The abuse of antibiotics has caused a serious threat to human life and health. It is urgent to develop sensors that can detect multiple antibiotics quickly and efficiently. Biosensors are widely used in the field of antibiotic detection because of their high specificity. Advanced artificial intelligence/machine learning algorithms have allowed for remarkable achievements in image analysis and face recognition, but have not yet been widely used in the field of biosensors. Herein, this paper reviews the biosensors that have been widely used in the simultaneous detection of multiple antibiotics based on different detection mechanisms and biorecognition elements in recent years, and compares and analyzes their characteristics and specific applications. In particular, this review summarizes some AI/ML algorithms with excellent performance in the field of antibiotic detection, and which provide a platform for the intelligence of sensors and terminal apps portability. Furthermore, this review gives a short review of biosensors for the detection of multiple antibiotics. In recent years, food safety incidents have prompted people to rethink issues such as drug residues and illegal additions in food safety monitoring. According to relative statistics, about 3000 people die from foodborne diseases annually in the United States . Among fA biosensor is a type of diagnostic device that uses immobilized biological components  or the organism itself  as sensitive elements. Due to the use of biological materials as sensitive elements, biosensors are highly selective and are an ideal analytical tool for quickly and directly obtaining compositional information of complex systems. The design of biosensors involves many disciplines such as chemistry, physics, biology, nanotechnology, communication systems, etc. . In receTherefore, the purpose of this review is to present a timely discussion of and perspectives on advanced technologies and their applications in multi-antibiotic detection. Based on the necessity and urgency of the simultaneous detection of multiple antibiotics proposed above, the biosensors using different biological materials as sensitive elements in antibiotic detection are summarized. In addition, the commonly used sensor types based on different detection mechanisms that can be used for the simultaneous detection of multiple antibiotics were reviewed, and the multidimensional features extracted from the detecting methods of sensors were analyzed. Importantly, novel algorithms suitable for antibiotics analysis are discussed with emphasis. Finally, the application and future development of the above technology in the simultaneous detection of multiple antibiotics are prospected.There are several main principles for biosensors to recognize antibiotics. One is to use immobilized antibodies as recognition elements. Immobilizing antibodies that specifically bind to antibiotics on the surface of the sensor can directly detect antibiotics . The secAntibodies are commonly used as biorecognition elements in biosensors to develop immunosensors. The principle of immune sensing is illustrated in However, the fluorescence detection method is time-consuming and hard to use on-site. LFT is a suitable choice for the rapid and instant determination of antibiotic residues. By designing detection in different areas of the paper, only one signal material is available to achieve multi-target detection. Usually, the signal materials include AuNPs, AgNPs, QDs, and amorphous CNPs ,20. Li eThe above-mentioned antibody-based immunoassay methods still have defects due to the unstable chemical properties of antibodies, easy changes in antibodies during synthesis, and alteration between antibody batches in the synthesis process. A promising improvement method is to improve the synthesis process of antibodies or to find alternative biorecognition receptors.As a powerful alternative to antibodies, aptamers have good thermal stability, less batch variation, low immunogenicity, and a low cost . AptamerDue to the high sensitivity and scalability of electrochemical detection systems, as well as the specificity of aptamers, electrochemical aptamers are considered to be efficient devices for the simultaneous detection of multiple target analytes . AccordiAlthough the cost of designing aptamers is lower than that of antibodies, similar to immunosensors, aptamer sensors also face unstable performance during point-of-care testing (POCT) detection because the biological activities will be easily affected by the environment. In addition, so far, only relatively few aptamers can meet the requirements for both selectivity and specificity, which limits the development of multiplex aptasensors.A new technology is based on molecularly imprinted polymers (MIPs) whose physical and chemical properties are similar to antibodies. Composite materials are used which are composed of functional monomers, crosslinkers, and template molecules that can withstand a more comprehensive range of pH and temperature than biological materials. MIP-electrochemical sensors mainly use the interaction between the analyte and the electrode surface to convert the analyzing signal. The current, voltage, etc., will be affected by this effect. The classic structure and principle of MIP-based sensors is illustrated in To track and quantify trace amounts of drugs in biological tissue samples, Liu et al.  proposedTherefore, MIPs are an ideal material that can eliminate sample matrix interference and effectively enrich trace antibiotics . As recoThe methods for the simultaneous detection of antibiotic residues mainly include the microbial method, electrochemical method, high-performance liquid chromatography and liquid-mass spectrometry, fluorescence method, Raman spectroscopy, etc. Different detection methods have their own advantages and disadvantages. There are also many defects in the development of methods for the simultaneous detection of multiple antibiotics. First, cross-reactivity cannot be neglected when the structure of the target analytes is similar. Second, multi-target detection requires different signal labels, and signal overlap and mutual interference are not conducive to detection and analysis. Third, complexity of the sample matrix will affect the detection results. In the past few years, more and more related studies have tried to overcome the above-mentioned problems ,34,35,36Fluorescent sensors have attracted considerable attention in the field of the multiplex detection of antibiotics due to their ease of manipulation, fast response, high sensitivity, and potential for instant detection. Among fluorescence methods, multiplex sensors based on Forster resonance energy transfer (FRET) have shown superior performance in the simultaneous detection of a few antibiotics . FluoresTo detect antibiotic residues in chicken meat, Li et al.  combinedSince the detection signal of antibiotic small molecules is usually too low to be detected, signal amplification strategy is another active area of research in this field, and the amplification part based on nanomaterials and DNA has attracted continuous attention ,41.An electrochemical sensor is a device for the qualitative or quantitative analysis of target substances. Its essence is that the sensing signal generated by the reaction of the measured substance with a specific sensing element will be converted into an identifiable electrical signal that is proportional to the concentration of the target substance through a specific sensor. Electrochemical methods can be generally divided into potentiometric methods, amperometric methods, conductometric methods, impedance methods, and voltammetric methods . Among tIn order to detect multiple antibiotics in milk, based on aptamers and quantum dots, PbS, CdS, and ZnS, Xue et al.  designedIn addition, how to improve the sensitivity of multi-channel electrochemical sensors is a key focus for researchers when designing sensors. There are two basic methods to improve the detection sensitivity of electrochemical multi-channel adaptive sensors. The first approach is the electrode modification method based on nanomaterials . Sin2+ and Pb2+ ions and applied double-stranded DNA markers. By the square wave voltammetry detection method, the peak currents of the labeled Cd2+ and Pb2+ corresponding to the concentration of kanamycin and ampicillin can realize the simultaneous detection of the two antibiotics within a range from 0.05 pM to 50 nM.Taking fish and milk as the detection substances, Shen et al.  prepared2 (S/N = 3) for thiram was obtained on apple peels with a correlation coefficient of 0.99.SERS is an ultrasensitive vibrational spectroscopy technique that enhances the vibrational spectroscopy of molecules that are adsorbed on or near metallic nanostructures or surfaces ,63. Due When using the SERS method to monitor antibiotic residues in food, methods such as liquid–liquid extraction and solid-phase extraction are commonly used to preprocess the sample to extract analytes from complex food samples. However, these methods are cumbersome, laborious, time-consuming, and not environmentally friendly, which limits the online analysis application of SERS technology. Jin et al.  proposedThe key principle of the colorimetric method is to analyze the color changes in the analyte for detection by the naked eye or portable, low-cost equipment instead of other more complicated equipment, and the output signal is directly visualized ,68,69. MAptamers are ideal biomolecules and sensing elements for colorimetric aptasensors. The key point to be solved in establishing AuNP-based colorimetric aptasensors is the aggregation and flocculation of unmodified AuNPs, which are induced by the passivating surface layer, ionic strength, pH, and temperature. A feasible method is to covalently link thiol groups of ssDNA on gold nanoparticles . For exacolorimetric, and electrochemical sensors are the common choice for high sensitivity and rapid detection, while SERS-based sensors are an ideal choice for the non-destructive detection of antibiotics in food because of their non-invasive detection. The above-mentioned types of sensors for multiplex antibiotic detection have shown a superior detection performance under the optimal conditions, but they are not suitable for on-site detection due to the large-scale equipment that is required. Based on the lateral-flow test strips (LFT), the microfluidic chip can meet the requirements of on-spot detection and is the development direction of future sensors due to it having the characteristics of miniaturization, portability, and easy-to-use analysis.However, since each method has its unique characteristics, so far, there is no optimal method for multiple antibiotic detection. Generally speaking, fluorescence, Nowadays, artificial intelligence and machine learning technology (AI/ML) have allowed for impressive progress. Some innovative algorithms have been successfully applied in many fields like image processing, face recognition, natural language processing, and medical data ,83,84,85In the process of traditional empirical model processing and the optimization of experimental methods for antibiotic detection, it is necessary to analyze multiple independent factor variables. Since only one variable is changed while all other variables are kept unchanged , this meOne of the applications of artificial intelligence in sensor design is to efficiently process complex matrices or large-sample sensor detection data. By selecting appropriate machine learning algorithms, the hidden relationship between the sample parameters and sensor signals can be discovered through data visualization and mine the relationship between the signal and the target detection samples. Traditional sensor data processing often applies a single feature of the collected data as an indicator of the concentration of the detected sample, and the relationship between them is established. However, one-dimensional data analysis is not enough to obtain a sensitive signal that is highly correlated with the type and quantity of the analyte, and it is necessary to combine multiple independent factor variables with artificial intelligence tools. Moreover, the complexity and multivariate analysis of biological systems and environments is another challenge for the current high-throughput sensing methods and multi-analyte identification design. For example, due to the reactions between substances when performing cyclic voltammetry testing of multi-materials, there are