Advanced Science最新文献

Magnetic Millirobots

In article number 2308382, Tian Qiu and co-workers report the first electrocauterization performed by a team of millirobots. They form a convoy to collaboratively transport an electric wire or a catheter through the bile duct. It opens up the possibility to use a team of miniature robots in future endoscopic surgery.

Cerebral amyloid angiopathy (CAA) is the leading cause of vascular dementia among the elderly. Neuropsychiatric symptoms are commonly manifested in cerebral amyloid angiopathy patients but are usually considered as consequences of cerebral amyloid angiopathy pathology. Here, it is reported that chronic stress promotes cerebral amyloid angiopathy progression, which enhances deposition of amyloid protein beta (Aβ) in brain blood vessels and exacerbates subsequent brain injury. Mechanistically, neutrophil is implicated in cerebral amyloid angiopathy development. Aβ that accumulates in brain vasculature induces neutrophil extracellular traps (NETs) by activating STAT6 signaling, which inhibits neutrophil apoptosis and switches the programmed cell death toward NETosis. During chronic stress, circulatory Norepinephrine (NE) strengthens STAT6 activation in neutrophil and promotes NET formation, thus exacerbates the NET-dependent angiopathy. It is demonstrated that inhibiting neutrophil chemotaxis towards brain or suppressing NET formation both ameliorate cerebral amyloid angiopathy severity in the context of chronic stress. Therefore, it is proposed that stress-associated psychological disorders and NETs are promising therapeutic targets in cerebral amyloid angiopathy.

Gut Microbiome-Distal Tumor Chip Platform

Polycarbonate organs-on-chip enhance control over growth conditions such as oxygen tension, enabling co-culture of gut epithelia and oxygen sensitive bacteria to model the gut microbiome. In article number 2309220 by Danielle S.K. Brasino and co-workers, a two-chip system is developed to study relationships between gut microbiota and distal tumors.

Emerging from the intricate interplay of topology and magnetism, the giant anomalous Hall effect (AHE) is the most known topological property of the recently discovered kagomé ferromagnetic Weyl semimetal Co₃Sn₂S₂ with the magnetic Co atoms arranged on a kagomé lattice. Here it is reported that the AHE in Co₃Sn₂S₂ can be fine-tuned by an applied magnetic field orientated within ≈2° of the kagomé plane, while beyond this regime, it stays unchanged. Particularly, it can vanish in magnetic fields parallel to the kagomé plane and even decrease in magnetic fields collinear with the spin direction. This tunable AHE can be attributed to local spin switching enabled by the geometrical frustration of the magnetic kagomé lattice, revealing that spins in a kagomé ferromagnet change their switching behavior as the magnetic field approaches the kagomé plane. These results also suggest a versatile way to tune the properties of a kagomé magnet.

Ferroelectric (FE) materials are key to advancing electronic devices owing to their non-volatile properties, rapid state-switching abilities, and low-energy consumption. FE-based devices are used in logic circuits, memory-storage devices, sensors, and in-memory computing. However, the primary challenge in advancing the practical applications of FE-based memory is its reliability. To address this problem, a novel polarization pruning (PP) method is proposed. The PP is designed to eliminate weakly polarized domains by applying an opposite-sign pulse immediately after a program or erase operation. Significant improvements in the reliability of ferroelectric devices are achieved by reducing the depolarization caused by weakly polarized domains and mitigating the fluctuations in the ferroelectric dipole. These enhancements include a 25% improvement in retention, a 50% reduction in read noise, a 45% decrease in threshold voltage variation, and a 72% improvement in linearity. The proposed PP method significantly improves the memory storage efficiency and performance of neuromorphic systems.

Metabolic Dysfunction-Associated Steatotic Liver Disease

The LIDPAD model, a single-mouse metabolic dysfunction-associated steatotic liver disease (MASLD) model using thermoneutral housing and refined diet, replicates key human MASLD features, such as metabolic syndrome, gut dysbiosis, multiorgan dysfunction, and neurobehavioral anomalies in a short period. Hepatic transcriptomic-guided staging confirms its close human relevancy, making it an invaluable tools for advancing translational liver disease research. More details can be found in article number 2404326 by Nguan Soon Tan, Walter Wahli, and co-workers.

