ChatGPT Combining Machine Learning for the Prediction of Nanozyme Catalytic Types and Activities.

The design of nanozymes with superior catalytic activities is a prerequisite for broadening their biomedical applications. Previous studies have exerted significant effort in theoretical calculation and experimental trials for enhancing the catalytic activity of nanozyme. Machine learning (ML) provides a forward-looking aid in predicting nanozyme catalytic activity. However, this requires a significant amount of human effort for data collection. In addition, the prediction accuracy urgently needs to be improved. Herein, we demonstrate that ChatGPT can collaborate with humans to efficiently collect data. We establish four qualitative models (random forest (RF), decision tree (DT), adaboost random forest (adaboost-RF), and adaboost decision tree (adaboost-DT)) for predicting nanozyme catalytic types, such as peroxidase, oxidase, catalase, superoxide dismutase, and glutathione peroxidase. Furthermore, we use five quantitative models (random forest (RF), decision tree (DT), Support Vector Regression (SVR), gradient boosting regression (GBR), and fully connected deep neuron network (DNN)) to predict nanozyme catalytic activities. We find that GBR model demonstrates superior prediction performance for nanozyme catalytic activities (R2 = 0.6476 for Km and R2 = 0.95 for Kcat). Moreover, an open-access web resource, AI-ZYMES, with a ChatGPT-based nanozyme copilot is developed for predicting nanozyme catalytic types and activities and guiding the synthesis of nanozyme. The accuracy of the nanozyme copilot's responses reaches more than 90% through the retrieval augmented generation. This study provides a new potential application for ChatGPT in the field of nanozymes.

Forkhead box P3 gene polymorphisms predispose to type 2 diabetes and diabetic nephropathy in the Han Chinese populations: a genetic-association and gender-based evaluation study.

BACKGROUND: Functional mutations or polymorphisms affecting forkhead box P3 (FOXP3) can lead to their abnormal FOXP3 gene expression and/or defective Treg cells generation, thus resulting in autoimmune disease and inflammatory disorders. FOXP3 also plays a key role in Type 2 diabetes mellitus (T2DM) and its complications, because the disease usually involves chronic low-grade inflammatory disorders and is associated with long-term immune system imbalance. This study aimed to investigate the association between FOXP3 polymorphisms and the susceptibility to T2DM and type 2 diabetes nephropathy (T2DN) within the Han Chinese populations. METHODS: Polymorphisms in rs3761548C/A and rs2294021C/T were examined in 400 patients (which include an equal number of T2DM and T2DN groups) and 200 healthy controls using PCR-HRM and sequence analysis. RESULTS: The genotype and allelic frequencies of the two single nucleotide polymorphisms (SNPs) were significantly different in T2DM and the progression of diabetes developing to T2DN. The further gender-based evaluation showed that in female subjects, rs3761548C/A was associated with an approximately 3-fold higher threat for T2DM and 4.5-fold for T2DN, while there was no noticeable association with rs2294021C/T; in males, the promoter polymorphism showed an increased predisposition of 5.4-fold and 3.4-fold predisposition to T2DM and T2DN, respectively, while rs2294021 polymorphism could impart a nearly 2-fold risk of developing T2DN. An additional analysis of combined genotypes (rs3761548 C/A-rs2294021C/T) revealed that CC-CC and CC-CT can be considered protective combinations in the predisposition of males with diabetes towards T2DN, while AA-CC and AA-TT have the opposite effect. CONCLUSIONS: This study demonstrated the possible involvement of individual and combined genetic associations of rs3761548C/A and rs2294021C/T polymorphisms with the susceptibility to diabetes and diabetic nephropathy in the Han Chinese population, as well as gender bias.

Saccharomyces cerevisiae mannan induces sheep beta-defensin-1 expression via Dectin-2-Syk-p38 pathways in ovine ruminal epithelial cells.

