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Glioblastoma multiforme (GBM) is an aggressive brain cancer with a poor prognosis and few treatment options. Here, building on the observation of elevated lactate (LA) in resected GBM, we develop biomimetic therapeutic nanoparticles (NPs) that deliver agents for LA metabolism-based synergistic therapy. Because our self-assembling NPs are encapsulated in membranes derived from glioma cells, they readily penetrate the blood-brain barrier and target GBM through homotypic recognition. After reaching the tumors, lactate oxidase in the NPs converts LA into pyruvic acid (PA) and hydrogen peroxide (H 2 O 2 ). The PA inhibits cancer cell growth by blocking histones expression and inducing cell-cycle arrest. In parallel, the H 2 O 2 reacts with the delivered bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate to release energy, which is used by the co-delivered photosensitizer chlorin e6 for the generation of cytotoxic singlet oxygen to kill glioma cells. Such a synergism ensures strong therapeutic effects against both glioma cell-line derived and patient-derived xenograft models. Targeting cancer-associated metabolism is evolving as a promising approach for cancer therapy. Here, the authors generate cancer cell-membrane encapsulated nanoparticles to induce cell cycle arrest and cytotoxicity in lactate-high cancer cells, reducing tumourigensis in glioblastoma cell-line and patient-derived models.

Teprotumumab, an IGF-1R monoclonal antibody, has shown significant efficacy in treating thyroid eye disease (TED). However, since teprotumumab was launched in 2020 and first approved in the United States, there were limited reports of post-marketing adverse events (AEs). In this study, we aimed to mine and analyze the AEs signals with teprotumumab on the basis of the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to provide instructions in clinical practice concerning adverse reactions and assistance in drug development and import/export into other countries. All AE reports were obtained from the FAERS database from the first quarter of 2020 to the fourth quarter of 2023. To comprehensively analyze the AEs, we applied four disproportionality analysis algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms. A total of 687 reports from 200 patients related to administration of teprotumumab were obtained, and 78% of the cases was female. Signal detection of teprotumumab at the system organ class (SOC) level included gastrointestinal disorders, ear and labyrinth disorders, general disorders and administration site conditions, nervous system disorders, and musculoskeletal and connective tissue disorders. AEs that ranked top five at the preferred terms (PTs) level were muscle spasms, fatigue, tinnitus, headache, and deafness. The median time to those AEs onsets was 48 days (interquartile range 19.0-92.0 days) after administering drugs. Additionally, our results indicated the AEs in reproductive system and breast disorders because the prevalence of TED was more common in women. This study identified many AEs associated with teprotumumab and unveiled potential new AE signals. These results can provide valuable evidence for further clinical application of teprotumumab and are important in enhancing clinical medication safety.

Single-stranded circular RNAs (circRNAs), generated through ‘backsplicing’, occur more extensively than initially anticipated. The possible functions of the vast majority of circRNAs remain unknown. Virus-derived circRNAs have recently been described in gamma-herpesviruses. We report that oncogenic human papillomaviruses (HPVs) generate circRNAs, some of which encompass the E7 oncogene (circE7). HPV16 circE7 is detectable by both inverse RT-PCR and northern blotting of HPV16-transformed cells. CircE7 is N 6 -methyladenosine (m 6 A) modified, preferentially localized to the cytoplasm, associated with polysomes, and translated to produce E7 oncoprotein. Specific disruption of circE7 in CaSki cervical carcinoma cells reduces E7 protein levels and inhibits cancer cell growth both in vitro and in tumor xenografts. CircE7 is present in TCGA RNA-Seq data from HPV-positive cancers and in cell lines with only episomal HPVs. These results provide evidence that virus-derived, protein-encoding circular RNAs are biologically functional and linked to the transforming properties of some HPV. The authors identify circular RNAs (circRNA) from human papillomavirus and show that circRNA-encoded E7 contributes to cancer cell growth in vitro and in tumor xenografts. Furthermore, circE7 is present in TCGA RNA-Seq data from HPV-positive cancers.

