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Conventional laser cavities require discontinuity of material property or disorder to localize a light field for feedback. Recently, an emerging class of materials, twisted van der Waals materials, have been explored for applications in electronics and photonics. Here we propose and develop magic-angle lasers, where the localization is realized in periodic twisted photonic graphene superlattices. We reveal that the confinement mechanism of magic-angle lasers does not rely on a full bandgap but on the mode coupling between two twisted layers of photonic graphene lattice. Without any fine-tuning in structure parameters, a simple twist can result in nanocavities with strong field confinement and a high quality factor. Furthermore, the emissions of magic-angle lasers allow direct imaging of the wavefunctions of magic-angle states. Our work provides a robust platform to construct high-quality nanocavities for nanolasers, nano light-emitting diodes, nonlinear optics and cavity quantum electrodynamics at the nanoscale. Twisted photonic graphene superlattices enable the realization of high-performance room-temperature magic-angle lasers.

Topological insulators are materials that behave as insulators in the bulk and as conductors at the edge or surface due to the particular configuration of their bulk band dispersion. However, up to date possible practical applications of this band topology on materials’ bulk properties have remained abstract. Here, we propose and experimentally demonstrate a topological bulk laser. We pattern semiconductor nanodisk arrays to form a photonic crystal cavity showing topological band inversion between its interior and cladding area. In-plane light waves are reflected at topological edges forming an effective cavity feedback for lasing. This band-inversion-induced reflection mechanism induces single-mode lasing with directional vertical emission. Our topological bulk laser works at room temperature and reaches the practical requirements in terms of cavity size, threshold, linewidth, side-mode suppression ratio and directionality for most practical applications according to Institute of Electrical and Electronics Engineers and other industry standards. We believe this bulk topological effect will have applications in near-field spectroscopy, solid-state lighting, free-space optical sensing and communication.The interface between photonic crystals with distinct in-band topologies confines electromagnetic modes and gives rise to lasing emission in the bulk.

The overall efficacy of chimeric antigen receptor modified T cells (CARTs) remain limited in solid tumors despite intensive studies that aim at targeting multiple antigens, enhancing migration, reducing tonic signaling, and improving tumor microenvironment. On the other hand, how the affinity and engaging kinetics of antigen-binding domain (ABD) affects the CART’s efficacy has not been carefully investigated. In this article, we first analyzed 38 published solid tumor CART trials and correlated the response rate to their ABD affinity. Not surprisingly, majority (25 trials) of the CARTs utilized high-affinity ABDs, but generated merely 5.7% response rate. In contrast, 35% of the patients treated with the CARTs built from moderate-affinity ABDs had clinical responses. Thus, CARTs with moderate-affinity ABDs not only have less off-target toxicity, but also are more effective. We then reviewed the effects of ABD affinity on the biology and function of CARTs, providing further evidence that moderate-affinity ABDs may be better in CART development. In the end, we propose that a fast-on/fast-off (high K on and K off ) kinetics of CART-target engagement in solid tumor allow CARTs to generate sufficient signaling to kill tumor cells without being driven to exhaustion. We believe that studying the ABD affinity and the kinetics of CART-tumor interaction may hold a key to designing effective CARTs for solid tumors.

Aqueous zinc batteries possess intrinsic safety and cost-effectiveness, but dendrite growth and side reactions of zinc anodes hinder their practical application. Here, we propose the extended substrate screening strategy for stabilizing zinc anodes and verify its availability (d substrate : d Zn(002)  = 1: 1→d substrate : d Zn(002) =n:1, n  = 1, 2). From a series of calculated phyllosilicates satisfying d substrate  ≈ 2d Zn(002) , we select vermiculite, which has the lowest lattice mismatch (0.38%) reported so far, as the model to confirm the effectiveness of “2d Zn(002) ” substrates for zinc anodes protection. Then, we develop a monolayer porous vermiculite through a large-scale and green preparation as a functional coating for zinc electrodes. Unique “planting Zn(002) seeds” mechanism for “2d Zn(002) ” substrates is revealed to induce the oriented growth of zinc deposits. Additionally, the coating effectively inhibits side reactions and promotes zinc ion transport. Consequently, the modified symmetric cells operate stably for over 300 h at a high current density of 50 mA cm −2 . This work extends the substrate screening strategy and advances the understanding of zinc nucleation mechanism, paving the way for realizing high-rate and stable zinc-metal batteries. The growth of dendrites and the occurrence of side reactions at zinc anodes currently impede the practical use of aqueous zinc batteries. Here, the authors present an advanced substrate screening approach aimed at stabilizing zinc anodes, thereby enabling the development of high-rate zinc-metal batteries.