The rumen epithelium of sheep serves as an immune interface with the environment and secretes antimicrobial peptides with bactericidal function against various pathogens. Sheep beta-defensin-1 (SBD-1), an antimicrobial peptide, is secreted from ovine ruminal epithelial cells (OREC) in response to microbial infections. Mannan, the main component of the Saccharomyces cerevisiae cell wall can stimulate innate and regulatory immune responses that could improve the gastrointestinal environment. We aimed at investigating the effects of mannan on SBD-1 expression and the downstream signaling pathways stimulated in OREC. We cultured OREC; assessed the effects of mannan on SBD-1 expression by qPCR and ELISA; and then investigated the underlying signaling pathways using qPCR, ELISA, Western blotting, immunohistochemistry, and immunohistofluorescence. Interestingly, mannan markedly upregulated SBD-1 expression in a concentration- and time-dependent manner. Dectin-2 Mouse mAb, Syk specific inhibitor R406, and specific inhibitors of the p38, ERK1/2, JNK, and NF-κB pathways attenuated mannan-induced SBD-1 expression to varying degrees. These results demonstrate that SBD-1 is upregulated by mannan via the Dectin-2-Syk axis, and this is regulated to a large extent through the mitogen-activated protein kinase (MAPK) p38 and less so through the ERK1/2 and JNK or the NF-κB pathway. Our findings highlight the immunomodulatory effects of mannan on OREC in terms of mannan-induced SBD-1 expression.

Modulation of ovine SBD-1 expression by Saccharomyces cerevisiae in ovine ruminal epithelial cells.

BACKGROUND: The ovine rumen is involved in host defense responses and acts as the immune interface with the environment. The ruminal mucosal epithelium plays an important role in innate immunity and secretes antimicrobial innate immune molecules that have bactericidal activity against a variety of pathogens. Defensins are cationic peptides that are produced by the mucosal epithelia and have broad-spectrum antimicrobial activity. Sheep ß-defensin-1 (SBD-1) is one of the most important antibacterial peptides in the rumen. The expression of SBD-1 is regulated by the probiotic, Saccharomyces cerevisiae (S.c); however, the regulatory mechanism has not yet been elucidated. In the current study, the effects of S.c on the expression and secretion of SBD-1 in ovine ruminal epithelial cells were investigated using quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). In addition, specific inhibitors were used to block the nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), p38, JNK, and ERK1/2 signalling pathways separately or simultaneously, to determine the regulatory mechanism(s) governing S.c-induced SBD-1 upregulation. RESULTS: Incubation with S.c induced release of SBD-1 by ovine ruminal epithelial cells, with SBD-1 expression peaking after 12 h of incubation. The highest SBD-1 expression levels were achieved after treatment with 5.2 × 107 CFU∙mL- 1 S.c. Treatment with S.c resulted in significantly increased NF-κB, p38, JNK, ERK1/2, TLR2, and MyD88 mRNA expression. Whereas inhibition of mitogen-activated protein kinases (MAPKs) and NF-κB gene expression led to a decrease in SBD-1 expression. CONCLUSIONS: S.c was induced SBD-1 expression and the S.c-induced up-regulation of SBD-1 expression may be related to TLR2 and MyD88 in ovine ruminal epithelial cells. This is likely simultaneously regulated by the MAPKs and NF-κB pathways with the p38 axis of the MAPKs pathway acting as the primary regulator. Thus, the pathways regulating S.c-induced SBD-1 expression may be related to TLR2-MyD88-NF-κB/MAPKs, with the TLR2-MyD88-p38 component of the TLR2-MyD88-MAPKs signalling acting as the main pathway.

Systems Pharmacology Dissection of Multiscale Mechanisms of Action for Herbal Medicines in Treating Rheumatoid Arthritis.

