Latest ArticlesPeripartum dairy cows commonly experience energy metabolism disorders, which lead to passive culling of postpartum cows and a decrease in milk quality. By using ketosis peripartum dairy cows as a model, this study aims to elucidate the metabolic mechanism of peripartum cows and provide a novel way for managing energy metabolic disorders. From a cohort of 211 cows, we integrated multi-omics data (metagenomics, metabolomics, and transcriptomics) to identify key microbes and then utilized an in vitro rumen fermentation simulation system and ketogenic hepatic cells to validate the potential mechanisms and the effects of postbiotics derived from key microbes. Postpartum cows with metabolic disorders compensate for glucose deficiency through mobilizing muscle proteins, which leads to marked decreases in milk protein content. Concurrently, these cows experience rumen microbiota disturbance, with marked decreases in the concentrations of volatile fatty acids and microbial protein, and the deficiency of alanine (Ala) in microbial protein is correlated with the metabolic disorder phenotype. Metagenomic binning and in vitro fermentation assays reveal that Ruminococcus_E bovis (MAG 189) is enriched in amino acid biosynthesis functions and responsible for Ala synthesis. Furthermore, transcriptomic and metabolomic analyses of the liver in metabolic disorder cows also show impaired amino acid metabolism. Supplementation with Ala can alleviate ketogenesis in liver cell models by activating the gluconeogenesis pathway. This study reveals that Ruminococcus_E bovis is associated with host energy metabolism homeostasis by supplying glucogenic precursors to the liver and suggests the use of Ala as a method for the treatment of energy metabolism disorders in peripartum cows.
Bacterial infections markedly strain healthcare systems financially, compounded by the rise of drug-resistant strains and biofilm-associated infections. Gas therapy has emerged as a notable solution, disrupting biofilms and targeting resistant bacteria through controlled gas release mechanisms. However, achieving precise and controlled gas release remains a critical challenge for the successful implementation of gas therapy. In this perspective, we summarize recent advancements in photocatalytic gas release for treating bacterial infections. It also outlines crucial challenges that must be addressed to fully leverage this promising therapeutic strategy, enhancing its precision and effectiveness in clinical settings.
Fusobacterium nucleatum (Fn), an oral anaerobic commensal, has recently been identified as a crucial oncogenic contributor to colorectal cancer pathogenesis through its ectopic colonization in the gastrointestinal tract. Accumulating evidence reveals its multifaceted involvement in colorectal cancer initiation, progression, metastasis, and therapeutic resistance to conventional treatments, including chemotherapy, radiotherapy, and immunotherapy. This perspective highlights recent advances in anti-Fn strategies, including small-molecule inhibitors, nanomedicines, and biopharmaceuticals, while critically analyzing the translational barriers in developing targeted antimicrobial interventions. We further propose potential strategies to overcome current challenges in Fn modulation, aiming to pave the way for more effective therapeutic interventions and better clinical outcomes.
Bariatric surgery has emerged as a promising intervention for obese women with polycystic ovary syndrome (PCOS), a condition strongly associated with obesity and anovulatory infertility. While weight management is a key therapeutic strategy, the optimal approach remains uncertain. A recent randomized controlled trial evaluated the impact of bariatric surgery on ovulation rates in obese women with PCOS. However, methodological limitations, including baseline body mass index discrepancies and minimal weight loss in the medical management group, necessitate cautious interpretation of the findings. To further investigate this issue, we conducted a prospective cohort study involving 192 women with PCOS who had undergone bariatric surgery. We assessed 30 reproductive and metabolic parameters at baseline and at 3, 6, and 12 months postoperatively. Most metabolic parameters improved significantly by 3 months postsurgery but plateaued thereafter, with only triglycerides and high-density lipoprotein cholesterol showing continued improvement. Reproductive outcomes demonstrated sustained improvements in ovulatory dysfunction, coinciding with a reduction in luteinizing hormone levels. However, testosterone levels and polycystic ovarian morphology showed limited improvement, while anti-Müllerian hormone levels remained unchanged. Despite the total weight loss exceeding 30%, further weight reduction did not proportionally enhance outcomes. These findings suggest that while bariatric surgery effectively improves metabolic health and ovulation in PCOS, its long-term hormonal and ovarian effects remain unclear and require further investigation. Head-to-head comparisons with emerging therapies are also urgently needed to refine weight management strategies for this high-risk population.
