Background and Aims: Metabolic syndrome (MS) is a progressive metabolic disease characterized by obesity and multiple metabolic disorders. Tryptophan (Trp) is an essential amino acid, and its metabolism is linked to numerous physiological functions and diseases. However, the mechanisms by which Trp affects MS are not fully understood.

Methods and Results: In this study, experiments involving a high-fat diet (HFD) and fecal microbiota transplantation (FMT) were conducted to investigate the role of Trp in regulating metabolic disorders. In a mouse model, Trp supplementation inhibited intestinal farnesoid X receptor (FXR) signaling and promoted hepatic bile acid (BA) synthesis and excretion, accompanied by elevated levels of conjugated BAs and the ratio of non-12-OH to 12-OH BAs in hepatic and fecal BA profiles. As Trp alters the gut microbiota and the abundance of bile salt hydrolase (BSH)-enriched microbes, we collected fresh feces from Trp-supplemented mice and performed FMT and sterile fecal filtrate (SFF) inoculations in HFD-treated mice. FMT and SFF not only displayed lipid-lowering properties but also inhibited intestinal FXR signaling and increased hepatic BA synthesis. This suggests that the gut microbiota play a beneficial role in improving BA metabolism through Trp. Furthermore, fexaramine (a gut-specific FXR agonist) reversed the therapeutic effects of Trp, suggesting that Trp acts through the FXR signaling pathway. Finally, validation in a finishing pig model revealed that Trp improved lipid metabolism, enlarged the hepatic BA pool, and altered numerous glycerophospholipid molecules in the hepatic lipid profile.

Conclusion: Our studies suggest that Trp inhibits intestinal FXR signaling mediated by the gut microbiota–BA crosstalk, which in turn promotes hepatic BA synthesis, thereby ameliorating MS.

Chirality has garnered significant attention in the scientific community since its discovery by Louis Pasteur over a century ago. It has been showing a profound impact on chemical, biomedical, and materials sciences. Significant progress has been made in controlling molecular chirality, as evidenced by the several Nobel Prizes in chemistry awarded in this area, particularly for advancements in the asymmetric catalytic synthesis of molecules with central and axial chirality. However, the exploration of new types of chirality has been largely stagnant for more than half a century, likely due to the complexity and challenges inherent in this field. In this work, we present the discovery of a novel type of chirality—staircase chirality as inspired by the design and synthesis of unnatural amino acid derivatives. The architecture of staircase chirality is characterized by 2 symmetrical phenyl rings anchored by a naphthyl pier, with the rings asymmetrically displaced due to the influence of chiral auxiliaries at their para positions. This unique staircase chiral framework has been thoroughly characterized using spectroscopic techniques, with its absolute configuration definitively confirmed by x-ray diffraction analysis. Remarkably, one of the staircase molecules exhibits 4 distinct types of chirality: central, orientational, turbo, and staircase chirality, a combination that has not been previously documented in the literature. Computational studies using density functional theory (DFT) calculations were conducted to analyze the relative energies of individual staircase isomers, and the results are in agreement with our experimental findings. We believe that this discovery will open up a new research frontier in asymmetric synthesis and catalysis, with the potential to make a substantial impact on the fields of chemistry, medicine, and materials science.

The contact time of the droplet impacting on solid surfaces can be markedly reduced by 40% to 50% by breaking the symmetric behaviors with the help of the surface structures and motion, which is crucial to diverse applications involving anti-icing, anti-erosion, self-cleaning, etc. Herein, it is interesting to note that the contact time can be further decreased up to 60% on a moving ridge surface because of corresponding synergy, inspired by flying insects or wind-dispersal seeds. In the present work, the synergistic mechanisms of the reduction in contact time have been revealed by analyzing the 3 basic features, called Leaf-type, Ear-type, and Butterfly-type, according to their morphological and dynamical behaviors. Therefore, a universal theoretical model has arrived by introducing normal and tangential Weber numbers, beyond previous descriptions. Importantly, our study discovers a generalized scaling law of −0.52 between the contact time and new composite Weber number (We_com), which is feasible to stationary and moving surfaces, suggesting that the limit reduction rate on a moving ridge surface tends to 78%. The present work provides an insight to optimize the corresponding application efficiency by coupling the surface structure and motion.

