Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

BACKGROUND:Primary cortical neurons and microglial cells play a crucial role in exploring cell therapies for neurological disorders,and most of the current methods for obtaining the two types of cells are cumbersome and require separate extraction.It is therefore crucial to find a convenient and rapid method to extract both types of cells simultaneously. OBJECTIVE:To explore a novel method for simultaneous extraction of primary cortical neurons and microglial cells. METHODS:Newborn suckling SD rats were taken within 24 hours.The brain was removed and placed in a dish with DMEM,and the pia mater was removed for later use.Primary neurons were extracted from the same brain tissue,and then the remaining brain tissue was used to extract microglial cells.The whole process was performed on ice.Extraction and culture steps of primary cortical neurons:The cerebral cortex was taken 2.0-3.0 mm with forceps,and the tissue was digested with papain for 20 minutes.After aborting digestion,the blown tissue presented an adherent tissue suspension.The supernatant cell suspension was obtained,filtered,and dispensed into 15 mL centrifuge tubes.After centrifugation and re-suspension,the cells were inoculated onto 6-well plate crawls coated with L-polylysine.Neuronal morphology was observed at 1-day intervals,and staining could be performed for identification using immunofluorescence staining of MAP2 and β-Tubulin by day 7.Microglia extraction and culture steps:The remaining brain tissue at 8-10 mm thick was subjected to microglial cell extraction,digested by trypsin for 20 minutes.After digestion was stopped,the tissue was blown to a homogenate,and then the homogenate was transferred to the culture bottle for culture.On day 14,the culture flasks were sealed and subjected to constant temperature horizontal shaking for 2 hours.Microglial cells were shed in the supernatant.Purified microglial cells were taken and continued to be cultured for 3 days for identification by Iba1 immunofluorescence staining. RESULTS AND CONCLUSION:(1)After 24 hours of culture,the neurons were adherent to the wall,the cytosol was enlarged,and some neurons developed synapses.After 3 and 5 days of culture,the cytosol was further enlarged,and most of the neurons were in the form of synapses,and some neurons were growing in clusters.On day 7,neuronal synapses were prolonged and thickened,and they were connected with each other to form a network.The neurons were identified by β-Tubulin and MAP2 immunofluorescence staining.(2)The cells grew close to the wall on day 1 of culture.On days 3,5,and 7,the density of microglial cells was small,and the cell morphology was bright oval or round,but the cells basically grew in clumps on the upper layer of other cells.On day 10,the density of microglial cells increased significantly.On day 14,microglial cells grew in dense clumps on the upper layer of other cells,and then they could be isolated and purified.The isolated and purified cells were taken and re-cultured to day 3 and identified as microglial cells by Iba1 immunofluorescence;their purity was greater than 95%.(3)The results show that primary cortical neurons and microglial cells obtained by this method after extraction and culture are of high purity,good morphology,and high viability.

BACKGROUND:Chondrocyte apoptosis is an important factor in the development of osteoarthritis,and Complanatoside A has a flavonoid effect,which can inhibit apoptosis of various cells,but its effect on chondrocyte apoptosis and the mechanism of action are not clear. OBJECTIVE:To investigate the intrinsic association and mechanism of Complanatoside A in chondrocyte apoptosis based on the Wnt/β-catenin signaling pathway. METHODS:(1)The cartilage tissues of the femur and tibia transected during knee arthroplasty were collected,and chondrocytes were isolated,cultured in vitro,and identified.(2)Cell counting kit-8 was used to detect the optimal intervention concentration of Complanatoside A in the concentration range of 0-160 μmol/L.(3)Chondrocytes were divided into blank group,sodium nitroprusside(1.5 mmol/L)-induced group,and sodium nitroprusside(1.5 mmol/L)+Complanatoside A(5 μmol/L)group.The viability and apoptosis rate of the cells in each group were detected by cell counting kit-8 and flow cytometry.The expression of type Ⅱ collagen and SOX9 was detected by immunofluorescence staining.The expression of apoptosis-related proteins and Wnt/β-catenin pathway proteins was detected by western blot assay. RESULTS AND CONCLUSION:The cells extracted in vitro were cultured and stained,and were clearly identified as chondrocytes.Complanatoside A had no obvious cytotoxicity to chondrocytes in the concentration range of 0-80 μmol/L,and significantly improved the chondrocyte viability in the concentration range of 2.5-10 μmol/L,especially when the concentration was 5 μmol/L.The apoptotic rate of chondrocytes was higher in the sodium nitroprusside-induced group than the blank control group,while the apoptotic rate was lower in the sodium nitroprusside+Complanatoside A group than the sodium nitroprusside-induced group.The fluorescence intensity of type Ⅱ collagen and SOX9 in chondrocytes was weaker in the sodium