. In conclusion, our research proposes a novel insight into the role of CLOCK and BMAL1 in tumor cells.

Atrazine induced oxidative stress and mitochondrial dysfunction in quail (Coturnix C. coturnix) kidney via modulating Nrf2 signaling pathway.

Atrazine (ATR) is a most used herbicide which is believed as a pivotal determinant of environmental nephrosis, but potential mechanism is still largely unclear. This study intends to reveal a novel mechanism of ATR-induced nephrotoxicity. Quail were treated with 0, 50, 250 and 500 mg ATR/kg/d by oral gavage for 45 days. Kidney coefficient was decreased, biochemical and morphologic indices reflecting the kidney injury were significantly increased in ATR-exposed quail. ATR exposure upregulated the expression of proapoptotic factors (Bax, Caspase 3 and FasL) and downregulated antiapoptotic factor (Bcl-2). Notably, cristae of mitochondria decreased, mitochondrial malformation and mitochondrial vacuolar degeneration were observed in ATR-exposed quail. ATR induced the disorder of mitochondrial function related factors expressions and promoted oxidative damage. Furthermore, ATR induced toxicities in the expression of Nrf2 and Nrf2-target genes. In conclusion, ATR altered the microstructure and function of quail kidney. ATR induced renal damage via causing mitochondrial dysfunction, influencing mitochondrial function related genes expression, modulating Nrf2 signaling pathway. This study suggested ATR induced the nephrotoxicity via disturbing the transcription of mitochondrial function related factors and Nrf2 signaling pathway.

Effectiveness and feasibility of acupuncture for knee osteoarthritis: a pilot randomized controlled trial.

OBJECTIVE:: To evaluate the effectiveness of acupuncture for pain relief and function improvement in patients with knee osteoarthritis and to determine the feasibility of an eight-week acupuncture intervention. DESIGN:: Pilot randomized controlled trial. SETTING:: Three teaching hospitals in China. SUBJECTS:: Patients with knee osteoarthritis (Kellgren grade II or III). INTERVENTIONS:: Patients were randomly assigned to an eight-week (three sessions per week) intervention of either traditional Chinese acupuncture or sham acupuncture. MAIN MEASURES:: The primary outcome was response rate-the proportion of patients achieving score ⩾36% decrease in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function at week 8 compared with baseline. Secondary outcomes included pain, function and quality of life. RESULTS:: Of 42 patients randomized, 36 (85.7%) completed the study. There was no significant difference in response rate between the traditional Chinese acupuncture and control groups: 61.9% (13 of 21) versus 42.9% (9 of 21) achieved score ⩾36% decrease in WOMAC pain and function at week 8 ( P = 0.217). The sum of WOMAC pain and function scores at week 8 was 11.6 (9.1) in the traditional Chinese acupuncture group compared with 16.3 (10.9) in the control group ( P = 0.183). There was no significant difference between groups. Three adverse events were recorded and were classified as mild. CONCLUSION:: It showed that three sessions per week acupuncture intervention of knee osteoarthritis was feasible and safe. No difference was observed between groups due to small sample size. Larger (sample size ⩾ 296) randomized controlled trials of this intervention appear justified.

Carbon dioxide-in-oil emulsions stabilized with silicone-alkyl surfactants for waterless hydraulic fracturing.

The design of surfactants for CO2/oil emulsions has been elusive given the low CO2-oil interfacial tension, and consequently, low driving force for surfactant adsorption. Our hypothesis is that waterless, high pressure CO2/oil emulsions can be stabilized by hydrophobic comb polymer surfactants that adsorb at the interface and sterically stabilize the CO2 droplets. The emulsions were formed by mixing with an impeller or by co-injecting CO2 and oil through a beadpack (CO2 volume fractions (ϕ) of 0.50-0.90). Emulsions were generated with comb polymer surfactants with a polydimethylsiloxane (PDMS) backbone and pendant linear alkyl chains. The C30 alkyl chains are CO2-insoluble but oil soluble (oleophilic), whereas PDMS with more than 50 repeat units is CO2-philic but only partially oleophilic. The adsorbed surfactants sterically stabilized CO2 droplets against Ostwald ripening and coalescence. The optimum surfactant adsorption was obtained with a PDMS degree of polymerization of ∼88 and seven C30 side chains. The emulsion apparent viscosity reached 18 cP at a ϕ of 0.70, several orders of magnitude higher than the viscosity of pure CO2, with CO2 droplets in the 10-150 µm range. These environmentally benign waterless emulsions are of interest for hydraulic fracturing, especially in water-sensitive formations.