several types of curves can be observed, such as separate current peaks, the coexistence of independent peaks and coupled peaks, and several peaks merged into one peak due to coupling reactions . Especia2), the relative error of prediction (REP), and root-mean-square difference (RMSD) can be adopted to evaluate the performance of the model.Designing an appropriate AI/ML model according to the type of data set and analysis purpose  will help us to extend detection methods to different data acquisition devices and application scenarios. To design an AI/ML model for a specific biosensing system, the following details in the process need to be focused: (1) the size of the input data set and the dimension of the input value. At present, biosensing data mainly include sequence data sets obtained from electrochemical and spectral biosensors or image data sets acquired by colorimetric and fluorometric biosensors. (2) The feature selection and feature extraction processes: through feature selection, the prediction accuracy of the model, computational cost, risk of overfitting, and interpretability of data can be improved. It is necessary to choose an appropriate feature selection method according to the specific situation to avoid the influence of too many features on the model. The main methods of feature selection include the filter, wrapper, and embedded methods. The main methods of feature extraction include principal component analysis, linear discriminant analysis (for sequence data), and the scale-invariant feature transform method (for image data). (3) The pre-processing and post-processing according to the application scenarios of the AI/ML model: general preprocessing methods include derivatives, denoising, Fourier transform, etc. The different preprocessing methods are applicable to data from different sources. For Raman spectra, each spectrum requires Savitzky-Golay smoothing, background subtraction, and min-max to  . Post-prRandom Forest (RF): As shown in Support Vector Machine (SVM): SVM is a supervised learning ML algorithm used for classification and regression tasks. The principle of the algorithm is to find a hyperplane in the feature space that can effectively separate samples of different categories and achieve the largest interval (Margin). 6 CFU) can be quickly detected and classified by analyzing the impedance test data after 8 min. Therefore, the BP-ANN method was applied to classify these bacteria. The key features included the measuring power, the I-V curve, and the first derivative and second derivative of I-V characteristics, and the classification accuracy reached almost 100%. Therefore, it can be applied as an early detection and classification tool in the food industry.Artificial Neural Networks (ANN): ANN are composed of multiple artificial neurons (nodes) and connections between neurons, and a layered artificial neural network generally includes input, output, and multiple hidden layers. The nodes process the given signals and transmit them to the next connected node. The output of a node depends on the weighted sum given by the nodes in the previous layer. The key parameter that significantly affects the performance of artificial neural networks is the size of the hidden layers . ContainConvolutional Neural Network (CNN): The core parts of CNNs include the convolution layer, pooling layer, convolution kernel, activation function, and fully connected layer . As the According to the information mentioned above, AI/ML algorithms can help to discover unknown complex relationships between similar data with a high inclusivity for the dimensionality of the data source. It can simplify the process of analyzing experiment results and improve the interpretation of complex sensing systems such as the detection of the coexistence of multiple antibiotics. Therefore, it is foreseen that AI/ML will be widely used in multi-antibiotic detection. However, in actual scientific research work, there are two unavoidable challenges. One is to find an efficient and suitable AI/ML algorithm for a specific biosensing system, and the other is how to provide a large number of training data for the established algorithm model in a short experimental time. Although many successful cases have proven that the AI/ML algorithm has excellent advantages in substance identification, up until now, there is still no suitable method that can effectively collect enough antibiotic sensing data sets. A promising solution is to find suitable sensing strategies coupled with AI/ML to effectively drive forward the development of technology for the detection of an environment. Furthermore, for quantitative detection, the algorithm has a satisfactory predictive effect only in a limited range, and higher precision algorithms still need to be developed. As for biosensors integrated with AI/ML algorithms, there are different statistical methods for performance indicators. However, each unique AI/ML algorithm has its own most-valuable types of input data, and unified evaluation indicators and methods are needed. Also, it is necessary to control information security during data collection, transmission, and the processing of sensor development.At present, the efficient and rapid detection of multi-antibiotics is of great significance. However, the main challenges are the selection of front-end modifiers and the rapid and accurate result output of the back end. This review introduces the current detection techniques, biometric probes, and nanomaterials that are commonly applied in multi-antibiotic detection. In particular, the application of AI/ML algorithms in multi-antibiotic detection is reviewed, and the impact of this emerging technology on multi-antibiotic detection is illustrated. Although the developed multi-antibiotic detection sensors have achieved satisfactory results, there are still limits in the laboratory testing environment and the operation of professionals, and there are still many challenges in practical applications. These challenges include the need to fix different biological receptors that are applied to constructing biosensor systems for ensuring the biocompatibility of materials and biometric molecules; the influence of non-uniformity of nanoparticles on the performance of biosensors; cross interference within antibiotics; and the effective connection between nanomaterials and biological recognition molecules.The detection of antibiotics in food is relatively mature. In the previous chapters, many methods for the detection of antibiotics in foods such as milk, honey, and eggs have been discussed. However, antibiotic contamination may occur in various situations, especially in aquatic environments, which is continuously harmful to human health. The pollution sources of antibiotics in water mainly include wastewater discharged from domestic sewage, medical wastewater, animal physiology, and aquaculture. Up until now, there are only a few methods can simultaneously be adopted to detect multiple antibiotics in water samples ,106,107.


Lung cancer is a complex and heterogeneous disease characterized by abnormal growth and proliferation of lung cells. It is the leading cause of cancer-related deaths worldwide, accounting for approximately 18% of all cancer deaths. In recent years, targeted therapy has emerged as a promising approach to treat lung cancer, which involves the use of drugs that selectively target specific molecules or signaling pathways that are critical for the growth and survival of cancer cells. Liquid–liquid phase separation (LLPS) is a fundamental biological process that occurs when proteins and other biomolecules separate into distinct liquid phases in cells. LLPS is essential for various cellular functions, including the formation of membraneless organelles, the regulation of gene expression, and the response to stress and other stimuli. Recent studies have shown that LLPS plays a crucial role in targeted therapy of lung cancer, including the sequestration of oncogenic proteins and the development of LLPS-based drug delivery systems. Understanding the mechanisms of LLPS in these processes could provide insights into new therapeutic strategies to overcome drug resistance in lung cancer cells. Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all lung cancer cases . The priLLPS occurs through the assembly of multivalent interactions between disordered regions of proteins or RNA molecules, leading to the formation of dense liquid droplets. There is emerging evidence suggesting that the formation of liquid droplets through LLPS plays a critical role in the response of lung cancer cells to targeted therapies , 12–18. The aberrant regulation of LLPS has been increasingly recognized as a critical factor in the development and progression of lung cancer . The majIn lung cancer cells, LLPS can occur through the interaction of disordered regions of proteins, such as the non-POU domain-containing octamer-binding protein (NONO), with RNA molecules. The resulting liquid droplets can function as sites of biochemical reactions and contribute to various cellular processes, including DNA repair and signal transduction . One keyIn addition of tumor suppressor proteins, LLPS of NONO has been found to recruit and enhance the interaction between EGFR and DNA-dependent protein kinase (DNA-PK), a key protein in the non-homologous end joining (NHEJ) pathway of DNA double-strand break repair. This interaction leads to the activation of pT2609-DNA-PK and promotes NHEJ-mediated DNA repair, which contributes to tumor radioresistance , 30–32.Furthermore, the phenomenon of liquid–liquid phase separation (LLPS) emerges as a key player in the intricate landscape of anti-tumor immune responses in lung cancer. Recent studies have shed light on the disruptive effects of perturbing the phase separation of KAT8–IRF1, resulting in a reduction in PD-L1 expression and a concomitant enhancement of the anti-tumor immune response . RemarkaIn addition, a number of recent studies have shown that LLPS is involved in the signaling activation of lung cancer carcinogenic pathways such as EGFR, ALK and KRAS , 29, 34.The activation of the EGFR signaling pathway through LLPS-mediated mechanisms is linked to the dysregulation of several downstream oncogenic pathways. In NSCLC, the activation of EGFR signaling can occur through several mechanisms, including mutations in the EGFR gene, gene amplification, or overexpression . For exaTargeting the aberrant regulation of LLPS in lung cancer cells could provide new opportunities for the development of more effective therapies for this devastating disease. The formation of LLPS droplets can recruit and activate EGFR and downstream signaling proteins, leading to increased cell proliferation, survival, angiogenesis, invasion, and radioresistance , 38. TheOverall, LLPS is an emerging area of research that provides new insights into the regulation of intracellular signaling pathways, and understanding the role of LLPS in cancer may lead to the development of new therapeutic approaches for the treatment of lung cancer.KRAS mutations are found in approximately 35% of all lung adenocarcinomas, making it a paramount driver of this particular lung cancer subtype . EML4-ALRecent discoveries have shed light on a captivating phenomenon: the liquid–liquid phase separation (LLPS) of EML4-ALK, which not only contributes to tumorigenesis but also exerts a profound influence on the KRAS signaling pathway . The fusMoreover, LLPS of SHP2 is involved in the regulation of the MAPK signaling pathway, which is frequently dysregulated in cancer, including lung cancer. Dysregulation of SHP2 contribute to the development and progression of lung cancer.SHP2 mutants undergo LLPS in the cytoplasm of cancer cells, enhancing MEK1/2 and ERK1/2 phosphorylation levels, and activating MAPK pathway, leading to increased proliferation, survival, and metastasis of lung cancer cells. Disrupting the LLPS of SHP2 and MAPK may be an effective strategy for inhibiting the oncogenic signaling pathways that promote the development and progression of lung cancer , 43–45.EZH2, a critical component of the Polycomb Repressive Complex 2 (PRC2), is known for its role in epigenetic regulation. It catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3), leading to gene silencing –48. On tEmerging evidence has revealed that the myristoylation modification of EZH2 enables its phase separation, a process by which intracellular components segregate into liquid-like condensates . MyristoTargeting the myristoylation