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BackgroundThe interleukin-22 cytokine (IL-22) has demonstrated efficacy in preclinical colitis models with non-immunosuppressive mechanism of action. Efmarodocokin alfa (UTTR1147A) is a fusion protein agonist that links IL-22 to the crystallisable fragment (Fc) of human IgG4 for improved pharmacokinetic characteristics, but with a mutation to minimise Fc effector functions.MethodsThis randomised, phase 1b study evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of repeat intravenous dosing of efmarodocokin alfa in healthy volunteers (HVs; n=32) and patients with ulcerative colitis (n=24) at 30–90 µg/kg doses given once every 2 weeks or monthly (every 4 weeks) for 12 weeks (6:2 active:placebo per cohort).ResultsThe most common adverse events (AEs) were on-target, reversible, dermatological effects (dry skin, erythema and pruritus). Dose-limiting non-serious dermatological AEs (severe dry skin, erythema, exfoliation and discomfort) were seen at 90 μg/kg once every 2 weeks (HVs, n=2; patients, n=1). Pharmacokinetics were generally dose-proportional across the dose levels, but patients demonstrated lower drug exposures relative to HVs at the same dose. IL-22 serum biomarkers and IL-22-responsive genes in colon biopsies were induced with active treatment, and microbiota composition changed consistent with a reversal in baseline dysbiosis. As a phase 1b study, efficacy endpoints were exploratory only. Clinical response was observed in 7/18 active-treated and 1/6 placebo-treated patients; clinical remission was observed in 5/18 active-treated and 0/6 placebo-treated patients.ConclusionEfmarodocokin alfa had an adequate safety and pharmacokinetic profile in HVs and patients. Biomarker data confirmed IL-22R pathway activation in the colonic epithelium. Results support further investigation of this non-immunosuppressive potential inflammatory bowel disease therapeutic.Trial registration number NCT02749630.

Chronic inflammation is an underlying feature of respiratory diseases such as chronic obstructive pulmonary disease (COPD). Novel therapies that target the inflammatory mechanisms driving acute exacerbations of COPD are required. The ST2 receptor, which binds the alarmin interleukin (IL)-33 to initiate an inflammatory response, is a potential target. Astegolimab, a fully human immunoglobulin G2 monoclonal antibody, which binds with high affinity to ST2 to prevent binding of IL-33, is a potential therapy for COPD. However, targeting inflammatory pathways that form part of the immune system may have unintended consequences, such as implications for the response to infection and cardiovascular function. Therefore, an understanding of astegolimab’s safety profile in clinical use is essential. This narrative review summarizes clinical safety data from published clinical trials of astegolimab with a focus on adverse events of interest, including infections and cardiac events. Astegolimab was shown to be well tolerated in > 580 patients with asthma, atopic dermatitis, COPD, and severe COVID-19 pneumonia who took part in Phase II trials. The frequency of adverse events (AEs) and serious AEs was similar between the astegolimab and placebo arms in each trial (AEs: 41–81% vs. 58–77%; serious AEs: 3–29% vs. 0–41%, respectively). The number of deaths was similar between treatment arms and there were no astegolimab-related deaths. Astegolimab did not increase the risk of infection or major adverse cardiac events. Ongoing Phase IIb and Phase III trials of astegolimab in patients with COPD who have a history of frequent acute exacerbation(s) of COPD will provide a future opportunity to confirm the safety profile of astegolimab.

Personalized dosing approaches play important roles in clinical practices to improve benefit: risk profiles. Whereas this is also important for drug development, especially in the context of drugs with narrow therapeutic windows, such approaches have not been fully evaluated during clinical development. Fazpilodemab (BFKB8488A) is an agonistic bispecific antibody which was being developed for the treatment of nonalcoholic steatohepatitis. The objective of this study was to characterize the exposure‐response relationships of fazpilodemab with the purpose of guiding dose selection for a phase II study, as well as to evaluate various personalized dosing strategies to optimize the treatment benefit. Fazpilodemab exhibited clear exposure‐response relationships for a pharmacodynamic (PD) biomarker and gastrointestinal adverse events (GIAEs), such as nausea and vomiting. Static exposure‐response analysis, as well as longitudinal adverse event (AE) analysis using discrete‐time Markov model, were performed to characterize the observations. Clinical trial simulations were performed based on the developed exposure‐response models to evaluate probability of achieving target PD response and the frequency of GIAEs to inform phase II dose selection. Dynamic simulation of personalized dosing strategies demonstrated that the AE‐based personalized dosing is the most effective approach for optimizing the benefit–risk profiles. The approach presented here can be a useful framework for quantifying the benefit of personalized dosing for drugs with narrow therapeutic windows.

