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Fibroblasts are important cells for the support of homeostatic tissue function. In inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease, fibroblasts take on different roles (a) as inflammatory cells themselves and (b) in recruiting leukocytes, driving angiogenesis, and enabling chronic inflammation in tissues. Recent advances in single-cell profiling techniques have transformed the ability to examine fibroblast states and populations in inflamed tissues, providing evidence of previously underappreciated heterogeneity and disease-associated fibroblast populations. These studies challenge the preconceived notion that fibroblasts are homogeneous and provide new insights into the role of fibroblasts in inflammatory pathology. In addition, new molecular insights into the mechanisms of fibroblast activation reveal powerful cell-intrinsic amplification loops that synergize with primary fibroblast stimuli to result in striking responses. In this Review, we focus on recent developments in our understanding of fibroblast heterogeneity and fibroblast pathology across tissues and diseases in rheumatoid arthritis and inflammatory bowel diseases. We highlight new approaches to, and applications of, single-cell profiling techniques and what they teach us about fibroblast biology. Finally, we address how these insights could lead to the development of novel therapeutic approaches to targeting fibroblasts in disease., Introduction Fibroblasts in health and disease Fibroblasts are mesenchymal cells that make up the stroma in organ tissues. This Review uses the term 'fibroblasts' to collectively describe non-epithelial, non-hematopoietic, and [...]

A theoretical study of the decomposition mechanism of gas-phase alpha-HMX is presented. Four distinct channels were studied using the B3LYP/cc-pVDZ level of theory. The rate constants of each elementary reaction were calculated using the transition-state theory.

A series of Zr-based metal–organic frameworks was prepared via the solvothermal route using sulfonic-rich linkers for the efficient capture of Pb2+ ions from aqueous medium. The factors affecting adsorption such as the solution pH, adsorbent dosage, contact time, adsorption isotherms, and mechanism were studied. Consequently, the maximum adsorption capacity of Pb2+ on the acidified VNU-23 was determined to be 617.3 mg g−1, which is much higher than that of previously reported adsorbents and MOF materials. Furthermore, the adsorption isotherms and kinetics of the Pb2+ ion are in good accordance with the Langmuir and pseudo-second-order kinetic model, suggesting that the uptake of Pb2+ is a chemisorption process. The reusability experiments demonstrated the facile recovery of the H+⊂VNU-23 material through immersion in an HNO3 solution (pH = 3), where its Pb2+ adsorption efficiency still remained at about 90% of the initial uptake over seven cycles. Remarkably, the adsorption mechanism was elucidated through a combined theoretical and experimental investigation. Accordingly, the Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, scanning electron microscopy connected to energy-dispersive X-ray mapping (SEM-EDX-mapping), and X-ray photoelectron spectroscopy (XPS) analysis of the Pb⊂VNU-23 sample and comparison with H+⊂VNU-23 confirmed that the electrostatic interaction occurs via the interaction between the SO3− moieties in the framework and the Pb2+ ion, leading to the formation of a Pb–O bond. In addition, the density functional theory (DFT) calculations showed the effective affinity of the MOF adsorbent toward the Pb2+ ion via the strong driving force mentioned in the experimental studies. Thus, these findings illustrate that H+⊂VNU-23 can be employed as a potential adsorbent to eliminate Pb2+ ions from wastewater. [ABSTRACT FROM AUTHOR]

Macrophages regulate protective immune responses to infectious microbes, but aberrant macrophage activation frequently drives pathological inflammation. To identify regulators of vigorous macrophage activation, we analyzed RNA-seq data from synovial macrophages and identified SLAMF7 as a receptor associated with a superactivated macrophage state in rheumatoid arthritis. We implicated IFN- as a key regulator of SLAMF7 expression and engaging SLAMF7 drove a strong wave of inflammatory cytokine expression. Induction of TNF- after SLAMF7 engagement amplified inflammation through an autocrine signaling loop. We observed SLAMF7-induced gene programs not only in macrophages from rheumatoid arthritis patients but also in gut macrophages from patients with active Crohn’s disease and in lung macrophages from patients with severe COVID-19. This suggests a central role for SLAMF7 in macrophage superactivation with broad implications in human disease pathology. [ABSTRACT FROM AUTHOR]