process, disrupting EZH2-STAT3 interactions within the condensates, or modulating the properties of EZH2 condensates may hold promise for developing novel therapeutic interventions.One of the concepts that formed stress granules was the LLPS process . Stress Stress granules dynamically interact with a key component of lung cancer’s pathway, mTOR and its regulators, influencing its localization, activity, and downstream signaling. This interplay modulates cellular responses to stress and contributes to the adaptive and survival mechanisms of lung cancer cells .The dysregulation of the Hippo signaling pathway, specifically the activation of downstream effectors Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), has been implicated in the development and progression of NSCLC , 55. Th. YAP andDanfeng Cai and colleagues have demonstrated that YAP is also involved in the LLPS process, which leads to the formation of liquid-like condensates in the nucleus within seconds of hyperosmotic stress. These condensates compartmentalized the YAP transcription factor TEAD1 and other YAP-related co-activators, such as TAZ, leading to the transcription of YAP-specific proliferation genes. Additionally, a tumor-promoting long non-coding RNA (lncRNA) known as small nucleolar RNA host gene 9 (SNHG9) has been found to identified to drive the liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibits the Hippo pathway. When the Hippo pathway is activated, upstream regulators such as MST, MAP4K, and TAOK phosphorylate and activate LATS1, which in turn sequesters YAP in the cytoplasm by facilitating YAP phosphorylation (S127) and leading to its degradation. During cancer development, lipid signaling related to PA is activated, resulting in the upregulation of SNHG9. These factors promote LATS1 LLPS, decrease LATS1 phosphorylation (S909), and reduce kinase activity in the cytoplasm, leading to YAP activation . HoweverOverall, the dysregulation of the Hippo signaling pathway and the LLPS of YAP and TAZ have important implications for the development of new therapeutic approaches for NSCLC. Disrupting the YAP/TAZ signaling axis and their LLPS may be an effective strategy for inhibiting the oncogenic signaling pathways that promote the development and progression of NSCLC.The role of LLPS in lung cancer progression has shed light on several potential targets for the development of LLPS-based therapies. One promising target is the EGFR signaling pathway, which is frequently dysregulated in lung cancer and plays a critical role in cancer cell proliferation, migration, and survival. Targeting the LLPS-mediated activation of EGFR and its downstream signaling pathways, such as MAPK, has emerged as a promising strategy for inhibiting tumor growth and metastasis. LLPS of other oncoproteins, such as SHP2, has been shown to play a role in lung cancer progression and resistance to therapy, making it another potential target for LLPS-based therapies. In addition to targeting specific oncoproteins, modulation of the biophysical properties of the cancer cell microenvironment through LLPS inhibitors could represent a novel approach for limiting tumor growth and metastasis. For instance, targeting the formation of liquid droplets within the tumor microenvironment, such as stress granules or P-bodies, could inhibit cancer cell survival and migration , 62. LLPTargeted therapies that focus on inhibiting the LLPS-mediated activation of the EGFR pathway represent a promising approach for treating lung cancer. One potential strategy is the use of LLPS inhibitors that can disrupt the formation of EGFR signaling complexes and inhibit downstream signaling pathways. Another approach is to target specific proteins involved in the LLPS-mediated activation of the EGFR pathway, such as the NOPOU, which plays a critical role in the nuclear accumulation and activation of EGFR in response to radiation. Small molecule inhibitors of NONO and other LLPS-associated proteins could be a potent therapeutic strategy for inhibiting the activation of the EGFR pathway and sensitizing cancer cells to conventional therapies , 31–32.LLPS-based targeted therapies of SHP2 and other oncoproteins in lung cancer represent another promising therapeutic approach. SHP2 is an oncoprotein that plays a critical role in the activation of the MAPK pathway and the promotion of cell proliferation and survival. Small molecule inhibitors of SHP2 have been developed and shown to be effective in preclinical studies, providing a potential avenue for the development of LLPS-based therapies targeting SHP2 in lung cancer. Other oncoproteins involved in the LLPS-mediated activation of oncogenic pathways, such as MET and ROS-1, are also promising targets for LLPS-based therapies. As research into the mechanisms and functions of LLPS in lung cancer continues, the development of targeted therapies that specifically disrupt the formation and activity of oncoprotein droplets could have significant therapeutic implications for patients with this devastating disease , 43. TheIn addition to targeting specific oncoproteins and their interactions with the ECM, LLPS-based therapies could also be used to sensitize lung cancer cells to conventional therapies such as chemotherapy and radiation. One potential strategy is to use LLPS inhibitors to enhance the efficacy of DNA damage repair, which is critical for cancer cell survival and resistance to therapy. By inhibiting LLPS-mediated repair mechanisms, such as the formation of DNA repair foci, LLPS inhibitors could sensitize cancer cells to DNA damage induced by conventional therapies, leading to improved treatment outcomes .In summary, LLPS has emerged as an important regulator of cellular processes in lung cancer, and its dysregulation plays a critical role in tumor growth, metastasis, and resistance to therapy. Targeting the LLPS-mediated activation of oncoproteins and their interactions with the cancer cell microenvironment represents a promising approach for developing novel therapies to improve the treatment of lung cancer. As research in this area continues, the development of targeted LLPS inhibitors and their use in combination with conventional therapies holds great promise for improving treatment outcomes and reducing the morbidity and mortality associated with this devastating disease.Recent advances in LLPS-based resistance against lung cancer have shown the potential of this approach in overcoming drug resistance and improving patient outcomes , 63–65. A promising target is the YAP protein, which is involved in the formation of liquid droplets that promote the survival of cancer cells. The efficacy of EVG in the inhibition of cancer cell growth through the targeting of SRC-1/YAP/TEAD droplets in a YAP-dependent manner has been demonstrated by selective disruption of the liquid–liquid phase separation (LLPS) of SRC-1 . And theTargeting the oncogenic signaling pathway has also been the primary focus of LLPS-based therapies, and several inhibitors have been developed to block EGFR accumulation in the nucleus and disrupt its oncogenic functions. For instance, the liquid-like condensates formed by NONO can be disrupted by 1,6-Hexanediol, which is known to disrupt hydrophobic interactions in such droplets . MoreoveTargeted drug delivery systems also provide a promising approach for treating lung cancer, taking advantage of the unique properties of LLPS. For example, liposomes can be designed to recognize specific cell surface markers or to respond to changes in the local environment of tumor tissues, which can enhance their accumulation and internalization in lung cancer cells .Despite the early stages of development, the potential for personalized cancer treatment through LLPS-based targeted therapies is significant, but challenges remain, such as identifying novel targets and optimizing LLPS inhibitors for clinical use. However, with further research, LLPS-based targeted therapies could become a cornerstone in the treatment of lung cancer, offering improved outcomes and reduced toxicities.LLPS-based therapies have shown great promise in lung cancer treatment. However, several challenges that must be addressed to translate these therapies into clinical practice. A major challenge is the lack of understanding of the specific mechanisms of LLPS in lung cancer and the complexity of signaling pathways involved. The development of efficient and specific LLPS inhibitors that can selectively target cancer cells is another challenge , 65. ResTo overcome these challenges, future research efforts should focus on further elucidating the mechanisms of LLPS in lung cancer and identifying novel LLPS regulators and targets. Advanced imaging techniques and organoid cultures could be used to achieve this goal. Comprehensive studies to evaluate the safety and efficacy of LLPS inhibitors in clinical settings are also needed. Biomarkers can be used to identify patient populations that are most likely to respond to LLPS-based therapies, and combination therapies that can overcome resistance mechanisms , 72.Finally, personalized LLPS-based therapies based on the unique characteristics of individual tumors can potentially improve treatment outcomes and minimize adverse effects. In summary, despite the challenges, LLPS-based therapies hold great potential for improving lung cancer treatment, and continued research in this area is crucial for the development of effective and safe targeted therapies. Combining LLPS-based therapies with immunotherapies is another potential direction for future research , 73. LLPIn summary, while LLPS-based therapies hold great potential for the treatment of lung cancer, several challenges need to be overcome before they can be successfully translated into clinical practice. These include the need for a deeper understanding of LLPS mechanisms and signaling pathways in lung cancer, the development of more efficient and specific LLPS inhibitors, and the evaluation of the safety and toxicity of these inhibitors. Nevertheless, ongoing research efforts, such as the development of new technologies and experimental models, as well as the exploration of combination therapies, offer promising avenues for overcoming these challenges. With further advancements and innovations in LLPS-based therapies, there is hope for significant improvements in the clinical outcomes of lung cancer patients.The dysregulation of LLPS in lung cancer provides an attractive target for the development of novel therapies. However, several challenges must be overcome to successfully translate LLPS-based therapies into clinical practice. The development of specific LLPS inhibitors and effective drug delivery systems, as well as the identification of robust biomarkers, are crucial for the development of successful LLPS-based therapies. Despite these challenges, the future prospects of LLPS-based therapies in the treatment of lung cancer are promising. Advances in our understanding of the biophysical properties of cancer cells and the underlying mechanisms of LLPS in cancer have created new opportunities for the development of targeted therapeutic strategies. LLPS-based therapies targeting specific oncoproteins and oncogenic signaling pathways may improve the efficacy and reduce the toxicity of current treatment strategies. Additionally, the integration of LLPS-based therapies with other modalities, such as immunotherapy and chemotherapy, may provide a synergistic effect and further improve clinical outcomes. Furthermore, the development of LLPS-based therapies may have implications beyond lung cancer. Dysregulation of LLPS is a common feature of many types of cancer, suggesting that the strategies developed for lung cancer may be applicable to other cancer types as well. The development of LLPS-based therapies may provide a new avenue for the treatment of cancers that are resistant to current treatment strategies.In conclusion, targeting LLPS represents a promising avenue for the development of novel therapies in the context of lung cancer. Significant advancements in our understanding of the biophysical properties of the cancer cell microenvironment and the mechanisms of LLPS in cancer have created opportunities for the development of innovative therapeutic strategies. Despite existing challenges, the future prospects of LLPS-based therapies in the targeted treatment of lung cancer are encouraging and offer substantial potential for enhancing clinical outcomes and ultimately mitigating the burden of this debilitating disease.


