Sustainable and Regenerable Alkali Metal-Containing Carbons Derived from Seaweed for CO2 Post-Combustion Capture

Alkali-based CO2 sorbents were prepared from a novel material (i.e., Laminaria hyperborea). The use of this feedstock, naturally containing alkali metals, enabled a simple, green and low-cost route to be pursued. In particular, raw macroalgae was pyrolyzed at 800 °C. The resulting biochar was activated with either CO2 or KOH. KOH–activated carbon (AC) had the largest surface area and attained the highest CO2 uptake at 35 °C and 1 bar. In contrast, despite much lower porosity, the seaweed-derived char and its CO2-activated counterpart outweighed the CO2 sorption performance of KOH–AC and commercial carbon under simulated post-combustion conditions (53 °C and 0.15 bar). This was ascribed to the greater basicity of char and CO2–AC due to the presence of alkali metal-based functionalities (i.e., MgO) within their structure. These were responsible for a sorption of CO2 at lower partial pressure and higher temperature. In particular, the CO2–AC exhibited fast sorption kinetics, facile regeneration and good durability over 10 working cycles. Results presented in the current article will be of help for enhancing the design of sustainable alkali metal-containing CO2 captors

A low-cost way to reduce greenhouse effects

Oak wood precursor was used for preparing low-cost CO2 sorbents. Adsorption is proposed as a cheaper alternative to chemical absorption, which is uneconomical, thus reducing the cost associated with the capture step. The raw material has been carbonised either by pyrolysis or by a hydrothermal carbonisation (HTC). Resulting biochars were then activated using CO2 . Initial chars and their activated counterparts were characterised by SEM imaging and N2 sorption measurements at 77 K. A significant rise in the BET surface area, total pore volume and micropore volume (textural parameters) occurred for all of the pristine chars after the activation process. Fast CO2 sorption kinetics (saturation reached in 3 mins.) and CO2 uptakes of up to ca. 6 wt. % have been measured by thermogravimetric analysis (TGA) at 35 ºC and 1 atm. The activated carbons (ACs) thus synthesised showed competitive performances compared to a commercial AC standard. Although the sorbents’ performances decreased at higher temperatures, they were easily regenerated after the capture stage

Allopregnanolone preclinical acute pharmacokinetic and pharmacodynamic studies to predict tolerability and efficacy for Alzheimer's disease.

To develop allopregnanolone as a therapeutic for Alzheimer's disease, we investigated multiple formulations and routes of administration in translationally relevant animal models of both sexes. Subcutaneous, topical (transdermal and intranasal), intramuscular, and intravenous allopregnanolone were bolus-administered. Pharmacokinetic analyses of intravenous allopregnanolone in rabbit and mouse indicated that peak plasma and brain levels (3-fold brain/plasma ratios) at 5min were sufficient to activate neuroregenerative responses at sub-sedative doses. Slow-release subcutaneous suspension of allopregnanolone displayed 5-fold brain/plasma ratio at Cmax at 30min. At therapeutic doses by either subcutaneous or intravenous routes, allopregnanolone mouse plasma levels ranged between 34-51ng/ml by 30min, comparable to published endogenous human level in the third trimester of pregnancy. Exposure to subcutaneous, topical, intramuscular, and intravenous allopregnanolone, at safe and tolerable doses, increased hippocampal markers of neurogenesis including BrdU and PCNA in young 3xTgAD and aged wildtype mice. Intravenous allopregnanolone transiently and robustly phosphorylated CREB within 5min and increased levels of neuronal differentiation transcription factor NeuroD within 4h. Neurogenic efficacy was achieved with allopregnanolone brain exposure of 300-500hr*ng/g. Formulations were tested to determine the no observable adverse effect level (NOAEL) and maximally tolerated doses (MTD) in male and female rats by sedation behavior time course. Sex differences were apparent, males exhibited ≥40% more sedation time compared to females. Allopregnanolone formulated in sulfobutyl-ether-beta-cyclodextrin at optimized complexation ratio maximized allopregnanolone delivery and neurogenic efficacy. To establish the NOAEL and MTD for Allo-induced sedation using a once-per-week intravenous regenerative treatment regimen: In female rats the NOAEL was 0.5mg/kg and MTD 2mg/kg. The predicted MTD in human female is 0.37mg/kg. In male rats the NOAEL and MTD were less than those determined for female. Outcomes of these PK/PD studies predict a safe and efficacious dose range for initial clinical trials of allopregnanolone for Alzheimer's disease. These findings have translational relevance to multiple neurodegenerative conditions

The impact of psychological distress on weight regain in post-bariatric patients during the COVID-19 pandemic: A latent profile analysis

