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Advanced oxidation processes (AOPs) based on peracetic acid (PAA) offer a promising strategy to address antibiotic wastewater pollution. In this study, Fe-doped graphitic carbon nitride (g-C 3 N 4 ) nanomaterials were used to construct Fe-N x sites, and the electronic structure was tuned by boron nitride quantum dots (BNQDs), thereby optimizing PAA activation for the degradation of antibiotics. The BNQDs-modified Fe-doped g-C 3 N 4 catalyst (BNQDs-FCN) achieved an excellent reaction rate constant of 0.0843 min -1 , marking a 21.6-fold improvement over the carbon nitride (CN)-based PAA system. DFT calculations further corroborate the superior adsorption capacity of the Fe-N x sites for PAA, facilitating its activation. Charge transfer mechanisms, with PAA serving as an electron acceptor, were identified as the source of high-valent iron-oxo species. Moreover, the BNQDs-FCN system preferentially targets oxygen-containing functional groups in antibiotic structures, elucidating the selective attack patterns of these highly electrophilic species. This research not only elucidates the pivotal role of high-valent iron-oxo species in pollutant degradation within the PAA-AOPs framework but also pioneers a wastewater treatment system characterized by excellent degradation efficiency coupled with low ecological risk, thereby laying the groundwork for applications in wastewater management and beyond.

Obesity-related functional iron disorder remains a major nutritional challenge. We evaluated the effects of djulis hull (DH) on iron metabolism in 50% high-fat-diet-induced obese rats supplemented with ferric citrate (2 g iron/kg diet) for 12 weeks. DH supplementation (5, 10, 15% dry weight/kg diet) significantly increased serum and hepatic iron but decreased appetite hormones, body weight, hepcidin, and liver inflammation (all p < 0.05). The Spearman correlation showed that appetite hormones were negatively associated with iron but positively correlated with liver hepcidin (all p < 0.05). A Western blot analysis showed that DH significantly downregulated hepatic hepcidin through the IL-6-JAK-STAT3 and enhanced ferroportin (Fpn) via the Keap1-Nrf2 and PHD2-HIF-2α. An in vitro study revealed that major bioactive compounds of DH, hexacosanol, and squalene suppressed LPS-induced IL-6 and hepcidin but enhanced Fpn expression in activated THP-1 cells. In conclusion, DH may exert nutraceutical properties for the treatment of functional iron disorder and restoration of iron efflux may have beneficial effects on weight control.

Bioengineering of ribosomally synthesized and post-translationally modified peptides (RiPPs) is an emerging approach to explore the diversity of pseudo-natural product structures for drug discovery purposes. However, despite the initial advances in this area, bioactivity reprogramming of multienzyme RiPP biosynthetic pathways remains a major challenge. Here, we report a platform for de novo discovery of functional thiopeptides based on reengineered biosynthesis of lactazole A, a RiPP natural product assembled by five biosynthetic enzymes. The platform combines in vitro biosynthesis of lactazole-like thiopeptides and mRNA display to prepare and screen large (≥10 12 ) combinatorial libraries of pseudo-natural products. We demonstrate the utility of the developed protocols in an affinity selection against Traf2- and NCK-interacting kinase (TNIK), a protein involved in several cancers, which yielded a plethora of candidate thiopeptides. Of the 11 synthesized compounds, 9 had high affinities for the target kinase (best K D = 1.2 nM) and 10 inhibited its enzymatic activity (best K i = 3 nM). X-ray structural analysis of the TNIK/thiopeptide interaction revealed the unique mode of substrate-competitive inhibition exhibited by two of the discovered compounds. The thiopeptides internalized to the cytosol of HEK293H cells as efficiently as the known cell-penetrating peptide Tat (4-6 μM). Accordingly, the most potent compound, TP15, inhibited TNIK in HCT116 cells. Altogether, our platform enables the exploration of pseudo-natural thiopeptides with favorable pharmacological properties in drug discovery applications.

A strategy for the synthesis of de novo discovered lactazole-like thiopeptides is reported. The approach revolves around a convergent and scalable preparation of the central triheterocyclic amino acid and its utilization in Fmoc solid-phase peptide synthesis for modular peptide chain assembly. A technique for preparing C-terminally functionalized thiopeptides for biological studies is also described. The syntheses of 11 TNIK-inhibitor thiopeptides and 6 of their derivatives in multimilligram quantities highlight the practical utility of the developed protocols.

Nontarget data acquisition for target analysis (nDATA) workflows using liquid chromatography-high-resolution accurate mass (LC-HRAM) spectrometry, spectral screening software, and a compound database have generated interest because of their potential for screening of pesticides in foods. However, these procedures and particularly the instrument processing software need to be thoroughly evaluated before implementation in routine analysis. In this work, 25 laboratories participated in a collaborative study to evaluate an nDATA workflow on high moisture produce (apple, banana, broccoli, carrot, grape, lettuce, orange, potato, strawberry, and tomato). Samples were extracted in each laboratory by quick, easy, cheap, effective, rugged, and safe (QuEChERS), and data were acquired by ultrahigh-performance liquid chromatography (UHPLC) coupled to a high-resolution quadrupole Orbitrap (QOrbitrap) or quadrupole time-of-flight (QTOF) mass spectrometer operating in full-scan mass spectrometry (MS) data-independent tandem mass spectrometry (LC-FS MS/DIA MS/MS) acquisition mode. The nDATA workflow was evaluated using a restricted compound database with 51 pesticides and vendor processing software. Pesticide identifications were determined by retention time ( t R , ±0.5 min relative to the reference retention times used in the compound database) and mass errors (δ M ) of the precursor (RTP, δ M ≤ ±5 ppm) and product ions (RTPI, δ M ≤ ±10 ppm). The elution profiles of all 51 pesticides were within ±0.5 min among 24 of the participating laboratories. Successful screening was determined by false positive and false negative rates of <5% in unfortified (pesticide-free) and fortified (10 and 100 μg/kg) produce matrices. Pesticide responses were dependent on the pesticide, matrix, and instrument. The false negative rates were 0.7 and 0.1% at 10 and 100 μg/kg, respectively, and the false positive rate was 1.1% from results of the participating LC-HRAM platforms. Further evaluation was achieved by providing produce samples spiked with pesticides at concentrations blinded to the laboratories. Twenty-two of the 25 laboratories were successful in identifying all fortified pesticides (0-7 pesticides ranging from 5 to 50 μg/kg) for each produce sample (99.7% detection rate). These studies provide convincing evidence that the nDATA comprehensive approach broadens the screening capabilities of pesticide analyses and provide a platform with the potential to be easily extended to a larger number of other chemical residues and contaminants in foods.

