A key regulator of tumor-associated neutrophils: the CXCR2 chemokine receptor.

In recent years, with the advance of research, the role of tumor-associated neutrophils (TANs) in tumors has become a research hotspot. As important effector cells in the innate immune system, neutrophils play a key role in the immune and inflammatory responses of the body. As the first line of defense against bacterial and fungal infections, neutrophils have the ability to kill invading pathogens. In the pathological state of malignant tumors, the phenotype of neutrophils is altered and has an important regulatory function in tumor development. The C-X-C motif chemokine receptor 2(CXCR2) is a key molecule that mediates the migration and aggregation signaling pathway of immune cells, especially neutrophils. This review focuses on the regulation of CXCR2 on TANs in the process of tumorigenesis and development, and emphasizes the application significance of CXCR2 inhibitors in blocking the migration of TANs to tumors.

Cobalt substitution-induced π-donation in NiMoO4 for enhanced electrochemical charge storage.

NiMoO4 (NM) has garnered significant attention due to its rich d-orbital electronic structure and multivalent electroactive cations. However, the inherently low electrical conductivity of NM limits its reaction kinetics. Herein, cobalt-substituted NM (Co-NM) nanorods were prepared via a hydrothermal reaction followed by subsequent thermal treatment. The incorporation of Ni-O-Co configurations stimulates an enhanced π-donation effect of the Co-O bond, facilitating the hybridization between the O 2p and Co 3d orbitals and thereby boosting charge transfer kinetics during electrochemical processes. The optimized 10 %Co-NM nanorods demonstrated a remarkable specific capacity of 557.8 C·g-1 at 1 A·g-1. Furthermore, an asymmetric supercapacitor constructed with 10 %Co-NM as the positive electrode and FeOOH as the negative electrode, achieved a significant energy density of 63.58 Wh·kg-1 at a power density of 805.38 W·kg-1. Thus, our work provides new insights into the rational design of stable bridging configurations to significantly improve electrochemical reaction kinetics.

A multidimensional strategy for uncovering comprehensive quality markers of Scutellariae Radix based on UPLC-Q-TOF-MS analysis, artificial neural network, network pharmacology analysis, and molecular simulation.

Introduction: Scutellariae Radix (SR), derived from the root of Scutellaria baicalensis Georgi, is a traditional Chinese medicine (TCM) for clearing heat and cooling blood. It has been used as a traditional herbal medicine and is popular as a functional food in Asian countries today. Methods: In this study, UPLC-Q-TOF-MS was first employed to identify the chemical components in the ethanol extract of SR. Then, the extraction process was optimized using star point design-response surface methodology. Fingerprints of different batches and processed products were established, and chemical markers were screened through a combination of various artificial neural network models. Finally, network pharmacology and molecular simulation techniques were utilized for verification to determine the quality markers. Results: A total of 35 chemical components in SR were identified, and the optimal extraction process was determined as follows: ultrasonic extraction with 80% methanol at a ratio of 120:1 for 70 minutes, with a soaking time of 30 minutes. Through discriminant analysis using various artificial neural network models, the samples of SR could be classified into two categories based on their growth years: Kuqin (dried roots of older plants) and Ziqin (roots of younger plants). Moreover, the samples within each category could be further clustered according to their origins. The four different processed products of SR could also be distinguished separately. Finally, through the integration of network pharmacology and molecular simulation techniques, it was determined that baicalin, baicalein, wogonin, norwogonin, norwogonin-8-O-glucuronide, skullcapflavone II, hispidulin, 8, 8"-bibaicalein, and oroxylin A-7-O-beta-D-glucuronide could serve as quality markers for SR. Discussion: The primary factors affecting the quality of SR were its growth years. The geographic origin of SR was identified as a secondary factor affecting its quality. Processing also had a significant impact on its quality. The selected quality markers have laid the foundation for the quality control of SR, and this research strategy also provides a research paradigm for improving the quality of TCM.

A review of the botany, phytochemistry, pharmacology, synthetic biology and comprehensive utilization of Silybum marianum.

