Hepatocellular carcinoma (HCC) is characterized by a profoundly hypoxic microenvironment, which drives tumor aggressiveness and poor clinical outcomes. However, the precise regulatory mechanisms through which hypoxia promotes HCC progression remain incompletely understood. Here, we identified ubiquitin conjugating enzyme E2 variant 1 (UBE2V1) as a novel hypoxia-responsive gene that is transcriptionally activated by hypoxia-inducible factor-1α (HIF-1α) through direct binding to a hypoxia-response element located between −208 and −201 bp in the UBE2V1 promoter. Overexpression of UBE2V1 was frequently detected in HCC tissues and correlated strongly with advanced tumor stage and unfavorable patient prognosis. Moreover, UBE2V1 facilitated the proliferation and migration of HCC cells. Further investigation revealed that up-regulated UBE2V1 competes with HIF-1α for binding to the β-domain of von Hippel–Lindau (VHL) protein and, in complex with UBE2S, catalyzes K11/K48-linked ubiquitination at VHL K196, leading to its proteasomal degradation. This disruption of VHL function attenuates HIF-1α ubiquitination and degradation, resulting in sustained HIF-1α stabilization, increased nuclear accumulation, and enhanced transcriptional activity. Consistent with these findings, genetic knockdown of UBE2V1 or pharmacological inhibition of HIF-1α markedly suppresses HCC tumorigenesis and metastasis in vivo. Altogether, our study unveils a previously unrecognized HIF-1α–UBE2V1 positive feedback loop that is self-reinforcing and critically sustains the hypoxic microenvironment to drive HCC progression, highlighting UBE2V1 as both a promising prognostic biomarker and a compelling therapeutic target for HCC.

Human activities have had complex, long-term impacts on forest function across New England—a trend expected to continue. To assess these impacts, we conducted a regional-scale modeling study using the PnET-CN-daily model, simulating multiple scenarios that reflect projected changes in land cover, climate, and air quality. The results suggest that while New England will continue to serve as a regional carbon sink, carbon accumulation in the southern portion of the region will slow and may shift to a net carbon source due to aggressive urban expansion. Carbon dioxide (CO₂) fertilization and carbon loss associated with urbanization are the dominant factors controlling future carbon dynamics. However, CO₂ fertilization may diminish over time due to nutrient limitations, while rising temperatures are expected to accelerate soil decomposition, further increasing carbon loss. The forecasts also show that urbanization will increasingly affect ecosystem nitrogen storage. Climate change and CO₂ fertilization along with declining nitrogen deposition from decreases in fossil fuel use are projected to drive nitrogen oligotrophication—slowing forest growth and becoming more severe as nitrogen inputs decrease. In addition, urbanization and climate change are expected to substantially reduce snowpack and shorten snow cover duration in southern New England, with potential consequences for regional water dynamics. These trends highlight the need to integrate future climate, air quality, and land-use projections into forest management strategies for both urban and rural ecosystems.

The emergence of embodied intelligence has brought a fundamental shift to the robotics field, emphasizing the integration of perception, cognition, and control in dynamic physical environments. Although substantial progress has been made in artificial intelligence models, control middleware, and industrial communication protocols within their respective domains, the fragmentation in semantic interaction and task-level coordination still limits the scalability and deployment of embodied intelligence systems. This review synthesizes the current research on system deployment and coordination in embodied intelligence, particularly focusing on the challenges in achieving task-level coordination and semantic interoperability across heterogeneous components. We examine key coordination requirements, such as context semantics, capability declaration, and workflow composition, and highlight the existing gaps in addressing these issues within current systems. In response, we propose the Embodied Context Protocol (ECP) as an emerging solution, designed to bridge these gaps and enhance interoperability across various subsystems. It then presents the design philosophy, interface specification, and execution workflow of ECP, followed by its current implementation progress validated through practical deployments, while also highlighting the future directions and unresolved challenges that will shape its standardization and large-scale adoption. As an interface protocol, ECP aims to evolve into a standardized interoperability ecosystem for embodied intelligence and industrial automation. Realizing this vision will require collaboration across academic and industrial communities to jointly advance the development, adoption, and standardization of ECP.