PCM-102 is a new organophosphine metal-organic framework (MOF) featuring diphosphine pockets that consist of pairs of offset trans- oriented P(III) donors. Postsynthetic addition of M(I) salts (M = Cu, Ag, Au) to PCM-102 induces single-crystal to single-crystal transformations and the formation of trans -[P 2 M] + solid-state complexes (where P = framework-based triarylphosphines). While the unmetalated PCM-102 has low porosity, the addition of secondary Lewis acids to install rigid P-M-P pillars is shown to dramatically increase both stability and selective gas uptake properties, with N 2 Brunauer-Emmett-Teller surface areas >1500 m 2 g -1 . The Ag(I) analogue can also be obtained via a simple, one-pot peri-synthetic route and is an ideal sacrificial precursor for materials with mixed bimetallic M A /M B pillars via postsynthetic, solvent-assisted metal exchange. Notably, the M-PCM-102 family of MOFs contain periodic trans -[P 2 M] + sites that are free of counter anions, unlike traditional analogous molecular complexes, since the precursor PCM-102 MOF is monoanionic, enabling access to charge-neutral metal-pillared materials. Four M-PCM-102 materials were evaluated for the separation of C2 hydrocarbons. The separation performance was found to be tunable based on the metal(s) incorporated, and density functional theory was employed to elucidate the nature of the unusual observed sorption preference, C 2 H 2 > C 2 H 6 > C 2 H 4 .

Sickle cell disease (SCD) is a genetic disorder caused by a single point mutation (β6 Glu → Val) on the β-chain of adult hemoglobin (HbA) that results in sickled hemoglobin (HbS). In the deoxygenated state, polymerization of HbS leads to sickling of red blood cells (RBC). Several downstream consequences of polymerization and RBC sickling include vaso-occlusion, hemolytic anemia, and stroke. We report the design of a noncovalent modulator of HbS, clinical candidate PF-07059013 ( 23 ). The seminal hit molecule was discovered by virtual screening and confirmed through a series of biochemical and biophysical studies. After a significant optimization effort, we arrived at 23 , a compound that specifically binds to Hb with nanomolar affinity and displays strong partitioning into RBCs. In a 2-week multiple dose study using Townes SCD mice, 23 showed a 37.8% (±9.0%) reduction in sickling compared to vehicle treated mice. 23 (PF-07059013) has advanced to phase 1 clinical trials.

Adsorption-driven heat transfer devices incorporating an efficient "adsorbent-water" working pair are attracting great attention as a green and sustainable technology to address the huge global energy demands for cooling and heating. Herein, we report the improved heat transfer performance of a defective Zr fumarate metal-organic framework (MOF) prepared in a water solvent ( Zr-Fum HT). This material exhibits an S-shaped water sorption isotherm ( P / P 0 = 0.05-0.2), excellent working capacity (0.497 mL H 2 O mL -1 MOF ) under adsorption-driven cooling/chiller working conditions ( T adsorption(ads) = 30 °C, T condensation (con) = 30 °C, and T desorption(des) = 80 °C), very high coefficient of performances for both cooling (0.83) and heating (1.76) together with a relatively low driving temperature at 80 °C, a remarkable heat storage capacity (423.6 kW h m -3 MOF ), and an outstanding evaporation heat (343.8 kW h m -3 MOF ). The level of performance of the resultant Zr-Fum HT MOF is above those of all existing benchmark water adsorbents including MOF-801 previously synthesized in the N , N -dimethylformamide solvent under regeneration at 80 °C which is accessible from the solar source. This is coupled with many other decisive advantages including green synthesis and high proven chemical and mechanical robustness. The microscopic water adsorption mechanism of Zr-Fum HT at the origin of its excellent water adsorption performance was further explored computationally based on the construction of an atomistic defective model online with the experimental data gained from a subtle combination of characterization techniques.

Fucoidans are heterologous polysaccharides commonly seen in brown macroalgae and are known for their biological activity including anticancer, antiangiogenic, immunomodulation, and antiviral properties. The brown macroalga Sargassum siliquosum was used for the extraction and analysis of fucoidan in this study. The S. siliquosum fucoidan was indicated as a galactofucoidan composed of sugars, uronate, and sulfate at a ratio of 12:1:4 and its purity was 85% based on the abovementioned three major components. Structural analysis by electrospray ionization collision-induced dissociation tandem mass spectroscopy revealed that the purified fucoidan consisted of a carbohydrate chain composed of (1→3)-linked or (1→4)-linked l-fucose residues, with sulfate groups at C-2 and C-4 positions. Galactose residues with (1→4)-linkages function as the branch points and they are located at the C-3 or C-4 position of fucose residues. Galactose residues are sulfated mainly at C-4 and C-6, while some sulfation can also be seen at C-2. The fucoidan purified from S. siliquosum demonstrated antioxidant, anti-inflammatory, and antilipogenic activities., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

