FKBP3 aggravates the malignant phenotype of diffuse large B-cell lymphoma by PARK7-mediated activation of Wnt/ß-catenin signalling.

Diffuse large B-cell lymphoma (DLBCL) is difficult to treat due to the high recurrence rate and therapy intolerance, so finding potential therapeutic targets for DLBCL is critical. FK506-binding protein 3 (FKBP3) contributes to the progression of various cancers and is highly expressed in DLBCL, but the role of FKBP3 in DLBCL and its mechanism are not clear. Our study demonstrated that FKBP3 aggravated the proliferation and stemness of DLBCL cells, and tumour growth in a xenograft mouse model. The interaction between FKBP3 and parkinsonism associated deglycase (PARK7) in DB cells was found using co-immunoprecipitation assay. Knockdown of FKBP3 enhanced the degradation of PARK7 through increasing its ubiquitination modification. Forkhead Box O3 (FOXO3) belongs to the forkhead family of transcription factors and inhibits DLBCL, but the underlying mechanism has not been reported. We found that FOXO3 bound the promoter of FKBP3 and then suppressed its transcription, eventually weakening DLBCL. Mechanically, FKBP3 activated Wnt/ß-catenin signalling pathway mediated by PARK7. Together, FKBP3 increased PARK7 and then facilitated the malignant phenotype of DLBCL through activating Wnt/ß-catenin pathway. These results indicated that FKBP3 might be a potential therapeutic target for the treatment of DLBCL.

Sorbremnoids A and B: NLRP3 Inflammasome Inhibitors Discovered from Spatially Restricted Crosstalk of Biosynthetic Pathways.

Crosstalk-oriented chemical evolution of natural products (NPs) is an efficacious strategy for generating novel skeletons through coupling reactions between NP fragments. In this study, two NOD-like receptor protein 3 (NLRP3) inflammasome inhibitors, sorbremnoids A and B (1 and 2), with unprecedented chemical architectures were identified from a fungus Penicillium citrinum. Compounds 1 and 2 exemplify rare instances of hybrid NPs formed via a major facilitator superfamily (MFS)-like enzyme by coupling reactive intermediates from two separate biosynthetic gene clusters (BGCs), pcisor and pci56. Both sorbremnoids A and B are NLRP3 inflammasome inhibitors. Sorbremnoid A demonstrated strong inhibition of IL-1ß by directly binding to the NLRP3 protein, inhibiting the assembly and activation of the NLRP3 inflammasome in vitro, with potential application in diabetic refractory wound healing through the suppression of excessive inflammatory responses. This research will inspire the development of anti-NLRP3 inflammasome agents as lead treatments and enhance knowledge pertaining to NPs derived from biosynthetic crosstalk.

Evolution-Based Discovery of Polyketide Acylated Valine from a Cytochalasin-Like Gene Cluster in Simplicillium lamelliciola HDN13430.

Utilizing a gene evolution-oriented approach for gene cluster mining, a cryptic cytochalasin-like gene cluster (sla) in Antarctic-derived Simplicillium lamelliciola HDN13430 was identified. Compared with the canonical cytochalasin biosynthetic gene clusters (BGCs), the sla gene cluster lacks the key α,ß-hydrolase gene. Heterologous expression of the sla gene cluster led to the discovery of a new compound, slamysin (1), characterized by an N-acylated amino acid structure and demonstrating weak anti-Bacillus cereus activity. These findings underscore the potential of genetic evolution in uncovering novel compounds and indicating specific adaptive evolution within specialized habitats.

Phenylhydrazone Alkaloids from the Deep-Sea Cold Seep Derived Fungus Talaromyces amestolkiae HDN21-0307.

Alkaloids with a phenylhydrazone architecture are rarely found in nature. Four unusual phenylhydrazone alkaloids named talarohydrazones A-D (1-4) were isolated from the deep-sea cold seep derived fungus Talaromyces amestolkiae HDN21-0307 using the one strain-many compounds (OSMAC) approach and MS/MS-based molecular networking (MN) combined with network annotation propagation (NAP) and the unsupervised substructure annotation method MS2LDA. Their structures were elucidated by spectroscopic data analysis, single-crystal X-ray diffraction, and quantum chemical calculations. Talarohydrazone A (1) possessed an unusual skeleton combining 2,4-pyridinedione and phenylhydrazone. Talarohydrazone B (2) represents the first natural phenylhydrazone-bearing azadophilone. Bioactivity evaluation revealed that compound 1 exhibited cytotoxic activity against NCI-H446 cells with an IC50 value of 4.1 µM. In addition, compound 1 displayed weak antibacterial activity toward Staphylococcus aureus with an MIC value of 32 µg/mL.

Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome.

Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.

Robotic dental implant placement workflow for edentulous jaws.

Yakebot, the first autonomous robotic dental implant system, provides a 1-stop solution for implant design, robot operation, real-time navigation, and precision analysis. This report describes the composition, principles, and implant operation procedures of the Yakebot dental implant robotic system in a patient for whom the robotic workflow procedure was used to place implants in the edentulous maxilla. The results showed that this workflow was more precise and predictable than traditional methods.

Discovery, Total Synthesis, and Anti-inflammatory Evaluation of Naturally Occurring Naphthopyrone-Macrolide Hybrids as Potent NLRP3 Inflammasome Inhibitors.

Numerous clinical disorders have been linked to the etiology of dysregulated NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome activation. Despite its potential as a pharmacological target, modulation of NLRP3 activity remains challenging. Only a sparse number of compounds have been reported that can modulate NLRP3 and none of them have been developed into a commercially available drug. In this research, we identified three potent NLRP3 inflammasome inhibitors, gymnoasins A-C (1-3), with unprecedented pentacyclic scaffolds, from an Antarctic fungus Pseudogymnoascus sp. HDN17-895, which represent the first naturally occurring naphthopyrone-macrolide hybrids. Additionally, biomimetic synthesis of gymnoasin A (1) was also achieved validating the chemical structure and affording ample amounts of material for exhaustive bioactivity assessments. Biological assays indicated that 1 could significantly inhibited in vitro NLRP3 inflammasome activation and in vivo pro-inflammatory cytokine IL-1ß release, representing a valuable new lead compound for the development of novel therapeutics with the potential to inhibit the NLRP3 inflammasome.

Correlation analysis of lung mucosa-colonizing bacteria with clinical features reveals metastasis-associated bacterial community structure in non-small cell lung cancer patients.

BACKGROUND: Microbes colonizing lower airways can regulate the host immune profile and consequently participate in lung disease. Increasing evidence indicate that individual microbes promote lung cancer progression and are involved in metastasis incidence. To date, however, no study has revealed the community structure of lung bacteria in metastatic non-small cell lung cancer (NSCLC) patients. METHODS: We prospectively enrolled 50 healthy subjects and 57 NSCLC patients. All healthy subjects and NSCLC patients underwent bronchoscope procedures for brush specimen collection. The 16 S ribosomal RNA gene was sequenced to characterize the community structure of lung mucosa-colonizing bacteria. The peripheral blood of NSCLC patients was also measured for leukocytes and cancer markers. RESULTS: The lung bacteria of healthy subjects and NSCLC patients were divided into four communities. All community 2 members showed increased abundance in NSCLC patients compared with healthy subjects, and most community 2 members showed increased abundance in the metastatic NSCLC patients compared with the non-metastatic group. These bacteria were significantly and positively correlated with eosinophils, neutrophils and monocytes in the metastatic NSCLC group. In addition, the correlation between lung bacteria and cancer markers differed between the metastatic and non-metastatic NSCLC patients. Furthermore, bronchoalveolar lavage fluid from lung adenocarcinoma patients directly promoted NSCLC cell migration. CONCLUSIONS: The community structure of lung mucosa-colonizing bacteria was relatively stable, but changed from the healthy population to NSCLC patients, especially the metastatic group. This distinct community structure and specific correlation with immune cells and cancer markers could help to distinguish NSCLC patients with or without metastasis.

Effect of Polylactic Acid Membrane on Guided Bone Regeneration in Anterior Maxillary Implantation.