The field of healthcare has witnessed remarkable progress in recent years, particularly in the area of advanced biomaterials for surface functionalization and controlled drug delivery. The editorial aims to highlight the key contributions to this Research Topic, shedding light on the design and synthesis of biomaterials, their impact on drug delivery, and their potential clinical applications.Conventional drug delivery methods often suffer from fluctuating drug concentrations, leading to potential side effects and reduced therapeutic efficacy. To address these challenges, researchers have developed approaches for controlled drug release, such as sustained-release technologies. These technologies involve the use of biomaterials that can release drugs over an extended period, reducing dosing frequency and improving patient outcomes.Li et al. It was demonstrated that the high hydrogels’ drug-carrying capacity and controlled drug release capabilities are ideal for delivering various substances such as chemotherapeutic drugs, radionuclides, immunosuppressants, hyperthermia agents, and phototherapeutic agents. They can trigger cascade reactions and respond intelligently to environmental changes, allowing for targeted drug delivery to specific locations. Some challenges such as inefficient and expensive synthesis hinder the adaptability; however, further research may revolutionize cancer treatment and improve outcomes for patients. The hydrogels can also be applied to repair and regenerate various defected tissues including bone, skin, muscle, and nerve tissues Li et al. For instance, this technique can be applied to repair cartilage defects. It introduces the principles of developing hydrogels for cartilage regeneration and the criteria for optimized outcomes, such as biocompatibility, cell affinity, and tissue integration properties. In order to produce hydrogels for cartilage repair, various materials, including synthetic polymers, polysaccharides, proteins, and peptides can be utilized Li et al. Hydrogels are also important for providing the biophysical and biochemical factors in regulating the fate of stem cells, thus enhancing tendon regeneration. To excel in this field, there are various challenges that need to be addressed with a careful consideration of various factors, including biocompatibility, cell affinity, tissue integration properties, feasibility, and the choice of materials.One of the articles focused on the use of hydrogel systems for targeted cancer therapy Zhang et al. It was identified that the photodynamic therapy (PDT) for oral squamous cell carcinoma (OSCC) can be attained using manganese-doped carbon dots (Mn-CDs). Mn-CDs characterizations confirmed the successful synthesis of Mn-CDs and provided insights into their morphology, size, surface charge, chemical bonds, crystal structure, and functional groups. These Mn-CDs demonstrated excellent photodynamic efficiency and satisfactory biosafety, both in vitro and in vivo, indicating their potential as a novel therapeutic agent for cancer treatment.Another promising approach for cancer treatment is presented by Zhang et al. also demonstrated that vancomycin-loaded silk fibroin microspheres in the injectable hydrogel system effectively deliver vancomycin, leading to improved antibacterial activity and enhanced bone regeneration compared to conventional treatment approaches Zhang et al. Silk fibroin microspheres were utilized as a carrier for vancomycin, a potent antibiotic commonly used to treat osteomyelitis. The microspheres were loaded with vancomycin and then incorporated into an injectable hydrogel system. The combination of the microspheres and hydrogel provided sustained release of vancomycin, allowing for prolonged and localized drug delivery at the site of infection. In vitro studies involved evaluating the release kinetics of vancomycin from the microspheres within the hydrogel, assessing antibacterial activity against relevant pathogens, and evaluating the biocompatibility of the system. In vivo studies comprised the implantation of the vancomycin-loaded silk fibroin microspheres in the injectable hydrogel system into an osteomyelitis model. The researchers assessed the therapeutic efficacy of the treatment by monitoring bacterial clearance, bone regeneration, and inflammation reduction.The study of Zwitterionic coating assisted by dopamine with metal-phenolic networks loaded on titanium with improved biocompatibility and antibacterial property for artificial heart” focused on the development of a surface coating for titanium-based artificial heart implants that enhances biocompatibility and antibacterial properties Meng et al. The study employed a combination of polydopamine and poly-(sulfobetaine methacrylate) (SBMA) to form a coating on the surface of titanium substrate. The coating process was initiated by copper ions (Cu2+). The research presented a zwitterionic coating assisted by dopamine with metal-phenolic networks loaded on titanium, improving the biocompatibility and antibacterial properties of artificial heart implants. The coating demonstrated effective antibacterial activity, antiplatelet adhesion properties, and stability in different environments. These findings have implications for the development of optimized surfaces for titanium-based substrates in artificial heart implants, with the potential to reduce the need for long-term prophylactic antibiotics and anti-thrombotic drugs.The article titled “Escobar et al. focused on the functionalization of breast implants using cyclodextrin in-situ polymerization as a local drug delivery system for augmentation mammaplasty. The article emphasized the need for surface modification techniques to overcome limitations and complications associated with silicone implants, such as the capsular contracture formation. Various drugs and polymers were explored to improve the performance of silicone implants and reduce complications. The polymerization process, optimization parameters, and the potential of cyclodextrin-based coatings for controlled drug release were also discussed. The research also highlighted the broader applications of cyclodextrin-based coatings in drug delivery systems and the need for further research to overcome complications associated with silicone implants.The study of In conclusion, the Research Topic on advanced healthcare biomaterials for surface functionalization and controlled drug delivery encompasses various scientific and technological advancements. From the design and synthesis of biomaterials to their clinical and commercial impact, researchers have made significant progress in improving drug delivery strategies and therapeutic outcomes. By harnessing the potential of designing and engineering biomaterials through advanced manufacturing and characterization techniques, healthcare professionals can revolutionize the field of medicine and improve the lives of countless individuals.


Background and Objectives: Congenital ureteral stenosis is one of the leading causes of impaired urinary drainage and subsequent dilatation of the urinary collecting system, known as hydronephrosis or ureterohydronephrosis. The mechanism that leads to obstruction is not clearly known. Multiple studies in rat models have shown increased angiotensin II and TGFβ levels in obstructed ureteral tissue. The aim of the study is to investigate the expression of fibrosis-related genes in obstructive and normal ureteral tissue. Material and Methods: It is a monocentric pilot study in which nineteen patients were selected prospectively. 17 patients underwent Hynes-Anderson pyeloplasty due to the PUJO; two patients underwent ureteroneocystostomy due to ureterovesical junction obstruction (UVJO); and six patients were chosen for the control group: five underwent nephrectomies due to the kidney tumor and one underwent upper pole heminephrectomy due to the duplex kidney with normal pyeloureteric junctions in all. Tissue RNA was chemically extracted after freezing the biopsy samples in liquid nitrogen, with cDNA synthesis performed immediately after nucleic acid isolation. qPCR was performed to evaluate the relative expression of Tgfb1, Mmp1, Timp1, Pai1, Ctgf, and Vegfa. Expression levels of the Gapdh and Gpi genes (geometric average) were used to calculate the relative expression of the investigated genes. Outliers were removed prior to calculating confidence intervals for the experimental groups, and a Wilcoxon rank-sum test was performed to determine the statistical significance of the differences. Results: Significant differences between healthy and stenotic tissue samples in Ctgf gene expression levels were observed, with the samples from afflicted tissue showing lower expression. No statistical difference in expression levels of Tgfb1, Timp1, Vegfa, Mmp1, and Pai1 was found. Conclusions: These findings suggest that tissue fibrosis, similar to other tissues and organs, is not the leading cause of stenosis, at least at the moment of surgery. Decreased CTGF expression is indicative of the developmental origin of obstruction. Congenital ureteral stenosis is the leading cause of impaired urinary drainage and subsequent dilatation of the urinary collecting system, and a condition known as hydronephrosis or ureterohydronephrosis, when ureteric dilatation is present. Ureteral obstruction is a very serious clinical condition, leading to the damage of renal parenchyma because of obstruction-induced increased pressure, reduced glomerular filtration, activation of profibrotic factors, cell apoptosis, and subsequent loss of kidney function, which has been investigated in animal models in a series of studies ,2. EarlySeveral theories of pathogenesis leading to the development of hydronephrosis were learned from animal models. The reasons for hydronephrosis can be generally regarded as obstructive and non-obstructive.In a systematic analysis that reviewed data from 10 articles, it was revealed that 15 genes had changed expression in ureteral stricture tissue. Genes which were upregulated were , and the expression of six genes was downregulated . The products of these genes are components of the HIF-1 signalling pathway and participate in the development of vasculature. Some of these factors act as inductors of signalling pathways and particularly affect the Ras signalling system. There may also be a connection between current factors and others that are related to tissue hypoxia, fibrosis, and inflammation .Histological studies of obstructed human ureters identified an excessive amount of collagen in the extracellular matrix, and impaired distribution of its isoforms, an increased proportion of elastin, and apoptosis of myocytes. Altogether it leads to the abnormal development of tissue ,6. On thThe aim of our pilot study was to analyze several fibrosis-related factors that are known to participate in the general mechanism of fibrosis in multiple sites of the human body and to discuss their involvement in previously described chains of pathogenesis. Tgfb1, Ctgf, Vegfa, Timp1, Pai1, and Mmp1 genes were chosen to be analyzed according to previous studies where they were analyzed as fibrosis-inducing factors  at the time of the surgery, and the median age of the control group (four boys and two girls) was 60 months .The expression of fibrosis-related genes in every specimen is depicted in the heatmap. . VariablCtgf gene expression level. We further decided to compare the confidence intervals between groups, and the intervals of the Ctgf gene showed little overlap, indicating differences between obstructed and control tissue samples.  