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Dynamic protein structures are crucial for deciphering their diverse biological functions. Two-dimensional infrared (2DIR) spectroscopy stands as an ideal tool for tracing rapid conformational evolutions in proteins. However, linking spectral characteristics to dynamic structures poses a formidable challenge. Here, we present a pretrained machine learning model based on 2DIR spectra analysis. This model has learned signal features from approximately 204,300 spectra to establish a spectrum-structure correlation, thereby tracing the dynamic conformations of proteins. It excels in accurately predicting the dynamic content changes of various secondary structures and demonstrates universal transferability on real folding trajectories spanning timescales from microseconds to milliseconds. Beyond exceptional predictive performance, the model offers attention-based spectral explanations of dynamic conformational changes. Our 2DIR-based pretrained model is anticipated to provide unique insights into the dynamic structural information of proteins in their native environments.

Thoracic aortic dissection (TAD) is a life-threatening vascular disease manifested as intramural bleeding in the medial layers of the thoracic aorta. The key histopathologic feature of TAD is medial degeneration, characterized by depletion of vascular smooth muscle cells (VSMCs) and degradation of extracellular matrix (ECM). MicroRNA, as essential epigenetic regulators, can inhibit the protein expression of target genes without modifying the sequences. This study aimed to elucidate the role and underlying mechanism of miR-20a, a member of the miR-17-92 cluster, in regulating ECM degradation during the pathogenesis of TAD. The expression of the miR-17-92 cluster was significantly increased in synthetic VSMCs derived from TAD lesions compared to contractile VSMCs isolated from normal thoracic aortas. Notably, the expression of miR-20a was increased in VSMCs in response to serum exposure and various stimuli. In TAD lesions, the expression of miR-20a was significantly negatively correlated with that of elastin. Elevated expression of miR-20a was also observed in thoracic aortas of TAD mice induced by β-aminopropionitrile fumarate and angiotensin II. Overexpression of miR-20a via mimic transfection enhanced the growth and invasive capabilities of VSMCs, with no significant impact on their migratory activity or the expression of phenotypic markers (α-SMA, SM22, and OPN). Silencing of miR-20a with inhibitor transfection mitigated the hyperactivation of MMP2 in VSMCs stimulated by PDGF-bb, as evidenced by reduced levels of active-MMP2 and increased levels of pro-MMP2. Subsequently, TIMP2 was identified as a novel target gene of miR-20a. The role of miR-20a in promoting the activation of MMP2 was mediated by the suppression of TIMP2 expression in VSMCs. In addition, the elevated expression of miR-20a was found to be directly driven by Nanog in VSMCs. Collectively, these findings indicate that miR-20a plays a crucial role in maintaining the homeostasis of the thoracic aortic wall during TAD pathogenesis and may represent a potential therapeutic target for TAD.

In this report, we describe combined polymorphisms of the UGT1A9, UGT1A7 and UGT1A1 genes in 100 unrelated, healthy Chinese Han subjects. The functional regions of these genes were sequenced and comprehensively analyzed for genetic polymorphisms. Thirty variants were detected, including five novel forms. Tentative functional predictions indicated that a Cys → Arg substitution at position 277 in the UGT1A7 gene could alter the protein conformation and that 12460T > G in the 3'UTR might influence protein translation through specifically expressed miRNAs. UGT1A9*1b was a major functional variant in the subjects examined whereas the *1f allele had a frequency of only 0.5%. A special functional haplotype (GAGAAC) was identified for UGT1A9, 1A7 and 1A1. These findings provide fundamental genetic information that may serve as a basis for larger studies designed to assess the metabolic phenotypes associated with UGT1A polymorphisms. They also provide important data for the implementation of personalized medicine in Chinese Han.

Akkermansia muciniphila (Akk) is an important probiotic that can help alleviate metabolic disorders. Recent research indicates that pasteurized Akkermansia muciniphila (P-Akk) is even more effective. To investigate the effect of P-Akk on improving lipid metabolism disorders caused by a high-fat diet (HFD) in fish, zebrafish were fed two HFDs containing 0 (HFD group, as control) and 1 × 109 CFU/g P-Akk (P-Akk group) for 28 days. The addition of P-Akk significantly decreased the number of lipid droplets in the liver and improved the mitochondrial structure in the intestine, while also altering gene expression related to lipid metabolism in HFD-fed zebrafish. Furthermore, intestinal transcriptomic network analysis and results from primary intestinal cells indicated that P-Akk may enhance mitochondrial function by activating the AMPK/PGC1α pathway. Although P-Akk did not significantly alter the composition of the gut microbiota, it did increase the steady-state index of intestinal microbiota. Moreover, P-Akk upregulated the abundance of beneficial probiotics, (Plesiomonas, Cetobacterium, and Bacillus), while downregulating the abundance of pathogens (Aeromonas, Pseudomonas, Acinetobacter, and Streptococcus). Collectively, these findings indicate that P-Akk has the potential to serve as a green and safe feed additive for improving HFD-induced lipid metabolism disorders in fish.

It has been proven that robot-assisted rehabilitation training can effectively promote the recovery of upper-limb motor function in post-stroke patients. Increasing patients’ active participation by providing assist-as-needed (AAN) control strategies is key to the effectiveness of robot-assisted rehabilitation training. In this paper, a greedy assist-as-needed (GAAN) controller based on radial basis function (RBF) network combined with 3 degrees of freedom (3-DOF) potential constraints was proposed to provide AAN interactive forces of an end-effect upper limb rehabilitation robot. The proposed 3-DOF potential fields were adopted to constrain the tangential motions of three kinds of typical target trajectories (one-dimensional (1D) lines, two-dimensional (2D) curves and three-dimensional (3D) spirals) while the GAAN controller was designed to estimate the motor capability of a subject and provide appropriate robot-assisted forces. The co-simulation (Adams-Matlab/Simulink) experiments and behavioral experiments on 10 healthy volunteers were conducted to validate the utility of the GAAN controller. The experimental results demonstrated that the GAAN controller combined with 3-DOF potential field constraints enabled the subjects to actively participate in kinds of tracking tasks while keeping acceptable tracking accuracies. 3D spirals could be better in stimulating subjects’ active participation when compared to 1D and 2D target trajectories. The current GAAN controller has the potential to be applied to existing commercial upper limb rehabilitation robots.

Abstract Existential state of solutes substantially affects the efficiency and direction of various chemical and biological processes, about which current consensus is still limited at macro and micro levels. At the trace level, solutes assume a pivotal role across a spectrum of critical fields. However, their existential states, especially at interfaces, remain largely elusive. Herein, an exceptional evolution of solute molecules is unveiled from micro to trace, solution to interface, with the aid of surface‐enhanced Raman spectroscopy, extinction, DLS and theoretical simulations. Given predominant existence of monomers within the solution, these aggregates dominate the interfacial behavior of solute molecules. Moreover, a universal, aggregate‐controlled mechanism is demonstrated that aggregates triggered by cosolvent, which can dramatically promote efficiency of catalytic reactions. The results provide novel insights into the interaction mechanisms between reactants and catalysts, potentially offering fresh perspectives for the manipulation of multiphase catalysis and related biological processes.