Synthesis and solution properties of a temperature-responsive PNIPAM–b-PDMS–b-PNIPAM triblock copolymer

In this paper, we report the synthesis and self-assembly of a novel thermoresponsive PNIPAM60–b-PDMS70–b-PNIPAM60 triblock copolymer in aqueous solution. The copolymer used a commercially available precursor modified with an atom transfer radical polymerization (ATRP) initiator to produce an ABA triblock copolymer via ATRP. Small-angle neutron scattering (SANS) was used to shed light on the structures of nanoparticles formed in aqueous solutions of this copolymer at two temperatures, 25 and 40 °C. The poly(dimethylsiloxane) block is very hydrophobic and poly(N-isopropylacrylamide) (PNIPAM) is thermoresponsive. SANS data at 25 °C indicates that the solutions of PNIPAM–b-PDMS–b-PNIPAM copolymers form well-defined aggregates with presumably core–shell structures below cloud point temperature. The scattering curves originating from nanoparticles formed at 40 °C in 100% D2O or 100% H2O were successfully fitted with the Beaucage model describing aggregates with hierarchical structure

Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR

Erratum in : Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR. [Cell. 2019]International audienceInnate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-likereceptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatorysignals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect theimmune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DC)are exacerbated by a high fatty acid (FA) metabolic environment. FA suppress the TLR-inducedhexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changesenhance mitochondrial reactive oxygen species (mtROS) production and, in turn, the unfolded proteinresponse (UPR) leading to a distinct transcriptomic signature, with IL-23 as hallmark. Interestingly,chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response.Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innateimmunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR

Thermal and Optical Characterization of Undoped and Neodymium-Doped Y3ScAl4O12 Ceramics

Y3–3xNd3xSc1Al4O12 (x = 0, 0.01, and 0.02) ceramics were fabricated by sintering at high temperature under vacuum. Unit cell parameter refinement and chemical analysis have been performed. The morphological characterization shows micrograins with no visible defects. The thermal analysis of these ceramics is presented, by measuring the specific heat in the temperature range from 300 to 500 K. Their values at room temperature are in the range 0.81–0.90 J g1–K–1. The thermal conductivity has been determined by two methods: by the experimental measurement of the thermal diffusivity by the photopyroelectric method, and by spectroscopy, evaluating the thermal load. The thermal conductivities are in the range 9.7–6.5 W K–1 m–1 in the temperature interval from 300 to 500 K. The thermooptic coefficients were measured at 632 nm by the dark mode method using a prism coupler, and the obtained values are in the range 12.8–13.3 × 10–6 K–1. The nonlinear refractive index values at 795 nm have been evaluated to calibrate the nonlinear optical response of these materials.This work is supported by the Spanish Government under projects MAT2011-29255-C02-01-02, MAT2013-47395-C4-4-R, and the Catalan Government under project 2014SGR1358. It was also funded by the European Commission under the Seventh Framework Programme, project Cleanspace, FP7-SPACE-2010-1-GA No. 263044

Molecular Tools for Monitoring the Ecological Sustainability of a Stone Bio-Consolidation Treatment at the Royal Chapel, Granada

Background: Biomineralization processes have recently been applied in situ to protect and consolidate decayed ornamental stone of the Royal Chapel in Granada (Spain). While this promising method has demonstrated its efficacy regarding strengthening of the stone, little is known about its ecological sustainability.Methodology/Principal Findings: Here, we report molecular monitoring of the stone-autochthonous microbiota before and at 5, 12 and 30 months after the bio-consolidation treatment (medium/long-term monitoring), employing the well-known molecular strategy of DGGE analyses. Before the bio-consolidation treatment, the bacterial diversity showed the exclusive dominance of Actinobacteria (100%), which decreased in the community (44.2%) after 5 months, and Gamma-proteobacteria (30.24%) and Chloroflexi (25.56%) appeared. After 12 months, Gamma-proteobacteria vanished from the community and Cyanobacteria (22.1%) appeared and remained dominant after thirty months, when the microbiota consisted of Actinobacteria (42.2%) and Cyanobacteria (57.8%) only. Fungal diversity showed that the Ascomycota phylum was dominant before treatment (100%), while, after five months, Basidiomycota (6.38%) appeared on the stone, and vanished again after twelve months. Thirty months after the treatment, the fungal population started to stabilize and Ascomycota dominated on the stone (83.33%) once again. Members of green algae (Chlorophyta, Viridiplantae) appeared on the stone at 5, 12 and 30 months after the treatment and accounted for 4.25%, 84.77% and 16.77%, respectively.Conclusions: The results clearly show that, although a temporary shift in the bacterial and fungal diversity was observed during the first five months, most probably promoted by the application of the bio-consolidation treatment, the microbiota tends to regain its initial stability in a few months. Thus, the treatment does not seem to have any negative side effects on the stone-autochthonous microbiota over that time. The molecular strategy employed here is suggested as an efficient monitoring tool to assess the impact on the stone-autochthonous microbiota of the application of biomineralization processes as a restoration/conservation procedure.This work was supported by the European Regional Development Fund (ERDF), Junta de Andalucía (Spain) and the “Fortalecimiento de la I+D+i” program from the University of Granada, co-financed by grant RNM-3493 and Research Group BIO-103 from Junta de Andalucía, as well as by the Spanish Government through “José Castillejo” program from the “Ministerio de Educación, Cultura y Deporte” (I+D+i 2008-2011), and by the Austrian Science Fund (FWF) under Grant “Elise-Richter V194-B20”

