SIDERITE: Unveiling hidden siderophore diversity in the chemical space through digital exploration.

In this work, we introduced a siderophore information database (SIDERTE), a digitized siderophore information database containing 649 unique structures. Leveraging this digitalized data set, we gained a systematic overview of siderophores by their clustering patterns in the chemical space. Building upon this, we developed a functional group-based method for predicting new iron-binding molecules with experimental validation. Expanding our approach to the collection of open natural products (COCONUT) database, we predicted a staggering 3199 siderophore candidates, showcasing remarkable structure diversity that is largely unexplored. Our study provides a valuable resource for accelerating the discovery of novel iron-binding molecules and advancing our understanding of siderophores.

Siderophore-mediated iron partition promotes dynamical coexistence between cooperators and cheaters.

Microbes shape their habitats by consuming resources and producing a diverse array of chemicals that can serve as public goods. Despite the risk of exploitation by cheaters, genes encoding sharable molecules like siderophores are widely found in nature, prompting investigations into the mechanisms that allow producers to resist invasion by cheaters. In this work, we presented the chemostat-typed "resource partition model" to demonstrate that dividing the iron resource between private and public siderophores can promote stable or dynamic coexistence between producers and cheaters in a well-mixed environment. Moreover, our analysis shows that when microbes not only consume but also produce resources, chemical innovation leads to stability criteria that differ from those of classical consumer resource models, resulting in more complex dynamics. Our work sheds light on the role of chemical innovations in microbial communities and the potential for resource partition to facilitate dynamical coexistence between cooperative and cheating organisms.

A 3D Scalable Chamber-Array Chip for Digital LAMP.

As an absolute quantification method at the single-molecule level, digital PCR (dPCR) offers the highest accuracy. In this work, we developed a 3D scalable chamber-array chip that multiplied the number of partitions by stacking chamber-array layers and realized digital loop-mediated isothermal amplification to quantify DNA molecules. It greatly increases the number of partitions to improve the performance of dPCR without increasing the chip size, the operation workflow complicity, and operation time. For the three-chamber-array-layer chip which contains 200,000 reactors of a 0.125 nL volume, it has been proved that the reagent filling and partition were finished within 3 min, and the whole detection could be finished within 1 h. The method demonstrated that it could be scalable to a six-chamber-array layer, which contains 400,000 reactors without increasing the size of the chip and the complication of filling/partition workflow but only takes an additional hour for scanning. Due to its potential for high throughput, low cost, and simple operation, our device may significantly expand the clinical application range of dPCR.

Dual-omics reveals temporal differences in acute sympathetic stress-induced cardiac inflammation following α1 and ß-adrenergic receptors activation.

Sympathetic stress is prevalent in cardiovascular diseases. Sympathetic overactivation under strong acute stresses triggers acute cardiovascular events including myocardial infarction (MI), sudden cardiac death, and stress cardiomyopathy. α1-ARs and ß-ARs, two dominant subtypes of adrenergic receptors in the heart, play a significant role in the physiological and pathologic regulation of these processes. However, little is known about the functional similarities and differences between α1- and ß-ARs activated temporal responses in stress-induced cardiac pathology. In this work, we systematically compared the cardiac temporal genome-wide profiles of acute α1-AR and ß-AR activation in the mice model by integrating transcriptome and proteome. We found that α1- and ß-AR activations induced sustained and transient inflammatory gene expression, respectively. Particularly, the overactivation of α1-AR but not ß-AR led to neutrophil infiltration at one day, which was closely associated with the up-regulation of chemokines, activation of NF-κB pathway, and sustained inflammatory response. Furthermore, there are more metabolic disorders under α1-AR overactivation compared with ß-AR overactivation. These findings provide a new therapeutic strategy that, besides using ß-blocker as soon as possible, blocking α1-AR within one day should also be considered in the treatment of acute stress-associated cardiovascular diseases.

A zero-sum game or an interactive frame? Iron competition between bacteria and humans in infection war.

ABSTRACT: Iron is an essential trace element for both humans and bacteria. It plays a vital role in life, such as in redox reactions and electron transport. Strict regulatory mechanisms are necessary to maintain iron homeostasis because both excess and insufficient iron are harmful to life. Competition for iron is a war between humans and bacteria. To grow, reproduce, colonize, and successfully cause infection, pathogens have evolved various mechanisms for iron uptake from humans, principally Fe 3+ -siderophore and Fe 2+ -heme transport systems. Humans have many innate immune mechanisms that regulate the distribution of iron and inhibit bacterial iron uptake to help resist bacterial invasion and colonization. Meanwhile, researchers have invented detection test strips and coupled antibiotics with siderophores to create tools that take advantage of this battle for iron, to help eliminate pathogens. In this review, we summarize bacterial and human iron metabolism, competition for iron between humans and bacteria, siderophore sensors, antibiotics coupled with siderophores, and related phenomena. We also discuss how competition for iron can be used for diagnosis and treatment of infection in the future.