Regulatory pathway underpinning the development of encephalitis after simian immunodeficiency virus infection in rhesus macaques (Macaca mulatta).

BACKGROUND: Simian immunodeficiency virus (SIV) infection in rhesus macaques (Macaca mulatta) can lead to the development of SIV encephalitis (SIVE), which is closely related to human immunodeficiency virus (HIV)-induced dementia. METHODS: This was done by analyzing SIV and SIVE encephalitis in infected M. mulatta hippocampus samples from two microarray data sets, identifying two groups of common differentially expressed genes and predicting associated protein interactions. RESULTS: We found that eight genes-MX1, B2M, IFIT1, TYMP, STAT1, IFI44, ISG15, and IFI27-affected the negative regulation of biological processes, hepatitis C and Epstein-Barr viral infection, and the toll-like receptor signaling pathway, which mediate the development of encephalitis after SIV infection. In particular, STAT1 played a central role in the process by regulating biopathological changes during the development of SIVE. CONCLUSION: These findings provide a new theoretical basis for the treatment of encephalopathy after HIV infection by targeting STAT1.

Effect of different dry matter content on fermentation characteristics and nutritional quality of Napier grass silage with novel lactic acid bacteria strains.

To investigate the characteristics of different LAB strains isolated from subtropics and their effects on Napier grass (Pennisetum purpureum Schum.) silage with two dry matter (DM) levels, sugar fermentation pattern, and growth profiles of three screened lactic acid bacteria (LAB) strains [Pediococcus pentosaceus (PP04), Weissella cibaria (WC10), and Lactobacillus plantarum (LP694)] were characterized, and then used either individually or in combination at 1.0 × 106 cfu g-1 fresh weight to inoculate grass having 15% or 25% DM. Treatments were applied: (1) no inoculant (control); (2) PP04; (3) WC10; (4) LP694; (5) M-1 (PP04: WC10 = 2:1); (6) M-2 (PP04: LP694 = 1:2); (7) M-3 (WC10: LP694 = 2:1); (8) M-4 (PP04: WC10: LP694 = 2:1:1). The results showed that all inoculations increased LAB, DM recovery, and lactic acid (LA) concentration, while decreasing pH, the ammonia nitrogen/total nitrogen (NH3-N/TN), and butyric acid (BA) concentration compared to control group in both DM. However, the effect of inoculations was very limited at 15% DM. Silages with inoculants achieved higher silage quality at 25% DM than 15% DM. The different LAB inoculants result in significant differences in silage quality, while W. cibaria decreased the pH and inhibited the growth of undesirable bacteria and those characteristics were not affected by the DM content.

Genome-wide identification of C2H2-type zinc finger gene family members and their expression during abiotic stress responses in orchardgrass (Dactylis glomerata).

The C2H2-type zinc finger protein (ZFP) family is one of the largest transcription factor families in the plant kingdom and its members are involved in plant growth, development, and stress responses. As an economically valuable perennial graminaceous forage crop, orchardgrass (Dactylis glomerata) is an important feedstuff resource owing to its high yield and quality. In this study, 125 C2H2-type ZFPs in orchardgrass (Dg-ZFPs) were identified and further classified by phylogenetic analysis. The members with similar gene structures were generally clustered into the same groups, with proteins containing the conserved QALGGH motif being concentrated in groups VIII and IX. Gene ontology and miRNA target analyses indicated that Dg-ZFPs likely perform diverse biological functions through their gene interactions. The RNA-seq data revealed differentially expressed genes across tissues and development phases, suggesting that some Dg-ZFPs might participate in growth and development regulation. Abiotic stress responses of Dg-ZFP genes were verified by qPCR and Saccharomyces cerevisiae transformation, revealing that Dg-ZFP125 could enhance the tolerance of yeasts to osmotic and salt stresses. Our study performed a novel systematic analysis of Dg-ZFPs in orchardgrass, providing a reference for this gene family in other grasses and revealing new insights for enhancing gene utilization.

