The bacterial cell cycle relies on coordinated and dynamic interactions between division and peptidoglycan synthesis proteins. However, visualizing these interactions in vivo remains technically challenging. Here, we established fluorescence-lifetime imaging microscopy combined with Förster resonance energy transfer (FLIM-FRET) as a robust, spatially resolved technique to visualize protein interactions in living Staphylococcus aureus. We set up and validated the method using cytosolic and membrane-anchored control proteins, achieving FRET efficiencies of up to 40%. Using FLIM-FRET, we mapped protein interactions of the glycosyltransferase FtsW within the septal peptidoglycan-synthesizing complex. We confirmed its interaction with the cognate transpeptidase PBP1 and the regulatory protein DivIB. Notably, we found that FtsW also self-interacts, suggesting that septal peptidoglycan synthesis is performed by a complex of multimers, able to synthesize more than one glycan strand. Inhibition of peptidoglycan synthesis by directly targeting PBP1 with the beta-lactam antibiotic imipenem, but not by targeting the lipid II flippase, therefore depleting the FtsW-PBP1 substrate from the outer surface of the cell membrane, weakened FtsW-PBP1 interaction. This suggests that alterations in FtsW interactions result primarily from antibiotic-induced conformational changes or from uncoupling FtsW-PBP1 activities, resulting in the presence of uncrosslinked glycans, rather than merely from a loss of peptidoglycan synthesis activity.

The high reactivity of isocyanate groups not only makes them excellent precursors for polyurethanes and polyureas, but it also leads to their degradation through reactions with atmospheric moisture. Conventionally, blocking reagents containing alcohol or amine groups have been used to protect isocyanate groups. However, such covalent protection approaches often require harsh deprotection conditions. Herein, we report a non-covalent supramolecular strategy that provides both high protection efficiency and facile deprotection of isocyanate compounds. In this approach, the isocyanate groups are encapsulated within crystalline pillar[n]arene macrocycles. Owing to the highly hydrophobic nature of the pillar[n]arene crystals, the isocyanate guests are effectively protected from water in the crystalline state: the isocyanate groups are active even after the crystalline complexes are exposed to water vapour or directly immersed in water. Furthermore, although the host-guest complex is stabilized in the crystalline state, simple dissolution in an appropriate reaction solvent simultaneously triggers deprotection, enabling subsequent polyurethane synthesis.

Heterogeneous catalyst systems hold significant potential for advanced water treatment, yet achieving sustainable catalytic processes capable of continuously generating reactive species remains a substantial challenge. In this work, we develop an integrated oxidation-reduction system that synergistically couples peracetic acid (PAA) with H2O2 under the guidance of an interfacial built-in electric field (BEF). Through a programmable self-assembly approach, a porous nitrogen-doped carbon (NC) layer encapsulating Co/CoO heterojunction was constructed. Experimental and theoretical results confirm that strong electronic coupling between metallic Co and semiconductor CoO spontaneously generates a robust BEF. This field not only optimizes the electronic configuration to enhance PAA adsorption and activation, but also enables the selective adsorption of H2O2 from the mixed oxidant solution. The adsorbed H2O2 acts as an electron donor to sustain the Co(II)/Co(III) redox cycle, facilitating continuous reactive oxygen species (ROS) generation for approximately 120 min. The system demonstrates exceptional catalytic performance, achieving high contaminant removal rate constants (0.3 to 0.6 min-1) with an ultralow catalyst dosage of 15 mg L-1 and significantly improved PAA utilization efficiency. This BEF-mediated "dual-enhancement" strategy offers a sustainable and efficient route for water purification by enabling high oxidant utilization while minimizing catalyst consumption.

Astrocytes play critical roles in neural circuit function, but how they contribute to cognitive impairment remains poorly understood. Here, we identify astrocyte-derived kynurenic acid (KYNA), a neuroactive metabolite known to modulate multiple neurotransmitter receptor systems, including the N-methyl-D-aspartate receptor (NMDA), as a mediator of cognitive dysfunction in the context of aberrant astrocyte activity. Using chemogenetic stimulation, pharmacological rescue, and astrocyte-specific knockdown of kynurenine aminotransferase II (KAT II) in mice, we show that elevated KYNA suppresses parvalbumin-positive interneuron activity in the prefrontal cortex, leading to disinhibition of pyramidal neurons and impairments in cognitive functions linked to cortical activity, including episodic-like and working memory as well as sensorimotor gating. These findings define an astrocyte-KYNA-interneuron axis that controls cortical excitability and cognition, linking glial metabolism to circuit imbalance and cognitive dysfunction with potential relevance to psychiatric and neurological disorders.

