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B-box (BBX) is a type of zinc finger transcription factor that contains a B-box domain. BBX transcription factors play important roles in plant photomorphogenesis, signal transduction, as well as abiotic and biological stress responses. However, the BBX gene family of Salvia miltiorrhiza has not been systematically investigated to date. For this study, based on the genomic data of Salvia miltiorrhiza, 27 SmBBXs genes were identified and clustered into five evolutionary branches according to phylogenetic analysis. The promoter analysis suggested that SmBBXs may be involved in the regulation of the light responses, hormones, stress signals, and tissue-specific development. Based on the transcriptome data, the expression patterns of SmBBXs under different abiotic stresses and plant hormones were analyzed. The results revealed that the expressions of the SmBBXs genes varied under different conditions and may play essential roles in growth and development. The transient expression analysis implied that SmBBX1, SmBBX4, SmBBX9, SmBBX20, and SmBBX27 were in the nucleus. A transcriptional activation assay showed SmBBX1, SmBBX4, SmBBX20, and SmBBX24 had transactivation activities, while SmBBX27 had none. These results provided a basis for further research on the role of SmBBXs in the development of Salvia miltiorrhiza.

Ralstonia Solanacearum is one of the most infectious soil-borne bacterial plant pathogens, causing tomato bacterial wilt (TBW). Nanotechnology is an emerging area of research, particularly the application of nanoparticles (NPs) as nanopesticides to manage plant disease is gaining attention nowadays. However, the interaction between NPs and rhizosphere bacterial communities remains largely elusive. This study indicated that metal NPs (CuO, ZnO, and FeO) reduced the incidence of bacterial wilt to varying degrees and affected the composition and structure of the rhizosphere bacterial community. The results revealed that the application of metal oxide NPs can improve the morphological and physiological parameters of TBW infected tomato plants. Among all, CuONPs amendments significantly increase the Chao1 and Shannon index. In the early stage (the second week), it significantly reduces the relative abundance of pathogens. However, the relative abundance of beneficial Streptomyces bacteria increased significantly, negatively correlated with the relative abundance of pathogenic bacteria. In addition, the nano-treatment group will enrich some potential beneficial bacteria such as species from Sphingomonadaceae, Rhizobiaceae, etc. In general, our research provides evidence and strategies for preventing and controlling soil-borne disease tomato bacterial wilt with metal oxide NPs.

When the bond lengths of 11 molecules containing van der Waals bonds are optimized by 572 methods and 20 basis sets, it is found that the best mean absolute deviations (MADs) of density-functional theory (DFT) methods are 0.005 Å (shown by APFD/6-311++G**), 0.007 Å (B2PLYPD3(Full)/aug-cc-pVQZ), and 0.010 Å (revDSDPBEP86/aug-cc-pVQZ), while the best MADs of ab initio methods are 0.008 Å (BD(T)/aug-cc-pVTZ) and 0.016 Å (MP4/aug-cc-pVQZ). Moreover, the best MADs calculated by 54 selected methods in combination with 60 other basis sets (such as 6-311++G, 6-31++G(3d′f,3p′d), and UGBS1V++) are not better. Therefore, these bond lengths can be calculated with extremely high accuracy by some special methods and basis sets, and CCSD(T) is also not as good as expected because its best MAD is only 0.023 Å (CCSD(T)/aug-cc-pVQZ).

Hyperosmolality-gated calcium-permeable channels (OSCA) are characterized as an osmosensor in plants; they are able to recognize and respond to exogenous and endogenous osmotic changes, and play a vital role in plant growth and adaptability to environmental stress. To explore the potential biological functions of OSCAs in maize, we performed a bioinformatics and expression analysis of the

Human mitochondrial transcription termination factor 1 (MTERF1) has been demonstrated to play an important role in mitochondrial gene expression regulation. However, the molecular mechanism of MTERF1 in colorectal cancer (CRC) remains largely unknown. Here, we found that MTERF1 expression was significantly increased in colon cancer tissues compared with normal colorectal tissue by Western blotting, immunohistochemistry, and tissue microarrays (TMA). Overexpression of MTERF1 in the HT29 cell promoted cell proliferation, migration, invasion, and xenograft tumor formation, whereas knockdown of MTERF1 in HCT116 cells appeared to be the opposite phenotype to HT29 cells. Furthermore, MTERF1 can increase mitochondrial DNA (mtDNA) replication, transcription, and protein synthesis in colorectal cancer cells; increase ATP levels, the mitochondrial crista density, mitochondrial membrane potential, and oxygen consumption rate (OCR); and reduce the ROS production in colorectal cancer cells, thereby enhancing mitochondrial oxidative phosphorylation (OXPHOS) activity. Mechanistically, we revealed that MTERF1 regulates the AMPK/mTOR signaling pathway in cancerous cell lines, and we also confirmed the involvement of the AMPK/mTOR signaling pathway in both xenograft tumor tissues and colorectal cancer tissues. In summary, our data reveal an oncogenic role of MTERF1 in CRC progression, indicating that MTERF1 may represent a new therapeutic target in the future.

MicroRNAs (miRNAs) play important roles in insect growth and development, but they were poorly studied in insects. In this study, a total of 883 miRNAs were detected from the early embryo (EE), late larva (LL), early pupa (EP), late pupa (LP), and early adult (EA) of Tribolium castaneum by microarray assay. Further analysis identified 179 differentially expressed unique miRNAs (DEmiRNAs) during these developmental stages. Of the DEmiRNAs, 102 DEmiRNAs exhibited stage-specific expression patterns during development, including 53 specifically highly expressed miRNAs and 20 lowly expressed miRNAs in EE, 19 highly expressed miRNAs in LL, 5 weakly expressed miRNAs in EP, and 5 abundantly expressed miRNAs in EA. These miRNAs were predicted to target 747, 265, 472, 234, and 121 genes, respectively. GO enrichment analysis indicates that the targets were enriched by protein phosphorylation, calcium ion binding, sequence-specific DNA binding transcription factor activity, and cytoplasm. An RNA interference-mediated knockdown of the DEmiRNAs tca-miR-6-3p, tca-miR-9a-3p, tca-miR-9d-3p, tca-miR-11-3p, and tca-miR-13a-3p led to defects in metamorphosis and wing development of T. castaneum. This study has completed the identification and characterization of development-related miRNAs in T. castaneum, and will enable us to investigate their roles in the growth and development of insect.