We report a method for the high-throughput reactivity profiling of genetically encoded libraries as a tool to study substrate fitness landscapes for RiPP (ribosomally synthesized and post-translationally modified peptide) biosynthetic enzymes. This method allowed us to rapidly analyze the substrate preferences of the lactazole biosynthetic pathway using a saturation mutagenesis mRNA display library of lactazole precursor peptides. We demonstrate that the assay produces accurate and reproducible in vitro data, enabling the quantification of reaction yields with temporal resolution. Our results recapitulate the previously established knowledge on lactazole biosynthesis and expand it by identifying the extent of substrate promiscuity exhibited by the enzymes. This work lays a foundation for the construction and screening of mRNA display-based combinatorial thiopeptide libraries for the discovery of lactazole-inspired thiopeptides with de novo designed biological activities.

Microporous 3D graphene-like carbons were synthesized in Faujasite (FAU)-, EMT-, and beta-zeolite templates using the recently developed Ca 2+ ion-catalyzed synthesis method. The microporous carbons liberated from these large-pore zeolites (0.7-0.9 nm) retain the structural regularity of zeolite. FAU-, EMT-, and beta zeolite-templated carbons (ZTCs) with faithfully constructed pore diameters of 1.2, 1.1, and 0.9 nm, respectively, and very large Brunauer-Emmet-Teller areas (2700-3200 m 2 g -1 ) were obtained. We have discovered that these schwarzite-like carbons exhibit preferential adsorption of ethane over ethylene at pressures in the range of 1-10 bar. The curved graphene structure, consisting of a diverse range of carbon polygons with a narrow pore size of ∼1 nm, provides abundant adsorption sites in micropores and retains its ethane selectivity at pressures up to 10 bar. After varying the oxygen content in the beta ZTC, the ethane and ethylene adsorption isotherms show that the separation ability is not significantly affected by surface oxygen groups. Based on these adsorption results, a breakthrough separation procedure using a C 2 H 4 /C 2 H 6 gas mixture (9:1 molar ratio) is demonstrated to produce ethylene with a purity of 99.9%.

The development of new water adsorbents that are hydrothermally stable and can operate more efficiently than existing materials is essential for the advancement of water adsorption-driven chillers. Most of the existing benchmark materials and related systems in this field suffer from clear limitations that must be overcome to meet global requirements for sustainable and green energy production and utilization. Here, we report the energy-efficient water sorption properties of three isostructural metal-organic frameworks (MOFs) based on the simple ligand pyridine-2,4-dicarboxylate, named M-CUK-1 [M 3 (μ 3 -OH) 2 (2,4-pdc) 2 ] (where M = Co 2+ , Ni 2+ , or Mg 2+ ). The highly hydrothermally stable CUK-1 series feature step-like water adsorption isotherms, relatively high H 2 O sorption capacities between P / P 0 = 0.10-0.25, stable cycling, facile regeneration, and, most importantly, benchmark coefficient of performance values for cooling and heating at a low driving temperature. Furthermore, these MOFs are prepared under green hydrothermal conditions in aqueous solutions. Our joint experimental-computational approach revealed that M-CUK-1 integrates several optimal features, resulting in promising materials as advanced water adsorbents for adsorption-driven cooling and heating applications.

This perspective discusses the use of liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) for multiresidue analysis of pesticides in foods and agricultural commodities. HRMS has the important distinction and advantage of mass-resolving power and, therefore, requires different concepts, experiments, and guidance for screening, identification, and quantitation of pesticides in complex food matrices over triple quadrupole mass spectrometry. HRMS approaches for pesticide screening, including full-scan experiments in conjunction with tandem mass spectrometry (MS/MS) experiments, are described. This approach results in the generation of chromatographic retention times and high-resolution mass spectra with accurate mass measurements that can be used to create compound databases. New data processing tools can create an efficient and optimized screening approach that can speed the analysis and identification of compounds, reduce the need for chemical standards, and harmonize pesticide analytical procedures.

ACM-1 is the first example of an organoarsine metal-organic framework (MOF), prepared using a new pyridyl-functionalized triarylarsine ligand coordinated to Ni(II) nodes. ACM-1 has micropores that are decorated with cis-diarsine coordination pockets. Postsynthetic metalation of ACM-1 with AuCl under facile conditions studied by single-crystal X-ray diffraction reveals the installation of dimeric Au 2 Cl 2 complexes via the formation of As-Au bonds. The Au(I) dimers display exceptionally short aurophilic bonds (2.76 Å) induced by the rigidity of the MOF, which acts as a unique solid-state ligand.

Through fragment-based drug design focused on engaging the active site of IRAK4 and leveraging three-dimensional topology in a ligand-efficient manner, a micromolar hit identified from a screen of a Pfizer fragment library was optimized to afford IRAK4 inhibitors with nanomolar potency in cellular assays. The medicinal chemistry effort featured the judicious placement of lipophilicity, informed by co-crystal structures with IRAK4 and optimization of ADME properties to deliver clinical candidate PF-06650833 (compound 40). This compound displays a 5-unit increase in lipophilic efficiency from the fragment hit, excellent kinase selectivity, and pharmacokinetic properties suitable for oral administration.

