Biocompatible Iron Sulphide Nanoparticles Against Neuroinflammation for Intracerebral Haemorrhage and Long-term Neurological Functional Recovery

BackgroundMass effects of haematoma, neuroinflammation, oxidative stress, and neuronal apoptosis are the major causes of poor prognosis of intracerebral haemorrhage (ICH). Our previous study suggests that biocompatible iron sulphide nanoparticles possess peroxidase-like activity and can release hydrogen polysulfanes, which may inhibit brain injury. The purpose of this study was to investigate the neuroprotective efficacy of diallyl disulfide (DADS)-nFeS in mice after ICH and preliminarily illustrate the potential mechanism. MethodsAdult male C57BL/6 mice (n = 176) were injected with bacterial collagenase in the striatum. In the first part, DADS-nFeS at different doses (25, 50, or 100 mg/kg) was intragastrically administered 2 h, 26 h, and 50 h before ICH. In the second and third parts, DADS-nFeS (50 mg/kg) was administered 2 h, 26 h, and 50 h before and after the induction of ICH in the pre-treatment group and post-treatment group, respectively. H&E staining was performed to detect drug toxicity. Haematoma volume measurement, Fluoro-Jade C (F-JC) staining, Nissl staining, immunofluorescence staining, western blotting, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining, malondialdehyde (MDA) and superoxide dismutase (SOD) assays, and neurobehavioural tests were performed. ResultsAll three doses of DADS-nFeS had neuroprotective effects, and 50 mg/kg resulted in the best outcome. DADS-nFeS reduced the haematoma volume and MDA content, inhibited the activation of microglia and astrocytes, progressive neuronal degeneration, and apoptosis, increased SOD activity and neuronal survival, and improved both short-term and long-term neurological functions in perihaematomal areas after ICH. Moreover, DADS-nFeS was associated with the downregulation of Iba-1, GFAP, TNF-α, IL-1β, 4-hydroxynonenal (4-HNE), and Bax/Bcl-2 levels in perihaematomal areas after ICH. Finally, post-treatment with DADS-nFeS had a better effect than pre-treatment with DADS-nFeS. ConclusionsOur study indicated that gavage administration of DADS-nFeS decreased the haematoma volume, suppressed neuroinflammation, oxidative stress, and neuronal apoptosis, and improved short- and long-term neurological functions, which was, at least in part, realized by inhibiting the activation of microglia and astrocytes, enhancing local SOD activity, and decreasing the recruitment of reactive oxygen species. Therefore, DADS-nFeS may serve as a potential therapeutic strategy via the diet against central nervous system diseases.

Lerf–Klinowski-type models of graphene oxide and reduced graphene oxide are robust in analyzing non-covalent functionalization with porphyrins

Graphene-based nanohybrids are good candidates for various applications. However, graphene exhibits some unwanted features such as low solubility in an aqueous solution or tendency to aggregate, limiting its potential applications. On the contrary, its derivatives, such as graphene oxide (GO) and reduced graphene oxide (RGO), have excellent properties and can be easily produced in large quantities. GO/RGO nanohybrids with porphyrins were shown to possess great potential in the field of photocatalytic hydrogen production, pollutant photodegradation, optical sensing, or drug delivery. Despite the rapid progress in experimental research on the porphyrin-graphene hybrids some fundamental questions about the structures and the interaction between components in these systems still remain open. In this work, we combine detailed experimental and theoretical studies to investigate the nature of the interaction between the GO/RGO and two metal-free porphyrins 5,10,15,20-tetrakis(4-aminophenyl) porphyrin (TAPP) and 5,10,15,20-tetrakis(4-hydroxyphenyl) porphyrin (TPPH)]. The two porphyrins form stable nanohybrids with GO/RGO support, although both porphyrins exhibited a slightly higher affinity to RGO. We validated finite, Lerf–Klinowski-type (Lerf et al. in J Phys Chem B 102:4477, 1998) structural models of GO ($$\hbox {C}_{59}\hbox {O}_{26}\hbox {H}_{26}$$ C 59 O 26 H 26 ) and RGO ($$\hbox {C}_{59}\hbox {O}_{17}\hbox {H}_{26}$$ C 59 O 17 H 26 ) and successfully used them in ab initio absorption spectra simulations to track back the origin of experimentally observed spectral features. We also investigated the nature of low-lying excited states with high-level wavefunction-based methods and shown that states’ density becomes denser upon nanohybrid formation. The studied nanohybrids are non-emissive, and our study suggests that this is due to excited states that gain significant charge-transfer character. The presented efficient simulation protocol may ease the properties screening of new GO/RGO-nanohybrids.

