Typically developing (TD) individuals can readily orient attention according to others' eye-gaze direction, an ability known as social attention, which involves both innate and acquired components. To distinguish between these two components, we used a critical flicker fusion technique to render gaze cues invisible to participants, thereby largely reducing influences from consciously acquired strategies. Results revealed that both visible and invisible gaze cues could trigger attentional orienting in TD adults (aged 20 to 30 years) and children (aged 6 to 12 years). Intriguingly, only the ability to involuntarily respond to invisible gaze cues was negatively correlated with autistic traits among all TD participants. This ability was substantially impaired in adults with autism spectrum disorder (ASD) and in children with high autistic traits. No such association or reduction was observed with visible gaze cues. These findings provide compelling evidence for the functional demarcation of conscious and unconscious gaze-triggered attentional orienting that emerges early in life and develops into adulthood, shedding new light on the differentiation of the innate and acquired aspects of social attention. Moreover, they contribute to a comprehensive understanding of social endophenotypes of ASD.

Protein loop modeling is a challenging yet highly nontrivial task in protein structure prediction. Despite recent progress, existing methods including knowledge-based, ab initio, hybrid, and deep learning (DL) methods fall substantially short of either atomic accuracy or computational efficiency. To overcome these limitations, we present KarmaLoop, a novel paradigm that distinguishes itself as the first DL method centered on full-atom (encompassing both backbone and side-chain heavy atoms) protein loop modeling. Our results demonstrate that KarmaLoop considerably outperforms conventional and DL-based methods of loop modeling in terms of both accuracy and efficiency, with the average RMSDs of 1.77 and 1.95 Å for the CASP13+14 and CASP15 benchmark datasets, respectively, and manifests at least 2 orders of magnitude speedup in general compared with other methods. Consequently, our comprehensive evaluations indicate that KarmaLoop provides a state-of-the-art DL solution for protein loop modeling, with the potential to hasten the advancement of protein engineering, antibody–antigen recognition, and drug design.

Micro/nanorobots (MNRs) are envisioned to provide revolutionary changes to therapies for infectious diseases as they can deliver various antibacterial agents or energies to many hard-to-reach infection sites. However, existing MNRs face substantial challenges in addressing complex infections that progress from superficial to deep tissues. Here, we develop swarming magnetic Fe₃O₄@polydopamine-tannic acid nanorobots (Fe₃O₄@PDA-TA NRs) capable of performing targeted bacteria elimination in complicated bacterial infections by integrating superficial photothermal and deep chemical strategies. The Fe₃O₄@PDA-TA nanoparticles (NPs), serving as building blocks of the nanorobots, are fabricated by in situ polymerization of dopamine followed by TA adhesion. When driven by alternating magnetic fields, Fe₃O₄@PDA-TA NPs can assemble into large energetic microswarms continuously flowing forward with tunable velocity. Thus, the swarming Fe₃O₄@PDA-TA NRs can be navigated to achieve rapid broad coverage of a targeted superficial area from a distance and rapidly eradicate bacteria residing there upon exposure to near-infrared (NIR) light due to their efficient photothermal conversion. Additionally, they can concentrate at deep infection sites by traversing through confined, narrow, and tortuous passages, exerting sustained antibacterial action through their surface TA-induced easy cell adhesion and subsequent membrane destruction. Therefore, the swarming Fe₃O₄@PDA-TA NRs show great potential for addressing complex superficial-to-deep infections. This study may inspire the development of future therapeutic microsystems for various diseases with multifunction synergies, task flexibility, and high efficiency.

Golgi protein 73 (GP73), a resident protein of the Golgi apparatus, is notably elevated in hepatocellular carcinoma (HCC). While its critical role in remodeling the tumor microenvironment (TME) is recognized, the intricate mechanisms are not fully understood. This study reveals that GP73 in HCC cells interacts with prolyl hydroxylase-2 (PHD-2) in a competitive manner, thereby impeding the hydroxylation of hypoxia-induced factor-1α (HIF-1α). The effect above promotes the production and secretion of vascular endothelial growth factor A (VEGFA). Moreover, exosomal GP73 derived from HCC cells can be internalized by human umbilical vein endothelial cells (HUVECs) and competitively interact with HECTD1, an E3 ubiquitin ligase targeting growth factor receptor-bound protein 2 (GRB2). This interaction stabilizes GRB2, thereby activating the Ras–mitogen-activated protein kinase (MAPK) signaling pathway. Consequently, escalated levels of GP73 intensify VEGF production in HCC cells and potentiate mitogenic signaling in vascular endothelial cells, fostering angiogenesis in the TME. Our findings propose that GP73 might serve as a novel target for anti-angiogenic therapy in HCC.

Amino acid bioconjugation technology has emerged as a pivotal tool for linking small-molecule fragments with proteins, antibodies, and even cells. The study in Nature by Chang and Toste introduces a redox-based strategy for tryptophan bioconjugation, employing N-sulfonyloxaziridines as oxidative cyclization reagents, demonstrating high efficiency comparable to traditional click reactions. Meanwhile, this tool provides feasible methods for investigating the mechanisms underlying functional tryptophan-related biochemical processes, paving the way for protein function exploration, activity-based proteomics for functional amino acid identification and characterization, and even the design of covalent inhibitors.