As a chronic inflammatory and angiogenic disease with increased morbidity and mortality, rheumatoid arthritis (RA) is characterized by the proliferation of synovial tissue and the accumulation of excessive mononuclear infiltration, which always results in the joint deformity, disability, and eventually the destruction of the bone and cartilage. Traditional Chinese Medicine (TCM), with rich history of proper effectiveness in treating the inflammatory joint disease containing RA, has long combated such illness from, actually, an integrative and holistic point of view. However, its "multi-components" and "multi-targets" features make it very difficult to decipher the molecular mechanisms of RA from a systematic perspective if employing only routine methods. Presently, an innovative systems-pharmacology approach was introduced, which combined the ADME screening model, drug targeting, and network pharmacology, to explore the action mechanisms of botanic herbs for the treatment of RA. As a result, we uncovered 117 active compounds and 85 key molecular targets from seven RA-related herbs, which are mainly implicated in four signaling pathways, that is, vascular endothelial growth factor, PI3K-Akt, Toll-like receptor, and T-cell-receptor pathways. Additionally, the network relationships among the active components, target proteins, and pathways were further built to uncover the pharmacological characters of these herbs. Besides, molecular dynamics (MD) simulations and molecular mechanics-Poisson-Boltzmann surface area calculations were carried out to explore the binding interactions between the compounds and their receptors as well as to investigate the binding affinity of the ligand to their protein targets. In vitro experiments by ligand binding assays validate the reliability of the drug-target interactions as well as the MD results. The high binding affinities and good inhibitions of the active compounds indicate that the potential therapeutic effects of these herbal medicines for treating RA are exerted probably through the modulation of these relevant proteins, which further validates the rationality and reliability of the drug-target interactions as well as our the network-based analytical methods. This work may be of help for not only understanding the action mechanisms of TCM and for discovering new drugs from plants for the treatment of RA, but also providing a novel potential method for modern medicine in treating complex diseases.

Mechanism Exploration of Arylpiperazine Derivatives Targeting the 5-HT2A Receptor by In Silico Methods.

As a G-protein coupled receptor, the 5-hydroxytryptamine 2A (5-HT2A) receptor is known for its critical role in the cognitive, behavioural and physiological functions, and thus is a primary molecular target to treat psychiatric diseases, including especially depression. With purpose to explore the structural traits affecting the inhibitory activity, currently a dataset of 109 arylpiperazine derivatives as promising 5-HT2A antagonists was built, based on which the ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) study by using both comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches was carried out. The resultant optimal CoMSIA model displays proper validity and predictability with cross-validated correlation coefficient Q² = 0.587, non-cross-validated correlation coefficient R²ncv = 0.900 and predicted correlation coefficient for the test set of compounds R²pre = 0.897, respectively. Besides, molecular docking was also conducted to investigate the binding mode between these ligands and the active site of the 5-HT2A receptor. Meanwhile, as a docking supplementary tool to study the antagonists' conformation in the binding cavity, molecular dynamics (MD) simulation was also performed, providing further elucidation about the changes in the ligand-receptor complex. Lastly, some new molecules were also newly-designed based on the above results that are potential arylpiperazine antagonists of 5-HT2A receptor. We hope that the present models and derived information may be of help for facilitating the optimization and design of novel potent antagonists as antidepressant drugs as well as exploring the interaction mechanism of 5-HT2A antagonists.

Computational Analysis of Structure-Based Interactions for Novel H1-Antihistamines.

As a chronic disorder, insomnia affects approximately 10% of the population at some time during their lives, and its treatment is often challenging. Since the antagonists of the H1 receptor, a protein prevalent in human central nervous system, have been proven as effective therapeutic agents for treating insomnia, the H1 receptor is quite possibly a promising target for developing potent anti-insomnia drugs. For the purpose of understanding the structural actors affecting the antagonism potency, presently a theoretical research of molecular interactions between 129 molecules and the H1 receptor is performed through three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques. The ligand-based comparative molecular similarity indices analysis (CoMSIA) model (Q² = 0.525, R²ncv = 0.891, R²pred = 0.807) has good quality for predicting the bioactivities of new chemicals. The cross-validated result suggests that the developed models have excellent internal and external predictability and consistency. The obtained contour maps were appraised for affinity trends for the investigated compounds, which provides significantly useful information in the rational drug design of novel anti-insomnia agents. Molecular docking was also performed to investigate the mode of interaction between the ligand and the active site of the receptor. Furthermore, as a supplementary tool to study the docking conformation of the antagonists in the H1 receptor binding pocket, molecular dynamics simulation was also applied, providing insights into the changes in the structure. All of the models and the derived information would, we hope, be of help for developing novel potent histamine H1 receptor antagonists, as well as exploring the H1-antihistamines interaction mechanism.

