Spatially Confined π-Complexation within Pore-Space-Partitioned Metal-Organic Frameworks for Enhanced Light Hydrocarbon Separation and Purification.

Ultramicroporous metal-organic frameworks (MOFs) are demonstrated to be advantageous for the separation and purification of light hydrocarbons such as C2H2, C2H4, and CH4. The introduction of transition metal sites with strong π-complexation affinity into MOFs is more effective than other adsorption sites for the selective adsorption of π-electron-rich unsaturated hydrocarbon gases from their mixtures. However, lower coordination numbers make it challenging to produce robust MOFs directly utilizing metal ions with π-coordination activity, such as Cu+, Ag+, and Pd2+. Herein, a series of novel π-complexing MOFs (SNNU-33s) with a pore size of 4.6 Å are precisely constructed by cleverly introducing symmetrically matched C3-type [Cu(pyz)3] (pyz = pyrazine) coordinated fragments into 1D hexagonal channels of MIL-88 prototype frameworks. Benifit from the spatial confinement combined with π-complex-active Cu+ of [Cu(pyz)3], pore-space-partitioned SNNU-33 MOFs all present excellent C2H2/CH4, C2H4/CH4, and CO2/CH4 separation ability. Notably, the optimized SNNU-33b adsorbent demonstrates top-level IAST selectivity values for C2H2/CH4 (597.4) and C2H4/CH4 (69.8), as well as excellent breakthrough performance. Theoretical calculations further reveal that such benchmark light hydrocarbon separation and purification ability is mainly ascribed to the extra-strong binding affinity between Cu+ and π-electron donor molecules via a spatially confined π-complexation process.

De-Linker-Enabled Exceptional Volumetric Acetylene Storage Capacity and Benchmark C2 H2 /C2 H4 and C2 H2 /CO2 Separations in Metal-Organic Frameworks.

An ideal adsorbent for separation requires optimizing both storage capacity and selectivity, but maximizing both or achieving a desired balance remain challenging. Herein, a de-linker strategy is proposed to address this issue for metal-organic frameworks (MOFs). Broadly speaking, the de-linker idea targets a class of materials that may be viewed as being intermediate between zeolites and MOFs. Its feasibility is shown here by a series of ultra-microporous MOFs (SNNU-98-M, M=Mn, Co, Ni, Zn). SNNU-98 exhibit high volumetric C2 H2 uptake capacity under low and ambient pressures (175.3 cm3 cm-3 @ 0.1 bar, 222.9 cm3 cm-3 @ 1 bar, 298 K), as well as extraordinary selectivity (2405.7 for C2 H2 /C2 H4 , 22.7 for C2 H2 /CO2 ). Remarkably, SNNU-98-Mn can efficiently separate C2 H2 from C2 H2 /CO2 and C2 H2 /C2 H4 mixtures with a benchmark C2 H2 /C2 H4 (1/99) breakthrough time of 2325 min g-1 , and produce 99.9999 % C2 H4 with a productivity up to 64.6 mmol g-1 , surpassing values of reported MOF adsorbents.

Competitive Coordination-Oriented Monodispersed Ruthenium Sites in Conductive MOF/LDH Hetero-Nanotree Catalysts for Efficient Overall Water Splitting in Alkaline Media.

