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.

[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.

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.

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.

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.

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.

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.

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.

CHAF1A promotes the proliferation and growth of epithelial ovarian cancer cells by affecting the phosphorylation of JAK2/STAT3 signaling pathway.

The molecular mechanism of chromatin assembly factor 1 unit A (CHAF1A) promoting the proliferation and growth of epithelial ovarian cancer (EOC) cells hasn't been reported at present. In this study, recombinant CHAF1A siRNA/overexpression plasmid (si-RNA1/pcDNA3.1-CHAF1A) was designed and constructed, and stable cell lines with knockdown or overexpression of CHAF1A were constructed. The changes of JAK2/STAT3 pathway were detected by Western blot. JAK2/STAT3 pathway was inhibited by Peficitinib, and then cell proliferation and growth ability were detected. Bioinformatics analysis suggested that CHAF1A was up-regulated in epithelial ovarian cancer. JAK2/STAT3 pathway phosphorylation was inhibited in si-RNA1 group, while it was increased in pcDNA3.1-CHAF1A group. After inhibiting JAK2/STAT3 pathway, the promoting effect of CHAF1A on epithelial ovarian cancer cell proliferation disappeared, meanwhile the inhibitory effect of CHAF1A on apoptosis enhanced. In conclusion, CHAF1A promotes the proliferation and growth of epithelial ovarian cancer cells by affecting the phosphorylation of JAK2/STAT3 signaling pathway.

Mechanical properties, in vitro biodegradable behavior, biocompatibility and osteogenic ability of additively manufactured Zn-0.8Li-0.1Mg alloy scaffolds.

Alloying and structural design provide flexibility to modulate performance of biodegradable porous implants manufactured by laser powder bed fusion (L-PBF). Herein, bulk Zn-0.8Li-0.1Mg was first fabricated to indicate the influence of the ternary alloy system on strengthening effect. Porous scaffolds with different porosities, including 60 % (P60), 70 % (P70) and 80 % (P80), were designed and fabricated to study the influence of porosity on mechanical properties, in vitro degradation behavior, biocompatibility and osteogenic ability. Pure Zn (Zn-P70) scaffolds with a porosity of 70 % were utilized for the comparison. The results showed Zn-0.8Li-0.1Mg bulks had an ultimate tensile strength of 460.78 ± 5.79 MPa, which was more than 3 times that of pure Zn ones and was the highest value ever reported for Zn alloys fabricated by L-PBF. The compressive strength (CS) and elastic modulus (E) of scaffolds decreased with increasing porosities. The CS of P70 scaffolds was 24.59 MPa, more than 2 times that of Zn-P70. The weight loss of scaffolds during in vitro immersion increased with increasing porosities. Compared with Zn-P70, a lower weight loss, better biocompatibility and improved osteogenic ability were observed for P70 scaffolds. P70 scaffolds also exhibited the best biocompatibility and osteogenic ability among all the used porosities. Influence mechanism of alloying elements and structural porosities on mechanical behaviors, in vitro biodegradation behavior, biocompatibility and osteogenic ability of scaffolds were discussed using finite element analysis and the characterization of degradation products. The results indicated that the proper design of alloying and porosity made Zn-0.8Li-0.1Mg scaffolds promising for biodegradable applications.

Surface modification of titanium implants with Mg-containing coatings to promote osseointegration.

Titanium (Ti) and Ti alloys are commonly used in dental implants, which have good biocompatibility, mechanical strength, processability, and corrosion resistance. However, the surface inertia of Ti implants leads to delayed integration of Ti and new bone, as well as problems such as aseptic loosening and inadequate osseointegration. Magnesium (Mg) ions can promote bone regeneration, and many studies have used Mg-containing materials to modify the Ti implant surface. This systematic review summarizes the methods, effects, and clinical applications of surface modification of Ti implants with Mg-containing coatings. Database collection was completed on Janury 1, 2023, and a total of 29 relevant studies were ultimately included. Mg can be compounded with different materials and coated to the surface of Ti implants using different methods. In vitro and in vivo experiments have shown that Mg-containing coatings promote cell adhesion and osteogenic differentiation. On the one hand, the surface roughness of implants increases with the addition of Mg-containing coatings, which is thought to have an impact on the osseointegration of the implant. On the other hand, Mg ions promote cell attachment through binding interactions between the integrin family and FAK-related signaling pathways. And Mg ions could induce osseointegration by activating PI3K, Notch, ERK/c-Fos, BMP-4-related signaling pathways and TRPM7 protein channels. Overall, Mg-based coatings show great potential for the surface modification of Ti implants to promote osseointegration. STATEMENT OF SIGNIFICANCE: The inertia surface of titanium (Ti) implants leads to delayed osseointegration. Magnesium (Mg) ions, known for promoting bone regeneration, have been extensively studied to modify the surface of Ti implants. However, no consensus has been reached on the appropriate processing methods, surface roughness and effective concentration of Mg-containing coatings for osseointegration. This systematic review focus on the surface modification of Ti implants with Mg-containing compounds, highlighting the effects of Mg-containing coatings on the surface properties of Ti implants and its associated mechanisms. Besides, we also provide an outlook on future directions to promote the clinical application of Mg-modified implants.

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.

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.

Sustained release of magnesium and zinc ions synergistically accelerates wound healing.

