Genome editing in rice using CRISPR/Cas12i3.

The CRISPR/Cas type V-I is a family of programmable nuclease systems that prefers a T-rich protospacer adjacent motif (PAM) and is guided by a short crRNA. In this study, the genome-editing application of Cas12i3, a type V-I family endonuclease, was characterized in rice. We developed a CRIPSR/Cas12i3-based Multiplex direct repeats (DR)-spacer Array Genome Editing (iMAGE) system that was efficient in editing various genes in rice. Interestingly, iMAGE produced chromosomal structural variations with a higher frequency than CRISPR/Cas9. In addition, we developed base editors using deactivated Cas12i3 and generated herbicide-resistant rice plants using the base editors. These CRIPSR/Cas12i3-based genome editing systems will facilitate precision molecular breeding in plants.

[Effect of printing orientation on physical and mechanical properties of 3D printing prosthodontic base resin materials].

OBJECTIVE: To analyze the influence of forming direction on the surface characteristics, elastic modulus, bending strength and fracture toughness of printed parts and the relationship between forming direction and force direction, and to provide scientific basis and guidance for the clinical application of oral denture base resin materials. METHODS: The 3D printing technology was used to print denture base resin samples. The shape and size of the samples referred to the current standard for testing conventional denture base materials. The samples used for physical performance testing were cylindrical (with a diameter of 15 mm and a thickness of 1 mm) and printed at different angles along the Z axis (0°, 45°, 90°). Scanning electron microscope was used to observe the microscopic topography of the different samples. The color stability of different samples was observed by color stabilizer. The surface roughness of the samples was analyzed by using surface roughness tester. The Vickers hardness was measured to analyze the hardness of the samples. The samples used for mechanical performance testing were rectangular (elastic modulus and bending strength: A length of 64 mm, a width of 10 mm, and a height of 3.3 mm; fracture toughness: A length of 39 mm, a width of 8 mm, and a height of 4 mm), divided into two groups: W group and H group. The W group was printed from the bottom up along the Z axis with the length × width as the bottom surface parallel to the X, Y axis plane, while the H group printed from the bottom up along the Z axis with the length × height as the bottom surface parallel to the X, Y axis plane. The forming angles of both groups were equally divided into 0°, 45°, and 90°. The elastic modulus, bending strength and fracture toughness of different samples were studied through universal mechanical testing machine. SPSS 22.0 software was used for statistical analysis. RESULTS: The microscopic topography and roughness of different samples were closely related to the printing direction, with significant differences between the 0°, 45°, and 90° specimens. The 0° specimens had the smoothest surface (roughness < 1 µm). The surface of the 45° specimen was the roughest (roughness>3 µm). The microhardness of the 0° sample was the best [(196.13±0.20) MPa], with a significant difference compared with the 90° sample [(186.62±4.81) MPa, P < 0.05]. The mechanical properties of different samples were also closely related to the printing direction. The elastic modulus, bending strength, and fracture toughness of the 45° samples in the W group were the highest compared with the other groups. The results of elastic modulus showed that in the H group, the 45° specimens had the highest elastic mo-dulus, which was significantly different from the 0° and 90° specimens (P < 0.05). The elastic modulus of 0° and 45° specimens in the W group were higher than those in 90° specimens (P < 0.05). The bending strength results showed that there was no significant difference between the specimens from dif-ferent angles in the H group. The bending strength of the 90° specimens in the W group was the smallest, and there was a significant difference between 90° and the 0° and 45° specimens (P < 0.05); And the bendind strength of the 0° and 45° specimens in the W group was significantly higher than that of the 0° and 45° specimens in the H group (P < 0.05). The fracture toughness results showed that the fracture toughness of the H group specimens was lower than 1.9 MPa m1/2, which was specified in the denture base standard. The 45° samples in the W group were the highest, with significant differences compared with the 0° and 90° samples (P < 0.05). And the 90° samples of the W group specimens were lower than 1.9 MPa m1/2. And the fracture toughness of the 45° specimen in the W group was significantly higher than that of all the specimens in the H group (P < 0.05). CONCLUSION: The 0° samples had relatively better physical properties. The 45° samples had the best mechanical properties. But the fracture toughness of specimens (H group and 90° samples of W group) did not yet meet clinical requirements. That indicated that the characteristics of the 3D printing denture base resin were affected by the printing direction. Only when the performance of the printed samples in all directions met the minimum requirements of the standard, they could be used in clinical practice.