Rational exploration of efficient, inexpensive, and robust electrocatalysts is critical for the efficient water splitting. Conjugated conductive metal-organic frameworks (cMOFs) with multicomponent layered double hydroxides (LDHs) to construct bifunctional heterostructure catalysts are considered as an efficient but complicated strategy. Here, the fabrication of a cMOF/LDH hetero-nanotree array catalyst (CoNiRu-NT) coupled with monodispersed ruthenium (Ru) sites via a controllable grafted-growth strategy is reported. Rich-amino hexaiminotriphenylene linkers coordinate with the LDH nanotrunk to form cMOF nanobranches, providing numerous anchoring sites to precisely confine and stabilize RuN4 sites. Moreover, monodispersed and reduced Ru moieties facilitate H2 O adsorption and dissociation, and the heterointerface between the cMOF and the LDH further modifies the chemical and electronic structures. Optimized CoNiRu-NT displays a significant increase in electrochemical water-splitting properties in alkaline media, affording low overpotentials of 22 mV at 10 mA cm-2 and 255 mV at 20 mA cm-2 for the hydrogen evolution reaction and oxygen evolution reaction, respectively. In an actual electrochemical system, CoNiRu-NT drives an overall water splitting at a low cell voltage of 1.47 V to reach 10 mA cm-2 . This performance is comparable to that of pure noble-metal-based materials and superior to most reported MOF-based catalysts.

Amide-Functionalized Metal-Organic Frameworks Coupled with Open Fe/Sc Sites for Efficient Acetylene Purification.

Acetylene (C2H2) purification is of great importance for many chemical synthesis and processes. Metal-organic frameworks (MOFs) are widely used for gas adsorption and separation due to their variable structure and porosity. However, the exploitation of ideal MOF adsorbents for C2H2 keeps a challenging task. Herein, a combination of open metal sites (OMSs) and Lewis basic sites (LBSs) in robust MOFs is demonstrated to effectively promote the C2H2 purification performance. Accordingly, SNNU-37(Fe/Sc), two isostructural MOFs constituted by [Fe3O(COO)6] or [Sc3O(COO)6] trinuclear clusters and amide-functionalized tricarboxylate linkers, were designed with extra-stable 3,6-connected new architectures. Derived from the coexistence of high-density OMSs and LBSs, the C2H2 adsorption amounts of SNNU-37(Fe/Sc) are much higher than those values for C2H4 and CO2. Theoretical IAST selectivity values of SNNU-37(Fe) are 2.4 for C2H2/C2H4 (50/50, v/v) and 9.9 for C2H2/CO2 (50/50, v/v) at 298 K and 1 bar, indicating an excellent C2H2 separation ability. Experimental breakthrough curves also revealed that SNNU-37(Fe) could effectively separate C2H2/C2H4 and C2H2/CO2 under ambient conditions. GCMC simulations further indicate that open Fe or Sc sites and amide groups mainly contribute to stronger adsorption sites for C2H2 molecules.

Precise Pore Space Partitions Combined with High-Density Hydrogen-Bonding Acceptors within Metal-Organic Frameworks for Highly Efficient Acetylene Storage and Separation.

The high storage capacity versus high selectivity trade-off barrier presents a daunting challenge to practical application as an acetylene (C2 H2 ) adsorbent. A structure-performance relationship screening for sixty-two high-performance metal-organic framework adsorbents reveals that a moderate pore size distribution around 5.0-7.5 Šis critical to fulfill this task. A precise pore space partition approach was involved to partition 1D hexagonal channels of typical MIL-88 architecture into finite segments with pore sizes varying from 4.5 Š(SNNU-26) to 6.4 Š(SNNU-27), 7.1 Š(SNNU-28), and 8.1 Š(SNNU-29). Coupled with bare tetrazole N sites (6 or 12 bare N sites within one cage) as high-density H-bonding acceptors for C2 H2 , the target MOFs offer a good combination of high C2 H2 /CO2 adsorption selectivity and high C2 H2 uptake capacity in addition to good stability. The optimized SNNU-27-Fe material demonstrates a C2 H2 uptake of 182.4 cm3 g-1 and an extraordinary C2 H2 /CO2 dynamic breakthrough time up to 91 min g-1 under ambient conditions.

Lignans and phenylpropanoids from the liquid juice of phyllostachys edulis.