This work investigates the mechanical properties, microstructures, and water-swelling behavior of a novel hydrogel filled with magnetic particles. The nanoparticles of magnetite (Fe3O4) and the micro-particles of carbonyl iron (CI) were selected and filled into a polyacrylamide (PAAM) hydrogel matrix to create two types of magnetic hydrogels. The isotropy and anisotropy of magnetic hydrogels are also presented in this study. The isotropic samples were cured without applying a magnetic field (MF), and the anisotropic samples were cured by applying an MF in the direction perpendicular to the thickness of the samples. The effects of the size, content, and inner structures of magnetic particles on the magneto-responsive and swelling properties of magnetic hydrogels were investigated. It was found that the magnetorheological (MR) effect of anisotropic samples was apparently higher than that of isotropic samples, and the hydrogels with CI exhibited a noticeable MR effect than those with Fe3O4. The storage modulus can be enhanced by increasing the filler content and size, forming an anisotropic structure, and applying an external MF. In addition, the magnetic hydrogels also have a swelling ability that can be tuned by varying the content and size of the particle fillers.

Chronic diseases and viral infections have threatened human life over the ages and constitute the main reason for increasing death globally. The rising burden of these diseases extends to negatively affecting the economy and trading globally, as well as daily life, which requires inexpensive, novel, and safe therapeutics. Therefore, scientists have paid close attention to probiotics as safe remedies to combat these morbidities owing to their health benefits and biotherapeutic effects. Probiotics have been broadly adopted as functional foods, nutraceuticals, and food supplements to improve human health and prevent some morbidity. Intriguingly, recent research indicates that probiotics are a promising solution for treating and prophylactic against certain dangerous diseases. Probiotics could also be associated with their essential role in animating the immune system to fight COVID-19 infection. This comprehensive review concentrates on the newest literature on probiotics and their metabolism in treating life-threatening diseases, including immune disorders, pathogens, inflammatory and allergic diseases, cancer, cardiovascular disease, gastrointestinal dysfunctions, and COVID-19 infection. The recent information in this report will particularly furnish a platform for emerging novel probiotics-based therapeutics as cheap and safe, encouraging researchers and stakeholders to develop innovative treatments based on probiotics to prevent and treat chronic and viral diseases.

Tea is widely consumed all over the world. Generally, tea is divided into six categories: White, green, yellow, oolong, black, and dark teas, based on the fermentation degree. Tea contains abundant phytochemicals, such as polyphenols, pigments, polysaccharides, alkaloids, free amino acids, and saponins. However, the bioavailability of tea phytochemicals is relatively low. Thus, some novel technologies like nanotechnology have been developed to improve the bioavailability of tea bioactive components and consequently enhance the bioactivity. So far, many studies have demonstrated that tea shows various health functions, such as antioxidant, anti-inflammatory, immuno-regulatory, anticancer, cardiovascular-protective, anti-diabetic, anti-obesity, and hepato-protective effects. Moreover, it is also considered that drinking tea is safe to humans, since reports about the severe adverse effects of tea consumption are rare. In order to provide a better understanding of tea and its health potential, this review summarizes and discusses recent literature on the bioactive components, bioavailability, health functions, and safety issues of tea, with special attention paid to the related molecular mechanisms of tea health functions.

Poly(methyl methacrylate) (PMMA) bone cements have been widely used in clinical practices. In order to enhance PMMA&rsquo, s imaging performance to facilitate surgical procedures, a supplementation of radiopaque agent is needed. However, PMMA bone cements are still facing problems of loosening and bacterial infection. In this study, a multifunctional coating to simultaneously encapsulate drug and prevent the infection of radiopaque agent has been developed. Barium sulfate (BaSO4), a common radiopaque agent, is used as a substrate material. We successfully fabricated porous BaSO4 microparticles, then modified with hexakis-(6-iodo-6-deoxy)-alpha-cyclodextrin (I-CD) and silver (Ag) to obtain porous BaSO4@PDA/I-CD/Ag microparticles. The porous nature and presence of PDA coating and I-CD on the surface of microparticles result in efficient loading and release of drugs such as protein. Meanwhile, the radiopacity of BaSO4@PDA/I-CD/Ag microparticles is enhanced by this multifunctional coating containing Ba, I and Ag. PMMA bone cements containing BaSO4@PDA/I-CD/Ag microparticles show 99% antibacterial rate against both Staphylococcus aureus (S. aureus) and Escherichia Coli (E. coli), yet without apparently affecting its biocompatibility. Together, this multifunctional coating possessing enhanced radiopacity, controlled drug delivery capability and exceptional antibacterial performance, may be a new way to modify radiopaque agents for bone cements.

Gender differences in pulmonary inflammation have been well documented. Although low molecular mass hyaluronan (LMMHA) is known to trigger pulmonary lung inflammation, sex differences in susceptibility to LMMHA are still unknown. In this study, we test the hypothesis that mice may display sex-specific differences after LMMHA administration. After LMMHA administration, male mice have higher neutrophil, cytokine, and chemokine counts compared to that of their female counterparts. Additionally, Ovariectomized (OVX) mice show greater LMMHA-induced inflammation compared to that of mice with intact ovaries. Injections of OVX mice with 17&beta, estradiol can decrease inflammatory responses in the OVX mice. These results show that ovarian hormones regulate LMMHA induced lung inflammation.

Banana (Musa acuminata, AAA group) is a representative climacteric fruit with essential nutrients and pleasant flavors. Control of its ripening determines both the fruit quality and the shelf life. NAC (NAM, ATAF, CUC2) proteins, as one of the largest superfamilies of transcription factors, play crucial roles in various functions, especially developmental processes. Thus, it is important to conduct a comprehensive identification and characterization of the NAC transcription factor family at the genomic level in M. acuminata. In this article, a total of 181 banana NAC genes were identified. Phylogenetic analysis indicated that NAC genes in M. acuminata, Arabidopsis, and rice were clustered into 18 groups (S1&ndash, S18), and MCScanX analysis disclosed that the evolution of MaNAC genes was promoted by segmental duplication events. Expression patterns of NAC genes during banana fruit ripening induced by ethylene were investigated using RNA-Seq data, and 10 MaNAC genes were identified as related to fruit ripening. A subcellular localization assay of selected MaNACs revealed that they were all localized to the nucleus. These results lay a good foundation for the investigation of NAC genes in banana toward the biological functions and evolution.

