Efficient direct reprogramming of mature amniotic cells into endothelial cells by ETS factors and TGFß suppression.

ETS transcription factors ETV2, FLI1, and ERG1 specify pluripotent stem cells into induced vascular endothelial cells (iVECs). However, iVECs are unstable and drift toward nonvascular cells. We show that human midgestation c-Kit(-) lineage-committed amniotic cells (ACs) can be reprogrammed into vascular endothelial cells (rAC-VECs) without transitioning through a pluripotent state. Transient ETV2 expression in ACs generates immature rAC-VECs, whereas coexpression with FLI1/ERG1 endows rAC-VECs with a vascular repertoire and morphology matching mature endothelial cells (ECs). Brief TGFß-inhibition functionalizes VEGFR2 signaling, augmenting specification of ACs into rAC-VECs. Genome-wide transcriptional analyses showed that rAC-VECs are similar to adult ECs in which vascular-specific genes are expressed and nonvascular genes are silenced. Functionally, rAC-VECs form stable vasculature in Matrigel plugs and regenerating livers. Therefore, short-term ETV2 expression and TGFß inhibition with constitutive ERG1/FLI1 coexpression reprogram mature ACs into durable rAC-VECs with clinical-scale expansion potential. Banking of HLA-typed rAC-VECs establishes a vascular inventory for treatment of diverse disorders.

Endothelial-derived angiocrine signals induce and sustain regenerative lung alveolarization.

To identify pathways involved in adult lung regeneration, we employ a unilateral pneumonectomy (PNX) model that promotes regenerative alveolarization in the remaining intact lung. We show that PNX stimulates pulmonary capillary endothelial cells (PCECs) to produce angiocrine growth factors that induce proliferation of epithelial progenitor cells supporting alveologenesis. Endothelial cells trigger expansion of cocultured epithelial cells, forming three-dimensional angiospheres reminiscent of alveolar-capillary sacs. After PNX, endothelial-specific inducible genetic ablation of Vegfr2 and Fgfr1 in mice inhibits production of MMP14, impairing alveolarization. MMP14 promotes expansion of epithelial progenitor cells by unmasking cryptic EGF-like ectodomains that activate the EGF receptor (EGFR). Consistent with this, neutralization of MMP14 impairs EGFR-mediated alveolar regeneration, whereas administration of EGF or intravascular transplantation of MMP14(+) PCECs into pneumonectomized Vegfr2/Fgfr1-deficient mice restores alveologenesis and lung inspiratory volume and compliance function. VEGFR2 and FGFR1 activation in PCECs therefore increases MMP14-dependent bioavailability of EGFR ligands to initiate and sustain alveologenesis.

Stability of influenza A virus in droplets and aerosols is heightened by the presence of commensal respiratory bacteria.

Aerosol transmission remains a major challenge for control of respiratory viruses, particularly those causing recurrent epidemics, like influenza A virus (IAV). These viruses are rarely expelled alone, but instead are embedded in a consortium of microorganisms that populate the respiratory tract. The impact of microbial communities and inter-pathogen interactions upon stability of transmitted viruses is well-characterized for enteric pathogens, but is under-studied in the respiratory niche. Here, we assessed whether the presence of five different species of commensal respiratory bacteria could influence the persistence of IAV within phosphate-buffered saline and artificial saliva droplets deposited on surfaces at typical indoor air humidity, and within airborne aerosol particles. In droplets, presence of individual species or a mixed bacterial community resulted in 10- to 100-fold more infectious IAV remaining after 1 h, due to bacterial-mediated flattening of drying droplets and early efflorescence. Even when no efflorescence occurred at high humidity or the bacteria-induced changes in droplet morphology were abolished by aerosolization instead of deposition on a well plate, the bacteria remained protective. Staphylococcus aureus and Streptococcus pneumoniae were the most stabilizing compared to other commensals at equivalent density, indicating the composition of an individual's respiratory microbiota is a previously unconsidered factor influencing expelled virus persistence.IMPORTANCEIt is known that respiratory infections such as coronavirus disease 2019 and influenza are transmitted by release of virus-containing aerosols and larger droplets by an infected host. The survival time of viruses expelled into the environment can vary depending on temperature, room air humidity, UV exposure, air composition, and suspending fluid. However, few studies consider the fact that respiratory viruses are not alone in the respiratory tract-we are constantly colonized by a plethora of bacteria in our noses, mouth, and lower respiratory system. In the gut, enteric viruses are known to be stabilized against inactivation and environmental decay by gut bacteria. Despite the presence of a similarly complex bacterial microbiota in the respiratory tract, few studies have investigated whether viral stabilization could occur in this niche. Here, we address this question by investigating influenza A virus stabilization by a range of commensal bacteria in systems representing respiratory aerosols and droplets.