BACKGROUND This study evaluated the clinical efficacy of polylactic acid (PLA) membranes in guiding bone regeneration in anterior maxillary implants. MATERIAL AND METHODS Forty-eight participants with maxillary anterior tooth loss requiring implantation with guided bone regeneration were recruited and randomly divided into 2 groups (n=24): the PLA membrane (experimental) and the Bio-Gide membrane (control) group. Wound healing was observed at 1 week and 1 month postoperatively. Cone beam CT was performed immediately and at 6 and 36 months postoperatively. Soft-tissue parameters were measured at 18 and 36 months postoperatively. Implant stability quotient (ISQ) and patient satisfaction were separately evaluated at 6 and 18 months after the operation. The independent sample t test and chi-square test were preformed to analyze quantitative and descriptive statistics, respectively. RESULTS No implants were lost and there were no statistically significant differences in ISQ between the 2 groups. The labial bone plates in the experimental group exhibited a non-significantly greater extent of absorption than did the control group at 6 and 18 months postoperatively. Soft-tissue parameters did not reveal inferior results for the experimental group. Patients in both groups were satisfied. CONCLUSIONS PLA membranes are comparable to Bio-Gide in terms of the effectiveness and safety and can be used as a barrier membrane to guide bone regeneration in clinical practice.

Autogenous solid dentin for horizontal ridge augmentation with simultaneous implantation in a severe bone defect: A 3.5-year follow-up clinical report.

Autogenous dental root placement is an available approach for horizontal alveolar ridge augmentation in patients with severe bony defects. However, in previous reports, bone augmentation has been done before the implant placement. This clinical report describes the use of dentin grafting for alveolar ridge augmentation and simultaneous implant placement in the maxillary left central incisor region with a severe horizontal bone defect. Under strict adherence to the recommended indications, dentin grafting and simultaneous implantation could be clinically feasible protocols.

[Correlations between appearance traits and internal quality of Bupleurum scorzonerifolium roots based on theory of "quality evaluation through morphological identification"].

It is generally believed that high-quality Bupleurum scorzonerifolium roots possess specific morphological characteristics, being red, robust, and long with strong odor. However, the scientific connotation of these characteristics has not been elucidated. According to the theory of "quality evaluation through morphological identification", we studied the correlations between appearance traits(the RGB value of root surface, root length, root diameter, dry weight, and ratio of phloem to xylem) and content of main chemical components(volatile oils, total saponins, total flavonoids, total polysaccharides, and seven saikosaponins) of B. scorzonerifolium roots. Epson Scanner and ImageJ were used to scan the root samples and measure the appearance traits. Ultraviolet spectrophotometry and HPLC were employed to determine the content of chemical components. The correlation, regression, and cluster analyses were performed to study the correlations between the appearance traits and the content of chemical components. The results showed that the content of volatile oils and saikosaponins were significantly correlated with RGB value, root length, and root diameter, indicating that within a certain range, the roots being redder, longer, and thicker had higher content of volatile oils and saikosaponins. According to the appearance traits and chemical component content, the 14 samples from different producing areas were classified into four grades, and the differences in morphological traits and chemical component content were consistent among different grades. The findings in this study demonstrate that appearance traits(RGB value, root length, and root diameter) can be used to evaluate the quality of B. scorzonerifolium roots. Meanwhile, this study lays a foundation for establishing an objective quality evaluation method for B. scorzonerifolium roots.

Brasilterpenes A-E, Bergamotane Sesquiterpenoid Derivatives with Hypoglycemic Activity from the Deep Sea-Derived Fungus Paraconiothyrium brasiliense HDN15-135.

Five bergamotane sesquiterpenoid derivatives, brasilterpenes A-E (1-5), bearing an unreported spiral 6/4/5 tricyclic ring system, were isolated from the deep sea-derived ascomycete fungus Paraconiothyrium brasiliense HDN15-135. Their structures, including absolute configurations, were established by extensive spectroscopic methods complemented by single-crystal X-ray diffraction analyses, electronic circular dichroism (ECD), and density-functional theory (DFT) calculations of nuclear magnetic resonance (NMR) data including DP4+ analysis. The hypoglycemic activity of these compounds was assessed using a diabetic zebrafish model. Brasilterpenes A (1) and C (3) significantly reduced free blood glucose in hyperglycemic zebrafish in vivo by improving insulin sensitivity and suppressing gluconeogenesis. Moreover, the hypoglycemic activity of compound 3 was comparable to the positive control, anti-diabetes drug rosiglitazone. These results suggested brasilterpene C (3) had promising anti-diabetes potential.

