Mengyu Liu

Skeletal muscle atrophy involves not only the loss of muscle mass and fiber size, but also a significant decline in contractile performance. Force decline often occurs before visible fiber atrophy, suggesting that early defects in neuromuscular transmission might trigger or exacerbate the wasting process. Therefore, we argue that neuromuscular junction (NMJ) degeneration is not a universal, conserved pathway across all atrophy syndromes. Instead, it should be viewed as a stage- and disease-specific event, with its actual contribution varying based on specific evidence. To explore this, we compare NMJ maintenance and degeneration across a broad spectrum of conditions, ranging from primary neuromuscular diseases (like denervation and motor neuron disorders) to systemic states such as aging, cachexia, and metabolic or respiratory diseases. Based on this, we propose a framework to evaluate NMJ involvement by timing, lesion type, and reversibility, drawing on diverse evidence from morphological, electrophysiological, and biomarker studies. Crucially, this approach distinguishes primary synaptic disorders from systemic conditions where NMJ damage acts merely as a secondary modifier. Ultimately, aligning specific molecular lesions with practical intervention windows will help refine patient stratification and guide the design of more targeted NMJ therapies.

The biological effects of molecular hydrogen are moving beyond the traditional explanatory framework of “selective antioxidation.” This article systematically integrates the basic, preclinical, and preliminary clinical evidence for hydrogen in metabolic diseases, neurodegenerative disorders, and cancer, centering on the two major themes of mitochondrial quality control and metabolic reprogramming. Current studies indicate that hydrogen can reshape redox homeostasis, coordinate mitochondrial biogenesis, dynamic balance, and mitophagy, and modulate key signaling axes such as AMPK/Sirtuins, PGC-1α, and PPARα, aimed at optimizing mitochondrial function, thereby influencing adaptive glucose and lipid metabolism as well as cellular bioenergetic homeostasis. Although its upstream initiating events and context dependency remain to be clarified, existing evidence supports the view that hydrogen is an important network regulator linking redox regulation, mitochondrial homeostasis, and metabolic adaptation.

Background: Wound healing is a complex and intricate biological process that involves multiple systems within the body and initiates a series of highly coordinated responses to repair damage and restore integrity and functionality. We previously identified that breathing hydrogen can significantly inhibit early inflammation, activate autologous stem cells, and promote the accumulation of extracellular matrix (ECM). However, the broader functions and downstream targets of hydrogen-induced ECM accumulation and tissue remodeling are unknown in the wound-healing process. Methods: Consequently, this thesis developed a hydrogen sustained-release dressing based on a micro storage material and reveals the mechanism of hydrogen in treating wound healing. Upon encapsulating the hydrogen storage materials, magnesium (Mg), and ammonia borane (AB), we found that SiO₂@Mg exhibits superior sustained-release performance, while SiO₂@AB demonstrates a higher hydrogen storage capacity. We used a C57/BL6 mouse full-thickness skin defect wound model to analyze and compare different hydrogen dressings. Results: It was identified that hydrogen dressings can significantly improve the healing rate of wounds by promoting epithelialization, angiogenesis, and collagen accumulation in wound tissue, and that the effect of slow-release dressings is better than of non-slow-release dressings. We also found that hydrogen dressing can promote transcriptome-level expression related to cell proliferation and differentiation and ECM accumulation, mainly through the Wnt1/β-catenin pathway and TGF-β1/Smad2 pathway. Conclusions: Overall, these results provide a novel insight into the field of hydrogen treatment and wound healing.

For decades, tissue regeneration has been a challenging issue in scientific modeling and human practices. Although many conventional therapies are already used to treat burns, muscle injuries, bone defects, and hair follicle injuries, there remains an urgent need for better healing effects in skin, bone, and other unique tissues. Recent advances in three-dimensional (3D) printing and real-time monitoring technologies have enabled the creation of tissue-like membranes and the provision of an appropriate microenvironment. Using tissue engineering methods incorporating 3D printing technologies and biomaterials for the extracellular matrix (ECM) containing scaffolds can be used to construct a precisely distributed artificial membrane. Moreover, advances in smart sensors have facilitated the development of tissue regeneration. Various smart sensors may monitor the recovery of the wound process in different aspects, and some may spontaneously give feedback to the wound sites by releasing biological factors. The combination of the detection of smart sensors and individualized membrane design in the healing process shows enormous potential for wound dressings. Here, we provide an overview of the advantages of 3D printing and conventional therapies in tissue engineering. We also shed light on different types of 3D printing technology, biomaterials, and sensors to describe effective methods for use in skin and other tissue regeneration, highlighting their strengths and limitations. Finally, we highlight the value of 3D bioengineered membranes in various fields, including the modeling of disease, organ-on-a-chip, and drug development.

The heterogeneous and highly plastic cell populations of macrophages are important mediators of cellular responses during all stages of wound healing, especially in the inflammatory stage. Molecular hydrogen (H₂), which has potent antioxidant and anti-inflammatory effects, has been shown to promote M2 polarization in injury and disease. However, more in vivo time series studies of the role of M1-to-M2 polarization in wound healing are needed. In the current study, we performed time series experiments on a dorsal full-thickness skin defect mouse model in the inflammatory stage to examine the effects of H₂ inhalation. Our results revealed that H₂ could promote very early M1-to-M2 polarization (on days 2–3 post wounding, 2–3 days earlier than in conventional wound healing), without disturbing the functions of the M1 phenotype. Time series analysis of the transcriptome, blood cell counts, and multiple cytokines further indicated that peripheral blood monocytes were a source of H₂-induced M2 macrophages and that the functions of H₂ in macrophage polarization were not only dependent on its antioxidant effects. Therefore, we believe that H₂ could reduce inflammation in wound care by shifting early macrophage polarization in clinical settings.

Molecular hydrogen (H₂) exhibits a wide breadth of botanical effects especially in improving the resistance to abiotic stress. However, the primary target is not clear. Bidirectional hydrogenases have been well studied in microbes and alga, but there is a paucity of research in higher plants. Here, we used real-time spectrophotometry, gas chromatography and H₂ sensor to detect the H₂-evolving and H₂-uptake activity of the plasma membrane (PM) vesicles of higher plants. Net H⁺, Na⁺ and K⁺ fluxes were measured using Non-invasive Micro-test Technology (NMT). We found that the PM vesicles of Vigna radiata hypocotyls and Capsicum annuum stems have the ability of both oxidizing and producing H₂. This two-way enzymatic activity coupled with the redox of ferricyanide/ferrocyanide and NADH/NAD⁺. H₂ affected the H⁺ and Na⁺ fluxes on the surface of V. radiata hypocotyls. These results demonstrate that the PM vesicles of higher plants have the abilities of H₂ evolution and absorption. The bidirectional activities may act as a valve to regulate the energy balance in plant cells.