PDFll: Predictors of Disorder and Function of Proteins from the Language of Life.

The identification of intrinsically disordered proteins and their functional roles is largely dependent on the performance of computational predictors, necessitating a high standard of accuracy in these tools. In this context, we introduce a novel series of computational predictors, termed PDFll (Predictors of Disorder and Function of proteins from the Language of Life), which are designed to offer precise predictions of protein disorder and associated functional roles based on protein sequences. PDFll is developed through a two-step process. Initially, it leverages large-scale protein language models (pLMs), trained on an extensive dataset comprising billions of protein sequences. Subsequently, the embeddings derived from pLMs are integrated into streamlined, yet sophisticated, deep-learning models to generate predictions. These predictions notably surpass the performance of existing state-of-the-art predictors, particularly those that forecast disorder and function without utilizing evolutionary information.

Fufang Duzheng tablet attenuates adjuvant rheumatoid arthritis by inhibiting arthritis inflammation and gut microbiota disturbance in rats.

Objective: To explore the treatment effect and potential mechanism on gut microbiota, nutrition, and metabolism of Fufang Duzheng Tablet (DZGP) on rheumatoid arthritis (RA). Methods: Collagen-induced arthritis rats' models were established and divided into three groups: model control group (FK), DZGP group (FZ, 0.45 g/kg/d), and methotrexate group (FM, 1.35 mg/kg), which were treated by gavage for 28 days. The physiopathologic changes of joints and body weight in each group were recorded; the morphology of synovial and ankle tissues was observed by hematoxylin-eosin staining, and the level of serum TNF-α and IL-1ß was tested by ELISA. UPLC/MS-MS and network pharmacological analysis were used to identify the serum components, and 16S rDNA sequencing analysis was applied to the intestinal contents of rats. Results: DZGP treatment significantly alleviated arthritis symptoms, pathological manifestations, toe thickness, and TNF-α and IL-1ß levels in RA rats. We identified 105 metabolites and 18 components in the serum of DZGP-group rats. The main therapeutic targets of DZGP for anti-RA were TP53, epidermal growth factor receptor, and AKT1. Molecular docking showed that there was good binding efficiency between core components and main targets. 16S rDNA sequencing showed that DZGP treatment regulated the structure of the gut microbiota. Conclusion: DZGP showed a good anti-inflammatory effect on RA and played an important role in improving the structure of the gut microbiota in RA rats.

CBGDA: a manually curated resource for gene-disease associations based on genome-wide CRISPR.

The field of understanding the association between genes and diseases is rapidly expanding, making it challenging for researchers to keep up with the influx of new publications and genetic datasets. Fortunately, there are now several regularly updated databases available that focus on cataloging gene-disease relationships. The development of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system has revolutionized the field of gene editing, providing a highly efficient, accurate, and reliable method for exploring gene-disease associations. However, currently, there is no resource specifically dedicated to collecting and integrating the latest experimentally supported gene-disease association data derived from genome-wide CRISPR screening. To address this gap, we have developed the CRISPR-Based Gene-Disease Associations (CBGDA) database, which includes over 200 manually curated gene-disease association data derived from genome-wide CRISPR screening studies. Through CBGDA, users can explore gene-disease association data derived from genome-wide CRISPR screening, gaining insights into the expression patterns of genes in different diseases, associated chemical data, and variant information. This provides a novel perspective on understanding the associations between genes and diseases. What is more, CBGDA integrates data from several other databases and resources, enhancing its comprehensiveness and utility. In summary, CBGDA offers a fresh perspective and comprehensive insights into the research on gene-disease associations. It fills the gap by providing a dedicated resource for accessing up-to-date, experimentally supported gene-disease association data derived from genome-wide CRISPR screening. Database URL: http://cbgda.zhounan.org/main.

Construction of Near-Infrared Probes with Remarkable Large Stokes Shift Based on a Novel Purine Platform for the Visualization of mtG4 Upregulation during Mitochondrial Disorder in Somatic Cells and Human Sperms.

