Biomedical subjects

Ruiqi Wang

Publications and source records attributed to Ruiqi Wang.

13 recordsLinked to original sources

PubMed2026

UFold-X: an enhanced Dual & Dynamic U-Mamba model for long-range RNA secondary structure prediction.

RNA secondary structure is essential for understanding the functions of non-coding RNAs, ribosomal RNAs, and viral genomes. However, accurate prediction of long RNA structures remains challenging due to complex long-range interactions and the limited availability of long-RNA training data. We present UFold-X, a dual-branch deep learning framework that combines a convolutional encoder for local structure modeling with a Mamba-based Visual State Space Module for capturing long-range dependencies. A dynamic gating mechanism adaptively integrates the two branches according to sequence length. UFold-X was evaluated on multiple benchmark datasets containing RNAs up to 5000 nucleotides. To rigorously assess generalization, we introduced a cross-clan benchmark for long RNAs. Under this stringent setting, UFold-X achieved performance comparable to state-of-the-art classical approaches while achieving the best performance among deep learning-based methods. Additional cross-family and within-family evaluations further demonstrated robust transferability and competitive predictive performance. UFold-X also maintained excellent computational efficiency, requiring only 0.08 s per sequence on average. To assess biological consistency, we developed a SHAPE-based reactivity prediction variant (UFold-X-R) and an integrated metric, the Hybrid Reactivity-Pairing Score (HRPS). UFold-X-R showed strong agreement with experimental icSHAPE data and achieved the highest HRPS among all evaluated methods. A user-friendly web server is available at https://ufold-x.ai4bread.com.

Nucleic Acid Conformation↗

PubMed2026

PAFAH1B1 governs follicular development by modulating the protein complex of CCNE1-CDK2-CDK1 to induce cell cycle arrest.

BACKGROUND: Ovarian follicle development plays a crucial role in mammalian fertility, which is primarily regulated by granulosa cell (GC) proliferation and cell cycle. Cell cycle dysregulation collectively might drive follicular atresia through GC dysfunction. However, the underlying molecular mechanisms remain largely unexplored. METHODS: The scRNA-seq and integrative analysis revealed that PAFAH1B1 was involved in cell cycle. Functional assays, including overexpression/knockdown, flow cytometry, EdU, HE, and TUNEL, confirmed that PAFAH1B1 regulated cell cycle and follicular development in vitro and in vivo. CoIP showed that PAFAH1B1 bound CCNE1-CDK2-CDK1 to arrest G2/M phase. Chromatin accessibility and CRISPR/dCas9-TET1 demonstrated that DNA methylation modulated PAFAH1B1 transcription. RESULTS: A novel regulator of cell cycle, PAFAH1B1, was identified in Pig Genotype-Tissue Expression (PigGTEx). During GC proliferation, we found that PAFAH1B1 transcription was correlated with the distribution rate of G1 phase in GCs. PAFAH1B1 protein was confirmed to specifically bind to CCNE1-CDK2-CDK1 to arrest G2/M phase. Notably, PAFAH1B1 appeared to hinder the development of follicles. Furthermore, the demethylation significantly promoted the transcription activity and chromatin accessibility of CpG island (-7 bp to +170 bp) of PAFAH1B1. Taken together, PAFAH1B1 physically interacted with the CCNE1-CDK2-CDK1 complex to arrest G2/M phase and inhibit the GCs proliferation and follicular development. Additionally, demethylation of CpG island significantly promoted the transcription of PAFAH1B1. CONCLUSION: These findings not only advance understanding of cell proliferation and cycle regulation but also identify PAFAH1B1 as a candidate gene for further investigation in follicular development.

CCNE1-CDK2-CDK1 complex↗

PubMed2026

Emergence of cefiderocol resistance in carbapenem-resistant Escherichia coli ST167 prior to clinical use: A multifactored resistance landscape.

OBJECTIVES: Cefiderocol is a novel siderophore cephalosporin with potent activity against multidrug-resistant Gram-negative bacteria. Here, we reported the prevalence and mechanisms of cefiderocol resistance in carbapenem-resistant Escherichia coli (CREC) in China before its clinical use. METHODS: A total of 443 non-duplicate CREC isolates collected from 67 hospitals in China (2013-2021) underwent antimicrobial susceptibility testing according to CLSI guidelines. Whole-genome sequencing, transcriptomic analysis, siderophore quantification, and targeted genetic manipulation were performed to investigate the underlying resistance mechanisms. RESULTS: Among the 443 CREC isolates, 102 (23.0%) were resistant to cefiderocol, and 34 (7.6%) showed intermediate susceptibility. Multivariable logistic regression identified ST167 lineage (OR, 3.05; 95% CI, 1.12-8.29; P = 0.028), blaNDM-5 carriage (OR, 9.04; 95% CI, 2.96-27.57; P < 0.001), and cirA truncation (OR, 49.56; 95% CI, 20.33-120.79; P < 0.001) as independent factors associated with cefiderocol resistance. Among ST167 isolates, cefiderocol-resistant isolates showed increased yersiniabactin carriage and siderophore production but comparable TonB-dependent transporter expression profiles. Phylogenetic analysis revealed that cefiderocol-resistant ST167 isolates clustered into a distinct subclade enriched with resistance-associated determinants, including a recurrent FhuA P50S substitution detected in 59/64 (92.2%) resistant isolates. Functional assays showed that the P50S substitution increased cefiderocol minimum inhibitory concentration (0.032-0.125 µg/mL), particularly in an NDM-5-producing background (0.032-0.5 µg/mL). CONCLUSIONS: Cefiderocol resistance is highly prevalent among high-risk ST167 CREC isolates before the clinical introduction of cefiderocol in China, highlighting the need for continued surveillance of this epidemic lineage. Cefiderocol resistance is mediated by multiple resistance determinants, and we identify the recurrent FhuA P50S substitution as a novel contributor to reduced cefiderocol susceptibility.

