Search

Single-layer molybdenum ditelluride (MoTe2) has attracted attention due to the smaller energy difference between the semiconducting (1H) and semimetallic (1T′) phases with respect to other two-dimensional transition metal dichalcogenides (TMDs). Understanding the phenomenon of polymorphism between these structural phases is of great fundamental and practical importance. In this paper, we report a 1H to 1T′ phase transition occurring during the chemical vapor deposition (CVD) synthesis of single-layer MoTe2 at 730 °C. The transformation originates at the heterocontact between monoclinic and hexagonal crystals and progresses to either yield a partial or complete 1H to 1T′ phase transition. Microscopic and spectroscopic analyses of the MoTe2 crystals reveal the presence of Te vacancies and mirror twin boundaries (MTB) domains in the hexagonal phase. The experimental observations and theoretical simulations indicate that the combination of heterocontact formation and Te vacancies are relevant triggering mechanisms in the observed transformation. By advancing in the understanding and controlling of the direct synthesis of lateral 1T′/1H heterostructures, this work contributes to the development of MoTe2-based electronic and optoelectronic devices with low contact resistance. [ABSTRACT FROM AUTHOR]

Unresolved inflammation, due to unfavorable imbalances between pro‐inflammatory and pro‐resolving mediators, leads to chronic inflammatory pathologies that are often sex‐biased and regulated by sex hormones, including inflammatory bowel disease. Lipid mediators (LM) produced from polyunsaturated fatty acids by various lipoxygenases (LOX) and cyclooxygenases govern all stages of inflammation, i.e., the initiation and progression by pro‐inflammatory eicosanoids and its resolution by specialized pro‐resolving mediators (SPM). Here, we reveal sex‐specific differences in murine experimental colitis with male preponderance, which was abolished by sex hormone deprivation using gonadectomy, and this correlated to the levels of inflammation‐relevant mediators in the colon. Oral dextran sodium sulfate administration caused more severe colon inflammation in male CD‐1 mice than in female counterparts during the acute phase. Colitis in males yielded higher colonic cytokine/chemokine levels but lower 12−/15‐LOX‐derived LM including SPM compared to female animals in the resolving phase. Sex hormone deprivation in male mice by orchidectomy ameliorated colitis and impaired pro‐inflammatory cytokine/chemokine levels but elevated 12−/15‐LOX products including SPM, thus abolishing the observed sex differences. Conversely, ovariectomy impaired the levels of those LM that dominated in females and that were increased in males after gonadectomy. Our findings suggest that male sex hormones promote the development of colitis connected to the biosynthesis of inflammatory cytokines, chemokines, and certain LM, especially pro‐resolving 12−/15‐LOX products that appear to be suppressed in the male colon due to androgens. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GC) are potent anti-inflammatory agents, broadly used to treat acute and chronic inflammatory diseases, e.g., critically ill COVID-19 patients or patients with chronic inflammatory bowel diseases. GC not only limit inflammation but also promote its resolution although the underlying mechanisms are obscure. Here, we reveal reciprocal regulation of 15-lipoxygenase (LOX) isoform expression in human monocyte/macrophage lineages by GC with respective consequences for the biosynthesis of specialized proresolving mediators (SPM) and their 15-LOX-derived monohydroxylated precursors (mono-15-OH). Dexamethasone robustly up-regulated pre-mRNA, mRNA, and protein levels of ALOX15B/15-LOX-2 in blood monocyte--derived macrophage (MDM) phenotypes, causing elevated SPM and mono-15-OH production in inflammatory cell types. In sharp contrast, dexamethasone blocked ALOX15/15-LOX-1 expression and impaired SPM formation in proresolving M2-MDM. These dexamethasone actions were mimicked by prednisolone and hydrocortisone but not by progesterone, and they were counteracted by the GC receptor (GR) antagonist RU486. Chromatin immunoprecipitation (ChIP) assays revealed robust GR recruitment to a putative enhancer region within intron 3 of the ALOX15B gene but not to the transcription start site. Knockdown of 15-LOX-2 in M1-MDM abolished GC-induced SPM formation and mono-15-OH production. Finally, ALOX15B/15-LOX-2 upregulation was evident in human monocytes from patients with GC-treated COVID-19 or patients with IBD. Our findings may explain the proresolving GC actions and offer opportunities for optimizing GC pharmacotherapy and proresolving mediator production. [ABSTRACT FROM AUTHOR]

