Confinement effects facilitate low-concentration carbon dioxide capture with zeolites.

Engineered systems designed to remove CO2 from the atmosphere need better adsorbents. Here, we report on zeolite-based adsorbents for the capture of low-concentration CO2. Synthetic zeolites with the mordenite (MOR)-type framework topology physisorb CO2 from low concentrations with fast kinetics, low heat of adsorption, and high capacity. The MOR-type zeolites can have a CO2 capacity of up to 1.15 and 1.05 mmol/g for adsorption from 400 ppm CO2 at 30 °C, measured by volumetric and gravimetric methods, respectively. A structure-performance study demonstrates that Na+ cations in the O33 site located in the side-pocket of the MOR-type framework, that is accessed through a ring of eight tetrahedral atoms (either Si4+ or Al3+: eight-membered ring [8MR]), is the primary site for the CO2 uptake at low concentrations. The presence of N2 and O2 shows negligible impact on CO2 adsorption in MOR-type zeolites, and the capacity increases to ∼2.0 mmol/g at subambient temperatures. By using a series of zeolites with variable topologies, we found the size of the confining pore space to be important for the adsorption of trace CO2. The results obtained here show that the MOR-type zeolites have a number of desirable features for the capture of CO2 at low concentrations.

Synthesis and Characterization of Silicoaluminophosphate CIT-16P and Its Transformation to SAPO-17.

A silicoaluminophosphate molecular sieve, CIT-16P, is synthesized using butane-1,4-bis(quinuclidinium) [(C7H13N)-(CH2)4-(NC7H13)]2+ dihydroxide (DiQ-C4-(OH)2) as an organic structure-directing agent (OSDA). Upon the removal of the OSDA, either by thermal treatment in air at temperatures exceeding 490 °C or by extended ozone treatment at 150 °C, CIT-16P transforms to SAPO-17 (ERI topology). The structure solution of CIT-16P in its as-synthesized form is obtained using a Rietveld refinement of the powder X-ray diffraction pattern. The primary composite building units (CBUs) of CIT-16P are highly distorted cancrinite (can) CBUs that transform into stable can units of the ERI-type framework as a result of the OSDA removal. The distortion of can CBU is maintained without transformation by the presence of tightly bound DiQ-C4 dications in the as-synthesized form of CIT-16P. The transformed material is characterized and evaluated as a catalyst in the methanol-to-olefins (MTO) reaction. The catalytic behavior of the formed SAPO-17 (Si/T-atom = 0.022) (T = Si + Al + P) at 400 °C and WHSV of 1.3 h-1 produces elevated C3+ olefin products (i.e., propylene, butenes, and pentenes) in early stages of the reaction. However, as the reaction proceeds, the C3+ fraction decreases in favor of more ethylene.

ß-Cyclodextrin-containing polymer treatment of cutaneous lupus and influenza improves outcomes.

Nucleic acid (NA)-containing damage- and pathogen-associated molecular patterns (DAMPs and PAMPs, respectively) are implicated in numerous pathological conditions from infectious diseases to autoimmune disorders. Nucleic acid-binding polymers, including polyamidoamine (PAMAM) dendrimers, have demonstrated anti-inflammatory properties when administered to neutralize DAMPs/PAMPs. The PAMAM G3 variant has been shown to have beneficial effects in a cutaneous lupus erythematosus (CLE) murine model and improve survival of mice challenged with influenza. Unfortunately, the narrow therapeutic window of cationic PAMAM dendrimers makes their clinical development challenging. An alternative nucleic acid-binding polymer that has been evaluated in humans is a linear ß-cyclodextrin-containing polymer (CDP). CDP's characteristics prompted us to evaluate its anti-inflammatory potential in CLE autoimmune and influenza infectious disease mouse models. We report that CDP effectively inhibits NA-containing DAMP-mediated activation of Toll-like receptors (TLRs) in cell culture, improves healing in lupus mice, and does not immunocompromise treated animals upon influenza infection but improves survival even when administered 3 days after infection. Finally, as anticipated, we observe limited toxicity in animals treated with CDP compared with PAMAM G3. Thus, CDP is a new anti-inflammatory agent that may be readily translated to the clinic to combat diseases associated with pathological NA-containing DAMPs/PAMPs.

Carbon dioxide capture with zeotype materials.