G-quadruplex structures within the nuclear genome (nG4) is an important regulatory factor, while the function of G4 in the mitochondrial genome (mtG4) still needs to be explored, especially in human sperms. To gain a better understanding of the relationship between mtG4 and mitochondrial function, it is crucial to develop excellent probes that can selectively visualize and track mtG4 in both somatic cells and sperms. Herein, based on our previous research on purine frameworks, we attempted for the first time to extend the conjugated structure from the C-8 site of purine skeleton and discovered that the purine derivative modified by the C-8 aldehyde group is an ideal platform for constructing near-infrared probes with extremely large Stokes shift (>220 nm). Compared with the compound substituted with methylpyridine (PAP), the molecule substituted with methylthiazole orange (PATO) showed better G4 recognition ability, including longer emission (∼720 nm), more significant fluorescent enhancement (∼67-fold), lower background, and excellent photostability. PATO exhibited a sensitive response to mtG4 variation in both somatic cells and human sperms. Most importantly, PATO helped us to discover that mtG4 was significantly increased in cells with mitochondrial respiratory chain damage caused by complex I inhibitors (6-OHDA and rotenone), as well as in human sperms that suffer from oxidative stress. Altogether, our study not only provides a novel ideal molecular platform for constructing high-performance probes but also develops an effective tool for studying the relationship between mtG4 and mitochondrial function in both somatic cells and human sperms.

Chinese traditional medicine DZGP beneficially affects gut microbiome, serum metabolites and recovery from rheumatoid arthritis through mediating NF-κB signaling pathway.

Rheumatoid arthritis (RA) is globally treated with several commercially available anti-inflammatory and analgesic drugs, which pose adverse side effects in many cases. Due to increasing population affected by autoimmune disorder of joints inflammation, it is crucial to use natural therapies, which are less toxic at metabolic level and promote gut health. In this study, we investigated the potential role of a locally developed traditional Chinese medicine (TCM), namely Duzheng tablet (DZGP) in controlling the RA. For this purpose, we introduced RA in male mice and divided them into 5 different groups. High throughput transcriptome analysis of synovial cells after DZGP treatment in arthritic mice revealed a significant alteration of gene expression. The correlation analysis of transcriptome with metabolites revealed that DZGP specifically targeted the B cells mediated immunity pathways. Treatment with DZGP inhibited the cytokines production, while reducing the production of inflammatory TNF-α, which led to the alleviation of inflammatory response in arthritic mice. Additionally, we applied integrated approach using 16S rDNA sequencing to understand the microbial population in relation to metabolites accumulation. The results showed that DZGP promoted the healthy gut microbiota by maintaining the ratio of Firmicutes and Bacteroidota and introduction of two additional phyla namely, Verrucomicrobiota and Cyanobacteria. Therefore, it is concluded that DZGP offers an advantage over commercial drug by changing the metabolic profile, gut microbiota while exhibiting lower cellular toxicity.

Identification of SLC7A11-AS1/SLC7A11 pair as a ferroptosis-related therapeutic target for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), a prevalent malignancy worldwide, poses significant challenges in terms of prognosis, necessitating innovative therapeutic approaches. Ferroptosis offers notable advantages over apoptosis, holding promise as a novel therapeutic approach for HCC complexities. Moreover, while the interaction between long non-coding RNAs (lncRNAs) and mRNAs is pivotal in various physiological and pathological processes, their involvement in ferroptosis remains relatively unexplored. In this study, we constructed a ferroptosis-related lncRNA-mRNA correlation network in HCC using Pearson correlation analysis. Notably, the SLC7A11-AS1/SLC7A11 pair, exhibiting high correlation, was identified. Bioinformatics analysis revealed a significant correlation between the expression levels of this pair and key clinical characteristics of HCC patients, including gender, pathology, Ishak scores and tumour size. And poor prognosis was associated with high expression of this pair. Functional experiments demonstrated that SLC7A11-AS1, by binding to the 3'UTR region of SLC7A11 mRNA, enhanced its stability, thereby promoting HCC cell growth and resistance to erastin- induced ferroptosis. Additionally, in vivo studies confirmed that SLC7A11-AS1 knockdown potentiated the inhibitory effects of erastin on tumour growth. Overall, our findings suggest that targeting the SLC7A11-AS1/SLC7A11 pair holds promise as a potential therapeutic strategy for HCC patients.

O-GlcNAcylation regulates the stability of transferrin receptor (TFRC) to control the ferroptosis in hepatocellular carcinoma cells.