Jasmonic acid (JA) carboxyl methyltransferase (JMT), a key enzyme in jasmonate-regulated plant responses, may be involved in plant defense and development by methylating JA to MeJA, thus influencing the concentrations of MeJA in plant. In this study, we isolated the JMT gene from Salvia miltiorrhiza, an important medicinal plant widely used to treat cardiovascular disease. We present a genetic manipulation strategy to enhance the production of phenolic acids by overexpresion SmJMT in S. miltiorrhiza. Global transcriptomic analysis using RNA sequencing showed that the expression levels of genes involved in the biosynthesis pathway of phenolic acids and MeJA were upregulated in the overexpression lines. In addition, the levels of endogenous MeJA, and the accumulation of rosmarinic acid (RA) and salvianolic acid (Sal B), as well as the concentrations of total phenolics and total flavonoids in transgenic lines, were significantly elevated compared with the untransformed control. Our results demonstrate that overexpression of SmJMT promotes the production of phenolic acids through simultaneously activating genes encoding key enzymes involved in the biosynthesis pathway of phenolic acids and enhancing the endogenous MeJA levels in S. miltiorrhiza.

Ginsenoside Rg1, a saponin that is a primary component of ginseng, has been demonstrated to protect hearts from diverse cardiovascular diseases with regulating multiple cellular signal pathways. In the present study, we investigated the protective role of ginsenoside Rg1 on doxorubicin-induced cardiotoxicity and its effects on endoplasmic reticulum stress and autophagy. After pre-treatment with ginsenoside Rg1 (50 mg/kg i.g.) for 7 days, male C57BL/6J mice were intraperitoneally injected with a single dose of doxorubicin (6 mg/kg) every 3 days for four injections. Echocardiographic and pathological findings showed that ginsenoside Rg1 could significantly reduce the cardiotoxicity induced by doxorubicin. Ginsenoside Rg1 significantly inhibited doxorubicin-induced formation of autophagosome. At the same time, ginsenoside Rg1 decreased the doxorubicin-induced cardiac microtubule-associated protein-light chain 3 and autophagy related 5 expression. Ginsenoside Rg1 can reduce endoplasmic reticulum dilation caused by doxorubicin. Compared with the doxorubicin group, the expression of cleaved activating transcription factor 6 and inositol-requiring enzyme 1 decreased in group ginsenoside Rg1. Treatment with ginsenoside Rg1 reduces the expression of TIF1 and increases the expression of glucose-regulated protein 78. In the ginsenoside Rg1 group, the expression of p-P70S6K, c-Jun N-terminal kinases 1 and Beclin1 declined. These results indicate that ginsenoside Rg1 may improve doxorubicin-induced cardiac dysfunction by inhibiting endoplasmic reticulum stress and autophagy.

Jasmonic acid (JA) carboxyl methyltransferase (JMT), a key enzyme in jasmonate-regulated plant responses, may be involved in plant defense and development by methylating JA to MeJA, thus influencing the concentrations of MeJA in plant. In this study, we isolated the JMT gene from Salvia miltiorrhiza, an important medicinal plant widely used to treat cardiovascular disease. We present a genetic manipulation strategy to enhance the production of phenolic acids by overexpresion SmJMT in S. miltiorrhiza. Global transcriptomic analysis using RNA sequencing showed that the expression levels of genes involved in the biosynthesis pathway of phenolic acids and MeJA were upregulated in the overexpression lines. In addition, the levels of endogenous MeJA, and the accumulation of rosmarinic acid (RA) and salvianolic acid (Sal B), as well as the concentrations of total phenolics and total flavonoids in transgenic lines, were significantly elevated compared with the untransformed control. Our results demonstrate that overexpression of SmJMT promotes the production of phenolic acids through simultaneously activating genes encoding key enzymes involved in the biosynthesis pathway of phenolic acids and enhancing the endogenous MeJA levels in S. miltiorrhiza.

IL-33 is a new member of the IL-1 family cytokines, which is expressed by different types of immune cells and non-immune cells. IL-33 is constitutively expressed in the nucleus, where it can act as a transcriptional regulator. So far, no direct target for nuclear IL-33 has been identified, and the regulation of IL-33 nuclear function remains largely unclear. Here, we report that the transcription of type 2 inflammatory cytokine IL-13 is positively regulated by nuclear IL-33. IL-33 can directly bind to the conserved non-coding sequence (CNS) before the translation initiation site in the IL13 gene locus. Moreover, IL-33 nuclear function and stability are regulated by the enzyme ubiquitin-specific protease 17 (USP17) through deubiquitination of IL-33 both at the K48 and at the K63 sites. Our data suggest that IL13 gene transcription can be directly activated by nuclear IL-33, which is negatively regulated by the deubiquitinase USP17.

Valine glycine repeat G (VgrG) proteins are regarded as one of two effectors of Type VI secretion system (T6SS) which is a complex multi-component secretion system. In this study, potential biological roles of T6SS structural and VgrG genes in a rice bacterial pathogen, Acidovorax avenae subsp. avenae (Aaa) RS-1, were evaluated under seven stress conditions using principle component analysis of gene expression. The results showed that growth of the pathogen was reduced by H2O2 and paraquat-induced oxidative stress, high salt, low temperature, and vgrG mutation, compared to the control. However, pathogen growth was unaffected by co-culture with a rice rhizobacterium Burkholderia seminalis R456. In addition, expression of 14 T6SS structural and eight vgrG genes was significantly changed under seven conditions. Among different stress conditions, high salt, and low temperature showed a higher effect on the expression of T6SS gene compared with host infection and other environmental conditions. As a first report, this study revealed an association of T6SS gene expression of the pathogen with the host infection, gene mutation, and some common environmental stresses. The results of this research can increase understanding of the biological function of T6SS in this economically-important pathogen of rice.

