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There are four representative commentaries on the Duren jing from the Southern Song and Yuan Dynasties, authored by Qingyuan Zhenren, Xiao Yingsou, Chen Guanwu, and Xue Jizhao. These four commentaries combine both philological interpretation and philosophical interpretation, but each emphasizes one over the other. The Qingyuan and Xue focus on philological interpretation, aiming to reveal the original meaning of the text. The former offers detailed and in-depth philological analysis, occasionally integrating ideas on self-cultivation; the latter provides concise explanations, avoiding speculation and forced analogies. The Xiao and Chen commentaries, on the other hand, emphasize philosophical interpretation. Though grounded in philology, they primarily use the scripture as a medium to construct and develop the theory of internal alchemy. Xiao’s commentary pioneered a systematic approach to internal alchemy, while Chen’s work inherited and further developed this approach. In terms of interpretive strategy, the Qingyuan and Xue commentaries primarily use Taoist texts to support philological mutual verification, while the Xiao and Chen commentaries widely reference Confucian, Buddhist, and Taoist resources to conduct philosophical mutual verification. The differences in their interpretive approaches essentially originate from the commentators’ distinctly different pre-understandings. Through textual interpretation, they achieved varying degrees of “fusion of horizons” between the text’s original historical horizon and the contemporary horizon of the Song and Yuan Dynasties. The evolution from “explaining the text based on its original meaning” to “elucidating new philosophical ideas through the scripture” not only reflects a shift in Taoism from external ritual practices to internal alchemical cultivation, but also demonstrates the dialectical relationship between objective explanation and creative understanding, and provides significant intellectual resources for the development of contemporary Chinese hermeneutics.

HighlightsInspired by metalloenzymes with well-defined coordination structures, a series of Cu-X metal–organic frameworks (MOFs) nanozymes with tunable copper active centers were successfully constructed.Experimental and theoretical results strongly supported that precisely tuning the coordination of halogen atoms could directly regulate the enzyme-like activities of Cu-X MOFs by influencing their spatial configuration and electronic structure.The optimal Cu–Cl MOF with excellent enzyme-mimicking activities could effectively relieve ocular chemical burns by possible antioxidant and antiapoptotic mechanisms.Metal–organic frameworks (MOFs) have attracted significant research interest in biomimetic catalysis. However, the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a significant challenge. Inspired by metalloenzymes with well-defined coordination structures, a series of MOFs containing halogen-coordinated copper nodes (Cu-X MOFs, X = Cl, Br, I) are employed to elucidate their structure–activity relationship. Intriguingly, experimental and theoretical results strongly support that precisely tuning the coordination of halogen atoms directly regulates the enzyme-like activities of Cu-X MOFs by influencing the spatial configuration and electronic structure of the Cu active center. The optimal Cu–Cl MOF exhibits excellent superoxide dismutase-like activity with a specific activity one order of magnitude higher than the reported Cu-based nanozymes. More importantly, by performing enzyme-mimicking catalysis, the Cu–Cl MOF nanozyme can significantly scavenge reactive oxygen species and alleviate oxidative stress, thus effectively relieving ocular chemical burns. Mechanistically, the antioxidant and antiapoptotic properties of Cu–Cl MOF are achieved by regulating the NRF2 and JNK or P38 MAPK pathways. Our work provides a novel way to refine MOF nanozymes by directly engineering the coordination microenvironment and, more significantly, demonstrating their potential therapeutic effect in ophthalmic disease.

Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: “Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities.” The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint.

Dry eye is one of the most common ocular surface diseases in the world and seriously affects the quality of life of patients. As an immune-related disease, the mechanism of dry eye has still not been fully elucidated. The cGAS-STING pathway is a recently discovered pathway that plays an important role in autoimmune and inflammatory diseases by recognizing dsDNA. As an important signal to initiate inflammation, the release of dsDNA is associated with dry eye. Herein, we focused on the pathophysiology of the immune-inflammatory response in the pathogenesis of dry eye, attempted to gain insight into the involvement of dsDNA in the dry eye immune response, and investigated the mechanism of the cGAS-STING pathway involved in the immune-inflammatory response. We further proposed that the cGAS-STING pathway may participate in dry eye as a new mechanism linking dry eye and the immune-inflammatory response, thus providing a new direction for the mechanistic exploration of dry eye.