nitroprusside-induced group than the blank control group,while the fluorescence intensity of type Ⅱ collagen and SOX9 in the sodium nitroprusside+Complanatoside A group was higher than that of the sodium nitroprusside-induced group.In the sodium nitroprusside-induced group,the protein expression of Bax,Caspase-3,matrix metalloproteinase 13,Wnt3a,Wnt5a and β-catenin was higher than that of the blank control group,while the protein expression of Bcl-2 was lower than that of the blank control group.In the sodium nitroprusside+Complanatoside A group,except for the protein expression of Bcl-2 which was higher than that of the sodium nitroprusside-induced group,the expression of the other aforementioned proteins was lower than that of the sodium nitroprusside-induced group.To conclude,Complanatoside A has a certain inhibitory effect on chondrocyte apoptosis,which could regulate apoptosis-related proteins and promote the expression of chondrocyte regulatory factors,and presumably might play a role through inhibiting the Wnt/β-catenin signaling pathway.

Depression is a psychiatric disorder whose main symptoms include low mood， loss of interest， anxiety， sleep disturbances， and changes in appetite. Orexin， a neuropeptide located in hypothalamic neurons， has a wide range of projections throughout the central nervous system and is involved in various behavioral modulations related to depression. This study systematically reviewed the effects of orexin and its receptor-related drugs on depression and found that orexin could exert complex regulatory effects on multiple brain regions by binding to related receptors， affecting emotions， sleep， anxiety， etc. The abnormal state of expression of plasma orexin in patients with depression was found. Exogenous orexin-A， selective orexin receptor 1 antagonists （SORA1s）， selective orexin receptor 2 antagonists （SORA2s）， and dual orexin receptor antagonists （DORAs） have demonstrated antidepressant-like effects in various animal models of depression. Among them， clinical trials involving exogenous orexin-A are relatively scarce. Drugs related to SORA1s and SORA2s， such as JNJ-61393215 and Setorexant， have made significant progress in the treatment of depression. DORAs， such as Suvorexant， Lemborexant， and Daridorexant， are primarily used to treat insomnia. Notably， Suvorexant has also shown potential in alleviating symptoms of anxiety and depression.

ObjectiveTo investigate the effect of icariin （ICA） on steroid-induced ferroptosis in bone microvascular endothelial cells （BMECs）. MethodsRat BMECs were selected and treated with 500 mg·L^-1 hydrocortisone for 1.5 h to establish a ferroptosis model of BMECs. The experimental cells were divided into a blank group， hormone group （500 mg·L^-1 hydrocortisone）， ICA group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA）， and ferroptosis agonist group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA + 2.7 mg·L^-1 erastin）. Cell viability was detected by CCK-8. The levels of ferrous ion， glutathione （GSH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and reactive oxygen species （ROS） were detected by related kit species. The ferroptosis-related proteins， such as glutathione peroxidase 4（GPX4）， ferritin light chain （FTL）， and transferrin receptor protein1 （sTfR） were detected by Western blot， as well as autophagy-related proteins including microtubule-associated protein 1 light chain 3B （LC3B）， Beclin1， B-cell lymphoma-2 （Bcl-2）， and Caspase-3. Results500 mg·L^-1 hydrocortisone intervention for 1.5 h could effectively induce ferroptosis in BMECs， and ferroptosis levels could reach a peak as the intervention continued. In terms of cellular antioxidant capacity， compared with those in the blank group， the cell vitality， GSH in the hormone group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions were significantly increased （P<0.01）. Compared with those in the hormone group， the cell viability， GSH were significantly increased， and the levels of ROS， SOD， MDA， and ferrous ions were decreased in the ICA group （P<0.01）. Compared with those in the ICA group， the cell vitality， GSH in the ferroptosis agonist group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions increased significantly （P<0.01）. In terms of the relationship between ferroptosis and autophagy， compared with the blank group， the hormone group had significantly increased expression levels of LC3B， sTfR， Beclin1， and FTL and significantly decreased expression levels of GPX4 （P<0.01）. Compared with the hormone group， The ICA group had significantly decreased expression levels of LC3B， sTfR， and FTL and significantly increased expression levels of Beclin 1 and GPX4 （P<0.01）. Compared with those in the ICA group， the expression levels of LC3B， sTfR， and FTL increased in the rapamycin group， and those of Beclin 1 and GPX4 decreased （P<0.01）. In terms of cell ferroptosis and apoptosis，compared with the blank group， the hormone group had significantly increased expression levels of FTL， sTfR and Caspase-3 and significantly decreased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with the hormone group， the ICA group had significantly decreased expression levels of FTL， sTfR and Caspase-3 and significantly increased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with those in the ICA group， the expression levels of FTL， sTfR and Caspase-3 in the ferroptosis agonist group were increased， and the expression levels of GPX4， and Bcl-2 were decreased （P<0.01）. In terms of cell function，compared with that in the blank group， the ability of cell migration and tube formation was significantly decreased in the hormone group （P<0.01）. Compared with that in the hormone group， the cell migration and tube formation ability in the ICA group were significantly increased （P<0.01）. ConclusionFerroptosis is involved in steroid-induced damage in BMECs. ICA can inhibit steroid-induced ferroptosis in BMECs， and the mechanism may be associated with the inhibition of ferroptosis by regulating autophagy.