Coalescence of Porous Coordination Cages into Crystalline and Amorphous Bulk Solids.

Discrete porous coordination cages are attractive as a solution processable material whose porosity is not predicated on a network structure. Here, we leverage the peripheral functionalization of these cage structures to obtain 12 novel, solution processable, porous coordination cages that afford crystalline and amorphous single-phase millimeter-scale monolithic bulk structures (six of each) upon solidification. These structures are based upon prototypal metal-organic polyhedra [Cu24(5-x-isophthalate)24] (where x = NH2, OH), wherein meta-substitution of linker ligands with acyl chloride or isocyanate moieties afforded amide and urethane functional groups, respectively. These porous cage structures were obtainable via direct synthesis between a metal salt and a ligand as well as postsynthetic modification of the cage and formed monoliths following centrifugation and drying of the product. We rationalize their self-assembly as colloidal packing of nanoscale cuboctahedral cages through weak interactions between their hydrophobic alkyl/aromatic surfaces. In general, amorphous solids were obtained via rapid precipitation from the mother liquor upon methanol addition, while crystalline solids could be obtained only following further chloroform and pyridine additions. The structure of the materials is confirmed via gas sorption and spectroscopic methods, while powder X-ray diffraction and transmission electron microscopy are used to determine the nature of these bulk solids.

Selective Synthesis of Defect-Rich LaMnO3 by Low-Temperature Anion Cometathesis.

The synthesis of complex oxides at low temperatures brings forward aspects of chemistry not typically considered. This study focuses on perovskite LaMnO3, which is of interest for its correlated electronic behavior tied to the oxidation state and thus the spin configuration of manganese. Traditional equilibrium synthesis of these materials typically requires synthesis reaction temperatures in excess of 1000 °C, followed by subsequent annealing steps at lower temperatures and different p(O2) conditions to manipulate the oxygen content postsynthesis (e.g., LaMnO3+x). Double-ion exchange (metathesis) reactions have recently been shown to react at much lower temperatures (500-800 °C), highlighting a fundamental knowledge gap for how solids react at lower temperatures. Here, we revisit the metathesis reaction, LiMnO2 + LaOX, where X is a halide or mixture of halides, using in situ synchrotron X-ray diffraction. These experiments reveal low reaction onset temperatures (ca. 450-480 °C). The lowest reaction temperatures are achieved by a mixture of lanthanum oxyhalide precursors: 2 LiMnO2 + LaOCl + LaOBr. In all cases, the resulting products are the expected alkali halide salt and defective La1-ϵMn1-ϵO3, where ϵ = x/(3 + x). We observe a systematic variation in defect concentration, consistent with a rapid stoichiometric local equilibration of the precursors and the subsequent global thermodynamic equilibration with O2 (g), as revealed by computational thermodynamics. Together, these results reveal how the inclusion of additional elements (e.g., Li and a halide) leads to the local equilibrium, particularly at low reaction temperatures for solid-state chemistry.

CASTing the net wider: A case report of PLACK syndrome associated with dilated cardiomyopathy.