BackgroundObservational studies have shown that gut microbiota is closely associated with inflammatory dermatoses such as psoriasis, rosacea, and atopic dermatitis (AD). However, the causal relationship between gut microbiota and inflammatory dermatosis remains unclear.MethodsBased on Maximum Likelihood (ML), MR-Egger regression, Inverse Variance Weighted (IVW), MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Weighted Mode, and Weighted Median Estimator (WME) methods, we performed a bidirectional two-sample Mendelian randomization (MR) analysis to explore the causal relationship between gut microbiota and inflammatory dermatosis. The genome-wide association study (GWAS) summary data of gut microbiota came from the MiBioGen consortium, while the GWAS summary data of inflammatory dermatosis (including psoriasis, AD, rosacea, vitiligo, acne, and eczema) came from the FinnGen consortium and IEU Open GWAS project. Cochran’s IVW Q test tested the heterogeneity among instrumental variables (IVs). The horizontal pleiotropy was tested by MR-Egger regression intercept analysis and MR-PRESSO analysis.ResultsEventually, the results indicated that 5, 16, 17, 11, 15, and 12 gut microbiota had significant causal effects on psoriasis, rosacea, AD, vitiligo, acne, and eczema, respectively, including 42 protective and 34 risk causal relationships. Especially, Lactobacilli and Bifidobacteria at the Family and Genus Level, as common probiotics, were identified as protective factors for the corresponding inflammatory dermatoses. The results of reverse MR analysis suggested a bidirectional causal effect between AD and genus Eubacterium brachy group, vitiligo and genus Ruminococcaceae UCG004. The causal relationship between gut microbiota and psoriasis, rosacea, acne, and eczema is unidirectional. There was no significant heterogeneity among these IVs. In conclusion, this bidirectional two-sample MR study identified 76 causal relationships between the gut microbiome and six inflammatory dermatoses, which may be helpful for the clinical prevention and treatment of inflammatory dermatoses.

Maternal immune activation (MIA) induced by lipopolysaccharides or polyinosinic:polycytidylic acid injections can induce behavioral abnormalities in adult mouse offspring. Here, we used the soluble tachyzoite antigen from Toxoplasma gondii , a parasite that infects approximately two billion people, to induce MIA in mice. The adult male offspring showed autism-relevant behaviors and abnormal brain microstructure, along with a pro-inflammatory T-cell immune profile in the periphery and upregulation of interleukin-6 in brain astrocytes. We show that adoptive transfer of regulatory T (T reg ) cells largely reversed these MIA-induced phenotypes. Notably, pathogen-activated maternal T reg cells showed greater rescue efficacy than those from control donors. Single-cell RNA sequencing identified and characterized a unique group of pathogen-activated T reg cells that constitute 32.6% of the pathogen-activated maternal T reg population. Our study establishes a new preclinical parasite-mimicking MIA model and suggests therapeutic potential of adoptive T reg cell transfer in neuropsychiatric disorders associated with immune alterations. Xu et al. developed and characterized a new animal model of maternal immune activation based on a parasite mimetic. They show that immune and behavioral abnormalities in adult offspring are reversed by adoptive transfer of regulatory T cells.

Immunotherapy is a vital treatment for patients with cutaneous melanoma (CM), but effective predictors to guide clinical immunotherapy are lacking. Cuproptosis is a newly discovered mode of cell death related to tumorigenesis. Exploring the relationship between the mode of cuproptosis and the effect of immunotherapy on CM could better guide clinical management. We clustered all patients with CM in the Cancer Genome Atlas (TCGA) database based on cuproptosis-related genes (CRGs). Prognosis, immunotherapeutic effect, tumor microenvironment score, expression of CD274, CTLA4, and PDCD1, and abundance of CD8 + T infiltration in group A were higher than in group B. Using a combination of LASSO and COX regression analysis, we identified 10 molecules significant to prognosis from differentially expressed genes between the two groups and constructed a cuproptosis-related scoring system (CRSS). Compared with the American Joint Committee on Cancer (AJCC) staging system, CRSS more accurately stratified CM patient risk and guided immunotherapy. CRSS successfully stratified risk and predicted the effect of immunotherapy in 869 patients with eight CM immunotherapy datasets and multiple other tumor immunotherapy cohorts. The nomogram model, which combined AJCC stage and CRSS, greatly improved the ability and accuracy of prognosis prediction. In general, our cuproptosis-related scoring system and nomogram model accurately stratified risk in CM patients and effectively predicted prognosis and the effect of immunotherapy in CM patients.