Objective To establish a chronic kidney disease-associated aortic calcification model in SD rats using different nephrectomy surgical methods, and to compare and evaluate surgical duration and survival time to explore a more optimized modeling method. Methods According to different surgical methods, the SD rats were divided into four groups: Group A: intraperitoneal resection of 2/3 of the left kidney followed by right total nephrectomy in the second stage; Group B: intraperitoneal resection of 2/3 of the left kidney and simultaneous right total nephrectomy; Group C: dorsal approach right total nephrectomy followed by resection of 2/3 of the left kidney in the second stage; Group D: dorsal approach resection of 2/3 of the left kidney followed by right total nephrectomy in the second stage. After comparing survival curves of SD rats undergoing intraperitoneal versus dorsal approaches, and staged versus single-stage nephrectomy, the optimal nephrectomy surgical method was determined. Then, twenty-four 8-week-old SPF-grade male SD rats were selected for nephrectomy combined with calcitriol-induced calcification. Experimental group (12 rats): the dorsal approach left 2/3 nephrectomy followed by right total nephrectomy, with intraperitoneal injection of 1 μg/kg calcitriol administered one week later to induce aortic calcification. Control group (12 rats): the intraperitoneal injection of 250 μL/kg physiological saline containing 1% DMSO one week after sham surgery. After intraperitoneal injection of drugs for 3 months, the survival status of rats in each group was observed. Under anesthesia, blood samples were collected from each group to measure serum phosphorus and calcium ion concentrations, as well as serum urea nitrogen and creatinine levels. After euthanizing the rats, a post-mortem examination was performed to observe the residual kidney morphology, and HE staining was used to observe the pathological changes in the coronal section of the kidney. Additionally, the entire aorta of each group was taken, and the degree of aortic calcification was observed by staining with Alizarin red S and von Kossa. Real-time fluorescence quantitative PCR was used to detect the gene expression of smooth muscle actin-associated protein alpha (Sm22), Runt-related transcription factor 2 (Runx2), and osteopontin (OPN) in rat aortic tissue to evaluate the effectiveness of the model. Results The exploratory optimization experiment of different surgical procedures found that the survival rate of group D rats,which underwent 2/3 left kidney resection followed by right whole kidney resection via the dorsal approach, was the highest, indicating that this surgical procedure was the best method for establishing a chronic kidney disease model with renal dysfunction. The experimental group rats treated with this surgical procedure combined with high-dose calcitriol injection had significantly lower serum calcium ion concentration than those in the sham-operated control group (P<0.05), while serum phosphorus ion concentration, serum creatinine, and serum urea nitrogen levels were significantly higher than those of the control group (P<0.05). HE staining of the kidneys showed significant organic changes in the kidneys of the experimental group rats, with a significant decrease in glomerular count compared to that of the control group (P<0.05), indicating the successful establishment of a renal failure model. Alizarin red S staining showed significant pigment deposition in the aortic media of the experimental group rats, while von Kossa staining showed significant silver nitrate deposition in the aortic media of the experimental group rats, which was consistent with the manifestation of aortic calcification in renal failure. Real-time fluorescence quantitative PCR showed that the expression level of Sm22 in the aortic tissue of the experimental group rats decreased (P<0.05), while the expression levels of OPN and Runx2 increased (P<0.05), indicating a transition of aortic smooth muscle cells from smooth muscle phenotype to bone-like phenotype and successful induction of an aortic calcification model. Conclusion The method of establishing an aortic calcification model of chronic kidney disease in SD rats by first removing two-thirds of the left kidney via the dorsal approach followed by right total nephrectomy, combined with high-dose calcitriol administration, shortens the surgical time, improves the success rate of modeling, and increases the animal survival rate.

