How do industrial land transfer modes impact carbon emissions? An intermediation perspective based on industrial structure.

Industrial land is currently the main carrier and important source of global carbon emissions, and as the world's largest developing country, China's large-scale and diversified industrial land supply has made it the world's largest carbon emitter. Therefore, researching the impact of different supply methods of industrial land on carbon emissions and its impact paths in China can help provide a reference for other countries to reduce carbon emissions from the perspective of urban industrial land management, which is of great significance for effectively promoting global carbon reduction. Based on this, this paper analyses the impact of different supply methods of industrial land on carbon emissions and its urban heterogeneity using the SYS-GMM and chain-mediated effects models for 285 cities in China from 2008 to 2020.

Pharmacokinetics, pharmacodynamics, and toxicity of a PD-1-targeted IL-15 in cynomolgus monkeys.

PF-07209960 is a novel bispecific fusion protein composed of an anti-PD-1 antibody and engineered IL-15 cytokine mutein with reduced binding affinity to its receptors. The pharmacokinetics (PK), pharmacodynamics (PD), and toxicity of PF-07209960 were evaluated following once every other week subcutaneous (SC) or intravenous (IV) administration to cynomolgus monkeys in a repeat-dose PKPD (0.01-0.

Urban land use carbon emission intensity in China under the "double carbon" targets: spatiotemporal patterns and evolution trend.

In-depth research on the spatiotemporal patterns and evolution trend of urban land use carbon emission intensity (ULUCEI) can reveal the internal relationship between urban land use and carbon emissions, which is crucial for achieving carbon emission reduction and "double carbon" targets. This paper proposed a conceptual framework of ULUCEI; the methods of kernel density estimation (KDE), exploratory spatial data analysis (ESDA), and spatial Markov chains were adopted for exploring the spatiotemporal patterns and evolution trend of China's ULUCEI from 2000 to 2017. The following conclusions are drawn through research.

The Spatial and Temporal Evolution of the Coordination Degree in Regard to Farmland Transfer and Cultivated Land Green Utilization Efficiency in China.

In many parts of the world, the shortage of cultivated land and the food crisis are worsening on a continued basis. Hence, the central and local governments of the PRC have successively issued various related policies to encourage the practice of farmland transfer, promote the eco-friendly utilization of cultivated land, and ameliorate the efficiency of cultivated land utilization. Under the context of large-scale farmland transfer and rural revitalization strategy in China, it is significant to ensure agricultural sustainability through the coordination of farmland transfer and the amelioration of cultivated land green utilization efficiency (CLGUE).

Has China's Low-Carbon City Construction Enhanced the Green Utilization Efficiency of Urban Land?

China has implemented the low-carbon city pilot (LCCP) policy in the hopes of efficiently limiting carbon emission intensity to combat global warming and promote green economic growth. Urban land utilization, the second-largest source of carbon emissions, is key to the LCCP policy being able to have the desired effect, which has attracted widespread attention. Based on the panel data from prefecture-level cities in China from 2006 to 2019, this study used the propensity score matching difference-in-differences method (PSM-DID) to examine the impacts of LCCP policy on green utilization efficiency of urban land (GUEUL).

Impact of Cereal Production Displacement from Urban Expansion on Ecosystem Service Values in China: Based on Three Cropland Supplement Strategies.

The acceleration of global urban expansion constantly occupies high-quality cropland and affects regional food security. The implementation of cropland protection policies has alleviated the pressure of cropland loss worldwide, and thus keeping a dynamic balance of cereal production. Such a displacement of cereal production from the lost cropland to the supplemented cropland has resulted in the massive losses of natural habitats (such as forests, grasslands, and wetlands) as well as ecosystem service values.

An Engineered IL15 Cytokine Mutein Fused to an Anti-PD1 Improves Intratumoral T-cell Function and Antitumor Immunity.

The use of cytokines for immunotherapy shows clinical efficacy but is frequently accompanied by severe adverse events caused by excessive and systemic immune activation. Here, we set out to address these challenges by engineering a fusion protein of a single, potency-reduced, IL15 mutein and a PD1-specific antibody (anti-PD1-IL15m). This immunocytokine was designed to deliver PD1-mediated, avidity-driven IL2/15 receptor stimulation to PD1 tumor-infiltrating lymphocytes (TIL) while minimally affecting circulating peripheral natural killer (NK) cells and T cells.

Utilization of lipopolysaccharide challenge in cynomolgus macaques to assess IL-10 receptor antagonism.