The prevalence of food allergies is increasing dramatically and causing serious public health concerns. Notably, melatonin metabolism imbalance in patients with food allergies; however, the role of melatonin in food allergies remains unclear. Here, we demonstrated that melatonin suppresses food allergy responses and reprograms the gut microbiota of food-allergic mice, while melatonin aggravates food allergy during gut microbiota depletion. Mechanistically, melatonin boosts the degranulation of mast cells by up-regulating the expression of membrane high-affinity immunoglobulin E (IgE) receptor (FcεRI). Melatonin increases the mRNA expression of Rabenosyn-5 (a component of factors for endosome recycling and Rab interactions) through melatonin receptor 2 (MT2)–extracellular signal-regulated kinase (ERK) signaling, thereby driving the recycling of FcεRI and elevating the abundance of membrane FcεRI. Likewise, the inhibition of MT2 attenuates melatonin-induced food allergy in mice with gut microbiota depletion. Collectively, our finding provides insights into the pathogenesis of food allergies and provides a potential therapeutic target for the prevention and treatment of food allergies.

Consumption of fried foods is highly prevalent in the Western dietary pattern. Western diet has been unfavorably linked with high risk of developing cardiovascular diseases. Heart failure (HF) as a cardiovascular disease subtype is a growing global pandemic with high morbidity and mortality. However, the causal relationship between long-term fried food consumption and incident HF remains unclear. Our population-based study revealed that frequent fried food consumption is strongly associated with 15% higher risk of HF. The causal relationship may be ascribed to the dietary acrylamide exposure in fried foods. Further cross-sectional study evidenced that acrylamide exposure is associated with an increased risk of HF. Furthermore, we discover and demonstrate that chronic acrylamide exposure may induce HF in zebrafish and mice. Mechanistically, we reveal that acrylamide induces energy metabolism disturbance in heart due to the mitochondria dysfunction and metabolic remodeling. Moreover, acrylamide exposure induces myocardial apoptosis via inhibiting NOTCH1-phosphatidylinositol 3-kinase/AKT signaling. In addition, acrylamide exposure could affect heart development during early life stage, and the adverse effect of acrylamide exposure is a threat for next generation via epigenetic change evoked by DNA methyltransferase 1 (DNMT1). In this study, we reveal the adverse effects and underlying mechanism of fried foods and acrylamide as a typical food processing contaminant on HF from population-based observations to experimental validation. Collectively, these results both epidemiologically and mechanistically provide strong evidence to unravel the mechanism of acrylamide-triggered HF and highlight the significance of reducing fried food consumption for lower the risk of HF.

The combination of all-inorganic perovskites (PVSKs) and polymers allows for free-standing flexible optoelectronic devices. However, solubility difference of the PVSK precursors and concerns over the compatibility between polymer carriers and PVSKs imply a great challenge to incorporate different kinds of PVSKs into polymer matrices by the same manufacturing process. In this work, PVSK precursors are introduced into poly(2-hydroxyethyl acrylate) (PHEA) hydrogels in sequence, in which the PVSK-gel composites are achieved with full-color emissions by simply varying the precursor species. Moreover, it is found that CsBr has a higher interaction energy with the (111) plane of CsPbBr₃ than the (110) plane; thus, the CsPbBr₃ crystals with a shape of truncated cube and tetragon are observed during the CsPbBr₃–Cs₄PbBr₆ phase transition over time. The PVSK-gel composites feature excellent bendability, elasticity, and stretchable deformation (tensile strain > 500%), which allows for 3D printing emissive customized stereoscopic architectures with shape-memory features.

The menace of drought has persistently loomed over global crop production, posing a serious threat to agricultural sustainability. Research on drought stress highlights the important role of the phytohormone abscisic acid (ABA) in orchestrating plant responses to drought conditions. ABA regulates various drought/dehydration-responsive genes, initiates stomatal closure, and influences cellular responses to drought stress. Additionally, plants employ a phosphate starvation response (PSR) mechanism to manage phosphate (Pi) deficiency, with ABA playing a role in its regulation. However, despite intensive research in these fields, the precise connection among PSRs, drought stress, and ABA signaling still needs to be determined. Recently, PSR-related gene induction has been reported to occur before the induction of ABA-responsive genes under progressive mild drought. Mild drought decreases Pi uptake and contents in plants, triggering PSRs, which play an important role in plant growth during mild drought. Both ABA-responsive and PSR-related gene expression could indicate plant perception of external moisture conditions. Thus, integrating the information regarding their associated gene expression with soil moisture contents and thermographic data can enable timely irrigation optimization to mitigate the effect of drought on crop productivity.

Lung cancer is the second most commonly diagnosed cancer and a leading cause of cancer-related death, with non-small cell lung cancer (NSCLC) being the most prevalent type. Over 70% of lung cancer patients require radiotherapy (RT), which operates through direct and indirect mechanisms to treat cancer. However, RT can damage healthy tissues and encounter radiological resistance, making it crucial to enhance its precision to optimize treatment outcomes, minimize side effects, and overcome radioresistance. Integrating nanotechnology into RT presents a promising method to increase its efficacy. This review explores various nano-assisted RT strategies aimed at achieving precision treatment. These include using nanomaterials as radiosensitizers, applying nanotechnology to modify the tumor microenvironment, and employing nano-based radioprotectors and radiation-treated cell products for indirect cancer RT. We also explore recent advancements in nano-assisted RT for NSCLC, such as biomimetic targeting that alters mesenchymal stromal cells, magnetic targeting strategies, and nanosensitization with high-atomic number nanomaterials. Finally, we address the existing challenges and future directions of precision RT using nanotechnology, highlighting its potential clinical applications.