In Situ Spatial Analysis of Metabolic Heterogeneity in Single Living Tumor Spheroids Using Nanocapillary-Based Electrospray Ionization Mass Spectroscopy.

Spatial metabolomic analysis of individual tumor spheroids can help investigate metabolic rearrangements in different cellular regions of a spheroid. In this work, a nanocapillary-based electrospray ionization mass spectroscopy (ESI-MS) method is established that could realize the spatial sampling of cellular components in different regions of a single living tumor spheroid and the subsequent MS analysis for a metabolic study. During the penetration of the nanocapillary into the spheroid for sampling, this "wound surface" at the outer layer of the spheroid takes only 0.1% of the whole area that maximally maintains the cellular activity inside the spheroid for the metabolic analysis. Using the ESI-MS analysis, different metabolic activities in the inner and outer (upper and lower) layers of a single spheroid are revealed, giving a full investigation of the metabolic heterogeneity inside one living tumor spheroid for the first time. In addition, the metabolic activities between the outer layer of the spheroid and two-dimensional (2D)-cultured cells show obvious differences, which suggests more frequent cell-cell and cell-extracellular environment interactions during the culture of the spheroid. This observation not only establishes a powerful tool for the in situ spatial analysis of the metabolic heterogeneity in single living tumor spheroids but also provides molecular information to elucidate the metabolic heterogeneity in this three-dimensional (3D)-cultured cell model.

Elevated serum anti-Saccharomyces cerevisiae antibody accompanied by gut mycobiota dysbiosis as a biomarker of diagnosis in patients with de novo Parkinson disease.

BACKGROUND AND PURPOSE: Intestinal inflammation and gut microbiota dysbiosis contribute to Parkinson disease (PD) pathogenesis, and growing evidence suggests associations between inflammatory bowel diseases (IBD) and PD. Considered as markers of chronic gastrointestinal inflammation, elevated serum anti-Saccharomyces cerevisiae antibody (ASCA) levels, against certain gut fungal components, are related to IBD, but their effect on PD is yet to be investigated. METHODS: Serum ASCA IgG and IgA levels were measured using an enzyme-linked immunosorbent assay, and the gut mycobiota communities were investigated using ITS2 sequencing and analyzed using the Qiime pipeline. RESULTS: The study included 393 subjects (148 healthy controls [HCs], 140 with PD, and 105 with essential tremor [ET]). Both serum ASCA IgG and IgA levels were significantly higher in the PD group than in the ET and HC groups. Combining serum ASCA levels and the occurrence of constipation could discriminate patients with PD from controls (area under the curve [AUC] = 0.81, 95% confidence interval [CI] = 0.76-0.86) and from patients with ET (AUC = 0.85, 95% CI = 0.79-0.89). Furthermore, the composition of the gut fungal community differed between the PD and HC groups. The relative abundances of Saccharomyces cerevisiae, Aspergillus, Candida solani, Aspergillus flavus, ASV601_Fungi, ASV866_Fungi, and ASV755_Fungi were significantly higher in the PD group, and enriched Malassezia restricta was found in the HC group. CONCLUSIONS: Our study identified elevated serum ASCA levels and enriched gut Saccharomyces cerevisiae in de novo PD.

Two Decarestrictine Analogs from the Soil-Derived Fungus Penicillium sp. YUD18003 Associated with Gastrodia elata.

Two new decarestrictine analogs decarestrictine P and penicitone, together with eight known homologous compounds were isolated from the soil fungus from the rhizosphere of Penicillium sp. YUD18003 related to Gastrodia elata. Their different structures include a decanolides decartestridine P and a long-chain polyhydroxyketone penicitone. The structures of new compounds were determined by nuclear magnetic resonance (NMR) spectroscopic analysis and high resolution electrospray ionization mass spectrometry (HR-ESI-MS), while their absolute configurations were determined by spectroscopic methods, DP4+ probability analysis, modified Snatzke's method and electron circular dichroism (ECD) calculations. All compounds were evaluated for antimicrobial activities.

pH Stimuli-Responsive, Rapidly Self-healable Coatings Enhanced the Corrosion Resistance and Osteogenic Differentiation of Mg-1Ca Osteoimplant.