family, particularly TGFs 1 to 3, sharing similar functions with minor structural differences . Out of −/− mice develop a significantly attenuated inflammatory response, suggesting that PAI-1 directly promotes infiltration of macrophages and T-cells [Among the disease-relevant ROS-dependent genomic targets (reactive oxygen species), TGF-beta1 stimulates expression of the potent profibrotic matricellular PAI-1 and CTGF genes as well as those that code ECM structural elements . PAI-1 is one of the most highly regulated parts of the TGFβ1/SMAD3-induced group, a prominent ROS-responsive gene involved in the tissue fibrosis process. As the main inhibitor of plasmin generation, PAI-1 limits ECM degradation, alleviating the accumulation of matrix structural elements at the injury site. PAI-1 deficiency is renal-protective, whereas transgenic PAI-1 overexpression promotes an increased fibrotic response with associated recruitment of inflammatory cells, macrophages, and myofibroblasts. As proof-of-concept, unilateral ureter-obstructed PAI-1 T-cells .However, it is worth mentioning that out of these studies, we could only identify one when polymerase chain reaction (PCR) analysis was applied in human ureters and showed that the amount of TGFβ1 mRNA in stenotic tissue was higher than in controls . AnotherWe found only one study analyzing the role of PAI-1 in an obstructed kidney model and showing that TIMP-1 and PAI-1 in rat models are involved in the progression of tubulointerstitial scarring of renal tissue .With regard to one of the theories of UB branching, AngII is named as one of the enhancers for this process. PAI-1 has also been described as a downstream target of AngII in endothelial cells . Is therWe were able to identify only one study where VEGF was investigated in UPJO and a control group in human specimens: no color staining of VEGF was found in both obstructed and control groups and subsequently showed no difference in staining potential regardless of obstruction pattern . Our resWe could not identify any previous publications regarding Ctgf expression profile in congenital ureteral obstruction.Our results have demonstrated that relative expression of Ctgf in stenotic ureteral tissue was significantly lower than in the control tissue, supporting the potential role of this gene in the processes of stricture development. Ctgf has important roles in many biological processes, including cell adhesion, migration, proliferation, angiogenesis, skeletal development, and tissue wound repair, and is critically involved in fibrotic disease and several forms of cancer ,24. It iEvident similarity in the expression of other studied genes may suggest that the fibrosis process is not the most important in the development of congenital PUJO, and we should rather concentrate on other aspects of development. Sox9, a homeobox gene, the loss of which led to smooth muscle cell differentiation arrest [Sox9 in the regulation of differentiation in the ureteric mesenchyme. Primary dilatation of the renal collecting system without ureteral obstruction was induced by Keap1 knockout and the expression of aquaporins with spontaneous mutations, which caused urinary hyperproduction and secondary dilatation of the renal collecting system [Considering other aspects of cell distribution, the most prominent alteration comprises interstitial cells of Cajal and telocytes, which are significantly reduced in comparison to normal ureteral tissue in both UPJO and UVJO. Differentiation of Cajal cells may be stimulated by overexpression of the CTGF gene . Furthern arrest . Anotherg system .The drawback of our study is the relatively low and heterogeneous age sample size. Although statistical analysis was possible, more specimens would be needed to elucidate the potential differences in the expression of our studied genes. Another drawback is a small and non-homogenous control group when five pyeloureteric junctions were obtained from renal tumor specimens and one pyeloureteric junction was obtained from the duplex kidney system. None of them had macroscopic signs of stricture; however, the results can be influenced by preoperative chemotherapy and maldevelopment of the ureteral wall when compared to normal ureters . ObserveCtgf expression in a strictured ureteral specimen may be a sign of a progressive failure determined by a genetic trigger occurring during the embryonic period. Further studies have to be conducted to verify hypotheses involving wider gene panels, proteomic analysis, and histological verification.In summary, our findings suggest that tissue fibrosis, similar to other tissues and organs, is not the leading cause of stenosis, at least at the moment of surgery. Decreased


The extracellular matrix (ECM) is a noncellular structure that plays an indispensable role in a series of cell life activities. Accumulating studies have demonstrated that ECM stiffness, a type of mechanical forces, exerts a pivotal influence on regulating organogenesis, tissue homeostasis, and the occurrence and development of miscellaneous diseases. Nevertheless, the role of ECM stiffness in ophthalmology is rarely discussed. In this review, we focus on describing the important role of ECM stiffness and its composition in multiple ocular structures  from a new perspective. The abnormal changes in ECM can trigger physiological and pathological activities of the eye, suggesting that compared with different biochemical factors, the transmission and transduction of force signals triggered by mechanical cues such as ECM stiffness are also universal in different ocular cells. We expect that targeting ECM as a therapeutic approach or designing advanced ECM-based technologies will have a broader application prospect in ophthalmology. A large number of studies are increasingly concerned with the physical properties of cells and tissues along with the influences of biophysical characteristics within tissue microenvironments on cell function –3. ThereECM stiffness, a source of mechanical stimulation, transfers the external physical force onto the cell, which is transformed into biochemical signals through a series of cascade reactions inside the cells to regulate various ocular physiological and pathological activities, including cell migration and proliferation, retinal vascular development, corneal homeostasis, maintenance of normal human trabecular mesh function, and IOP as well as the occurrence of glaucoma and subconjunctival fibrosis , 15–17.In this review, we summarize the major components and physical properties of ECM and its underlying mechanisms for regulating normal ocular physiological and pathological activities. We aim to provide new insights into how the multiple signals are integrated to modulate ocular cell behaviors for the development of novel therapeutic strategies for ocular tissue repair and regeneration while targeting ECM as a therapeutic modality.β1 (TGF-β1) is released into the stromal space after injury and can promote the differentiation of dormant keratocytes into myofibroblasts, the phenotypic transition of corneal keratocytes is linked to signaling downstream of TGF-β1 . Th. Thβ2 , aggrecan, neurocan, and brevican, are critical for maintaining the normal function of the optic nerve –70. Tenaα-SMA signaling and its colocalization with actin stress fibers , 9087, 9Interestingly, the ocular delivery of collagen mimetic peptide (CMP) compensates for the damage caused by the biochemical degradation and remodeling of ocular ECMs, preventing the functional defect of RGC projected to the brain after the increase of IOP in the most prevalent model of experimental glaucoma, microbead occlusion Figures  98, 99], 9998, 9Combining the tunable mechanical and biochemical properties of an electrospun polymer sheet with ECM or ECM-derived meterials, endowing the bio-hybrid scaffold the advantages of higher tensile strength and controllable degradation rates , 100. ReECM provides attachment and adhesion for cells, regulates intercellular communication, and supports the integrity of multicellular structures. ECM is highly tissue-specific, and its components vary with multicellular structure, affecting a variety of cell life processes. ECM stiffness is a form of mechanical force, and mechanical mechanics is an essential factor in the modulation of cell function and behavior. However, the role of ECM stiffness is rarely discussed in the field of ophthalmology. In this paper, we focus on describing the important role of ECM stiffness and its composition in multiple ocular structures  from a new perspective. Abnormal changes in ECM stiffness and its composition can trigger physiological and pathological activities of the eye in response. This also suggests that, compared with different biochemical factors, ECM stiffness, a mechanical cue, is universal in the transmission and transduction of force signals in different ocular cell types. In addition, we summarized the advantages of using ECM technology as regenerative medicine in the treatment of ocular diseases and emphasized that ECM has great research value and clinical application prospects in the field of ophthalmology.


