Tyrosinase Inhibitor Activity of Coumarin-Resveratrol Hybrids

In the present work we report on the contribution of the coumarin moiety to tyrosinase inhibition. Coumarin-resveratrol hybrids 1-8 have been resynthesized to investigate the structure-activity relationships and the IC50 values of these compounds were measured. The results showed that these compounds exhibited tyrosinase inhibitory activity. Compound 3-(3’,4’,5’-trihydroxyphenyl)-6,8-dihydroxycoumarin (8) is the most potent compound (0.27 mM), more so than umbelliferone (0.42 mM), used as reference compound. The kinetic studies revealed that compound 8 caused non-competitive tyrosinase inhibition

2,7-Bis(pyridin-3-ylethynyl)fluoren-9-one

2,7-bis(pyridin-3-ylethynyl)fluoren-9-one [(3-PyE)2FO] was synthesized in one step by the Sonogashira coupling reaction between 3-ethynylpyridine and 2,7-dibromofluoren-9-one. The title compound was fully characterized, and its crystal structure was determined through single-crystal XRD analysis

From mining wastes to mineral sources - investigating the REE-bearing occurrences in the Arburèse District (SW Sardinia)

In recent years, the search for possible sources of REE minerals in Europe involved numerous old mine areas with high volumes of mining wastes that may offer significant amounts of Critical Raw Materials (CRMs). In some cases, strong evidence of CRMs anomalous concentrations arises from environmental characterization of wastes, so that an interesting problem is that of finding their sources, i.e., the original CRMs - rich mineral phases in the residual ore. An excellent example is provided by the Arburèse district of SW Sardinia, for about 150 years a major Pb-Zn source in Italy, now an area under study for remediation of its severe environmental problems, including >10 Mt of waste deposits. The district exploited a large system (>10 km) of low-temperature polymetallic veins hosted in Lower Paleozoic siliciclastic rocks belonging to the Variscan Nappe zone, arranged in two main geometrical trends relative to the late Variscan Arbus pluton: “peripheral” and “intersecting”. Recent investigations in the Montevecchio mine area discovered high Zn (up to 2.65 wt.%) and Pb (1.23 wt.%) grades in stratified tailing materials belonging to the Sanna old processing plant. Remarkably, ICP-MS analyses on the same materials revealed total REE+ Y contents attaining about 600 ppm. XRD studies confirmed a tailing composition essentially made of gangue minerals (quartz, siderite and micas) with goethite, baryte and traces of Zn carbonates and Pb sulfates. Chondrite-normalized REE patterns are coherent with the hydrothermal character of the source: however, both the REE mineralogical host(s) in tailings and in the Montevecchio ore are still undetermined. In the search of REE-bearing phases in the ores, some relevant insights are provided by studies on the southern branch of the Arburèse system, where the veins of “peripheral” system are hosted in late Ordovician-Silurian sedimentary sequences. In this part of the district the polymetallic veins assume the character of five-elements (Ni-Co-As-Bi-Ag) veins, with a rich Ni-Co-Fe arsenide – quartz association (1) overprinted by a Zn-Pb-Cu sulfide – siderite – quartz association (2), very similar to that dominating in Montevecchio. Investigations in the Pira Inferida mine sector highlighted the presence of LREE fluorocarbonates (synchysite-Ce and bastnaesite-Ce) and phosphates (monazite) associated with rutile and apatite. LREE minerals have been detected by SEM-EDS as tiny crystals in the quartz-sericitic gangue of the Montevecchio-type (2) mineral association. The same minerals are found in millimetric aggregates in the oxide zone of the veins, sporadically reported by mineral collectors in other mine sites of the same system. Overall, these occurrences, similar to those found in other low-temperature vein systems of Sardinia (e.g., Silius vein system), appear reliable mineral REE sources for Montevecchio mine wastes; they may be therefore used as proxies for REE exploration and assessment in the district

Crystal structure of 4,4′-(disulfanediyl)dipyridinium chloride triiodide

4,4 '-(Disulfanediyl)dipyridinium chloride triiodide, C10H10N2S22+center dot Cl-center dot I-3(-), (1) was synthesized by reaction of 4,4 '-dipyridyldisulfide with ICl in a 1:1 molar ratio in dichloromethane solution. The structural characterization of 1 by SC-XRD analysis was supported by elemental analysis, FT-IR, and FT-Raman spectroscopic measurements

An unprecedented non-classical polyinterhalogen anion made of [I2Cl]− and I2 at the 2-(p-tolyl)selenopheno[2,3-b]pyridinium cation template