PLACK syndrome (OMIM 616295) is a rare genodermatosis associated with peeling skin, leukonychia, acral punctate keratosis, cheilitis, and knuckle pads and is caused by loss-of-function mutations in the CAST gene, which encodes calpastatin, a calcium-dependent protease. This case report highlights a case of PLACK syndrome presenting with the unique findings of striate hyperkeratosis on the palms as well as life-threatening cardiomyopathy. We review why CAST mutations might impact cardiac function and raise awareness of the potential association between PLACK syndrome and cardiac manifestations.

Densified HKUST-1 Monoliths as a Route to High Volumetric and Gravimetric Hydrogen Storage Capacity.

We are currently witnessing the dawn of hydrogen (H2) economy, where H2 will soon become a primary fuel for heating, transportation, and long-distance and long-term energy storage. Among diverse possibilities, H2 can be stored as a pressurized gas, a cryogenic liquid, or a solid fuel via adsorption onto porous materials. Metal-organic frameworks (MOFs) have emerged as adsorbent materials with the highest theoretical H2 storage densities on both a volumetric and gravimetric basis. However, a critical bottleneck for the use of H2 as a transportation fuel has been the lack of densification methods capable of shaping MOFs into practical formulations while maintaining their adsorptive performance. Here, we report a high-throughput screening and deep analysis of a database of MOFs to find optimal materials, followed by the synthesis, characterization, and performance evaluation of an optimal monolithic MOF (monoMOF) for H2 storage. After densification, this monoMOF stores 46 g L-1 H2 at 50 bar and 77 K and delivers 41 and 42 g L-1 H2 at operating pressures of 25 and 50 bar, respectively, when deployed in a combined temperature-pressure (25-50 bar/77 K → 5 bar/160 K) swing gas delivery system. This performance represents up to an 80% reduction in the operating pressure requirements for delivering H2 gas when compared with benchmark materials and an 83% reduction compared to compressed H2 gas. Our findings represent a substantial step forward in the application of high-density materials for volumetric H2 storage applications.

Hypomorphic alleles pose challenges in rare disease genomic variant interpretation.

Exon skipping associated with an ATP7B intronic variant in a patient with Wilson's disease. (A) Sashimi plot visualization of aligned RNA sequencing data from proband liver tissue at ATP7B exons 14-13-12. The red track shows traditional RNA-seq data; the blue track shows RNA-seq enriched with exon capture (cDNA-cap) which achieves higher depth of protein-coding transcripts. The histogram indicates overall sequencing depth while arcs tabulate the number of junction-spanning reads supporting exon pairs. (B) The domain structure (top) and exon structure (bottom) of ATP7B. Loss of exon 13 (dashed box) would remove a transmembrane domain and disrupt the first phosphorylation domain.

Ultra-low-power four-wave mixing wavelength conversion in high-Q chalcogenide microring resonators.

A compact Ge11.5As24Se64.5 chalcogenide microring resonator is fabricated with an intrinsic quality factor of 3.0×105 in the telecom band. By taking advantage of the strong nonlinearity and cavity enhancement, highly efficient wavelength conversion via four-wave mixing is demonstrated using a microring resonator. Conversion efficiency of -33.7dB is obtained by using an ultra-low pump power of 63.8 µW. This work shows that Ge11.5As24Se64.5 chalcogenide microring devices are promising for quantum photonics.

Active Reaction Control of Cu Redox State Based on Real-Time Feedback from In Situ Synchrotron Measurements.

We achieve a target material state by using a recursive algorithm to control the material reaction based on real-time feedback on the system chemistry from in situ X-ray absorption spectroscopy. Without human intervention, the algorithm controlled O2:H2 gas partial pressures to approach a target average Cu oxidation state of 1+ for γ-Al2O3-supported Cu. This approach represents a new paradigm in autonomation for materials discovery and synthesis optimization; instead of iterating the parameters following the conclusion of each of a series of reactions, the iteration cycle has been scaled down to time points during an individual reaction. Application of the proof-of-concept illustrated here, using a feedback loop to couple in situ material characterization and the reaction conditions via a decision-making algorithm, can be readily envisaged in optimizing and understanding a broad range of systems including catalysis.