Concentration optimization of combinatorial drugs using Markov chain-based models.

BACKGROUND: Combinatorial drug therapy for complex diseases, such as HSV infection and cancers, has a more significant efficacy than single-drug treatment. However, one key challenge is how to effectively and efficiently determine the optimal concentrations of combinatorial drugs because the number of drug combinations increases exponentially with the types of drugs. RESULTS: In this study, a searching method based on Markov chain is presented to optimize the combinatorial drug concentrations. In this method, the searching process of the optimal drug concentrations is converted into a Markov chain process with state variables representing all possible combinations of discretized drug concentrations. The transition probability matrix is updated by comparing the drug responses of the adjacent states in the network of the Markov chain and the drug concentration optimization is turned to seek the state with maximum value in the stationary distribution vector. Its performance is compared with five stochastic optimization algorithms as benchmark methods by simulation and biological experiments. Both simulation results and experimental data demonstrate that the Markov chain-based approach is more reliable and efficient in seeking global optimum than the benchmark algorithms. Furthermore, the Markov chain-based approach allows parallel implementation of all drug testing experiments, and largely reduces the times in the biological experiments. CONCLUSION: This article provides a versatile method for combinatorial drug screening, which is of great significance for clinical drug combination therapy.

Molecular Mapping of Quantitative Trait Loci for Fusarium Head Blight Resistance in a Doubled Haploid Population of Chinese Bread Wheat.

Fusarium head blight (FHB) is a destructive disease of wheat worldwide, particularly in China. To map genetic loci underlying FHB resistance, a doubled haploid (DH) population consisting of 174 lines was developed from a cross between widely grown Chinese cultivars Yangmai 16 and Zhongmai 895. The DH population and parents were evaluated in field nurseries at Wuhan in 2016 to 2017 and 2017 to 2018 crop seasons with both spray inoculation and natural infection, and at Jingzhou in 2017 to 2018 crop season with grain-spawn inoculation. The DH lines were genotyped with a wheat 660K SNP array. The FHB index, plant height, anther extrusion, and days to anthesis were recorded and used for quantitative trait loci (QTL) analysis. Seven QTL for FHB resistance were mapped to chromosome arms 3BL, 4AS, 4BS, 4DS, 5AL, 6AL, and 6BS in at least two environments. QFhb.caas-4BS and QFhb.caas-4DS co-located with semi-dwarfing alleles Rht-B1b and Rht-D1b, respectively, and were associated with anther extrusion. The other five QTL were genetically independent of the agronomic traits, indicating their potential value when breeding for FHB resistance. Based on correlations between FHB indices and agronomic traits in this population, we concluded that increasing plant height to some extent would enhance FHB resistance, that anther extrusion had a more important role in environments with less severe FHB, and that days to anthesis were independent of the FHB response when viewed across years. PCR-based markers were developed for the 3BL and 5AL QTL, which were detected in more than three environments. The InDel marker InDel_AX-89588684 for QFhb.caas-5AL was also validated on a wheat panel, confirming its effectiveness for marker-assisted breeding for improvements in FHB resistance.

Genome-wide association analysis of stripe rust resistance in modern Chinese wheat.

BACKGROUND: Stripe rust (yellow rust) is a significant disease for bread wheat (Triticum aestivum L.) worldwide. A genome-wide association study was conducted on 240 Chinese wheat cultivars and elite lines genotyped with the wheat 90 K single nucleotide polymorphism (SNP) arrays to decipher the genetic architecture of stripe rust resistance in Chinese germplasm. RESULTS: Stripe rust resistance was evaluated at the adult plant stage in Pixian and Xindu in Sichuan province in the 2015-2016 cropping season, and in Wuhan in Hubei province in the 2013-2014, 2016-2017 and 2018-2019 cropping seasons. Twelve stable loci for stripe rust resistance were identified by GWAS using TASSEL and GAPIT software. These loci were distributed on chromosomes 1B, 1D, 2A, 2B, 3A, 3B, 4B (3), 4D, 6D, and 7B and explained 3.6 to 10.3% of the phenotypic variation. Six of the loci corresponded with previously reported genes/QTLs, including Sr2/Yr30/Lr27, while the other six (QYr.hbaas-1BS, QYr.hbaas-2BL, QYr.hbaas-3AL, QYr.hbaas-4BL.3, QYr.hbaas-4DL, and QYr.hbaas-6DS) are probably novel. The results suggest high genetic diversity for stripe rust resistance in this population. The resistance alleles of QYr.hbaas-2AS, QYr.hbaas-3BS, QYr.hbaas-4DL, and QYr.hbaas-7BL were rare in the present panel, indicating their potential use in breeding for stripe rust resistance in China. Eleven penta-primer amplification refractory mutation system (PARMS) markers were developed from SNPs significantly associated with seven mapped QTLs. Twenty-seven genes were predicted for mapped QTLs. Six of them were considered as candidates for their high relative expression levels post-inoculation. CONCLUSION: The resistant germplasm, mapped QTLs, and PARMS markers developed in this study are resources for enhancing stripe rust resistance in wheat breeding.