The removal of nitrogen-containing compounds (NCCs) from fossil fuels prior to combustion is currently of particular importance, and so we investigated an adsorptive method using metal-organic frameworks (MOFs) for the removal of indole (IND) and quinoline (QUI), which are two of the main NCCs present in fossil fuels. We herein employed an amino (-NH 2 )-functionalized MIL-125 (MIL-125-NH 2 ) MOF, which was further modified by protonation (P-MIL-125-NH 2 ). These modified MOFs exhibited extraordinary performance in the adsorption of both IND (as representative neutral NCC) and QUI (as representative basic NCC). These MOFs were one of the most efficient adsorbents for the removal of NCCs. For example, P-MIL-125-NH 2 showed the highest adsorption capacity for QUI among ever reported adsorbent. The improved adsorption of IND was explained by H-bonding and cation-π interactions for MIL-125-NH 2 and P-MIL-125-NH 2 , respectively, while the mechanisms for QUI were H-bonding and acid-base interactions, respectively. This is a rare phenomenon for a single material (especially not with very high porosity) to exhibit such remarkable performances in the adsorption of both basic QUI and neutral IND. The adsorption results obtained using regenerated MIL-125-NH 2 and P-MIL-125-NH 2 also showed that these materials can be used several times without any severe degradation.

([Sc2(OH)2(BPTC)]) (H4BPTC = biphenyl-3,3',5,5'-tetracarboxylic acid), MFM-400 (MFM = Manchester Framework Material, previously designated NOTT), and ([Sc(OH)(TDA)]) (H2TDA = thiophene-2,5-dicarboxylic acid), MFM-401, both show selective and reversible capture of CO2. In particular, MFM-400 exhibits a reasonably high CO2 uptake at low pressures and competitive CO2/N2 selectivity coupled to a moderate isosteric heat of adsorption (Qst) for CO2 (29.5 kJ mol(-1)) at zero coverage, thus affording a facile uptake-release process. Grand canonical Monte Carlo (GCMC) and density functional theory (DFT) computational analyses of CO2 uptake in both materials confirmed preferential adsorption sites consistent with the higher CO2 uptake observed experimentally for MFM-400 over MFM-401 at low pressures. For MFM-400, the Sc-OH group participates in moderate interactions with CO2 (Qst = 33.5 kJ mol(-1)), and these are complemented by weak hydrogen-bonding interactions (O···H-C = 3.10-3.22 Å) from four surrounding aromatic -CH groups. In the case of MFM-401, adsorption is provided by cooperative interactions of CO2 with the Sc-OH group and one C-H group. The binding energies obtained by DFT analysis for the adsorption sites for both materials correlate well with the observed moderate isosteric heats of adsorption for CO2. GCMC simulations for both materials confirmed higher uptake of EtOH compared with nonpolar vapors of toluene and cyclohexane. This is in good correlation with the experimental data, and DFT analysis confirmed the formation of a strong hydrogen bond between EtOH and the hydrogen atom of the hydroxyl group of the MFM-400 and MFM-401 framework (FW) with H-OEtOH···H-OFW distances of 1.77 and 1.75 Å, respectively. In addition, the accessible regeneration of MFM-400 and MFM-401 and release of CO2 potentially provide minimal economic and environmental penalties.

Ultrahigh-performance liquid chromatography using positive electrospray ionization and quadrupole orbital ion trap high-resolution mass spectrometry was evaluated for analyzing mycotoxins in finished cereal and nut products. Optimizing the orbital ion trap mass analyzer in full-scan mode using mycotoxin-fortified matrix extracts gave mass accuracies, δM, of < ± 2.0 ppm at 70,000 full width at half maximum (FWHM) mass resolution (RFWHM). The limits of quantitation were matrix- and mycotoxin-dependent, ranging from 0.02 to 11.6 μg/kg. Mean recoveries and standard deviations for mycotoxins from acetonitrile/water extraction at their relevant fortification levels were 91 ± 10, 94 ± 10, 98 ± 12, 91 ± 13, 99 ± 15, and 93 ± 17% for corn, rice, wheat, almond, peanut, and pistachio, respectively. Nineteen mycotoxins with concentrations ranging from 0.3 (aflatoxin B1 in peanut and almond) to 1175 μg/kg (fumonisin B1 in corn flour) were found in 35 of the 70 commercial grain and nut samples surveyed. Mycotoxins could be identified at δM < ± 5 ppm by identifying the precursor and product ions in full-scan MS and data-dependent MS/MS modes. This method demonstrates a new analytical approach for monitoring mycotoxins in finished grain and nut products.

We present a simple and industrially accessible method of producing liquid crystalline lipid nanoparticles with various internal structures based on phytantriol, Pluronic F127, and vitamin E acetate. Bilayer vesicles were produced when an ethanolic solution dissolving the lipid components was mixed with deionized water. After the evaporation of ethanol from the aqueous mixture, vesicles were transformed into lipid-filled liquid crystalline nanoparticles with well-defined internal structures such as hexagonal lattices (mostly inverted cubic Pn3m), lined or coiled pattern (inverted hexagonal H2), and disordered structure (inverse microemulsion, L2), depending on the compositions. Further studies suggested that their internal structures were also affected by temperature. The internal structures were characterized from cryo-TEM and small-angle X-ray scattering results. Microcalorimetry studies were performed to investigate the degree of molecular ordering/crystallinity of lipid components within the nanostructures. From the comparative studies, we demonstrated the present method could produce the lipid nanoparticles with similar characteristics to those made from a conventional method. More importantly, the production only requires simple tools for mixing and ethanol evaporation and it is possible to produce 10 kg or so per batch of aqueous lipid nanoparticles dispersions, enabling the large-scale production of the liquid crystalline nanoparticles for various biomedical applications.