Ferroptosis is an iron-dependent programmed cell death (PCD) enforced by lipid peroxidation accumulation. Transferrin receptor (TFRC), one of the signature proteins of ferroptosis, is abundantly expressed in hepatocellular carcinoma (HCC). However, post-translational modification (PTM) of TFRC and the underlying mechanisms for ferroptosis regulation remain less understood. In this study, we found that TFRC undergoes O-GlcNAcylation, influencing Erastin-induced ferroptosis sensitivity in hepatocytes. Further mechanistic studies found that Erastin can trigger de-O-GlcNAcylation of TFRC at serine 687 (Ser687), which diminishes the binding of ubiquitin E3 ligase membrane-associated RING-CH8 (MARCH8) and decreases polyubiquitination on lysine 665 (Lys665), thereby enhancing TFRC stability that favors labile iron accumulation. Therefore, our findings report O-GlcNAcylation on an important regulatory protein of ferroptosis and reveal an intriguing mechanism by which HCC ferroptosis is controlled by an iron metabolism pathway.

Identification of glycogene-based prognostic signature and validation of B3GNT7 as a potential biomarker and therapeutic target in breast cancer.

BACKGROUND: Breast cancer is the most common cancer worldwide, with the fifth highest mortality rate among all cancers and high risk of metastasis. However, potential biomarkers and molecular mechanisms underlying the stratification of breast cancer in terms of clinical outcomes remain to be investigated. Therefore, we aimed to find a novel prognostic biomarker and therapeutic target for breast cancer patients. METHODS: Unsupervised hierarchical clustering was used to perform comprehensive transcriptomic study of total 185 glycogenes in public datasets of breast cancer with clinicopathological and survival information. A glycogene-based signature for subtype classification was discovered using Limma packages, and relevance to four known molecular features was identified by GSVA. Experimental verification was performed and biological functions of B3GNT7 were characterized by quantitative RT-PCR, western blot, transwell assays, and lectin immunofluorescence staining in breast cancer cells. RESULTS: A 23-glycogene signature was identified for the classification of breast cancer. Among the 23 glycogenes, B3GNTs showed significantly positive associations with ER-/Her2- subtype in breast cancer patients (n = 2655). Overexpressed B3GNT7 were correlated with poor prognosis in breast cancer patients based on public datasets. B3GNT7 depletion inhibited cell proliferation, migration, and invasion, and decreased global fucosylation in MDA-MB-231 and HCC1937 breast cancer cells. CONCLUSIONS: Herein, we discovered a unique 23-gene signature for breast cancer patient glycogene-type classification. Among these genes, B3GNT7 was shown to be a potential biomarker for unfavorable outcomes and therapeutic target of breast cancer.

G-Quadruplex Structures as a "Switch" Regulate ATF4 Expression in Ferroptotic HepG2 Cells.

G-quadruplex (G4) is a noncanonical structure folded in a widespread manner by guanine-rich tandem repeated sequences. As a key response factor, activating transcription factor 4 (ATF4) has dual functions in managing iron-dependent ferroptosis by regulating amino acid synthesis and antioxidant-related gene expression. In our study, the activity of ATF4 expression was elevated in HepG2 cells induced by erastin. Based on preliminary bioinformatics analyses, the G-tract region, named WT, had high potential to form G4, and it was found that PDS could markedly weaken the increase of ATF4 expression by reducing the sensitivity of HepG2 cells toward erastin. In circular dichroism spectra, WT oligonucleotides showed characteristic molar ellipticity at specific wavelengths of parallel G4 structures, while corresponding single-base mutants possessed a weaker ability to form G4, which were consistent with immunostaining results. In addition, endogenous G4 formed by the WT motif was significantly destroyed in HepG2 cells treated with erastin. After being transfected with WT oligonucleotides, the levels of ATF4 mRNA decreased significantly regardless of being treated with erastin or not. Meanwhile, mutations of G-tracts could advantageously impact the luciferase expression downstream of an ATF4 promoter in reporter assays, manifesting that the decrease of endogenous G4 in the ATF4 promoter was positively associated with the expression enhanced by erastin in HepG2 cells.

Moderate Hyperglycemia-Preventive Effect and Mechanism of Action of Periplaneta americana Oligosaccharides in Streptozotocin-Induced Diabetic Mice.

