Klebsiella pneumoniae (KP), recognized for its pronounced antibiotic resistance, is a prevalent agent of nosocomial infections such as hospital-acquired pneumonia. The alarming rate of serious infections and associated mortality renders KP a significant public health threat. Extracellular vesicles (EVs) are pivotal in KP's physiological and pathological mechanisms, facilitating material and information transfer and mediating interactions between the bacteria and the host. The critical role of EVs enhances our understanding of KP pathophysiology, disease progression, and strategies for infection control. This review emphasizes the mechanics of KP's antibiotic resistance and the instrumental role of EVs in the bacterium-host interplay, proposing EVs as a promising research focus for advancing KP diagnosis, therapy, and prevention.
After more than 20 years of development, synthetic biology has emerged as an interdisciplinary field that integrates biology, medicine, mathematics, and engineering. By constructing and regulating genetic elements, networks, and pathways, artificially engineered bacteria, cells, or viruses can directly interact with the human body to enable disease treatment via synthetic biology. Additionally, synthetic biology platforms have been employed in the production of medical biomaterials (MBMs), indirectly contributing to the maintenance of human health. In this review, we present a range of typical MBMs derived from synthetic biology platforms, including polylactic acid, polyhydroxyalkanoates, hyaluronic acid, collagen, poly(β-hydroxybutyrate), poly(β-malic acid), poly-γ-glutamic acid, alginate, chitosan, bacterial cellulose, and antimicrobial peptides. We also introduce the key synthetic biology techniques and tools involved, such as chassis cell design, gene expression regulation and editing tools represented by CRISPRi, metabolic engineering, cell morphology engineering, and cell-free systems. Furthermore, we summarize recent advancements and strategies including enhancing production and cost-reduction, biosynthesis of novel materials, regulating material characteristics and diversity, minimizing toxicity in biosynthetic systems, and designing engineered living materials in the research applications and clinical translation of synthetic biology for MBMs. Finally, we discuss emerging trends that may shape the future biomedical applications of synthetic biology.
The skin, as the body's largest organ, plays essential roles in protection, immune regulation, and homeostasis. Skin trauma, especially chronic wounds such as diabetic ulcers, poses significant clinical challenges. Traditional treatments, while often effective, can be costly and pose risks. Herbal remedies offer a promising alternative given their rich history of use and multitarget therapeutic actions. This review explores bioactive compounds in herbs-such as saponins, phenolic compounds, polysaccharides, oils, amino acids, and quinones—and their functions in wound healing. These bioactive substances modulate cellular and molecular pathways, including vascular endothelial growth factor, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2-STAT3), and Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), enhancing processes like angiogenesis, epithelial proliferation, granulation, and immune regulation. Additionally, innovative wound dressings infused with these bioactives, including hydrogels, sponges, and bioadhesives, provide multifunctional benefits such as moisture retention, antimicrobial activity, and improved mechanical strength. Design principles in these dressings focus on enhancing biocompatibility, stability, and therapeutic efficacy using bioactive compounds to support healing and tissue regeneration. This comprehensive review underscores the potential of bioactive herbal materials in wound care, highlighting their diverse mechanisms and adaptability in developing effective multifunctional dressings. Future research should optimize these bioactive-infused dressings for clinical applications, ensuring efficacy and safety in managing complex wounds.
Bacterial extracellular vesicles (BEVs) are nanoscale vesicles secreted by bacteria. They possess lipid bilayer membranes and contain multiple periplasmic and cytoplasmic components, facilitating their intercellular communications through transferring of various bioactive molecules. Considering their intrinsic structure, delivery capacity, immunogenic property, facile production, and versatile modification, more and more studies have exploited BEVs directly as therapeutic agents or engineered as delivery vehicles for the disease treatment. Nevertheless, the unprecedented upsurge of studies in BEVs highlighted the burgeoning need for tailoring them with enhanced therapeutic efficacies including specific targeting, subcellular penetration, pathological site retention, and so on. With this aspect, functional peptides with either targeting, penetrating, immunostimulating, specific biofunctions, or self-assembly exhibit their power to open new avenues. Functional peptides can be either modified on the surface, encapsulated inside the bilayer membranes, or even self-assembled into hydrogel embedding around BEVs to fully unleash the therapeutic potential of BEVs. Herein, the present perspective is dedicated to overview the most recent advancements in exploring functional peptides for bridging BEVs to disease treatment, and to provide valuable insights for the future development of innovative therapeutic modalities.