Seven lignans and eight phenylpropanoids, including one new lignan, 7S,8R,8'R-5,5'-dimethoxyariciresinol-4-O-ß-D-glucopyranoside (1), were isolated from the liquid juice of Phyllostachys edulis. Their structures were established by extensive spectroscopic analyses. The absolute configuration of the new compound was determined by comparing its experimental electronic circular dichroism (ECD) spectra with calculated ECD spectra. All compounds were evaluated for their anti-inflammatory activity and xanthine oxidase inhibitor activity, and the results showed that compound 9 exhibited a moderate activity in these two bioassays. In addition, all the compounds can be detected in health panda faeces by LC-MS.

Tuning the Pore Surface of an Ultramicroporous Framework for Enhanced Methane and Acetylene Purification Performance.

Both methane (CH4) and acetylene (C2H2) are important energy source and raw chemicals in many industrial processes. The development of an energy-efficient and environmentally friendly separation and purification strategy for CH4 and C2H2 is necessary. Ultramicroporous metal-organic framework (MOF) materials have shown great success in the separation and purification of small-molecule gases. Herein, the synergy effect of tritopic polytetrazolate and ditopic terephthalate ligands successfully generates a series of isoreticular ultramicroporous cadmium tetrazolate-carboxylate MOF materials (SNNU-13-16) with excellent CH4 and C2H2 purification performance. Except for the uncoordinated tetrazolate N atoms serving as Lewis base sites, the pore size and pore surface of MOFs are systematically engineered by regulating dicarboxylic acid ligands varying from OH-BDC (SNNU-13) to Br-BDC (SNNU-14) to NH2-BDC (SNNU-15) to 1,4-NDC (SNNU-16). Benefiting from the ultramicroporous character (3.8-5.9 Å), rich Lewis base N sites, and tunable pore environments, all of these ultramicroporous MOFs exhibit a prominent separation capacity for carbon dioxide (CO2) or C2 hydrocarbons from CH4 and C2H2. Remarkably, SNNU-16 built by 1,4-NDC shows the highest ideal adsorbed solution theory CO2/CH4, ethylene (C2H4)/CH4, and C2H2/CH4 separation selectivity values, which are higher than those of most famous MOFs with or without open metal sites. Dynamic breakthrough experiments show that SNNU-16 can also efficiently separate the C2H2/CO2 mixtures with a gas flow rate of 4 mL min-1 under 1 bar and 298 K. The breakthrough time (18 min g-1) surpasses most best-gas-separation MOFs and nearly all other metal azolate-carboxylate MOF materials under the same conditions. The above prominently CH4 and C2H2 purification abilities of SNNU-13-16 materials were further confirmed by the Grand Canonical Monte Carlo (GCMC) simulations.

Multimetal Incorporation into 2D Conductive Metal-Organic Framework Nanowires Enabling Excellent Electrocatalytic Oxidation of Benzylamine to Benzonitrile.

As an important organic intermediate, benzonitrile (BN) is widely involved in organic synthetic chemistry and pharmaceutical and dyestuff industries. However, the exploration of a more efficient and controllable synthesis technique and the corresponding greener catalysts for the synthesis of BN still poses a great challenge. Herein, with multimetallic two-dimensional conductive metal-organic frameworks (2D cMOF) as anodic electrocatalysts, we develop a green, convenient, and highly efficient electrochemical synthesis strategy for BN. Thanks to the intrinsic 2D electrically conductive structure and the optimized the multimetallic coupling catalytic effect, the resulting multimetallic 2D cMOFs exhibit excellent benzylamine (BA) electrooxidation performance. Especially, the trimetallic 2D cMOF (NiCoFe-CAT) requires an ultralow potential of 1.29 V vs reversible hydrogen electrode (RHE) to achieve a 10 mA·cm-2 current density, which indicates the fastest reaction and the most favorable thermodynamic condition. A very high yield (0.058 mmol·mg-1·h-1) and faradic efficiency (∼87%) of benzonitrile are both achieved during the BA electrooxidation reaction at 1.45 V. The reaction mechanism investigations indicated that the various redox mediators of MII/MIII (Ni, Co, Fe) may be regarded as multimetal active species to promote BA conversion. Also, the excellent cycling durability of multimetallic 2D cMOFs further promotes their potential practical applications. These electrocatalytic performances are considered excellent and nearly surpass all other reported Ni-based inorganics or MOF-based electrocatalysts for the electrocatalytic oxidation of benzylamine.