Silybum marianum (L.) Gaertn, a herbaceous plant with a long history in traditional medicine for the treatment of hepatobiliary diseases, particularly in Europe, which has attracted attention for its remarkable therapeutic effect. This review systematically summarizes the research progress in the botany, phytochemistry, pharmacology, comprehensive utilization and synthetic biology of S. marianum. Up to now, more than 20 types of flavonolignan components have been isolated from S. marianum. In addition, the rearch on fatty acids and triterpenoids is also constantly improving. Among them, silybin is the most active compound in flavonolignans components. Its pharmacological effects in vivo and in vitro include anti-inflammatory, antioxidant, anti-tumour, hypoglycaemic, neuroprotective and immunoregulatory properties. The use of coniferyl alcohol and taxifolin as substrates to produce silybin and isosilybin under the action of enzyme catalysis is the commonly used biosynthetic pathway of silymarin, which provides support for a comprehensive analysis of the synthetic pathway of silymarin. In addition to medicinal use, the extracts of plants also have broad application prospects in the production of food, healthcare products, cosmetics and other aspects. In addition, the chemical composition, pharmacological mechanism and synthetic biology of S. marianum need to be further studied, which is very important for its clinical efficacy and resource development.

Genome-wide identification of bZIP transcription factors and their expression analysis in Platycodon grandiflorus under abiotic stress.

The Basic Leucine Zipper (bZIP) transcription factors (TFs) family is among of the largest and most diverse gene families found in plant species, and members of the bZIP TFs family perform important functions in plant developmental processes and stress response. To date, bZIP genes in Platycodon grandiflorus have not been characterized. In this work, a number of 47 PgbZIP genes were identified from the genome of P. grandiflorus, divided into 11 subfamilies. The distribution of these PgbZIP genes on the chromosome and gene replication events were analyzed. The motif, gene structure, cis-elements, and collinearity relationships of the PgbZIP genes were simultaneously analyzed. In addition, gene expression pattern analysis identified ten candidate genes involved in the developmental process of different tissue parts of P. grandiflorus. Among them, Four genes (PgbZIP5, PgbZIP21, PgbZIP25 and PgbZIP28) responded to drought and salt stress, which may have potential biological roles in P. grandiflorus development under salt and drought stress. Four hub genes (PgbZIP13, PgbZIP30, PgbZIP32 and PgbZIP45) mined in correlation network analysis, suggesting that these PgbZIP genes may form a regulatory network with other transcription factors to participate in regulating the growth and development of P. grandiflorus. This study provides new insights regarding the understanding of the comprehensive characterization of the PgbZIP TFs for further exploration of the functions of growth and developmental regulation in P. grandiflorus and the mechanisms for coping with abiotic stress response.

The Rhododendron Chrysanthum Pall.s' Acetylation Modification of Rubisco Enzymes Controls Carbon Cycling to Withstand UV-B Stress.

Lysine acetylation of proteins plays a critical regulatory function in plants. A few advances have been made in the study of plant acetylproteome. However, until now, there have been few data on Rhododendron chrysanthum Pall. (R. chrysanthum). We analyzed the molecular mechanisms of photosynthesis and stress resistance in R. chrysanthum under UV-B stress. We measured chlorophyll fluorescence parameters of R. chrysanthum under UV-B stress and performed a multi-omics analysis. Based on the determination of chlorophyll fluorescence parameters, R. chrysanthum Y(NO) (Quantum yield of non-photochemical quenching) increased under UV-B stress, indicating that the plant was damaged and photosynthesis decreased. In the analysis of acetylated proteomics data, acetylated proteins were found to be involved in a variety of biological processes. Notably, acetylated proteins were significantly enriched in the pathways of photosynthesis and carbon fixation, suggesting that lysine acetylation modifications have an important role in these activities. Our findings suggest that R. chrysanthum has decreased photosynthesis and impaired photosystems under UV-B stress, but NPQ shows that plants are resistant to UV-B. Acetylation proteomics revealed that up- or down-regulation of acetylation modification levels alters protein expression. Acetylation modification of key enzymes of the Calvin cycle (Rubisco, GAPDH) regulates protein expression, making Rubisco and GAPDH proteins expressed as significantly different proteins, which in turn affects the carbon fixation capacity of R. chrysanthum. Thus, Rubisco and GAPDH are significantly differentially expressed after acetylation modification, which affects the carbon fixation capacity and thus makes the plant resistant to UV-B stress. Lysine acetylation modification affects biological processes by regulating the expression of key enzymes in photosynthesis and carbon fixation, making plants resistant to UV-B stress.