Periplaneta americana is a kind of medicinal and edible insect, and its oligosaccharides (PAOS) have been reported to exert anti-inflammatory effects by regulating immunity, reducing oxidative stress, and meliorating gut microbiota. We hypothesized PAOS might benefit experimental diabetes mellitus (DM), an inflammatory disease coordinated by both innate and adaptive immunity. This study aimed to evaluate the effect of PAOS on glycemia and its potential mechanisms. Mice model of diabetes was established, and then the potential effects of PAOS was tested in vivo. Here, we found that PAOS triggered a moderate hyperglycemia-preventive effect on DM mice, showing markedly alleviated symptoms of DM, reduced blood glucose, and meliorated functions of liver and pancreas ß cell. Deciphering the underlying mechanism of PAOS-improving diabetes, the results revealed that PAOS downregulated the blood glucose level by activating PI3K/AKT/mTOR and Keap/Nrf2/HO-1 pathways, meanwhile inhibiting TLR4/MAPK/NF-κB, Beclin1/LC3, and NLRP3/caspase1 pathways in vivo. Furthermore, analyses of the microbial community intriguingly exhibited that PAOS promoted the communities of bacteria producing short-chain fatty acids (SCFAs), whereas attenuating lipopolysaccharides (LPS)-producing ones that favored inflammatory tolerance. Collectively, balancing the intestinal bacterial communities by PAOS, which favored anabolism but suppressed inflammatory responses, contributed substantially to the glycemia improvement of PAOS in DM mice. Accordingly, PAOS might function as complementary and alternative medicine for DM.

Neuroprotective Effects of Oligosaccharides From Periplaneta Americana on Parkinson's Disease Models In Vitro and In Vivo.

Parkinson's disease (PD) is one of the neurodegenerative diseases that is characterized by obvious motor and some nonmotor symptoms. Various therapeutics failed in the effective treatment of PD because of impaired neurological function in the brain and various complications. Periplaneta Americana oligosaccharides (OPA), the main active ingredients extracted from the medicine residues of Periplaneta Americana (P. Americana), have been reported to exert anti-inflammatory effects. The purpose of this study was to evaluate the possible mechanisms of OPA against 1-methyl-4-phenylpyridinium (MPP+)-induced apotosis in SH-SY5Y cells and its potential neuroprotective effects in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD subacute model mice. The data demonstrated that OPA significantly reversed the MPP+-induced decrease in SH-SY5Y cell viability, reduced the proportion of apoptotic cells, and protected SH-SY5Y cells from apoptosis in a dose-dependent manner by regulating the expression of apoptosis-related genes. Furthermore, OPA also alleviated the motor dysfunction of PD model mice, prevented the loss of tyrosine hydroxylase positive cells, suppressed the apoptosis of substantia nigra cells, and improved the dysbiosis of gut microbiota in vivo, suggesting that OPA demonstrated a significantly neuroprotective effect on PD model mice. These results indicated that OPA might be the possibility of PD therapeutics with economic utility and high safety.

Research Progress of Ferroptosis: A Bibliometrics and Visual Analysis Study.

Background: Ferroptosis is a type of cell death with major topic of debate under current research and plays an important role in disease regulation. Objective: In this study, the literature management software Bibexcel and knowledge graph tool VOSviewer were used to summarize and analyze the international research trends and hotspots about ferroptosis in recent years, which highlight the disease mechanism, diagnosis, and treatment related to ferroptosis. Material/Methods. The core collection database of Web of Science was used for retrieving ferroptosis research literature. The information such as the amount of text, the country, the period, the institution, the fund, and the keywords was extracted by the bibliometric tool Bibexcel. The cooccurrence and clustering function of VOSviewer were used to analyze the high-frequency keywords and the cooperative network of the author, institution, and country. Results: The research of ferroptosis started late and was formally proposed in 2012. It has developed rapidly and presented an "exponential" growth trend. China, the United States, Germany, Japan, and France are the main national forces of ferroptosis research development. The United States and China have a relatively high degree of support and attention to ferroptosis. Exploring oxidative stress, inducers/inhibitors, synergistic antitumor effect, relationships with other cell death types, GSH/GPX4 and iron metabolism imbalance related mechanisms of ferroptosis, and ferroptosis in the nervous system disease, ischemia-reperfusion injury, tumor, inflammation, and age-related diseases are the hot research directions. Conclusion: Ferroptosis has been a research hotspot in the field of biomedicine in recent years and has attracted the attention of scholars all over the world. The occurrence mechanism of ferroptosis and its application in neurological diseases, ischemia and reperfusion injury, tumors, inflammation, and aging are the hot directions of current research. In the future, ferroptosis can be appropriately considered for strengthening new approaches, new diseases, new inductors, new inhibitors, clinical transformation, and traditional medicine research.