Twisted nylon actuators (TNAs) are widely recognized in soft robotics for their excellent load-to-weight ratio and cost-effectiveness. However, their limitations in deformation and output force restrict their ability to support more advanced applications. Here, we report 3 performance-enhancing strategies inspired by the construction process of chromosome, which are validated through 3 novel types of TNAs. First, we design a dual-level helical structure, demonstrating remarkable improvements in the deformation (60.2% vertically and approximately 100% horizontally) and energy storage capability (launching a miniature basketball to 131 cm in height). Second, we present a parallel-twisted method, where the output force of TNAs reaches 11.0 N, achieving 12.1% contraction under a load of 15 N (10,000 times its weight). Additionally, we construct the dual-level helical structure based on parallel-twisted TNAs, resulting in a 439.7% improvement in load capability. We have adopted TNAs for several applications: (a) two bionic elbows capable of rotating and shooting a miniature basketball over 130 cm; (b) a robot that can rapidly jump over 30 cm; and (c) a soft finger that achieves contracting (15.3% contraction under 2 kg load), precise bending (tracking errors less than 2.0%), and twisting motions. This work presents approaches for fabricating high-performance soft actuators and explores the potential applications of these actuators for driving soft robots with multifunctional capabilities.
Accurately reconstructing the intricate structure of natural organisms is the long-standing goal of 3-dimensional (3D) bioprinting. Projection-based 3D printing boasts the highest resolution-to-manufacturing time ratio among all 3D-printing technologies, rendering it a highly promising technique in this field. However, achieving standardized, high-fidelity, and high-resolution printing of composite structures using bioinks with diverse mechanical properties remains a marked challenge. The root of this challenge lies in the long-standing neglect of multi-material printability research. Multi-material printing is far from a simple physical assembly of different materials; rather, effective control of material interfaces is a crucial factor that governs print quality. The current research gap in this area substantively hinders the widespread application and rapid development of multi-material projection-based 3D bioprinting. To bridge this critical gap, we developed a multi-material projection-based 3D bioprinter capable of simultaneous printing with 6 materials. Building upon this, we established a fundamental framework for multi-material printability research, encompassing its core logic and essential process specifications. Furthermore, we clarified several critical issues, including the cross-linking behavior of multicomponent bioinks, mechanical mismatch and interface strength in soft–hard composite structures, the penetration behavior of viscous bioinks within hydrogel polymer networks, liquid entrapment and adsorption phenomena in porous heterogeneous structures, and error source analysis along with resolution evaluation in multi-material printing. This study offers a solid theoretical foundation and guidance for the quantitative assessment of multi-material projection-based 3D bioprinting, holding promise to advance the field toward higher precision and the reconstruction of more intricate biological structures.
The metaverse enables immersive virtual healthcare environments, presenting opportunities for enhanced care delivery. A key challenge lies in effectively combining multimodal healthcare data and generative artificial intelligence abilities within metaverse-based healthcare applications, which is a problem that needs to be addressed. This paper proposes a novel multimodal learning framework for metaverse healthcare, MMLMH, based on collaborative intra- and intersample representation and adaptive fusion. Our framework introduces a collaborative representation learning approach that captures shared and modality-specific features across text, audio, and visual health data. By combining modality-specific and shared encoders with carefully formulated intrasample and intersample collaboration mechanisms, MMLMH achieves superior feature representation for complex health assessments. The framework's adaptive fusion approach, utilizing attention mechanisms and gated neural networks, demonstrates robust performance across varying noise levels and data quality conditions. Experiments on metaverse healthcare datasets demonstrate MMLMH's superior performance over baseline methods across multiple evaluation metrics. Longitudinal studies and visualization further illustrate MMLMH's adaptability to evolving virtual environments and balanced performance across diagnostic accuracy, patient–system interaction efficacy, and data integration complexity. The proposed framework has a unique advantage in that a similar level of performance is maintained across various patient populations and virtual avatars, which could lead to greater personalization of healthcare experiences in the metaverse. MMLMH's successful functioning in such complicated circumstances suggests that it can combine and process information streams from several sources. They can be successfully utilized in next-generation healthcare delivery through virtual reality.