Aging and homeostasis of the hypodermis in the age-related deterioration of skin function.

Adipose tissues in the hypodermis, the crucial stem cell reservoir in the skin and the endocrine organ for the maintenance of skin homeostasis undergo significant changes during skin aging. Dermal white adipose tissue (dWAT) has recently been recognized as an important organ for both non-metabolic and metabolic health in skin regeneration and rejuvenation. Defective differentiation, adipogenesis, improper adipocytokine production, and immunological dissonance dysfunction in dWAT lead to age-associated clinical changes. Here, we review age-related alterations in dWAT across levels, emphasizing the mechanisms underlying the regulation of aging. We also discuss the pathogenic changes involved in age-related fat dysfunction and the unfavorable consequences of accelerated skin aging, such as chronic inflammaging, immunosenescence, delayed wound healing, and fibrosis. Research has shown that adipose aging is an early initiation event and a potential target for extending longevity. We believe that adipose tissues play an essential role in aging and form a potential therapeutic target for the treatment of age-related skin diseases. Further research is needed to improve our understanding of this phenomenon.

Development of an algorithm for proton dose calculation in magnetic fields.

BACKGROUND: The advantages of proton therapy can be further enhanced with online magnetic resonance imaging (MRI) guidance. One of the challenges in the realization of MRI-guided proton therapy (MRPT) is accurately calculating the radiation dose in the presence of magnetic fields. PURPOSE: This study aims to develop an efficient and accurate proton dose calculation algorithm adapted to the presence of magnetic fields. METHODS: An analytical-numerical radiation dose calculation algorithm, Proton and Ion Dose Engine (PRIDE), was developed. The algorithm combines the pencil beam algorithm (PBA) with a novel iterative voxel-based ray-tracing algorithm. The new ray-tracing method uses fewer assumptions and ensures broader applicability for proton beam trajectory prediction in magnetic fields, and has been compared to Wolf's method and Schellhammer's method. The accuracy of PRIDE algorithm was validated on three phantoms and two practical plans (one single-field water plan and one prostate tumor plan) in different magnetic field strengths up to 3.0 T. The validation was performed by comparing the results against the Monte Carlo (MC) simulations, using the global gamma index criteria of 2%/2 mm and 3%/3 mm with a 10% threshold. RESULTS: PRIDE showed good agreement with MC in homogeneous and slab heterogeneous phantom, achieving gamma passing rates (%GPs) above 99% for 2%/2 mm criteria when magnetic field strength is not greater than 1.5 T. Although the agreement decreased for scenarios involving high proton energy (240 MeV) and strong magnetic field (3.0 T), the 2%/2 mm %GPs still remained above 98%. In lateral heterogeneous phantom, the accuracy of PRIDE decreased due to the PBA's limitation. For the two practical plans in different magnetic fields, %GPs exceeded 98% and 99% for 2%/2 mm and 3%/3 mm criteria, respectively. CONCLUSIONS: PRIDE can perform efficient and accurate proton dose calculation in magnetic fields up to 3.0 T, and is expected to work as a useful tool for proton dose calculation in MRPT.

The CXCR2 chemokine receptor: A new target for gastric cancer therapy.