Acid sphingomyelinase deficiency protects mitochondria and improves function recovery after brain injury.

Traumatic brain injury (TBI) is one of the leading causes of disability worldwide and a prominent risk factor for neurodegenerative diseases. The expansion of nervous tissue damage after the initial trauma involves a multifactorial cascade of events, including excitotoxicity, oxidative stress, inflammation, and deregulation of sphingolipid metabolism that further mitochondrial dysfunction and secondary brain damage. Here, we show that a posttranscriptional activation of an acid sphingomyelinase (ASM), a key enzyme of the sphingolipid recycling pathway, resulted in a selective increase of sphingosine in mitochondria during the first week post-TBI that was accompanied by reduced activity of mitochondrial cytochrome oxidase and activation of the Nod-like receptor protein 3 inflammasome. TBI-induced mitochondrial abnormalities were rescued in the brains of ASM KO mice, which demonstrated improved behavioral deficit recovery compared with WT mice. Furthermore, an elevated autophagy in an ASM-deficient brain at the baseline and during the development of secondary brain injury seems to foster the preservation of mitochondria and brain function after TBI. Of note, ASM deficiency attenuated the early stages of reactive astrogliosis progression in an injured brain. These findings highlight the crucial role of ASM in governing mitochondrial dysfunction and brain-function impairment, emphasizing the importance of sphingolipids in the neuroinflammatory response to TBI.

Comparative evaluation of BioHPP and titanium as a framework veneered with composite resin for implant-supported fixed dental prostheses.

STATEMENT OF PROBLEM: High rates of veneering chipping are a common prosthodontic complication of restorations with a titanium framework. A new bio high-performance polymer (BioHPP) based on polyetheretherketone (PEEK) has been introduced for denture superstructures. Clinical reports suggest that BioHPP could be used as an alternative framework material to support complete-arch restorations. However, peer-reviewed information is lacking regarding the performance of BioHPP as a framework material for implant-supported screw-retained fixed dental prostheses (FDPs) veneered with composite resin. PURPOSE: The purpose of this in vitro study was to evaluate and compare the bond strength of modified PEEK (BioHHP) and titanium with a veneering composite resin and compare the marginal fit and fracture resistance of implant-supported screw-retained FDPs fabricated by using computer-aided design and computer-aided manufacturing (CAD-CAM) frameworks veneered with composite resin. MATERIAL AND METHODS: A composite resin was bonded to 2 framework materials (n=20/group): pure titanium (Ti) and BioHPP (Bi). The shear bond strength (SBS) was determined after 24-hour wet storage. Furthermore, 20 3-unit CAD-CAM BioHPP and titanium frameworks were fabricated (n=10/group). The marginal fit between frameworks and abutments was evaluated by scanning electron microscopy by using the single-screw test. After thermocycling and mastication simulation, the fracture resistance of FDPs veneered with the composite resin was examined. The independent sample t test was used to evaluate differences (α=.05). RESULTS: Significantly higher shear bond strengths were obtained in group Bi (31.1 ±3.5 MPa) than in group Ti (20.5 ±1.8 MPa). The mean marginal gap width was 19 ±4 µm in group Bi and 16 ±6 µm in group Ti. Statistical tests showed no significant differences (P>.05). After loading, veneering chipping was observed at a load of 1960 ±233 N in group Ti. Although the BioHPP frameworks fractured at 1518 ±134 N, no chipping occurred. CONCLUSIONS: The bond strength of BioHPP with the composite resin was greater than that of titanium. CAD-CAM BioHPP frameworks exhibit good marginal fit and fracture resistance. BioHPP may be a suitable alternative to metal as a framework to be veneered with composite resin.