Systems pharmacology dissection of the anti-inflammatory mechanism for the medicinal herb Folium eriobotryae.

Inflammation is a hallmark of many diseases like diabetes, cancers, atherosclerosis and arthritis. Thus, lots of concerns have been raised toward developing novel anti-inflammatory agents. Many alternative herbal medicines possess excellent anti-inflammatory properties, yet their precise mechanisms of action are yet to be elucidated. Here, a novel systems pharmacology approach based on a large number of chemical, biological and pharmacological data was developed and exemplified by a probe herb Folium Eriobotryae, a widely used clinical anti-inflammatory botanic drug. The results show that 11 ingredients of this herb with favorable pharmacokinetic properties are predicted as active compounds for anti-inflammatory treatment. In addition, via systematic network analyses, their targets are identified to be 43 inflammation-associated proteins including especially COX2, ALOX5, PPARG, TNF and RELA that are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway, the rheumatoid arthritis pathway and NF-κB signaling pathway. All these demonstrate that the integrated systems pharmacology method provides not only an effective tool to illustrate the anti-inflammatory mechanisms of herbs, but also a new systems-based approach for drug discovery from, but not limited to, herbs, especially when combined with further experimental validations.

Insight into hemostatic performance and mechanism of natural mixed-dimensional Attapulgite clay.

Clay minerals have attracted wide attention as biomedical materials due to the unique crystal structure, abundant morphology and good biocompatibility. However, the relevant studies on the abundant natural mixed clay deposits were scarcely reported. Herein, the hemostatic performance of natural mixed-dimensional attapulgite clay (MDAPT) composed of one-dimensional attapulgite and multiple two-dimensional clay were systematically investigated based on the structural evolution using oxalic acid for different time. The results of hemostatic evaluation showed that MDAPT leached by oxalic acid with 1 h presented the shortest clotting time (134 ± 12.17 s), a 15.09 % and 41.74 % reduction of relative hemoglobin absorbance at 180 s and 120 s when compared with the control group, respectively, and an increase of 19.45 % of the blood clotting index in vitro, as well as MDAPT obtained the shortest bleeding time (158.5 ± 6.9 s), nearly 66 % and 31 % reduction blood loss as compared to the blank group and the YNBY group in vivo. This improvement was primarily ascribed to the synergistic effect of lamellar non-expandable illite, and nano rod-like attapulgite. Furthermore, the rapid hemostasis of MDAPT was also due to the joint effect of superhydrophobic property toward blood, minimizing blood loss, surface negative charge, metal ions from MDAPT structural skeleton, promoting an average increase of 21 % for platelet activation. The results suggested that MDAPT could be served as a promising efficient inorganic hemostatic materials, which provided a feasible strategy to realize the high-valued utilization of natural mixed clay resources.

Dencichine/palygorskite nanocomposite incorporated chitosan/polyvinylpyrrolidone film for accelerating wound hemostasis.

The development of efficient, safe, environmentally friendly, and user-friendly hemostatic dressings remains a great challenge for researchers. A variety of clay minerals and plant extracts have garnered considerable attention due to their outstanding hemostatic efficacy and favorable biosafety. In this study, a facile solution casting strategy was employed to prepare nanocomposite films by incorporating natural nanorod-like palygorskite (Pal) and herb-derived hemostat dencichine (DC) based on chitosan and polyvinylpyrrolidone. The dynamic blood clotting index demonstrated that the nanocomposite film with a DC addition of 1.0 wt% exhibited significantly superior hemostatic properties compared to both pure DC powder or commercial hemostatic agent Yunnan Baiyao. This improvement was primarily attributed to proper blood affinity, increased porosity, enhanced adhesion of platelets and erythrocytes, as well as the accelerated activation of coagulation factors and platelets. Under the synergistic effect of Pal and DC, the nanocomposite film displayed suitable tensile strength (20.58 MPa) and elongation at break (47.29 %), which may be due to the strong intermolecular hydrogen bonding and electrostatic interaction between Pal/DC and macropolymers. Notably, the nanocomposite film exhibited remarkable antibacterial effectiveness and desirable cytocompatibility, as well as the capability of promoting wound healing in vitro. Taken together, the nanocomposite film synergized with Pal and DC is expected to be an efficacious and suitable wound dressing.