Periplaneta americana Oligosaccharides Exert Anti-Inflammatory Activity through Immunoregulation and Modulation of Gut Microbiota in Acute Colitis Mice Model.

The incidence and prevalence of inflammatory bowel disorders (IBD) are increasing around the world due to bacterial infection, abnormal immune response, etc. The conventional medicines for IBD treatment possess serious side effects. Periplaneta americana (P. americana), a traditional Chinese medicine, has been used to treat arthritis, fever, aches, inflammation, and other diseases. This study aimed to evaluate the anti-inflammatory effects of oligosaccharides from P. Americana (OPA) and its possible mechanisms in vivo. OPA were purified and biochemical characterization was analyzed by HPGPC, HPLC, FT-IR, and GC-MS. Acute colitis mice model was established, the acute toxicity and anti-inflammatory activity were tested in vivo. The results showed OPA with molecular mass of 1.0 kDa were composed of 83% glucose, 6% galactose, 11% xylose, and the backbone was (1→4)-Glcp. OPA had potent antioxidant activities in vitro and significantly alleviated the clinical symptoms of colitis, relieved colon damage without toxic side effects in vivo. OPA exhibited anti-inflammatory activity by regulating Th1/Th2, reducing oxidative stress, preserving intestinal barrier integrity, and inhibiting TLR4/MAPK/NF-κB pathway. Moreover, OPA protected gut by increasing microbial diversity and beneficial bacteria, and reducing pathogenic bacteria in feces. OPA might be the candidate of complementary and alternative medicines of IBD with low-cost and high safety.

Erratum: Ceramide synthase-4 orchestrates the cell proliferation and tumor growth of liver cancer in vitro and in vivo through the nuclear factor-κB signaling pathway.

[This corrects the article DOI: 10.3892/ol.2017.6365.].

Identifying selective agonists targeting LXRß from terpene compounds of alismatis rhizoma.

Hyperlipidemia is thought of as an important contributor to coronary disease, diabetes, and fatty liver. Liver X receptor ß (LXRß) was considered as a validated target for hyperlipidemia therapy due to its role in regulating cholesterol homeostasis and immunity. However, many current drugs applied in clinics are not selectively targeting LXRß, and they can also activate LXRα which activates SREBP-1c that worked as an activator of lipogenic genes. Therefore, exploiting agonists selectively targeting LXRß is urgent. Here, computational tools were used to screen potential agonists selectively targeting LXRß from 112 terpenes of alismatis rhizoma. Firstly, a structural analysis between selective and nonselective agonists was used to explore key residues of selective binding with LXRß. Our data indicated that Phe271, Ser278, Met312, His435, and Trp457 were important to compounds binding with LXRß, suggesting that engaging ligand interaction with these residues may provide directions for the development of ligands with improved selective profiles. Then, ADMET analysis, molecular docking, MD simulations, and calculation of binding free energy and its decomposition were executed to screen the agonists whose bioactivity was favorable from 112 terpenes of alismatis rhizoma. We found that two triterpenes 16-hydroxy-alisol B 23-acetate and alisol M 23-acetate showed favorable ADMET properties and high binding affinity against LXRß. These compounds could be considered as promising selective agonists targeting LXRß. Our work provides an alternative strategy for screening agonists selectively targeting LXRß from alismatis rhizoma for hyperlipidemia disease treatment.

Identification of Potential Inhibitors Against the TGF-ß/BMPs-Activin Receptor- like Kinase 1 Signal Pathway.