This study used two LC columns of different adsorbents and liquid chromatography-electrospray ionization-high-resolution mass spectrometry to study the relationship between matrix effects (ME), the LC separations, and elution patterns of pesticides and those of matrix components. Using calibration standards of 381 pesticides at three dilution levels of 1×, 1/10×, and 1/100×, 108 samples were prepared in solvent and five different sample matrices for the study. Results obtained from principal component analysis and slope ratios of calibration curves provided measurements of the ME and showed the 1/100× sample dilution could minimize suppression ME for most pesticides analyzed. Should a pesticide coeluting with matrix components have a peak intensity of 25 times or higher, the suppression for that pesticide would persist even at 1/100× dilution. The number of pesticides had enhancement ME increased with increasing dilution from 1× to 1/100×, with those early eluting, hydrophilic pesticides affected the most.

The synthesis optimization and scale-up of the benchmarked microporous zirconium terephthalate UiO-66(Zr) were investigated by evaluating the impact of several parameters (zirconium precursors, acidic conditions, addition of water, and temperature) over the kinetics of crystallization by time-resolved in situ energy-dispersive X-ray diffraction. Both the addition of hydrochloric acid and water were found to speed up the reaction. The use of the less acidic ZrOCl2·8H2O as the precursor seemed to be a suitable alternative to ZrCl4·xH2O, avoiding possible reproducibility issues as a consequence of the high hygroscopic character of ZrCl4. ZrOCl2·8H2O allowed the formation of smaller good quality UiO-66(Zr) submicronic particles, paving the way for their use within the nanotechnology domain, in addition to higher reaction yields, which makes this synthesis route suitable for the preparation of UiO-66(Zr) at a larger scale. In a final step, UiO-66(Zr) was prepared using conventional reflux conditions at the 0.5 kg scale, leading to a rather high space-time yield of 490 kg m(-3) day(-1), while keeping physicochemical properties similar to those obtained from smaller scale solvothermally prepared batches.

The influence of the metal ion in the mesoporous metal trimesate MIL-100(Al(3+), Cr(3+), Fe(3+), V(3+)) on the adsorptive removal of N/S-heterocyclic molecules from fuels has been investigated by combining isotherms for adsorption from a model fuel solution with microcalorimetric and IR spectroscopic characterizations. The results show a clear influence of the different metals (Al, Fe, Cr, V) on the affinity for the heterocyclic compounds, on the integral adsorption enthalpies, and on the uptake capacities. Among several factors, the availability of coordinatively unsaturated sites and the presence of basic sites next to the coordinative vacancies are important factors contributing to the observed affinity differences for N-heterocyclic compounds. These trends were deduced from IR spectroscopic observation of adsorbed indole molecules, which can be chemisorbed coordinatively or by formation of hydrogen bonded species. On the basis of our results we are able to propose an optimized adsorbent for the deep and selective removal of nitrogen contaminants out of fuel feeds, namely MIL-100(V).

An adsorbent performance indicator (API) is proposed in an effort to initially highlight porous materials of potential interest for PSA separation processes. This expression takes into account working capacities, selectivities, and adsorption energies and additionally uses weighting factors to reflect the specific requirements of a given process. To demonstrate the applicability of the API, we have performed the adsorption of carbon dioxide and methane at room temperature on a number of metal-organic frameworks, a zeolite and a molecular sieve carbon. The API is calculated for two different CO2/CH4 separation case scenarios: "bulk separation" and "natural gas purification". This comparison highlights how the API can be more versatile than previously proposed comparison factors for an initial indication of potential adsorbent performance.

A rapid and noninvasive quantification method for cellular lipids in Chlorella vulgaris is demonstrated in this study. This method applied near-infrared Raman spectroscopy to monitor the change of signal intensities at 1440 cm(-1) and 2845-3107 cm(-1) along the nitrogen depletion period, and calibration curves relating signal intensity and cellular lipid abundance were established. The calibration curves show that signal intensity at 2845-3107 cm(-1) and cellular lipid abundance were highly correlated. When the calibration curve was applied on the lipid quantification of two unknown samples, the differences between lipid abundances estimated by the calibration curve and measured by gas chromatography were less than 2 wt %. Carotenoids produced a strong and broad peak near 1440 cm(-1), and it weakened the correlation between signal intensity and lipid abundance. The consistency of detection and effects of cellular contents and water on the Raman spectrogram of Chlorella vulgaris were also addressed. The sample pretreatment only involved centrifugation, and the time required for lipid quantification was shortened to less than 1.5 h. The rapid detection has great potential in high-throughput screening of microalgae and also provides valuable information for monitoring the quality of microalgae culture and determining parameters for the mass production of biodiesel from microalgae.

A high-throughput gas adsorption apparatus is presented for the evaluation of adsorbents of interest in gas storage and separation applications. This instrument is capable of measuring complete adsorption isotherms up to 40 bar on six samples in parallel using as little as 60 mg of material. Multiple adsorption cycles can be carried out and four gases can be used sequentially, giving as many as 24 adsorption isotherms in 24 h. The apparatus has been used to investigate the effect of metal center (MIL-100) and functional groups (CAU-10) on the adsorption of N(2), CO(2), and light hydrocarbons on MOFs. This demonstrates how it can serve to evaluate sample quality and adsorption reversibility, to determine optimum activation conditions and to estimate separation properties. As such it is a useful tool for the screening of novel adsorbents for different applications in gas separation, providing significant time savings in identifying potentially interesting materials.

PCM-16 is a phosphine coordination material comprised of Dy(III) and triphenylphosphine oxide, which displays the highest reported CO2 BET surface area for a Ln(III) coordination polymer of 1511 m(2) g(-1). PCM-16 also adsorbs 2.7 wt % H2 and 65.1 wt % O2 at 77 K and 0.97 bar. The adsorption-desorption behavior of a series of organic vapors has been studied in PCM-16 to probe the nature of certain host-guest interactions in the pores. Aromatic and polar guest species showed high uptakes and marked adsorption/desorption hysteresis, while aliphatic vapors were less easily adsorbed. The surface area of PCM-16 could be increased significantly (to 1814 m(2) g(-1)) via exchange of Me2NH2(+) cations in the pores with smaller NH4(+) groups.

