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Today, monoclonal immunoglobulin gamma (IgG) antibodies have become a major option in cancer therapy especially for the patients with advanced or metastatic cancers. Efficacy of monoclonal antibodies (mAbs) is achieved through both its antigen-binding fragment (Fab) and crystallizable fragment (Fc). Fab can specifically recognize tumor-associated antigen (TAA) and thus modulate TAA-linked downstream signaling pathways that may lead to the inhibition of tumor growth, induction of tumor apoptosis, and differentiation. The Fc region can further improve mAbs' efficacy by mediating effector functions such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cell-mediated phagocytosis. Moreover, Fc is the region interacting with the neonatal Fc receptor in a pH-dependent manner that can slow down IgG's degradation and extend its serum half-life. Loss of the antibody Fc region dramatically shortens its serum half-life and weakens its anticancer effects. Given the essential roles that the Fc region plays in the modulation of the efficacy of mAb in cancer treatment, Fc engineering has been extensively studied in the past years. This review focuses on the recent advances in therapeutic Fc engineering that modulates its related effector functions and serum half-life. We also discuss the progress made in aglycosylated mAb development that may substantially reduce the cost of manufacture but maintain similar efficacies as conventional glycosylated mAb. Finally, we highlight several Fc engineering-based mAbs under clinical trials.

We examine whether and how individual auditors affect audit outcomes using a large set of archival Chinese data. We analyze approximately 800 individual auditors and find that they exhibit significant variation in audit quality. The effects that individual auditors have on audit quality are both economically and statistically significant, and are pronounced in both large and small audit firms. We also find that the individual auditor effects on audit quality can be partially explained by auditor characteristics, such as educational background, Big N audit firm experience, rank in the audit firm, and political affiliation. Our findings highlight the importance of scrutinizing and understanding audit quality at the individual auditor level.

Several studies report an audit fee premium for auditor industry expertise measured at the office level. We extend this line of research by examining whether there is a fee premium for auditor industry expertise measured at the partner level. Using Australian data, we show that the coefficient for partner-level industry expertise is highly significant and economically important. This is consistent with industry knowledge or expertise residing in the human capital of individual engagement partners. Inconsistent with prior research, we show that there is no auditor industry expertise fee premium at the audit office level when partner-level expertise is controlled for. Consistent with prior research, we find little evidence of a fee premium at the national level. The results suggest that the auditor industry expertise fee premium is mainly a partner-level phenomenon, casting doubt on the belief that industry knowledge or expertise is distributed across engagement partners within an audit office.

Therapeutic monoclonal antibodies have become molecules of choice to treat autoimmune disorders, inflammatory diseases, and cancer. Moreover, bispecific/multispecific antibodies that target more than one antigen or epitope on a target cell or recruit effector cells (T cell, natural killer cell, or macrophage cell) toward target cells have shown great potential to maximize the benefits of antibody therapy. In the past decade, many novel concepts to generate bispecific and multispecific antibodies have evolved successfully into a range of formats from full bispecific immunoglobulin gammas to antibody fragments. Impressively, antibody fragments such as bispecific T-cell engager, bispecific killer cell engager, trispecific killer cell engager, tandem diabody, and dual-affinity-retargeting are showing exciting results in terms of recruiting and activating self-immune effector cells to target and lyse tumor cells. Promisingly, crystallizable fragment (Fc) antigen-binding fragment and monomeric antibody or half antibody may be particularly advantageous to target solid tumors owing to their small size and thus good tissue penetration potential while, on the other hand, keeping Fc-related effector functions such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cell-mediated phagocytosis, and extended serum half-life interaction with neonatal Fc receptor. This review, therefore, focuses on the progress of Fc engineering in generating bispecific molecules and on the use of small antibody fragment as scaffolds for therapeutic development.