Objective To establish a chronic kidney disease-associated aortic calcification model in SD rats using different nephrectomy surgical methods, and to compare and evaluate surgical duration and survival time to explore a more optimized modeling method. Methods According to different surgical methods, the SD rats were divided into four groups: Group A: intraperitoneal resection of 2/3 of the left kidney followed by right total nephrectomy in the second stage; Group B: intraperitoneal resection of 2/3 of the left kidney and simultaneous right total nephrectomy; Group C: dorsal approach right total nephrectomy followed by resection of 2/3 of the left kidney in the second stage; Group D: dorsal approach resection of 2/3 of the left kidney followed by right total nephrectomy in the second stage. After comparing survival curves of SD rats undergoing intraperitoneal versus dorsal approaches, and staged versus single-stage nephrectomy, the optimal nephrectomy surgical method was determined. Then, twenty-four 8-week-old SPF-grade male SD rats were selected for nephrectomy combined with calcitriol-induced calcification. Experimental group (12 rats): the dorsal approach left 2/3 nephrectomy followed by right total nephrectomy, with intraperitoneal injection of 1 μg/kg calcitriol administered one week later to induce aortic calcification. Control group (12 rats): the intraperitoneal injection of 250 μL/kg physiological saline containing 1% DMSO one week after sham surgery. After intraperitoneal injection of drugs for 3 months, the survival status of rats in each group was observed. Under anesthesia, blood samples were collected from each group to measure serum phosphorus and calcium ion concentrations, as well as serum urea nitrogen and creatinine levels. After euthanizing the rats, a post-mortem examination was performed to observe the residual kidney morphology, and HE staining was used to observe the pathological changes in the coronal section of the kidney. Additionally, the entire aorta of each group was taken, and the degree of aortic calcification was observed by staining with Alizarin red S and von Kossa. Real-time fluorescence quantitative PCR was used to detect the gene expression of smooth muscle actin-associated protein alpha (Sm22), Runt-related transcription factor 2 (Runx2), and osteopontin (OPN) in rat aortic tissue to evaluate the effectiveness of the model. Results The exploratory optimization experiment of different surgical procedures found that the survival rate of group D rats,which underwent 2/3 left kidney resection followed by right whole kidney resection via the dorsal approach, was the highest, indicating that this surgical procedure was the best method for establishing a chronic kidney disease model with renal dysfunction. The experimental group rats treated with this surgical procedure combined with high-dose calcitriol injection had significantly lower serum calcium ion concentration than those in the sham-operated control group (P<0.05), while serum phosphorus ion concentration, serum creatinine, and serum urea nitrogen levels were significantly higher than those of the control group (P<0.05). HE staining of the kidneys showed significant organic changes in the kidneys of the experimental group rats, with a significant decrease in glomerular count compared to that of the control group (P<0.05), indicating the successful establishment of a renal failure model. Alizarin red S staining showed significant pigment deposition in the aortic media of the experimental group rats, while von Kossa staining showed significant silver nitrate deposition in the aortic media of the experimental group rats, which was consistent with the manifestation of aortic calcification in renal failure. Real-time fluorescence quantitative PCR showed that the expression level of Sm22 in the aortic tissue of the experimental group rats decreased (P<0.05), while the expression levels of OPN and Runx2 increased (P<0.05), indicating a transition of aortic smooth muscle cells from smooth muscle phenotype to bone-like phenotype and successful induction of an aortic calcification model. Conclusion The method of establishing an aortic calcification model of chronic kidney disease in SD rats by first removing two-thirds of the left kidney via the dorsal approach followed by right total nephrectomy, combined with high-dose calcitriol administration, shortens the surgical time, improves the success rate of modeling, and increases the animal survival rate.