Astegolimab, a fully human immunoglobulin G2 monoclonal antibody, binds with high affinity to ST2, the interleukin‐33 receptor, thereby blocking ST2/interleukin‐33 binding and subsequent inflammatory cascades involved in inflammatory diseases. Here, we present three randomized, double‐blind, placebo‐controlled, Phase I studies evaluating the safety, tolerability, pharmacokinetics, and immunogenicity of single‐ascending doses of astegolimab in healthy participants and patients with mild atopic asthma (NCT01928368), multiple‐ascending doses in healthy participants (NCT02170337), and single‐ascending doses in healthy Japanese and White adults. Overall, 152 participants were enrolled, randomized, and treated with single‐ or multiple‐ascending doses of astegolimab (n = 112) or placebo (n = 40) subcutaneously (2.1–560 mg) or intravenously (210 or 700 mg). No deaths, serious adverse events, or discontinuations due to adverse events occurred during the studies. No clinically meaningful differences in incidence of TEAEs were observed between treatment arms. Pharmacokinetic exposure increased more than dose proportionally over 2.1–420 mg for single‐ascending doses but were approximately dose proportional for single‐ and multiple‐ascending doses ≥ 70 mg following subcutaneous administration. No pharmacokinetic differences were observed based on ethnicity between Japanese and White participants following body weight adjustments. Incidence of antidrug antibodies to astegolimab in healthy participants in the single‐ and multiple‐ascending dose studies was 14%–23% and 33%–50% for subcutaneous and intravenous administration, respectively. Astegolimab was well tolerated in these Phase I studies with no safety concerns identified. Thus, further assessment of astegolimab in targeted patient populations was justified; the Phase IIb ALIENTO and Phase III ARNASA trials in patients with chronic obstructive pulmonary disease are ongoing.

The present paper reports the effective utilization of marble sludge powder (MSP) for the recovery of potash values from waste mica scrap using chlorination roasting-water leaching method. Characterization studies indicated the presence of dolomite as the major mineral phase in MSP, whereas muscovite and quartz were observed in the mica sample. The acid leaching studies suggest a maximum of 22% potash recovery under conditions: 4 M H 2 SO 4 acid, particle size of ∼100 µm, stirring speed of 600 r/min, leaching temperature of 75°C, and leaching time of 90 min. The chlorination roasting-water leaching process was adopted to achieve the lowest level of 80%–90% potash recovery. The optimum conditions for the recovery of ∼93% potash from mica (∼8.6wt% K 2 O) requires 900°C roasting temperature, 30 min roasting time, and 1:1:0.75 mass ratio of mica: MSP: NaCl. The roasting temperature and amount of NaCl are found to be the most important factors for the recovery process. The reaction mechanism suggests the formation of different mineral phases, including sylvite (KCl), wollastonite, kyanite, and enstatite, during roasting, which were confirmed by X-ray diffraction (XRD) analyses and scanning electron microscopy (SEM) morphologies. The MSP-blended NaCl additive is more effective for potash recovery compared with the other reported commercial roasting additives.

The present study attempted to observe the perception and adaptation strategies of farmers in the context of climate change. It observes that the majority of the farmers are aware of climate change and understand that they are facing problems due to it. The major problems faced by the farmers are the long duration of dryness due to lack of rainfall, weed pressure, very high temperatures, and crop disease. However, farmers are not very aware of technological adaptation and have changed the cropping time due to changes in the time of monsoon. The study recommends that there is a need for intensive micro and macro policy initiatives in terms of modern green sustainable technology along with awareness and skill development of the farmers. The government should also focus more on policy initiatives for sustainable agricultural practices in line with sustainable development goals.

A facile and green approach has been developed for the in situ synthesis of hybrid nanomaterials based on dendrite-shaped Pd nanostructures supported on graphene （RG）. The as-synthesized hybrid nanomaterials （RG-PdnDs） have been thoroughly characterized by high resolution transmission electron microscopy, X-ray photoelectron spectroscop）~ atomic force microscop）~ Raman spectroscopy and electrochemical techniques. The mechanism of formation of such dendrite- shaped Pd nanostructures on the graphene support has been elucidated using transmission electron microscopy （TEM） measurements. The RG induces the formation of, and plays a decisive role in shaping, the dendrite morphology of Pd nanostructures on its surface. Cyclic voltammetry and chronoamperometry techniques have been employed to evaluate the electrochemical performance of RG-PdnDs towards oxidation of methanol. The electrochemical （EC） activities of RG-PdnDs are compared with graphene-supported spherical-shaped Pd nanostructures, Pd nanodendrites alone and a commercial available Pd/C counterpart. The combined effect of the graphene support and the dendrite morphology of RG-PdnDs triggers the high electrocatalytic activity and results in robust tolerance to CO poisoning.