The uptake and adsorption enthalpy of carbon dioxide at 0.2 bar have been studied in three different topical porous MOF samples, HKUST-1, UiO-66(Zr), and MIL-100(Fe), after having been pre-equilibrated under different relative humidities (3, 10, 20, 40%) of water vapor. If in the case of microporous UiO-66, CO(2) uptake remained similar whatever the relative humidity, and correlations were difficult for microporous HKUST-1 due to its relative instability toward water vapor. In the case of MIL-100(Fe), a remarkable 5-fold increase in CO(2) uptake was observed with increasing RH, up to 105 mg g(-1) CO(2) at 40% RH, in parallel with a large decrease in enthalpy measured. Cycling measurements show slight differences for the initial three cycles and complete reversibility with further cycles. These results suggest an enhanced solubility of CO(2) in the water-filled mesopores of MIL-100(Fe).

Powder, agglomerates, and tablets of the microporous zirconium(IV) terephthalate metal-organic framework UiO-66 were evaluated for the selective adsorption and separation of xylene isomers in the liquid phase using n-heptane as the eluent. Pulse experiments, performed at 313 K in the presence of n-heptane, revealed the o-xylene preference of this material, which was further confirmed by binary and multicomponent breakthrough experiments in the presence of m- and p-xylene, resulting in selectivities at 313 K of 1.8 and 2.4 with regards to m-xylene and p-xylene, respectively. Additionally, because p-xylene is the less retained isomer, UiO-66 presents a selectivity pattern that is reverse of that of the xylenes' molecular dimension with respect to shape selectivity. The shaping of the material as tablets did not significantly change its selectivity toward the o-xylene isomer or toward p-xylene, which was the less retained isomer, despite a loss in capacity. Finally, the selectivity behavior of UiO-66 in the liquid n-heptane phase makes it a suitable material for o-xylene separation in the extract (heavy product) or p-xylene separation in the raffinate (light product) by simulated moving bed technology.

Although a number of gas-phase chemical mechanisms, such as CBM-IV, RADM2, and SAPRC have been successful in studying gas-phase atmospheric chemical processes, they all used different combinations of lumped organic species to describe the role of organics in gas-phase chemical processes. Photochemical Assessment Monitoring Stations (PAMS) have been in use for over a decade and yet it is not clear how the detailed organic species measured by PAMS compare to the lumped modeled species. By developing a detailed mechanism specifically for the PAMS organics and embedding this diagnostic model within a regional-scale transport and chemistry model, one can then directly compare PAMS observation with regional-scale model simulations. By means of this comparison one can perhaps better evaluate model performance. The Taiwan Air Quality Model (TAQM) was modified by adding a submodel with transport processes and chemical mechanism for interactions of the 56 species observed by PAMS. It is assumed that TAQM can simulate the overall regional-scale environment including time evolution of oxidants and radicals; these results are then used to simulate the evolution of PAMS organics with species-specific source functions, meteorological transport, and chemical interactions. Model simulations of each PAMS organic were compared with PAMS hourly surface measurements. A case study with data collected at three sites in central Taiwan showed that when meteorological simulations were comparable with observations, diurnal patterns of most organics performed well with PAMS data after emissions were corrected. It is found emissions of over half of the PAMS species require correction, some by surprisingly large factors. With such correlation, simulated time evolution of ratios of ethylbenzene/m,p-xylenes and ethane/n-butane showed similar behaviors as shown by observation data. From the results of PAMS organics diurnal variations as well as indicator ratios, one can conclude that PAMS Air Quality Model (PAMS-AQM) has been successfully developed and can be applied to the study of evolution of PAMS organics in regional and urban environments. Further, one finds that an existing VOC emissions estimation procedure heavily dependent on U.S.-data based emissions speciation factors is suspect in application in Taiwan and perhaps in other countries as well. A protocol, using PAMS-AQM for testing consistency between detailed VOC emissions and PAMS observations, has been developed and demonstrated.

A twofold interpenetrating polyhedron-based metal-organic framework with high hydrothermal stability was prepared using a rigid and bent C(2)-symmetric ligand containing two 3,5-benzenedicarboxylate units, which have large surface area and high uptake capacities for various gas molecules.

A new porous metal-organic framework, PCN-20 with a twisted boracite net topology, was constructed based on a highly conjugated planar tricarboxylate ligand; PCN-20 possesses a large Langmuir surface area of over 4200 m(2)/g as well as demonstrates a high hydrogen uptake capacity of 6.2 wt % at 77 K and 50 bar.

Three isomorphous porous metal-organic frameworks (MOFs; PCN-9 (Co/Fe/Mn)) with entatic metal centers have been constructed on the basis of the trigonal planar H(3)TATB ligand and a novel square-planar secondary building unit. N(2) adsorption isotherms at 77 K confirmed the permanent porosities of the three porous MOFs. Variable-temperature adsorption measurements of H(2) revealed that the H(2) affinities of the three porous MOFs are related to the nature of entatic metal centers, which reversely affect their H(2) uptake capacities.