Enhanced stimulated raman scattering of solvent due to anharmonic energy transfer from resonance raman solute molecules.

A new nonlinear optical process, named enhanced stimulated Raman scattering (ESRS), is reported for the first time from resonance Raman in ß-carotene-methanol solution. It is well known that absorption decreases the efficiency of the nonlinear optical and laser processes; however, we observed enhanced stimulated Raman peaks at the first and second Stokes from methanol solvent at 2834 cm-1 with the addition of ß-carotene solutes. This enhanced SRS effect in methanol is attributed to the resonance Raman (RR) process in ß-carotene, which creates a significant number of vibrations from RR and the excess vibrations are transferred to methanol from anharmonic vibrational interactions between the ß-carotene solutes and the methanol solvent, and consequently leads to the increased Raman gain.

Molecularly Mixed Composite Membranes: Challenges and Opportunities.

The fabrication of porous molecules, such as metal-organic polyhedra (MOPs), porous organic cages (POCs) and others, has given rise to the potential for creating "solid solutions" of molecular fillers and polymers. Such solid solutions circumvent longstanding interface issues associated with mixed matrix membranes (MMMs), and are referred to as molecularly mixed composite membranes (MMCMs) to distinguish them from traditional two-phase MMMs. Early investigations of MMCMs highlight the advantages of solid solutions over MMMs, including dispersion of the filler, anti-plasticization of the polymer network, and removal of deleterious interfacial issues. However, the exact microscopic structure as well as the transport modality in this new class of membrane are not well understood. Moreover, there are clear engineering challenges that need to be addressed for MMCMs to transition into the field. In this Minireview, the authors outline several scientific and technological challenges associated with the aforementioned questions and their suggestions to tackle them.

Defect-Accommodating Intermediates Yield Selective Low-Temperature Synthesis of YMnO3 Polymorphs.

In the synthesis of complex oxides, solid-state metathesis provides low-temperature reactions where product selectivity can be achieved through simple changes in precursor composition. The influence of precursor structure, however, is less understood in solid-state synthesis. Here we present the ternary metathesis reaction (LiMnO2 + YOCl → YMnO3 + LiCl) to target two yttrium manganese oxide products, hexagonal and orthorhombic YMnO3, when starting from three different LiMnO2 precursors. Using temperature-dependent synchrotron X-ray and neutron diffraction, we identify the relevant intermediates and temperature regimes of reactions along the pathway to YMnO3. Manganese-containing intermediates undergo a charge disproportionation into a reduced Mn(II,III) tetragonal spinel and oxidized Mn(III,IV) cubic spinel, which lead to hexagonal and orthorhombic YMnO3, respectively. Density functional theory calculations confirm that the presence of Mn(IV) caused by a small concentration of cation vacancies (∼2.2%) in YMnO3 stabilizes the orthorhombic polymorph over the hexagonal. Reactions over the course of 2 weeks yield o-YMnO3 as the majority product at temperatures below 600 °C, which supports an equilibration of cation defects over time. Controlling the composition and structure of these defect-accommodating intermediates provides new strategies for selective synthesis of complex oxides at low temperatures.

Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis.