Systematic Regulation of C2H2/CO2 Separation by 3p-Block Open Metal Sites in a Robust Metal-Organic Framework Platform.

The separation of a mixture of C2H2 and CO2 is a great challenge due to their similar molecular sizes and shapes. Al-based metal-organic frameworks (Al-MOFs) have great promise for gas separation applications due to their light weight, high stability, and low cost. However, the cultivation of suitable Al-MOF single crystals is extremely difficult and has limited their explorations up to now. Since In, Ga, and Al are all 3p-block metal elements, a systematic application of the periodic law to investigate 3p-MOFs will undoubtedly help in the understanding and development of worthy Al-MOF materials. Herein, we report the design of a robust 3p metal-organic framework platform (SNNU-150) and the systematic regulation of C2H2/CO2 separation by open 3p-block metal sites. X-ray single-crystal diffraction analysis reveals that SNNU-150 is a 3,6-connected 3D framework consisting of [M3O(COO)6] trinuclear secondary building units (SBUs) and tritopic nitrilotribenzoate (NTB) linkers. Small {[M3O(COO)6]4(NTB)6} tetrahedral cages and extra-large {[M3O(COO)6]10(NTB)14} polyhedral cages connect with each other to generate a hierarchically porous architecture. These 3p-MOFs present very high water, thermal, and chemical stability, especially for SNNU-150-Al, which can maintain its framework at 85 °C in water for 24 h and in a room-temperature environment for more than 30 days. IAST calculations, breakthrough experiments, and GCMC simulations all show that SNNU-150 MOFs have top-level C2H2/CO2 separation performance and follow the order Al-MOF > Ga-MOF > In-MOF.

Globally stabilized bent carbon-carbon triple bond by hydrogen-free inorganic-metallic scaffolding Al4F6.

For over 100 years, known bent C[triple bond, length as m-dash]C compounds have been limited to those with organic (I) and all-carbon (II) scaffoldings. Here, we computationally report a novel type (III) of bent C[triple bond, length as m-dash]C compound, i.e., C2Al4F6-01, which is the energetically global minimum isomer and bears an inorganic-metallic scaffolding and unexpected click reactivity.

Mimic of Ferroalloy To Develop a Bifunctional Fe-Organic Framework Platform for Enhanced Gas Sorption and Efficient Oxygen Evolution Electrocatalysis.

It is well-known that the formation of ferroalloy with the addition of the second or third metal during the steel-making process usually can improve the performance of the iron. Inspired by ferroalloy materials, it is speculated that the pore environment, framework charge, and catalytic properties of metal-organic frameworks (MOFs) could be optimized dramatically via the introduction of ferroalloy-like inorganic building blocks. However, different to ferroalloy, the accurate integration of different metals into one MOF platform is still challenging. Herein, taking advantages of the good compatibility for metals in trigonal prismatic trinuclear cluster, a series of Fe-based alloy-like [M3O(O2C)6] motifs (M3 = Fe3, Fe1.5Ni1.5, Fe1.5Co1.5, Fe1.5Ti1.5, FeCoNi, and FeTiCo) are successfully generated, which further lead to a robust Fe-MOF material family (SNNU-5s). These multicomponent MOFs not only provide a good chance to explore the impact of pore environment on gas adsorption/separation but also offer an opportunity to the efficient electrocatalytic reaction directly. Accordingly, compared with the SNNU-5-Fe parent structure, the pore characters of heterometallic SNNU-5 MOFs are clearly regulated by the type of alloy-like building blocks. SNNU-5-FeTi displays more superior gas separation performance for CO2/CH4, C2H2/CH4, C2H4/CH4, and C2H2/CO2 gas mixtures. What is more, benefited from the multimetallic active sites and their catalytic synergy, FeCoNi-ternary alloy-like cluster-based SNNU-5 MOF material exhibits an exceptional oxygen evolution reaction activity in aqueous solution at pH = 13, which delivers a low overpotential (ηj=10 = 317 mV), a fast reaction kinetics (Tafel slope = 37 mV dec-1), and excellent catalytic stability. This facile multialloy-like building block strategy holds promise to accurately design and improve the performance of MOFs, as well as open an avenue to understand the related mechanisms.