МУКОРМИКОЗ У ДЕТЕЙ С ГЕМАТОЛОГИЧЕСКИМИ И ОНКОЛОГИЧЕСКИМИ ЗАБОЛЕВАНИЯМИ В САНКТ-ПЕТЕРБУРГЕ

In prospective multicenter study were included 20 pediatriconcohematologic patients with mucormycosis. Age: 3 – 17 yy (median – 11), females – 60%. The diagnosiswas made according to EORTC/MSG 2008 criteria (post mortem – 25%). The main underlying disease was acutel eukemia (70%), risk factors – prolong severe neutropenia (median – 31 d) and lymphocytopenia (median – 33 d) after cytostatic chemotherapy or hematopoietic stem cells transplantation. Etiology agents were Lichtheimia corуmbifera, Rhizopus spp. and Rhizomucor spp. Main sites of infection were lungs (65%) and paranasal synuses (30%), dissemination – 45%. Antifungal therapy (amphotericin B lipid coplex, posaconazole, caspofungin, amphotericin B) was used in 75% patients, surgery – 30%. Overall mortality in 12 weeks was 70%.В проспективное многоцентровое исследование включили 20 детей с гематологическими и онкологическими заболеваниями, осложнившимися мукормикозом. Возраст – от 3 до 17 лет (медиана – 11 лет), девочки – 60%. Диагноз мукормикоза был установлен согласно критериям EORTC/MSG, 2008 (post mortem – 25%). Установлено, что мукормикоз развивается преимущественно у больных острым лейкозом (70%), на фоне длительного агранулоцитоза (медиана – 31 день) и лимфоцитопении (медиана – 33 дня) после интенсивной цитостатической и/или иммуносупрессивной терапии, а также трансплантации гемопоэтических стволовых клеток. Возбудители: Lichtheimia corуmbifera, Rhizopus spp. и Rhizomucor spp. Заболевание начинается с поражения легких (65%) и придаточных пазух носа (30%), диссеминацию выявили у 45% пациентов. Антимикотическую терапию (липидный комплекс амфотерицина В, позаконазол, каспофунгин, амфотерицин В) проводили 75% больных, хирургическое лечение – 30%. Общая летальность в течение 12 недель составила 70%

СОСТОЯНИЕ ИММУННОГО СТАТУСА У ГЕМАТОЛОГИЧЕСКИХ ПАЦИЕНТОВ С ИНВАЗИВНЫМ АСПЕРГИЛЛЕЗОМ

Invasive aspergillosis – is severe mycotic infection that often occurs in hematological patients and is characterized by high mortality. We examined the immunological parameters of hematological patients with invasive aspergillosis developed after cytostatic chemotherapy. Was founded, disruption of all parts of the immune respons: reduction in the absolute number of T-helper cells (CD4 +), natural killer cells (CD16 +), lowering of IFN-γ and IL-10 production, reduction in the number of B-lymphocytes and immunoglobulin levels of all classes, suppression killer ability of neutrophils are features of immune status in hematological patients with invasive aspergillosis receiving cytostatic chemotherapy.Инвазивный аспергиллез – тяжелая микотическая инфекция, которая наиболее часто возникает у гематологических больных и характеризуется высокой летальностью. Мы впервые изучили иммунологические показатели гематологических больных, у которых инвазивный аспергиллез развился после цитостатической полихимиотерапии. Установлено, что особенностью иммунного статуса у гематологических пациентов с инвазивным аспергиллезом, получающих цитостатическую полихимиотерапию, является нарушение всех звеньев иммунного ответа: снижение абсолютного числа Т-хелперов (CD4+), естественных киллеров (CD16+), продукцисов, угнетение киллерной способности нейтрофилов

Инвазивный аспергиллез, обусловленный Aspergillus non-fumigatus, у взрослых пациентов после аллогенной трансплантации гемопоэтических стволовых клеток