Due to its inherent ductility, Ag₂S shows promise as a flexible thermoelectric material for harnessing waste heat from diverse sources. However, its thermoelectric performance remains subpar, and existing enhancement strategies often compromise its ductility. In this study, a novel Sn-doping-induced biphasic structuring approach is introduced to synergistically control electron and phonon transport. Specifically, Sn-doping is incorporated into Ag₂S_0.7Se_0.3 to form a biphasic composition comprising (Ag, Sn)₂S_0.7Se_0.3 as the primary phase and Ag₂S_0.7Se_0.3 as the secondary phase. This biphasic configuration achieves a competitive figure-of-merit ZT of 0.42 at 343 K while retaining exceptional ductility, exceeding 90%. The dominant (Ag, Sn)₂S_0.7Se_0.3 phase bolsters the initially low carrier concentration, with interfacial boundaries between the phases effectively mitigating carrier scattering and promoting carrier mobility. Consequently, the optimized power factor reaches 5 µW cm^-1 K^-2 at 343 K. Additionally, the formation of the biphasic structure induces diverse micro/nano defects, suppressing lattice thermal conductivity to a commendable 0.18 W m^-1 K^-1, thereby achieving optimized thermoelectric performance. As a result, a four-leg in-plane flexible thermoelectric device is fabricated, exhibiting a maximum power density of ≈49 µW cm^-2 under the temperature difference of 30 K, much higher than that of organic-based flexible thermoelectric devices.

The Food and Drug Administration's recent decision to eliminate mandatory animal testing for drug approval marks a significant shift to alternative methods. Similarly, the European Parliament is advocating for a faster transition, reflecting public preference for animal-free research practices. In vitro tissue models are increasingly recognized as valuable tools for regulatory assessments before clinical trials, in line with the 3R principles (Replace, Reduce, Refine). Despite their potential, barriers such as the need for standardization, availability, and cost hinder their widespread adoption. To address these challenges, the Robotic Enabled Biological Automation (ReBiA) system is developed. This system uses a dual-arm robot capable of standardizing laboratory processes within a closed automated environment, translating manual processes into automated ones. This reduces the need for process-specific developments, making in vitro tissue models more consistent and cost-effective. ReBiA's performance is demonstrated through producing human reconstructed epidermis, human airway epithelial models, and human intestinal organoids. Analyses confirm that these models match the morphology and protein expression of manually prepared and native tissues, with similar cell viability. These successes highlight ReBiA's potential to lower barriers to broader adoption of in vitro tissue models, supporting a shift toward more ethical and advanced research methods.

Certain metabolites in the tumor microenvironment (TME) can alter innate immunity. Here, it is shown how phosphomevalonate kinase (PMVK) allows hepatocellular carcinoma (HCC) cells to overcome the anti-tumor immunity mediated by CD8⁺ T cells. In HCCs, depletion of PMVK is required to facilitate CD8⁺ T cell activation and their subsequent suppression of tumor growth. Mechanistically, PMVK phosphorylates and stabilizes glutamate decarboxylase 1 (GAD1), thus increasing the synthesis of γ-aminobutyric acid (GABA), which normally functions as a neurotransmitter. However, PMVK also recruits acetyl-CoA acetyltransferase 1 (ACAT1) and allows it to convert GABA, to 4-acetaminobutyric acid (4-Ac-GABA), which is released into the TME. There, 4-Ac-GABA activates the GABAA receptor (GABAAR) on CD8⁺ T cells, which inhibits AKT1 signaling. This in turn suppresses CD8⁺ T cell activation, intratumoral infiltration, and the anti-tumor response. Inhibiting PMVK or GABAAR in HCC mouse models overcomes resistance to anti-PD-1 immune checkpoint therapy. These findings reveal non-canonical and cooperative functions among the key metabolic enzymes PMVK, GAD1, and ACAT1 that reprogram glutamine metabolism to synthesize a potent CD8⁺ T cell inhibitor 4-Ac-GABA. Blocking 4-Ac-GABA signaling in CD8⁺ T cells, particularly when combined with immune checkpoint inhibition, potentially represents a new and potent form of immunotherapy.