Ultramicroporous Building Units as a Path to Bi-microporous Metal-Organic Frameworks with High Acetylene Storage and Separation Performance.

A strategy called ultramicroporous building unit (UBU) is introduced. It allows the creation of hierarchical bi-porous features that work in tandem to enhance gas uptake capacity and separation. Smaller pores from UBUs promote selectivity, while larger inter-UBU packing pores increase uptake capacity. The effectiveness of this UBU strategy is shown with a cobalt MOF (denoted SNNU-45) in which octahedral cages with 4.5 Špore size serve as UBUs. The C2 H2 uptake capacity at 1 atm reaches 193.0 cm3 g-1 (8.6 mmol g-1 ) at 273 K and 134.0 cm3 g-1 (6.0 mmol g-1 ) at 298 K. Such high uptake capacity is accompanied by a high C2 H2 /CO2 selectivity of up to 8.5 at 298 K. Dynamic breakthrough studies at room temperature and 1 atm show a C2 H2 /CO2 breakthrough time up to 79 min g-1 , among top-performing MOFs. Grand canonical Monte Carlo simulations agree that ultrahigh C2 H2 /CO2 selectivity is mainly from UBU ultramicropores, while packing pores promote C2 H2 uptake capacity.

CCR4 expression on host T cells is a driver for alloreactive responses and lung rejection.

Despite current immunosuppressive strategies, long-term lung transplant outcomes remain poor due to rapid allogenic responses. Using a stringent mouse model of allo-airway transplantation, we identify the CCR4-ligand axis as a central node driving secondary lymphoid tissue homing and activation of the allogeneic T cells that prevent long-term allograft survival. CCR4 deficiency on transplant recipient T cells diminishes allograft injury and when combined with CTLA4-Ig leads to an unprecedented long-term lung allograft accommodation. Thus, we identify CCR4-ligand interactions as a central mechanism driving allogeneic transplant rejection and suggest it as a potential target to enhance long-term lung transplant survival.

New global minima of 6-vertex dicarboranes: classical but unexpected.

Dicarboranes generally adopt global minimum predicted by the well-known Wade-Mingos rules, although one classical non-closo structure in the benzvalene form has long been pursued and later synthesized. Here we predicted two new non-closo global minima for 6-vertex dicarboranes (C2B4R6), i.e., trigonal bipyramid (R = SH) and butterfly (R = Cl, NH2, OH, F). The long expected classical benzvalene-like structure, however, is not the global minimum for any of the nine substituents.

Comparative Effects of Monosialoganglioside versus Citicoline on Apoptotic Factor, Neurological Function and Oxidative Stress in Newborns with Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: To determine the comparative effect of monosialoganglioside versus citicoline on the content changes of serum apoptotic factors (PDCD5, sFas and sFasL), neurological function indices (BDNF, NSE, S100-ß and NGF) and oxidative stress indices (SOD, MDA and GSH-PX) in newborns with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Emergency Department, Affiliated Children's Hospital of Zhengzhou University, China, from October 2016 to February 2018. METHODOLOGY: A total of 90 newborns with HIE were randomly divided into a treatment group and a control group, with 45 cases in each group. In addition to the conventional treatment, the treatment group was given monosialoganglioside treatment, while the control group was given citicoline treatment. Both groups were treated for 10 days. After treatment, the content differences of serum apoptosis factors (PDCD5, sFas and sFasL), neurological function indices (BDNF, NSE, S100-ß and NGF) and oxidative stress indices (SOD, MDA and GSH-PX) were observed in the two groups. RESULTS: After treatment, the levels of serum PDCD5, sFas, sFasL, MDA, NSE and S100-ß in the treatment group were lower than those in the control group (all p<0.001). The contents of serum SOD, GSH-PX, BDNF and NGF in the treatment group were higher than those in the control group (all p<0.001). CONCLUSION: Monosialoganglioside can effectively improve the apoptotic factors, neurological function and oxidative stress indices in newborns and maintain the stability of the internal environment, so it is worthy of promotion and application.