Objective To explore the influencing factors of coronary artery lesion severity in patients with acute coronary syndrome (ACS). Methods Clinical data of ACS patients admitted to Zhongshan Hospital, Fudan University from December 2017 to December 2019 were consecutively collected. The modified Gensini score was used to assess the severity of coronary artery lesions. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with coronary artery lesion severity. Results A total of 1 689 ACS patients were included, with an average age of (64.04±11.45) years; 1 353 (80.11%) were male, and the mean modified Gensini score was (8.12±4.03). Multivariate linear regression analysis revealed that sex (β＝0.97, P＝0.001), age (β＝0.03, P＝0.021), estimated glomerular filtration rate (eGFR; β＝－0.03, P＜0.001), low-density lipoprotein cholesterol (LDL-C; β＝0.58, P＜0.001), apolipoprotein A1 (Apo A1; β＝－1.28, P＝0.012), lipoprotein(a) [Lp(a); β＝0.001, P＝0.033], and glycated hemoglobin A_1C (HbA_1C; β＝0.45, P＜0.001) were independent influencing factors of the modified Gensini score. Conclusions Metabolic indicators, including Apo A1, LDL-C, HbA_1C, and Lp(a), may serve as risk factors for coronary artery lesion severity in ACS patients, with Apo A1 demonstrating the strongest impact.

OBJECTIVE To explore the clinical efficacy and safety of Huangkui capsule combined with cyclophosphamide and prednisone in the treatment of immunoglobulin A （IgA） nephropathy with renal insufficiency. METHODS A total of 117 patients with IgA nephropathy and renal insufficiency who were hospitalized in the department of nephrology of the Second Affiliated Hospital of Dalian Medical University from February 2021 to March 2024 were divided into prednisone group （n＝38）， cyclophosphamide group （n＝39） and Huangkui group （n＝40） according to the random number table method. On the basis of standardized basic treatment， the three groups were treated with prednisone， prednisone + cyclophosphamide， and prednisone + cyclophosphamide + Huangkui capsule， respectively， with a course of 6 months. The clinical efficacy， renal function indexes， immunoglobulin levels， inflammatory factor levels before and after treatment， and the incidence of adverse reactions during treatment were compared among the three groups. RESULTS Finally， 107 patients completed the study （35 in prednisone group， 37 in cyclophosphamide group， and 35 in Huangkui group）. After 6 months of treatment， there was a statistically significant difference in the total effective rate among the three groups （P＝0.028）， and the total effective rate of the Huangkui group was significantly higher than that of the prednisone group （P＝0.023）. In terms of renal function， the levels of blood urea nitrogen （BUN）， serum creatinine （Scr）， and urinary microalbumin （Umalb） in the three groups after treatment were significantly lower than those before treatment， while the estimated glomerular filtration rate （eGFR） was significantly higher than that before treatment （P＜0.05）. Among them， the Huangkui group was superior to the other two groups in reducing BUN level （P＜0.05）， and both the Huangkui group and cyclophosphamide group were superior to the prednisone group in improving Scr， Umalb and eGFR （P＜0.05）. In terms of immunology， both the Huangkui group and cyclophosphamide group were superior to the prednisone group in increasing IgG level and decreasing IgA and IgM levels （P＜0.05）. In terms of inflammatory factors， E-mail：amychina0411@163.com the Huangkui group was superior to the prednisone group and cyclophosphamide group in reducing tumor necrosis factor-α level （P＜0.05）， and superior to the prednisone group in reducing interleukin-6 level （P＜0.05）. There was no statistically significant difference in the total incidence of adverse reactions among the three groups （P＞0.05）. CONCLUSIONS Huangkui capsule combined with cyclophosphamide and prednisone has a good therapeutic effect on IgA nephropathy with renal insufficiency. It can further improve patients’ renal function and immune function， regulate inflammatory status， and has good safety.

