Antibody therapies have become an important class of therapeutics in recent years as they have exhibited outstanding efficacy and safety in the treatment of several major diseases including cancers, immune-related diseases, infectious disease and hematological disease. There has been significant progress in the global research and development (R&D) landscape of antibody therapies in the last decade. In this review, we have collected available data from the Umabs Antibody Therapies Database (Umabs-DB,https://umabs.com) as of June 30th, 2022. The Umabs-DB shows that 162 antibody therapies have been approved by at least one regulatory agency in the world, including 122 approvals in the US, followed by 114 in Europe, 82 in Japan and 73 in China, whereas biosimilar, diagnostic and veterinary antibodies are not included in our statistics. While the US and Europe have been at the leading position for decades, rapid advancement has been witnessed in Japan and China in the last decade. The approved antibody therapies include 115 canonical antibodies, 14 antibody-drug conjugates (ADCs), 7 bispecific antibodies, 8 antibody fragments, 3 radiolabeled antibodies, 1 antibody-conjugate immunotoxin, 2 immunoconjugates and 12 Fc-Fusion proteins. They have been developed against 91 drug targets, of which PD-1 is the most popular, with 14 approved antibody-based blockades for cancer treatment in the world. This review outlined the global landscape of the approved antibody therapies with respect to the regulation agencies, therapeutic targets and indications, aiming to provide an insight into the trends of the global development of antibody therapies.
The soybean (Glycine max L. Merr.) is a crop with a high demand for nitrogen (N). The root nodules that form in soybeans can fix atmospheric N effectively, yet the goal of achieving high yields cannot be met by relying solely on nodule-fixed N. Nonetheless, the application of N fertilizer may inhibit nodule formation and biological N fixation (BNF), but the underpinning mechanisms are still unclear. In this study, we grafted the roots of non-nodulated soybeans onto nodulated soybeans to generate plants with dual root system. The experiment included three treatments conducted under sand culture conditions with NO 3 − and NH 4 + as N sources. Treatment I: The non-nodulated roots on one side received 50 mg·L−1 15 NO 3 − or 15NH4+, and the nodulated roots on the other side were not treated. Treatment II: The non-nodulated roots received 50 mg·L−1 15 NO 3 − or 15 NH 4 + , and the nodulated roots received 50 mg·L−1 14 NO 3 − or 14 NH 4 + . Treatment III: Both non-nodulated and nodulated roots received 50 mg·L−1 15 NO 3 − or 15 NH 4 + . The results showed the following: (1) Up to 81.5%–87.1% of the N absorbed by the soybean roots and fixed by the root nodules was allocated to shoot growth, leaving 12.9%–18.5% for root and nodule growth. Soybeans preferentially used fertilizer N in the presence of a NO 3 − or NH 4 + supply. After the absorbed fertilizer N and nodule-fixed N was transported to the shoots, a portion of it was redistributed to the roots and nodules. The N required for root growth was primarily derived from the NO 3 − or NH 4 + assimilated by the roots and the N fixed by the nodules, with a small portion translocated from the shoots. The N required for nodule growth was primarily contributed by nodule-fixed N with a small portion translocated from the shoots, whereas the NO 3 − or NH 4 + that was assimilated by the roots was not directly supplied to the nodules. (2) Based on observations of the shoots and one side of the roots and nodules in the dual root system as an N translocation system, we proposed a method for calculating the N translocation from soybean shoots to roots and nodules during the R1–R5 stages based on the difference in the 15N abundance. Our calculations showed that when adding N at a concentration of 50 mg·L−1, the N translocated from the shoots during the R1–R5 stages accounts for 29.6%–52.3% of the N accumulation in nodulated roots (Rootn) and 9.4%–16.6% of the N accumulation in Nodulen of soybeans. Through the study of this experiment, the absorption, distribution and redistribution characteristics of fertilizer N and root nodule N fixation in soybean can be clarified, providing a theoretical reference for analyzing the mechanisms of the interaction between fertilizer N and nodule-fixed N.