Silver-decorated black phosphorus: a synergistic antibacterial strategy.

Black phosphorus (BP) exhibits great potential as antibacterial materials due to its unique photocatalytic activity. However, the unsatisfactory optical absorption and quick recombination of photoinduced electron-hole pairs restrain its photocatalytic antibacterial performance. In this work, silver nanoparticles (AgNPs) were decorated on BP to construct BP@AgNPs nanohybrids and then introduced into poly-l-lactic acid scaffold. Combining the tunable bandgap of BP and the LSPR effect of AgNPs, BP@AgNPs nanohybrids displayed the broaden visible light absorption. Furthermore, AgNPs acted as electron acceptors could accelerate charge transfer and suppress electron-hole recombination. Therefore, BP@AgNPs nanohybrids achieved synergistically enhanced photocatalytic antibacterial activity under visible light irradiation. Fluorescence probe experiment verified that BP@AgNPs promoted the generation of reactive oxygen species, which could disrupt bacteria membrane, damage DNA and oxide proteins, and finally lead to bacteria apoptosis. As a result, the scaffold possessed strong antibacterial efficiency with a bactericidal rate of 97% under light irradiation. Moreover, the scaffold also exhibited good cytocompatibility. This work highlighted a new strategy to develop photocatalytic antibacterial scaffold for bone implant application.

A rat study model of depression-driven chronic prostatitis by modulating the PI3K/Akt/mTOR network.

Depression and chronic prostatitis (CP) are two common diseases that affect the human population worldwide. Clinically, it has been demonstrated that andrological patients often simultaneously suffer from depression and CP. Prior investigations have established that depression acts as an independent risk factor for CP. Herein, we explored the correlation between depression and CP using bioinformatics tools and through animal experiments. The potential targets and signalling pathways involved in depression and CP were predicted using bioinformatics tool, while depression in the rat model was established through chronic restraint stress. The expression of the related proteins and mRNA was assessed by Western blotting and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Relative to those in the control rats, the protein contents of PI3K, p-Akt, and p-mTOR were lower in the model rats (p < 0.05). Similarly, the transcript levels of PI3K, Akt, and mTOR was also relatively lower in the model rats (p < 0.05). And PI3K/Akt agonists reduced inflammation in rat prostate tissue, accompanied by significant increases in the transcript and protein expression levels of PI3K, Akt, and mTOR. Thus, we proposed that depression model rats may induce CP as a result of mediation by the negative regulation of the PI3K/Akt/mTOR signalling network.

Genome-wide identification, phylogenetic analysis, and expression analysis of the SPL gene family in orchardgrass (Dactylis glomerata L.).

SPL (SQUAMOSA promoter binding protein-like) is a plant-specific transcription factor family that contains the conserved SBP domain, which plays a vital role in the vegetative-to-reproductive phase transition, flowering development and regulation, tillering/branching, and stress responses. Although the SPL family has been identified and characterized in various plant species, limited information about it has been obtained in orchardgrass, which is a critical forage crop worldwide. In this study, 17 putative DgSPL genes were identified among seven chromosomes, and seven groups that share similar gene structures and conserved motifs were determined by phylogenetic analysis. Of these, eight genes have potential target sites for miR156. cis-Element and gene ontology annotation analysis indicated DgSPLs may be involved in regulating development and abiotic stress responses. The expression patterns of eight DgSPL genes at five developmental stages, in five tissues, and under three stress conditions were determined by RNA-seq and qRT-PCR. These assays indicated DgSPLs are involved in vegetative-to-reproductive phase transition, floral development, and stress responses. The transient expression analysis in tobacco and heterologous expression assays in yeast indicated that miR156-targeted DG1G01828.1 and DG0G01071.1 are nucleus-localized proteins, that may respond to drought, salt, and heat stress. Our study represents the first systematic analysis of the SPL family in orchardgrass. This research provides a comprehensive assessment of the DgSPL family, which lays the foundation for further examination of the role of miR156/DgSPL in regulating development and stress responses in forages grasses.