Ionothermal synthesis of novel Pb-OH-Cu-X (X = Cl, Br and I) quaternary heterometallic frameworks with tunable optical properties.

Reported herein is the new application of ionothermal synthesis for inorganic optical materials. Under ionothermal conditions with different imidazolium ionic liquids, novel quaternary heterometallic frameworks based on [Pb4(OH)4] cubane and [CuCl4] or [CuBr4] chains and [Cu2I6] binuclear clusters have been successfully produced. Simple chlorine, bromine and iodine replacement leads to not only the space group change (tetragonal I41/acd for 1 and 2, and orthorhombic Fddd for 3) but also the topological net transformation (8,12-net for 1 and 2, and 6,6-net for 3). Notably, compounds 1, 2 and 3 all show tunable solid-state semiconducting and luminescence properties.

Theoretical Prediction on [5]Radialene Sandwich Complexes (CpM)2(C10H10) (Cp = η5-C5H5; M = Fe, Co, Ni): Geometry, Spin States, and Bonding.

[5]Radialene, the missing link for synthesis of radialene family, has been finally obtained via the preparation and decomplexation of the [5]radialene-bis-Fe(CO)3 complex. The stability of [5]radialene complex benefits from the coordination with Fe(CO)3 by losing free 1,3-butadiene structures to avoid polymerization. In light of the similar coordination ability of half-sandwiches CpM(Cp = η5-C5H5; M = Fe, Co, Ni), there is a great possibility that the sandwiched complexes of [5]radialene with CpM are available. Herein, we present the first theoretical prediction on the geometry, spin states and bonding of (CpM)(C10H10) and (CpM)2(C10H10). For M = Fe, Co, Ni, the ground states of (CpM)(C10H10) and (CpM)2(C10H10) are doublet and triplet, singlet and singlet, and doublet and triplet states, where each Fe, Co, and Ni adopts 17, 18, and 19 electron-configuration, respectively. In particular, (CpFe)2(C10H10) and (CpNi)2(C10H10) have considerable open-shell singlet features. Generally the trans isomers of (CpM)2(C10H10) with two CpM fragments on the opposite sides of the [5]radialene plane are apparently more stable than the cis ones with CpM fragments on the same side. However, for the singlet and triplet isomers of (CpNi)2(C10H10) (both cis and trans isomers), the energy differences are relatively small, indicating that these isomers all have the opportunity to exist. Besides, the easy Diels-Alder (DA) dimerization between the [3]dendralene-like fragments of (CpM)(C10H10) suggests the great difficulty in isolating the (CpM)(C10H10) monomer.

Theoretical Designs for Organoaluminum C2Al4R4 with Well-Separated Al(I) and Al(III).

