Recent Loss of Vitamin C Biosynthesis Ability in Bats

The traditional assumption that bats cannot synthesize vitamin C (Vc) has been challenged recently. We have previously shown that two Old World bat species (Rousettus leschenaultii and Hipposideros armiger) have functional L-gulonolactone oxidase (GULO), an enzyme that catalyzes the last step of Vc biosynthesis de novo. Given the uncertainties surrounding when and how bats lost GULO function, exploration of gene evolutionary patterns is needed. We therefore sequenced GULO genes from 16 bat species in 5 families, aiming to establish their evolutionary histories. In five cases we identified pseudogenes for the first time, including two cases in the genus Pteropus (P. pumilus and P. conspicillatus) and three in family Hipposideridae (Coelops frithi, Hipposideros speoris, and H. bicolor). Evolutionary analysis shows that the Pteropus clade has the highest ω ratio and has been subjected to relaxed selection for less than 3 million years. Purifying selection acting on the pseudogenized GULO genes of roundleaf bats (family Hipposideridae) suggests they have lost the ability to synthesize Vc recently. Limited mutations in the reconstructed GULO sequence of the ancestor of all bats contrasts with the many mutations in the ancestral sequence of recently emerged Pteropus bats. We identified at least five mutational steps that were then related to clade origination times. Together, our results suggest that bats lost the ability to biosynthesize vitamin C recently by exhibiting stepwise mutation patterns during GULO evolution that can ultimately lead to pseudogenization

ACP-DRL: an anticancer peptides recognition method based on deep representation learning

Cancer, a significant global public health issue, resulted in about 10 million deaths in 2022. Anticancer peptides (ACPs), as a category of bioactive peptides, have emerged as a focal point in clinical cancer research due to their potential to inhibit tumor cell proliferation with minimal side effects. However, the recognition of ACPs through wet-lab experiments still faces challenges of low efficiency and high cost. Our work proposes a recognition method for ACPs named ACP-DRL based on deep representation learning, to address the challenges associated with the recognition of ACPs in wet-lab experiments. ACP-DRL marks initial exploration of integrating protein language models into ACPs recognition, employing in-domain further pre-training to enhance the development of deep representation learning. Simultaneously, it employs bidirectional long short-term memory networks to extract amino acid features from sequences. Consequently, ACP-DRL eliminates constraints on sequence length and the dependence on manual features, showcasing remarkable competitiveness in comparison with existing methods

DataSheet1_ACP-DRL: an anticancer peptides recognition method based on deep representation learning.PDF

Cancer, a significant global public health issue, resulted in about 10 million deaths in 2022. Anticancer peptides (ACPs), as a category of bioactive peptides, have emerged as a focal point in clinical cancer research due to their potential to inhibit tumor cell proliferation with minimal side effects. However, the recognition of ACPs through wet-lab experiments still faces challenges of low efficiency and high cost. Our work proposes a recognition method for ACPs named ACP-DRL based on deep representation learning, to address the challenges associated with the recognition of ACPs in wet-lab experiments. ACP-DRL marks initial exploration of integrating protein language models into ACPs recognition, employing in-domain further pre-training to enhance the development of deep representation learning. Simultaneously, it employs bidirectional long short-term memory networks to extract amino acid features from sequences. Consequently, ACP-DRL eliminates constraints on sequence length and the dependence on manual features, showcasing remarkable competitiveness in comparison with existing methods.</p

Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development

The lymphatic system plays a key role in tissue fluid homeostasis. Lymphatic dysfunction contributes to the pathogenesis of many human diseases, including lymphedema and tumor metastasis. However, the mechanisms regulating lymphangiogenesis remain largely unknown. Here, we show that COUP-TFII (also known as Nr2f2), an orphan member of the nuclear receptor superfamily, mediates both developmental and pathological lymphangiogenesis in mice. Conditional ablation of COUP-TFII at an early embryonic stage resulted in failed formation of pre-lymphatic ECs (pre-LECs) and lymphatic vessels. COUP-TFII deficiency at a late developmental stage resulted in loss of LEC identity, gain of blood EC fate, and impaired lymphatic vessel sprouting. siRNA-mediated downregulation of COUP-TFII in cultured primary human LECs demonstrated that the maintenance of lymphatic identity and VEGF-C–induced lymphangiogenic activity, including cell proliferation and migration, are COUP-TFII–dependent and cell-autonomous processes. COUP-TFII enhanced the pro-lymphangiogenic actions of VEGF-C, at least in part by directly stimulating expression of neuropilin-2, a coreceptor for VEGF-C. In addition, COUP-TFII inactivation in a mammary gland mouse tumor model resulted in inhibition of tumor lymphangiogenesis, suggesting that COUP-TFII also regulates neo-lymphangiogenesis in the adult. Thus, COUP-TFII is a critical factor that controls lymphangiogenesis in embryonic development and tumorigenesis in adults