Hydrogen-sorption studies have been carried out for the catenation isomer pairs of PCN-6 and PCN-6' (both have the formula of Cu(3)(TATB)(2), where TATB represents 4,4',4''-s-triazine-2,4,6-triyl-tribenzoate with a formula of C(24)H(12)N(3)O(6)). Inelastic neutron scattering (INS) studies reveal that the initial sites occupied by adsorbed H(2) are the open Cu centers of the paddlewheel units with comparable interaction energies in the two isomers. At high H(2) loadings, where the H(2) molecules adsorb mainly on or around the organic linkers, the interaction is found to be substantially stronger in catenated PCN-6 than in noncatenated PCN-6', leading to much higher H(2) uptake in the isomer with catenation. Hydrogen sorption measurements at pressures up to 50 bar demonstrate that framework catenation can be favorable for the enhancement of hydrogen adsorption. For example, the excess hydrogen uptake of PCN-6 is 72 mg/g (6.7 wt %) at 77 K/50 bar or 9.3 mg/g (0.92 wt %) at 298 K/50 bar, respectively, and that for PCN-6' is 42 mg/g (4.0 wt %) at 77 K/50 bar or 4.0 mg/g (0.40 wt %) at 298 K/50 bar. Importantly, PCN-6 exhibits a total hydrogen uptake of 95 mg/g (8.7 wt %) (corresponding to a total volumetric value of 53.0 g/L, estimated based on crystallographic density) at 77 K/50 bar and 15 mg/g (1.5 wt %) at 298 K/50 bar. Significantly, the expected usable capacity of PCN-6 is as high as 75 mg/g (or 41.9 g/L) at 77 K, if a recharging pressure of 1.5 bar is assumed.

Mesoporous MOFs MIL-100 and MIL-101 adsorb huge amounts of CO2 and CH4. Characterization was performed using both manometry and gravimetry in different laboratories for isotherms coupled with microcalorimetry and FTIR to specify the gas-solid interactions. In particular, the uptake of carbon dioxide in MIL-101 has been shown to occur with a record capacity of 40 mmol g(-1) or 390 cm3STP cm(-3) at 5 MPa and 303 K.

Amorphous silica is increasingly used in diagnostic and biomedical research because of its ease of production and relatively low cost. It is generally regarded as safe and has been approved for use as a food or animal feed ingredient. Recent literature reveals that amorphous silica may present toxicity concerns at high doses. In anticipation of potential human exposure to silica, it is advisable to examine its toxicity to cells of different organs. Consequently, we investigated the response of several normal fibroblast and tumor cells to varying doses of amorphous silica or composite nanoparticles of silica and chitosan. A cell proliferation assay indicates that silica nanoparticles are nontoxic at low dosages but that cell viability decreases at high dosages. A lactate dehydrogenase (LDH) assay indicates that high dosages of silica induce cell membrane damage. Both assays reveal that fibroblast cells with long doubling times are more susceptible to injury induced by silica exposure than tumor cells with short doubling times. In contrast, silica-chitosan composite nanoparticles induce less inhibition in cell proliferation and less membrane damage. This study suggests that the cytotoxicity of silica to human cells depends strongly on their metabolic activities but that it could be significantly reduced by synthesizing silica with chitosan.

A porous hybrid inorganic/organic material, NaNi3(OH)(SIP)2 [SIP = 5-sulfoisophthalate][1], is shown to strongly bind molecular hydrogen at coordinatively unsaturated metal sites. A combination of H2 sorption isotherms, temperature programmed desorption, and inelastic neutron scattering spectroscopy show the existence of a considerable number of such strong binding sites in [1] along with other sites where hydrogen is more weakly physisorbed. The overall capacity for hydrogen of this material as well as the much stronger binding of hydrogen than in typical porous material represent an important step toward a possible utilization of porous media for hydrogen storage.

Several nanoporous aluminophosphates (AlPOs) have been used to analyze the effect of pore diameter on the hydrogen adsorption characteristics. The heat of adsorption and adsorption capacity per unit micropore volume increase with decreasing pore size. AlPOs with smaller micropores favorably adsorb hydrogen at relatively low pressures. This work demonstrates that small pore size and large micropore volume are beneficial for high hydrogen uptake.

Acyl-CoA: cholesterol acyltransferase (ACAT), which plays a role in the absorption, storage, and production of cholesterol, has been explored as a potential target for pharmacological intervention of hyperlipidemia and atherosclerotic disease. In our search for ACAT inhibitors from natural sources, the petroleum ether extract of Panax ginseng showed moderate inhibition of ACAT enzyme from rat liver microsomes. Bioactivity-guided fractionations led to the isolation of one new polyacetylenic compound, (9R,10S)-epoxy-16-heptadecene-4, 6-diyne-3-one (1), in addition to the previously reported polyacetylenic compounds 2 and 3. Their chemical structures were elucidated on the basis of spectroscopic evidence (UV, IR, NMR, and MS). The compounds 1, 2, and 3 showed significant ACAT inhibition with IC(50) values of 35, 47, and 21 microM, respectively.

The transition-metal-incorporated nickel phosphate molecular sieves (TMI-VSB-5) have been hydrothermally synthesized at 453 K in weak basic conditions under microwave irradiation. By means of X-ray diffraction, inductively coupled plasma (ICP), ultraviolet-visible (UV-vis) diffuse reflectance, and Mössbauer spectroscopies, successful isomorphous (at least partial) substitution of transition-metal ions in the VSB-5 framework has been verified. Characterization results show that the framework structure of nanoporous VSB-5 can accommodate a substantial level of isomorphous substitution of transition-metal ions up to about 10, 5, and 3 atom % for Fe, Mn, and V, respectively, in both octahedral nickel sites (Mn and Fe) and tetrahedral phosphorus sites (V). The isomorphous substitution including the replacement mechanism was studied by not only the change of unit cell parameters but also spectroscopic analysis. The unit cell parameters of TMI-VSB-5 including a unit cell volume and a-axis length relied on the ionic radii difference between the incorporated ion and the original framework ions such as Ni or P (RTMI - RNi or RTMI - RP).