Gastric cancer (GC) is one of the most common malignant tumors in the world, and current treatments are still based on surgery and drug therapy. However, due to the complexity of immunosuppression and drug resistance, the treatment of gastric cancer still faces great challenges. Chemokine receptor 2 (CXCR2) is one of the most common therapeutic targets in targeted therapy. As a G protein-coupled receptor, CXCR2 and its ligands play important roles in tumorigenesis and progression. The abnormal expression of these genes in cancer plays a decisive role in the recruitment and activation of white blood cells, angiogenesis, and cancer cell proliferation, and CXCR2 is involved in various stages of tumor development. Therefore, interfering with the interaction between CXCR2 and its ligands is considered a possible target for the treatment of various tumors, including gastric cancer.

Family cumulative risk, life satisfaction, and anxiety and depression in adolescents: A developmental cascades model.

INTRODUCTION: Family cumulative risk (FCR) is predominantly regarded as an antecedent for adolescent mental health, as the prevailing perspective continues to emphasize the influential role of parents, despite recognizing the child's influence. To identify the interplay between family adversity (FCR, process-related FCR, and sociodemographic-related FCR), life satisfaction (LS), and anxiety and depression (AD), this study examined the cascade effects among these constructs. METHOD: Participants (N = 707; 52.9% male; grades 10 and 11) from four high schools in Wuhan, China, were recruited to participate, and they completed the measures in October 2018, April 2019, and November 2019. Family sociodemographic risk (e.g., single parenthood) and family process risk (e.g., low family cohesion) were simulated in the models for FCR, sociodemographic-related FCR, and process-related FCR. RESULTS: The random intercept cross-lagged panel models (RI-CLPMs) revealed a lagged effect from LS to FCR; lagged effects from LS and AD to process-related FCR at the within-person level; and significant associations between LS, AD, and family adversity at the between-person level. CONCLUSIONS: The lagged effects provide evidence for the influential child perspective and suggest that FCR and family process risk are sensitive to adolescent well-being and psychopathological symptoms. School mental health prevention and intervention programs that take a complete mental health approach to enhance children's well-being and alleviate symptoms would help prevent increases in family risk.

Presodiation Architected Robust Surface Enables Packaging Optimal Performance of Sodium-Ion Batteries.

Presodiation has shown great promise in compensating sodium storage losses. In the absence of a mechanistic understanding of how presodiation affects the surface of an electrode material, packaging optimization is restricted. Focusing on interfaces, we illustrate the working principle of presodiation in virtue of short-circuiting internal circuits. The presodiated carbon nanotubes (PS-CNTs) provide a thin, denser, and more robust solid electrolyte interfacial layer, enabling a high initial Coulombic efficiency (ICE), high power density, and cycling stability with the merits of uniformly distributed NaF. As a result, our assembled sodium-ion battery (SIB) full cell with PS-CNT has an ICE of 91.6% and an energy density of 226 Wh kg-1, which was superior to the pristine CNT control electrode (ICE of 42.9% and energy density of 163 Wh kg-1). The gained insights can be practically applied to directly promote the commercial uses of carbon-based materials in sodium-ion batteries.

Cloning, Expression Characteristics of Farnesyl Pyrophosphate Synthase Gene from Platycodon grandiflorus and Functional Identification in Triterpenoid Synthesis.

Platycodon grandiflorus is a medicinal plant whose main component is platycodins, which have a variety of pharmacological effects and nutritional values. The farnesyl pyrophosphate synthase (FPS) is a key enzyme in the isoprenoid biosynthesis pathway, which catalyzes the synthesis of farnesyl diphosphate (FPP). In this study, we cloned the FPS gene from P. grandiflorus (PgFPS) with an ORF of 1260 bp, encoding 419 amino acids with a deduced molecular weight and theoretical pI of 46,200.98 Da and 6.52, respectively. The squalene content of overexpressed PgFPS in tobacco leaves and yeast cells extract was 1.88-fold and 1.21-fold higher than that of the control group, respectively, and the total saponin content was also increased by 1.15 times in yeast cells extract, which verified the biological function of PgFPS in terpenoid synthesis. After 48 h of MeJA treatment and 6 h of ethephon treatment, the expression of the PgFPS gene in roots and stems reached its peak, showing a 3.125-fold and 3.236-fold increase compared to the untreated group, respectively. Interestingly, the expression of the PgFPS gene in leaves showed a decreasing trend after exogenous elicitors treatment. The discovery of this enzyme will provide a novel perspective for enhancing the efficient synthesis of platycodins.