Proinflammatory leukotrienes (LTs) are produced by 5-lipoxygenase (5-LO) aided by 5-LO-activating protein (FLAP). LT biosynthesis inhibitors are currently under clinical investigation as treatments for respiratory and cardiovascular diseases. Here, we have revealed a sex bias in the efficiency of clinically relevant LT biosynthesis inhibitors, showing that their effects are superior in females. We found that androgens cause these sex differences by impeding the LT-biosynthetic 5-LO/FLAP complex assembly. Lower doses of the FLAP inhibitor MK886 were required to reduce [LTB.sub.4] levels in exudates of female versus male mice and rats. Following platelet-activating factor-induced shock, MK886 increased survival exclusively in female mice, and this effect was abolished by testosterone administration. FLAP inhibitors and the novel-type 5-LO inhibitors licofelone and sulindac sulfide exhibited higher potencies in human blood from females, and bioactive 5-LO/FLAP complexes were formed in female, but not male, human and murine leukocytes. Supplementation of female blood or leukocytes with 5[alpha]-dihydrotestosterone abolished the observed sex differences. Our data suggest that females may benefit from anti-LT therapy to a greater extent than males, prompting consideration of sex issues in LT modifier development., Introduction Leukotrienes (LTs) are potent lipid mediators of inflammation and immunity, with established roles in asthma and allergic rhinitis, but also in atherosclerosis, cardiovascular disease, and cancer (1, 2). For [...]

Specialized pro‐resolving mediators (SPM), primarily produced in innate immune cells, exert crucial bioactions for resolving inflammation. Among various lipoxygenases (LOX), 15‐LOX‐1 is key for SPM biosynthesis, but cellular activation principles of 15‐LOX‐1 are unexplored. It was shown that 3‐O‐acetyl‐11‐keto‐β‐boswellic acid (AKBA) shifts 5‐LOX regiospecificity from 5‐ to 12‐lipoxygenation products. Here, it is demonstrated that AKBA additionally activates cellular 15‐LOX‐1 via an allosteric site accomplishing robust SPM formation in innate immune cells, particularly in M2 macrophages. Compared to ionophore, AKBA‐induced LOX activation is Ca2+‐ and phosphorylation‐independent, with modest induction of 5‐LOX products. AKBA docks into a groove between the catalytic and regulatory domains of 15‐LOX‐1 interacting with R98; replacement of R98 by alanine abolishes AKBA‐induced 15‐LOX product formation in HEK293 cells. In zymosan‐induced murine peritonitis, AKBA strikingly elevates SPM levels and promotes inflammation resolution. Together, targeted allosteric modulation of LOX activities governs SPM formation and offers new concepts for inflammation resolution pharmacotherapy. [ABSTRACT FROM AUTHOR]

The opto-electronic properties of semiconducting 2D materials can be flexibly manipulated by engineering the atomic-scale environment. This can be done by including 2D materials in tailored van der Waals (vdW) stacks, whose optical response is a function of the number and the type of adjacent 2D layers. This work reports a systematic investigation of the dielectric function of 2D semiconducting WS2 in various stacking configurations: monolayer, 3R/2H homobilayer, and WS2/MoS2 heterobilayer. Reliable, Kramers-Kronigconsistent dielectric functions are obtained for WS2 in each configuration by means of spectroscopic ellipsometry (SE) and related parametric optical modeling in a wide spectral range (1.55-3.10 eV). The results of SE are combined with photoluminescence and absorbance spectra to identify the spectral position of the main excitonic features in WS2, which manifest sizable redshifts depending on the stacking configuration. These results represent a consistent reference set for the dielectric function of WS2 in vdW stacking configurations of particular interest for the scientific and technological field, and can be fruitfully exploited for reliable predictions of the optical response of WS2-containing systems. [ABSTRACT FROM AUTHOR]