Computational modeling of cotranscriptional RNA folding.

An RNA folds as it is transcribed. RNA folding during transcription differs fundamentally from thermodynamic folding. While thermodynamic folding reaches an equilibrium ensemble of structures, cotranscriptional folding is a kinetic process where the RNA structure evolves as the chain elongates during transcription.

Co-transcriptional folding orchestrates sequential multi-effector sensing by a glycine tandem riboswitch.

Riboswitches are non-coding RNA motifs that regulate gene expression in response to ligand binding. The glycine tandem riboswitch (GTR) is notable because it comprises two distinct glycine aptamers that interact extensively. These inter-aptamer contacts drive conformational changes in the downstream expression platform to control gene expression.

Enhancing RNA 3D Structure Prediction in CASP16: Integrating Physics-Based Modeling With Machine Learning for Improved Predictions.

During the 16th Critical Assessment of Structure Prediction (CASP16), the Vfold team participated in the two RNA categories: RNA Monomers and RNA Multimers. The Vfold RNA structure prediction method is hierarchical and hybrid, incorporating physics-based models (Vfold2D and VfoldMCPX) for 2D structure prediction, template-based and molecular dynamics simulation-based models (Vfold-Pipeline, IsRNA and RNAJP) for 3D structure prediction. Additionally, Vfold integrates knowledge from templates and the state-of-the-art machine learning model AlphaFold3 into our physics-based models.

[Effect of the sequence of intermediate instrumentation and distraction-reduction of the injured vertebra on the treatment of thoracolumbar burst fractures with high rate of spinal canal encroachment].

Objective: To investigate the effect of the sequence of intermediate instrumentation and distraction-reduction of the injured vertebra on the surgical efficacy of short-segment percutaneous pedicle screw fixation for thoracolumbar burst fractures with high rate of spinal canal encroachment.

Methods: From January 2016 to January 2022, 38 patients with thoracolumbar burst fractures with high rate of spinal canal encroachment (spinal canal encroachment rate >40%, complete posterior longitudinal ligament, no flipping bone block in the posterior marginal of the vertebra) without spinal cord injury who were were treated with short-segment percutaneous pedicle screw fixation were retrospectively analyzed. During the operation, 18 cases were used distraction-reduction first and then intermediate instrumentation on injured vertebral and sequential distraction-reduction again(the distraction-reduction first group) including 8 females and 10 males with a mean age of 46.

Harnessing Computational Approaches for RNA-Targeted Drug Discovery.

RNA molecules have emerged as promising therapeutic targets due to their diverse functional and regulatory roles within cells. Computational modeling in RNA-targeted drug discovery presents a significant opportunity to expedite the discovery of novel small molecule compounds. However, this field encounters unique challenges compared to protein-targeted drug design, primarily due to limited experimental data availability and current models' inability to adequately address RNA's conformational flexibility during ligand recognition.

Plant exudates-driven microbiome recruitment and assembly facilitates plant health management.

Plant-microbiome symbiotic interactions play a crucial role in regulating plant health and productivity. To establish symbiotic relationships, the plant secretes a variety of substances to facilitate microbial community recruitment and assembly. In recent years, important progress has been made in studying how plant exudates attract beneficial microorganisms and regulate plant health.

Circulatory CCL2 distinguishes Duchenne muscular dystrophy dogs.

To establish a minimally invasive approach to studying body-wide muscle inflammation in the canine Duchenne muscular dystrophy (DMD) model, we evaluated 13 cytokines/chemokines in frozen sera from 90 affected (239 sera) and 73 normal (189 sera) dogs (0.00 to 45.2 months of age).

Proton-Conducting Hydrogen-Bonded Framework of a Cobalt(II) Single-Ion Magnet Sulfonate.

Diamagnetic metal sulfonates have been widely reported, while paramagnetic species are very rare, especially those that exhibit interesting magnetic and/or proton conduction properties. Herein, we report the synthesis, structure, magnetic, and proton-conducting properties of a hydrogen-bonded cobalt(II) organosulfonate complex. The coordination self-assembly of Co salts and 8-quinolinesulfonic acid ligands affords a mononuclear Co sulfonate featuring both coordinated and noncoordinated sulfonic acid O atoms and axial coordinated water molecules.

mRNA vaccine sequence and structure design and optimization: Advances and challenges.

Messenger RNA (mRNA) vaccines have emerged as a powerful tool against communicable diseases and cancers, as demonstrated by their huge success during the coronavirus disease 2019 (COVID-19) pandemic. Despite the outstanding achievements, mRNA vaccines still face challenges such as stringent storage requirements, insufficient antigen expression, and unexpected immune responses. Since the intrinsic properties of mRNA molecules significantly impact vaccine performance, optimizing mRNA design is crucial in preclinical development.

smFRET-assisted RNA structure prediction.