Isoliquiritigenin (ILTG) possesses many pharmacological properties. However, its poor solubility and stability in water hinders its wide applications. The solubility of bioactive compounds can often be enhanced through preparation and delivery of various cyclodextrin (CD) inclusion complexes. The 6-O-α-D-maltosyl-β-CD (G2-β-CD), as one of the newest developments of CDs, has high aqueous solubility and low toxicity, especially stable inclusion characteristics with bioactive compounds. In this work, we for the first time construct and characterize the supermolecular structure of ILTG/G2-β-CD by scanning electron microscopy (SEM), ultraviolet-visible spectroscopy (UV), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffractometry (XRD). The solubility of ILTG in water at 25 °C rises from 0.003 to 0.717 mg/mL by the encapsulation with G2-β-CD. Our experimental observations on the presence of the ILTG/G2-β-CD inclusion complex are further supported by the ONIOM(our Own N-layer Integrated Orbital molecular Mechanics)-based QM/MM (Quantum Mechanics/Molecular Mechanics) calculations, typically substantiating these supermolecular characteristics, such as detailed structural assignments, preferred binding orientations, selectivity, solvent effects, interaction energies and forces of the ILTG/G2-β-CD inclusion complex. Our results have elucidated how ILTG interacts with G2-β-CD, demonstrating the primary host-guest interactions between ILTG and G2-β-CD, characterized by hydrogen bonds, hydrophobic interactions, electrostatic forces, and conformational effects, are favored for the formation of the ILTG/G2-β-CD inclusion.

Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases.

The Type VI secretion system (T6SS) is a class of macromolecular machine that is required for the virulence of gram-negative bacteria. However, it is still not clear what the role of T6SS in the virulence of rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae (Aaa) is. The aim of the current study was to investigate the contribution of T6SS in Aaa strain RS2 virulence using insertional deletion mutation and complementation approaches. This strain produced weak virulence but contains a complete T6SS gene cluster based on a genome-wide analysis. Here we compared the virulence-related phenotypes between the wild-type (RS-2) and 25 T6SS mutants, which were constructed using homologous recombination methods. The mutation of 15 T6SS genes significantly reduced bacterial virulence and the secretion of Hcp protein. Additionally, the complemented 7 mutations ΔpppA, ΔclpB, Δhcp, ΔdotU, ΔicmF, ΔimpJ, and ΔimpM caused similar virulence characteristics as RS-2. Moreover, the mutant ΔpppA, ΔclpB, ΔicmF, ΔimpJ and ΔimpM genes caused by a 38.3~56.4% reduction in biofilm formation while the mutants ΔpppA, ΔclpB, ΔicmF and Δhcp resulted in a 37.5~44.6% reduction in motility. All together, these results demonstrate that T6SS play vital roles in the virulence of strain RS-2, which may be partially attributed to the reductions in Hcp secretion, biofilm formation and motility. However, differences in virulence between strain RS-1 and RS-2 suggest that other factors may also be involved in the virulence of Aaa.

Many studies have indicated that consumption of vegetables and fruits are positively related to lower incidence of several chronic noncommunicable diseases. Although composition of fruit and vegetable juices is different from that of the edible portion of fruits and vegetables, they contain polyphenols and vitamins from fruits and vegetables. Drinking vegetable and fruit juices is very popular in many countries, and also an efficient way to improve consumption of fruits and vegetables. The studies showed that fruit and vegetable juices affect cardiovascular risk factors, such as lowering blood pressure and improving blood lipid profiles. The main mechanisms of action included antioxidant effects, improvement of the aspects of the cardiovascular system, inhibition of platelet aggregation, anti-inflammatory effects, and prevention of hyperhomocysteinemia. Drinking juices might be a potential way to improve cardiovascular health, especially mixtures of juices because they contain a variety of polyphenols, vitamins, and minerals from different fruits and vegetables. This review summarizes recent studies on the effects of fruit and vegetable juices on indicators of cardiovascular disease, and special attention is paid to the mechanisms of action.

Natural antioxidants are widely distributed in food and medicinal plants. These natural antioxidants, especially polyphenols and carotenoids, exhibit a wide range of biological effects, including anti-inflammatory, anti-aging, anti-atherosclerosis and anticancer. The effective extraction and proper assessment of antioxidants from food and medicinal plants are crucial to explore the potential antioxidant sources and promote the application in functional foods, pharmaceuticals and food additives. The present paper provides comprehensive information on the green extraction technologies of natural antioxidants, assessment of antioxidant activity at chemical and cellular based levels and their main resources from food and medicinal plants.

Natural medicines have attracted wide attention in recent years. It is of great significance to clarify the pharmacological mechanisms of natural medicines. In prior studies, we established a method for elucidating pharmacological mechanisms of natural products contained in connectivity map (cMap), in terms of module profiles of gene expression in chemical treatments. In this study, we explore whether this methodology is applicable to dissecting the pharmacological mechanisms of natural medicines beyond the agents contained in cMap. First, the gene expression profiles of curcumin (a typical isolated natural medicine) and Si-Wu-Tang (a classic traditional Chinese medicine formula) treatments were merged with those of cMap-derived 1309 agents, respectively. Then, a biclustering analysis was performed using FABIA method to identify gene modules. The biological functions of gene modules provide preliminary insights into pharmacological mechanisms of both natural medicines. The module profile can be characterized by a binary vector, which allowed us to compare the expression profiles of natural medicines with those of cMap-derived agents. Accordingly, we predicted a series of pharmacological effects for curcumin and Si-Wu-Tang by the indications of cMap-covered drugs. Most predictions were supported by experimental observations, suggesting the potential use of this method in natural medicine dissection.

Bmi1 is a member of the polycomb group family of proteins, and it drives the carcinogenesis of various cancers and governs the self-renewal of multiple types of stem cells. Our previous studies have revealed that Bmi1 acts as an oncogene in hepatic carcinogenesis in an INK4a/ARF locus independent manner. However, whether Bmi1 can be used as a potential target for hepatocellular carcinoma treatment has not been fully confirmed yet. Here, we show that perturbation of Bmi1 expression by using short hairpin RNA can inhibit the tumorigenicity and tumor growth of hepatocellular carcinoma cells both in vitro and in vivo. Importantly, Bmi1 knockdown can block the tumor growth, both in the initiating stages and the fast growing stages. Cellular biology analysis revealed that Bmi1 knockdown induces cell cycle arrest and apoptosis. Our findings verify Bmi1 as a qualified treatment target for hepatocellular carcinoma (HCC) and support Bmi1 targeting treatment with chemotherapeutic agents.