The accumulation of carbon dioxide (CO2) in the atmosphere has been recognized as one of the primary factors attributed to global warming. Various strategies have been proposed to mitigate the amount of atmospheric CO2 such as its separation from emission streams with storage or utilization in fuels and chemicals. Zeolite-based materials (zeotype materials), a class of microporous solids with: (i) structural features of high surface area, chemical tunability and high stability, and (ii) a long history of global scale industrial use, have been extensively investigated for CO2 capture. In this review, a comprehensive summary and discussion of the progress in the design and use of zeotype materials, e.g., cation and amine modifications, composites and templated carbons, for the capture of CO2 is presented. The CO2 adsorption mechanisms in these materials are described, and the factors that determine their performance are discussed. The application of zeotype materials for CO2 capture under conditions such as post-combustion, indoor air cleaning and direct air capture are presented. Further, the mechanisms of water-zeolites interaction as well as their impacts on CO2 adsorption performance are discussed. The review closes with a brief presentation on the challenges and opportunities for future research in the field.

Integration of thermochemical water splitting with CO2 direct air capture.

Renewable production of fuels and chemicals from direct air capture (DAC) of CO2 is a highly desired goal. Here, we report the integration of the DAC of CO2 with the thermochemical splitting of water to produce CO2, H2, O2, and electricity. The produced CO2 and H2 can be converted to value-added chemicals via existing technologies. The integrated process uses thermal solar energy as the only energy input and has the potential to provide the dual benefits of combating anthropogenic climate change while creating renewable chemicals. A sodium-manganese-carbonate (Mn-Na-CO2) thermochemical water-splitting cycle that simultaneously drives renewable H2 production and DAC of CO2 is demonstrated. An integrated reactor is designed and fabricated to conduct all steps of the thermochemical water-splitting cycle that produces close to stoichiometric amounts (∼90%) of H2 and O2 (illustrated with 6 consecutive cycles). The ability of the cycle to capture 75% of the ∼400 ppm CO2 from air is demonstrated also. A technoeconomic analysis of the integrated process for the renewable production of H2, O2, and electricity, as well as DAC of CO2 shows that the proposed scheme of solar-driven H2 production from thermochemical water splitting coupled with CO2 DAC may be economically viable under certain circumstances.

Zinc Containing Small-Pore Zeolites for Capture of Low Concentration Carbon Dioxide.

The capture of low concentration CO2 presents numerous challenges. Here, we report that zinc containing chabazite (CHA) zeolites can realize high capacity, fast adsorption kinetics, and low desorption energy when capturing ca. 400 ppm CO2 . Control of the state and location of the zinc ions in the CHA cage is critical to the performance. Zn2+ loaded onto paired anionic sites in the six-membered rings (6MRs) in the CHA cage are the primary sites to adsorb ca. 0.51 mmol CO2 /g-zeolite with Si/Al=ca. 7, a 17-fold increase compared to the parent H-form. The capacity is increased further to ca. 0.67 mmol CO2 /g-zeolite with Si/Al=ca. 2 due to more paired sites for zinc exchange. Zeolites with double six-membered rings (D6MRs) that orient 6MRs into the cages give enhanced uptakes for CO2 adsorption with zinc exchange. The results reveal that zinc exchanged CHA and several other small pore, cage containing zeolites merit further investigation for the capture of low concentration CO2 .

Structure Elucidation and Computationally Guided Synthesis of SSZ-43: A One-Dimensional 12-Ring Zeolite with Unique Sinusoidal Channels.

The structure of zeolite SSZ-43 was determined by 3D electron diffraction, synchrotron X-ray powder diffraction, and high-resolution transmission electron microscopy. The SSZ-43 framework forms one-dimensional, sinusoidal 12-ring channels from 54 61 butterfly units commonly found in other zeolites, but with unique 6.5×6.5 Šapertures and 12-ring 6.5×8.9 Šwindows perpendicular to the channels. SSZ-43 crystals are intergrowths of two polytypes: ≈90 % orthorhombic polytype A with ABAB stacking of the 12-rings, and ≈10 % monoclinic polytype B with ABCABC stacking. Molecular modeling performed on the idealized Si-SSZ-43 structure along with empirical relationships for zeolite selectivity in boron- and aluminum-containing synthesis gels were used in a combined approach to design new di-quaternary ammonium organic structure-directing agents (OSDAs). Experimental trials demonstrated that the new OSDAs produced SSZ-43 over a broader range of compositions than previous mono-quaternary OSDAs.

Inhibition of interleukin-6 on matrix protein production by glomerular mesangial cells and the pathway involved.