Crosses with spelt improve tolerance of South Asian spring wheat to spot blotch, terminal heat stress, and their combination

Spot blotch and terminal heat are two of the most important stresses for wheat in South Asia. A study was initiated to explore the use of spelt (Triticum spelta) to improve tolerance to these stresses in spring wheat (T. aestivum). We assessed 185 recombinant inbred lines (RILs) from the cross T. spelta (H + 26) × T. aestivum (cv. HUW234), under the individual stresses and their combination. H + 26 showed better tolerance to the single stresses and also their combination; grain yield in RILs was reduced by 21.9%, 27.7% and 39.0% under spot blotch, terminal heat and their combined effect, respectively. However, phenological and plant architectural traits were not affected by spot blotch itself. Multivariate analysis demonstrated a strong negative correlation between spikelet sterility and grain yield under spot blotch, terminal heat and their combination. However, four recombinant lines demonstrated high performance under both stresses and also under their combined stress. The four lines were significantly superior in grain yield and showed significantly lower AUDPC than the better parent. This study demonstrates the potential of spelt wheat in enhancing tolerance to spot blotch and terminal heat stresses. It also provides comprehensive evidence about the expression of yield and phenological traits under these stresses.

The crystal structure of (azido)-κ1 N-6,6′-((cyclohexane-1,2-diylbis(azanylylidene)) bis(methanylylidene))bis(3-bromophenolato- κ 4 N,N,O,O)-(methanol)-manganese(III)–methanol(1/1), C 22 H 26 Br 2 MnN 5 O 4

C22H26Br2MnN5O4, monoclinic, P21/n (no. 14), a = 8.0106(4) Å, b = 14.5925(7) Å, c = 21.0425(11) Å, β = 100.330(2)°, V = 2419.9(2) Å3, Z = 4, R gt (F) = 0.0372, wR ref (F 2) = 0.0766, T = 296.15 K.

Clinical characteristics, management and health related quality of life in young to middle age adults with COVID-19

Background The outbreak of COVID-19 has rapidly spread to Italy, including Pesaro-Urbino province. Data on young to middle age adults with COVID-19 are lacking. We report the characteristics, management and health-related quality of life (HRQoL) in patients with COVID-19 aging ≤50 years. Methods A retrospective analysis was performed in all patients ≤50 years with a confirmed diagnosis of COVID-19 admitted to Emergency department (ED) of San Salvatore Hospital in Pesaro from February 28th to April 8th, 2020. Data were collected from electronical medical records. HRQoL was investigated after 1 month from hospital discharge using the SF-36 questionnaire. Outcomes were evaluated between hospitalized and not hospitalized patients. Results Among 673 patients admitted to the ED and diagnosed with COVID-19, 104 (15%) were ≤ 50 years old: 74% were discharged at home within 48 h, 26% were hospitalized. Fever occurred in 90% of the cases followed by cough (56%) and dyspnoea (34%). The most frequent coexisting conditions were hypertension (11%), thyroid dysfunction (8%) and neurological and/or mental disorders [NMDs] (6%). Mean BMI was 27. Hypokalaemia and NMDs were significantly more common in patients who underwent mechanical ventilation. Regardless of hospitalization, there was an impairment in both the physical and mental functioning. Conclusions Overweight and hypertension are frequent conditions in young to middle age adults with COVID-19. Hypokalaemia and NMDs are commonly associated with progressive disease. A significant impact on HRQoL in the early stage of post-discharge is common in this population.

Crystal structure, Hirshfeld surface analysis and DFT study of 1-ethyl-3-phenyl-1,2-dihydroquinoxalin-2-one

In the title molecule, C16H14N2O, the dihydroquinoxaline moiety is not planar as there is a dihedral angle of 4.51 (5)° between the constituent rings. In the crystal, C—H...O hydrogen bonds form helical chains about the crystallographic 21 screw axis in the b-axis direction. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H...H (51.7%), H...C/C...H (26%) and H...O/O...H (8.5%) interactions. The optimized structure calculated using density functional theory (DFT) at the B3LYP/6–311 G(d,p) level is compared with the experimentally determined structure in the solid state. The calculated HOMO–LUMO energy gap is 3.8918 eV.