It is well-known that the chemistry of aluminum is dominated by Al(III) in the +3 oxidation state. Only during the past 2 decades has the chemistry of Al(I) and Al(II) been rapidly developed. However, if Al(I) and Al(III) are combined, the inherently high reactivities of Al(I) and Al(III) mostly result in their coupling with each other or interacting with surrounding elements, which easily results in significant deactivation or quenching of the desired oxidation states, as in the case of reported mixed valent Al-compounds. In this article, we report an unprecedented type of organoaluminum system, C2Al4R4 (R = H, SiH3, Si(C6H5)3, SiiPrDis2, SiMe(SitBu3)2), whose lowest-energy structure, C2Al4R4-01, contains two Al(I) and two Al(III) atoms. The global nature and bonding motif of the parent C2Al4R4-01 (R = H) were supported by an extensive global isomeric search, CBS-QB3 energy calculations, adaptive natural density partitioning, and bond order analysis. Interestingly and in sharp contrast to most organoaluminum species, C2Al4R4-01 is associated with little multicenter bonding. C2Al4R4-01 has a high feasibility of being observed either in the gas or condensed phases (with suitable substitutents). With well-separated Al(I) and Al(III), C2Al4R4-01 (with suitable substitutents) could serve as the first Al/Al frustrated Lewis pair.

CD4(+)CD25(hi)Foxp3(+) Cells Exacerbate Bleomycin-Induced Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is a fatal lung disease with a median survival of 2 to 5 years. A decade of studies has downplayed inflammation contributing to its pathogenesis. However, these studies preceded the discovery of regulatory T cells (Tregs) and all of their functions. On the basis of human studies demonstrating Tregs can decrease graft-versus-host disease and vasculitides, there is consideration of their use to treat idiopathic pulmonary fibrosis. We hypothesized that Treg therapy would attenuate the fibroplasia involved in a preclinical murine model of pulmonary fibrosis. IL-2 complex was used in vivo to expand CD4(+)CD25(hi)Foxp3(+) cells in the lung during intratracheal bleomycin challenge; however, this unexpectedly led to an increase in lung fibrosis. More important, this increase in fibrosis was a lymphocyte-dependent process. We corroborated these results using a CD4(+)CD25(hi)Foxp3(+) cellular-based therapy. Mechanistically, we demonstrated that CD4(+)CD25(hi)Foxp3(+) cells undergo alterations during bleomycin challenge and the IL-2 complex had no effect on profibrotic (eg, transforming growth factor-ß) or type 17 immune response cytokines; however, there was a marked down-regulation of the type 1 and augmentation of the type 2 immune response cytokines from the lungs. Collectively, our animal studies show that a specific lung injury can induce Treg alterations, which can augment pulmonary fibrosis.

Effects of maternal food restriction on offspring lung extracellular matrix deposition and long term pulmonary function in an experimental rat model.

Intrauterine growth restriction (IUGR) increases the risk of respiratory compromise throughout postnatal life. However, the molecular mechanism(s) underlying the respiratory compromise in offspring following IUGR is not known. We hypothesized that IUGR following maternal food restriction (MFR) would affect extracellular matrix deposition in the lung, explaining the long-term impairment in pulmonary function in the IUGR offspring. Using a well-established rat model of MFR during gestation to produce IUGR pups, we found that at postnatal day 21, and at 9 months (9M) of age the expression and abundance of elastin and alpha smooth muscle actin (αSMA), two key extracellular matrix proteins, were increased in IUGR lungs when compared to controls (P < 0.05, n = 6), as determined by both Western and immunohistochemistry analyses. Compared to controls, the MFR group showed no significant change in pulmonary resistance at baseline, but did have significantly decreased pulmonary compliance at 9M (P < 0.05 vs. control, n = 5). In addition, MFR lungs exhibited increased responsiveness to methacholine challenge. Furthermore, exposing cultured fetal rat lung fibroblasts to serum deprivation increased the expression of elastin and elastin-related genes, which was blocked by serum albumin supplementation, suggesting protein deficiency as the predominant mechanism for increased pulmonary elastin deposition in IUGR lungs. We conclude that accompanying the changes in lung function, consistent with bronchial hyperresponsiveness, expression of the key alveolar extracellular matrix proteins elastin and αSMA increased in the IUGR lung, thus providing a potential explanation for the compromised lung function in IUGR offspring.