Freezing process influences cake appearance of a lyophilized amorphous protein formulation with low solid content and high fill configuration.

Low solid content and high fill drug product configuration pose special challenges for achieving elegant cake appearance after lyophilization. In this study, such a configuration for a protein formulation required lyophilization within a narrow primary drying operating space to obtain elegant cakes. Freezing process optimization was explored as a solution. A Design of Experiment (DoE) approach was used to evaluate the effect of shelf cooling rate, annealing temperature, and their interaction on cake appearance. The slope of product resistance (Rp) vs. dried layer thickness (Ldry) was used as the quantitative response because elegant cake appearance correlated with a lower initial Rp and positive slope. As the Rp vs. Ldry slope can be experimentally established within the first 1/6th of the total primary drying duration, partial lyophilization runs were executed, allowing for rapid screening. The DoE model revealed that a slow cooling rate (≤0.3 °C/min) and high annealing temperature (≥-10 °C) resulted in a better cake appearance. Furthermore, X-ray micro-computed tomography showed that elegant cakes exhibited uniform porous structure and larger pores, while inelegant cakes showed dense top layers with smaller pores. With the optimized freezing process, the primary drying operating space was broadened with improved cake appearance and batch homogeneity.

Central environmental inspection and corporate environmental investment: evidence from Chinese listed companies.

As a new type of environmental policy, the central environmental inspection (CEI) policy is an important innovative strategy in economic transition. Using the panel data of Chinese listed companies from 2011 to 2018, we apply the extended STIRPAT model to examine the direct impact of CEI policy on corporate environmental investment and its heterogeneity effects. The main findings are as follows: (1) The CEI policy has a positive influence on the environmental investment of all listed companies. (2) The promotion effect of CEI policy is quite different among five-round campaigns; while companies in later rounds fails to learn some experiences and lessons from the earlier rounds. (3) Due to the differences in property rights, industries, and environmental situations, the positive effect of CEI policy will be more significant in non-SOEs, companies in non-heavy-pollution industries, and companies in provinces with poor environment performance. This study supplements the research of environmental regulations, potentially contributing to the next stage of green and sustainable development in China.

The health consequences of greenhouse gas emissions: a potential pathway.

Excessive greenhouse gas emissions might be the major culprit for environmental degradation, which have direct and indirect adverse impacts in various ways. As the largest emitter of carbon emissions, China suffered great harm from climate change during the past 40 years. Therefore, it becomes necessary to study the impact of carbon emissions on health issues and their potential mechanism. Using the panel data from 30 provinces in China between 2002 and 2017, this study employes and extends the Stochastic Impacts by Regression on Population, Affluence, and Technology (STIRPAT) model and mediating effect model to analyze the direct and indirect effects of carbon emissions. The main results are as follows: (1) Carbon emissions has a certain negative impact on public health, which would increase with the rise of temperature. (2) The increase in carbon emissions has a more significant negative effect on health with the average temperature exceeding 17.75 °C, indicating that the temperature has a threshold effect. (3) The potential health risks become higher with the development of urbanization, but there is no obvious spillover effect in the health consequences. The results remain robust after controlling other factors. This study supplements the literature of climate governance and human health, potentially contributing to the next stage of high-quality and sustainable development.

Fixed asset changes with carbon regulation: The cases of China.

Carbon regulation might threaten corporate competitiveness and thus guide their production and investment behaviours. Using the difference-in-differences (DID) model, we analyze the impact of China's carbon emission trading (CET) pilots on the fixed asset and its investment. The main findings are as follows: (1) CET reduces the fixed assets value and investment of regulated companies. (2) The decline in the fixed asset and its investment represents more significantly in the economically developed areas, pilots with grandfathering allocation, energy and manufacturing industries, and state-owned enterprises. (3) Potential influence channel estimation indicates that the fixed-asset investment decreases through investment diversion, rather than operation transfer. (4) CET reduces the over-investment in the fixed assets of regulated companies and improves their fixed-asset investment efficiency. This study supplements the literature on carbon regulation and corporate behaviours, potentially contributing to the next stage of climate governance and global decarbonization.

Do carbon emissions impact the health of residents? Considering China's industrialization and urbanization.

Industrialization and urbanization have aggravated the contradiction between environmental protection and economic growth, leading to health issues. While there are considerable interests in understanding the health effects of carbon emissions in the context of climate change, little is observed at regional scale and by econometric methods. Applying regression analysis on 2002-2017 Chinese provincial-level panel data, this study explores the intermediary mechanisms and regional differences of carbon emissions on residents' health. The results indicate that: (1) Carbon emissions have a long-term adverse impact on residents' health-a 1% rise in carbon emission adds 0.298% more outpatients and 0.162% more inpatients; (2) The rise in carbon emissions impairs residents' health mainly by raising the temperature; (3) In areas with high levels of industrialization and urbanization, increased carbon emissions bring greater health risks; and (4) In terms of China's unique "leading industrialization and lagging urbanization" situation, only by upgrading industrial structure, improving urbanization quality, and promoting coordinated industrialization and urbanization can the harm of carbon emissions to residents' health be reduced. Therefore, the "one-size-fits-all" policy model is not suitable for China's current situation. To address global "climate change" issues, China must act according to local conditions by applying mitigating (adaptive) measures in economically developed (less developed) regions. Simultaneously, the authorities must focus on the interaction and synergy between industrialization and urbanization.

Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 3: Importance of the indole orientation.

A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin dependant kinase. Inhibitory activities against the enzyme ranged from 10nM to >20microM and were dependant upon both the nature of the aryl group and the tether joining the basic amine to the indolyl maleimide core of the inhibitors. Key interactions with the kinase ATP site and hinge region, predicted by homology modeling, were confirmed.

Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 1: SAR of the aryl region.

A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin dependant kinase. Inhibitory activities against the enzyme ranged from 34nM to >20microM and were dependant upon both the nature of the aryl group and the hydrogen bond donating potential of the maleimide ring. Key interactions with the kinase ATP site and hinge region were found to be consistent with homology modeling predictions.

Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 2: SAR of the amine tether.

A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin-dependant kinase. Inhibitory activities against the enzyme ranged from 34nM to >20microM and were dependant upon both the nature of the aryl group and the tether joining the basic amine to the indolyl maleimide core. Key interactions with the kinase ATP site and hinge region, predicted by homology modeling, were confirmed.