Mg-Ca alloys have emerged as a promising research direction for biomedical implants in the orthopedic field. However, their clinical use is deterred by their fast corrosion rate. In this work, a pH stimuli-responsive silk-halloysite (HNT)/phytic acid (PA) self-healing coating (Silk-HNT/PA) is constructed to slow down the corrosion rate of Mg-1Ca alloy and its cell viability and osteogenic differentiation ability are enhanced. The Silk-HNT/PA coating exhibits appealing active corrosion protection, by eliciting pH-triggerable self-healing effects, while simultaneously affording superior biocompatibility and osteogenic differentiation ability. Moreover, in vivo studies by histological analysis also demonstrate better osseointegration for the Silk-HNT/PA coated Mg-1Ca alloy. In summary, the Silk-HNT/PA coating in the present study has great potential in enhancing the biomedical utility of Mg alloys.

Mg/Al-LDH as a nano-adjuvant for pertussis vaccine: a evaluation compared with aluminum hydroxide adjuvant.

Background. Layered double hydroxide (LDH) has been demonstrated as a highly efficient antigen platform to induce effective and durable immune response. However, whether LDH nanoparticles could act as an adjuvant for pertussis vaccines is still unknown. Here we evaluated the potential of Mg/Al-LDH as a nano-adjuvant to improve immune response against pertussis and compared it with commercial aluminum hydroxide (AH) adjuvant.Method. The Mg/Al-LDH nanoparticles were synthesized by a hydrothermal reaction. The morphology, structure and size of Mg/Al-LDH were characterized by transmission electron microscope, x-ray diffraction and MALVERN particle analysis. The ovalbumin and Pertussis toxin (PTd) was adsorbed to Mg/Al-LDH. The immune response of antigen-LDH complex was evaluated in mice, compared with commercial adjuvant alum. Hematoxylin-eosin staining was used to evaluate the inflammatory response at injection site.Results. The synthetic Mg/Al-LDH nanoparticles showed a typical hexagonal lamellar structure. The average size of synthetic nanoparticles was 102.9 nm with PDI of 0.13 and zeta potential was 44.4 mV. Mg/Al-LDH nanoparticles effectively adsorbed protein antigen and mediated antigen uptake by DC cells. Animal experiments showed that Mg/Al-LDH gave enhancement in anti-pertussis toxin (PTd) humoral immune response, which was considerable to commercial AH adjuvant. Finally, Mg/Al-LDH produced a slighter inflammatory response than AH at injection site and this injury was quickly recovered.Conclusion. Our study demonstrated the potential of Mg/Al-LDH as an effective adjuvant for pertussis vaccine, which induced comparable antibody response and had a better safety compared with commercial AH adjuvant.

Nucleocapsid protein of SARS-CoV-2 is a potential target for developing new generation of vaccine.

BACKGROUND: SARS-CoV-2 has spread worldwide causing more than 400 million people with virus infections since early 2020. Currently, the existing vaccines targeting the spike glycoprotein (S protein) of SARS-CoV-2 are facing great challenge from the infection of SARS-CoV-2 virus and its multiple S protein variants. Thus, we need to develop a new generation of vaccines to prevent infection of the SARS-CoV-2 variants. Compared with the S protein, the nucleocapsid protein (N protein) of SARS-CoV-2 is more conservative and less mutations, which also plays a vital role in viral infection. Therefore, the N protein may have the great potential for developing new vaccines. METHODS: The N protein of SARS-CoV-2 was recombinantly expressed and purified in Escherichia coli. Western Blot and ELISA assays were used to demonstrate the immunoreactivity of the recombinant N protein with the serum of 22 COVID-19 patients. We investigated further the response of the specific serum antibodies and cytokine production in BALB/c mice immunized with recombinant N protein by Western Blot and ELISA. RESULTS: The N protein had good immunoreactivity and the production of IgG antibody against N protein in COVID-19 patients was tightly correlated with disease severity. Furthermore, the N protein was used to immunize BALB/c mice to have elicited strong immune responses. Not only high levels of IgG antibody, but also cytokine-IFN-γ were produced in the N protein-immunized mice. Importantly, the N protein immunization induced a high level of IgM antibody produced in the mice. CONCLUSION: SARS-CoV-2 N protein shows a great big bundle of potentiality for developing a new generation of vaccines in fighting infection of SARS-CoV-2 and its variants.