Single-molecule Förster Resonance Energy Transfer (smFRET) is a powerful biophysical technique that utilizes the distance-dependent energy transfer between donor and acceptor dyes linked to individual molecules, providing insights into molecular conformational changes and interactions at the single-molecule level. Prior investigations leveraged smFRET to study the conformational dynamics of single truncated Ubc4 pre-mRNA molecules during splicing, yet these efforts did not prioritize structural modeling. In this study, we develop an smFRET-assisted RNA prediction method to predict the 2D and 3D structures of this pre-mRNA.

SPRank─A Knowledge-Based Scoring Function for RNA-Ligand Pose Prediction and Virtual Screening.

The growing interest in RNA-targeted drugs underscores the need for computational modeling of interactions between RNA molecules and small compounds. Having a reliable scoring function for RNA-ligand interactions is essential for effective computational drug screening. An ideal scoring function should not only predict the native pose for ligand binding but also rank the affinity of the binding for different ligands.

Efficacy and safety of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer: a retrospective analysis.

Objective: This retrospective analysis aimed to evaluate the efficacy and adverse reactions of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer (NSCLC).

Methods: NSCLC patients undergoing metronomic oral vinorelbine as second- and later-line regimens in Fujian Cancer Hospital from October 2018 to October 2022 were enrolled, and patients' demographic and clinical characteristics were collected. The efficacy and safety of metronomic oral vinorelbine monotherapy and its combination therapy regimens were compared.

Cracking the Code: Enhancing Molecular Tools for Progress in Nanobiotechnology.

Nature continually refines its processes for optimal efficiency, especially within biological systems. This article explores the collaborative efforts of researchers worldwide, aiming to mimic nature's efficiency by developing smarter and more effective nanoscale technologies and biomaterials. Recent advancements highlight progress and prospects in leveraging engineered nucleic acids and proteins for specific tasks, drawing inspiration from natural functions.

Kinetic pathway of HIV-1 TAR cotranscriptional folding.

The Trans-Activator Receptor (TAR) RNA, located at the 5'-end untranslated region (5' UTR) of the human immunodeficiency virus type 1 (HIV-1), is pivotal in the virus's life cycle. As the initial functional domain, it folds during the transcription of viral mRNA. Although TAR's role in recruiting the Tat protein for trans-activation is established, the detailed kinetic mechanisms at play during early transcription, especially at points of temporary transcriptional pausing, remain elusive.

SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors.

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression. However, the precise molecular mechanisms governing the nuclear import of YAP are not fully understood. In this study, we have uncovered a crucial role of SOX9 in the activation of YAP.

Propagation of a rapid cell-to-cell HO signal over long distances in a monolayer of cardiomyocyte cells.

Cell-to-cell communication plays a cardinal role in the biology of multicellular organisms. HO is an important cell-to-cell signaling molecule involved in the response of mammalian cells to wounding and other stimuli. We previously identified a signaling pathway that transmits wound-induced cell-to-cell HO signals within minutes over long distances, measured in centimeters, in a monolayer of cardiomyocytes.

Machine learning in RNA structure prediction: Advances and challenges.

RNA molecules play a crucial role in various biological processes, with their functionality closely tied to their structures. The remarkable advancements in machine learning techniques for protein structure prediction have shown promise in the field of RNA structure prediction. In this perspective, we discuss the advances and challenges encountered in constructing machine learning-based models for RNA structure prediction.

Propagation of a rapid cell-to-cell H O signal over long distances in a monolayer of cardiomyocyte cells.

Unlabelled: Cell-to-cell communication plays a cardinal role in the biology of multicellular organisms. H O is an important cell-to-cell signaling molecule involved in the response of mammalian cells to wounding and other stimuli. We previously identified a signaling pathway that transmits wound-induced cell-to-cell H O signals within minutes over long distances, measured in centimeters, in a monolayer of cardiomyocytes.

Advancing RNA 3D structure prediction: Exploring hierarchical and hybrid approaches in CASP15.

In CASP15, we used an integrated hierarchical and hybrid approach to predict RNA structures. The approach involves three steps. First, with the use of physics-based methods, Vfold2D-MC and VfoldMCPX, we predict the 2D structures from the sequence.

RNAJP: enhanced RNA 3D structure predictions with non-canonical interactions and global topology sampling.

RNA 3D structures are critical for understanding their functions. However, only a limited number of RNA structures have been experimentally solved, so computational prediction methods are highly desirable. Nevertheless, accurate prediction of RNA 3D structures, especially those containing multiway junctions, remains a significant challenge, mainly due to the complicated non-canonical base pairing and stacking interactions in the junction loops and the possible long-range interactions between loop structures.