Breast cancer (BC) often spreads to bones, leading to bone metastasis (BM). Current targeted therapies have limited effectiveness in the treatment of this condition. Osteoclasts, which contribute to bone destruction, are crucial in supporting tumor cell growth in the bones. Breast cancer bone metastasis (BCBM) treatments have limited efficacy and can cause adverse effects. Ononin exhibits anticancer properties against various cancers. The study examined the impact of ononin on the BCBM and the signaling pathways involved. Our study utilized a variety of experimental techniques, including cell viability assays, colony formation assays, wound-healing assays, Transwell migration assays, Western blot analysis, and tartrate-resistant acid phosphatase (TRAP) staining. We examined the effects of ononin on osteoclastogenesis induced in MDA-MB-231 conditioned medium- and RANKL-treated RAW 264.7 cells. In a mouse model of BCBM, ononin reduced tumor-induced bone destruction. Ononin treatment effectively inhibited proliferation and colony formation and reduced the metastatic capabilities of MDA-MB-231 cells by suppressing cell adhesion, invasiveness, and motility and reversing epithelial–mesenchymal transition (EMT) markers. Ononin markedly suppressed osteoclast formation and osteolysis-associated factors in MDA-MB-231 cells, as well as blocked the activation of the mitogen-activated protein kinase (MAPK) pathway in RAW 264.7 cells. Ononin treatment down-regulated the phosphorylation of MAPK signaling pathways, as confirmed using MAPK agonists or inhibitors. Ononin treatment had no adverse effects on the organ function. Our findings suggest that ononin has therapeutic potential as a BCBM treatment by targeting the MAPK pathway.

Concrete is the most widely used and highest-volume basic material in the word today. Enhancing its toughness, including tensile strength and deformation resistance, can boost the structural load-bearing capacity, minimize cracking, and decrease the amount of concrete and steel required in engineering projects. These advancements are crucial for the safety, durability, energy efficiency, and emission reduction of structural engineering. This paper systematically summarized the brittle characteristics of concrete and the various structural factors influencing its performance at multiple scales, including molecular, nano-micro, and meso-macro levels. It outlines the principles and impacts of concrete toughening and crack prevention from both internal and external perspectives, and discusses recent advancements and engineering applications of toughened concrete. In situ polymerization and fiber reinforcement are currently practical and highly efficient methods for enhancing concrete toughness. These techniques can boost the matrix's flexural strength by 30% and double its fracture energy, achieving an ultimate tensile strength of up to 20 MPa and a tensile strain exceeding 0.6%. In the future, achieving breakthroughs in concrete toughening will probably rely heavily on the seamless integration and effective synergy of multi-scale toughening methods.

Neutrophils are essential in combating invading pathogens such as Plasmodium parasites, but the participation of their subpopulations and mechanisms in resistance to parasite infection are not fully understood. Our study identified a marked increase in Ly6G⁺ neutrophils in response to P. berghei ANKA infection. Depletion of these cells rendered mice more susceptible to infection. Elevated interleukin-17 (IL-17) levels, which increased the Ly6G⁺ neutrophil population, were also found to contribute to this protective effect. IL-17 depletion led to reduced neutrophil numbers and increased susceptibility. Furthermore, dihydroartemisinin (DHA) treatment enhanced neutrophil-mediated immune responses through up-regulation of CD18 and CXCR4 factors. These findings revealed key mechanisms of neutrophil and IL-17 interactions in malaria protection and highlighted DHA's potential to promote neutrophil function in combating malaria.