Integrated Analysis of Single-Molecule Real-Time Sequencing and Next-Generation Sequencing Eveals Insights into Drought Tolerance Mechanism of Lolium multiflorum.

Lolium multiflorum is widely planted in temperate and subtropical regions globally, and it has high economic value owing to its use as forage grass for a wide variety of livestock and poultry. However, drought seriously restricts its yield and quality. At present, owing to the lack of available genomic resources, many types of basic research cannot be conducted, which severely limits the in-depth functional analysis of genes in L. multiflorum. Therefore, we used single-molecule real-time (SMRT) and next-generation sequencing (NGS) to sequence the complex transcriptome of L. multiflorum under drought. We identified 41,141 DEGs in leaves, 35,559 DEGs in roots, respectively. Moreover, we identified 1243 alternative splicing events under drought. LmPIP5K9 produced two different transcripts with opposite expression patterns, possibly through the phospholipid signaling pathway or the negatively regulated sugar-mediated root growth response to drought stress, respectively. Additionally, 13,079 transcription factors in 90 families were obtained. An in-depth analysis of R2R3-MYB gene family members was performed to preliminarily demonstrate their functions by utilizing subcellular localization and overexpression in yeast. Our data make a significant contribution to the genetics of L. multiflorum, offering a current understanding of plant adaptation to drought stress.

Comparative transcriptome analyses reveal different mechanism of high- and low-tillering genotypes controlling tiller growth in orchardgrass (Dactylis glomerata L.).

BACKGROUND: Tillering is an important agronomic trait underlying the yields and reproduction of orchardgrass (Dactylis glomerata), an important perennial forage grass. Although some genes affecting tiller initiation have been identified, the tillering regulatory network is still largely unknown, especially in perennial forage grasses. Thus, unraveling the regulatory mechanisms of tillering in orchardgrass could be helpful in developing selective strategies for high-yield perennial grasses. In this study, we generated high-throughput RNA-sequencing data from multiple tissues of tillering stage plants to identify differentially expressed genes (DEGs) between high- and low-tillering orchardgrass genotypes. Gene Ontology and pathway enrichment analyses connecting the DEGs to tillering number diversity were conducted. RESULTS: In the present study, approximately 26,282 DEGs were identified between two orchardgrass genotypes, AKZ-NRGR667 (a high-tillering genotype) and D20170203 (a low-tillering genotype), which significantly differed in tiller number. Pathway enrichment analysis indicated that DEGs related to the biosynthesis of three classes of phytohormones, i.e., strigolactones (SLs), abscisic acid (ABA), and gibberellic acid (GA), as well as nitrogen metabolism dominated such differences between the high- and low-tillering genotypes. We also confirmed that under phosphorus deficiency, the expression level of the major SL biosynthesis genes encoding DWARF27 (D27), 9-cis-beta-carotene 9',10'-cleaving dioxygenase (CCD7), carlactone synthase (CCD8), and more axillary branching1 (MAX1) proteins in the high-tillering orchardgrass genotype increased more slowly relative to the low-tillering genotype. CONCLUSIONS: Here, we used transcriptomic data to study the tillering mechanism of perennial forage grasses. We demonstrated that differential expression patterns of genes involved in SL, ABA, and GA biosynthesis may differentiate high- and low-tillering orchardgrass genotypes at the tillering stage. Furthermore, the core SL biosynthesis-associated genes in high-tillering orchardgrass were more insensitive than the low-tillering genotype to phosphorus deficiency which can lead to increases in SL biosynthesis, raising the possibility that there may be distinct SL biosynthesis way in tillering regulation in orchardgrass. Our research has revealed some candidate genes involved in the regulation of tillering in perennial grasses that is available for establishment of new breeding resources for high-yield perennial grasses and will serve as a new resource for future studies into molecular mechanism of tillering regulation in orchardgrass.