Liver kinase B1 (LKB1), known as a serine/threonine kinase, has been identified as a critical cancer suppressor in many cancer cells. It is a master upstream kinase of 13 AMP-activated protein kinase (AMPK)-related protein kinases, and possesses versatile biological functions. LKB1 gene is mutated in many cancers, and its protein can form different protein complexes with different cellular localizations in various cell types. The expression of LKB1 can be regulated through epigenetic modification, transcriptional regulation and post-translational modification. LKB1 dowcnstream pathways mainly include AMPK, microtubule affinity regulating kinase (MARK), salt-inducible kinase (SIK), sucrose non-fermenting protein-related kinase (SNRK) and brain selective kinase (BRSK) signalings, etc. This review, therefore, mainly discusses recent studies about the expression, regulation, downstream signaling and cancer suppressive function of LKB1, which can be helpful for better understanding of this molecular and its significance in cancers.

Due to the diverse medicinal effects, polyphenols are among the most intensively studied natural products. However, it is a great challenge to elucidate the polypharmacological mechanisms of polyphenols. To address this challenge, we establish a method for identifying multiple targets of chemical agents through analyzing the module profiles of gene expression upon chemical treatments. By using FABIA algorithm, we have performed a biclustering analysis of gene expression profiles derived from Connectivity Map (cMap), and clustered the profiles into 49 gene modules. This allowed us to define a 49 dimensional binary vector to characterize the gene module profiles, by which we can compare the expression profiles for each pair of chemical agents with Tanimoto coefficient. For the agent pairs with similar gene expression profiles, we can predict the target of one agent from the other. Drug target enrichment analysis indicated that this method is efficient to predict the multiple targets of chemical agents. By using this method, we identify 148 targets for 20 polyphenols derived from cMap. A large part of the targets are validated by experimental observations. The results show that the medicinal effects of polyphenols are far beyond their well-known antioxidant activities. This method is also applicable to dissect the polypharmacology of other natural products.

Sulfuretin is one of the major flavonoid components in Rhus verniciflua Stokes (Anacardiaceae) isolates. In this study, we investigated the protective effects of sulfuretin against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury. The results indicated that the addition of sulfuretin before t-BHP treatment significantly inhibited cytotoxicity and reactive oxygen species (ROS) production in human liver-derived HepG2 cells. Sulfuretin up-regulated the activity of the antioxidant enzyme heme oxygenase (HO)-1 via nuclear factor E2-related factor 2 (Nrf2) translocation into the nucleus and increased the promoter activity of the antioxidant response element (ARE). Moreover, sulfuretin exposure enhanced the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2), which are members of the mitogen-activated protein kinase (MAPK) family. Furthermore, cell treatment with a JNK inhibitor (SP600125) and ERK inhibitor (PD98059) reduced sulfuretin-induced HO-1 expression and decreased its protective effects. Taken together, these results suggest that the protective effect of sulfuretin against t-BHP-induced oxidative damage in human liver-derived HepG2 cells is attributable to its ability to scavenge ROS and up-regulate the activity of HO-1 through the Nrf2/ARE and JNK/ERK signaling pathways. Therefore, sulfuretin could be advantageous as a bioactive source for the prevention of oxidative injury.

Innate immunity is the first line of defense in human beings against pathogen infection, monocytes/macrophages are the primary cells of the innate immune system. Recently, macrophages/monocytes have been discovered to participate in LPS clearance, and the clearance efficiency determines the magnitude of the inflammatory response and subsequent organ injury. Previously, we reported that artesunate (AS) protected sepsis mice against heat-killed E. coli challenge. Herein, we further confirmed that AS protected cecal ligation/puncture (CLP) sepsis mice. Its protection on sepsis mice was related to not only reduction of pro-inflammatory cytokines and serum LPS levels but also improvement of liver function. Based on the fact that AS did not directly bind and neutralize LPS, we hypothesized that the reduction of serum LPS level might be related to enhancement of LPS internalization and subsequent detoxification. Our results showed that AS increased FITC-LPS internalization by peritoneal macrophage and liver Kupffer cell, but enhancement of LPS internalization by AS was not related to the clathrin-dependent pathway. However, AS induced mRNA expression of important scavenger receptors (SRs), SR-A and MARCO mRNA expression was upregulated, suggesting that AS enhancement of LPS internalization and inhibition of pro-inflammatory cytokines was related to changes in mRNA expression of SRs.

Cytoplasmic male sterility (CMS) is an important agronomic feature and provides an effective tool for heterosis utilization of crops. This study reports the comparative transcriptomic sketches between a novel allohexaploid cotton progeny CMS line LD6A and its maintainer line LD6B using de novo transcriptome sequencing technology at the pollen abortion stage. A total of 128,901 Unigenes were identified, in which 2007 were upregulated and 11,864 were downregulated. The significantly differentially expressed genes (DEGs) in LD6A show a distant and diverse genetic nature due to their distant hybrid hexaploidy progeny. Further analysis revealed that most of the DEGs participated in the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, histone acetyltransferase activity, sepal development, stigma development, cotyledon development and microsporogenesis. A highly differentially expressed toxic protein, Abrin, was identified in the CMS line LD6A, which can catalyze the inactivation of ribosomes and consequently lead to cell death through the mitochondrial pathway in human cells. Twelve DEGs were selected randomly to validate transcriptome data using quantitative reverse-transcribed PCR (qRT-PCR). This study will contribute to new ideas and foundations related to the molecular mechanism of CMS and the innovation of cotton germplasm resources.

Species identification of oaks (Quercus) is always a challenge because many species exhibit variable phenotypes that overlap with other species. Oaks are notorious for interspecific hybridization and introgression, and complex speciation patterns involving incomplete lineage sorting. Therefore, accurately identifying Quercus species barcodes has been unsuccessful. In this study, we used chloroplast genome sequence data to identify molecular markers for oak species identification. Using next generation sequencing methods, we sequenced 14 chloroplast genomes of Quercus species in this study and added 10 additional chloroplast genome sequences from GenBank to develop a DNA barcode for oaks. Chloroplast genome sequence divergence was low. We identified four mutation hotspots as candidate Quercus DNA barcodes, two intergenic regions (matK-trnK-rps16 and trnR-atpA) were located in the large single copy region, and two coding regions (ndhF and ycf1b) were located in the small single copy region. The standard plant DNA barcode (rbcL and matK) had lower variability than that of the newly identified markers. Our data provide complete chloroplast genome sequences that improve the phylogenetic resolution and species level discrimination of Quercus. This study demonstrates that the complete chloroplast genome can substantially increase species discriminatory power and resolve phylogenetic relationships in plants.