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder affecting the elderly, leading to important impairments in cognitive function and the ability to live independently. This results in substantial disability and places an increasing burden on families and society. Currently, the therapeutic approaches adopted in clinical practice predominantly hinge upon cholinesterase inhibitors and the N-methyl-d-aspartate (NMDA) receptor antagonist memantine. Nevertheless, these medications merely alleviate symptoms and fail to tackle the pathological characteristics of AD. In recent years, monoclonal antibodies such as lecanemab and donanemab against β-amyloid (Aβ) have shown good efficacy in clinical practice for early-stage AD patients. However, the early diagnosis of AD remains a challenge. Against this backdrop, endovascular brain–computer interface (EBCI) offers an integrated solution for the early diagnosis and neuroregulatory treatment of AD patients, with minimal invasiveness. This review comprehensively examines the safety and feasibility of EBCI for AD patients, focusing on 3 major application areas: early diagnosis, deep brain stimulation targeting specific brain regions, such as the fornix and the basal nuclei of Meynert, and the use of external neurofeedback devices. Furthermore, we explore future development trends in this field, including miniaturization, integration, and the exploration of deep brain regions.

Early mammalian embryos undergo crucial cell divisions despite lacking fully functional centrosomes, presenting a paradox of how mitotic fidelity is maintained. This commentary discusses a seminal study by Hernandez et al. that overturns the microtubule-centric model of early embryonic mitosis by revealing 2 essential, complementary F-actin networks. First, a formin-dependent nuclear F-actin network, cross-linked by anillin, positions prophase chromosomes and then drives their centripetal congregation upon nuclear envelope breakdown via a novel depolymerization-based contraction mechanism. Second, a branched, Arp2/3-dependent peri-spindle actin shell acts as a physical brake to restrain spindle elongation. Using advanced live imaging and targeted perturbations in mouse and human embryos, the study demonstrates that these actin assemblies collectively ensure accurate chromosome segregation by compensating for weak centrosomal activity. These findings redefine the mechanical landscape of early embryonic cell division, with profound implications for understanding the origins of aneuploidy and advancing reproductive medicine.

Magnetic resonance imaging (MRI) signal acquisition relies heavily on radio frequency (RF) coils, which play a critical role in obtaining high-quality images. However, traditional RF coils are often rigid and bulky and require complex decoupling mechanisms, limiting their adaptability and effectiveness for anatomically curved or dynamic regions. In this study, we present a novel high-impedance nonlinear metasurface (HINM) coil based on a “building bricks” concept to overcome these limitations. The HINM coil features a lightweight, flexible, wireless, and compact design that enables direct attachment to various anatomical regions, providing localized signal enhancement without the need for intricate adjustments for decoupling. This innovative approach utilized a flexible coaxial cable with a shielded design, ensuring stable frequency characteristics under bending, stretching, and dynamic conditions. Furthermore, the HINM coil with passive detuning did not alter the RF transmit field distribution while improving the signal-to-noise ratio (SNR) up to 87% in the surface region, as demonstrated by the phantom studies. In the knee and hand imaging, the SNR in the joint and finger areas was also doubled when using the HINM arrays. Enhanced image quality was achieved, and more subtle blood vessels were revealed in the hand vascular imaging with the use of the HINM arrays in combination with the commercial RF coils. Additionally, the HINM arrays were applied for the knee and hand imaging at 0.5 T, which achieved up to 74% SNR improvement, demonstrating its effectiveness for both low-field and ultrahigh-field MRI. By offering a versatile and adaptable solution, the HINM coil demonstrates its potential to transform MRI coil designs, particularly for imaging anatomically complex and dynamic environments.