Genome-wide identification, structural analysis and expression profiles of GRAS gene family in orchardgrass.

The GRAS gene family is a family of transcription factors that regulates plant growth and development. Despite being well-studied in many plant species, little is known about this gene family in orchardgrass (Dactylis glomerata L.), one of the top four economically important perennial forage grasses cultivated worldwide. We identified 46 GRAS genes in orchardgrass and analyzed their characteristics by phylogenetic, gene structural, motifs and expression patterns analysis. The phylogenetic analysis of eight species revealed that DgGRAS family had the evolutional conservation and closer homology relationship with the GRAS family of rice, barley and Brachypodium distachyon. Moreover, 46 DgGRAS proteins were divided into eight subfamilies based on the tree topology and rice or Arabidopsis classification, and LISCL subfamily was the largest one. Besides, we found that the motif 15 may be unique to the orchardgrass LISCL subfamily, and the motif 6 and motif 17 had indispensable functions in the orchardgrass LISCL subfamily. We further analyzed the expression profiles of DgGRAS genes at mature and seeding stage. And we found that DgGRAS17 played an important role in the growth and development no matter what stage it was at. DgGRAS5, DgGRAS28, DgGRAS31, DgGRAS42 and DgGRAS44 got involved in processes of the growth and development at seeding stage instead of mature stage. These results indicated that the major expression patterns and detailed functions of the DgGRAS genes varied with developmental stages. Taken together, this is the first systematic analysis of the GRAS gene family in the orchardgrass genome and the results provide insights into the potential functions of GRAS genes.

[The Sun Glint Area Reflectance Calculation of VIIRS Middle Infrared Channel in South Indian Ocean Based on Improved Nonlinear Split Window Model].

The energy received through remote sensing sensors contains the amount of reflected solar energy and emitted energy of objects in middle-wave infrared (MWIR, 3~5 µm). Usually, the reflected solar energy is weak in MWIR spectrum. In some certain situations like sun glint area in sea surface, however, the energy is relatively significant and less sensitive to atmospheric effects. Meanwhile, for the satellite sensor which equipped with onboard calibration system, its onboard radiation performance of MWIR(using blackbody calibration)is quite stable. Therefore, the MWIR reflectance in sea surface glint area can be considered as a reference for cross-calibration between the solar reflected bands. Based on this idea, this paper constructed an improved non-linear split window model that is suitable for VIIRS (visible infrared imaging radiometer) MWIR band and used this model to calculate the MWIR reflectance of sun glint area in southern Indian Ocean. This model made statistics, getting the relationship between the reflectance of VIIRS M12 and M13 bands at first, and then used the non-linear split window algorithm to calculate the actual sea surface reflectance. The uncertainty of the simulation model was 0.83%. On this basis, this paper calculated sea surface reflectance of selected sample regions based on the data of VIIRS M12 band (center wavelength: 3.697 µm) in sun glint areas. And then verified the reflectance accuracy by two methods, getting the two accuracies were about 0.239% and 0.23%, respectively. It proves that the calculation model in this paper can greatly improve the accuracy compared to the situation when the sea surface reflectance is between M12 and M13 which are assumed to be equal (accuracy of 2.48% and 1.03%, respectively). It also indicated that the model is feasible and effective to calculate the reflectance in sea surface glint area with VIIRS M12 MWIR band, and the accuracy can meet the requirements of MWIR sea surface reflectance as a calibration reference among bands.

A novel mycovirus identified from the rice false smut fungus Ustilaginoidea virens.

