GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.

Membrane proteins are integral components of cellular membranes, accounting for approximately 30% of the mammalian proteome and serving as targets for 60% of FDA-approved drugs. They are critical to both physiological functions and disease mechanisms. Their functional protein-protein interactions form the basis for many physiological processes, such as signal transduction, material transport, and cell communication. Membrane protein interactions are characterized by membrane environment dependence, spatial asymmetry, weak interaction strength, high dynamics, and a variety of interaction sites. Therefore, in situ analysis is essential for revealing the structural basis and kinetics of these proteins. This paper introduces currently available in situ analytical techniques for studying membrane protein interactions and evaluates the characteristics of each. These techniques are divided into two categories: label-based techniques (e.g., co-immunoprecipitation, proximity ligation assay, bimolecular fluorescence complementation, resonance energy transfer, and proximity labeling) and label-free techniques (e.g., cryo-electron tomography, in situ cross-linking mass spectrometry, Raman spectroscopy, electron paramagnetic resonance, nuclear magnetic resonance, and structure prediction tools). Each technique is critically assessed in terms of its historical development, strengths, and limitations. Based on the authors’ relevant research, the paper further discusses the key issues and trends in the application of these techniques, providing valuable references for the field of membrane protein research. Label-based techniques rely on molecular tags or antibodies to detect proximity or interactions, offering high specificity and adaptability for dynamic studies. For instance, proximity ligation assay combines the specificity of antibodies with the sensitivity of PCR amplification, while proximity labeling enables spatial mapping of interactomes. Conversely, label-free techniques, such as cryo-electron tomography, provide near-native structural insights, and Raman spectroscopy directly probes molecular interactions without perturbing the membrane environment. Despite advancements, these methods face several universal challenges: (1) indirect detection, relying on proximity or tagged proxies rather than direct interaction measurement; (2) limited capacity for continuous dynamic monitoring in live cells; and (3) potential artificial influences introduced by labeling or sample preparation, which may alter native conformations. Emerging trends emphasize the multimodal integration of complementary techniques to overcome individual limitations. For example, combining in situ cross-linking mass spectrometry with proximity labeling enhances both spatial resolution and interaction coverage, enabling high-throughput subcellular interactome mapping. Similarly, coupling fluorescence resonance energy transfer with nuclear magnetic resonance and artificial intelligence (AI) simulations integrates dynamic structural data, atomic-level details, and predictive modeling for holistic insights. Advances in AI, exemplified by AlphaFold’s ability to predict interaction interfaces, further augment experimental data, accelerating structure-function analyses. Future developments in cryo-electron microscopy, super-resolution imaging, and machine learning are poised to refine spatiotemporal resolution and scalability. In conclusion, in situ analysis of membrane protein interactions remains indispensable for deciphering their roles in health and disease. While current technologies have significantly advanced our understanding, persistent gaps highlight the need for innovative, integrative approaches. By synergizing experimental and computational tools, researchers can achieve multiscale, real-time, and perturbation-free analyses, ultimately unraveling the dynamic complexity of membrane protein networks and driving therapeutic discovery.

ObjectiveTo evaluate the effects of phases on the pharmacokinetic behavior of seven components from Banxia Xiexintang（BXT） in normal rats by investigating and comparing their pharmacokinetic profiles in different phase samples. MethodsThe phase separation of BXT was carried out by centrifugation-dialysis method， and three phase samples were obtained， including the precipitated phase（PP）， colloidal phase（CP） and true solution phase（TP）. A total of 24 male SD rats were randomly divided into BXT， PP， CP and TP groups（n=6）. The BXT group was gavaged at a dose of 24.1 g·kg^-1（calculated by the dosage of raw materials）. After proper treatments， PP， CP and TP groups were administrated at the same dose as that of BXT group， respectively. Blood was collected from each group at set time points after gavage of BXT and the phase samples. The contents of 7 components（baicalin， wogonoside， wogonin， berberine， palmatine， ammonium glycyrrhizinate and isoliquiritin） in rat plasma were determined by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）， and the pharmacokinetic parameters of each component were analyzed by DAS 2.0. ResultsThe peak concentration of baicalin was the highest among the blood-entered components in each group， followed by wogonoside. The results of the concentration-time curves and pharmacokinetic parameters of the 7 components showed that the area under the concentration-time curve（AUC） of isoliquiritin in the BXT group was the highest， followed by that in the CP group. AUC values of baicalin， wogonoside， wogonin and ammonium glycyrrhizinate in the BXT group were similar to those of the CP group， and AUC of palmatine in the BXT group was similar to that of the PP group. The elimination half-life（t_1/2） values of baicalin and wogonoside in the BXT group was the longest， the t_1/2 values of ammonium glycyrrhizinate and berberine were similar to those of the CP group， and the t_1/2 of palmatine was similar to that of the PP group. The t_1/2 of wogonin was the longest in the PP group， and the t_1/2 of isoliquiritin was the longest in the TP group was the longest， which was similar to that in the PP group. Except for isoliquiritin， the other 6 components showed double peaks in the concentration-time curve of the PP group， indicating that the above components might be reabsorbed through the enterohepatic circulation in vivo， which resulted in the maintenance of high plasma concentrations for a long time， and consequently exhibited sustained-release properties. ConclusionThe pharmacokinetic characteristics of the components in different phases were different， and the CP phase may be the effective phase from the perspective of the pharmacological action of BXT. Compared with the BXT group， the in vivo action times of some components in the CP and PP groups were prolonged. The study explores the phase differences of traditional Chinese medicine（TCM） compound decoction in the aspect of pharmacokinetics， and verifies that the phase states from TCM compound decoction will affect the pharmacokinetic behaviors of the active components， which may consequently lead to the difference in in vivo effects.