Dynamic Model for Characterizing Contractile Behaviors and Mechanical Properties of a Cardiomyocyte.

Studies on the contractile dynamics of heart cells have attracted broad attention for the development of both heart disease therapies and cardiomyocyte-actuated micro-robotics. In this study, a linear dynamic model of a single cardiomyocyte cell was proposed at the subcellular scale to characterize the contractile behaviors of heart cells, with system parameters representing the mechanical properties of the subcellular components of living cardiomyocytes. The system parameters of the dynamic model were identified with the cellular beating pattern measured by a scanning ion conductance microscope. The experiments were implemented with cardiomyocytes in one control group and two experimental groups with the drugs cytochalasin-D or nocodazole, to identify the system parameters of the model based on scanning ion conductance microscope measurements, measurement of the cellular Young's modulus with atomic force microscopy indentation, measurement of cellular contraction forces using the micro-pillar technique, and immunofluorescence staining and imaging of the cytoskeleton. The proposed mathematical model was both indirectly and qualitatively verified by the variation in cytoskeleton, beating amplitude, and contractility of cardiomyocytes among the control and the experimental groups, as well as directly and quantitatively validated by the simulation and the significant consistency of 90.5% in the comparison between the ratios of the Young's modulus and the equivalent comprehensive cellular elasticities of cells in the experimental groups to those in the control group. Apart from mechanical properties (mass, elasticity, and viscosity) of subcellular structures, other properties of cardiomyocytes have also been studied, such as the properties of the relative action potential pattern and cellular beating frequency. This work has potential implications for research on cytobiology, drug screening, mechanisms of the heart, and cardiomyocyte-based bio-syncretic robotics.

Eight new cucurbitane triterpenoids from "Xue Dan," the roots of Hemsleya pengxianensis.

Eight new natural products (four new cucurbitane aglycones, hemslepencins A-D (1-4), four new cucurbitane glucosides, hemslepensides F-I (5-8), along with seven known compounds (9-15), were isolated from the roots of Hemsleya pengxianensis. The structures of 1-8 were elucidated using IR, HRESIMS, and NMR. Compound 3 exhibited cytotoxic activity against the human cancer cell lines.

Effect of the Serum Inhibited Gene (Si1) on Autophagy and Apoptosis in MCF-7 Breast Cancer Cells.

BACKGROUND/AIMS: The serum inhibited gene (Si1) was named according to its inhibited expression in response to serum exposure. Si1 has an important relationship with tumors. Autophagy and apoptosis are two types of cell death. However, there are few studies regarding the association between Si1 and autophagy, or apoptosis in tumors. In this, we investigated the effect of Si1 on the proliferation and cell cycle progression of MCF-7 cells and its influence on autophagy and apoptosis in MCF-7 cells. METHODS: To investigate these functions of Si1 in tumor cells, we firstly constructed a pEGFP-Si1 overexpression vector and a pSilencer-Si1 interference vector, and we subsequently tested the proliferation and cell cycle progression of MCF-7 cells using the MTT assay and flow cytometry, and we then detected autophagy by western blotting and MDC (Monodansylcadaverine) staining as well as apoptosis by western blotting and Hoechst 33258 staining. RESULTS: We found that the Si1 gene can significantly inhibit the viability of MCF-7 cells and arrest the cell cycle at the G2/M phase. Si1 can induce autophagy through upregulation of LC3-II and Beclin1, it can induce apoptosis through cleavage of PARP in MCF-7 cells. CONCLUSION: Altogether, our study indicated that Si1 can inhibit cell proliferation of MCF-7, and also induces autophagy and apoptosis. This study firstly investigated the effect of Si1 on autophagy and apoptosis in MCF-7 cells. Moreover, it also improves the current understanding of the mechanisms related to the effect of Si1 on tumor cells and also provides a foundation for gene-targeted therapy.