The complete sequence of a novel mycovirus infecting Ustilaginoidea virens, the causal agent of false smut of rice, is reported here and designated as Ustilaginoidea virens unassigned RNA virus HNND-1 (UvURV-HNND-1). This virus has an undivided dsRNA genome of 2903 nt in length and contains two non-overlapping open reading frames (ORF1 and 2), with the small ORF1 encoding a protein of unknown function that showed sequence similarity to the comparable protein in virus Alternaria longipes dsRNA virus 1(AlRV1) and a larger ORF2 encoded the protein showing identities to the RNA-dependent RNA polymerases of AlRV1 and some other unassigned dsRNA viruses. Phylogenetic analysis showed that UvURV-HNND-1 is more closely related to unclassified viruses such as AlRV1 and distinct from distantly related members of the family Partitiviridae. Here, we propose in accordance with previous reports that UvURV-HNND-1 might belong to a new mycovirus genus together with AlRV1 and other similar viruses.

Removal of chromium from aqueous solutions using modified lettuce leaves.

This article reports on an investigation into the ability of modified lettuce leaves to extract chromium ions from aqueous solutions. These exciting new materials were prepared via rapid (5 h) environmentally friendly synthesis routes avoiding any secondary pollution. The influence of pH, metal concentration, the adsorption of the added amount, and water temperature on the selectivity and sensitivity of the removal process was investigated. The maximum theoretical adsorption rate of modified lettuce leaves, evaluated by the Langmuir adsorption model, was 99.98%. The proposed method was applied in the determination of Cr(6+) in a sample of aqueous solution and was validated by comparison with activated carbon.

Identifying competing endogenous RNA regulatory networks and hub genes in alcoholic liver disease for early diagnosis and potential therapeutic target insights.

Alcoholic liver disease (ALD) has a complex pathogenesis. Although early-stage ALD can be reversed by ceasing alcohol consumption, early symptoms are difficult to detect, and several factors contribute to making alcohol difficult to quit. Continued alcohol abuse worsens the condition, meaning it may gradually progress into alcoholic hepatitis and cirrhosis, ultimately, resulting in irreversible consequences. Therefore, effective treatments are urgently needed for early-stage ALD. Current research mainly focuses on preventing the progression of alcoholic fatty liver to alcoholic hepatitis and cirrhosis. However, challenges remain in identifying key therapeutic targets and understanding the molecular mechanisms that underlie the treatment of alcoholic hepatitis and cirrhosis, such as the limited discovery of effective therapeutic targets and treatments. Here, we downloaded ALD microarray data from Gene Expression Omnibus and used bioinformatics to compare and identify the hub genes involved in the progression of alcoholic fatty liver to alcoholic hepatitis and cirrhosis. We also predicted target miRNAs and long non-coding RNAs (lncRNAs) to elucidate the regulatory mechanisms (the mRNA-miRNA-lncRNA axis) underlying this progression, thereby building a competitive endogenous RNA (ceRNA) mechanism for lncRNA, miRNA, and mRNA. This study provides a theoretical basis for the early treatment of alcoholic hepatitis and cirrhosis and identifies potential therapeutic targets.

A tumor-microenvironment-activated nanoplatform of modified SnFe2O4 nanozyme in scaffold for enhanced PTT/PDT tumor therapy.