Comparative transcriptomic analysis reveals mechanisms of divergence in osmotic regulation of the turbot Scophthalmus maximus.

The turbot Scophthalmus maximus has evolved extensive physiological ability to adapt to multiple environmental salinities. The morphological changes of the kidney indicated the adaptability difference and similarity of turbot to salinity stress. Identify transcriptome-wide differences between low-salinity seawater (LSW, salinity 5)- and high-salinity seawater (HSW, salinity 50)-acclimated kidneys of turbot to decipher the osmotic regulation mechanism. We identified 688 differentially expressed genes (DEGs) in the LSW-acclimated kidneys and 2441 DEGs in the HSW-acclimated kidneys of turbot compared with seawater-acclimated kidneys, respectively. We investigated three patterns of gene regulation to salinity stress that involved in ion channels and transporters, functions of calcium regulation, organic osmolytes, energy demand, cell cycle regulation, and cell protection. Additionally, protein-protein interaction (PPI) analysis of DEGs suggested the presence of a frequent functional interaction pattern and that crucial genes in the PPI network are involved in hyper-osmotic regulation. Based on the analysis of comparative transcriptome data and related literature reports, we conclude that the mechanisms responsible for osmotic regulation and its divergence in turbot are related to various genes that are involved in canonical physiological functions. These findings provide insight into the divergence in osmoregulation of turbot and valuable information about osmoregulation mechanisms that will benefit other studies in this field.

Cloning and molecular characterization of PRL and PRLR from turbot (Scophthalmus maximus) and their expressions in response to short-term and long-term low salt stress.

The pituitary hormone prolactin (PRL) regulates salt and water homeostasis by altering ion retention and water uptake through peripheral osmoregulatory organs. To understand the role of PRL and its receptor (PRLR) in hypoosmoregulation of turbot (Scophthalmus maximus), we characterized the PRL and PRLR gene and analyzed the tissue distribution of the two genes and their gene transcriptional patterns in the main expressed tissues under long-term and short-term low salt stress. The PRL cDNA is 1486 bp in length, incorporating an ORF of 636 bp with a putative primary structure of 211 residues. And the PRLR cDNA is 2849 bp in length, incorporating an ORF of 1944 bp with a putative primary structure of 647 residues. The deduced amino acid sequences of these two genes shared highly conserved structures with those from other teleosts. Quantitative real-time PCR results showed that PRL transcripts were strongly expressed in the pituitary and very weakly in brain, but were hardly expressed in other tissues. PRLR transcripts were most abundant in the kidney, to a lesser extent in the gill, intestine, brain, and spleen, and at low levels in the pituitary and other tissues examined. The expression of PRL in the pituitary increased after short-term or long-term low salt stress, and the highest expression level appeared 12 h after stress (P < 0.05). And there is no significant difference between both low salt group (5 ppt and 10 ppt) at each sampling point. The variation of PRLR expression in gill under short-term low salt stress is similar to that of PRL gene in pituitary, with highest value in 12 h (P < 0.05). However, the expression under long-term low salt stress was significantly higher than control group even than 12 h group under 5 ppt (P < 0.05). The expression of PRLR in the kidney increased first and then decreased after low salt stress, and the highest value also appeared in 12 h after stress and there was no significant difference between the salinity groups. After long-term low salt stress, the expression level also increased significantly (P < 0.05), but it was flat with 24 h, which was lower than 12 h. The variation of PRLR expression in the intestine was basically consistent with that in the kidney. The difference was that the expression level of 24 h after stress in the 5 ppt group was significantly higher than that of the 10 ppt group (P < 0.05). After a comprehensive analysis of the expression levels of the two genes, it can be found that the expression level increased and peaked at 12 h after short-term low salt stress, indicating that this time point is the key point for the regulation of turbot in response to low salt stress. This also provides very important information for studying the osmotic regulation of turbot. In addition, our results also showed that the expression of PRLR was stable in the kidney and intestine after long-term low salt stress, while the expression in the gill was much higher than short-term stress. It suggested that PRL and its receptors mainly exert osmotic regulation function in the gill under long-term low salt stress. At the same time, such a result also brings a hint for the low salt selection of turbot, focusing on the regulation of ion transport in the gill.

