"Weibing" is a fundamental concept in traditional Chinese medicine (TCM), representing a transitional state characterized by diminished self-regulatory abilities without overt physiological or social dysfunction. This perspective delves into the biological foundations and quantifiable markers of Weibing, aiming to establish a research framework for early disease intervention. Here, we propose the "Health Quadrant Classification" system, which divides the state of human body into health, sub-health, disease-susceptible state, and disease. We suggest the disease-susceptible stage emerges as a pivotal point for TCM interventions. To understand the intrinsic dynamics of this state, we propose laboratory and clinical studies utilizing time-series experiments and stress-induced disease susceptibility models. At the molecular level, bio-omics technologies and bioinformatics approaches are highlighted for uncovering intricate changes during disease progression. Furthermore, we discuss the application of mathematical models and artificial intelligence in developing early warning systems to anticipate and avert the transition from health to disease. This approach resonates with TCM's preventive philosophy, emphasizing proactive health maintenance and disease prevention. Ultimately, our perspective underscores the significance of integrating modern scientific methodologies with TCM principles to propel Weibing research and early intervention strategies forward.

Effective annotation of in vivo drug metabolites using liquid chromatography-mass spectrometry (LC-MS) remains a formidable challenge. Herein, a metabolic reaction-based molecular networking (MRMN) strategy is introduced, which enables the "one-pot" discovery of prototype drugs and their metabolites. MRMN constructs networks by matching metabolic reactions and evaluating MS² spectral similarity, incorporating innovations and improvements in feature degradation of MS² spectra, exclusion of endogenous interference, and recognition of redundant nodes. A minimum 75% correlation between structural similarity and MS² similarity of neighboring metabolites was ensured, mitigating false negatives due to spectral feature degradation. At least 79% of nodes, 49% of edges, and 97% of subnetworks were reduced by an exclusion strategy of endogenous ions compared to the Global Natural Products Social Molecular Networking (GNPS) platform. Furthermore, an approach of redundant ions identification was refined, achieving a 10%-40% recognition rate across different samples. The effectiveness of MRMN was validated through a single compound, plant extract, and mixtures of multiple plant extracts. Notably, MRMN is freely accessible online at https://yaolab.network, broadening its applications.

Organic carbonates (OCs) are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups. They exist in either linear or cyclic forms, of which the majority encountered in nature adopt a pentacyclic structure. However, the enzymatic basis for pentacyclic carbonate ring formation remains elusive. Here, we reported that a four-protein metabolon (AlmUII-UV) assembled by a small peptide protein (AlmUV) appends a reactive

Fusidane-type antibiotics, represented by helvolic acid, fusidic acid and cephalosporin P

A chemical investigation on

Accelerated forgetting has been identified as a feature of Alzheimer's disease (AD), but the therapeutic efficacy of the manipulation of biological mechanisms of forgetting has not been assessed in AD animal models. Ras-related C3 botulinum toxin substrate 1 (Rac1), a small GTPase, has been shown to regulate active forgetting in Drosophila and mice. Here, we showed that Rac1 activity is aberrantly elevated in the hippocampal tissues of AD patients and AD animal models. Moreover, amyloid-beta 42 could induce Rac1 activation in cultured cells. The elevation of Rac1 activity not only accelerated 6-hour spatial memory decay in 3-month-old APP/PS1 mice, but also significantly contributed to severe memory loss in aged APP/PS1 mice. A similar age-dependent Rac1 activity-based memory loss was also observed in an AD fly model. Moreover, inhibition of Rac1 activity could ameliorate cognitive defects and synaptic plasticity in AD animal models. Finally, two novel compounds, identified through behavioral screening of a randomly selected pool of brain permeable small molecules for their positive effect in rescuing memory loss in both fly and mouse models, were found to be capable of inhibiting Rac1 activity. Thus, multiple lines of evidence corroborate in supporting the idea that inhibition of Rac1 activity is effective for treating AD-related memory loss.

