Commensal enterococci with pathogenic potential often facilitate the growth of diverse pathogens, thereby exacerbating infections. However, there are few effective therapeutic strategies to prevent and intervene in enterococci-mediated polymicrobial infections. Here, we find that enterococci at high density drive the expansion and pathogenicity of enteric Salmonella enterica serotype Typhimurium (S. Tm). Subsequently, we show that the driving role of enterococci in such infections is counteracted by dietary coumarin glycosides in vivo. Enterococci, which are tolerant of iron-deficient environments, produce β-glucosidases to hydrolyze coumarin glycosides into bioactive aglycones, inhibiting S. Tm growth and ameliorating the severity of S. Tm-induced symptoms by inducing iron limitation. Overall, we demonstrate that coumarin glycosides as a common diet effectively reverse enterococci-facilitated enteric infections, providing an alternative intervention to combat polymicrobial infections.

Pushing the information states’ acquisition efficiency has been a long-held goal to reach the measurement precision limit inside scattering spaces. Recent studies have indicated that maximal information states can be attained through engineered modes; however, partial intrusion is generally required. While non-invasive designs have been substantially explored across diverse physical scenarios, the non-invasive acquisition of information states inside dynamic scattering spaces remains challenging due to the intractable non-unique mapping problem, particularly in the context of multi-target scenarios. Here, we establish the feasibility of non-invasive information states’ acquisition experimentally for the first time by introducing a tandem-generated adversarial network framework inside dynamic scattering spaces. To illustrate the framework’s efficacy, we demonstrate that efficient information states’ acquisition for multi-target scenarios can achieve the Fisher information limit solely through the utilization of the external scattering matrix of the system. Our work provides insightful perspectives for precise measurements inside dynamic complex systems.

Infection with severe acute respiratory syndrome coronavirus 2 Omicron variants still causes neurological complications in elderly individuals. However, whether and how aging brains are affected by Omicron variants in terms of neuroinvasiveness and neurovirulence are unknown. Here, we utilize resected paracarcinoma brain tissue from elderly individuals to generate primary brain spheroids (BSs) for investigating the replication capability of live wild-type (WT) strain and Omicron (BA.1/BA.2), as well as the mechanisms underlying their neurobiological effects. We find that both WT and Omicron BA.1/BA.2 are able to enter BSs but weakly replicate. There is no difference between Omicron BA.1/BA.2 and WT strains in neurotropism in aging BSs. However, Omicron BA.1/BA.2 exhibits ameliorating neurological damage. Transcriptional profiling indicates that Omicron BA.1/BA.2 induces a lower neuroinflammatory response than WT strain in elderly BSs, suggesting a mechanistic explanation for their attenuated neuropathogenicity. Moreover, we find that both Omicron BA.1/BA.2 and WT strain infections disrupt neural network activity associated with neurodegenerative disorders by causing neuron degeneration and amyloid-β deposition in elderly BSs. These results uncover Omicron-specific mechanisms and cellular immune responses associated with severe acute respiratory syndrome coronavirus 2-induced neurological complications.

4,4-Dimethylsterols constitute a unique class of phytosterols responsible for regulating endogenous cannabinoid system (ECS) functions. However, precise mechanism through which 4,4-dimethylsterols affect fat metabolism and the linkage to the ECS remain unresolved. In this study, we identified that 4,4-dimethylsterols, distinct from 4-demethseterols, act as inhibitors of fatty acid amide hydrolases (FAAHs) both in vivo and in vitro. Genetic ablation of FAAHs (faah-1) abolishes the effects of 4,4-dimethylsterols on fat accumulation and locomotion behavior in a Caenorhabditis elegans model. We confirmed that dietary intervention with 4,4-dimethylsterols in a high-fat diet (HFD) mouse model leads to a significant reduction in body weight (>11.28%) with improved lipid profiles in the liver and adipose tissues and increased fecal triacylglycerol excretion. Untargeted and targeted metabolomics further verified that 4,4-dimethylsterols influence unsaturated fatty acid biosynthesis and elevate oleoyl ethanolamine levels in the intestine. We propose a potential molecular mechanism in which 4,4-dimethylsterols engage in binding interactions with the catalytic pocket (Ser241) of FAAH-1 protein due to the shielded polarity, arising from the presence of 2 additional methyl groups (CH₃). Consequently, 4,4-dimethylsterols represent an unexplored class of beneficial phytosterols that coordinate with FAAH-1 activity to reduce fat accumulation, which offers new insight into intervention strategies for treating diet-induced obesity.