The innate immune response is the main pathophysiological process of ocular surface diseases exposed to multiple environmental stresses. The epithelium is central to the innate immune response, but whether and how innate immunity is initiated by ocular epithelial cells in response to various environmental stresses in ocular surface diseases, such as dry eye, is still unclear. By utilizing two classic experimental dry eye models—a mouse ocular surface treated with benzalkonium chloride (BAC) and a mouse model with surgically removed extraorbital lachrymal glands, as well as dry eye patient samples—along with human corneal epithelial cells (HCE) exposed to hyperosmolarity, we have discovered a novel innate immune pathway in ocular surface epithelial cells. Under stress, mitochondrial DNA (mtDNA) was released into the cytoplasm through the mitochondrial permeability transition pore (mPTP) and further activated the cyclic GMP-AMP synthase (cGAS)—stimulator of interferon genes (STING) pathway, aggravating downstream inflammatory responses and ocular surface damage. Genetic deletion or pharmacological suppression of STING and inhibition of mtDNA release reduced inflammatory responses, whereas mtDNA transfection supported cytoplasmic mtDNA-induced inflammatory responses by activating the cGAS-STING pathway. Our study clarified the cGAS-STING pathway-dependent sensing of mitochondrial DNA-mediated ocular surface inflammation, which elucidated a new mechanism of ocular surface diseases in response to multiple environmental stresses.

Dry eye can damage the ocular surface and result in mild corneal epithelial defect to blinding corneal pannus formation and squamous metaplasia. Significant progress in the treatment of dry eye has been made in the last two decades; progressing from lubricating and hydrating the ocular surface with artificial tear to stimulating tear secretion; anti-inflammation and immune regulation. With the increase in knowledge regarding the pathophysiology of dry eye, we propose in this review the concept of ocular surface microenvironment. Various components of the microenvironment contribute to the homeostasis of ocular surface. Compromise in one or more components can result in homeostasis disruption of ocular surface leading to dry eye disease. Complete evaluation of the microenvironment component changes in dry eye patients will not only lead to appropriate diagnosis, but also guide in timely and effective clinical management. Successful treatment of dry eye should be aimed to restore the homeostasis of the ocular surface microenvironment.

Inhibition of stearoyl-CoA desaturase 1 (SCD1) has been found to effectively suppress tumor cell proliferation and induce apoptosis in numerous neoplastic lesions. However, mechanism underlying SCD1-mediated anti-tumor effect has maintained unclear. Herein, we reported endo-lipid messenger ceramides played a critical role in tumor fate modulated by SCD1 inhibition. In vitro study in colorectal cancer cells demonstrated inhibition of SCD1 activity promoted apoptosis attributed to mitochondria dysfunctions, upregulation of reaction oxygen species (ROS), alteration of mitochondrial transmembrane potential and translocation of mitochondrial protein cytochrome C. While these effects were mediated by intracellular ceramide signals through induction of ceramide biosynthesis, rather than exclusive SFA accumulation. In vivo study in xenograft colorectal cancer mice showed pharmacologic administration of SCD1 inhibitor A939 significantly delayed tumor growth, which was reversed by L-cycloserine, an inhibitor of ceramide biosynthesis. These results depicted the cross-talk of SCD1-mediated lipid pathway and endo-ceramide biosynthesis pathway, indicating roles of ceramide signals in SCD1-mediated anti-tumor property.