Soil microorganisms could obtain energy and nutrients during litter decomposition with the help of soil extracellular enzymes. The litter types were among the most critical factors that affect soil extracellular enzyme activities. However, how litter types modulate the soil extracellular enzyme activity with grassland gradation is unclear. Here, we conducted a 240-day experiment of two different types of litter decomposition on soil extracellular enzyme activity and stoichiometry in different degraded grasslands. We found that C-acquiring enzyme activity and the enzyme stoichiometry of C/N were higher in Chloris virgata litter than in Leymus chinensis litter at lightly degraded level and C-acquiring enzyme activity in C. virgata was 16.96% higher than in L. chinensis . P-acquiring enzyme activity had the same trend with litter types in moderately and highly degraded levels and it was 20.71% and 30.89% higher in C. virgata than that in L. chinensis , respectively. The change of the enzyme stoichiometry with litter types was only showed in the enzyme stoichiometry of C/N at lightly degraded level, suggesting that litter types only affected the microbial C limitation in lightly degraded grassland. Almost all soil extracellular enzyme activities and extracellular enzyme stoichiometry, except the enzyme stoichiometry of N/P, decreased with grassland degraded level increasing. All vector angles were less than 45° suggesting that soil microorganisms were limited by N rather than by P during the decomposition process. Enzyme vector analysis revealed that soil microbial communities were co-limited by C and N during litter decomposition. Moreover, based on Random Forest (explaining more than 80%), we found that soil total nitrogen, total carbon, total phosphorus, dissolved organic C, pH and EC were important factors affecting soil enzyme activities by degradation levels. Our results emphasized that degradation levels could modulate the influences of litter types on soil extracellular enzyme activity. Our study enhanced our understanding in resource requirements for microbial communities to litter resources in degraded grassland and helped us to provide new ideas for improving degraded grassland ecosystems.

This study examines how the legal and regulatory changes in China affect the relationship between client economic importance and audit quality. At the individual auditor level, we find that the propensity to issue modified audit opinions (MAOs) is negatively correlated with client importance from 1995 to 2000. However, from 2001 to 2004, when the institutional environment became more investor-friendly, the propensity to issue MAOs is positively associated with client importance. These findings are corroborated by an analysis of regulatory sanctions. Although client importance measured at the office level is also negatively related to the propensity for MAOs from 1995 to 2000 without controlling for the auditor-level client importance, this result is sensitive to model specification and sample composition. Our results suggest that (1) institutional improvements prompt auditors to prioritize the costs of compromising quality over the economic benefits gained from important clients; and (2) the impact of client importance on audit decisions appears to be different at the individual auditor and office levels.

Altitudinal changes in the diversity of plants and animals have been well documented; however, soil animals received little attention in this context and it is unclear whether their diversity follows general altitudinal distribution patterns. Changbai Mountain is one of few well‐conserved mountain regions comprising natural ecosystems on the Eurasian continent. Here, we present a comprehensive analysis of the diversity and community composition of Collembola along ten altitudinal sites representing five vegetation types from forest to alpine tundra. Among 7834 Collembola individuals, 84 morphospecies were identified. Species richness varied marginally significant with altitude and generally followed a unimodal relationship with altitude. By contrast, the density of Collembola did not change in a consistent way with altitude. Collembola communities changed gradually with altitude, with local habitat‐related factors (soil and litter carbon‐to‐nitrogen ratio, litter carbon content, and soil pH) and climatic variables (precipitation seasonality) identified as major drivers of changes in Collembola community composition. Notably, local habitat‐related factors explained more variation in Collembola assemblages than climatic variables. The results suggest that local habitat‐related factors including precipitation and temperature are the main drivers of changes in Collembola communities with altitude. Specifically, soil and litter carbon‐to‐nitrogen ratio correlated positively with Collembola communities at high altitudes, whereas soil pH correlated positively at low altitudes. This documents that altitudinal gradients provide unique opportunities for identifying factors driving the community composition of not only above‐ but also belowground invertebrates. The results suggest that local habitat‐related factors including precipitation and temperature are the main drivers of changes in Collembola communities with altitude. Specifically, soil and litter carbon‐to‐nitrogen ratio correlated positively with Collembola communities at high altitudes, whereas soil pH correlated positively at low altitudes. This documents that altitudinal gradients provide unique opportunities for identifying factors driving the community composition of not only above‐ but also belowground invertebrates.