Objective: The COVID-19 pandemic has caused a global health crisis disrupting healthcare delivery for people with severe obesity who have undergone bariatric surgery. This study examined the role of psychological distress during the first Italian COVID-19 lockdown in predicting post-operative outcomes in post-bariatric patients reaching the end of the 12-18 months follow-up during the lockdown. By using a person-centered approach, groups of patients with different psychological distress profiles were identified. We hypothesized that compared to post-bariatric patients with low psychological distress, post-bariatric patients with high psychological distress will be more at risk of weight regain. Methods: A total of 67 patients (71.6% female, Mage = 45.9) participated in this observational retrospective cohort study. Patients' anthropometric data were gathered from medical records while the weight at the end of the lockdown through phone interviews. Psychological distress, operationalized with anxiety symptoms, depressive symptoms, and sleep disturbances, was assessed by an online self-report questionnaire. Results: Significant differences were highlighted in the high and low psychological distressed group in weight changes, F(1,58) = 5.2, p < 0.001, η2 = 0.3. Specifically, compared to post-bariatric patients in the low psychological distress group, those in the high psychological distressed group reported weight regained (95% CI = 1.0, 2.6). Conclusion: Results highlight the need to target post-bariatric patients with high psychological distress who are at risk for weight regain during the COVID-19 pandemic. Interventions mitigating psychological distress and obesogenic behaviors during future pandemics or in post-COVID times are needed in vulnerable post-bariatric patients reporting high psychological distress

Preclinical characterization of zuranolone (SAGE-217), a selective neuroactive steroid GABAA receptor positive allosteric modulator

Zuranolone (SAGE-217) is a novel, synthetic, clinical stage neuroactive steroid GABAA receptor positive allosteric modulator designed with the pharmacokinetic properties to support oral daily dosing. In vitro, zuranolone enhanced GABAA receptor current at nine unique human recombinant receptor subtypes, including representative receptors for both synaptic (γ subunit-containing) and extrasynaptic (δ subunit-containing) configurations. At a representative synaptic subunit configuration, α1β2γ2, zuranolone potentiated GABA currents synergistically with the benzodiazepine diazepam, consistent with the non-competitive activity and distinct binding sites of the two classes of compounds at synaptic receptors. In a brain slice preparation, zuranolone produced a sustained increase in GABA currents consistent with metabotropic trafficking of GABAA receptors to the cell surface. In vivo, zuranolone exhibited potent activity, indicating its ability to modulate GABAA receptors in the central nervous system after oral dosing by protecting against chemo-convulsant seizures in a mouse model and enhancing electroencephalogram β-frequency power in rats. Together, these data establish zuranolone as a potent and efficacious neuroactive steroid GABAA receptor positive allosteric modulator with drug-like properties and CNS exposure in preclinical models. Recent clinical data support the therapeutic promise of neuroactive steroid GABAA receptor positive modulators for treating mood disorders; brexanolone is the first therapeutic approved specifically for the treatment of postpartum depression. Zuranolone is currently under clinical investigation for the treatment of major depressive episodes in major depressive disorder, postpartum depression, and bipolar depression

Selective Small-Molecule Agonists of G Protein–Coupled Receptor 40 Promote Glucose-Dependent Insulin Secretion and Reduce Blood Glucose in Mice

OBJECTIVE— Acute activation of G protein–coupled receptor 40 (GPR40) by free fatty acids (FFAs) or synthetic GPR40 agonists enhances insulin secretion. However, it is still a matter of debate whether activation of GPR40 would be beneficial for the treatment of type 2 diabetes, since chronic exposure to FFAs impairs islet function. We sought to evaluate the specific role of GPR40 in islets and its potential as a therapeutic target using compounds that specifically activate GPR40

Pharmacological Properties and Biological Functions of the GPR17 Receptor, a Potential Target for Neuro-Regenerative Medicine

In 2006, cells heterologously expressing the "orphan" receptor GPR17 were shown to acquire responses to both uracil nucleotides and cysteinyl-leukotrienes, two families of signaling molecules accumulating in brain or heart as a result of hypoxic/traumatic injuries. In subsequent years, evidence of GPR17 key role in oligodendrogenesis and myelination has highlighted it as a "model receptor" for new therapies in demyelinating and neurodegenerative diseases. The apparently contrasting evidence in the literature about the role of GPR17 in promoting or inhibiting myelination can be due to its transient expression in the intermediate stages of differentiation, exerting a pro-differentiating function in early oligodendrocyte precursor cells (OPCs), and an inhibitory role in late stage maturing cells. Meanwhile, several papers extended the initial data on GPR17 pharmacology, highlighting a "promiscuous" behavior of this receptor; indeed, GPR17 is able to respond to other emergency signals like oxysterols or the pro-inflammatory cytokine SDF-1, underlying GPR17 ability to adapt its responses to changes of the surrounding extracellular milieu, including damage conditions. Here, we analyze the available literature on GPR17, in an attempt to summarize its emerging biological roles and pharmacological properties

Eco-friendly synthesis of selective CO2 sorbents for post-combustion capture: The key role of basicity