Acetylation proteomics and metabolomics analyses reveal the involvement of starch synthase undergoing acetylation modification during UV-B stress resistance in Rhododendron Chrysanthum Pall.

BACKGROUND: Rhododendron chrysanthum Pall. (R. chrysanthum) is a plant that lives in high mountain with strong UV-B radiation, so R. chrysanthum possess resistance to UV-B radiation. The process of stress resistance in plants is closely related to metabolism. Lysine acetylation is an important post-translational modification, and this modification process is involved in a variety of biological processes, and affected the expression of enzymes in metabolic processes. However, little is known about acetylation proteomics during UV-B stress resistance in R. chrysanthum. RESULTS: In this study, R. chrysanthum OJIP curves indicated that UV-B stress damaged the receptor side of the PSII reaction center, with a decrease in photosynthesis, a decrease in sucrose content and an increase in starch content. A total of 807 differentially expressed proteins, 685 differentially acetylated proteins and 945 acetylation sites were identified by quantitative proteomic and acetylation modification histological analysis. According to COG and subcellular location analyses, DEPs with post-translational modification of proteins and carbohydrate metabolism had important roles in resistance to UV-B stress and DEPs were concentrated in chloroplasts. KEGG analyses showed that DEPs were enriched in starch and sucrose metabolic pathways. Analysis of acetylation modification histology showed that the enzymes in the starch and sucrose metabolic pathways underwent acetylation modification and the modification levels were up-regulated. Further analysis showed that only GBSS and SSGBSS changed to DEPs after undergoing acetylation modification. Metabolomics analyses showed that the metabolite content of starch and sucrose metabolism in R. chrysanthum under UV-B stress. CONCLUSIONS: Decreased photosynthesis in R. chrysanthum under UV-B stress, which in turn affects starch and sucrose metabolism. In starch synthesis, GBSS undergoes acetylation modification and the level is upregulated, promotes starch synthesis, making R. chrysanthum resistant to UV-B stress.

A dynamic individual method for yak heifer live body weight estimation using the YOLOv8 network and body parameter detection algorithm.

Live body weight (LBW) is one of the most important parameters for supervising the growth and development of livestock. The yak (Bos grunniens) is a special species of cattle that lives on the Qinghai-Tibetan Plateau. Yaks are more untamed than regular cattle breeds, so it is more challenging to measure their LBW. In this study, YOLOv8 yak detection and LBW estimation models were used to automatically estimate yak LBW in real time. First, the proper posture (normal posture) and individual yak identification was confirmed and then the YOLOv8 detection model was used for LBW estimation from 2-dimensional images. Yak LBW was estimated through yak body parameter extraction and a simple linear regression between the estimated yak LBW and the actual measured yak LBW. The results showed that the overall detection performance for normal yak posture was described by precision, recall, and mean average precision 50 (mAP50) indicators, reaching 81.8%, 86.0%, and 90.6%, respectively. The best yak identification results were represented by precision, recall, and mAP50 values of 97.8%, 96.4%, and 99.0%, respectively. The yak LBW estimation model achieved better results for the 12-mo-old yaks with shorter hair, with values for R2, root mean square error, mean absolute percentage error, and multiple R of 0.96, 2.43 kg, 1.69%, and 0.98, respectively. The results demonstrate that yak LBW can be estimated and monitored in real time using this approach. This study has the potential to be used for daily yak LBW monitoring in an unstressed manner and to save considerable labor resources for large-scale livestock farms. In the future, to reduce the limitations caused by the impacts of yak hair and light condition, datasets of dairy cows and yaks of different ages will be used to improve and generalize the model.