Antimicrobial resistance↗

PubMed2006

Synchronizing a multicellular system by external input: an artificial control strategy.

MOTIVATION: Although there are significant advances on elucidating the collective behaviors on biological organisms in recent years, the essential mechanisms by which the collective rhythms arise remain to be fully understood, and further how to synchronize multicellular networks by artificial control strategy has not yet been well explored. RESULTS: A control strategy is developed to synchronize gene regulatory networks in a multicellular system when spontaneous synchronization cannot be achieved. We first construct an impulsive control system to model the process of periodically injecting coupling substances with constant or random impulsive control amounts into the common extracellular medium, and further study its effects on the dynamics of individual cells. We derive the threshold of synchronization induced by the periodic substance input. Therefore, we can synchronize the multicellular network to a specific collective behavior by changing the frequency and amplitude of the periodic stimuli. Moreover, a two-stage scheme is proposed to facilitate the synchronization in this paper. We show that the presence of the external input may also initiate different dynamics. The multicellular network of coupled repressilators is used to show the effectiveness of the proposed method. The results not only provide a perspective to understand the interactions between external stimuli and intrinsic physiological rhythms, but also may lead to development of realistic artificial control strategy and medical therapy. AVAILABILITY CONTACT: aihara@sat.t.u-tokyo.ac.jp.

Animals↗

PubMed2006

Construction of genetic oscillators with interlocked feedback networks.

To understand how a gene regulatory network functioning as an oscillator is built, a precise mathematical description of the network and its dynamical properties are developed in this paper. Our approach is based on analyzing the effect of interactions between smaller subnetworks with simple dynamics. We relate an oscillatory behavior of the network to the destabilization phenomenon of a steady state caused by the interactions in a simple discrete map. When source of the instability of the steady state rather than the oscillatory behavior itself is considered, linear stability analysis and feedback control theory can be employed. Moreover, the amplitudes robust against change in delay can also be obtained from the discrete map. The main ideas are illustrated by constructing a genetic oscillator termed a "repressilator" and analyzing the occurrence of cellular rhythms, although the theoretical results hold for a general class of biological systems. The method can be directly applied to design, construct genetic oscillators, and further control their dynamics, even for large-scale networks.

Animals↗

PubMed2005

Excitation functions of coupling.

The responses of nonlinear dynamics of two classes to coupling are investigated. It is shown both analytically and numerically that coupling has an excitation ability in a network of the linearly coupled systems. That is, when an uncoupled system is degenerated to a stable steady state from a limit cycle but in the "marginal" state due to the system parameter, an appropriate coupling strength can excite the limit cycle such that the coupled systems exhibit synchronous oscillation; when the uncoupled system is in a stable limit cycle but close to a chaotic attractor, a certain coupling strength can induce the chaotic attractor such that the coupled systems reach chaotic synchronization. Such excitation functions of coupling are different from its traditional role where coupling mainly synchronizes the coupled systems with the original dynamics of the uncoupled system.

Journal Article↗

PubMed2005

Noise-induced cooperative behavior in a multicell system.

MOTIVATION: All cell components exhibit intracellular noise on account of random births and deaths of individual molecules, and extracellular noise because of environment perturbations. Gene regulation in particular, is an inherently noisy process with transcriptional control, alternative splicing, translation, diffusion and chemical modification reactions, all of which involve stochastic fluctuations. Such stochastic noises may not only affect the dynamics of the entire system but may also be exploited by living organisms to actively facilitate certain functions, such as cooperative behavior and communication. RESULTS: We have provided a general model and an analytic tool to examine the cooperative behavior of a multicell system with both intracellular and extracellular stochastic fluctuations. A multicell system with a synthetic gene network is adopted to demonstrate the effects of noises and coupling on collective dynamics. These results establish not only a theoretical foundation but also a quantitative basis for understanding essential roles of noises on cooperative dynamics, such as synchronization and communication among cells.

Adaptation, Physiological↗

PubMed2005

Modelling periodic oscillation in gene regulatory networks by cyclic feedback systems.