Activation of immunological pathways and disturbances of extracellular matrix (ECM) dynamics are important contributors to the pathogenesis of chronic kidney diseases. Glomerular mesangial cells (MCs) are critical for homeostasis of glomerular ECM dynamics. Interleukin-6 (IL-6) can act as a pro/anti-inflammatory agent relative to cell types and conditions. This study investigated whether IL-6 influences ECM protein production by MCs and the regulatory pathways involved. Experiments were carried out in cultured human MCs (HMCs) and in mice. We found that overexpression of IL-6 and its receptor decreased the abundance of fibronectin and collagen type IV in MCs. ELISA and immunoblot analysis demonstrated that thapsigargin [an activator of store-operated Ca2+ entry (SOCE)], but not the endoplasmic reticulum stress inducer tunicamycin, significantly increased IL-6 content. This thapsigargin effect was abolished by GSK-7975A, a selective inhibitor of SOCE, and by silencing Orai1 (the channel protein mediating SOCE). Furthermore, inhibition of NF-κB pharmacologically and genetically significantly reduced SOCE-induced IL-6 production. Thapsigargin also stimulated nuclear translocation of the p65 subunit of NF-κB. Moreover, MCs overexpressing IL-6 and its receptor in HMCs increased the content of the glucagon-like peptide-1 receptor (GLP-1R), and IL-6 inhibition of fibronectin was attenuated by the GLP-1R antagonist exendin 9-39. In agreement with the HMC data, specific knockdown of Orai1 in MCs using the targeted nanoparticle delivery system in mice significantly reduced glomerular GLP-1R levels. Taken together, our results suggest a novel SOCE/NF-κB/IL-6/GLP-1R signaling pathway that inhibits ECM protein production by MCs.

Nanoparticles Containing a Combination of a Drug and an Antibody for the Treatment of Breast Cancer Brain Metastases.

In women with human epidermal growth factor 2 (HER2)-positive breast cancer, the improved control of systemic disease with new therapies has unmasked brain metastases that historically would have remained clinically silent. The efficacy of therapeutic agents against brain metastases is limited by their inability to permeate the blood-brain and blood-tumor barriers (BBB and BTB) in therapeutic amounts. Here, we investigate the potential of mucic acid-based, targeted nanoparticles designed to transcytose the BBB/BTB to deliver a small molecule drug, camptothecin (CPT), and therapeutic antibody, Herceptin, to brain metastases in mice. Treatment with BBB-targeted combination CPT/Herceptin nanoparticles significantly inhibits tumor growth compared to free CPT/Herceptin and BBB-targeted nanoparticles carrying CPT alone. Though not as efficacious, BBB-targeted nanoparticles carrying only Herceptin also elicit considerable antitumor activity. These results demonstrate the potential of the targeted nanoparticle system for the delivery of an antibody alone or in combination with other drugs across the BBB/BTB to improve the therapeutic outcome.

Small-Pore Zeolites: Synthesis and Catalysis.

In the past decade or so, small-pore zeolites have received greater attention than large- and medium-pore molecular sieves that have historically dominated the literature. This is primarily due to the commercialization of two major catalytic processes, NOx exhaust removal and methanol conversion to light olefins, that take advantage of the properties of these materials with smaller apertures. Small-pore zeolites possess pores that are constructed of eight tetrahedral atoms (Si4+ and Al3+), each time linked by a shared oxygen These eight-member ring pores (8MR) provide small molecules access to the intracrystalline void space, e.g., to NOx during car exhaust cleaning (NOx removal) or to methanol en route to its conversion into light olefins, while restricting larger molecule entrance and departure that is critical to overall catalyst performance. In total, there are forty-four structurally different small-pore zeolites. Forty-one of these zeolites can be synthesized, and the first synthetic zeolite (KFI, 1948) was in fact a small-pore material. Although the field of 8MR zeolite chemistry has expanded in many directions, the progress in synthesis is framework-specific, leaving insights and generalizations difficult to realize. This review first focuses on the relevant synthesis details of all 8MR zeolites and provides some generalized findings and related insights. Next, catalytic applications where 8MR zeolites either have been commercialized or have dominated investigations are presented, with the aim of providing structure-activity relationships. The review ends with a summary that discusses (i) both synthetic and catalytic progress, (ii) a list of opportunities in the 8MR zeolite field, and (iii) a brief future outlook.

Enantiomerically enriched, polycrystalline molecular sieves.