Agricultural Wireless Sensor Networks (AWSNs) are essential for real-time monitoring in precision farming, yet their lifetime is severely constrained by limited node energy and the difficulty of battery replacement in large-scale deployments. This study proposes a Quantum Adaptive Clonal Genetic Algorithm (QACGA) to achieve energy-efficient clustering in AWSNs. The algorithm combines quantum-inspired adaptive operators with dynamic adjustments in cluster-head selection, mutation, and cloning rates, while integrating multi-objective constraints related to node distribution, residual energy, and communication distance. Simulation results demonstrate that QACGA consistently reduces energy consumption compared with established clustering algorithms, achieving savings of up to 38.1% relative to PSO, SFLA, and WOA, and also surpassing MRCH under equivalent conditions. In addition to lowering energy costs, QACGA improves clustering stability and extends overall network lifetime across diverse deployment scales. These findings highlight QACGA as a robust and practical optimization framework, providing new benchmarks for energy management in AWSNs and offering valuable insights for smart agriculture applications.

Aiming at the problem of complex background interference and insufficient weld detection accuracy in steel structure weld recognition task, this paper proposes a target detection algorithm based on improved YOLOv5. By introducing the Coordinate Attention (CA) mechanism in the backbone network and integrating the CA with the C3 structure, the C3CA module is designed to effectively enhance the model’s perception of the spatial position of the weld and the detection accuracy of the weld. Experiments show that the improved YOLOv5s-C3CA model achieves 93.79% mAP@ 0.5 on the self-made weld data set, which is 2.48% higher than the original model. At the same time, the amount of model parameters is reduced by 8.53%, and the floating point operation is reduced by 10.6%, which achieves a balance between detection accuracy and calculation efficiency. This study verifies the effectiveness of the coordinate attention mechanism in improving the feature expression ability of the model, and provides a solution for the automatic detection of welds in industrial scenarios.

The α 1A- adrenergic receptor (α 1A AR) belongs to the family of G protein-coupled receptors that respond to adrenaline and noradrenaline. α 1A AR is involved in smooth muscle contraction and cognitive function. Here, we present three cryo-electron microscopy structures of human α 1A AR bound to the endogenous agonist noradrenaline, its selective agonist oxymetazoline, and the antagonist tamsulosin, with resolutions range from 2.9 Å to 3.5 Å. Our active and inactive α 1A AR structures reveal the activation mechanism and distinct ligand binding modes for noradrenaline compared with other adrenergic receptor subtypes. In addition, we identified a nanobody that preferentially binds to the extracellular vestibule of α 1A AR when bound to the selective agonist oxymetazoline. These results should facilitate the design of more selective therapeutic drugs targeting both orthosteric and allosteric sites in this receptor family. α 1A -adrenergic receptor (α 1A AR) regulates smooth muscle contraction and cognitive functions. Here, authors provide structural insight into α 1A AR activation and binding modes of the orthosteric ligands and an extracellular allosteric nanobody.

Aqueous activities on Mars have gradually declined since the Noachian (>3.7 Ga). Although water can be stored in the subsurface during the latest epochs, geomorphological evidence is still limited. In this study, we used in situ imaging and spectral data acquired by China's Zhurong rover, as well as high‐resolution remote‐sensing data, to investigate the transverse aeolian ridges (TARs) in the Zhurong landing region of Utopia Planitia. A two‐stage evolutionary scenario of the TARs is proposed and polygonal features with hydrated minerals are identified for the first time on the surface of Martian TARs. We discussed the possible formation mechanisms of the polygonal features, and proposed that they could be related to recent aqueous activity and atmosphere‐surface water exchange on Mars, which sheds light on the hydrological cycle of Mars in current cold and dry climate. Plain Language Summary The history of water on the surface of Mars has been studied for a long time. Since about 3.7 billion years ago, the role of water has gradually declined. Although the existence of subsurface ice on present‐day Mars has been confirmed, evidence for surface water is still limited. Transverse aeolian ridges (TARs), a kind of ripple‐like aeolian landform, are widely distributed on Mars and usually thought to be active within the last ∼3 million years. They are also identified in southern Utopia Planitia, the landing region of China's Mars exploration rover Zhurong. We analyzed the morphology and evolution of the TARs in the Zhurong landing region, and found some polygonal features with hydrated minerals such as gypsum on the surface of the latest‐formed TARs. We discussed the possible origins of these polygons, and proposed that they represent very recent aqueous activity on the Martian surface, which will help us better understand the hydrological cycle on current Mars. Key Points Morphology and evolution of the transverse aeolian ridges (TARs) in the Zhurong landing region are studied Polygonal features with hydrated minerals are identified on some of the TARs investigated by the Zhurong rover The polygons could be related to very recent aqueous activity and atmosphere‐surface water exchange on Mars