Ultrasonic vibration-assisted laser welding is a very promising and innovative method, which uses the ultrasonic cavitation effect to suppress weld pool defects and improve weld quality. During ultrasonic-assisted laser welding, the high temperature of the weld will transfer to the ultrasonic system due to the long-time contact between the tool head and the weld, and the high temperature will cause the eigenfrequency of the ultrasonic oscillator to drift and unstable energy output. So, it is a very important and urgent problem to be solved. A frequency model of the ultrasonic oscillator is first established, and an optimization design method coupled finite element genetic algorithm and heat for the ultrasonic oscillator is proposed. This method can quickly predict the frequency mode and solve such problems as ultrasonic oscillator eigenfrequency drift and the existence of multiple resonance peaks in the design. Numerical simulation indicates that both sizes of the composite Ti-6Al-4 V conical horn and the tool head are negatively correlated with the eigenfrequency. The optimized total lengths of both the horn and the tool head are 77 mm and 65 mm, respectively. The eigenfrequency of the optimized ultrasonic oscillator satisfies the frequency tracking range (35 ± 0.5 kHz) in a wide temperature range. The experiment shows that no other non-working modes appear near the working frequency, which improves the output properties of ultrasonic energy, and the eigenfrequency of the optimized ultrasonic oscillator is 34, 790.3 Hz, which is agreement with the optimization, and the mechanical quality factor is up to 2899.2. The experimental and simulation results show that the theoretical and numerical optimization methods proposed in this paper can be applied not only in the structural design of the ultrasonic system for assisted laser welding, but also in the design and optimization of ultrasonic structures under other complex temperature conditions (glass molding, fouling removal, etc.).

This study was to explore a novel IL-33/ST2/IL-9/IL-9R signaling pathway that disrupts ocular surface barrier and amplifies allergic inflammation. Two murine models of experimental allergic conjunctivitis (EAC) and IL-9 topical challenge in wild type Balb/c and ST2−/− mice, and two culture models of primarily human corneal epithelial cells (HCECs) and mouse CD4+ T cells were performed. Clinical manifestations, Oregon-Green Dextran (OGD) staining, the apical junction complexes (AJCs), IL-33/ST2 and IL-9/IL-9R signaling molecules were evaluated in ocular surface and its draining cervical lymph nodes (CLNs) by RT-qPCR, immunostaining and ELISA. The typical allergic signs, enhanced OGD staining intensity, disrupted morphology of AJCs, including ZO-1, claudin 1, occludin, and E-cadherin, and the stimulated signaling of IL-33/ST2 and IL-9/IL-9R were observed in ocular mucosa and draining CLNs in EAC-Balb/c mice, but significantly reduced or eliminated in EAC-ST2−/− mice. Topical challenge of IL-9 resulted in the obvious OGD staining and disrupted ocular surface AJCs in Balb/c mice and in HCECs in vitro. IL-9 production was found to be stimulated by IL-33 in CD4+ cells from Balb/c mice in vitro. Our findings uncovered a novel phenomenon and mechanism by which ocular surface barrier integrity is disrupted in allergic conjunctivitis by IL-33/ST2/IL-9/IL-9R signaling pathway, which may amplify the allergic inflammation.

Dry eye, recognized as the most prevalent ocular surface disorder, has risen to prominence as a significant public health issue, adversely impacting the quality of life for individuals across the globe. Despite decades of extensive research into the chronic inflammation that characterizes dry eye, the intricate mechanisms fueling this persistent inflammatory state remain incompletely understood. Among the various cellular components under investigation, mitochondria—essential for cellular energy production and homeostasis—have attracted increasing attention for their role in dry eye pathogenesis. This involvement points to mechanisms such as oxidative stress, apoptosis, and sustained inflammation, which are central to the progression of the disease. This review aims to provide a thorough exploration of mitochondrial dysfunction in dry eye, shedding light on the critical roles played by mitochondrial oxidative stress, apoptosis, and mitochondrial DNA damage. It delves into the mechanisms through which diverse pathogenic factors may trigger mitochondrial dysfunction, thereby contributing to the onset and exacerbation of dry eye. Furthermore, it lays the groundwork for an overview of current therapeutic strategies that specifically target mitochondrial dysfunction, underscoring their potential in managing this complex condition. By spotlighting this burgeoning area of research, our review seeks to catalyze the development of innovative drug discovery and therapeutic approaches. The ultimate goal is to unlock promising avenues for the future management of dry eye, potentially revolutionizing treatment paradigms and improving patient outcomes. Through this comprehensive examination, we endeavor to enrich the scientific community’s understanding of dry eye and inspire novel interventions that address the underlying mitochondrial dysfunctions contributing to this widespread disorder.