Atom-by-atom optimizing the surface termination of Fe-Pt intermetallic catalysts for alkaline hydrogen evolution reaction.

Controlling the atomic arrangement of elemental atoms in intermetallic catalysts to govern their surface and subsurface properties is a crucial but challenging endeavor in electrocatalytic reactions. In hydrogen evolution reaction (HER), adjusting the d-band center of the conventional noble-metallic Pt by introducing Fe enables the optimization of catalytic performance. However, a notable gap exists in research on the effective transition from disordered Fe/Pt alloys to highly ordered intermetallic compounds (IMCs) such as FePt3 in the alkaline HER, hampering their broader application. In this study, a series of catalysts FePt3-xH (x = 5, 6, 7, 8 and 9) supported on carbon nanotubes (CNTs) were synthesized via a simple impregnation method, along with a range of heat treatment processes, including annealing in a reductive atmosphere, to regulate the order degree of the arrangement of Fe/Pt atoms within the FePt3 catalyst. By using advanced microscopy and spectroscopy techniques, we systematically explored the impact of the order degree of FePt3 in the HER. The as-prepared FePt3-8H exhibited notable HER catalytic activity with low overpotentials (η = 37 mV in 1.0 mol L-1 KOH) at j = 10 mA cm-2. The surface of the L12 FePt3-8H catalyst was demonstrated to be Pt-rich. The Pt on the surface was not easily oxidized due to the unique Fe/Pt coordination, resulting in significant enhancement of HER performance.

Sex differences in stress-induced hyperalgesia and its mechanisms.

Chronic stress induces a variety of physiological and/or psychological abnormalities, including hyperalgesia. Researchers have discovered sex differences in the prevalence of stress-induced hyperalgesia (SIH) in recent years. Sex differences may be one of the reasons for the heterogeneity of susceptibility to stress-related diseases. In this review, the potential mechanisms of sex differences in SIH are discussed, such as hypothalamus-pituitary-adrenal axis responses, regulation of sex hormones, and immune system responses.

GETV nsP2 plays a critical role in the interferon antagonism and viral pathogenesis.

Getah virus (GETV) was becoming more serious and posing a potential threat to animal safety and public health. Currently, there is limited comprehension regarding the pathogenesis and immune evasion mechanisms employed by GETV. Our study reveals that GETV infection exhibits the capacity for interferon antagonism. Specifically, the nonstructural protein nsP2 of GETV plays a crucial role in evading the host immune response. GETV nsP2 effectively inhibits the induction of IFN-ß by blocking the phosphorylation and nuclear translocation of IRF3. Additionally, GETV nsP2 hinders the phosphorylation of STAT1 and its nuclear accumulation, leading to significantly impaired JAK-STAT signaling. Furthermore, the amino acids K648 and R649, situated in the C-terminal region of GETV nsP2, play a crucial role in facilitating nuclear localization. Not only do they affect the interference of nsP2 with the innate immune response, but they also exert an influence on the pathogenicity of GETV in mice. In summary, our study reveals novel mechanisms by which GETV evades the immune system, thereby offering a foundation for comprehending the pathogenic nature of GETV. Video Abstract.

Multi-Omic Analysis Reveals the Molecular Mechanism of UV-B Stress Resistance in Acetylated RcMYB44 in Rhododendron chrysanthum.