Deep Neural Networks (DNNs) have been shown to be vulnerable to adversarial examples, significantly hindering the development of deep learning technologies in high-security domains. A key challenge is that current defense methods often lack universality, as they are effective only against certain types of adversarial attacks. This study addresses this challenge by focusing on analyzing adversarial examples through changes in model attention, and classifying attack algorithms into attention-shifting and attention-attenuation categories. Our main novelty lies in proposing two defense modules: the Feature Pyramid-based Attention Space-guided (FPAS) module to counter attention-shifting attacks, and the Attention-based Non-Local (ANL) module to mitigate attention-attenuation attacks. These modules enhance the model’s defense capability with minimal intrusion into the original model. By integrating FPAS and ANL into the Wide-ResNet model within a boosting framework, we demonstrate their synergistic defense capability. Even when adversarial examples are embedded with patches, our models showed significant improvements over the baseline, enhancing the average defense rate by 5.47% and 7.74%, respectively. Extensive experiments confirm that this universal defense strategy offers comprehensive protection against adversarial attacks at a lower implementation cost compared to current mainstream defense methods, and is also adaptable for integration with existing defense strategies to further enhance adversarial robustness.

The α 2 adrenergic receptors (α 2 ARs) are G protein-coupled receptors (GPCRs) that respond to adrenaline and noradrenaline and couple to the Gi/o family of G proteins. α 2 ARs play important roles in regulating the sympathetic nervous system. Dexmedetomidine is a highly selective α 2 AR agonist used in post-operative patients as an anxiety-reducing, sedative medicine that decreases the requirement for opioids. As is typical for selective αAR agonists, dexmedetomidine consists of an imidazole ring and a substituted benzene moiety lacking polar groups, which is in contrast to βAR-selective agonists, which share an ethanolamine group and an aromatic system with polar, hydrogen-bonding substituents. To better understand the structural basis for the selectivity and efficacy of adrenergic agonists, we determined the structure of the α 2B AR in complex with dexmedetomidine and Go at a resolution of 2.9 Å by single-particle cryo-EM. The structure reveals the mechanism of α 2 AR-selective activation and provides insights into Gi/o coupling specificity. A cryo-EM structure of the GPCR α 2B adrenergic receptor (α 2B AR) in complex with the selective agonist dexmedetomidine and the G protein Go suggests a mechanism of selective activation and provides insights into G-protein coupling activity.

Proliferating cells, compared with quiescent cells, are more dependent on glucose for their growth. Although glucose transport in keratinocytes is mediated largely by the Glut1 facilitative transporter, we found that keratinocyte-specific ablation of Glut1 did not compromise mouse skin development and homeostasis. Ex vivo metabolic profiling revealed altered sphingolipid, hexose, amino acid, and nucleotide metabolism in Glut1 -deficient keratinocytes, thus suggesting metabolic adaptation. However, cultured Glut1- deficient keratinocytes displayed metabolic and oxidative stress and impaired proliferation. Similarly, Glut1 deficiency impaired in vivo keratinocyte proliferation and migration within wounded or UV-damaged mouse skin. Notably, both genetic and pharmacological Glut1 inactivation decreased hyperplasia in mouse models of psoriasis-like disease. Topical application of a Glut1 inhibitor also decreased inflammation in these models. Glut1 inhibition decreased the expression of pathology-associated genes in human psoriatic skin organoids. Thus, Glut1 is selectively required for injury- and inflammation-associated keratinocyte proliferation, and its inhibition offers a novel treatment strategy for psoriasis. Keratinocytes require glucose for injury- or inflammation-driven but not homeostatic proliferation, and glucose-transport blockade blocks psoriasis-like pathology in experimental models.