Cancer-associated fibroblasts (CAFs) are the most abundant stromal cell population in breast tumors. A functionally diverse population of CAFs increases the dynamic complexity of the tumor microenvironment (TME). The intertwined network of the TME facilitates the interaction between activated CAFs and breast cancer cells, which can lead to the proliferation and invasion of breast cells. Considering the special transmission function of CAFs, the aim of this review is to summarize and highlight the crosstalk between CAFs and breast cancer cells in the TME as well as the relationship between CAFs and extracellular matrix (ECM), soluble cytokines, and other stromal cells in the metastatic state. The crosstalk between cancer-associated fibroblasts and tumor microenvironment also provides a plastic therapeutic target for breast cancer metastasis. In the course of the study, the inhibitory effects of different natural compounds on targeting CAFs and the advantages of different drug combinations were summarized. CAFs are also widely used in the diagnosis and treatment of breast cancer. The cumulative research on this phenomenon supports the establishment of a targeted immune microenvironment as a possible breakthrough in the prevention of invasive metastasis of breast cancer. Metastasis of breast cancer is the main cause of cancer-related death among women worldwide . AlthougTo date, the attempts the programs to reverse or and reshape the TME have mainly focused on cutting off the relationship between different elements in the tumor environment. In this context, we focus on the effects of crosstalk between CAFs and different elements of the TME on factors of tumor metastasis, specifically chemokines, growth factors, immune cells, ECM, and other factors promoting tumor progression, we summarize how fibroblast differentiation and tumor metastasis can be inhibited by regulating various factors in the TME. In addition, the integrated application of natural products and nanomaterials has attracted wide attention as a new approach for targeting the TME or inhibiting tumor metastasis through CAFs . SolvingAs a novel cell population, CAFs are extremely heterogeneous and can originate from totally different cell precursors and locations. However, in the context of breast cancer, sources of CAFs are limited. As shown in Fig. In normal human tissues, resting fibroblasts are identified (under a microscope) as monolayer cells, with a slender spindle shape, that originate from the mesoderm and are fusiform . Under nCAFs drive breast cancer progression by allowing cancer cells to acquire an aggressive phenotype through the cross-reaction of different factors, which result in the unlimited proliferation of breast tumors, colonization and dissemination of tumors before metastatic spread, and increased permeability of the endothelial cell layer in a specific way that enables tumor cells to escape from the primary site to other distant organs , 27. In Tumor metastasis includes a series of biological events, and the gradual acquisition of the ability of primary tumor cells to invade deeper tissues through the mucosa is considered to be the first step in the beginning of tumor metastasis . When thBreast CAFs and cancer cells accumulate and then circulate in the peripheral blood of patients with metastatic breast cancer to form a niche for distant organ metastasis, ultimately completing the metastatic cascade. Breast cancer fibroblasts play an important role in the transmission of the pro-cascade, whether in the infinite proliferation of cells, intravasation of cells, or formation of metastatic niches. There is also a communication mechanism between primary tumor and distant metastasis. Metastatic cancer cells usually exist in dormant state in distal tissues and organs . As the In this process, CAFs secrete a variety of cytokines, such as growth factors and chemokines, which regulate the TME and adapt it to sustain tumor growth; CAFs also recruit immune cells that change the immune microenvironment. In addition, CAFs increase the deposition and remodeling of ECM, increase the tension and stiffness of cells and tissues, and change the tissue structure , 40. CAFThe effects of activated CAFs on tumors are multifaceted and include tumor colonization, metastasis, and unlimited dissemination , 43. An CAFs secrete various cytokines including growth factors, chemokines, and interleukin. These factors not only act as important stimulators to directly activate CAFs but also target key signal axes to promote tumor progression . Among tSome growth factors not only activate fibroblasts directly as stimulating factors but also regulate the environment by secreting a large number of autocrine and paracrine cytokines and other tumor-promoting factors by CAFs to build an environment conducive to tumor growth and transplantation , 46.The most representative growth factor is transforming growth factor-β (TGF-β), which is often involved in ECM mechanical sensing and myofibroblast differentiation . StudiesIn addition to the typical TGF-β pathway, other growth factors play an important role in metastasis. Researchers have found that hepatocyte growth factor (HGF) secreted by CAFs may be one of the contributing factors to the tumorigenic difference between CAFs and NFs. Breast cancer cells reprogram the surrounding fibroblasts to secrete HGF, which is positively related to the enhancement of breast tumorigenesis, migration, and invasion . In addiNerve growth factor(NGF) is also an important growth factor in other growth factors. CAFs has been shown to activate YAP1/TEAD1 signal and increase the score of NGF in prostate cancer . MoreoveChemokines and their receptors mediate chemotaxis, which is strongly involved in the dynamic processes of tumor development and progression. Chemokines, as a key factor in the secretion of CAFs, become the “booster” of breast cancer progression . ChemokiCAFs and chemokine CXCL12 are the most often studied in the invasive progression of breast cancer. CAF-derived chemokines secrete CXCL12 to regulate the mdia2-directed cytoskeleton in breast tumor cells to affect the movement of breast tumor cells . In addiThe stimulation of inflammatory factors by chemokines and the TME cannot be ignored. When tumor cells interact with stromal cells in the presence of pro-inflammatory stimuli, this interaction lays the foundation for pro-inflammatory signals to activate Notch1, resulting in an increase in CXCL8 production and increased metastatic activity . Unlike In addition to chemokines and growth factors, interleukin contribute to the crosstalk in the TME. We investigated the interactions between interleukin and fibroblasts in breast cancer. Interleukin-6 (IL-6) is the most widely studied cytokine. It is undeniable that IL-6 is usually secreted at high levels in the breast cancer microenvironment. Isolation of stromal fibroblasts from breast cancer tissue and analysis of the supernatant showed that IL-6 downregulated the tumor suppressor HIC1 and promoted the development of breast cancer in the TME through paracrine or autocrine signals . In addiExosomes are important communication media between tumors and CAFs that encapsulate a variety of proteins, lipids, mRNA, microRNAs, and lncRNAs. Crosstalk between various tumor cells is an important factor that cannot be ignored as a factor in tumor progression. Crosstalk between tumor cells and the microenvironment is not unidirectional. MicroRNAs not only regulate the relationship between NFs and CAFs, but exosomes secreted by tumor cells also play a role in regulating the upstream of CAFs . In turnExosome miRNAs promote tumor metastasis and progression by delivery to recipient cells to regulate the expression of target genes. Patient-derived exosome miR500a-5p can endow breast cancer cells with an invasive phenotype , and CAFTumor-associated macrophages (TAMs), derived from circulating monocyte precursors, are the most abundant type of innate immune cells in the immune microenvironment. CAFs and TAMs are active participants in tumor progression and metastasis and play a synergistic role in the TME. Investigators have found that in the vicinity of the accumulation area of CAFs, there was a high infiltration of TAMs around the tumor nest in TNBC  which prIn most studies of the synergistic effect of CAFs and TAMs, researchers use the co-culture incubation mode, in which cytokines, such as chemokines, can regulate the phenotype of other stromal cells, and the cytokines secreted by CAFs are more often used as active triggers to regulate the phenotype of macrophages. CAF-derived IL-33 significantly enhances TAM recruitment and induces M2 phenotype activation. At the molecular level, the IL-33-ST2-NF-κB-MMP9-laminin signaling pathway mediates cross-communication among various cellular components involved in cancer metastasis . CAF-derParacrine regulation also occurs between CAFs, TAMs, and tumor cells. OPN secreted by TAMs enhances the secretion of OPN by CAFs, thus, increasing the malignancy of cancer cells. OPN is the key molecule in the tumor–CAF–TAM interaction . A correIn many steps of tumor progression and metastasis, we observed that TAMs and tumor-associated neutrophils (TANs) are similar, and TANs are abundant immune cells in the TME. Both TAMs and TANs can regulate antitumor immunity and have a polarization effect . FibroblMalignant cells crosstalk with a variety of tumor stroma in the TME, including CAFs, TAMs, and other immune cells, to support their growth and metastasis. CAFs cause various forms of secretion by activating various signaling pathways. These secretions provide a medium for driving immune escape in tumors. Cytokines secreted by CAFs actively trigger factors that regulate macrophages or paracrine regulatory links between CAFs, TAMs, and tumor cells to increase cell migration. These findings suggest that eliminating the crosstalk between CAFs and other stromal cells may be a potential therapeutic strategy for blocking tumor immune escape.ECM remodeling is not only a necessary step in tumor invasion and metastasis, but also the result of comprehensive effects. The ECM is a complex mixture of structural proteins, proteoglycans, and glycoproteins. The mechanical properties of the ECM are closely related to the role of CAFs. Dynamic remodeling of the ECM leads to changes in tumor cell density, hardness, or tissue changes. Changes in the structure of the TME triggered by mechano-transduction promote the directional migration and invasion of cancer cells, and the biomechanical and physico-mechanical properties unique to the ECM may be important factors in the formation of the metastatic niche and cancer progression . The harThe first step in invasion and metastasis is the adhesion and interaction between ECM cells. The ECM affects breast tumor growth and metastasis through signaling pathways, key proteins, and related enzymes. CAFs produce a large number of ECM structural components related to tumor-promoting activities; for example, collagen XII is mainly secreted by CAFs and regulates collagen I fibrillar tissue to promote cancer cell invasion and breast cancer metastasis . In addiFurthermore, matrix modification and mechanical transduction regulate various signaling pathways, of which the YAP/TAZ pathway is an important connection between breast CAFs and matrix remodeling. CAF-driven YAP-dependent matrix sclerosis may lead to the proximity of some cancer cells to the rigid matrix. In the co-culture model, CAFs were the most effective in promoting the invasion of breast cancer cells. Moreover, their ability to promote matrix remodeling and invasion, which can regulate the contractile actomyosin cytoskeleton and reduce matrix remodeling of CAFs by blocking MYL9/MLC function, increases with an increase in the stage of the disease . In addiTumor cells first come in contact with receptors on the surface of the basement membrane and then secrete degrading enzymes or induce stromal cells to secrete enzymes that degrade the basement membrane and matrix. For example, lysyl oxidase is an important component for the cross-linking and stabilization of the ECM. High expression of lysyl oxidase in breast CAFs induces ECM remodeling, invasion, and metastasis of breast cancer cells in vitro and in vivo. CAF-derived lysyl oxidase is an important mediator of intercellular communication in the TME and a potential therapeutic target , 103. GlIn the process of CAF-induced hardening of the tumor shape to promote tumor invasiveness, mechanical signal-induced skeleton tension is an important factor in maintaining tumor stability; consequently, structural collapse is regarded as an important step in preventing or reversing the formation of CAF-induced tumors.Prunella vulgaris polysaccharides exert anticancer effects on breast CAFs by inhibiting the expression of bFGF [In addition to the above micro-environment crosstalk factors, angiogenesis is another necessary step in tumor invasion and metastasis. Angiogenesis is an important condition for niche formation prior to metastasis to the TME . The bal of bFGF .CAFs can affect the TME and promote tumor metastasis by secreting cytokines, remodeling the ECM, and promoting angiogenesis. For example, CAF-derived adrenomedullin plays