Phototherapy has attracted widespread attention for cancer treatment due to its noninvasiveness and high selectivity. However, severe hypoxia, overexpressed glutathione and high levels of hydrogen peroxide (H2O2) of tumor microenvironment limit the antitumor efficiency of phototherapy. Herein, inspired by the specific response of nanozymes to the tumor microenvironment, a simple and versatile nanozyme-mediated synergistic dual phototherapy nanoplatform is constructed. In this study, tin ferrite (SnFe2O4, SFO) nanozyme as a photosensitizer was surface modified with polydopamine (denoted as P-SFO) and incorporated into poly(l-lactide) to fabricate an antitumor scaffold fabricated by selective laser sintering. On one hand, SFO nanozyme could act as a photoabsorber to convert light energy into heat for photothermal therapy (PTT). On the other hand, it played a role of photosensitizer in transferring the photon energy to generate reactive oxygen species (ROS) for photodynamic therapy (PDT). Importantly, its multivalent metal ions redox couples would decompose H2O2 into O2 for enhancing O2-dependent PDT and consume glutathione to relieve antioxidant capability of the tumors. Besides, polydopamine as a photothermal conversion agent further enhanced the photothermal performance of SFO. The results revealed the PLLA/P-SFO scaffold possessed a photothermal conversion efficiency of 43.52% for PTT and a high ROS generation capacity of highly toxic ·O2- and ·OH for PDT. Consequently, the scaffold displayed a prominent phototherapeutic effect with antitumor rate of 96.3%. In addition, the PLLA/P-SFO scaffolds possessed good biocompatibility for cell growth. These advantages endow PLLA/P-SFO scaffold with extensive applications in biomedical fields and opened up new avenue towards nanozyme-mediated synergistic phototherapy.

Hyaluronic acid encapsulated silver metal organic framework for the construction of a slow-controlled bifunctional nanostructure: Antibacterial and anti-inflammatory in intrauterine adhesion repair.

Intrauterine adhesion (IUA) is a common gynecological disease caused by endometrial injury, which might result in abnormal menstruation, miscarriage, and even fetal deaths. Nevertheless, existing treatment strategies such as intrauterine device and uterine cavity balloons only provide a physical barrier, and not circumvent inflammation of endometrial microenvironment and retrograde infection. In this study, a slow-controlled bifunctional nanostructure was developed via encapsulating hyaluronic acid (HA) on surface of silver-metal organic framework (Ag-MOF), and then loaded in poly lactic-co-glycolic acid scaffold to prevent IUA. In therapy, macro-molecule of HA provided anti-inflammatory function by the adjustment of signal transduction pathways of macrophage surface receptors, whereas Ag-MOF inactivated bacteria by destroying bacterial membrane and producing reactive oxygen. Significantly, the coated HA effectively avoided burst release of Ag+, thus achieving long-term antibacterial property and good biocompatibility. Antibacterial results showed antibacterial rate of the scaffold reached 87.8 % against staphylococcus aureus. Anti-inflammatory assays showed that the scaffold inhibited the release of inflammatory cytokines and promoted the release of anti-inflammatory cytokines. Moreover, in vitro cell tests revealed that the scaffold effectively inhibited fibroblast growth, indicating its good ability to prevent IUA. Taken together, the scaffold may be a promising candidate for IUA treatment.

Accelerated anode and cathode reaction due to direct electron uptake and consumption by manganese dioxide and titanium dioxide composite cathode in degradation of iron composite.

The movement towards the clinical application of iron (Fe) has been hindered by the slow degradation rate in physiological environments. Herein, manganese dioxide (MnO2) particles were compounded with titanium dioxide (TiO2) particles by mechanical ball milling, and then the mixed powders were incorporated into Fe and fabricated into an implant using selective laser melting. On the one hand, MnO2 had a higher work function (5.21 eV) than Fe (4.48 eV), which inclined electrons to transfer from Fe to MnO2 to accelerate the anode reaction. On the other hand, MnO2 catalysed the oxygen reduction reaction (ORR) through a four-step proton-electron-coupled reaction, which caused more oxygen to flow into the sample to improve the cathode performance. Besides, anatase TiO2 with high conductivity was compounded with MnO2 to construct a composite cathode, which facilitated electron transport from the cathode to the electrolyte, further consuming electrons and promoting cathode reaction. Results showed that Fe-MnO2-TiO2 had a high limiting current density of 5.32 mA·cm-2 and a large half-wave potential of -767.4 mV, indicating an enhanced ORR activity. More significantly, Fe-MnO2-TiO2 had a higher average electron transfer number (2.9) than Fe-MnO2 (2.5), demonstrating a faster electronic consumption reaction and higher cathode performance. In addition, the Fe-MnO2-TiO2 also exhibited fast instantaneous and long-term degradation rates (0.33 ± 0.03 and 0.19 ± 0.02 mm/year), suggesting a high anode dissolution rate. In conclusion, introducing the cathode with high work function and ORR activity provides novel pathways for accelerating the degradation rate of Fe-based implants.