The hemostatic performance and mechanism of palygorskite with structural regulate by oxalic acid gradient leaching.

Palygorskite (Pal) is a naturally available one-dimensional clay mineral, featuring rod-shaped morphology, nanoporous structure, permanent negative charges as well as abundant surface hydroxyl groups, exhibiting promising potential as a natural hemostatic material. In this study, the hemostatic performance and mechanisms of Pal were systematically investigated based on the structural regulate induced by oxalic acid (OA) gradient leaching from perspectives of structure, surface attributes and ion release.In vitroandin vivohemostasis evaluation showed that Pal with OA leaching for 1 h exhibited a superior blood procoagulant effect compared with the raw Pal as well as the others leached for prolonging time. This phenomenon might be ascribed to the synergistic effect of the intact nanorod-like morphology, the increase in the surface negative charge, the release of metal ions (Fe3+and Mg2+), and the improved blood affinity, which promoted the intrinsic coagulation pathway, the fibrinogenesis and the adhesion of blood cells, thereby accelerating the formation of robust blood clots. This work is expected to provide experimental and theoretical basis for the construction of hemostatic biomaterials based on clay minerals.

New insight into the mechanisms of Ginkgo biloba leaves in the treatment of cancer.

BACKGROUND: Ginkgo biloba leaves (GBLs), as an herbal dietary supplement and a traditional Chinese medicine, have been used in treating diseases for hundred years. Recently, increasing evidence reveals that the extracts and active ingredients of GBLs have anti-cancer (chemo-preventive) properties. However, the molecular mechanism of GBLs in anti-cancer has not been comprehensively summarized. PURPOSE: To systematically summarize the literatures for identifying the molecular mechanism of GBLs in cellular, animal models and clinical trials of cancers, as well as for critically evaluating the current evidence of efficacy and safety of GBLs for cancers. METHODS: Employing the search terms "Ginkgo biloba" and "cancer" till July 25, 2023, a comprehensive search was carried out in four electronic databases including Scopus, PubMed, Google Scholar and Web of Science. The articles not contained in the databases are performed by manual searches and all the literatures on anti-cancer research and mechanism of action of GBLs was extracted and summarized. The quality of methodology was assessed independently through PRISMA 2020. RESULTS: Among 84 records found in the database, 28 were systematic reviews related to GBLs, while the remaining 56 records were related to the anticancer effects of GBLs, which include studies on the anticancer activities and mechanisms of extracts or its components in GBLs at cellular, animal, and clinical levels. During these studies, the top six cancer types associated with GBLs are lung cancer, hepatocellular carcinoma, gastric cancer, breast cancer, colorectal cancer, and cervical cancer. Further analysis reveals that GBLs primarily exert their anticancer effects by stimulating cancer cell apoptosis, inhibiting cell proliferation, invasion and migration of cancers, exhibiting anti-inflammatory and antioxidant properties, and modulating signaling pathways. Besides, the pharmacology, toxicology, and clinical research on the anti-tumor activity of GBLs have also been discussed. CONCLUSIONS: This is the first paper to thoroughly investigate the pharmacology effect, toxicology, and the mechanisms of action of GBLs for anti-cancer properties. All the findings will reinforce the need to explore the new usage of GBLs in cancers and offer comprehensive reference data and recommendations for future research on this herbal medicine.

Comprehensive Exploration of the Neuroprotective Mechanisms of Ginkgo biloba Leaves in Treating Neurological Disorders.