Zeolite and zeolite-like molecular sieves are being used in a large number of applications such as adsorption and catalysis. Achievement of the long-standing goal of creating a chiral, polycrystalline molecular sieve with bulk enantioenrichment would enable these materials to perform enantioselective functions. Here, we report the synthesis of enantiomerically enriched samples of a molecular sieve. Enantiopure organic structure directing agents are designed with the assistance of computational methods and used to synthesize enantioenriched, polycrystalline molecular sieve samples of either enantiomer. Computational results correctly predicted which enantiomer is obtained, and enantiomeric enrichment is proven by high-resolution transmission electron microscopy. The enantioenriched and racemic samples of the molecular sieves are tested as adsorbents and heterogeneous catalysts. The enantioenriched molecular sieves show enantioselectivity for the ring opening reaction of epoxides and enantioselective adsorption of 2-butanol (the R enantiomer of the molecular sieve shows opposite and approximately equal enantioselectivity compared with the S enantiomer of the molecular sieve, whereas the racemic sample of the molecular sieve shows no enantioselectivity).

Host immune response to anti-cancer camptothecin conjugated cyclodextrin-based polymers.

INTRODUCTION: Efficacy and safety are critical concerns when designing drug carriers. Nanoparticles are a particular type of carrier that has gained recent attention in cancer therapeutics. METHODS: In this study, we assess the safety profile of IT-101, a nanoparticle formed by self-assembly of camptothecin (CPT) conjugated cyclodextrin-based polymers. IT-101 delivers CPT to target cancer cells in animal models of numerous human cancers and in humans. Previous data from preclinical and clinical trials indicate that IT-101 has no notable immunological side effects. However, there have been no published studies focused on evaluating the effects of IT-101 on host immune systems. RESULTS: In this work, we demonstrate that IT-101 diminished initial host immune response following first injection of the nanopharmaceutical and induced NK cell activation and T cell proliferation upon further IT-101 exposure. Additionally, IT-101 could attenuate tumor growth more efficiently than CPT treatment only. CONCLUSIONS: Drugs administration in whole-body circulation may lead to poorly bioavailable in central nervous system and often has toxic effects on peripheral tissues. Conjugated with cyclodextrin-based polymers not only reduce adverse effects but also modulate the immune responses to elevate drug efficacy. These immune responses may potentially facilitate actions of immune blockage, such as PD1/PDL1 in cancer treatment.

CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing.

Nanoparticle-based therapeutics are being used to treat patients with solid tumors. Whereas nanoparticles have been shown to preferentially accumulate in solid tumors of animal models, there is little evidence to prove that intact nanoparticles localize to solid tumors of humans when systemically administered. Here, tumor and adjacent, nonneoplastic tissue biopsies are obtained through endoscopic capture from patients with gastric, gastroesophageal, or esophageal cancer who are administered the nanoparticle CRLX101. Both the pre- and postdosing tissue samples adjacent to tumors show no definitive evidence of either the nanoparticle or its drug payload (camptothecin, CPT) contained within the nanoparticle. Similar results are obtained from the predosing tumor samples. However, in nine of nine patients that were evaluated, CPT is detected in the tumor tissue collected 24-48 h after CRLX101 administration. For five of these patients, evidence of the intact deposition of CRLX101 nanoparticles in the tumor tissue is obtained. Indications of CPT pharmacodynamics from tumor biomarkers such as carbonic anhydrase IX and topoisomerase I by immunohistochemistry show clear evidence of biological activity from the delivered CPT in the posttreatment tumors.

Further Studies on How the Nature of Zeolite Cavities That Are Bounded by Small Pores Influences the Conversion of Methanol to Light Olefins.

A series of small-pore zeolites are synthesized and investigated as catalysts for the methanol-to-olefins (MTO) reaction. Small-pore zeolites SSZ-13, SSZ-16, SSZ-27, SSZ-28, SSZ-52, SSZ-98, SSZ-99, SSZ-104, SSZ-105 and an ITQ-3-type material are synthesized, and the results from their use as catalytic materials in the MTO reaction compared to those obtained from SAPO-34. The production of propane that tends to correlate with catalytic material lifetime (higher initial propane yields lead to shorter lifetimes) declines with increasing Si/Al (as has been observed previously for SSZ-13), and a larger cage dimension leads to higher propane yields at a fixed Si/Al. Data from these materials and others reported previously, for example, SSZ-39 and Rho, that were tested at the same reaction conditions, revealed four different patterns of light olefin selectivities: 1) ethylene greater than propylene with low butene, for example, SSZ-17, SSZ-98, SSZ-105, 2) ethylene equal to propylene and low butene, for example, SAPO-34, SSZ-13, SSZ-16, SSZ-27, SSZ-52, SSZ-99, SSZ-104, 3) propylene greater than ethylene with butene similar to ethylene, for example, SSZ-28, SSZ-39, and 4) ethylene equal to propylene equal to butene, for example, Rho. No clear relationships between zeolite cage architecture and light olefin selectivity emerged from this investigation, although several trends are presented as suggestions for further study.