In order to study the influence of tympanic membrane lesion and ossicular erosion caused by otitis media on the hearing compensation performance of round-window stimulation, a human ear finite element model including cochlear asymmetric structure was established by computed tomography (CT) technique and reverse engineering technique. The reliability of the model was verified by comparing with the published experimental data. Based on this model, the tympanic membrane lesion and ossicular erosion caused by otitis media were simulated by changing the corresponding tissue structure. Besides, these simulated diseases' effects on the round-window stimulation were studied by comparing the corresponding basilar-membrane's displacement at the frequency-dependent characteristic position. The results show that the thickening and the hardening of the tympanic membrane mainly deteriorated the hearing compensation performance of round-window stimulation in the low frequency; tympanic membrane perforation and the minor erosion of ossicle with ossicular chain connected slightly effected the hearing compensation performance of round-window stimulation. Whereas, different from the influence of the aforementioned lesions, the ossicular erosion involving the ossicular chain detachment increased its influence on performance of round-window stimulation at the low frequency. Therefore, the effect of otitis media on the hearing compensation performance of round-window stimulation should be considered comprehensively when designing its actuator, especially the low-frequency deterioration caused by the thickening and the hardening of the tympanic membrane; the actuator's low-frequency output should be enhanced accordingly to ensure its postoperative hearing compensation performance.
Acoustic Stimulation ; Ear Ossicles ; pathology ; Finite Element Analysis ; Hearing ; Humans ; Otitis Media ; physiopathology ; Reproducibility of Results ; Round Window, Ear ; physiology ; Tomography, X-Ray Computed ; Tympanic Membrane Perforation

Fusidic acid is the only fusidane-type antibiotic that has been clinically used. However, biosynthesis of this important molecule in fungi is poorly understood. We have recently elucidated the biosynthesis of fusidane-type antibiotic helvolic acid, which provides us with clues to identify a possible gene cluster for fusidic acid ( cluster). This gene cluster consists of eight genes, among which six are conserved in the helvolic acid gene cluster except and . Introduction of the two genes into the NSAR1 expressing the conserved six genes led to the production of fusidic acid. A stepwise introduction of and revealed that the two genes worked independently without a strict reaction order. Notably, we identified two short-chain dehydrogenase/reductase genes and in the cluster, which showed converse stereoselectivity in 3-ketoreduction. This is the first report on the biosynthesis and heterologous expression of fusidic acid.

Four interesting sequoiatones stereoisomers (-) were isolated from a wetland soil-derived fungusby chiral HPLC. On the basis of comprehensive NMR and mass analyses, their planar structures were elucidated as the same as that of sequoiatone B. Among them,and(orand) were a pair of enantiomers, andand(orand) were a pair of stereoisomers with epimerization at C-12, which indicated that sequoiatione-type metabolites exist as enantiomers rather than as optically pure compounds in some strains. With the quantum chemical ECD calculations, the absolute configurations of C-8 in-were determined, which is the first report to establish the absolute configuration of C-8 in sequoiatones. However, the absolute configurations of C-12 in sequoiatones are still unsolved.

Objective To explore the formation process of vacuum pressure differential of micro power negative pressure technology to facilitate its clinical application.MethodsThe formation of negative pressure differential and changes of negative pressure values in enclosure space were studied which was formed by liquid aspiration after the compressive polyvinyl alcohol foam material was enclosed.Micro power negative pressure technology was applied to the treatment of the right ear necrosis patient after focal cleaning,and the efficacy was observed.Results Medical adhesive film was raised gradually during the expansion of polyvinyl alcohol foam due to liquid aspiration,and then the enclosure space extended increasingly to form local vacuum negative pressure.The range of maximal negative pressure was between-110 and-200 Pa,and the mean maximal negative pressure value was-132.7 Pa.Micro power negative pressure technology behaved well in healing the wound.Conclusion Micro power negative pressure technology gains advantages in reliability and easy operation over other technologies and products,and may be a new choice for healing of refractory wounds.