As part of an effort to improve plant-derived foods such as potatoes, eggplants, and tomatoes, the antiproliferative activities against human colon (HT29) and liver (HepG2) cancer cells of a series of structurally related individual compounds were examined using a microculture tetrazolium (MTT) assay. The objective was to assess the roles of the carbohydrate side chain and aglycon part of Solanum glycosides in influencing inhibitory activities of these compounds. Evaluations were carried out with four concentrations each (0.1, 1, 10, and 100 microg/mL) of the the potato trisaccharide glycoalkaloids alpha-chaconine and alpha-solanine; the disaccharides beta(1)-chaconine, beta(2)-chaconine, and beta(2)-solanine; the monosaccharide gamma-chaconine and their common aglycon solanidine; the tetrasaccharide potato glycoalkaloid dehydrocommersonine; the potato aglycon demissidine; the tetrasaccharide tomato glycoalkaloid alpha-tomatine, the trisaccharide beta(1)-tomatine, the disaccharide gamma-tomatine, the monosaccharide delta-tomatine, and their common aglycon tomatidine; the eggplant glycoalkaloids solamargine and solasonine and their common aglycon solasodine; and the nonsteroidal alkaloid jervine. All compounds were active in the assay, with the glycoalkaloids being the most active and the hydrolysis products less so. The effectiveness against the liver cells was greater than against the colon cells. Potencies of alpha-tomatine and alpha-chaconine at a concentration of 1 microg/mL against the liver carcinoma cells were higher than those observed with the anticancer drugs doxorubicin and camptothecin. Because alpha-chaconine, alpha-solanine, and alpha-tomatine also inhibited normal human liver HeLa (Chang) cells, safety considerations should guide the use of these compounds as preventative or therapeutic treatments against carcinomas.

Hydrogen sorption in the nanoporous nickel phosphates VSB-1 and VSB-5 has been studied with a combination of BET, temperature programmed desorption (TPD), and inelastic neutron scattering (INS) measurements. H(2) BET isotherms for VSB-1 are similar to those seen in nanoporous zeolites, while VSB-5 adsorbs substantially more hydrogen due to a steep initial uptake at low partial pressures. TPD data show that hydrogen interacts strongly with VSB-5, with desorption peaks at 109 and 149 K in a nitrogen flow, whereas the absence of similar peaks for VSB-1 suggests a weaker interaction. INS spectra of the rotational tunnel transition of the adsorbed H(2) also reveal a strong interaction with the VSB-5 host. These data strongly suggest the existence of coordinatively unsaturated Ni(2+) sites accessible to H(2) molecules in the pores of VSB-5.

Carbonic anhydrase inhibitors are effective in lowering intraocular pressure, the primary indication of glaucoma. Human carbonic anhydrase II, and possibly carbonic anhydrase IV (CAII and CAIV, respectively), help regulate fluid secretion into the anterior chamber of the eye. Because inhibitors currently formulated as drugs to treat glaucoma were designed to target CAII, an understanding of the structural basis of CAII-CAIV discrimination by inhibitors would be useful for probing the role of each isozyme in the etiology of the disease. Here, we report the X-ray crystal structures of three novel thieno[3,2-e]-1,2-thiazine-6-sulfonamides complexed with CAII and the computationally predicted structures of the same compounds complexed with CAIV. All three compounds bind with similar affinity to CAII, but they bind with up to 100-fold lower affinities to CAIV. Comparisons of experimentally determined structures of CAII-inhibitor complexes and computationally predicted structures of CAIV-inhibitor complexes allow us to rationalize these affinity trends and outline molecular features that may contribute to high-affinity inhibitor binding to CAIV. This study demonstrates how experimental structure determination methods and computational structure prediction methods can be used together to answer questions that cannot be answered by either method alone.

A recent report that microinjection of the SH3 domain of PLC-gamma1 could induce DNA synthesis raised the functional importance of the SH3 domain of PLC-gamma1 in mitogenic signaling. In this report, we provide evidence that SOS1, a p21Ras-specific guanine nucleotide exchange factor, directly binds to the SH3 domain of PLC-gamma1, and that the SH3 domain of PLC-gamma1 is involved in SOS1-mediated p21Ras activation. SOS1 was coprecipitated with the GST-fused SH3 domain of PLC-gamma1 in vitro. The interaction between SOS1 and the PLC-gamma1 SH3 domain is mediated by direct physical interaction. The carboxyl-terminal proline-rich domain of SOS1 is involved in the interaction with the PLC-gamma1 SH3 domain. Moreover, PLC-gamma1 could be co-immunoprecipitated with SOS1 antibody in cell lysates. From transient expression studies, we could demonstrate that the SH3 domain of PLC-gamma1 is necessary for the association with SOS1 in vivo. Intriguingly, overexpression of the SH3 domain of PLC-gamma1, lipase-inactive PLC-gamma1, or wild-type PLC-gamma1 elevated p21Ras activity and ERK activity when compared with vector transfected cells. The PLC-gamma1 mutant lacking the SH3 domain could not activate p21Ras. p21Ras activities in cell lines overexpressing either PLC-gamma1 or the SH2-SH2-SH3 domain of PLC-gamma1 were elevated about 2-fold compared to vector transfected cells. This study is the first to demonstrate that the PLC-gamma1 SH3 domain enhances p21Ras activity, and that the SH3 domain of PLC-gamma1 may be involved in the SOS1-mediated signaling pathway.

[figure: see text] Linear free energy relationships between binding affinity and hydrophobicity for a library of fluoroaromatic inhibitors of F131V carbonic anhydrase II (CA) implicate three modes of interaction. X-ray crystal structures suggest that F131 interacts with fluoroaromatic inhibitors, while P202, on the opposite side of the active site cleft, serves as the site of the hydrophobic contact in the case of the F131V mutant. 2-Fluorinated compounds bind more tightly, perhaps due to the field effect of the nearby fluorine on the acidity of the amide proton.