Chemical or traumatic damage to the liver is frequently associated with aberrant healing (fibrosis) that overrides liver regeneration. The mechanism by which hepatic niche cells differentially modulate regeneration and fibrosis during liver repair remains to be defined. Hepatic vascular niche predominantly represented by liver sinusoidal endothelial cells deploys paracrine trophogens, known as angiocrine factors, to stimulate regeneration. Nevertheless, it is not known how pro-regenerative angiocrine signals from liver sinusoidal endothelial cells is subverted to promote fibrosis. Here, by combining an inducible endothelial-cell-specific mouse gene deletion strategy and complementary models of acute and chronic liver injury, we show that divergent angiocrine signals from liver sinusoidal endothelial cells stimulate regeneration after immediate injury and provoke fibrosis after chronic insult. The pro-fibrotic transition of vascular niche results from differential expression of stromal-derived factor-1 receptors, CXCR7 and CXCR4 (refs 18, 19, 20, 21), in liver sinusoidal endothelial cells. After acute injury, CXCR7 upregulation in liver sinusoidal endothelial cells acts with CXCR4 to induce transcription factor Id1, deploying pro-regenerative angiocrine factors and triggering regeneration. Inducible deletion of Cxcr7 in sinusoidal endothelial cells (Cxcr7(iΔEC/iΔEC)) from the adult mouse liver impaired liver regeneration by diminishing Id1-mediated production of angiocrine factors. By contrast, after chronic injury inflicted by iterative hepatotoxin (carbon tetrachloride) injection and bile duct ligation, constitutive FGFR1 signalling in liver sinusoidal endothelial cells counterbalanced CXCR7-dependent pro-regenerative response and augmented CXCR4 expression. This predominance of CXCR4 over CXCR7 expression shifted angiocrine response of liver sinusoidal endothelial cells, stimulating proliferation of desmin(+) hepatic stellate-like cells and enforcing a pro-fibrotic vascular niche. Endothelial-cell-specific ablation of either Fgfr1 (Fgfr1(iΔEC/iΔEC)) or Cxcr4 (Cxcr4(iΔEC/iΔEC)) in mice restored the pro-regenerative pathway and prevented FGFR1-mediated maladaptive subversion of angiocrine factors. Similarly, selective CXCR7 activation in liver sinusoidal endothelial cells abrogated fibrogenesis. Thus, we demonstrate that in response to liver injury, differential recruitment of pro-regenerative CXCR7-Id1 versus pro-fibrotic FGFR1-CXCR4 angiocrine pathways in vascular niche balances regeneration and fibrosis. These results provide a therapeutic roadmap to achieve hepatic regeneration without provoking fibrosis.

Localized quantum walks in quasi-periodic Fibonacci arrays of waveguides.

New quasi-periodic arrays of waveguides (AWs) constructed with Fibonacci sequences are proposed to realize localized quantum walks (LQWs). The proposed Fibonacci arrays of waveguides (FAWs) are simple and straightforward to make, but have a rich set of properties that are of potential use for applications in quantum communication. Our simulations show that, in contrast with randomly disordered AWs, LQWs in FAWs are highly controllable due to the deterministic disorder nature of quasi-periodic systems. Furthermore, unique LQWs with symmetrical probability distribution can be conveniently realized in the FAWs.

Coordination Network That Reversibly Switches between Two Nonporous Polymorphs and a High Surface Area Porous Phase.

We report a 2-fold interpenetrated primitive cubic (pcu) network X-pcu-5-Zn, [Zn2(DMTDC)2(dpe)] (H2DMTDC = 3,4-dimethylthieno[2,3- b]thiophene-2,5-dicarboxylic acid, dpe = 1,2-di(4-pyridyl)ethylene), that exhibits reversible switching between an as-synthesized "open" phase, X-pcu-5-Zn-α, and two nonporous or "closed" polymorphs, X-pcu-5-Zn-ß and X-pcu-5-Zn-γ. There are two unusual features of X-pcu-5-Zn. The first relates to its sorption properties, which reveal that the α form exhibits high CO2 uptake (ca. 255 cm3/g at 195 K) via reversible closed-to-open switching (type F-IV isotherm) of the type desirable for gas and vapor storage; there are only three other reports of porous materials that combine these two features. Second, we could only isolate the ß form by activation of the CO2 loaded α form and it persists through multiple CO2 adsorption/desorption cycles. We are unaware of a new polymorph having been isolated in such a manner. That the observed phase changes of X-pcu-5-Zn-α occur in single-crystal-to-single-crystal fashion enabled structural characterization of the three forms; γ is a coordination isomer of α and ß, both of which are based upon "paddlewheel" clusters.