Tandem catalysis for the production of alkyl lactates from ketohexoses at moderate temperatures.

Retro-aldol reactions have been implicated as the limiting steps in catalytic routes to convert biomass-derived hexoses and pentoses into valuable C2, C3, and C4 products such as glycolic acid, lactic acid, 2-hydroxy-3-butenoic acid, 2,4-dihydroxybutanoic acid, and alkyl esters thereof. Due to a lack of efficient retro-aldol catalysts, most previous investigations of catalytic pathways involving these reactions were conducted at high temperatures (≥160 °C). Here, we report moderate-temperature (around 100 °C) retro-aldol reactions of various hexoses in aqueous and alcoholic media with catalysts traditionally known for their capacity to catalyze 1,2-intramolecular carbon shift (1,2-CS) reactions of aldoses, i.e., various molybdenum oxide and molybdate species, nickel(II) diamine complexes, alkali-exchanged stannosilicate molecular sieves, and amorphous TiO2-SiO2 coprecipitates. Solid Lewis acid cocatalysts that are known to catalyze 1,2-intramolecular hydride shift (1,2-HS) reactions that enable the formation of α-hydroxy carboxylic acids from tetroses, trioses, and glycolaldehyde, but cannot readily catalyze retro-aldol reactions of hexoses and pentoses at these moderate temperatures, are shown to be compatible with the aforementioned retro-aldol catalysts. The combination of a distinct retro-aldol catalyst with a 1,2-HS catalyst enables lactic acid and alkyl lactate formation from ketohexoses at moderate temperatures (around 100 °C), with yields comparable to best-reported chemocatalytic examples at high temperature conditions (≥160 °C). The use of moderate temperatures enables numerous desirable features such as lower pressure and significantly less catalyst deactivation.

Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core.

Most therapeutic agents are excluded from entering the central nervous system by the blood-brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the blood side of the BBB, but separate from their multidentate Tf-TfR interactions upon acidification during the transcytosis process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis.

A Chromium Hydroxide/MIL-101(Cr) MOF Composite Catalyst and Its Use for the Selective Isomerization of Glucose to Fructose.

A metal-organic framework (MOF)-based catalyst, chromium hydroxide/MIL-101(Cr), was prepared by a one-pot synthesis method. The combination of chromium hydroxide particles on and within Lewis acidic MIL-101 accomplishes highly selective conversion of glucose to fructose in the presence of ethanol, matching the performance of optimized Sn-containing Lewis acidic zeolites. Differently from zeolites, NMR spectroscopy studies with isotopically labeled molecules demonstrate that isomerization of glucose to fructose on this catalyst, proceeds predominantly via a proton transfer mechanism.

Negative regulation of Smad1 pathway and collagen IV expression by store-operated Ca2+ entry in glomerular mesangial cells.

Collagen IV (Col IV) is a major component of expanded glomerular extracellular matrix in diabetic nephropathy and Smad1 is a key molecule regulating Col IV expression in mesangial cells (MCs). The present study was conducted to determine if Smad1 pathway and Col IV protein abundance were regulated by store-operated Ca2+ entry (SOCE). In cultured human MCs, pharmacological inhibition of SOCE significantly increased the total amount of Smad1 protein. Activation of SOCE blunted high-glucose-increased Smad1 protein content. Treatment of human MCs with ANG II at 1 µM for 15 min, high glucose for 3 days, or TGF-ß1 at 5 ng/ml for 30 min increased the level of phosphorylated Smad1. However, the phosphorylation of Smad1 by those stimuli was significantly attenuated by activation of SOCE. Knocking down Smad1 reduced, but expressing Smad1 increased, the amount of Col IV protein. Furthermore, activation of SOCE significantly attenuated high-glucose-induced Col IV protein production, and blockade of SOCE substantially increased the abundance of Col IV. To further verify those in vitro findings, we downregulated SOCE specifically in MCs in mice using small-interfering RNA (siRNA) against Orai1 (the channel protein mediating SOCE) delivered by the targeted nanoparticle delivery system. Immunohistochemical examinations showed that expression of both Smad1 and Col IV proteins was significantly greater in the glomeruli with positively transfected Orai1 siRNA compared with the glomeruli from the mice without Orai1 siRNA treatment. Taken together, our results indicate that SOCE negatively regulates the Smad1 signaling pathway and inhibits Col IV protein production in MCs.