Capn4 Enhances Osteopontin Expression through Activation of the Wnt/ß-Catenin Pathway to Promote Epithelial Ovarian Carcinoma Metastasis.

BACKGROUND AND AIM: Increasing evidence shows that the calpain regulatory subunit Capn4 can modulate the proliferation and metastasis of cancer cells, and plays an important role in the development of malignant tumors. However, there is no information on the clinical significance of Capn4 in epithelial ovarian carcinoma (EOC) or the molecular mechanisms by which Capn4 promotes the growth and metastasis of EOC. Therefore, the aim of this study was to clarify the role of Capn4 in EOC. METHODS: We evaluated Capn4 and osteopontin (OPN) expression in EOC cell lines and tissues from patients with ovarian cancer by western blotting and immunohistochemical analysis. We then created cell lines with downregulated and upregulated Capn4 expression, using Capn4-targeting small interfering RNA and a pcDNA3.1-Capn4 overexpression vector, respectively, to investigate its function in EOC in vitro. In addition, we investigated the potential mechanism underlying the function of Capn4 by examining the effect of modifying Capn4 expression on Wnt/ß-catenin signaling pathway-related genes by western blotting. RESULTS: Capn4 was overexpressed in clinical EOC tissues compared with that in normal ovarian epithelial tissue, and was associated with poor clinical outcomes. Upon silencing or overexpressing Capn4 in EOC cells, we concluded that Capn4 promotes cell proliferation and migration in vitro. Furthermore, Capn4 promoted EOC metastasis by interacting with the Wnt/ß-catenin signaling pathway to upregulate OPN expression. CONCLUSION: Our study indicates that Capn4 plays a critical role in the progression and metastasis of EOC, and could be a potential therapeutic target for EOC management.

Over-expression of CHAF1A in Epithelial Ovarian Cancer can promote cell proliferation and inhibit cell apoptosis.

Chromatin Assembly Factor 1, subunit A (CHAF1A) can regulate cell proliferation, DNA repair and epigenetic changes in embryonic stem cells and it has been reported that over-expression of CHAF1A is associated with several human diseases including cancer. However, the expression and function of CHAF1A in Epithelial Ovarian Cancer (EOC) are rarely reported at present. In this study, we found that the positive staining of CHAF1A in EOC was higher than that in normal tissues and over-expression of CHAF1A was strongly associated with cancer stage and lymph node metastasis. Knockdown of CHAF1A by siRNA in EOC inhibited cell proliferation, reduced colony formation, caused G0/G1 phase arrest and promoted cell apoptosis. Taken together, the high expression of CHAF1A promotes cell proliferation and inhibits cell apoptosis and CHAF1A may be developed as a prognosis biomarker and potential therapeutic target of EOC.

Immunological characterization and expression of lily-type lectin in response to environmental stress in turbot (Scophthalmus maximus).

Lectins are a superfamily of carbohydrate-binding proteins that are widely distributed throughout living organisms. In earlier work, we identified lily-type lectin (SmLTL) in the skin mucus of turbot Scophthalmus maximus, and we characterized the protein in the present study. Results from qRT-PCR indicated that SmLTL was expressed highly in skin, intestine and gill tissue. Changes in SmLTL expression occurred in these tissues in response to environmental stressors including ciliate infection, high temperature and salinity. Recombinant SmLTL purified from Escherichia coli was able to haemagglutinate mouse erythrocytes in the absence of calcium, and was inhibited by d-mannose. In addition, SmLTL displayed selective binding to bacterial species including Edwardsiella tarda and Vibrio anguillarum, and exhibited toxicity towards Philasterides dicentrarchi, with a mortality of over 60% after 24 h at a concentration of only 100 µgml-1. To investigate this toxicity further, we measured binding of SmLTL after incubating the ciliate in FITC-SmLTL solution. Surface fluorescence decreased substantially in the presence of 400 mM d-mannose. Together these results suggest that lily-type lectins serve as the first line of defence against microbial attack and play a pivotal role in the mucosal immune system.

Alantolactone induces G1 phase arrest and apoptosis of multiple myeloma cells and overcomes bortezomib resistance.