Fructus crataegi (hawthorn) is the common name of all plant species in the genus Crataegus of the Rosaceae family. In the present study, three monomers of (+)-catechin (C), (−)-epicatechin gallate (ECg) and (−)-epigallocatechin (EGC) were isolated from the hawthorn under the guide of antibacterial sensitization activity. The bioactivity of the composite fraction in enhancing the antibacterial effect of oxacillin against methicillin-resistant Staphylococcus aureus (MRSA) was greater than that of the individual monomer of the hawthorn extract in vitro. Two-fold dilution and checkerboard methods were used to analyze antibacterial activity and screen for the combination and proportion of monomers with the best bioactivity. The result showed that C (128 mg/L) combined with ECg (16 mg/L) had the greatest effect and the combination also reduced the bacterial load in blood of septic mice challenged with a sublethal dose of MRSA, increased daunomycin accumulation within MRSA and down-regulated the mRNA expression of norA, norC and abcA, three important efflux pumps of MRSA. In summary, C and ECg enhanced the antibacterial effect of β-lactam antibiotics against MRSA in vitro and in vivo, which might be related to the increased accumulation of antibiotics within MRSA via suppression of important efflux pumps’ gene expression.

Adlay (Coix larchryma-jobi L.) was the commonly used Traditional Chinese Medicine (TCM) with high content of seed storage protein. The hydrolyzed bioactive oligopeptides of adlay have been proven to be anti-hypertensive effective components. However, the structures and anti-hypertensive mechanism of bioactive oligopeptides from adlay were not clear. To discover the definite anti-hypertensive oligopeptides from adlay, in silico proteolysis and virtual screening were implemented to obtain potential oligopeptides, which were further identified by biochemistry assay and molecular dynamics simulation. In this paper, ten sequences of adlay prolamins were collected and in silico hydrolyzed to construct the oligopeptide library with 134 oligopeptides. This library was reverse screened by anti-hypertensive pharmacophore database, which was constructed by our research team and contained ten anti-hypertensive targets. Angiotensin-I converting enzyme (ACE) was identified as the main potential target for the anti-hypertensive activity of adlay oligopeptides. Three crystal structures of ACE were utilized for docking studies and 19 oligopeptides were finally identified with potential ACE inhibitory activity. According to mapping features and evaluation indexes of pharmacophore and docking, three oligopeptides were selected for biochemistry assay. An oligopeptide sequence, NPATY (IC50 = 61.88 ± 2.77 µM), was identified as the ACE inhibitor by reverse-phase high performance liquid chromatography (RP-HPLC) assay. Molecular dynamics simulation of NPATY was further utilized to analyze interactive bonds and key residues. ALA354 was identified as a key residue of ACE inhibitors. Hydrophobic effect of VAL518 and electrostatic effects of HIS383, HIS387, HIS513 and Zn2+ were also regarded as playing a key role in inhibiting ACE activities. This study provides a research strategy to explore the pharmacological mechanism of Traditional Chinese Medicine (TCM) proteins based on in silico proteolysis and virtual screening, which could be beneficial to reveal the pharmacological action of TCM proteins and provide new lead compounds for peptides-based drug design.

Previous studies have shown that fruits have different effects on alcohol metabolism and alcohol-induced liver injury. The present work selected three fruits and aimed at studying the effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on alcohol-induced liver injury in mice. The animals were treated daily with alcohol and fruit juices for fifteen days. Chronic treatment with alcohol increased the levels of aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL), triglyceride (TG), malondialdehyde (MDA), and decreased total protein (TP). Histopathological evaluation also showed that ethanol induced extensive fat droplets in hepatocyte cytoplasm. Syzygium samarangense and Passiflora edulis normalized various biochemical parameters. Solanum muricatum increased the level of ALT and induced infiltration of inflammatory cells in the liver. These results strongly suggest that treatment with Syzygium samarangense and Passiflora edulis could protect liver from the injury of alcohol, while Solanum muricatum could aggravate the damage.

Tissue engineering-based urethral replacement holds potential for repairing large segmental urethral defects, which remains a great challenge at present. This study aims to explore the potential of combining biodegradable poly(l-lactide) (PLLA)/poly(ethylene glycol) (PEG) scaffolds and human amniotic mesenchymal cells (hAMSCs) for repairing urethral defects. PLLA/PEG fibrous scaffolds with various PEG fractions were fabricated via electrospinning. The scaffolds were then seeded with hAMSCs prior to implantation in New Zealand male rabbits that had 2.0 cm-long defects in the urethras. The rabbits were randomly divided into three groups. In group A, hAMSCs were grown on PLLA/PEG scaffolds for two days and then implanted to the urethral defects. In group B, only the PLLA/PEG scaffolds were used to rebuild the rabbit urethral defect. In group C, the urethral defect was reconstructed using a regular urethral reparation technique. The repair efficacy was compared among the three groups by examining the urethral morphology, tissue reconstruction, luminal patency, and complication incidence (including calculus formation, urinary fistula, and urethral stricture) using histological evaluation and urethral radiography methods. Findings from this study indicate that hAMSCs-loaded PLLA/PEG scaffolds resulted in the best urethral defect repair in rabbits, which predicts the promising application of a tissue engineering approach for urethral repair.