Neurological disorders (NDs) are diseases that seriously affect the health of individuals worldwide, potentially leading to a significant reduction in the quality of life for patients and their families. Herbal medicines have been widely used in the treatment of NDs due to their multi-target and multi-pathway features. Ginkgo biloba leaves (GBLs), one of the most popular herbal medicines in the world, have been demonstrated to present therapeutic effects on NDs. However, the pharmacological mechanisms of GBLs in the treatment of neurological disorders have not been systematically summarized. This study aimed to summarize the molecular mechanism of GBLs in treating NDs from the cell models, animal models, and clinical trials of studies. Four databases, i.e., PubMed, Google Scholar, CNKI, and Web of Science were searched using the following keywords: "Ginkgo biloba", "Ginkgo biloba extract", "Ginkgo biloba leaves", "Ginkgo biloba leaves extract", "Neurological disorders", "Neurological diseases", and "Neurodegenerative diseases". All items meeting the inclusion criteria on the treatment of NDs with GBLs were extracted and summarized. Additionally, PRISMA 2020 was performed to independently evaluate the screening methods. Out of 1385 records in the database, 52 were screened in relation to the function of GBLs in the treatment of NDs; of these 52 records, 39 were preclinical trials and 13 were clinical studies. Analysis of pharmacological studies revealed that GBLs can improve memory, cognition, behavior, and psychopathology of NDs and that the most frequently associated GBLs are depression, followed by Alzheimer's disease, stroke, Huntington's disease, and Parkinson's disease. Additionally, the clinical studies of depression, AD, and stroke are the most common, and most of the remaining ND data are available from in vitro or in vivo animal studies. Moreover, the possible mechanisms of GBLs in treating NDs are mainly through free radical scavenging, anti-oxidant activity, anti-inflammatory response, mitochondrial protection, neurotransmitter regulation, and antagonism of PAF. This is the first paper to systematically and comprehensively investigate the pharmacological effects and neuroprotective mechanisms of GBLs in the treatment of NDs thus far. All findings contribute to a better understanding of the efficacy and complexity of GBLs in treating NDs, which is of great significance for the further clinical application of this herbal medicine.

Research on privacy protection in the context of healthcare data based on knowledge map.

With the rapid development of emerging information technologies such as artificial intelligence, cloud computing, and the Internet of Things, the world has entered the era of big data. In the face of growing medical big data, research on the privacy protection of personal information has attracted more and more attention, but few studies have analyzed and forecasted the research hotspots and future development trends on the privacy protection. Presently, to systematically and comprehensively summarize the relevant privacy protection literature in the context of big healthcare data, a bibliometric analysis was conducted to clarify the spatial and temporal distribution and research hotspots of privacy protection using the information visualization software CiteSpace. The literature papers related to privacy protection in the Web of Science were collected from 2012 to 2023. Through analysis of the time, author and countries distribution of relevant publications, we found that after 2013, research on the privacy protection has received increasing attention and the core institution of privacy protection research is the university, but the countries show weak cooperation. Additionally, keywords like privacy, big data, internet, challenge, care, and information have high centralities and frequency, indicating the research hotspots and research trends in the field of the privacy protection. All the findings will provide a comprehensive privacy protection research knowledge structure for scholars in the field of privacy protection research under the background of health big data, which can help them quickly grasp the research hotspots and choose future research projects.

Prostaglandin D2 is involved in the regulation of inflammatory response in Staphylococcus aureus-infected mice macrophages.