Viscoelastic diamine surfactant for stable carbon dioxide/water foams over a wide range in salinity and temperature.

HYPOTHESIS: The viscosity and stability of CO2/water foams at elevated temperature can be increased significantly with highly viscoelastic aqueous lamellae. The slow thinning of these viscoelastic lamellae leads to greater foam stability upon slowing down Ostwald ripening and coalescence. In the aqueous phase, the viscoelasticity may be increased by increasing the surfactant tail length to form more entangled micelles even at high temperatures and salinity. EXPERIMENTS: Systematic measurements of the steady state shear viscosity of aqueous solutions of the diamine surfactant (C16-18N(CH3)C3N(CH3)2) were conducted at varying surfactant concentrations and salinity to determine the parameters for formation of entangled wormlike micelles. The apparent viscosity and stability of CO2/water foams were compared for systems with viscoelastic entangled micellar aqueous phases relative to those with much less viscous spherical micelles. FINDINGS: We demonstrated for the first time stable CO2/water foams at temperatures up to 120 °C and CO2 volumetric fractions up to 0.98 with a single diamine surfactant, C16-18N(CH3)C3N(CH3)2. The foam stability was increased by increasing the packing parameter of the surfactant with a long tail and methyl substitution on the amine to form entangled viscoelastic wormlike micelles in the aqueous phase. The foam was more viscous and stable compared to foams with spherical micelles in the aqueous lamellae as seen with C12-14N(EO)2 and C16-18N(EO)C3N(EO)2.

The avian egg exhibits general allometric invariances in mechanical design.

The avian egg exhibits extraordinary diversity in size, shape and color, and has a key role in avian adaptive radiations. Despite extensive work, our understanding of the underlying principles that guide the "design" of the egg as a load-bearing structure remains incomplete, especially over broad taxonomic scales. Here we define a dimensionless number C, a function of egg weight, stiffness and dimensions, to quantify how stiff an egg is with respect to its weight after removing geometry-induced rigidity. We analyze eggs of 463 bird species in 36 orders across five orders of magnitude in body mass, and find that C number is nearly invariant for most species, including tiny hummingbirds and giant elephant birds. This invariance or "design guideline" dictates that evolutionary changes in shell thickness and Young's modulus, both contributing to shell stiffness, are constrained by changes in egg weight. Our analysis illuminates unique reproductive strategies of brood parasites, kiwis, and megapodes, and quantifies the loss of safety margin for contact incubation due to artificial selection and environmental toxins. Our approach provides a mechanistic framework for a better understanding of the mechanical design of the avian egg, and may provide clues to the evolutionary origin of contact incubation of amniote eggs.

Clock1a affects mesoderm development and primitive hematopoiesis by regulating Nodal-Smad3 signaling in the zebrafish embryo.

Circadian clock and Smad2/3/4-mediated Nodal signaling regulate multiple physiological and pathological processes. However, it remains unknown whether Clock directly cross-talks with Nodal signaling and how this would regulate embryonic development. Here we show that Clock1a coordinated mesoderm development and primitive hematopoiesis in zebrafish embryos by directly up-regulating Nodal-Smad3 signaling. We found that Clock1a is expressed both maternally and zygotically throughout early zebrafish development. We also noted that Clock1a alterations produce embryonic defects with shortened body length, lack of the ventral tail fin, or partial defect of the eyes. Clock1a regulates the expression of the mesodermal markers ntl, gsc, and eve1 and of the hematopoietic markers scl, lmo2, and fli1a Biochemical analyses revealed that Clock1a stimulates Nodal signaling by increasing expression of Smad2/3/4. Mechanistically, Clock1a activates the smad3a promoter via its E-box1 element (CAGATG). Taken together, these findings provide mechanistic insight into the role of Clock1a in the regulation of mesoderm development and primitive hematopoiesis via modulation of Nodal-Smad3 signaling and indicate that Smad3a is directly controlled by the circadian clock in zebrafish.