Purpose This study aims to investigate the conditional volatility of the Asian stock market concerning Bitcoin and global crude oil price movement. Design/methodology/approach This study uses the newest Dynamic Conditional Correlation (DCC)-Generalized Autoregressive Conditional Heteroskedasticity (GARCH) model to examine the conditional volatility of the stock market for Bitcoin and crude oil prices in the Asian perspective. The sample stock market includes Chinese, Indian, Japanese, Malaysian, Pakistani, Singaporean, South Korean and Turkish stock exchanges, with daily time series data ranging from 4 April 2015−31 July 2023. Findings The outcome reveals the presence of volatility clustering on the return series of crude oil, Bitcoin and all selected stock exchanges of the current study. Secondly, the outcome of DCC, manifests that there is no short-run volatility spillover from crude oil to the Malaysian, Pakistani and South Korean and Turkish stock markets, whereas Chinese, Indian, Japanese, Singapore stock exchanges show the short-run volatility spillover from crude oil in the short run. On the other hand, in the long run, there is a volatility spillover effect from crude oil to all the stock exchanges. Thirdly, the findings suggest that there is no immediate spillover of volatility from Bitcoin to the stock markets return volatility of China, India, Malaysia, Pakistan, South Korea and Singapore. In contrast, both the Japanese and Turkish stock exchanges exhibit a short-term volatility spillover from Bitcoin. In the long term, a volatility spillover effect from Bitcoin is observed in all stock exchanges except for Malaysia. Lastly, based on the outcome of conditional variance, it can be concluded that there was increase in the return volatility of stock exchanges during the period of the COVID-19 pandemic. Research limitations/implications The analysis below does not account for the bias induced due to certain small sample properties of DCC-GARCH model. There exists a huge literature that suggests other methodologies for small sample corrections such as the DCC connectedness approach. On the other hand, decisive corollaries of the conclusions drawn above have been made purely based on a comprehensive investigation of eight Asian stock exchange economies. However, there is scope for inclusive examination by considering other Nordic and Western financial markets with panel data approach to get more robust inferences about the reality. Originality/value Most of the empirical analysis in this perspective skewed towards the Nordic and Western countries. In addition to that many empirical investigations examine either the impact of crude oil price movement or Bitcoin performance on the stock market return volatility. However, none of the examinations quests the crude oil and Bitcoin together to unearth their implication on the stock market return volatility in a single study, especially in the Asian context. Hence, current investigation endeavours to examine the ramifications of Bitcoin and crude oil price movement on the stock market return volatility from an Asian perspective, which has significant implications for the investors of the Asian financial market.

After the enormous success of graphene, researchers have been extensively searching for similar materials to explore potential future insights for nanotechnology applications. In 2015, an emerging material called borophene was synthesized on an Ag substrate. Because of the unique physical and electronic properties of borophene, it has been recognized as a prospective material for the advancement of cutting-edge technology. In this review, we have summarized the computational study of one of the most promising gas-capture materials, borophene, i.e., the gas adsorption of gases such as sulfur dioxide (SO2), carbon monoxide (CO), carbon dioxide (CO2), hydrogen sulfide (H2S), hydrogen cyanide (HCN), methanal (HCOH), adenine (AD), dimethylamine (DMA), trimethylamine (TMA), nitric oxide (NO), ammonia (NH3), and nitrogen dioxide (NO2), and volatile organic compounds (VOCs) like benzene (C6H6), ethylene (C2H4), ethane (C2H6), toluene (Ph-CH3), methanol (H3COH), methyl chloride (H3CCl), formic acid (HCOOH), and formaldehyde (H2CO) on the borophene surface using density functional theory (DFT). Furthermore, in the abovementioned study, the adsorption energy (Ead) and the density of states (DOS) of the respective gases are explained.

Technological advancement towards the quantum era requires secure communication, quantum computation and ultra-sensitive sensing capabilities. Layered quantum materials (LQMs) have remarkable optoelectronic and quantum properties that can usher us into the quantum era. Electron microscopy is the tool of choice for measuring these LQMs at an atomic and nanometre scale. On the other hand, electron-irradiation of LQMs can modify various material properties, including the creation of structural defects. We review different types of structural defects, as well as electron elastic- and inelastic-scattering induced processes. Controlled modification of optoelectronic and quantum properties of LQMs using electron-irradiation, including creation of single-photon emitters is discussed. Protection of electron-irradiation induced damage of LQMs via encapsulation by other layered materials is encouraged. We finally give insights into challenges and opportunities, including creating novel structures using an electron beam.