Clathrin-mediated endocytosis (CME) is a critical process by which cells internalize macromolecular substances and initiate vesicle trafficking, serving as the foundation for many cellular activities. Central to this process are clathrin-coated structures (CCSs), which consist of clathrin-coated pits (CCPs) and clathrin plaques. While clathrin-coated pits are well-established in the study of endocytosis, clathrin plaques represent a more recently discovered but equally important component of this system. These plaques are large, flat, and extended clathrin-coated assemblies found on the cytoplasmic membrane. They are distinct from the more typical clathrin-coated pits in terms of their morphology, larger surface area, and longer lifespan. Recent research has revealed that clathrin plaques play roles that go far beyond endocytosis, contributing to diverse cellular processes such as cellular adhesion, mechanosensing, migration, and pathogen invasion. Unlike traditional clathrin-coated pits, which are transient and dynamic structures involved primarily in the internalization of molecules, clathrin plaques are more stable and extensive, often persisting for extended periods. Their extended lifespan suggests that they serve functions beyond the typical endocytic role, making them integral to various cellular processes. For instance, clathrin plaques are involved in the regulation of intercellular adhesion, allowing cells to better adhere to one another or to the extracellular matrix, which is crucial for tissue formation and maintenance. Furthermore, clathrin plaques act as mechanosensitive hubs, enabling the cell to sense and respond to mechanical stress, a feature that is essential for processes like migration, tissue remodeling, and even cancer progression. Recent discoveries have also highlighted the role of clathrin plaques in cellular signaling. These plaques can serve as scaffolds for signaling molecules, orchestrating the activation of various pathways that govern cellular behavior. For example, the recruitment of actin-binding proteins such as F-actin and vinculin to clathrin plaques can influence cytoskeletal dynamics, helping cells adapt to mechanical changes in their environment. This recruitment also plays a pivotal role in regulating cellular migration, which is crucial for developmental processes. Additionally, clathrin plaques influence receptor-mediated signal transduction by acting as platforms for the assembly of signaling complexes, thereby affecting processes such as growth factor signaling and cellular responses to extracellular stimuli. Despite the growing body of evidence that supports the involvement of clathrin plaques in a wide array of cellular functions, much remains unknown about the precise molecular mechanisms that govern their formation, maintenance, and turnover. For example, the factors that regulate the recruitment of clathrin and other coat proteins to form plaques, as well as the signaling molecules that coordinate plaque dynamics, remain areas of active research. Furthermore, the complex interplay between clathrin plaques and other cellular systems, such as the actin cytoskeleton and integrin-based adhesion complexes, needs further exploration. Studies have shown that clathrin plaques can respond to mechanical forces, with recent findings indicating that they act as mechanosensitive structures that help the cell adapt to changing mechanical environments. This ability underscores the multifunctional nature of clathrin plaques, which, in addition to their role in endocytosis, are involved in cellular processes such as mechanotransduction and adhesion signaling. In summary, clathrin plaques represent a dynamic and versatile component of clathrin-mediated endocytosis. They play an integral role not only in the internalization of macromolecular cargo but also in regulating cellular adhesion, migration, and signal transduction. While much has been learned about their structural and functional properties, significant questions remain regarding the molecular mechanisms that regulate their formation and their broader role in cellular physiology. This review highlights the evolving understanding of clathrin plaques, emphasizing their importance in both endocytosis and a wide range of other cellular functions. Future research is needed to fully elucidate the mechanisms by which clathrin plaques contribute to cellular processes and to better understand their implications for diseases, including cancer and tissue remodeling. Ultimately, clathrin plaques are emerging as crucial hubs that integrate mechanical, biochemical, and signaling inputs, providing new insights into cellular function and the regulation of complex cellular behaviors.