To explore whether the metabolic state reprogramming approach may be used to explore previously unknown metabolic pathways that contribute to antibiotic resistance, especially those that have been neglected in previous studies, pyruvate reprogramming was performed to reverse the resistance of multidrug-resistant Edwardsiella tarda. Surprisingly, we identified a pyruvate-regulated glutathione system that occurs by boosting glycine, serine, and threonine metabolism. Moreover, cysteine and methionine metabolism played a key role in this reversal. This process involved pyruvate-depressed glutathione and pyruvate-promoted glutathione oxidation, which was attributed to the elevated glutathione peroxidase and depressed glutathione reductase that was inhibited by glycine. This regulation inhibited reactive oxygen species (ROS) degradation and thereby elevated ROS to eliminate E. tarda. Loss of metB, gpx, and gor of the metabolic pathways increased and decreased resistance, respectively, both in vitro and in vivo, thereby supporting the hypothesis of a pyruvate–cysteine–glutathione system/glycine–ROS metabolic pathway. The role of this metabolic pathway in drug resistance and reprogramming reversal was demonstrated in laboratory-evolved gentamicin-resistant E. tarda and other clinically isolated multidrug- and carbapenem-resistant pathogens. Thus, we reveal a less studied antibiotic resistance metabolic pathway along with the mechanisms involved in its reversal.

The wide-bandgap semiconductor material Ga₂O₃ exhibits great potential in solar-blind deep-ultraviolet (DUV) photodetection applications, including none-line-of-sight secure optical communication, fire warning, high-voltage electricity monitoring, and maritime fog dispersion navigation. However, Ga₂O₃ photodetectors have traditionally faced challenges in achieving both high responsivity and fast response time, limiting their practical application. Herein, the Ga₂O₃ solar-blind DUV photodetectors with a suspended structure have been constructed for the first time. The photodetector exhibits a high responsivity of 1.51 × 10¹⁰ A/W, a sensitive detectivity of 6.01 × 10¹⁷ Jones, a large external quantum efficiency of 7.53 × 10¹² %, and a fast rise time of 180 ms under 250-nm illumination. Notably, the photodetector achieves both high responsivity and fast response time simultaneously under ultra-weak power intensity excitation of 0.01 μW/cm². This important improvement is attributed to the reduction of interface defects, improved carrier transport, efficient carrier separation, and enhanced light absorption enabled by the suspended structure. This work provides valuable insights for designing and optimizing high-performance Ga₂O₃ solar-blind photodetectors.

Osteoporosis presents a marked global public health challenge, characterized by deficient osteogenesis and a deteriorating immune microenvironment. Conventional clinical interventions primarily target osteoclast-mediated bone damage, yet lack a comprehensive therapeutic approach that balances bone formation and resorption. Herein, we introduce a bone-targeted nanocomposite, A-Z@Pd(H), designed to address these challenges by integrating diverse functional components. The nanocomposite incorporates internal hydrogen-carrying nanozymes, which effectively scavenge multiple reactive oxygen species (ROS) and synergistically engage the autophagy–lysosome pathway to accelerate endogenous ROS degradation in macrophages. This mechanism disrupts the vicious cycle of autophagic dysfunction–ROS accumulation–macrophage inflammation. In addition, external metal–organic frameworks release zinc ions (Zn²⁺) in response to the acidic osteoporotic environment, thereby promoting osteogenesis. In a murine model of osteoporosis, intravenous administration of A-Z@Pd(H) leads to preferential accumulation in the femur, thereby remodeling the osteoporotic microenvironment through immune regulation, osteogenesis promotion, and osteoclast inhibition. These findings suggest that this system composed of hydrogen therapy and ion therapy may be a promising candidate for bone-targeted comprehensive therapy in osteoporosis.

Radiative cooling has witnessed substantial progress while its performance is constrained by the thermal reciprocal Kirchhoff's law. Violating Kirchhoff's law to pursue nonreciprocal radiative cooling seems promising; however, the energy conservation requirement and radiant flux integrated over the entire hemisphere make the nonreciprocal benefit insignificant. This commentary discusses the practical limits of nonreciprocal radiative cooling and points toward the future direction of directional radiative cooling.