A bifunctional zoledronate sustained-release system in scaffold: Tumor therapy and bone repair.

It is of great challenges to repair bone defect and prevent tumor recurrence in bone tumors postoperative treatment. Bone scaffolds loaded with zoledronate (ZOL) are expected to solve these issues due to its osteogenesis and anti-tumor ability. Furthermore, ZOL needs to be sustained release to meet the requirement of long-term therapy. In this study, ZOL was loaded into amination functionalized mesoporous silicon (SBA15NH2), and then incorporated into poly (L-lactic acid) to prepare PLLA/SBA15NH2-ZOL scaffold via selective laser sintering technology. On one hand, ZOL of local release not only can inhibit growth and proliferation of bone tumor cells but also inhibit osteoclast differentiation through competitive binding of receptor activator of nuclear factor (NF)-kB (RANK) in osteoclast precursors. On the other hand, amination function could change the surface charge of mesoporous silica to positive charge to enhance the absorption of ZOL, mesoporous structure and abundant amino groups of SBA15NH2 play a barrier role and form hydrogen bond with phosphate groups of ZOL, respectively, thereby achieving its sustained release. The results showed that the loading amount of ZOL was 236.53 mg/g, and the scaffold could sustainedly release ZOL for more than 6 weeks. The scaffold inhibited proliferation of osteosarcoma cells through inducing apoptosis and cell cycle arrest. TRAP staining and F-actin ring formation experiment showed the scaffold inhibited differentiation and mature of osteoclast. Pit formation assay indicated that bone resorption activity was inhibited strongly.

A spatiotemporal drug release scaffold with antibiosis and bone regeneration for osteomyelitis.

INTRODUCTION: Scaffolds loaded with antibacterial agents and osteogenic drugs are considered essential tools for repairing bone defects caused by osteomyelitis. However, the simultaneous release of two drugs leads to premature osteogenesis and subsequent sequestrum formation in the pathological situation of unthorough antibiosis. OBJECTIVES: In this study, a spatiotemporal drug-release polydopamine-functionalized mesoporous silicon nanoparticle (MSN) core/shell drug delivery system loaded with antibacterial silver (Ag) nanoparticles and osteogenic dexamethasone (Dex) was constructed and introduced into a poly-l-lactic acid (PLLA) scaffold for osteomyelitis therapy. METHODS: MSNs formed the inner core and were loaded with Dex through electrostatic adsorption (MSNs@Dex), and then polydopamine was used to seal the core through the self-assembly of dopamine as the outer shell (pMSNs@Dex). Ag nanoparticles were embedded in the polydopamine shell via an in situ growth technique. Finally, the Ag-pMSNs@Dex nanoparticles were introduced into PLLA scaffolds (Ag-pMSNs@Dex/PLLA) constructed by selective laser sintering (SLS). RESULTS: The Ag-pMSNs@Dex/PLLA scaffold released Ag+ at the 12th hour, followed by the release of Dex starting on the fifth day. The experiments verified that the scaffold had excellent antibacterial performance against Escherichia coli and Staphylococcus aureus. Moreover, the scaffold significantly enhanced the osteogenic differentiation of mouse bone marrow mesenchymal stem cells. CONCLUSION: The findings suggested that this spatiotemporal drug release scaffold had promising potential for osteomyelitis therapy.

Silicon dioxide nanoparticles decorated on graphene oxide nanosheets and their application in poly(l-lactic acid) scaffold.