With increasing numbers of young female cancer survivors following chemotherapy, chemotherapy-induced fertility loss must be considered. Menstrual disorder and infertility are of particular concern in female cancer patients. We showed that treatment with the alkylating agent cyclophosphamide (CTX) could cause severe primordial follicle loss and growing follicle apoptosis, resulting in loss of ovarian reserve. SPF C57BL/6 female mice were treated with a single dose of 120 mg/kg of CTX or saline as a control, and both sides of ovaries were collected three or seven days after injection. Following CTX treatment, the ovaries were mostly composed of collapsed oocytes and presented marked cortical fibrosis and a reduced number of follicles, especially primordial follicles. The loss of primordial follicles was confirmed by primordial follicle counting, immunohistochemistry and Western blot detection of DDx4/MVH. Follicle apoptosis was tested by a TUNEL assay and the number of TUNEL-positive follicle cells increased, as expected, in CTX-treated mice. Furthermore, expression of APAF-1 and cleaved caspase-3 was also increased after CTX treatment. Analysis of the PI3K/Akt/mTOR signaling pathway showed that CTX increased phosphorylation of Akt, mTOR and downstream proteins without affecting total levels. These results demonstrated that the CTX treatment led to the hyperactivation of the PI3K/Akt/mTOR signaling pathway in ovaries which may be related to primordial follicle loss and growing follicle apoptosis.

Agarwood is the fragrant resinous material mainly formed from species of Aquilaria. 2-(2-phenylethyl)chromones, especially the highly oxidized 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones, are the main representative compounds from agarwood. It is important to determine whether agarwood in trade is from cultivated trees or natural trees in the Convention on the International Trade in Endangered Species (CITES). We characterized the 2-(2-phenylethyl)chromones in agarwood by ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC–ESI-QTOF-MS) and differentiated wild from cultivated agarwood by metabolomic analysis. A total of 141 chromones including 50 potentially new compounds were evaluated as belonging to four structural classes (unoxidized 2-(2-phenylethyl)chromones, 5,6,7,8-tetrahydro-2-(2-phenylethyl)-chromones, bi-2-(2-phenylethyl)chromones, and tri-2-(2-phenylethyl)chromones). The metabolic difference between wild and cultivated agarwood was analyzed by component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Fourteen markers of metabolisms in wild and cultivated agarwood were constructed (e.g., 6,7-dimethoxy-2-(2-phenylethyl)chromone, 6,8-dihydroxy-2-(2-phenylethyl)chromone, 6-methoxy-2-(2-phenylethyl)chromone, etc.). These results indicated that UPLC–ESI-QTOF-MS-based metabonomics analysis in agarwood may be useful for distinguishing wild agarwood from cultivated agarwood.

Nonalcoholic beverages are usually consumed accompanying alcoholic drinks, and their effects on alcohol metabolism are unclear in vivo. In this study, the effects of 20 nonalcoholic beverages on alcohol metabolism and liver injury caused by alcohol were evaluated in mice. Kunming mice were orally fed with alcohol (52%, v/v) and beverages. The concentrations of ethanol and acetaldehyde in blood as well as the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in liver were assessed to indicate alcohol metabolism. The levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) in serum as well as the levels of malonaldehyde (MDA) and superoxide dismutase (SOD) in liver were measured to reflect the alcohol-induced liver injury. The results showed that the treatment of soda water, green tea and honey chrysanthemum tea could accelerate ethanol metabolism and prevent liver injuries caused by alcohol when companied with excessive alcohol drinking. They might be potential dietary supplements for the alleviation of harmful effects from excessive alcohol consumption. On the contrary, some beverages such as fresh orange juice and red bull are not advised to drink when companied with alcohol consumption due to their adverse effects on ethanol induced liver injury.

Fruit wastes are one of the main sources of municipal waste. In order to explore the potential of fruit wastes as natural resources of bioactive compounds, the antioxidant potency and total phenolic contents (TPC) of lipophilic and hydrophilic components in wastes (peel and seed) of 50 fruits were systematically evaluated. The results showed that different fruit residues had diverse antioxidant potency and the variation was very large. Furthermore, the main bioactive compounds were identified and quantified, and catechin, cyanidin 3-glucoside, epicatechin, galangin, gallic acid, homogentisic acid, kaempferol, and chlorogenic acid were widely found in these residues. Especially, the values of ferric-reducing antioxidant power (FRAP), trolox equivalent antioxidant capacity (TEAC) and TPC in the residues were higher than in pulps. The results showed that fruit residues could be inexpensive and readily available resources of bioactive compounds for use in the food and pharmaceutical industries.

Oleanolic acid and ursolic acid are the main active components in fruit of Ligustrum lucidum Ait, and possess anticancer, antimutagenic, anti-inflammatory, antioxidative and antiprotozoal activities. In this study, microwave-assisted extraction of oleanolic acid and ursolic acid from Ligustrum lucidum was investigated with HPLC-photodiode array detection. Effects of several experimental parameters, such as type and concentration of extraction solvent, ratio of liquid to material, microwave power, extraction temperature and microwave time, on the extraction efficiencies of oleanolic acid and ursolic acid from Ligustrum lucidum were evaluated. The influence of experimental parameters on the extraction efficiency of ursolic acid was more significant than that of oleanolic acid (p < 0.05). The optimal extraction conditions were 80% ethanol aqueous solution, the ratio of material to liquid was 1:15, and extraction for 30 min at 70 °C under microwave irradiation of 500 W. Under optimal conditions, the yields of oleanolic acid and ursolic acid were 4.4 ± 0.20 mg/g and 5.8 ± 0.15 mg/g, respectively. The results obtained are helpful for the full utilization of Ligustrum lucidum, which also indicated that microwave-assisted extraction is a very useful method for extraction of oleanolic acid and ursolic acid from plant materials.

In order to supply new information on the antioxidant function of selected beverages for nutritionists and the general public, total phenolic contents of 51 kinds of herbal and tea infusions made in China were measured by the Folin-Ciocalteu method, and their antioxidant capacities were evaluated using ferric reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC) assays. A significant correlation between FRAP and TEAC values suggested that antioxidant components in these beverages were capable of reducing oxidants and scavenging free radicals. The high correlation between antioxidant capacities and total phenolic contents indicated that phenolic compounds could be one of the main components responsible for antioxidant activities of these beverages. Generally, these beverages had high antioxidant capacities and total phenolic contents, and could be important dietary sources of antioxidant phenolics for prevention of diseases caused by oxidative stress.

Antioxidant capacities of 56 selected Chinese medicinal plants were evaluated using the Trolox equivalent antioxidant capacity (TEAC) and ferric reducing antioxidant power (FRAP) assays, and their total phenolic content was measured by the Folin-Ciocalteu method. The strong correlation between TEAC value and FRAP value suggested that the antioxidants in these plants possess free radical scavenging activity and oxidant reducing power, and the high positive correlation between antioxidant capacities and total phenolic content implied that phenolic compounds are a major contributor to the antioxidant activity of these plants. The results showed that Dioscorea bulbifera, Eriobotrya japonica, Tussilago farfara and Ephedra sinica could be potential rich sources of natural antioxidants.

