Biology subjects

Rong, M.

Publications and source records attributed to Rong, M..

5 recordsLinked to original sources

bioRxiv2026

An allosteric pocket in KV1.3 defines a distinct chemical space for immunomodulator design

KV1.3 is a validated autoimmune drug target, yet all disclosed inhibitors converge on a narrow set of conserved binding sites, suffering from poor selectivity or clinical failure. Whether KV1.3 harbors a distinctive, druggable pocket amenable to selective targeting has remained unknown. Here we report MPiN, a highly selective, state-dependent KV1.3 inhibitor with in vivo efficacy in a mouse psoriasis model, which engages a previously uncharacterized extracellular allosteric pocket framed by the PP1-PP2 turret loops, the pore helix and the outer S5/S6 helices, acting through a bidirectional pore-to-sensor coupling that simultaneously constricts the selectivity filter and facilitates the voltage sensor toward activation. Unexpectedly, despite the extensive structural conservation of this pocket across KV1 paralogs, subtype selectivity is dictated by the peripheral residues G427 and H451, which define pocket geometry without directly contacting the ligand, thereby establishing a geometry-driven "non-contact selectivity" mechanism. By opening an unrecognized, structurally distinct chemical space on KV1.3 and redefining how selectivity is achieved within a conserved channel family, this work lays the structural and conceptual foundation for rational, structure-guided design of next-generation KV1.3 immunomodulators.

biochemistry↗

bioRxiv2025

Domain-General Brain Networks Support Language Development

Understanding the neural basis of verbal intelligence across development requires disentangling the contributions of domain-general and language-selective brain systems. Although language is often considered a domain-specific function, complex language tasks also engage domain-general networks, such as the Default-Mode (DM) and Multiple-Demand (MD) systems. Yet how these systems contribute to the maturation of verbal competence remains poorly understood. Here, we examined this question using gray matter volume measures in an accelerated longitudinal dataset of children and adolescents from Beijing (N = 170), using the Verbal Comprehension Index (VCI) from the Wechsler Intelligence Scale as a benchmark for verbal abilities. We observed that individual differences in VCI were more strongly associated with structural maturation of domain-general networks (DM and MD) than with the language-selective network, and that these effects varied with age. Targeted validation in an independent cohort from Chongqing (N = 150) confirmed significant contributions of domain-general networks in adolescence (13-15 years), highlighting the robustness of these developmental effects. These findings suggest that domain-general cortical systems play a critical and previously underappreciated role in the emergence of verbal intelligence during adolescence, with implications for understanding how large-scale brain networks support the development of abstract verbal reasoning.

neuroscience↗

bioRxiv2024

A chromosome-level genome assembly of Dracaena cambodiana and comparative genomics analysis highlights the distinct biological features of two resource species of dragon's blood

This study reports a chromosome-level genome for Dracaena cambodiana, one of two typical dracaena species in China. This work will help to deepen the understanding of the dracaena species and the conservation and development of plant resources. The final assembly consisted of 54 scaffolds, spanning 1.08 Gb, with a scaffold N50 size of 52.29 Mb, encoded 36860 predicted protein-coding genes. A total of 1,064,810,157 bp of genome sequences were located on 20 chromosomes (2n = 40), accounting for 98.46%. We investigate the possible mechanisms of the longevity of dracaena, the longest-lived plant in the world, which involve DNA repair and post-translational modification. We also performed comparative genomic analysis of the previously assembled genome of Dracaena cochinchinesis with this genome, and found that the two involved interaction of plant-pathogen interaction and ubiquitin mediated proteolysis, which may reveal why Dracaena has environmental adaptability and longevity characteristics.

genomics↗

bioRxiv2022

ECD of PepT1 interacts with TM1 to facilitate substrate transport

Mammalian peptide transporters, PepT1 and PepT2, mediate uptake of a wide variety of di- and tri-peptides and are essential for the absorption of dietary peptides in the digestive tract and the recovery of peptides in renal filtrate. PepT also mediates absorption of many drugs and prodrugs to enhance their bioavailability. PepT has 12 transmembrane (TM) helices that fold into two domains, the N-terminal domain (NTD, TM1-6) and C-terminal domain (CTD, TM7-12), and a large extracellular domain (ECD) of [~]200 amino acids between TM9 and TM10. It is known that peptide transport involves large motions of the N- and C-domains, but the role of ECD remains unclear. Here we report the structure of PepT1 from Equus caballus (horse) determined by cryo-electron microscopy. The structure shows that ECD interacts with TM1 and bridges the N- and C-domains. Deletion of the ECD or mutations to the TM1-ECD interface both impair the transport activity. These results demonstrate a role of ECD in structure and function of PepT1 and enhance our understanding of the mechanism of transport in PepT1.

biochemistry↗

bioRxiv2021

The First High-Quality Reference Genome of Sika Deer Provides Insights for High-Tannin Adaptation

Sika deer are known to prefer oak leaves, which are rich in tannins and toxic to most mammals; however, the genetic mechanisms underlying their unique ability to adapt to living in the jungle are still unclear. In identifying the mechanism responsible for the tolerance of a highly toxic diet, we have made a major advancement in the elucidation of the genomics of sika deer. We generated the first high-quality, chromosome-level genome assembly of sika deer and measured the correlation between tannin intake and RNA expression in 15 tissues through 180 experiments. Comparative genome analyses showed that the UGT and CYP gene families are functionally involved in the adaptation of sika deer to high-tannin food, especially the expansion of UGT genes in a subfamily. The first chromosome-level assembly and genetic characterization of the tolerance toa highly toxic diet suggest that the sika deer genome will serve as an essential resource for understanding evolutionary events and tannin adaptation. Our study provides a paradigm of comparative expressive genomics that can be applied to the study of unique biological features in non-model animals.

genomics↗