an important role in breast cancer growth and neovascularization by providing and amplifying the signals necessary for pathological angiogenesis . SimilarIn addition to the above factors, sex steroids are also an important part of the crosstalk between fibroblasts and TME. Specifically, steroid hormone receptors are closely related to specific cancer types. For example, androgen receptor (AR) signaling is a major driver of prostate cancer (PCa) progression .In contr(1) The diagnostic and prognostic value of CAFs in BCs (2) The role of CAF in drug resistance (3) Natural products and the application of targeted CAF in combination therapy.The interweaving of CAFs and tumor metastasis permeates in all aspects of tumor development. It also reminds researchers that CAFs as a prognostic marker may contribute to the development of promising therapeutic drugs. In the combination therapy of targeting tumor cells, CAFs is expected to become a new strategy to improve clinical effect and overcome drug resistance. At present, aiming at the metastatic mechanism of breast cancer, the studies on the diagnosis and treatment of breast cancer by CAFs mainly include CAFs infiltration and activation of CAFs-related signaling pathways are closely related to the progression and prognosis of BCs. Therefore, there are a large number of studies trying to find CAFs-related biomarkers and evaluate their value in the prognosis and early diagnosis of BC. Busch found that the loss of TGFBR2 expression in BC-related CAFs was related to tumorigenesis and metastasis. By analyzing the expression level of TGFBR2 in CAFs of 564 patients with invasive BC, it was found that the expression of CAFs-specific TGFBR2 was related to relapse-free survival . In addiIn addition, CAFs can also realize its value as an effective safeguard in predicting recurrence and metastasis when other independent prognostic factors are limited. Circulating tumor cells (CTC) are detected in both early and metastatic cancers, which makes CTC unstable as an independent prognostic factor. The addition of CAFs makes it possible to predict the metastasis and recurrence of early solid tumors. In a patient with metastatic breast cancer, CAF was detected, but the absence of CTC is a good indication of the importance of CAFs . In moreIn the process of clinical treatment of tumor, the problem of toxicity and side effects limits the long-term application of traditional treatment in clinical practice. Many patients are prone to drug resistance and recurrence in the late stage Broad. Researcher found that CAFs can protect breast cancer cells from the effects of adriamycin. When tumor cells were co-cultured with CAFs, the expression of interferon(IFN) in CAFs was increased, and the IFN signal pathway was activated by paracrine to induce chemotherapy resistance. IFN blocking antibody can inhibit the protective effect of CAFs on cancer cells. It is not only the paracrine of CAF that affects drug resistance, but also the paracrine of drug resistant cells can induce the activation of CAF and further drug resistance . ChandraA large number of beneficial natural compounds that can be used to counteract cancer-related inflammation or cancer progression  The succThe classification of the properties of natural drugs targeting breast tumor fibroblasts is not specific, and it widely involves various types of compounds, of which polyphenols and flavonoids are the main components. In addition, there are anthraquinones, alkaloids, polysaccharides and so on. This seemingly irregular attribute distribution also shows that natural medicines play a role in many ways, and do not simply rely on the division of attributes. In the process of tumor progression, the wide range of effectiveness of natural drugs also fully shows that natural products are an important therapeutic means to reverse tumor-related fibroblasts into static fibroblasts.Prunella vulgaris polysaccharides can exert anticancer effects on breast CAFs by inhibiting the expression and biological activity of bFGF [When tumor growth and progression cannot be suppressed, natural products may be an important tool for controlling the pre-metastatic niche, as shown by the inhibition of the ability of breast active fibroblasts to induce metastatic EMT processes. Inhibition of metastasis is an important mechanism by which natural products target breast tumor-related fibroblasts, and metastasis is involved in almost all applications. Direct intervention is possible, as in the inhibitory effect of resveratrol on CAF-induced migration and invasion of breast cancer MDA-MB-231 cells . Breast  of bFGF . There aThe bioavailability of many natural compounds is usually far from satisfactory, and this limits the efficacy of natural drugs to some extent. Accordingly, nanocarriers are widely used by researchers. Nanotechnology helps to improve targeting efficiency, and CAF is the main participant in limiting drug penetration. Elimination of CAF may reduce the content of collagen in ECM and improve the accumulation and penetration of nanoparticles in tumors , 144. FiAt present, the application of natural products in anti-breast tumor fibroblasts is mainly concentrated in three different stages. First of all, kill the growth of the tumor at the “source”. Secondly, when the body is unable to suppress the growth and progress of the tumor, natural products may be an important weapon to control the niche before metastasis. it is shown by inhibiting the ability of breast cancer cells to promote metastasis and inhibiting angiogenesis. Finally, in the field of application, the combination of natural products with nanomaterials and chemotherapeutic drugs fully avoids the problems of low oral utilization and drug absorption of natural products, and gives full play to the characteristics of natural products in the treatment of breast tumors.The metastasis and recurrence of breast cancer are owing to not only the existence of invasive tumor cells but also the appropriate microenvironment, which is an important driving factor of metastasis . The casIt is necessary to block communication between tumor cells and fibroblasts. Both soluble cytokines and exocrine bodies act as transmitters that promote the metastasis cascade. It has been confirmed that not only is the influence between tumors and fibroblasts not in a single direction but the factors secreted by fibroblasts and exocrine bodies can also aggravate the progression of tumors. Cutting off the communication between the tumor and fibroblasts is an important strategy for breaking this vicious circle. At present, efforts to develop this solution have mainly focused on the relevant signal axis, such as growth factor-related TGF-β 1/Smad or chemokine-related CXCL1/CXCR12 signal axis. The crosstalk between fibroblasts and immune cells is mainly concentrated on macrophages in innate immune cells. Between CAFs, M2 polarized macrophages, and tumors, the spread and metastasis of cancer cells are realized through cross-interactions between stromal cells, cancer cells, and secreted cytokines. In the process of targeting CAFs, ECM acts as a barrier to protect cancer from treatment and support tumor progression. Destruction of the ECM is the defense layer that destroys TME, so targeting ECM is a potential strategy for anti-malignant therapy . In addiNatural products play an important role in preventing fibroblasts from promoting tumor cell transformation. Comprehensive studies on natural products in tumor-related fibroblasts have focused on reversing tumor metastasis. It is undeniable that at present, the combination of natural products and other chemotherapeutic drugs to target CAF is a very potential development direction, which not only makes up for the shortcomings of natural products, but also gives full play to its advantages .Although targeted CAFs have great application prospects and therapeutic potential, the heterogeneity of breast cancer fibroblasts requires further study. In the case of breast cancer, there was no significant relationship between the expression of CAF-related proteins and molecular subtypes. By contrast, CAFs were found to be correlated with metastatic organs . Secondl


It isn't fair. But we can change this .”1 Moreover, in this region, cancer was the cause of a quarter of deaths because of noncommunicable diseases in 2019, making AP the region that bears the heaviest burden of cancer worldwide.2 This is occurring at a time that AP is rapidly evolving a vital role in global health. It is the fastest growing economic region that comprises a diverse group of income countries , mortality is significantly higher.4 Given the diverse health systems, particularly in relation to government schemes for financial coverage, the stark reality is that a cancer diagnosis can potentially push families into poverty.5One half of all cancer cases and 58% of cancer deaths occur in Asia Pacific (AP), where more than 60% of the world's population reside.Each of the AP countries and territories has a distinctive cultural, linguistic, and geographic landscape which is reflected in variations in cancer risk factors, incidence, unique needs, and challenges in delivering equitable, high-quality cancer care. To highlight these challenges and increase awareness of the complex landscape of oncology across AP, this special series compiles articles focused on three domains: (1) cancer screening and treatment patterns, (2) culturally sensitive cancer care, and (3) global and regional partnership in cancer care.2 Among the cancers of which early diagnosis has been proven to effectively reduce mortality are lung and cervical cancer, both highly prevalent in the AP region.Primary prevention and early detection are keys to reducing the cancer burden. Therefore, raising public awareness and access to cancer screening and diagnosis needs to be prioritized on the national agenda.2 Although smoking cessation is the most effective primary prevention, screening with low-dose computed tomography (LDCT) has significantly reduced mortality in large randomized controlled trials. Nevertheless, only 22% of the countries in the Western Pacific Region have implemented lung cancer screening. Nightingale et al6 summarized the numerous barriers and challenges for lung cancer screening in this area, including limited evidence about the effective recruitment strategies of high-risk individuals in the region, resource limitation, and infrastructure challenges. The review addresses the importance of primary care practitioners in encouraging the participation of high-risk individuals, the need to improve health care professionals' competency in interpreting LDCT, and subsequently managing suspicious nodules or incidental findings. Finally, greater advocacy for LDCT within LMICs requires careful consideration of competing health priorities, health system capacity, and local cost-effectiveness analysis of individual countries.Lung cancer is responsible for the most cancer-related deaths worldwide; the Western Pacific Region Fig  contribu7 Cervical cancer has been referred to as a disease of inequity, given that up to 90% of mortality occurs in LMICs, where screening remains low.8 For example, screening coverage is 4% in the Western Pacific and 18% in Southeast Asia, far below the WHO recommendation of 70% screening coverage of eligible women. Self-collection screening of cervical cancer has been proven effective in high-income countries and has the potential to overcome many of the identified barriers to accessing screening in LMICs, namely eliminating the need for a pelvic examination, a clinic setting, and a trained clinician. A review by Creagh et al9 summarized the feasibility and acceptability of self-collection screening of cervical cancer in low-, middle-, and high-income settings across the AP region. This review concludes that screen-and-treat models with point-of-care testing are feasible to implement within low-resource settings but that further capacity building for self-collection requires more data evaluating the sustainability of individual programs and their health economic impact.Cervical cancer is a highly preventable cancer but remains one of the most commonly diagnosed cancers worldwide; more than half of all cases occur in AP.10 Charonpongsuntorn et al11 conducted the first multicenter prospective study to generate local data regarding the efficacy and safety profiles of this combination therapy among Thai patients with unresectable hepatocellular carcinoma. This study showed that combination therapy could improve patients' survival and quality of life and confirms the efficacy of this therapy beyond high-income countries. Further advocacy for adoption in Thailand and other limited-resource settings should now focus on the health economic impact.Another prevailing cancer in AP is liver cancer, with Thailand, Vietnam, China, and South Korea ranked among the top 10 countries with the highest incidence worldwide. Not only incidence but mortality is also significantly higher in LMIC AP countries, where the modern standard-of-care therapeutics, such as combination of atezolizumab and bevacizumab, are not routinely accessible.12 Therefore, medical decision making is often family-centered, concealment of information is