   Objective. To study the features of invasive aspergillosis (IA) due to A. non-fumigatus versus A. fumigatus in adult (≥ 18 years) recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 2016-2021.   Materials and methods. The study included 33 patients with IA caused by A. non-fumigatus (n = 20) and A. fumigatus (n = 13). A comparative analysis of cases of IA, the results of therapy and outcomes in patients after allo-HSCT in the RM Gorbacheva Research Institute was performed. Diagnostic criteria EORTC / MSGERC 2020 were used.   Results. Invasive aspergillosis caused by A. non-fumigatus made up the majority (60.6 %) of IA cases with an identified pathogen registered in patients after allo-HSCT in the period from 2016 to 2021. The main etiological agents in the A. non-fumigatus group were A. niger in 13 (65 %) patients, A. flavus – in 4 (20 %). The median day of diagnosis of A. non-fumigatus IAwas + 110 days (17–2093), for A. fumigatus it was + 46 days (2–866) (p = 0.171). Overall 12-week survival was 55 % and 59.2 % in the A. non-fumigatus and A. fumigatus groups, respectively (p = 0.617). The majority of patients in both the A. fumigatus (n = 10, 77 %) and A. non-fumigatus (n = 16, 80 %) groups received voriconazole as initial antifungal therapy. Second-linetherapy was required in 2 (10 %) patients with A. non-fumigatus IA: liposomal amphotericin B and echinocandins with or with-out posaconazole, and 2 (15 %) patients in the A. fumigatus group: liposomal amphotericin B and voriconazole in combination with echinocandins. A comparative analysis showed that in patients from the two groups, none of the assessed signs (gender, age, underlying disease, disease status at the time of transplantation, time from diagnosis to allo-HSCT, source of hematopoietic stem cells, conditioning regimen, donor type, antifungal prophylaxis, cytomegalovirus reactivation, severe acute and chronic graft-versus-host disease) did not differ significantly.   Conclusions. A. niger is the main causative agent of IA caused by A. non-fumigatus. Patients characteristics, their treatment and outcomes did not differ significantly between the A. non-fumigatus and A. fumigatus groups.   Цель: изучить особенности инвазивного аспергиллеза, обусловленного A. не-fumigatus в сравнении с A. fumigatus, у взрослых (≥ 18 лет) реципиентов аллогенной трансплантации гемопоэтических стволовыхклеток в 2016–2021 гг.   Материалы и методы. В исследование включили 33 пациента с инвазивным аспергиллезом, обусловленным A. не-fumigatus (n=20) и A. fumigatus (n=13), после аллогенной трасплантации гемопоэтических клеток, выполненной в клинике Научно-исследовательского института детской онкологии, гематологии и трансплантологии им. Р. М. Горбачевой. Использовали диагностические критерии EORTC / MSGERC, 2020.   Результаты. Обусловленный A. не-fumigatus инвазивный аспергиллез составил большую часть (60,6 %) случаев инвазивного аспергиллеза с идентифицированным возбудителем у пациентов после алло-трансплантации гемопоэтических стволовых клеток в 2016–2021 гг. В группе A. не-fumigatus основными возбудителями были A. niger (13, 65 %) и A. flavus (4, 20 %). Сравнительный анализ показал, что в группах сравнения ни один из оцениваемых признаков (пол, возраст, диагноз, статус заболевания на момент трансплантации, время от постановки диагноза до аллотрансплантации гемопоэтических стволовых клеток, источник гемопоэтических стволовых клеток, режим кондиционирования, тип донора, противогрибковая профилактика, реактивация цитомегаловируса, тяжелая острая и хроническая реакция трансплантат против хозяина) достоверно не различались. Медиана срока постановки диагноза A. не-fumigatus инвазивного аспергиллеза составила 110 дней (17 – 2093) после алло-трансплантации гемопоэтических стволовых клеток, A. fumigatus инвазивного аспергиллеза – 46 дней (2 – 866) (p = 0,171). Большинство пациентов с A. fumigatus инвазивным аспергиллезом (n = 10, 77 %) и A. не-fumigatus инвазивным аспергиллезом (n = 16, 80 %) в качестве стартовой противогрибковой терапии получали вориконазол. Терапия второй линии потребовалась 2 (10 %) пациентам с A. не-fumigatus инвазивным аспергиллезом (липосомальный амфотерицин В, эхинокандины и позаконазол) и 2 (15 %) пациентам с А. fumigatus инвазивным аспергиллезом (липосомальный амфотерицин В, вориконазол в комбинации с эхинокандином). Общая выживаемость пациентов с A. неfumigatus инвазивным аспергиллезом в течение 12 недель составила 55 %, A. fumigatus инвазивным асппергиллезом – 59,2 % (p = 0,617).   Выводы. A. niger – основной возбудитель инвазивного аспергиллеза, обусловленного A. non-fumigatus. Характеристики пациентов, их лечение и исходы достоверно не различались между группами A. не-fumigatus и A. fumigatus