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.

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.

Personalized healthcare monitoring is a transformative tool for preventing potential risks and enhancing health status, particularly through molecular-level insights. Advances in nanotechnology, smart devices, and artificial intelligence (AI) have revolutionized personalized healthcare, especially in point-of-care testing (POCT), enabling early detection and timely intervention. Recently, surface-enhanced Raman spectroscopy (SERS) technology, particularly with flexible chips, has shown immense promise in this field due to its in situ, rapid, specific, and efficient detection capabilities. In this review, we highlight recent advancements in flexible SERS chips for personalized healthcare monitoring, demonstrating their effectiveness in target sampling and detection. Importantly, we provide a comprehensive overview of potential applications of flexible SERS chips in personalized healthcare, address current challenges, and propose future development directions. We also explore the future development of miniaturized Raman devices to broaden their applications in personalized healthcare monitoring. Additionally, we underscore the important role of AI in enhancing data processing and analysis. Our aim is to offer a thorough guide on integrating SERS into personalized healthcare monitoring, promising a new era of health management.

The effective and translational strategy to regenerate knee meniscal fibrocartilage remained challenging. Herein, we first identified vascular smooth muscle cells (VSMCs) transdifferentiated into fibrochondrocytes and participated in spontaneous meniscal regeneration using smooth muscle cell lineage tracing transgenic mice meniscal defect model. Then, we identified low-intensity pulsed ultrasound (LIPUS) acoustic stimulus enhanced fibrochondrogenic transdifferentiation of VSMCs in vitro and in vivo. Mechanistically, LIPUS stimulus could up-regulate mechanosensitive ion channel Piezo1 expression and then activate the transforming growth factor β1 (TGFβ1) signal, following repression of the Notch signal, consequently enhancing fibrochondrogenic transdifferentiation of VSMCs. Finally, we demonstrated that the regular LIPUS stimulus enhanced anisotropic native-like meniscal fibrocartilage tissue regeneration in a beagle canine subtotal meniscectomy model at 6 months postoperatively. The single-cell RNA sequencing analysis confirmed the role of VSMC fibrochondrogenic transdifferentiation in meniscal regeneration.

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.

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.

The current biopsychosocial medical models have substantial limitations and require to form an improved scientific medical model. This new model should consider human health holistically, emphasizing the integrity of life and focusing on the impact of physiological spaces, natural factors, and the interaction between individuals and their environment. We propose a “life–society–nature medical model” that provides novel perspectives for innovation in basic medical theory, the integration of Traditional Chinese and Western medicine, disease diagnosis, therapy and prevention, as well as the development of new therapeutic agents, scientific instruments, and approaches to medical education.

Photoelectrochemistry provides an important application in the production of high-value-added chemicals. However, photoelectrochemical organic transformation with high product selectivity remains a challenge. Until now, various technologies have been developed to promote the selectivity of photoelectrochemical high-value-added chemical production. Herein, a novel ion-shielding heterogeneous photoelectrocatalysis strategy for the production of trifluoromethyl group (CF₃)-containing compounds with high selectivity is described.

Exposure to airborne fine particulate matter (PM_2.5) is strongly associated with poor fertility and ovarian damage. However, the mechanism underlying this remains largely unclear. Here, we found that PM_2.5 markedly impaired murine ovarian reserve, decreased hormone levels, and aggravated ovarian inflammation. Circulating interleukin-6 (IL-6) was elevated in PM_2.5-exposed mice and was further confirmed to mediate this damage by IL-6 recombinant protein intervention. PM_2.5 exposure led to increased alveolar macrophage infiltration in the lungs. However, alveolar macrophage clearance with clodronate liposomes could not fully reverse the elevated IL-6 levels and ovarian injury, suggesting that alveolar macrophages were probably not the only source of circulating IL-6. Further experiments indicated that IL-6 mainly targeted ovarian theca–interstitial cells and impaired testosterone synthesis via suppressing the peroxisome proliferator-activated receptor γ (PPARγ) pathway. In addition, apoptosis of granulosa cells and restriction of follicular growth were observed in co-cultures with IL-6-treated theca–interstitial cells, which could be further reversed by the PPARγ agonist. Moreover, IL-6-neutralizing antibodies ameliorated PM_2.5-induced ovarian damage. Notably, increased levels of circulating IL-6 were observed in premature ovarian aging patients and were inversely associated with their ovarian function. In summary, our findings offer a mechanistic explanation for PM_2.5-induced ovarian dysfunction and verify IL-6 as a biomarker and potential therapeutic target.