Biofilm formation is important for virulence of a large number of plant pathogenic bacteria. Indeed, some virulence genes have been found to be involved in the formation of biofilm in bacterial fruit blotch pathogen Acidovorax citrulli. However, some virulent strains of A. citrulli were unable to format biofilm, indicating the complexity between biofilm formation and virulence. In this study, virulence-related genes were identified in the biofilm-defective strain A1 of A. citrulli by using Tn5 insertion, pathogenicity test, and high-efficiency thermal asymmetric interlaced PCR (hiTAIL-PCR). Results from this study indicated that 22 out of the obtained 301 mutants significantly decreased the virulence of strain A1 compared to the wild-type. Furthermore, sequence analysis indicated that the obtained 22 mutants were due to the insertion of Tn5 into eight genes, including Aave 4244 (cation diffusion facilitator family transporter), Aave 4286 (hypothetical protein), Aave 4189 (alpha/beta hydrolase fold), Aave 1911 (IMP dehydrogenase/GMP reductase domain), Aave 4383 (bacterial export proteins, family 1), Aave 4256 (Hsp70 protein), Aave 0003 (histidine kinase, DNA gyrase B, and HSP90-like ATPase), and Aave 2428 (pyridoxal-phosphate dependent enzyme). Furthermore, the growth of mutant Aave 2428 was unaffected and even increased by the change in incubation temperature, NaCl concentration and the pH of the LB broth, indicating that this gene may be directly involved in the bacterial virulence. Overall, the determination of the eight pathogenicity-related genes in strain A1 will be helpful to elucidate the pathogenesis of biofilm-defective A. citrulli.

Infectious diseases caused by pathogens and food poisoning caused by spoilage microorganisms are threatening human health all over the world. The efficacies of some antimicrobial agents, which are currently used to extend shelf-life and increase the safety of food products in food industry and to inhibit disease-causing microorganisms in medicine, have been weakened by microbial resistance. Therefore, new antimicrobial agents that could overcome this resistance need to be discovered. Many spices—such as clove, oregano, thyme, cinnamon, and cumin—possessed significant antibacterial and antifungal activities against food spoilage bacteria like Bacillus subtilis and Pseudomonas fluorescens, pathogens like Staphylococcus aureus and Vibrio parahaemolyticus, harmful fungi like Aspergillus flavus, even antibiotic resistant microorganisms such as methicillin resistant Staphylococcus aureus. Therefore, spices have a great potential to be developed as new and safe antimicrobial agents. This review summarizes scientific studies on the antibacterial and antifungal activities of several spices and their derivatives.

Liver injuries and diseases are serious health problems worldwide. Various factors, such as chemical pollutants, drugs, and alcohol, could induce liver injuries. Liver diseases involve a wide range of liver pathologies, including hepatic steatosis, fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocarcinoma. Despite all the studies performed up to now, therapy choices for liver injuries and diseases are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries and diseases remains a priority. Melatonin is a well-known natural antioxidant, and has many bioactivities. There are numerous studies investigating the effects of melatonin on liver injuries and diseases, and melatonin could regulate various molecular pathways, such as inflammation, proliferation, apoptosis, metastasis, and autophagy in different pathophysiological situations. Melatonin could be used for preventing and treating liver injuries and diseases. Herein, we conduct a review summarizing the potential roles of melatonin in liver injuries and diseases, paying special attention to the mechanisms of action.

Information about the interface sites of Protein–Protein Interactions (PPIs) is useful for many biological research works. However, despite the advancement of experimental techniques, the identification of PPI sites still remains as a challenging task. Using a statistical learning technique, we proposed a computational tool for predicting PPI interaction sites. As an alternative to similar approaches requiring structural information, the proposed method takes all of the input from protein sequences. In addition to typical sequence features, our method takes into consideration that interaction sites are not randomly distributed over the protein sequence. We characterized this positional preference using protein complexes with known structures, proposed a numerical index to estimate the propensity and then incorporated the index into a learning system. The resulting predictor, without using structural information, yields an area under the ROC curve (AUC) of 0.675, recall of 0.597, precision of 0.311 and accuracy of 0.583 on a ten-fold cross-validation experiment. This performance is comparable to the previous approach in which structural information was used. Upon introducing the B-factor data to our predictor, we demonstrated that the AUC can be further improved to 0.750. The tool is accessible at http://bsaltools.ym.edu.tw/predppis.

Wild fruits are exotic or underutilized. Wild fruits contain many bioactive compounds, such as anthocyanins and flavonoids. Many studies have shown that wild fruits possess various bioactivities and health benefits, such as free radical scavenging, antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. Therefore, wild fruits have the potential to be developed into functional foods or pharmaceuticals to prevent and treat several chronic diseases. In the present article, we review current knowledge about the bioactivities and health benefits of wild fruits, which is valuable for the exploitation and utilization of wild fruits.

While titanium (Ti) implants have been extensively used in orthopaedic and dental applications, the intrinsic bioinertness of untreated Ti surface usually results in insufficient osseointegration irrespective of the excellent biocompatibility and mechanical properties of it. In this study, we prepared surface modified Ti substrates in which silicon (Si) was doped into the titanium dioxide (TiO2) nanotubes on Ti surface using plasma immersion ion implantation (PIII) technology. Compared to TiO2 nanotubes and Ti alone, Si-doped TiO2 nanotubes significantly enhanced the expression of genes related to osteogenic differentiation, including Col-I, ALP, Runx2, OCN, and OPN, in mouse pre-osteoblastic MC3T3-E1 cells and deposition of mineral matrix. In vivo, the pull-out mechanical tests after two weeks of implantation in rat femur showed that Si-doped TiO2 nanotubes improved implant fixation strength by 18% and 54% compared to TiO2-NT and Ti implants, respectively. Together, findings from this study indicate that Si-doped TiO2 nanotubes promoted the osteogenic differentiation of osteoblastic cells and improved bone-Ti integration. Therefore, they may have considerable potential for the bioactive surface modification of Ti implants.