Staphylococcus aureus (S. aureus) is one of the most infamous and widespread bacterial pathogens, causing a hard-to-estimate number of uncomplicated skin infections and probably hundreds of thousands to millions of more severe, invasive infections globally per year. S. aureus may also be acquired from animals, especially in the livestock industry. The interaction mechanism of host and S. aureus has significance for finding ways to against S. aureus infection and control inflammatory response of host, while the molecular biological activities after S. aureus infection, particular in inflammatory and immune cells are not fully clear. The present study aimed to explore whether pattern recognition receptors (PRRs) mediate prostaglandin D2 (PGD2) synthesis and PGD2 participates in the regulation of inflammatory response in macrophages during S. aureus infection or synthetic bacterial lipopeptide (Pam2CSK4) stimulation. PGD2 secretion level was enhanced by mice peritoneal macrophages infected with the S. aureus. The results indicated that PGD2 secretion was impaired in S. aureus infected-macrophages from toll-like receptors 2 (TLR2)-deficient and NLR pyrin domain-containing 3 (NLRP3)-deficient mice. PGD2 synthetase (hematopoietic PGD synthase, HPGDS) inhibitors could reduce the activation of macrophage mitogen-activated protein kinase (MAPK)/nuclear factor-κ-gene binding (NF-κB) signaling pathways. HPGDS inhibition impaired cytokines (TNF-α, IL-1ß, IL-10 and RANTES) secretion and macrophage phagocytosis during S. aureus infection. In addition, inhibition of endogenous PGD2 synthesis was unable to affect the TLR2 and NLRP3 expression in S. aureus-infected macrophages. Taken together, macrophage PGD2 secretion after S. aureus infection depended on receptors TLR2 and NLRP3, and the induced PGD2 participated in the regulation of inflammatory response in S. aureus-infected macrophages. Interestingly, it was found that exogenous PGD2 down-regulated the cytokines secretion and had no effect on phagocytosis in the S. aureus-infected macrophages.

Progress and future prospects of hemostatic materials based on nanostructured clay minerals.

The occurrence of uncontrolled hemorrhage is a significant threat to human life and health. Although hemostatic materials have made remarkable advances in the biomaterials field, it remains a challenge to develop safe and effective hemostatic materials for global medical use. Natural clay minerals (CMs) have long been used as traditional inorganic hemostatic agents due to their good hemostatic capability, biocompatibility and easy availability. With the advancement of science, technology and ideology, CM-based hemostatic materials have undergone continuous innovations by integrating new inspirations with conventional concepts. This review systematically summarizes the hemostatic mechanisms of different natural CMs based on their nanostructures. Moreover, it also comprehensively reviews the latest research progress for CM-based hemostatic hybrid and nanocomposite materials, and discusses the challenges and developments in this field.

Novel targets for gastric cancer: The tumor microenvironment (TME), N6-methyladenosine (m6A), pyroptosis, autophagy, ferroptosis and cuproptosis.

Gastric cancer (GC) is a fatal illness, and its mortality rate is very high all over the world. At present, it is a serious health problem for any country. It is a multifactorial disease due to the rising drug resistance and the increasing global cancer burden, the treatment of GC still faces many obstacles and problems. In recent years, research on GC is being carried out continuously, and we hope to address the new targets of GC treatment through this review. At the same time, we also hope to discover new ways to fight GC and create more gospel for clinical patients. First, we discuss the descriptive tumor microenvironment (TME), N6-methyladenosine (m6A), pyroptosis, autophagy, ferroptosis, and cuproptosis. Finally, we expounded on the new or potential targets of GC treatment.

Systematic investigation of the mechanism of herbal medicines for the treatment of prostate cancer.

Due to various unpleasant side effects and general ineffectiveness of current treatments for prostate cancer (PCa), more and more people with PCa try to look for complementary and alternative medicine such as herbal medicine. However, since herbal medicine has multi-components, multi-targets and multi-pathways features, its underlying molecular mechanism of action is not yet known and still needs to be systematically explored. Presently, a comprehensive approach consisting of bibliometric analysis, pharmacokinetic assessment, target prediction and network construction is firstly performed to obtain PCa-related herbal medicines and their corresponding candidate compounds and potential targets. Subsequently, a total of 20 overlapping genes between DEGs in PCa patients and the target genes of the PCa-related herbs, as well as five hub genes, i.e., CCNA2, CDK2, CTH, DPP4 and SRC were determined employing bioinformatics analysis. Further, the roles of these hub genes in PCa were also investigated through survival analysis and tumour immunity analysis. Moreover, to validate the reliability of the C-T interactions and to further explore the binding modes between ingredients and their targets, the molecular dynamics (MD) simulations were carried out. Finally, based on the modularization of the biological network, four signaling pathways, i.e., PI3K-Akt, MAPK, p53 and cell cycle were integrated to further analyze the therapeutic mechanism of PCa-related herbal medicine. All the results show the mechanism of action of herbal medicines on treating PCa from the molecular to systematic levels, providing a reference for the treatment of complex diseases using TCM.