Selective CO2 sorbents were successfully synthesized through carbonisation and physical (CO2) activation of oak wood. ACs thus synthesized along with a commercial carbon (GAC) included for comparison purposes were tested for CO2 capture. Under pure CO2 and 35 °C, although having much lower surface areas (highest SBET = 627 m2/g), oak wood-derived carbons exhibited similar uptakes as those achieved by the commercial AC (SBET = 1231 m2/g). On the other hand, upon changing to post-combustion conditions (ca. 53 °C, 15 % CO2/85 % N2), oak wood-based sorbents exhibited as large as (OW250PA) or even greater (OW800PA) sorption capacity than the commercial AC. The higher selectivity shown by oak wood derivatives was associated with their substantial amount of Ca-based inorganic fraction (up to nearly 12 wt. % for OW800PA), evidently related to their outstanding basicity (up to 93 % for OW800PA). Conversely, commercial AC is characterized by a negligible inorganic content (less than 1 wt. %) and lower basicity (ca. 67 %). Accordingly, it was proved that under post-combustion conditions the contribution of a more favoured (basic) surface chemistry outweighs the texture effect. Basic functionalities ensured stronger interactions with the carbon dioxide molecule, therefore implying a more selective sorption at lower gas concentration. Moreover, sorbents selectivity toward CO2 was obtained exploiting the advantageous properties (basicity) of the raw precursor rather than applying expensive and environmentally unsustainable chemical treatments

Optimised PEI impregnation of activated carbons - Enhancement of CO2 capture under post-combustion conditions

An activated carbon was successfully modified through Polyethylenimine (PEI) impregnation. Virgin and PEI-impregnated samples were tested for CO2 capture under post-combustion conditions (53 °C, 15 % CO2/85 % N2) by using a thermogravimetric analyser (TGA). The influence of different factors (e.g. PEI loading, type of solvent and stirring time) onto the CO2 sorption capacity of the modified carbons was assessed. In particular, compared to the conventional procedure [1], a longer agitation of the mixture PEI solution/carbon entailed attaining higher uptakes, likely due to a better dispersion of the polymer onto the support’s pores. Moreover, using water as solvent rather than methanol allowed achieving better performances, with the additional advantage of carrying out a more eco-friendly route. Despite a moderate pore blockage exhibited by all the modified samples, after the chemical treatment the virgin carbon’s CO2 capacity increased more than three folds. This outstanding enhancement was attributed to the N-based functionalities incorporated onto pristine carbon’s surface after the PEI impregnation. These were detected by XPS analyses, which confirmed the effectiveness of the surface modification. This result is corroborated by the increased N content measured for PEI-modified samples by elemental analysis (CHNS). Basic groups ensured a higher selectivity of the sorbents toward carbon dioxide molecule. Furthermore, PEI-impregnated carbon showed larger uptakes and faster kinetics than those attained by Z13X included for comparison purposes. Overall, it was demonstrated that the improved PEI impregnation was an effective route to obtain selective CO2 sorbents starting from activated carbons. PEI-loaded sorbents are a promising alternative to liquid amines for post-combustion capture of CO2

Optimised PEI impregnation of activated carbons - Enhancement of CO2 capture under post-combustion conditions

A virgin activated carbon, denoted as AR, was successfully modified through Polyethylenimine (PEI) impregnation. Virgin and PEI-impregnated samples were tested for CO2 capture under post-combustion conditions (53 °C, 15 % CO2/85 % N2) by using a thermogravimetric analyser (TGA). The influence of the PEI/AR ratio, the stirring time of the mixture PEI/solvent/AR and the solvent type on the CO2 sorption capacity of the modified carbons was also assessed. Maximum uptakes were given by the following conditions: PEI addition up to 80 % of initial weight, stirring time of 8 h and methanol as solvent. In particular, longer agitation (which was never studied before according to the author’s knowledge) facilitated higher uptakes. This was likely due to a better dispersion of the polymer onto the support’s pores. N2 adsorption measurements revealed a reduction of surface areas and pore volumes due to the presence of the polymer inside the carbon’s pores. Nevertheless, all the modified samples exhibited larger uptakes than that of the virgin carbon, whose CO2 capacity was increased by up to four times. This outstanding enhancement was attributed to the N-based functionalities incorporated onto the pristine carbon’s surface after the PEI impregnation. These were detected by appropriate techniques, confirming the effectiveness of the surface modification. This result is corroborated by the increased N content measured for PEI-modified samples by elemental analysis (CHNS). The presence of N-containing groups ensured a higher selectivity of the sorbents toward carbon dioxide. Furthermore, the optimally PEI-impregnated carbon showed larger uptakes and faster kinetics than those attained by Zeolite-13X, included for comparison purposes. In addition to this, its CO2 sorption capacity under post-combustion conditions remained nearly unaltered over 10 Temperature Swing Adsorption (TSA) cycles. The durability shown by the optimally modified carbon was likely due to the thermal stability of the polymer. The cyclic test also showed that the sorbent was easily regenerated at 120 °C, thus potentially implying a low energy penalty for a fossil-fueled power plant. These findings indicate that optimised PEI impregnation is an effective route to enhance the post-combustion CO2 capture performance of activated carbon. Moreover, PEI impregnated carbon could represent a competitive alternative to the use of liquid amines in the conventional absorption process