In the context of global change, mountain ecosystems are facing more threats than ever. Therefore, understanding spatial distribution patterns of diversity and their driving factors on mountains is gaining increasing attention. Although comprising an essential component of terrestrial ecosystems, the structure of soil fauna communities in mountain ecosystems and their driving factors have been little studied. Changbai Mountain harbors one of the most well‐preserved forest ecosystems in the temperate zone. Its high biodiversity provides an ideal setting for investigating biodiversity patterns along elevation gradients. We investigated the diversity, biomass, and community composition of two key soil predator taxa—centipedes and spiders—across eight elevations ranging from 800 to 1850 m a.s.l. Furthermore, we explored correlations between community characteristics and environmental factors. A total of 26 centipede species were identified among 2796 individuals, while 76 spider species were recorded from 2327 individuals. Both centipede and spider richness, biomass, as well as spider density, decreased with increasing elevation. Climatic variables and litter quality were identified as the primary drivers influencing the richness, biomass, and community composition of both taxa. Specifically, changes in temperature and precipitation associated with elevation were identified as the main drivers of changes in diversity, biomass, and community composition. Litter quality, including litter pH, total phosphorus, total carbon, total nitrogen, and N/P ratio, was of secondary importance. Overall, the results provide critical insights into the vulnerability of soil fauna to global climate change and highlight the need for conservation strategies that account for the complex interactions between biodiversity and environmental change. Changes in density, diversity, and biomass with elevation differ between centipedes and spiders. Compared to centipedes, spiders are more strongly affected by environmental changes. Climatic variables act as the main drivers of centipede and spider density, diversity, and biomass, with local habitat–related factors being of secondary importance.

Risky decision-making is critical to survival and development, which has been compromised in elderly populations. However, the neural substrates of altered financial risk-taking behavior in aging are still under-investigated. Here we examined the intrinsic putamen network in modulating risk-taking behaviors of Balloon Analogue Risk Task in healthy young and older adults using resting-state fMRI. Compared with the young group, the elderly group showed significantly different task performance. Based on the task performance, older adults were further subdivided into two subgroups, showing young-like and over-conservative risk behaviors, regardless of cognitive decline. Compared with young adults, the intrinsic pattern of putamen connectivity was significantly different in over-conservative older adults, but not in young-like older adults. Notably, age-effects on risk behaviors were mediated via the putamen functional connectivity. In addition, the putamen gray matter volume showed significantly different relationships with risk behaviors and functional connectivity in over-conservative older adults. Our findings suggest that reward-based risky behaviors might be a sensitive indicator of brain aging, highlighting the critical role of the putamen network in maintaining optimal risky decision-making in age-related cognitive decline.

The spatial patterns of field arthropod communities are an essential part of ecology and can provide fundamental data regarding field ecological processes and reveal the mechanism of ecosystem biodiversity maintenance. This study investigated the spatial distribution pattern of field insect communities to detect the spatial relationships between insect communities in farmland. The study site was located at the Dehui Agro-ecological Experimental Station of Black Soil, Jilin, China. Insect communities and environmental factors were sampled at 121 uniformly distributed points in a 400 × 400 m plot in August, September, and October 2015. The analysis revealed that insect communities from June to October demonstrated significant spatial correlation, and 6085 samples of 47 species and 47 families in 11 orders were collected from the insect community in the farmland. The farmland insect community structure changes and dynamic changes of nutritional function groups occur with time. According to the 400 x 400 m plot, the diversity of farmland insect communities and functional groups is maintained at a relatively high and stable level. In this study, a total of 6085 samples of corn farmland insects were obtained using the fluke method and direct observation method, including 11 orders, 26 families and 47 species, 4 absolute dominant populations, 6 main dominant populations, and 37 other populations. These studies can provide help for pest control in the spring corn area of Northeast China.