ObjectiveTo evaluate the effects of phases on the pharmacokinetic behavior of seven components from Banxia Xiexintang（BXT） in normal rats by investigating and comparing their pharmacokinetic profiles in different phase samples. MethodsThe phase separation of BXT was carried out by centrifugation-dialysis method， and three phase samples were obtained， including the precipitated phase（PP）， colloidal phase（CP） and true solution phase（TP）. A total of 24 male SD rats were randomly divided into BXT， PP， CP and TP groups（n=6）. The BXT group was gavaged at a dose of 24.1 g·kg^-1（calculated by the dosage of raw materials）. After proper treatments， PP， CP and TP groups were administrated at the same dose as that of BXT group， respectively. Blood was collected from each group at set time points after gavage of BXT and the phase samples. The contents of 7 components（baicalin， wogonoside， wogonin， berberine， palmatine， ammonium glycyrrhizinate and isoliquiritin） in rat plasma were determined by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）， and the pharmacokinetic parameters of each component were analyzed by DAS 2.0. ResultsThe peak concentration of baicalin was the highest among the blood-entered components in each group， followed by wogonoside. The results of the concentration-time curves and pharmacokinetic parameters of the 7 components showed that the area under the concentration-time curve（AUC） of isoliquiritin in the BXT group was the highest， followed by that in the CP group. AUC values of baicalin， wogonoside， wogonin and ammonium glycyrrhizinate in the BXT group were similar to those of the CP group， and AUC of palmatine in the BXT group was similar to that of the PP group. The elimination half-life（t_1/2） values of baicalin and wogonoside in the BXT group was the longest， the t_1/2 values of ammonium glycyrrhizinate and berberine were similar to those of the CP group， and the t_1/2 of palmatine was similar to that of the PP group. The t_1/2 of wogonin was the longest in the PP group， and the t_1/2 of isoliquiritin was the longest in the TP group was the longest， which was similar to that in the PP group. Except for isoliquiritin， the other 6 components showed double peaks in the concentration-time curve of the PP group， indicating that the above components might be reabsorbed through the enterohepatic circulation in vivo， which resulted in the maintenance of high plasma concentrations for a long time， and consequently exhibited sustained-release properties. ConclusionThe pharmacokinetic characteristics of the components in different phases were different， and the CP phase may be the effective phase from the perspective of the pharmacological action of BXT. Compared with the BXT group， the in vivo action times of some components in the CP and PP groups were prolonged. The study explores the phase differences of traditional Chinese medicine（TCM） compound decoction in the aspect of pharmacokinetics， and verifies that the phase states from TCM compound decoction will affect the pharmacokinetic behaviors of the active components， which may consequently lead to the difference in in vivo effects.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

Algorithmic systems based on artificial intelligence(AI)and machine learning(ML)have undergone rapid advancement in recent years, demonstrating extensive application across diverse ophthalmic disorders. Owing to the public availability of multiple global databases, significant progress has been achieved in the training and development of AI-integrated algorithms utilizing multimodal ophthalmic imaging modalities, including fundus photography and optical coherence tomography(OCT). These advancements have established a foundation for precision medicine and efficient healthcare delivery. The diagnosis of macular diseases relies on the identification of subtle alterations in tissue anatomy, where AI demonstrated exceptional performance in detecting intraocular biomarkers and evaluating anatomical changes during disease progression, with particularly prominent utility in the field of macular pathologies. This article provides a comprehensive review of the current applications of AI in macular diseases, aiming to synthesize existing research achievements and current challenges, while proposing visionary prospects for the broader implementation of AI in ophthalmology and even systemic medicine in the future.