BTG2 and SerpinB5, a novel gene pair to evaluate the prognosis of lung adenocarcinoma.

Introduction: Lung adenocarcinoma (LUAD), as the most frequent pathological subtype of non-small cell lung cancer, is often characterized by poor prognosis and low 5-year survival rate. Exploriton of new biomarkers and accurate molecular mechanisms for effectively predicting the prognosis of LUAD patients is still necessary. Presently, BTG2 and SerpinB5, which play important roles in tumors, are studied as a gene pair for the first time with the aim of exploring whether they can be used as potential prognostic markers. Methods: Using the bioinformatics method to explore whether BTG2 and SerpinB5 can become independent prognostic factors, and explore their clinical application value and whether they can be used as immunotherapeutic markers. In addition, we also verify the conclusions obtained from external datasets, molecular docking, and SqRT-PCR. Results: The results show that compared with normal lung tissue, BTG2 expression level was down-regulated and SerpinB5 was up-regulated in LUAD. Additionally, Kaplan-Meier survival analysis demonstrate that the prognosis of low expression level of BTG2 was poor, and that of high expression level of SerpinB5 was poor, suggesting that both of them can be used as independent prognostic factors. Moreover, the prognosis models of the two genes were constructed respectively in this study, and their prediction effect was verified by external data. Besides, ESTIMATE algorithm reveals the relationship between this gene pair and the immune microenvironment. Furthermore, patients with a high expression level of BTG2 and a low expression level of SerpinB5 have higher immunophenoscore for CTLA-4 and PD-1 inhibitors than patients with a low expression level of BTG2 and a high expression level of SerpinB5, indicating that such patients have a more obvious effect of immunotherapy. Discussion: Collectively, all the results demonstrate that BTG2 and SerpinB5 might serve as potential prognostic biomarkers and novel therapeutic targets for LUAD.

Identification of Breast Cancer Subtypes by Integrating Genomic Analysis with the Immune Microenvironment.

Objectives: We aim to identify the breast cancer (BC) subtype clusters and the crucial gene classifier prognostic signatures by integrating genomic analysis with the tumor immune microenvironment (TME). Methods: Data sets of BC were derived from the Cancer Genome Atlas (TCGA), METABRIC, and Gene Expression Omnibus (GEO) databases. Unsupervised consensus clustering was carried out to obtain the subtype clusters of BC patients. Weighted gene coexpression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO), and univariate and multivariate regression analysis were employed to obtain the gene classifier signatures and their biological functions, which were validated by the BC dataset from the METABRIC database. Additionally, to evaluate the overall survival rates of BC patients, Kaplan-Meier survival analysis was carried out. Moreover, to assess how BC subtype clusters are related to the TME, single-cell analysis was performed. Finally, the drug sensitivity and the immune cell infiltration for different phenotypes of BC patients were also calculated by the CIBERSORT and ESTIMATE algorithms. Results : TCGA-BC samples were divided into three subtype clusters, S1, S2, and S3, among which the prognosis of S2 was poor and that of S1 and S3 were better. Three key pathways and 10 crucial prognostic-related gene signatures are screened. Finally, single-cell analysis suggests that S1 samples have the most types of immune cells, S2 with more sensitivity to tumor treatment drugs are enriched with more neutrophils, and more multilymphoid progenitor cells are involved in subtype cluster S3. Conclusions: Our novelty was to identify the BC subtype clusters and the gene classifier signatures employing a large-amount dataset combined with multiple bioinformatics methods. All of the results provide a basis for clinical precision treatment of BC.