Hepatitis B virus (HBV) infection represents a significant global public health threat, often progressing to severe complications such as liver cirrhosis and hepatocellular carcinoma (HCC). Despite the World Health Organization’s 2030 challenge to eliminate HBV, achieving a functional cure remains a major milestone in the fight against the disease. However, even with functional cure, the risk of HCC persists, necessitating ongoing surveillance. Hopefully, advances in technological innovations, artificial intelligence, and the establishment of data platforms have enhanced both functional cure prediction and surveillance strategies. This review examines recent advancements in HBV therapies, prediction models for chronic hepatitis B (CHB) functional cure (such as the GOLDEN model) for evaluating these new approaches, and the current state of HCC surveillance. Furthermore, the potential of novel biomarkers is highlighted in the context of precision medicine to improve CHB functional cure and HCC risk assessment.
Brain-Computer Interface (BCI) based on motor imagery (MI) has attracted great interest as a new rehabilitation method for stroke. Riemannian geometry-based classification algorithms are widely used in MI-BCI due to their strong robustness and generalization capabilities. However, the clustering performance of current algorithms needs to be improved due to unsuitable clustering criteria for electroencephalography (EEG) characteristics of lower limbs. This study proposed two classification methods based on Riemannian clustering: margin based Riemannian clusters (MBRC) and statistics based Riemannian clusters (SBRC) to address this issue. Our methods divide all samples into subclusters based on the Riemannian distance and innovate clustering criteria. We introduced cluster margin distance and the Riemannian potato algorithm as two clustering criteria to achieve a more robust classification of lower limb MI-EEG. MBRC and SBRC were tested on an experimental dataset and a public Yi2014 dataset. For the experimental dataset, the average accuracies of MBRC and SBRC were 71.29% and 73.12%, respectively, higher than that of the baseline algorithms. For the Yi2014 dataset, MBRC and SBRC performed better than the comparison algorithms under different training sample numbers, particularly when the number of samples was limited. These findings suggest that the proposed algorithms are more effective for classifying lower limb MI EEGs.
The clinical significance, digital attributes, and underlying high-dimensional information in medical images make them a key area for the artificial intelligence (AI) revolution in health care. Generative AIs (GAIs) provide unprecedented abilities in synthesizing diverse and accurate simulated medical images for AI model training as well as personalized disease management. However, several hurdles must be overcome prior to clinical implementation, such as biases introduced during training in synthesized images and the risk of medical and research falsification. This review outlines the current landscape of medical image synthesis through GAIs, with a specific focus on the variety of medical images to be synthesized, various real-world issues to be solved, and the evaluation of the quality and utility of the synthesized images. We finally summarize the key challenges, propose potential solutions, and highlight promising directions for future research, with the aim of providing guidance for upcoming research.
The establishment of new functional connections through axon regeneration is essential for functional recovery following spinal cord injury (SCI). With the rapid advancement of nanotechnology, nanomaterial (NM)-based therapies have emerged as promising approaches to promote axon regeneration after SCI. Specifically, NMs can limit the spread of damage, maintain homeostasis in the extracellular environment surrounding injured axons, and ultimately facilitate axon growth following SCI. In particular, NMs with enzyme-like properties, such as cerium oxide and manganese dioxide, can clear reactive oxygen species in the damaged area, thereby promoting axon regeneration. Additionally, NMs with electromagnetic properties can promote and guide axon regeneration under the influence of magnetic or electric fields. Importantly, the biological mechanisms by which NMs promote axon regeneration are summarized and discussed to explore promising NM-based strategies for achieving functional recovery after SCI. Together, elucidating the physicochemical properties of NMs and the biological basis for their promotion of axon regeneration after SCI can help fill the gaps in our understanding of how NMs can be used to treat SCI and further the clinical translation of NMs in the future.