Several sesquiterpene lactones have been extracted and demonstrated to exert various pharmacological functions in a variety of cancers. Here, we investigated anti-tumor effect of alantolactone, an allergenic sesquiterpene lactone, on human multiple myeloma (MM) and showed alantolactone inhibited growth of MM cells, both in the presence or absence of bone marrow (BM)-derived stromal cells (HS-5), and subsequent G1 phase arrest, and apoptosis as demonstrated by increased Annexin-V/7-AAD binding, caspase-3 or caspase-9 activation and down-modulation of activation of extracellular signal-regulated kinases 1/2. In addition, alantolactone reduced the secretion of MM survival and growth-related cytokines, vascular endothelial growth factor, from MM cells or HS-5 cells, and inhibited cytokine-induced osteoclastogenesis. Notably, alantolactone also inhibited cell proliferation in bortezomib-resistant MM cells. Taken together, alantolactone exerted anti-tumor effect on MM by suppressing cell proliferation, triggering apoptosis, partly damaging the BM microenvironment and overcoming proteasome inhibitor resistance, suggesting alantolactone may be a novel therapeutic approach for the treatment of human MM.

CeO2 Nanoparticles to Promote Wound Healing: A Systematic Review.

Cerium (Ce) is a hot topic in the field of materials research due to its electronic layer structure and the unique antioxidant abilities of its oxide (CeO2 ). Cerium oxide nanoparticles (CeO2 NPs) demonstrate their potential as an antioxidant and antibacterial agent. Current research focuses on whether they can be used to promote wound healing and in what manner. This article provides a systematic review of the various forms of CeO2 NPs that are used in wound-healing materials over the past decade, as well as the effectiveness demonstrated by in vivo and in vitro experiments, with a focus on the relationship between concentration and effectiveness. CeO2 NPs are expected to become effective ingredients in dressings that require antibacterial, antioxidant, and wound healing promoting properties. This article serves as a reference for further research and clinical applications of nano-sized CeO2 in wound healing.

Zeolite imidazolate framework-8 in bone regeneration: A systematic review.

Zeolite imidazolate framework-8 (ZIF-8) is a biomaterial that has been increasingly studied in recent years. It has several applications such as bone regeneration, promotion of angiogenesis, drug loading, and antibacterial activity, and exerts multiple effects to deal with various problems in the process of bone regeneration. This systematic review aims to provide an overview of the applications and effectiveness of ZIF-8 in bone regeneration. A search of papers published in the PubMed, Web of Science, Embase, and Cochrane Library databases revealed 532 relevant studies. Title, abstract, and full-text screening resulted in 39 papers being included in the review, including 39 in vitro and 22 animal studies. Appropriate concentrations of nano ZIF-8 can promote cell proliferation and osteogenic differentiation by releasing Zn2+ and entering the cell, whereas high doses of ZIF-8 are cytotoxic and inhibit osteogenic differentiation. In addition, five studies confirmed that ZIF-8 exhibits good vasogenic activity. In all in vivo experiments, nano ZIF-8 promoted bone formation. These results indicate that, at appropriate concentrations, materials containing ZIF-8 promote bone regeneration more than materials without ZIF-8, and with characteristics such as promoting angiogenesis, drug loading, and antibacterial activity, it is expected to show promising applications in the field of bone regeneration. STATEMENT OF SIGNIFICANCE: This manuscript reviewed the use of ZIF-8 in bone regeneration, clarified the biocompatibility and effectiveness in promoting bone regeneration of ZIF-8 materials, and discussed the possible mechanisms and factors affecting its promotion of bone regeneration. Overall, this study provides a better understanding of the latest advances in the field of bone regeneration of ZIF-8, serves as a design guide, and contributes to the design of future experimental studies.

Biomaterials science and surface engineering strategies for dental peri-implantitis management.

Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.

Near-infrared light responsive gold nanoparticles coating endows polyetheretherketone with enhanced osseointegration and antibacterial properties.