Store-operated calcium entry suppressed the TGF-ß1/Smad3 signaling pathway in glomerular mesangial cells.

Our previous study demonstrated that the abundance of extracellular matrix proteins was suppressed by store-operated Ca2+ entry (SOCE) in mesangial cells (MCs). The present study was conducted to investigate the underlying mechanism focused on the transforming growth factor-ß1 (TGF-ß1)/Smad3 pathway, a critical pathway for ECM expansion in diabetic kidneys. We hypothesized that SOCE suppressed ECM protein expression by inhibiting this pathway in MCs. In cultured human MCs, we observed that TGF-ß1 (5 ng/ml for 15 h) significantly increased Smad3 phosphorylation, as evaluated by immunoblot. However, this response was markedly inhibited by thapsigargin (1 µM), a classical activator of store-operated Ca2+ channels. Consistently, both immunocytochemistry and immunoblot showed that TGF-ß1 significantly increased nuclear translocation of Smad3, which was prevented by pretreatment with thapsigargin. Importantly, the thapsigargin effect was reversed by lanthanum (La3+; 5 µM) and GSK-7975A (10 µM), both of which are selective blockers of store-operated Ca2+ channels. Furthermore, knockdown of Orai1, the pore-forming subunit of the store-operated Ca2+ channels, significantly augmented TGF-ß1-induced Smad3 phosphorylation. Overexpression of Orai1 augmented the inhibitory effect of thapsigargin on TGF-ß1-induced phosphorylation of Smad3. In agreement with the data from cultured MCs, in vivo knockdown of Orai1 specific to MCs using a targeted nanoparticle small interfering RNA delivery system resulted in a marked increase in abundance of phosphorylated Smad3 and in nuclear translocation of Smad3 in the glomerulus of mice. Taken together, our results indicate that SOCE in MCs negatively regulates the TGF-ß1/Smad3 signaling pathway.

Synthesis of terephthalic acid via Diels-Alder reactions with ethylene and oxidized variants of 5-hydroxymethylfurfural.

Terephthalic acid (PTA), a monomer in the synthesis of polyethylene terephthalate (PET), is obtained by the oxidation of petroleum-derived p-xylene. There is significant interest in the synthesis of renewable, biomass-derived PTA. Here, routes to PTA starting from oxidized products of 5-hydroxymethylfurfural (HMF) that can be produced from biomass are reported. These routes involve Diels-Alder reactions with ethylene and avoid the hydrogenation of HMF to 2,5-dimethylfuran. Oxidized derivatives of HMF are reacted with ethylene over solid Lewis acid catalysts that do not contain strong Brønsted acids to synthesize intermediates of PTA and its equally important diester, dimethyl terephthalate (DMT). The partially oxidized HMF, 5-(hydroxymethyl)furoic acid (HMFA), is reacted with high pressure ethylene over a pure-silica molecular sieve containing framework tin (Sn-Beta) to produce the Diels-Alder dehydration product, 4-(hydroxymethyl)benzoic acid (HMBA), with 31% selectivity at 61% HMFA conversion after 6 h at 190 °C. If HMFA is protected with methanol to form methyl 5-(methoxymethyl)furan-2-carboxylate (MMFC), MMFC can react with ethylene in the presence of Sn-Beta for 2 h to produce methyl 4-(methoxymethyl)benzenecarboxylate (MMBC) with 46% selectivity at 28% MMFC conversion or in the presence of a pure-silica molecular sieve containing framework zirconium (Zr-Beta) for 6 h to produce MMBC with 81% selectivity at 26% MMFC conversion. HMBA and MMBC can then be oxidized to produce PTA and DMT, respectively. When Lewis acid containing mesoporous silica (MCM-41) and amorphous silica, or Brønsted acid containing zeolites (Al-Beta), are used as catalysts, a significant decrease in selectivity/yield of the Diels-Alder dehydration product is observed.