As magnetic nanomaterials, nanomagnetic beads are constantly being innovated in various applications. With the advantages of superparamagnetism and rapid magnetic response, nanomagnetic beads can be controlled for various type of movements under external magnetic fields, such as fixation, aggregation, or dispersion. Meanwhile, the nanomagnetic beads can be composited with multiple functional materials, therefore, expanding the applications in biomedical, environmental monitoring, and food safety. For example, the integration of nanomagnetic beads with magnetoresistive sensors can amplify the detection signals through the superparamagnetic properties. With the modification of recognition components, nanomagnetic beads can function by specifically binding target analytes, serving as sensitive elements for biosensing. In this review, we firstly summarized the fabrication approaches of nanomagnetic beads, supporting fundamental information for their applications. Then, roles of nanomagnetic beads in the field of biosensing were systematically discussed, such as sample preparation, sensitive elements immobilization, signal amplification, and sensitive detection. Through the investigation of nanomagnetic beads applications on biosensing, we finally evaluated current bottlenecks in the development of biosensors and predicted the future opportunities and challenges of biosensors based on the advancement of nanomagnetic beads.
Extracellular vesicles (EVs) are nano-sized structures released by cells into the surrounding milieu, enclosed within a lipid bilayer, and play a pivotal role in facilitating intercellular communication. Although mammalian-derived EVs possess clinical potential, their production and safety concerns restrict their application. Plant nanovesicles, have emerged as promising alternatives to mammalian-derived EVs due to their abundance, high yield extraction, low toxicity, and low immunogenicity. In particular, Chinese herbal medicine-derived extracellular vesicle-like particles (CHM-EVLP) paved the way for the modernization of Chinese medicine and hold significant potential as novel pharmacodynamic substances in traditional Chinese medicine. This article presents a comprehensive overview of the latest advancements in CHM-EVLP research, explores its potential as an innovative therapeutic approach, and proposes research ideas and key focal points for the future advancement of CHM-EVLP.
3D bioprinting is a transformative technology for fabricating biomimetic tissue constructs with significant potential in tissue engineering and regenerative medicine. However, developing sustainable bio-inks that achieve good printability, mechanical strength, and stability under physiological conditions without costly and time-consuming chemical modifications remains a major challenge. In this study, we present a cost-effective and sustainable physically crosslinked gelatin-based bio-ink (Gel-X) composed of gelatin, gellan gum, and Laponite XLG for multi-modal bioprinting. The composite Gel-X bio-ink is prepared in a straightforward and rapid manner (∼1 h) by simply stirring the different polymers in deionized water, eliminating the need for chemical crosslinkers. This formulation offers improved printability, mechanical properties, and controlled degradation and dimensional stability. Notably, the incorporation of Laponite XLG strengthens the gel network, further improving the structural integrity and mechanical robustness over time. Our results demonstrate that the cell-laden Gel-X tissue constructs maintain their structural integrity and robustness under physiological conditions, effectively addressing the rapid degradation and poor mechanical performance associated with conventional physically crosslinked bio-inks. Furthermore, Gel-X tissue constructs exhibit good biocompatibility, enabling the fabrication of highly complex and robust 3D structures suitable for bioprinting applications. By eliminating the reliance on chemical crosslinkers, Gel-X bio-ink provides a sustainable solution for advanced multi-modal bioprinting. This innovation not only overcomes existing limitations in bio-ink design but also broadens the accessibility and utility of 3D bioprinting.
Death represents the end of all living organisms. The pattern of brain activity disappearance following death, however, has not been fully elucidated. Here we investigated brain activity dynamics following cardiac arrest using ultra-high field 11.7 T magnetic resonance imaging (MRI) in longitudinal approach and multi-modal analyses. Initially, the functional connectivity (FC) analysis revealed a non-linear trajectory of whole-brain network disassembly. Subsequently, through dynamic FC analysis, we identified two discrete FC patterns in the whole brain that showed opposite changes from life to death, representing the dissipation process of local brain function specificity. In addition, the default mode network (DMN), sensorimotor network (SMN), and interoceptive network (IN) were identified during the live stage by independent component analysis. However, results of dynamic functional network connectivity analysis showed that SMN and IN preferentially disappeared after cardiopulmonary arrest, which is the critical turning point of death. Notably, the surviving DMN showed a decreased spatial map but stronger FC with the right dorsolateral thalamus, retrosplenial cortex, and corpus callosum during the near-death stage. This suggests that DMN may be the final regulator of systemic brain shutdown. This study aims to address the limited understanding of brain function changes during death from an imaging perspective and provides inspirations for the definition of death and the inference of death time.