Chronic stress significantly impacts cancer progression by activating the sympathetic nervous system, leading to increased tumor growth, metastasis, and resistance to chemotherapy. To address these challenges, we develop biomimetic hybrid nanovesicles (Pro@hNVs) by fusing M1 macrophage-derived vesicles with pH-sensitive liposomes (hNVs) to encapsulate the β-adrenergic receptor (ADRB) blocker propranolol (Pro). Leveraging the tumor-targeting properties of M1 macrophage-derived vesicles and their matrix metalloproteinase-mediated degradation of tumor extracellular matrix, Pro@hNVs effectively accumulate and deeply penetrate tumor tissues, followed by the release of Pro in response to the acidic tumor microenvironment. Pro subsequently inhibits the sympathetic nerve-cancer cell crosstalk by blocking ADRB2 signaling. Meanwhile, Pro@hNVs effectively reprogram adrenergic signal-induced M2-like tumor-associated macrophages (TAMs) into the M1 phenotype through the released Pro and hNVs, thereby amplifying TNF-mediated neurotoxicity and effectively disrupting sympathetic nerve-macrophage crosstalk. This dual-action mechanism of Pro@hNVs significantly inhibits the sympathetic nerve function promoted by gemcitabine, resulting in the improved chemotherapy efficacy and enhanced antitumor immune response under chronic stress. These findings highlight the potential of Pro@hNVs as a promising strategy to enhance chemotherapy outcomes in cancer patients experiencing chronic stress, offering a viable therapeutic avenue for overcoming treatment resistance.

Complex spatial structure, with partially isolated subpopulations, and environment heterogeneity, such as gradients in nutrients, oxygen, and drugs, both shape the evolution of natural populations. We investigate the impact of environment heterogeneity on mutant fixation in spatially structured populations with demes on the nodes of a graph. When migrations between demes are frequent, we find that environment heterogeneity can amplify natural selection and simultaneously accelerate mutant fixation and extinction, thereby fostering the quick fixation of beneficial mutants. We demonstrate this effect in the star graph, and more strongly in the line graph. We show that amplification requires mutants to have a stronger fitness advantage in demes with stronger migration outflow, and that this condition allows amplification in more general graphs. As a baseline, we consider circulation graphs, where migration inflow and outflow are equal in each deme. In this case, environment heterogeneity has no impact to first order, but increases the fixation probability of beneficial mutants to second order. Finally, when migrations between demes are rare, we show that environment heterogeneity can also foster amplification of selection, by allowing demes with sufficient mutant advantage to become refugia for mutants.

The performance of all-perovskite tandem solar cells is critically hindered by the defective and high-roughness surfaces of lead-tin narrow-bandgap subcells, which induce non-radiative recombination and impede carrier extraction. Herein, we report a robust and multifunctional strategy to convert the above narrow-bandgap perovskite surface into an efficient and smooth one by a picosecond ultraviolet pulsed laser polishing technology combined with surface reconstruction. The polished surface is decoded as [PbI₆]⁴⁻/[SnI₆]⁴⁻ octahedral frameworks with metastable A-site vacancies. By screening guanidinium bromide as an A-site passivator, the polished surface is reconstructed into a guanidinium-cesium-based perovskite phase, substantially enhancing carrier extraction and suppressing ion migration. The resulting single-junction lead-tin and tandem solar cells, fabricated via an antisolvent-free method, achieve efficiencies of 23.47% (certified) and 29.80%, respectively, alongside exceptional operational stability. This versatile interface engineering paradigm surmounts a pivotal barrier in the advancement of next-generation photovoltaic technologies.

Aging involves morphological and functional changes across different organs, but how these changes are linked among the different organs remains to be elucidated. Here, we uncover a central role of platelets in systemic aging. In aged mice, the levels of platelet-secreted pro-inflammatory factors (PSPF) increased greatly in the serum and platelets, leading to a diffuse increase of platelet infiltration in the brain, liver, lung, kidney, and aortic root. The RNA-binding protein HuR/ELAVL1, a major regulator of RNA metabolism, promoted the production of PSPF in platelets. Platelet-specific deletion of HuR reduced the expression of PSPF in platelets, alleviated platelet infiltration in the brain, liver, lung, kidney, and aortic root, and delayed systemic aging. By using single-nucleus sequencing, platelet-specific HuR ablation was found to alleviate p53 and pro-inflammatory signaling pathways in liver, lung, and brain tissues in aged mice. Our findings highlight a role of platelets in coordinating aging traits across organs.

Pleiotropic conflict, where a genetic locus has antagonistic effects on different traits, is a common phenomenon observed in animals and plants. While pleiotropy has been widely reported in humans, there is no systematic study of pleiotropic conflict in humans. Here, we leverage summary statistics from genome-wide association studies of complex diseases and traits derived from large-scale population cohorts to identify pleiotropic regions with conflicting effects. Through a multi-trait colocalization approach, we identified 219 independent regions containing variants showing pleiotropic conflict, which cover ~11.4% of linkage disequilibrium blocks in the human genome. Antagonistic variants are observed to be enriched for genetic variants with intermediate minor allele frequencies and antagonistic regions show signatures of positive/balancing selection. Our results suggest that antagonistic variants are pervasive in humans and indicate their role in maintaining phenotypic and genetic diversity in humans.

Given the large number of record-breaking tropical cyclones (TCs) in recent years, there is a pressing need to investigate how strong TCs respond to climate change. Here we find that the annual maximum lifetime maximum intensity (LMI) of TC in the western North Pacific is strongly correlated with the temperature of a subsurface water mass, exhibiting a multi-decadal V-shaped structure in the past four decades. This water mass originally forms and is subducted in the eastern North Pacific under the center of the North Pacific High (NPH). It is then transported along a subsurface path over approximately four years to the western boundary. Correspondingly, the annual maximum LMI can be predicted several years in advance based on the intensity of NPH. We propose a mechanism in which the highly variable heat content of the subsurface water mass modulates the under-storm sea surface temperature through TC-induced mixing and upwelling process.