Changes in Snow Depth, Snow Cover Duration, and Potential Snowmaking Conditions in Austria, 1961–2020—A Model Based Approach

We used the spatially distributed and physically based snow cover model SNOWGRID-CL to derive daily grids of natural snow conditions and snowmaking potential at a spatial resolution of 1 × 1 km for Austria for the period 1961–2020 validated against homogenized long-term snow observations. Meteorological driving data consists of recently created gridded observation-based datasets of air temperature, precipitation, and evapotranspiration at the same resolution that takes into account the high variability of these variables in complex terrain. Calculated changes reveal a decrease in the mean seasonal (November–April) snow depth (HS), snow cover duration (SCD), and potential snowmaking hours (SP) of 0.15 m, 42 days, and 85 h (26%), respectively, on average over Austria over the period 1961/62–2019/20. Results indicate a clear altitude dependence of the relative reductions (−75% to −5% (HS) and −55% to 0% (SCD)). Detected changes are induced by major shifts of HS in the 1970s and late 1980s. Due to heterogeneous snowmaking infrastructures, the results are not suitable for direct interpretation towards snow reliability of individual Austrian skiing resorts but highly relevant for all activities strongly dependent on natural snow as well as for projections of future snow conditions and climate impact research.

Capacidad parasítica de Beauveria bassiana sobre el picudo del palmito (Metamasius hemipterus). (Coleoptera: Dryophthoridae).

Capacidad parasítica de Beauveria bassiana sobre el picudo del palmito (Metamasius hemipterus) (Coleoptera: Dryophthoridae). El objetivo fue identificar una cepa de B. bassiana, eficaz contra adultos de Metamasius hemipterus a fin de que sea utilizada en el manejo de la plaga. El estudio se realizó en los laboratorios del Instituto Nacional de Innovación y Transferencia en Tecnología Agropecuaria (INTA) y se concluyó en el año 2013. El ensayo se estableció con un diseño completamente al azar con siete tratamientos y 20 repeticiones. Se estudiaron seis cepas del hongo codificadas como INTA H-25, INTA H-26, INTA H-28, INTA H-29, INTA H-31 e INTA H-50. Los insectos adultos, fueron expuestos al hongo a una concentración de 1X108 conidias/ml, se observaron diariamente hasta una semana después de la muerte. Se realizó un ANDEVA y una prueba de separación de medias mediante la prueba Duncan con un 95% de confianza. Se encontraron diferencias altamente significativas entre los tiempos letales TL50 y TL90 (P<0,0001). La cepa INTA-H-25 eliminó el 90% de la población antes de los cinco días y las cepas INTA-H-26, INTA H-31 e INTA-H-50 eliminaron el 50 % de la población de picudos antes de los cinco días, superando al resto de tratamientos. En el parasitismo se observó, que la cepa INTA-H-50 fue la que produjo más micelio sobre el insecto y la cepa INTA-H-31 la mayor cantidad de conidias; siendo estas características importantes para la diseminación del hongo e infección del insecto. Los mejores tratamientos fueron INTA-H-25, INTA-H-26, INTA-H-31 e INTA-H-50.Palabras clave: Control biológico, pejibaye, hongo entomopatógeno.

185 Serum-dependent and serum-independent effects of prolactin and progesterone during the completion of invitro maturation on metaphase II chromosomes in bovine oocytes