Since the scarcity of bandwidth resources has become increasingly critical in modern communication systems, orbital angular momentum (OAM) with a higher degree of freedom in information modulation has become a promising solution to alleviate the shortage of spectrum resources. Consequently, the integration of OAM with millimeter-wave technology has emerged as a focal point in next-generation communication research. Recently, programmable metasurfaces have gained considerable attention as essential devices for OAM generation due to real-time tunability, but their profiles are relatively high as a result of the external feed source. This paper proposes a conformal radiation-type programmable metasurface operating in the millimeter-wave band. By employing a series–parallel hybrid feed network to replace conventional external feed sources, the overall profile of the metasurface system can be reduced to less than 0.1λ. Furthermore, the proposed innovation design could also achieve a conformal cross-shaped architecture, which is ultraportable and very effective in integrating with the front ends of satellites or aircraft and eliminating issues such as feed source blockage as well as energy spillover losses in conventional metasurfaces. The proposed metasurface could achieve a realized gain of 22.54 dB with an aperture efficiency of 21.75%, thus generating high-purity OAM waves with topological charges of l = 0, l = +1, l = +2, and l = +3. Additionally, by incorporating beam scanning techniques, OAM waves could be deflected to accommodate scenarios with moving receivers, demonstrating substantial potential for future high-speed wireless communication applications.
Plant diseases caused by vegetable viruses are an important threat to global food security, presenting a major challenge for the development of antiviral agrochemicals. Functional proteins of plant viruses play a crucial role in the viral life cycle, and targeted inhibition of these proteins has emerged as a promising strategy. However, the current discovery of antiviral small molecules is hampered by the limitations of synthetic approaches and the narrow range of targets. Herein, we report a practical application of organocatalysis for serving pesticide discovery that bears a unique molecular basis. An N-heterocyclic carbene-modulated reaction is first designed to asymmetrically functionalize diverse natural phenols with phthalides. Our designed method is capable of producing a series of new phthalidyl ethers under mild conditions with good yields, enantioselectivity, and functional group tolerance. Among these, compound (R)-3w exhibits excellent and enantioselectivity-preferred curative activity against potato virus Y (PVY). Mechanistically, it is proposed that (R)-3w interacts with the nuclear inclusion body A (Nia) protein of PVY at the His150 residue. This binding impairs Nia's function to cleavage polyprotein, thereby inhibiting formation of viral replication complex. The study provides insights into advancing synthetic protocol to facilitate agrochemical discovery, and our identified (R)-3w may serve as a potential lead for future research and development PVY-Nia inhibitors.
Adoptive T cell therapy has shown great promise in the treatment of solid tumors, which, however, poses a great challenge to obtain autologous tumor-reactive T cells in a cost-effective manner. Here, we present a dynamic tumor immunology-on-a-chip, mimicking immune responses, for achieving the enrichment and expansion of tumor-reactive T cells. Tumor spheroids with uniform size can be generated by seeding tumor cells in hydrogel-embedded micropillar arrays, and could be trapped upon removal of hydrogel. Then, T cells were infused and fully contacted with these tumor spheroids under biomimetic flow conditions provided by herringbone-patterned microgrooves arrays. We found that the tamed tumor-reactive T cells could be fully activated and a rapid clonal proliferation was realized during the cultivation. In addition, these tumor-reactive T cells exhibited a specific and powerful tumor-killing capability in vitro. Thus, the suggested dynamic microfluidic chips with staged structure-transformable properties realize both the producible formation of tumor spheroids and the recapitulation of tumor-immune crosstalk to expand tumor-reactive T cells. These features indicate that the dynamic and reproducible tumor immunology-on-a-chip has potential in the preparation of therapeutic T cell products for clinical cancer immunotherapy.