Polyetheretherketone (PEEK) is considered as a promising dental implant material owing to its excellent physicochemical and mechanical properties. However, its wide range of applications is limited by its biologically inert nature. In this study, a near-infrared (NIR) light responsive bioactive coating with gold nanoparticles (AuNPs) and metronidazole adhered to the PEEK surface via dopamine polymerization. Compared to pure PEEK, the hydrophilicity of the treated PEEK surface was significantly improved. In addition, under NIR light, the surface coating exhibited photothermal conversion effect, and gold nanoparticles and the antibiotic can be released from the coating. This improved the antibacterial properties of PEEK materials. Moreover, the coating was more conducive to the early adhesion of bone mesenchymal stem cells. The results of in vitro and in vivo osteogenic activity studies showed that the developed coating promoted osseointegration of PEEK implants, and NIR light irradiation further improved the antibacterial ability and osteogenic activity of PEEK implants. Through RNA sequencing, the potential underlying mechanism of promoting bone formation of the AuNPs coating combined metronidazole was interpreted. In summary, the developed coating is a potential surface treatment strategy that endows PEEK with enhanced osseointegration and antibacterial properties.

Composited silk fibroins ensured adhesion stability and magnetic controllability of Fe3O4-nanoparticle coating on implant for biofilm treatment.

Magnetic propulsion of nano-/micro-robots is an effective way to treat implant-associated infections by physically destroying biofilm structures to enhance antibiotic killing. However, it is hard to precisely control the propulsion in vivo. Magnetic-nanoparticle coating that can be magnetically pulled off does not need precise control, but the requirement of adhesion stability on an implant surface restricts its magnetic responsiveness. Moreover, whether the coating has been fully pulled-off or not is hard to ensure in real-time in vivo. Herein, composited silk fibroins (SFMA) are optimized to stabilize Fe3O4 nanoparticles on a titanium surface in a dry environment; while in an aqueous environment, the binding force of SFMA on titanium is significantly reduced due to hydrophilic interaction, making the coating magnetically controllable by an externally-used magnet but still stable in the absence of a magnet. The maximum working distance of the magnet can be calculated using magnetomechanical simulation in which the yielding magnetic traction force is strong enough to pull Fe3O4 nanoparticles off the surface. The pulling-off removes the biofilms that formed on the coating and enhances antibiotic killing both in vitro and in a rat sub-cutaneous implant model by up to 100 fold. This work contributes to the practical knowledge of magnetic propulsion for biofilm treatment.

Multi-Clinical Factors Combined with an Artificial Intelligence Algorithm Diagnosis Model for HIV-Infected People with Bloodstream Infection.

Purpose: Although highly active antiretroviral therapy (HA-ART) can effectively suppress the disease process in patients with acquired immunodeficiency syndrome (AIDS), opportunistic infections, mainly bloodstream infections (BSI), are still the main cause of death in people living with HIV. There is no effective diagnostic strategy for HIV-infected people with BSI. This study aimed to develop an AI diagnostic model with high sensitivity to improve the early detection of HIV-infected people with BSI. Patients and Methods: This study retrospectively analyzed the 40 clinical factors of 498 HIV-infected people (171 with BSI positive and 327 with BSI negative) who admitted to Wenzhou Central Hospital from September 2014 to July 2021. This study used the hospital information management system to collect the clinical characteristics, laboratory and imaging examination results, and clinical diagnosis of the two groups. The diagnostic results of all patients were in line with the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of AIDS (2021 Edition), and the BSI diagnosis was in line with the diagnostic criteria of sepsis and bacteremia in Practical Internal Medicine (13th Edition). On this basis, various risk prediction models were established by combining 8 artificial intelligence (AI) algorithms in the training set and validating the diagnosis performance in the testing set. The model with the best diagnostic performance was selected as the final diagnostic model. Results: The clinical characteristics of HIV-infected people with BSI are atypical, and the pathogens in this area are mainly fungi. Ten risk factors were selected: low level of hemoglobin, CD4+T cell and platelets, high level of lactate dehydrogenase and blood urea nitrogen, splenomegaly, without ART treatment, strip shadow, nodular shadow, and shock. The combination of the ten risk factors, age, gender and the "svmRadial" model can identify the HIV-infected people with BSI from the HIV-infected people without BSI with an area under the curve of 0.916 and a sensitivity and specificity of 0.824 and 0.855, respectively. Conclusion: The model showed excellent performance in diagnosing HIV-infected people with BSI. Internal and external validation showed that the diagnosis model had high clinical application value.