Secure Quantum Key Distribution over 421 km of Optical Fiber.

We present a quantum key distribution system with a 2.5 GHz repetition rate using a three-state time-bin protocol combined with a one-decoy approach. Taking advantage of superconducting single-photon detectors optimized for quantum key distribution and ultralow-loss fiber, we can distribute secret keys at a maximum distance of 421 km and obtain secret key rates of 6.5 bps over 405 km.

Water Vapor Sorption in Hybrid Pillared Square Grid Materials.

We report water vapor sorption studies on four primitive cubic, pcu, pillared square grid materials: SIFSIX-1-Cu, SIFSIX-2-Cu-i, SIFSIX-3-Ni, and SIFSIX-14-Cu-i. SIFSIX-1-Cu, SIFSIX-3-Ni, and SIFSIX-14-Cu-i were observed to exhibit negative water vapor adsorption at ca. 40-50% relative humidity (RH). The negative adsorption is attributed to a water-induced phase transformation from a porous pcu topology to nonporous sql and sql-c* topologies. Whereas the phase transformation of SIFSIX-1-Cu was found to be irreversible, SIFSIX-3-Ni could be regenerated by heating and can therefore be recycled. In contrast, SIFSIX-2-Cu-i, which is isostructural with SIFSIX-14-Cu-i, exhibited a type V isotherm and no phase change. SIFSIX-2-Cu-i was observed to retain both structure and gas sorption properties after prolonged exposure to heat and humidity. The hydrolytic stability of SIFSIX-2-Cu-i in comparison to its structural counterparts is attributed to structural features and therefore offers insight into the design of hydrolytically stable porous materials.

Age-dependent association between pulmonary tuberculosis and common TOX variants in the 8q12-13 linkage region.

Only a small fraction of individuals infected with Mycobacterium tuberculosis develop clinical tuberculosis (TB) in their lifetime. Genetic epidemiological evidence suggests a genetic determinism of pulmonary TB (PTB), but the molecular basis of genetic predisposition to PTB remains largely unknown. We used a positional-cloning approach to carry out ultrafine linkage-disequilibrium mapping of a previously identified susceptibility locus in chromosomal region 8q12-13 by genotyping 3,216 SNPs in a family-based Moroccan sample including 286 offspring with PTB. We observed 44 PTB-associated SNPs (p < 0.01), which were genotyped in an independent set of 317 cases and 650 controls from Morocco. A single signal, consisting of two correlated SNPs close to TOX, rs1568952 and rs2726600 (combined p = 1.1 × 10(-5) and 9.2 × 10(-5), respectively), was replicated. Stronger evidence of association was found in individuals who developed PTB before the age of 25 years (combined p for rs1568952 = 4.4 × 10(-8); odds ratio of PTB for AA versus AG/GG = 3.09 [1.99-4.78]). The association with rs2726600 (p = 0.04) was subsequently replicated in PTB-affected subjects under 25 years in a study of 243 nuclear families from Madagascar. Stronger evidence of replication in Madagascar was obtained for additional SNPs in strong linkage disequilibrium with the two initial SNPs (p = 0.003 for rs2726597), further confirming the signal. We thus identified around rs1568952 and rs2726600 a cluster of SNPs strongly associated with early-onset PTB in Morocco and Madagascar. SNP rs2726600 is located in a transcription-factor binding site in the 3' region of TOX, and further functional explorations will focus on CD4 T lymphocytes.

Using state tomography for characterizing input principal modes in optically scattering medium.

We propose two new methods to measure principal modes, or Eisenbud-Wigner-Smith eigenstates in optically scattering medium. Both methods use similar techniques as in quantum state tomography, and are based on direct measurement of temporal delays. The first method requires N2 different input launching conditions, and only the mean signal delay of these input states are needed to obtain full information of the principal modes. When the mode delay differences are large and all modes are non-degenerate, a second method can be used, which only requires 3N - 2 input launching conditions.