The reactivity between 2-(p-tolyl)selenopheno[2,3-b]pyridine (L) and ICl in MeCN is presented. Single crystal structure analysis revealed the formation of two distinct crystalline materials both featuring the protonated 2-(p-tolyl)selenopheno[2,3-b]pyridinium cation [HL]+. Colourless crystals were identified as the dihydrate salt [HL]Cl·2H2O (1), and dark-red crystals as compound {[HL]+[I2Cl]−}3·1/2I2 (2) that features the peculiar presence of the rare non-classical [I2Cl]− interhalide. Halogen Bonds (XBs) between the cocrystallized I2 molecule and [I2Cl]− anions led to the novel overall discrete [I10Cl4]4−H-shaped polyinterhalide formation, which is stabilized through hydrogen bonds (HBs) with the templating [HL]+ cations. The experimental observations are supported by extensive theoretical calculations at the DFT level that were employed to study the role played by non-covalent interactions in the formation of the presented unique polyinterhalide

Efficacy and Safety of Adalimumab in Conjunction With Surgery in Moderate to Severe Hidradenitis Suppurativa:The SHARPS Randomized Clinical Trial

IMPORTANCE: Surgery is a mainstay in the management of hidradenitis suppurativa (HS). Adalimumab is the first drug approved for HS. OBJECTIVE: To investigate the efficacy and safety of adalimumab in combination with wide-excision surgery followed by secondary intention healing. DESIGN, SETTING, AND PARTICIPANTS: The Safety and Efficacy of Adalimumab for Hidradenitis Suppurativa Peri-Surgically (SHARPS) trial was a phase 4, randomized, double-blind, placebo-controlled study of adalimumab in conjunction with surgery. Patients were enrolled in 45 sites across 20 countries from July 18, 2016, to February 2, 2019, with the last patient visit on October 16, 2019. Eligible patients (aged 18-65 years) had moderate to severe HS that required radical surgery in an axillary or inguinal region and had 2 other anatomical regions affected, with 1 or more regions at Hurley stage II or III. Analysis was conducted in November 2019. INTERVENTIONS: Patients were randomized 1:1 to receive continuous adalimumab, 40 mg, or placebo during presurgery (12 weeks), perioperative (2 weeks), and postoperative (10 weeks) periods. MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of patients achieving HS clinical response across all body regions at week 12. RESULTS: Overall, 103 patients were randomized to adalimumab and 103 to matching placebo. Among all patients, 51% (n = 106) were women, 94% (n = 193) were White, and the mean (SD) age was 37.6 (11.3) years. At week 12, significantly more patients receiving adalimumab (49 of 103 [48%]) vs placebo (35 of 103 [34%]; P = .049) achieved HS clinical response across all body regions (treatment difference, 14% [95% CI, 0%-27%]). Treatment-emergent adverse events were reported in 74 of 103 patients (72%) and 69 of 103 patients (67%) in the adalimumab and placebo groups, respectively. No increased risk of postoperative wound infection, complication, or hemorrhage was observed with adalimumab vs placebo. Two deaths occurred in the adalimumab group; neither was considered as having a reasonable possibility of relationship to study drug. CONCLUSIONS AND RELEVANCE: Adalimumab was efficacious in conjunction with wide-excision surgery followed by secondary intention healing, with no need to interrupt treatment prior to surgery. These data support further investigation of adalimumab as an adjuvant therapy to surgery in patients with moderate to severe HS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0280897

Impairment of platelet function in both mild and severe COVID-19 patients

Abnormalities of platelet function were reported in patients with severe COVID-19 (severe-C), but few data are available in patients with mild COVID-19 (mild-C) and after COVID-19 recovery. The aim of this study was to investigate platelet parameters in mild-C patients (n = 51), with no evidence of pneumonia, and severe-C patients (n = 49), during the acute phase and after recovery, compared to 43 healthy controls. Both mild-C and severe-C patients displayed increased circulating activated platelets, low d-granule content (ADP, serotonin), impaired platelet activation by collagen (light transmission aggregometry) and impaired platelet thrombus formation on collagen-coated surfaces under controlled flow conditions (300/s shear rate). The observed abnormalities were more marked in severe-C patients than in mild-C patients. Overall, 61% (30/49) of mild-C and 73% (33/45) of severe-C patients displayed at least one abnormal platelet parameter. In a subgroup of just 13 patients who showed no persisting signs/symptoms of COVID-19 and were re-evaluated at least 1 month after recovery, 11 of the 13 subjects exhibited normalization of platelet parameters. In conclusion, mild abnormalities of platelet parameters were present not only in severe-C but also, albeit to a lesser extent, in mild-C patients during the acute phase of COVID-19 and normalized in most tested patients after clinical recovery