Ultraviolet-B (UV-B) radiation is a significant environmental factor influencing the growth and development of plants. MYBs play an essential role in the processes of plant responses to abiotic stresses. In the last few years, the development of transcriptome and acetylated proteome technologies have resulted in further and more reliable data for understanding the UV-B response mechanism in plants. In this research, the transcriptome and acetylated proteome were used to analyze Rhododendron chrysanthum Pall. (R. chrysanthum) leaves under UV-B stress. In total, 2348 differentially expressed genes (DEGs) and 685 differentially expressed acetylated proteins (DAPs) were found. The transcriptome analysis revealed 232 MYB TFs; we analyzed the transcriptome together with the acetylated proteome, and screened 4 MYB TFs. Among them, only RcMYB44 had a complete MYB structural domain. To investigate the role of RcMYB44 under UV-B stress, a homology tree was constructed between RcMYB44 and Arabidopsis MYBs, and it was determined that RcMYB44 shares the same function with ATMYB44. We further constructed the hormone signaling pathway involved in RcMYB44, revealing the molecular mechanism of resistance to UV-B stress in R. chrysanthum. Finally, by comparing the transcriptome and the proteome, it was found that the expression levels of proteins and genes were inconsistent, which is related to post-translational modifications of proteins. In conclusion, RcMYB44 of R. chrysanthum is involved in mediating the growth hormone, salicylic acid, jasmonic acid, and abscisic acid signaling pathways to resist UV-B stress.

Panax japonicus C.A. Meyer: a comprehensive review on botany, phytochemistry, pharmacology, pharmacokinetics and authentication.

BACKGROUND: Panax japonicus C.A. Meyer (Zhujieshen) is widely used in traditional medicine as a tonic hemostatic and anti-inflammatory agent in China, Japan, and Korea. Furthermore, it is used as an important substitute for ginseng roots by minority ethnic groups in China. The purpose of this review is to summarize the latest research on Zhujieshen in recent years, aiming at providing a systematic overview of the current knowledge, and perspectives for future research and exploitation. MAIN BODY: This review examines the research advances in botanical profile, phytochemicals, pharmacology, pharmacokinetics, and authentication of Zhujieshen. Various compounds have been reported as active components, mainly including saponins, volatile oils, and polysaccharides. Pharmacological investigations have demonstrated that Zhujieshen is an important herb with significant bioactivities, such as anti-inflammatory, hepato-protective, cardio-protective, neuro-protective, anti-tumor, anti-oxidant, anti-thrombotic and immunomodulatory activities. CONCLUSION: Currently, research on Zhujieshen is in the preliminary stages, and further research is required to understand the active compounds present and mechanisms of action. We hope that this comprehensive review of Zhujieshen will serve as a background for future research and exploitation.

Targeting MyD88: Therapeutic mechanisms and potential applications of the specific inhibitor ST2825.

BACKGROUND: Myeloid differentiation factor-88 (MyD88) is a crucial adapter protein that coordinates the innate immune response and establishes an adaptive immune response. The interaction of the Toll/Interleukin-1 receptor (IL-1R) superfamily with MyD88 triggers the activation of various signalling pathways such as nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), promoting the production of a variety of immune and inflammatory mediators and potentially driving the development of a variety of diseases. OBJECTIVE: This article will explore the therapeutic potential and mechanism of the MyD88-specific inhibitor ST2825 and describe its use in the treatment of several diseases. We envision future research and clinical applications of ST2825 to provide new ideas for the development of anti-inflammatory drugs and disease-specific drugs to open new horizons for the prevention and treatment of related inflammatory diseases. MATERIALS AND METHODS: This review analysed relevant literature in PubMed and other databases. All relevant studies on MyD88 inhibitors and ST2825 that were published in the last 20 years were used as screening criteria. These studies looked at the development and improvement of MyD88 inhibitors and ST2825. RESULTS: Recent evidence using the small-molecule inhibitor of ST2825 has suggested that blocking MyD88 activity can be used to treat diseases such as neuroinflammation, inflammatory diseases such as acute liver/kidney injury, or autoimmune diseases such as systemic lupus erythematosus and can affect transplantation immunity. In addition, ST2825 has potential therapeutic value in B-cell lymphoma with the MyD88 L265P mutation. CONCLUSION: Targeting MyD88 is a novel therapeutic strategy, and scientific research is presently focused on the development of MyD88 inhibitors. The peptidomimetic compound ST2825 is a widely studied small-molecule inhibitor of MyD88. Thus, ST2825 may be a potential therapeutic small-molecule agent for modulating host immune regulation in inflammatory diseases and inflammatory therapy.