INTRODUCTION: The aggregation of graphene oxide (GO) is considered as main challenge, although GO possesses excellent mechanical properties which arouses widespread attention as reinforcement for polymers. OBJECTIVES: In this study, silicon dioxide (SiO2) nanoparticles were decorated onto surface of GO nanosheets through in situ growth method for promoting dispersion of GO in poly(l-lactic acid) (PLLA) bone scaffold. METHODS: Hydroxyl and carboxyl functional groups of GO provided sites for SiO2 nucleation, and SiO2 grew with hydrolysis and polycondensation of tetraethyl orthosilicate (TEOS) and finally formed nanoparticles onto surface of GO with covalent bonds. Then, the GO@ SiO2 nanocomposite was blended with PLLA for the fabrication of bone scaffold by selective laser sintering (SLS). RESULT: The results indicated that the obtained SiO2 were distributed relatively uniformly on surface of GO under TEOS concentration of 0.10 mol/L (GO@SiO2-10), and the covering of SiO2 on GO could increase interlayer distance of GO nanosheets from 0.799 nm to 0.894 nm, thus reducing van der Waals forces between GO nanosheets and facilitating the dispersion. Tensile and compressive strength of scaffold containing GO@SiO2 hybrids were significantly enhanced, especially for the scaffold containing GO@SiO2-10 hybrids with enhancement of 30.95 % in tensile strength and 66.33 % in compressive strength compared with the scaffold containing GO. Additionally, cell adhesion and fluorescence experiments demonstrated excellent cytocompatibility of the scaffold. CONCLUSIONS: The good dispersion of GO@SiO2 enhances the mechanical properties and cytocompatibility of scaffold, making it a potential candidate for bone tissue engineering applications.

Bioinformatics Analysis of Novel Targets for Treating Cervical Cancer by Immunotherapy Based on Immune Escape.

BACKGROUND/AIM: Cervical cancer (CC) is a high-risk disease in women, and advanced CC can be difficult to treat even with surgery, radiotherapy, and chemotherapy. Hence, developing more effective treatment methods is imperative. Cancer cells undergo a renewal process to escape immune surveillance and then attack the immune system. However, the underlying mechanisms remain unclear. Currently, only one immunotherapy drug has been approved by the Food and Drug Administration for CC, thus indicating the need for and importance of identifying key targets related to immunotherapy. MATERIALS AND METHODS: Data on CC and normal cervical tissue samples were downloaded from the National Center for Biotechnology Information database. Transcriptome Analysis Console software was used to analyze differentially expressed genes (DEGs) in two sample groups. These DEGs were uploaded to the DAVID online analysis platform to analyze biological processes for which they were enriched. Finally, Cytoscape was used to map protein interaction and hub gene analyses. RESULTS: A total of 165 up-regulated and 362 down-regulated genes were identified. Among them, 13 hub genes were analyzed in a protein-protein interaction network using the Cytoscape software. The genes were screened out based on the betweenness centrality value and average degree of all nodes. The hub genes were as follows: ANXA1, APOE, AR, C1QC, CALML5, CD47, CTSZ, HSP90AA1, HSP90B1, NOD2, THY1, TLR4, and VIM. We identified the following 12 microRNAs (miRNAs) that target the hub genes: hsa-miR-2110, hsa-miR-92a-2-5p, hsa-miR-520d-5p, hsa-miR-4514, hsa-miR-4692, hsa-miR-499b-5p, hsa-miR-5011-5p, hsa-miR-6847-5p, hsa-miR-8054, hsa-miR-642a-5p, hsa-miR-940, and hsa-miR-6893-5p. CONCLUSION: Using bioinformatics, we identified potential miRNAs that regulated the cancer-related genes and long noncoding RNAs (lncRNAs) that regulated these miRNAs. We further elucidated the mutual regulation of mRNAs, miRNAs, and lncRNAs involved in CC occurrence and development. These findings may have major applications in the treatment of CC by immunotherapy and the development of drugs against CC.