INTRODUCTION: In many diseased states, especially fibrosis and cancer, TGF-ß family members are overexpressed and the outcome of signaling is diverted toward disease progression. As the result of activin receptor-like kinase 1 (ALK1) plays a key role in TGF-ß signaling, discovering inhibitors of ALK1 to block TGF-ß signaling for a therapeutic benefit has become an effective strategy. METHODS: In this work, ZINC15894217 and ZINC12404282 were identified as potential ALK1 inhibitors using molecular docking, molecular dynamics simulation and MM/PBSA calculations studies. The analysis of energy decomposition found that Val208, Val216, Lys229, Gly283, Arg334 and Leu337 acted as crucial residues for ligand binding and system stabilizing. RESULTS: In addition, these compounds displayed excellent pharmacological and structural properties, which can be further evaluated through in vitro and in vivo experiments for the inhibition of ALK1 to be developed as drugs against fibrosis and tumor. CONCLUSION: Overall, our study illustrated a time- and cost-effective computer aided drug design procedure to identify potential ALK1 inhibitors. It would provide useful information for further development of ALK1 inhibitors to improve disease related to TGF-ß signal pathway.

A novel mannose-binding lectin from Liparis nervosa with anti-fungal and anti-tumor activities.

Plant lectins are carbohydrate-binding proteins with nonimmune origin, which can reversibly bind with carbohydrates, agglutinate cells, and precipitate polysaccharides and glycoconjugates. Plant lectins have attracted much attention for their anti-virus, anti-proliferation, and pro-apoptosis properties. Thus the exploration of new lectins has received special attention. Here we purified a mannose-binding lectin from the rhizomes of Liparis nervosa by ion exchange chromatography on DEAE-Sepharose, affinity chromatography on Mannose-Sepharose 4B, and gel filtration chromatography on Sephacryl S-100. The purified L. nervosa lectin (LNL) was identified to be a monomeric protein with a molecular mass of 13 kDa. LNL exhibited hemagglutinating activity towards rabbit erythrocytes, and its activity could be strongly inhibited by D-mannose, N-acetyl glucosamine and thyroglobulin. In vitro experiments showed that LNL exhibited a comparable anti-fungal activity against Piricularia oryzae (Cavara), Bipolaris maydis, Fusarium graminearum, and Sclerotium rolfsii, and anti-proliferation activity against tumor cells by inducing apoptosis. The full-length cDNA sequence of LNL is 715 bp in length and contains a 525 bp open reading frame (ORF) encoding a 110-residue mature protein. It was predicted to have three mannose-binding conserved motifs 'QXDXNXVXY'. The binding pattern of LNL was further revealed by homology modeling and molecular docking. We demonstrated that LNL is not only a potential therapeutic candidate against tumor but also a new anti-fungal agent.

The Prospects of Therapeutic Potential and Drug Development Targeting Autophagy in Cancer.

Autophagy is a self-protection mechanism of cells. Cells can degrade damaged organelles and macromolecules in this way to guarantee the growth and development of cells. In recent years, more and more researches have found that autophagy also plays a certain role in the occurrence and development of tumors. The dual role of autophagy in the development of tumors includes inhibiting the development of tumors; meanwhile, under the condition of insufficient nutrition, autophagy degrades organelles to reduce oxidative stress and provide nutrition and energy for tumor cells so as to protect tumor cells. The regulation of autophagy depends on the development of the tumor, and the corresponding autophagy inducers or inhibitors are constantly emerging, which provides a new direction for tumor treatment.

Progress of Anti-aging Drugs Targeting Autophagy.

Senescence is a progressive process of degeneration that occurs when cells and organisms mature. Many studies have shown that autophagy is closely related to senescence. Autophagy gradually decreases with the senescence activity of cells, and vice versa. Therefore, moderate autophagy can protect the body and inhibit cell senescence. The inactivation of genes encoding nematode insulin-like tyrosine kinase receptor (daf-2) inhibited the activity of type I PI3K (age-1), Akt molecules (akt1, akt2), PDK (pdk-1), and TOR, and increased the lifespan and autophagy of Caenorhabditis elegans.

Drug Development and Treatment of Autophagy in Other Diseases.

In addition to tumors and aging that are associated with autophagy, many other diseases are also regulated by autophagy, including liver disease, myopathy, immune pathogen infection, cardiovascular disease, and so on. This chapter will detail the relationship between autophagy and these diseases and their underlying molecular mechanisms. We summarized the current research status of autophagy as a target for the treatment of related diseases, and prospected the development of related drugs and therapeutic strategies. We hope to provide new ideas for finding new therapeutic targets through the autophagic signaling pathways.