The current era of drug discovery has been marked by a significant increase in the development of immune modulating agents to address a range of diseases such as cancer, chronic inflammation, and other conditions of dysregulated immunity. Non-clinical evaluation of these agents in animal models can be challenging, as the presence of an active immune state is often required in order to detect the effects of the test agent. Modulation of interleukin (IL)-10 signaling represents this type of situation in that altering IL-10 action can be difficult to appreciate in the absence of an ongoing immune response.

Preclinical Efficacy and Safety Comparison of CD3 Bispecific and ADC Modalities Targeting BCMA for the Treatment of Multiple Myeloma.

The restricted expression pattern of B-cell maturation antigen (BCMA) makes it an ideal tumor-associated antigen (TAA) for the treatment of myeloma. BCMA has been targeted by both CD3 bispecific antibody and antibody-drug conjugate (ADC) modalities, but a true comparison of modalities has yet to be performed. Here we utilized a single BCMA antibody to develop and characterize both a CD3 bispecific and 2 ADC formats (cleavable and noncleavable) and compared activity both and with the aim of generating an optimal therapeutic.

Enhancing antisense efficacy with multimers and multi-targeting oligonucleotides (MTOs) using cleavable linkers.

The in vivo potency of antisense oligonucleotides (ASO) has been significantly increased by reducing their length to 8-15 nucleotides and by the incorporation of high affinity RNA binders such as 2', 4'-bridged nucleic acids (also known as locked nucleic acid or LNA, and 2',4'-constrained ethyl [cET]). We now report the development of a novel ASO design in which such short ASO monomers to one or more targets are co-synthesized as homo- or heterodimers or multimers via phosphodiester linkers that are stable in plasma, but cleaved inside cells, releasing the active ASO monomers. Compared to current ASOs, these multimers and multi-targeting oligonucleotides (MTOs) provide increased plasma protein binding and biodistribution to liver, and increased in vivo efficacy against single or multiple targets with a single construct.

A mathematical model of the effect of immunogenicity on therapeutic protein pharmacokinetics.

A mathematical pharmacokinetic/anti-drug-antibody (PK/ADA) model was constructed for quantitatively assessing immunogenicity for therapeutic proteins. The model is inspired by traditional pharmacokinetic/pharmacodynamic (PK/PD) models, and is based on the observed impact of ADA on protein drug clearance. The hypothesis for this work is that altered drug PK contains information about the extent and timing of ADA generation.

Modeling, simulation, and translation framework for the preclinical development of monoclonal antibodies.

The industry-wide biopharmaceutical (i.e., biologic, biotherapeutic) pipeline has been growing at an astonishing rate over the last decade with the proportion of approved new biological entities to new chemical entities on the rise.

Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of visual dysfunction worldwide. Amyloid β (Aβ) peptides, Aβ1-40 (Aβ40) and Aβ1-42 (Aβ42), have been implicated previously in the AMD disease process. Consistent with a pathogenic role for Aβ, we show here that a mouse model of AMD that invokes multiple factors that are known to modify AMD risk (aged human apolipoprotein E 4 targeted replacement mice on a high-fat, cholesterol-enriched diet) presents with Aβ-containing deposits basal to the retinal pigmented epithelium (RPE), histopathologic changes in the RPE, and a deficit in scotopic electroretinographic response, which is reflective of impaired visual function.

Therapeutic monoclonal antibody concentration monitoring: free or total?

Most therapeutic monoclonal antibodies are designed to bind a specific antigen to elicit pharmacological effects. Accurate quantification of a therapeutic monoclonal antibody in biological matrices is essential for assessing its pharmacokinetics and selecting an effective dosing regimen. Therapeutic antibodies may exist in free, partially bound and fully bound forms in the bloodstream.

CR011, a fully human monoclonal antibody-auristatin E conjugate, for the treatment of melanoma.

Purpose: Advanced melanoma is a highly drug-refractory neoplasm representing a significant unmet medical need. We sought to identify melanoma-associated cell surface molecules and to develop as well as preclinically test immunotherapeutic reagents designed to exploit such targets.

Experimental Design And Results: By transcript profiling, we identified glycoprotein NMB (GPNMB) as a gene that is expressed by most metastatic melanoma samples examined.

A Drosophila protein-interaction map centered on cell-cycle regulators.

Background: Maps depicting binary interactions between proteins can be powerful starting points for understanding biological systems. A proven technology for generating such maps is high-throughput yeast two-hybrid screening. In the most extensive screen to date, a Gal4-based two-hybrid system was used recently to detect over 20,000 interactions among Drosophila proteins.