The final stages of IVM are of great importance for the developmental competence of mammalian oocytes. The goal of the present work was to study effects of prolactin (PRL) and progesterone (PG) during the completion of IVM in serum-containing and serum-free media on destructive and apoptotic changes of MII chromosomes in bovine oocytes. Cumulus-oocyte complexes (COCs) were matured for 16h in TCM-199 containing 10% fetal calf serum (FCS), 10μgmL−1 porcine FSH, and 10μgmL−1 ovine LH at 38.5°C and 5% CO2. Thereafter, the COCs were transferred to and cultured for either 8 or 26h in the following systems: TCM-199 containing 10% FCS (Control-1) and TCM-199 containing 3mgmL−1 bovine serum albumin (BSA; Control-2). In both systems, the medium of experimental groups was supplemented with 50ngmL−1 bovine PRL or 50ngmL−1 PG. All treatments were repeated 4 to 5 times using 80 to 108 oocytes per group. The state of the oocyte nuclear material was evaluated by Tarkowski's method. Apoptosis in MII oocytes was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Arcsine-transformed data were analysed by ANOVA. At the end of culture, the rate of MII oocytes was similar in all the groups (83.4-93.9%). Following 8h of IVM, the frequency of MII chromosome abnormalities (decondensation, adherence, clumping) was reduced (P&lt;0.01) in the PRL-1 and PG-1 groups compared with Control-1 (Table 1). This effect was still observed in the PG-1 group (P&lt;0.001) but disappeared in the PRL-1 group after 26h of prolonged oocyte culture. In contrast, a decrease in the rate of MII oocytes with abnormal chromosomes occurred only in the PG-2 group by the end of 8h of culture (P&lt;0.01), whereas the decrease was revealed in both the PG-2 and PRL-2 groups after 26h of culture (P&lt;0.001). Furthermore, the rate of MII oocytes with apoptotic signs following 8h was lower in the PRL-1 and PG-1 groups than in Control-1 (P&lt;0.05). During the 26-hculture, this rate increased in all groups, being higher in Control-1 than in the PG-1 group (P&lt;0.05). The rate of apoptotic oocytes was 2.8 times (8h) and 1.8 times (26h) lower in Control-2 than in Control-1 (P&lt;0.01). Neither PRL nor PG affected oocyte apoptosis in system 2. Thus, during the completion of IVM, PRL can exert a short-term and serum-dependent inhibitory effect on destructive changes of MII chromosomes in bovine oocytes, whereas the similar effect of PG is long-term and serum-independent. Anti-apoptotic effects of both PRL and P4 on the oocytes are determined by serum. Table 1.Effects of prolactin (PRL) and progesterone (PG) on MII chromosomes in bovine oocytes Group % of MII oocytes With abnormal chromosomes With apoptotic signs 8 h 26 h 8 h 26 h Control-1 36.5±3.1a 68.0±2.2a 19.4±1.1a 65.5±2.9a PRL-1 23.6±3.2bc 68.3±2.6a 9.8±3.3b 51.2±7.8abc PG-1 23.4±2.4bc 49.4±0.6b 8.0±3.1b 53.6±0.7b Control-2 31.7±2.7ac 62.7±1.0a 6.9±1.3b 37.3±3.3cd PRL-2 32.6±2.5ac 45.9±0.9b 7.4±2.9b 28.1±2.1d PG-2 20.0±2.5b 47.2±1.6b 6.8±0.9b 29.9±3.9cd a-dValues within a column differ (at least P&lt;0.05). This study was supported by RFBR (No. 17-29-08035).

Effect of Diet on Bloom Time of Beef

ObjectivesThe objective of the study was to assess the evolution of the bloom color in beef aged for 8 d to establish the moment of measurement in which values of L*, a* and b* stabilize and are representative of the characteristic color of the meat from beef fed different diets.Materials and MethodsIn the current study, eight young Pirenaica bulls were used. The bulls were born and reared on a private commercial Protected Denomination Origin (PDO)-approved farm located in the region of Navarra (Northern Spain). After weaning at approximately 4 mo of age, the calves were administered the same diet until month 12. The bulls were separated in two groups and each of group was fed a different energy level diet (High energy, H: 2914.2 kcal/kg vs. Low energy, L: 2548.4kcal/kg) until slaughter at 18 mo of age. Diet was based on barley (H: 26% vs. L: 22%), corn (H: 50% vs. L: 45%) and soja (H: 17% and L: 17%). The research was conducted under the highest standards of humane care and use of animals in accordance with European guidelines (EU). Longissimus dorsi muscle was removed after 24 h. post-mortem from the left side of the carcasses, pH was measured, and the meat was transported to the Meat Science Laboratory at the Public University of Navarra (Pamplona, Spain) under refrigeration. Steaks were aged in vacuum for 8 d post-mortem, which is the typical period for this type of meat under the PDO Ternera de Navarra. After aging, L*, a*, and b*were recorded every 3 min (5 repetitions per sample) for 102 min with a Minolta CM 2002 Spectrophotocolorimeter. Data were analyzed using the Linear General Model procedure with the IBM SPSS Statistics 24, and significance was determined at P < 0.05.ResultsThe pH values were 5.56 (H) and 5.50 (L) (P < 0.05) thus, no DFD meat was observed. Color differed depending on diet (L*H: 28.88 vs. L*L: 34.26, P < 0.01; a*H: 26.33 vs. a*L: 18.11, P < 0.001; b*H: 11.58 vs. b*L: 7.94, P < 0.001) even if the initial pigment content was not statistically different (H: 5.34 mg/g vs. L: 4.74 g/g; P = 0.107). In fact, beef from the H diet showed higher a* and b* values, and lower L* values than beef from the L diet (P < 0.05). Nonetheless, the time of stabilization for a practical color measurement did not differ between diets.ConclusionIn conclusion, despite the effect of diet on the initial beef color differences, the results of the current study showed that 15 min of meat exposure to oxygen is the minimum in either cases prior to taking measurements of color on beef aged 8 d.