The drive for complementary transistors with ultra-steep subthreshold swing (SS) and minimal power consumption has intensified interest in integrating low-dimensional semiconductors with wide-bandgap materials, as silicon scaling approaches its physical limits in the post-Moore era. A central bottleneck, however, lies in dielectric/semiconductor interface engineering: existing strategies based on van der Waals transfer or nonnative dielectric deposition compromise interface quality, wafer-scale uniformity, and process compatibility, preventing practical large-scale integration. Here, we demonstrate a previously unexplored in situ oxidation strategy that directly forms a high-κ gallium oxide (GaO_x) dielectric on heavily doped n-type gallium nitride (GaN) substrates, enabling high-performance, energy-efficient complementary inverters based on n-type molybdenum disulfide (MoS₂) and p-type carbon nanotube transistors. Leveraging the excellent dielectric properties of the GaN/GaO_x heterostructure, MoS₂ field-effect transistors achieve an interface trap density of 1.18 × 10¹¹ cm⁻² eV⁻¹, an SS at the thermionic limit of 60 mV dec⁻¹, an on/off ratio above 10⁸ at 0.87 V, and a voltage gain of 134.5 at 2 V for inverters. These results establish GaN/GaO_x as a native, scalable, and complementary metal-oxide-semiconductor-compatible integration platform, offering a transformative route toward wafer-scale, low-power electronics in the post-Moore era.

Cell fate determination is a complex and dynamic process. Across diverse cellular contexts, various protein modifications (PTMs) are involved throughout the entire process of cell fate determination. Linear ubiquitination is a specific type of PTM. Under the catalysis of linear ubiquitin chain assembly complex, multiple ubiquitin molecules form a unique linear ubiquitin chain and modify the substrate. A growing number of studies have shown that linear ubiquitination is an important regulatory target in the cell fate determination pathway, and that once the linear ubiquitination process of key proteins is defective, the cell fate determination process will be disrupted and lead to the development of various diseases. In this review, we systematically elaborated the key links between linear ubiquitination and cell fate determination from the aspects of cell proliferation, differentiation, senescence, and survival/death. Furthermore, we provide an in-depth exploration of the molecular mechanisms through which homeostatic imbalance of linear ubiquitination contributes to numerous diseases, including neoplastic, neurodegenerative, infectious, inflammatory, and metabolic disorders. Finally, we fully affirm the significance of linear ubiquitination as a promising therapeutic target for future drug discovery and development. Our critical appraisal and synthesis of the literature provide a foundational framework for future investigations and inform novel strategies for the treatment and management of related diseases.

Robotic exoskeletons have emerged as promising motion-assistive technologies to meet the growing demand for structured, personalized cancer rehabilitation. This review critically examines their application in enhancing functional recovery, alleviating cancer-related fatigue, and improving quality of life among cancer patients and survivors. We first outline current evidence-based exercise strategies in cancer rehabilitation, followed by an analysis of how robotic exoskeletons complement and extend these approaches by restoring mobility, strengthening musculature, and supporting psychological well-being. Additionally, we assess how well they combine with multimodal interventions like nutritional, psychological, and digital therapeutics and their benefits. The convergence of artificial intelligence, wearable sensors, and telemedicine is also reshaping the landscape of remote, adaptive rehabilitation. Despite encouraging preliminary data, widespread clinical adoption remains limited due to challenges related to cost, exoskeleton system accessibility, safety, and long-term efficacy. We call for large-scale clinical trials, interdisciplinary collaboration, and policy reforms to promote equitable access to robotic-assisted rehabilitation. Collectively, this review offers a comprehensive perspective on the technical principles, therapeutic potential, and future directions of robotic exoskeletons as innovative tools in cancer recovery.

Biomacromolecules are now widely employed in the therapy of major diseases such as tumors, infections, cardiovascular diseases, metabolic diseases, and autoimmune diseases. Although significant advances have been made in their application, their administration is largely dependent on professional injection, which causes pain, massive medical waste, and high medical burden. As a novel delivery system, microneedles pierce the stratum corneum to assist in intradermal drug delivery, exhibiting minimal invasiveness, high delivery efficiency, and improved patient compliance. The evolution of biomaterials and tissue engineering has broadened microneedle utilization to encompass oral and cardiovascular therapies. Herein, we discuss research advancements regarding the development of biomacromolecule-laden microneedles for treating major diseases. We present detailed examples on how to devise functional microneedles to cross drug delivery barriers in the skin, heart, and blood vessels for improved therapeutic outcomes. Furthermore, we discuss the critical barriers in industrial-scale fabrication and transitioning into clinical practice of microneedles, aiming to provide insightful solutions. Moreover, we explore the future applications of microneedles, including the development of microneedle tacks, robots, and biomimetics to combat intractable diseases. We believe that this review will aid in the designing of microneedles for biomacromolecule delivery, opening up a new avenue for the treatment of major diseases.