The accumulation of senescent cells in kidneys is considered to contribute to age-related diseases and organismal aging. Mitochondria are considered a regulator of cell senescence process. Atrazine as a triazine herbicide poses a threat to renal health by disrupting mitochondrial homeostasis. Melatonin plays a critical role in maintaining mitochondrial homeostasis. The present study aims to explore the mechanism by which melatonin alleviates atrazine-induced renal injury and whether parkin-mediated mitophagy contributes to mitigating cell senescence. The study found that the level of parkin was decreased after atrazine exposure and negatively correlated with senescent markers. Melatonin treatment increased serum melatonin levels and mitigates atrazine-induced renal tubular epithelial cell senescence. Mechanistically, melatonin maintains the integrity of mitochondrial crista structure by increasing the levels of mitochondrial contact site and cristae organizing system, mitochondrial transcription factor A (TFAM), adenosine triphosphatase family AAA domain-containing protein 3A (ATAD3A), and sorting and assembly machinery 50 (Sam50) to prevent mitochondrial DNA release and subsequent activation of cyclic guanosine 5′-monophosphate–adenosine 5′-monophosphate synthase pathway. Furthermore, melatonin activates Sirtuin 3–superoxide dismutase 2 axis to eliminate the accumulation of reactive oxygen species in the kidney. More importantly, the antisenescence role of melatonin is largely determined by the activation of parkin-dependent mitophagy. These results offer novel insights into measures against cell senescence. Parkin-mediated mitophagy is a promising drug target for alleviating renal tubular epithelial cell senescence.

Cement-based materials are the foundation of modern buildings but suffer from intensive energy consumption. Utilizing cement-based materials for efficient energy storage is one of the most promising strategies for realizing zero-energy buildings. However, cement-based materials encounter challenges in achieving excellent electrochemical performance without compromising mechanical properties. Here, we introduce a biomimetic cement-based solid-state electrolyte (labeled as l-CPSSE) with artificially organized layered microstructures by proposing an in situ ice-templating strategy upon the cement hydration, in which the layered micropores are further filled with fast-ion-conducting hydrogels and serve as ion diffusion highways. With these merits, the obtained l-CPSSE not only presents marked specific bending and compressive strength (2.2 and 1.2 times that of traditional cement, respectively) but also exhibits excellent ionic conductivity (27.8 mS·cm⁻¹), overwhelming most previously reported cement-based and hydrogel-based electrolytes. As a proof-of-concept demonstration, we assemble the l-CPSSE electrolytes with cement-based electrodes to achieve all-cement-based solid-state energy storage devices, delivering an outstanding full-cell specific capacity of 72.2 mF·cm⁻². More importantly, a 5 × 5 cm² sized building model is successfully fabricated and operated by connecting 4 l-CPSSE-based full cells in series, showcasing its great potential in self-energy-storage buildings. This work provides a general methodology for preparing revolutionary cement-based electrolytes and may pave the way for achieving zero-carbon buildings.

As a key executioner of pyroptosis, Gasdermin D (GSDMD) plays a crucial role in host defense and emerges as an essential therapeutic target in the treatment of inflammatory diseases. So far, the understanding of the mechanisms that regulate the protein level of GSDMD to prevent detrimental effects and maintain homeostasis is currently limited. Here, we unveil that ubiquitin-specific peptidase 18 (USP18) works as a negative regulator of pyroptosis by targeting GSDMD for degradation and preventing excessive innate immune responses. Mechanically, USP18 recruits E3 ubiquitin ligase mind bomb homolog 2 (MIB2) to catalyze ubiquitination on GSDMD at lysine (K) 168, which acts as a recognition signal for the selective autophagic degradation of GSDMD. We further confirm the alleviating effect of USP18 on LPS-triggered inflammation in vivo. Collectively, our study demonstrates the role of USP18 in regulating GSDMD-mediated pyroptosis and reveals a previously unknown mechanism by which GSDMD protein level is rigorously controlled by selective autophagy.

Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), and closely associated with a high risk of liver-related morbidity and mortality. Although enhanced neutrophil infiltration of the liver is a histological hallmark of MASH, the morphological pattern of hepatic neutrophils and their relevance to the definition of MASH remain unknown. This clinicopathological study aimed to determine the association of neutrophilic crown-like structures (CLSs) in liver biopsies and evaluate their relevance to the histological diagnosis of MASH. A total of 483 morbidly obese adults who underwent bariatric surgery were recruited. Neutrophilic CLSs in liver biopsies were detected by immunohistochemistry for neutrophil elastase and proteinase 3. All participants were classified into 4 histological subgroups: no MASLD (118, 24.4%), MASLD (76, 15.7%), borderline MASH (185, 38.3%), and definite MASH (104, 21.5%). In the discovery cohort (n = 379), the frequency of neutrophilic CLSs increased in line with the severity of liver disease. The number of neutrophilic CLSs was positively correlated with established histological characteristics of MASH. At a cutoff value of <0.3 per 20× microscopic field, the number of neutrophilic CLSs yielded a robust diagnostic accuracy to discriminate no MASLD and MASLD from borderline MASH and definite MASH; a cutoff at >1.3 per 20× microscopic field exhibited a statistically significant accuracy to distinguish definite MASH from other groups (no MASLD, MASLD, and borderline MASH). The significance of neutrophilic CLSs in identifying borderline MASH and definite MASH was confirmed in an external validation cohort (n = 104). The frequency of neutrophilic CLSs was significantly higher than that of macrophagic CLSs. In conclusion, neutrophilic CLSs in the liver represent a typical histological characteristic of MASH and may serve as a promising indicator to improve the diagnostic accuracy of MASH during histological assessment of liver biopsies.

The conductive polymer poly-3,4-ethylenedioxythiophene (PEDOT), recognized for its superior electrical conductivity and biocompatibility, has become an attractive material for developing wearable technologies and bioelectronics. Nevertheless, the complexities associated with PEDOT’s patterning synthesis on diverse substrates persist despite recent technological progress. In this study, we introduce a novel deep eutectic solvent (DES)-induced vapor phase polymerization technique, facilitating nonrestrictive patterning polymerization of PEDOT across diverse substrates. By controlling the quantity of DES adsorbed per unit area on the substrates, PEDOT can be effectively patternized on cellulose, wood, plastic, glass, and even hydrogels. The resultant patterned PEDOT exhibits numerous benefits, such as an impressive electronic conductivity of 282 S·m⁻¹, a high specific surface area of 5.29 m²·g⁻¹, and an extensive electrochemical stability range from −1.4 to 2.4 V in a phosphate-buffered saline. To underscore the practicality and diverse applications of this DES-induced approach, we present multiple examples emphasizing its integration into self-supporting flexible electrodes, neuroelectrode interfaces, and precision circuit repair methodologies.

Consuming a high-fat diet (HFD) is widely recognized to cause obesity and result in chronic brain inflammation that impairs cognitive function. Repetitive transcranial magnetic stimulation (rTMS) has shown effectiveness in both weight loss and cognitive improvement, although the exact mechanism is still unknown. Our study examined the effects of rTMS on the brain and intestinal microecological dysfunction. rTMS successfully reduced cognitive decline caused by an HFD in behavioral assessments involving the Y maze and novel object recognition. This was accompanied by an increase in the number of new neurons and the transcription level of genes related to synaptic plasticity (spindlin 1, synaptophysin, and postsynaptic protein-95) in the hippocampus. It was reached that rTMS decreased the release of high mobility group box 1, activation of microglia, and inflammation in the brains of HFD rats. rTMS also reduced hypothalamic hypocretin levels and improved peripheral blood lipid metabolism. In addition, rTMS recovered the HFD-induced gut microbiome imbalances, metabolic disorders, and, in particular, reduced levels of the microvirus. Our research emphasized that rTMS enhanced cognitive abilities, resulting in positive impacts on brain inflammation, neurodegeneration, and the microbiota in the gut, indicating the potential connection between the brain and gut, proposing that rTMS could be a new approach to addressing cognitive deficits linked to obesity.