A new porphyrinic vanadium-based metal–organic framework (MOF), namely V-MOF-10 [V2(OH)2(H2TCPP)], constructed from {V(OH)O4}∞ chains and 4-tetracarboxyphenylporphyrin linkers, was synthesized by a solvothermal procedure. Structural analysis indicated that V-MOF-10 possesses orthorhombic symmetry featuring two types of pores (5.2 × 11.9 Å and 3.5 × 11.9 Å). Full characterization of V-MOF-10 was performed by powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and elemental analysis (EA). The N2 isotherm of V-MOF-10 at 77 K shows a reversible uptake and permanent porosity with a high BET (Langmuir) surface area of 1477 m2 g−1 (1553 m2 g−1). The optical band gap of V-MOF-10, measured by UV-vis diffuse reflectance spectroscopy, is calculated to be 1.71 eV, resulting in a shift of absorption wavelength to the visible light region. Furthermore, our density functional theory (DFT) calculations confirm an acceptable correspondence of the band gap value with the mentioned experimental investigation, similar to the incorporated experimental and theoretical observations in the previous literature. Remarkably, V-MOF-10 exhibits an excellent photocatalytic property of organic dyes with the degradation efficiency of 100% for methylene blue (MB) and 89% for methylene orange (MB) after 120 min under illumination by visible light. These results suggest that V-MOF-10 could be used as a promising candidate in further photocatalytic studies. [ABSTRACT FROM AUTHOR]

Fibroblasts are important cells for the support of homeostatic tissue function. In inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease, fibroblasts take on different roles (a) as inflammatory cells themselves and (b) in recruiting leukocytes, driving angiogenesis, and enabling chronic inflammation in tissues. Recent advances in single-cell profiling techniques have transformed the ability to examine fibroblast states and populations in inflamed tissues, providing evidence of previously underappreciated heterogeneity and disease-associated fibroblast populations. These studies challenge the preconceived notion that fibroblasts are homogeneous and provide new insights into the role of fibroblasts in inflammatory pathology. In addition, new molecular insights into the mechanisms of fibroblast activation reveal powerful cell-intrinsic amplification loops that synergize with primary fibroblast stimuli to result in striking responses. In this Review, we focus on recent developments in our understanding of fibroblast heterogeneity and fibroblast pathology across tissues and diseases in rheumatoid arthritis and inflammatory bowel diseases. We highlight new approaches to, and applications of, single-cell profiling techniques and what they teach us about fibroblast biology. Finally, we address how these insights could lead to the development of novel therapeutic approaches to targeting fibroblasts in disease. [ABSTRACT FROM AUTHOR]

The coupled reference interaction site model (RISM)/molecular dynamics (MD) solvation free-energy approach is used to study the hydration effect upon the tautomeric equilibria of 2-hydroxypyridine and 2-oxopyridine and of cytosine in water. The conclusion states that the coupled RISM/MD method requires a single MD simulation as compared to the computationally demanding free-energy simulation methods.

Fibroblasts regulate tissue homeostasis, coordinate inflammatory responses, and mediate tissue damage. In rheumatoid arthritis (RA), synovial fibroblasts maintain chronic inflammation which leads to joint destruction. Little is known about fibroblast heterogeneity or if aberrations in fibroblast subsets relate to pathology. Here, we show functional and transcriptional differences between fibroblast subsets from human synovial tissues using bulk transcriptomics of targeted subpopulations and single-cell transcriptomics. We identify seven fibroblast subsets with distinct surface protein phenotypes, and collapse them into three subsets by integrating transcriptomic data. One fibroblast subset, characterized by the expression of proteins podoplanin, THY1 membrane glycoprotein and cadherin-11, but lacking CD34, is threefold expanded in patients with RA relative to patients with osteoarthritis. These fibroblasts localize to the perivascular zone in inflamed synovium, secrete proinflammatory cytokines, are proliferative, and have an in vitro phenotype characteristic of invasive cells. Our strategy may be used as a template to identify pathogenic stromal cellular subsets in other complex diseases. [ABSTRACT FROM AUTHOR]