common, and social harmony is often valued over individual autonomy. Additionally, if a paternalistic communication style prevails among doctors, patients may have little involvement in decision making.13 Mori et al14 reviewed evidence on the communication practices with patients with cancer and their families in the AP, showing that despite the traditional scenarios of implicit communication, partial or nondisclosure of information, and family-centered decision making, recent studies show a gradual shift toward open communication in cancer diagnosis, prognosis, advance care planning, and end-of-life discussions. This review has implications for the cancer care of AP populations both within and outside the region. Such cultural sensitivity requires health care professionals to understand the common features of the patients' culture while avoiding stereotypical characterizations. The development of communication tools with strategies to acknowledge these cultural considerations has been shown to be helpful.To enable equitable access to cancer care, every patient should be offered the opportunity to be involved in the decision making around their care. Meaningful engagement requires patients to have a sufficient understanding of their illness; however, providing medical information and sharing decision making are culturally sensitive processes for both the affected individual and their families and carers. Asian countries are primarily collectivist-oriented, where care for an individual is viewed mainly as a family task.15 shared the experience of recognizing Indonesia's unique social system and local culture to facilitate a community approach to palliative care. Indonesia is the fourth most populated nation worldwide, with more than 16,000 islands. More than 70% of Indonesian patients with cancer are admitted in their advanced stage, and only 1% can access palliative care.16 Because of the limited and unevenly distributed palliative care in health care facilities, most palliative cases in the community rely on charity and activities from various nongovernmental organizations.17 Eng's report focuses on the unique Indonesian philosophy of gotong royong or mutual assistance, which signifies social solidarity within the smaller bubbles of the community, which was identified as an enabler of a compassionate community in Jakarta.Understanding the local culture not only facilitates communication with individual patients but can build partnerships with communities, optimizing their role in supporting cancer care in the public setting. Eng et al18 A survey among Tamil and Sinhalese patients with breast cancer in Sri Lanka, a country with multiethnic  and multilinguistic societies with three different official languages , is reported in this Special Edition. Thanabalasingam et al19 showed that patients who speak the same language as their health care providers showed a higher level of satisfaction with the care received.One of the most important elements of culture is language. Equal access to care for every patient with cancer requires careful consideration and targeted efforts for linguistically diverse populations. When the language of care provision is not the same as the patient's primary language, it has been shown that patients tend to be more vulnerable to experiencing inequities.20 Diaz et al21 audited Australian online information resources to explore the publicly accessible information about cardiovascular health after cancer, an issue that is important for survivorship care, particularly for indigenous Aboriginal and Torres Strait Islander people. This study showed that among the dearth of Australian online information resources on cardio-oncology, none was directed at, designed, or even included Aboriginal and Torres Strait Islander people. Given the persistent inequalities in cancer and cardiovascular disease outcomes for Aboriginal and Torres Strait Islander people, the development of resources that take into consideration their readability, understandability, actionability, and inclusivity among Aboriginal and Torres Strait Islander people is imperative.Alongside the need for the provision of language-concordant care is the provision of high-quality, freely accessible and culturally congruent health information. This is especially true among indigenous populations who are at higher risk of significant disparities in cancer care around the world.22 reported gross inequities in cancer survivorship care and research across the Indo-Pacific. Concern for progression, recurrence, access to care, and coordination of care were among the most reported unmet needs in LMICs. Pleasingly, the study also outlines emerging regional partnerships in survivorship care delivery and research development.Over the past decades, the pace of innovation in cancer care has been remarkable, spanning novel diagnostics to broad therapeutics. Despite these significant advances, disparities remain wide, with huge variations of needs and health system capability across the AP. Koczwara et al23 shared the experience of the collaboration between the APRC and ASCO in adapting the leadership development program through project-based learning. The paper outlines initiatives relevant to other regions when creating a culturally adapted leadership pathway that fits best with local context and culture.To learn more about the diverse needs and landscapes of oncology in the AP, ASCO launched the Asia Pacific Regional Council (APRC) in 2019 to advise on the member needs and encourage the involvement of regional cancer health care professionals in ASCO's global activities. Highly prioritized was the need to create leaders in the region. Understanding that the traditional Western leadership program may not be well suited to an Asian context, a culturally modified training program was deemed essential. de Guzman et al24 Trainer skills were taught in the trainer program, and a reservoir of local health care champions was built to ensure the sustainability of the palliative care service in Sarawak. The collaborative effort also led to translational work of the education materials, ensuring language is not a barrier in learning palliative care. Yip shared a similar collaborative effort between professionals from high-income countries working with colleagues from the Solomon islands, a resource-limited country in South Pacific aimed toward establishing a sustainable oncology unit.25 This collaboration provides a blueprint for other startup units in the region.The collaborative effort between ASCO and AP countries through APRC went beyond the adaptation of a training program to improving the quality of cancer care in medical institutions in LMICs. Wong et al provided a report of the international cancer corps program in 2019, where ASCO collaborated with the team in Sarawak Malaysia to conduct palliative care educational programs, which resulted in positive changes in the practice of oncology care in Sarawak General Hospital.26 shared the complexities of coordinating multinational clinical trials in AP, because of cultural, linguistic, and economic diversity. Among the challenges were regulatory complexity, communication and logistical barriers, limited funding and resources, disparate experience with trial conduct and trial infrastructure, recruitment holds because of changes in local laws  and patient attrition, and disruptions caused by the COVID-19 pandemic. Despite all, significant opportunities are identified, and this paper highlights the potential contributions of opening up trials to the AP population, not only for participation but also for leadership.Finally, evidence-based, high-quality cancer care depends on high-quality research. Currently, cancer research is heavily skewed toward high-income countries, with little research conducted in, and relevant to, the problems of LMICs. Day et alJGO will cultivate many more collaborative efforts in the region so that high-quality cancer care can be provided to the many of millions of people wherever they live.It is evident that closing the cancer care gap, in a region so rich in culture and language, with a clear distinction between high- and low-income countries, requires significant attention and resources, along with support, collaboration, and cultural humility. We hope this issue of


Together, these applications will broaden our understanding of brain functions at the cellular level and in health and disease.The development of tools and applications in cellular neuroscience research has rapidly advanced over the past decade and opened new avenues of research. In this Research Topic, we showcase the latest methods and analyses that yield exciting advancements in cellular neuropathology. We highlight techniques used to label and manipulate specific brain cell types, molecular profiling of low abundance cells, improvements in regenerative medicine protocols and Dorgans et al. generated and validated novel AAV vectors to target the inferior olivary nucleus (ION) neurons. The authors applied custom AAV vectors to the ION of the cerebellum, an area that gates essential timely-related signals to the cerebellum for motor control. This new tool is helpful for the explicit labeling of ION cells, and it allows calcium imaging approaches to monitor even subtle activity signatures in specific cell types in vitro and in vivo. This warrants a more detailed investigation into the circuits and connectivity of the olivo-cerebellar system in vivo under normal conditions and pathology.The adeno-associated viral (AAV) vectors offer a powerful tool for labeling, monitoring, and modulation of brain cell activity in a cell-type-specific fashion. Xu et al. and Ji et al. bring high sensitivity detection and transcriptome profiling of low abundance cells and protein posttranslational modifications.The latest technical advances used in Xu et al. have applied 10x Genomics single-cell RNA sequencing to cochlear sensory epithelial cells embedded in the temporal bone, both in low number and challenging to profile. Here, the authors characterized the transcriptome of various cell types, including hair cells, supporting cells, and immune cells in the juvenile and mature cochlea, and have mapped genes related to pathology, such as deafness genes, to corresponding cell types. This technique also allowed identifying novel long non-coding RNAs expressed at different developmental stages opening new directions of research. The study provides an invaluable resource for cochlear maturation at single-cell resolution.Single-cell RNA sequencing has been extensively used in the past years to profile brain cells, providing unprecedented knowledge of cell heterogeneity and vulnerability to different neurological pathologies, regulatory interactions, and biomarkers  are involved in brain development and the pathophysiological mechanisms of neurodegenerative diseases  sciatic nerve insult, with potential applications in neuropathic pain. In spinal cord injury, a combination therapy involving modulation of local inflammation and BM-MSC transplantation may improve motor survival and help myelination.Over the past few decades, much research has focused on promoting axonal regeneration, replenishing brain cells, and rebuilding lost pathways after nervous system injuries and neurodegenerative conditions. A growing body of evidence suggests that multipotent stromal cells or mesenchymal stem cells (MSC), derived from adipose tissue (A-MSC) or bone marrow (BM-MSC), are strong candidates for nervous system regeneration due to their potential for neuronal differentiation and the safety of transplantation  cell line and propose its use for modeling Parkinson's disease-like neuroinflammatory profile in vitro.Cell culture models mimicking the cellular interactions of the brain cells are used to improve our understanding of structures, functions, and environment at the microscopic level. Significant progress was made in the two-dimensional and three-dimensional models over the past decades. However, more work is needed to answer essential mechanistic questions and efficiently test therapeutics in preclinical studies in complex neurological diseases, including neurodegeneration  concept emerged in 2001 and refers to the relationship between brain cells and blood vessels in the maintenance of the blood-brain barrier (BBB) and regulation of blood supply to the brain. NVU dysfunctions have been recently associated with most neurodegenerative diseases  that catalyzes the breakdown of acetylcholine neurotransmitters and is essential for the termination of signal transmission. AChE inhibition, therefore, results in increased cholinergic signaling leading to several dysfunctions in both the peripheral and central nervous system, such as disruption of voluntary movement, loss of consciousness and seizure. This Research Topic highlights a small sample from the broad range of emerging approaches that enable discoveries in cellular neuropathology. We want to share our excitement with the readers and witness novel directions that these methods will bring in the near future.GB drafted, edited, and reviewed the manuscript. MY edited and reviewed the final manuscript. All authors contributed to the article and approved the submitted version.