In this paper, we develop a new methodology to analyze and design periodic oscillators of biological networks, in particular gene regulatory networks with multiple genes, proteins and time delays, by using negative cyclic feedback systems. We show that negative cyclic feedback networks have no stable equilibria but stable periodic orbits when certain conditions are satisfied. Specifically, we first prove the basic properties of the biological networks composed of cyclic feedback loops, and then extend our results to general cyclic feedback network with less restriction, thereby making our theoretical analysis and design of oscillators easy to implement, even for large-scale systems. Finally, we use one circadian network formed by a period protein (PER) and per mRNA, and one biologically plausible synthetic gene network, to demonstrate the theoretical results. Since there is less restriction on the network structure, the results of this paper can be expected to apply to a wide variety of areas on modelling, analyzing and designing of biological systems.

Animals↗

PubMed2005

Synchronizing genetic oscillators by signaling molecules.

The authors examine collective rhythms in a general multicell system with both linearly diffusive and nondiffusive couplings. The effect of coupling on synchronization through intercellular signaling in a population of Escherichia coli cells is studied. In particular, a synchronization solution is given through the auxiliary individual system for 2 types of couplings. The sufficient conditions for the global synchronization of such a coupled system are derived based on the Lyapunov function method. The authors show that an appropriate design of the coupling and the inner-linking matrix can ensure global synchronization of the coupled synthetic biological system. Moreover, they demonstrate that the dynamics of an individual cell with coupling and without coupling may be qualitatively different; one is oscillatory, and the other is steady state. The change from a nonoscillatory state to an oscillatory one is induced by appropriate coupling, which also entrains all cells to synchronization. These results establish not only a theoretical foundation but also a quantitative basis for understanding the essential cooperative dynamics, such as collective rhythms or synchronization, in a population of cells.

Algorithms↗

PubMed2005

Comparison of protein structures by multi-objective optimization.

We propose a novel method for solving the structure comparison problem for proteins, based on a decomposition technique. We define the structure alignment as a multi-objective optimization problem with both discrete and continuous variables, i.e., maximizing the number of aligned atoms and minimizing their root mean square distance. By controlling a single distance-related parameter, theoretically we can obtain a variety of optimal alignments corresponding to different optimal matching patterns, i.e., from a large matching portion to a small portion. The number of variables in our algorithm increases with the number of atoms of protein pairs in almost a linear manner. The software is available upon request, or from http://zhangroup.aporc.org/bioinfo/samo/.

Algorithms↗

PubMed2004

Dynamics of gene regulatory networks with cell division cycle.

This paper focuses on modeling and analyzing the nonlinear dynamics of gene regulatory networks with the consideration of a cell division cycle with duplication process of DNA, in particular for switches and oscillators of synthetic networks. We derive two models that may correspond to the eukaryotic and prokaryotic cells, respectively. A biologically plausible three-gene model ( lac, tetR, and cI ) and a repressilator as switch and oscillator examples are used to illustrate our theoretical results. We show that the cell cycle may play a significant role in gene regulation due to the nonlinear dynamics of a gene regulatory network although gene expressions are usually tightly controlled by transcriptional factors.

Animals↗

PubMed2004

[Clinical examination of mizolastine in the seasonal allergic rhinitis].

OBJECTIVE: An open randomized comparative study versus loratadine was conducted in order to examine the efficacy and safety of mizolastine in the treatment of seasonal allergic rhinitis (SAR). METHOD: Six-seven adult patients completed mizolastine 10 mg (34/67) and loratadine 10 mg (33/67) once daily for 14 days. Other 5 patients withdrew or dropped out from the trial. RESULT: All symptom score decreased significantly after treatment in both groups. Efficacy assessment based on symptom score reducing index showed that the efficacy of Mizolastine was 82.4%, and the excellent rate was 20.6%, while the efficacy of Loratadine was 66.7%, and the excellent rate was 6.1%. No serious adverse events were reported in the two groups. The incidences of adverse drug reactions (ADRs) of Mizolastine and Loratadine were 38.2% and 33.3% respectively. The mild or moderate drowsiness and dry mouth in Mizolastine group were 26.5% and 8.8% respectively, and in Loratadine group they were 18.2% and 9.0%. There were no significant changes in laboratory examinations including blood and urine routine tests, liver and renal functions and ECG. CONCLUSION: Mizolastine is effective in relieving SAR symptoms. The efficacy and ADR of mizolastine is similar to Loratadine in the treatment of SAR.

Adolescent↗

PubMed2004

Intercellular communications induced by random fluctuations.

This paper investigates a general coupled noisy system for a cell-cell communication in a multi-cell system. The main conclusion is that appropriate noise intensity and coupling strength are capable of driving the coupled system to synchrony, which may be exploited by biological organisms to actively facilitate mutual communication. A multi-cell system with a synthetic gene network with both noises and delays is adopted to demonstrate the effect of noises on cellular communication.

Adaptation, Physiological↗