Dust aerosols play key roles in affecting regional and global climate through their direct, indirect, and semi-direct effects. Dust events have decreased rapidly since the 1980s in East Asia, particularly over northern China, primarily because of changes in meteorological parameters (e.g. surface wind speed and precipitation). In this study, we found that winter (December–January–February) Arctic amplification associated with weakened temperature gradients along with decreased zonal winds is primarily responsible for the large decline in following spring (March–April–May) dust event occurrences over northern China since the mid-1980s. A dust index was developed for northern China by combining the daily frequency of three types of dust event (dust storm, blowing dust, and floating dust). Using the empirical orthogonal function (EOF) analysis, the first pattern of dust events was obtained for spring dust index anomalies, which accounts for 56.2% of the variability during 1961–2014. Moreover, the enhanced Arctic amplification and stronger Northern Hemisphere annular mode (NAM) in winter can result in the anticyclonic anomalies over Siberia and Mongolia, while cyclonic anomalies over East Europe in spring. These results are significantly correlated with the weakened temperature gradients, increased precipitation and soil moisture, and decreased snow cover extent in the mid-latitude over Northern Hemisphere. Based on the future predictions obtained from the Fifth Climate Models Intercomparison Project (CMIP5), we found that the dust event occurrences may continually decrease over northern China due to the enhanced Arctic amplification in future climate.

Walnut (Juglans regia L.) is unique for its extensive biological activities and pharmaceutical properties. There are few studies on walnut oligopeptides (WOPs), which are small molecule peptides extracted from walnuts. This study aimed to evaluate the anti-fatigue effects of WOPs on ICR mice and explore the possible underlying mechanism. Mice were randomly divided into four experimental sets and each set of mice were then randomly divided into four groups. The vehicle group was administered distilled water, and the three WOP intervention groups were orally administered WOP solution at a dose of 110, 220, and 440 mg/kg of body weight, respectively. After 30 days of WOP intervention, the anti-fatigue activity of WOPs were evaluated using the weight-loaded swimming test and by measuring the change of biochemical parameters, glycogen storage and energy metabolism enzymes, anti-oxidative capacity and mitochondrial function. It was observed that WOPs could significantly prolong the swimming time, decrease the accumulation of lactate dehydrogenase (LDH), creatine kinase (CK), blood urea nitrogen (BUN) and blood lactic acid (BLA), and increased the glycogen storage of liver and gastrocnemius muscle. WOPs also markedly inhibited fatigue induced oxidative stress by increasing the activity of superoxide dismutase (SOD), glutathione peroxidase (GPX) and decreasing the content malondialdehyde (MDA). Notably, WOPs improved the activity of pyruvate kinase (PK), succinate dehydrogenase (SDH), Na+-K+-ATPase, and enhanced the mRNA expression of mitochondrial biogenesis factors and mitochondrial DNA content in skeletal muscles of mice. These results suggest that WOPs have beneficial anti-fatigue effects, which may be attributed to their positive effects on increasing glycogen storage, improving energy metabolism, inhibiting oxidative stress, enhancing mitochondrial function in skeletal muscle, and ameliorating the cell damage and the muscular injury.

Patients with neurogenic rosacea (NR) frequently demonstrate pronounced neurological manifestations, often unresponsive to conventional therapeutic approaches. A molecular-level understanding and diagnosis of this patient cohort could significantly guide clinical interventions. In this study, we amalgamated our sequencing data ( n  = 46) with a publicly accessible database ( n  = 38) to perform an unsupervised cluster analysis of the integrated dataset. The eighty-four rosacea patients were partitioned into two distinct clusters. Neurovascular biomarkers were found to be elevated in cluster 1 compared to cluster 2. Pathways in cluster 1 were predominantly involved in neurotransmitter synthesis, transmission, and functionality, whereas cluster 2 pathways were centered on inflammation-related processes. Differential gene expression analysis and WGCNA were employed to delineate the characteristic gene sets of the two clusters. Subsequently, a diagnostic model was constructed from the identified gene sets using linear regression methodologies. The model's C index, comprising genes PNPLA3, CUX2, PLIN2, and HMGCR, achieved a remarkable value of 0.9683, with an area under the curve (AUC) for the training cohort's nomogram of 0.9376. Clinical characteristics from our dataset ( n  = 46) were assessed by three seasoned dermatologists, forming the NR validation cohort (NR, n  = 18; non-neurogenic rosacea, n  = 28). Upon application of our model to NR diagnosis, the model's AUC value reached 0.9023. Finally, potential therapeutic candidates for both patient groups were predicted via the Connectivity Map. In summation, this study unveiled two clusters with unique molecular phenotypes within rosacea, leading to the development of a precise diagnostic model instrumental in NR diagnosis.