The specific mechanisms by which nitrogen affects the nodulation and nitrogen fixation of soybean plants are unclear. Investigating the relationship between nitrogen, nodulation and nitrogen fixation can provide new insights for the rational and proper use of nitrogen fertilizer in soybean plants. In this study, we grafted soybean roots to construct a dual-root system with a single nodulated side. Experiment I was performed at the third trifoliate leaf to initial seed filling (V3-R3) growth stages (for 30 days) for long-term nitrogen supply, and Experiment II was performed at the third trifoliate leaf to fourth trifoliate leaf (V3-V4) growth stages (for 5 days) for short-term nitrogen supply. For the two experiments, a nutrient solution providing 15NH415NO3 or NH4NO3 as the nitrogen source was added to the non-nodulated side, while a nitrogen-free nutrient solution was added to the nodulated side. The concentrations of nitrogen supplied were 0 mg/L, 25 mg/L, 50 mg/L, 75 mg/L, and 100 mg/L. The results showed the following: (1) Short-term nitrogen supply systematically regulated the specific nitrogenase activity (SNA), thereby inhibiting the acetylene reduction activity (ARA). Under long-term nitrogen supply, the recovery of SNA was generally consistent across treatments, and the concentration of nitrogen supplied systematically regulated the growth of root nodules, thereby inhibiting the ARA. (2) Using the 15N tracer method, the concentration of fertilizer nitrogen was positively correlated with the amount of nitrogen redistributed to other organs. Although the percentage of nitrogen derived from the atmosphere (Ndfa%) decreased significantly with increasing concentrations of nitrogen supplied, the effect on the accumulation of nitrogen fixed by nodules (Naccumulation of nodules) was not significant. By establishing the relationships between the ARA (measured by the acetylene reduction method), Ndfa% (based on 15N calculations), and Naccumulation nodules (based on 15N calculations), it was found that the ARA reliably reflected the Ndfa% but not the Naccumulation of nodules.
The specific mechanism by which nitrogen application affects nodulation and nitrogen fixation in legume crops remains uncertain. To further study the effects of nitrogen application on soybean nodulation and nitrogen accumulation, three consecutive tests were performed during the VC-V4, V4-R1 (10 days), and R1-R2 (10 days) growth periods of soybean. In a dual-root soybean system, seedlings on one side were watered with a nutrient solution containing NH 4 + or NO 3 − as the N source (N+ side), and those on the other side were watered with a nitrogen-free nutrient solution (N-side). During the VC-R2 period, on the N+ side, high nitrogen treatment inhibited nodule growth and nitrogenase activity (EC 1.18.6.1), and the inhibition was significantly increased with increasing high nitrogen supply time (10 days, 20 days). When the high nitrogen treatment time reached 20 days, the specific nitrogenase activity (C 2 H 4 μmol −1 g −1 nodule dry mass h −1 ) was similar to that in the low nitrogen treatment, indicating that the nitrogen fixation capacity per gram of dry mass nodules was almost the same. Therefore, it is assumed that long-term high nitrogen treatment mainly reduces nitrogen fixation by reducing the nodule number. The effect of nitrogen concentration on the roots on the N+ side was greater than that on the N-side. Taken together, these results indicate that nitrogen application affects a contact-dependent local inhibition of root nodule growth, nitrogenase activity, and nitrogen accumulation. The whole plant systematically regulates specific nitrogenase activity, and high nitrogen inhibition is recoverable.
Excessive plant height is an important factor that can lead to lodging, which is closely related to soybean yield. Gibberellins are widely used as plant growth regulators in agricultural production. Gibberellic acid (GA3), one of the most effective active gibberellins, has been used to regulate plant height and increase yields. The mechanism through which GA3 regulates internode elongation has been extensively investigated. In 2019 and 2020, we applied GA3 to the stems, leaves, and roots of two soybean cultivars, Heinong 48 (a high-stalk cultivar) and Henong 60 (a dwarf cultivar), and GA3 was also applied to plants whose apical meristem was removed or to girded plants to compare the internode length and stem GA3 content of soybean plants under different treatments. These results suggested that the application of GA3 to the stems, leaves, and roots of soybean increased the internode length and GA3 content in the stems. Application of GA3 decreased the proportion of the pith in the soybean stems and primary xylem while increasing the proportion of secondary xylem. The apical meristem is an important site of GA3 synthesis in soybean stems and is involved in the regulation of stem elongation. GA3 was shown to be transported acropetally through the xylem and laterally between the xylem and phloem in soybean stems. We conclude that the GA3 level in stems is an important factor affecting internode elongation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.