Skin wounds are a major medical challenge that threaten human health. Functional hydrogel dressings demonstrate great potential to promote wound healing. In this study, magnesium (Mg) and zinc (Zn) are introduced into methacrylate gelatin (GelMA) hydrogel via low-temperature magnetic stirring and photocuring, and their effects on skin wounds and the underlying mechanisms are investigated. Degradation testing confirmed that the GelMA/Mg/Zn hydrogel released magnesium ions (Mg2+) and zinc ions (Zn2+) in a sustained manner. The Mg2+ and Zn2+ not only enhanced the migration of human skin fibroblasts (HSFs) and human immortalized keratinocytes (HaCats), but also promoted the transformation of HSFs into myofibroblasts and accelerated the production and remodeling of extracellular matrix. Moreover, the GelMA/Mg/Zn hydrogel enhanced the healing of full-thickness skin defects in rats via accelerated collagen deposition, angiogenesis and skin wound re-epithelialization. We also identified the mechanisms through which GelMA/Mg/Zn hydrogel promoted wound healing: the Mg2+ promoted Zn2+ entry into HSFs and increased the concentration of Zn2+ in HSFs, which effectively induced HSFs to differentiate into myofibroblasts by activating the STAT3 signaling pathway. The synergistic effect of Mg2+ and Zn2+ promoted wound healing. In conclusion, our study provides a promising strategy for skin wounds regeneration.

The biological functions of europium-containing biomaterials: A systematic review.

The biological functions of rare-earth elements (REEs) have become a focus of intense research. Recent studies have demonstrated that ion doping or alloying of some REEs can optimize the properties of traditional biomaterials. Europium (Eu), which is an REE with low toxicity and good biocompatibility, has promising applications in biomedicine. This article systematically reviews the osteogenic, angiogenic, neuritogenic, antibacterial, and anti-tumor properties of Eu-containing biomaterials, thereby paving the way for biomedical applications of Eu. Data collection for this review was completed in October 2022, and 30 relevant articles were finally included. Most articles indicated that doping of Eu ions or Eu-compound nanoparticles in biomaterials can improve their osteogenic, angiogenic, neuritogenic, antibacterial, and anti-tumor properties. The angiogenic, antibacterial, and potential neuritogenic effects of Eu(OH)3 nanoparticles have also been demonstrated.

Systematic in vitro and in vivo study on biodegradable binary Zn-0.2 at% Rare Earth alloys (Zn-RE: Sc, Y, La-Nd, Sm-Lu).

Biomedical implants and devices for tissue engineering in clinics, mainly made of polymers and stiff metallic materials, require possibly secondary surgery or life-long medicine. Biodegradable metals for biomedical implants and devices exhibit huge potential to improve the prognosis of patients. In this work, we developed a new type of biodegradable binary zinc (Zn) alloys with 16 rare earth elements (REEs) including Sc, Y, La to Nd, and Sm to Lu, respectively. The effects of REEs on the alloy microstructure, mechanical properties, corrosion behavior and in vitro and in vivo biocompatibility of Zn were systematically investigated using pure Zn as control. All Zn-RE alloys generally exhibited improved mechanical properties, and biocompatibilities compared to pure Zn, especially the tensile strength and ductility of Zn-RE alloys were dramatically enhanced. Among the Zn-RE alloys, different REEs presented enhancement effects at varied extent. Y, Ho and Lu were the three elements displaying greatest improvements in majority of alloys properties, while Eu, Gd and Dy exhibited least improvement. Furthermore, the Zn-RE alloys were comparable with other Zn alloys and also exhibited superior properties to Mg-RE alloys. The in vivo experiment using Zn-La, Zn-Ce, and Zn-Nd alloys as tibia bone implants in rabbit demonstrated the excellent tissue biocompatibility and much more obvious osseointegration than the pure Zn control group. This work presented the significant potential of the developed Zn-RE binary alloys as novel degradable metal for biomedical implants and devices.

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.

Fungal polyketides from a rhizospheric soil-derived Penicillium sp. YUD17004 associated with Gastrodia elata.

Five unprecedented polyketide metabolites were isolated and characterized from a rhizospheric soil-derived Penicillium sp. YUD17004. Their diverse structures included two indanone-type polyketides penicillyketides A and B, a phthalide-like polyketides penicillyketide C, a symmetrical chromone dimer penicillyketide D, along with a pyrone derivative pyranlyketide, which were elucidated by spectroscopic data interpretation and quantum chemical electronic circular dichroism calculation. Notably, the structures of penicillyketides A and B feature a highly functionalized indanone ring nucleus, but differ from other indanone-containing polyketides by the alkyl substitution pattern. The structure of penicillyketide C comprises a furanone ring instead of the hydroxycyclopentenone ring characteristic for penicillyketides A and B, and represents an undescribed arrangement within C17 polyketides. Penicillyketide D represented the first example of a chromone homodimer with the bridge at C-2/2'. Penicillyketide B exhibited weak anti-inflammatory activity with an IC50 value of 32 ± 1.0 µM. Penicillyketide D displayed weak cytotoxicity against MCF-7 cell line with an IC50 value of 25 ± 0.9 µM.

Additively manufactured pure zinc porous scaffolds for critical-sized bone defects of rabbit femur.

Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures. Biodegradable Zn metals are revolutionary materials for orthopedic implants. In this study, pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion (L-PBF) technology. First, the mechanical properties, corrosion behavior, and biocompatibility of the pure Zn porous scaffolds were characterized in vitro. The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks. The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone, as well as relatively suitable degradation rates for bone regeneration. A benign host response was observed using hematoxylin and eosin (HE) staining of the heart, liver, spleen, lungs, and kidneys. Moreover, the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability in vivo. This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.

Biomimetic AgNPs@antimicrobial peptide/silk fibroin coating for infection-trigger antibacterial capability and enhanced osseointegration.

Endowing implant surfaces with combined antibacterial and osteogenic properties by drug-loaded coatings has made great strides, but how to achieve the combined excellence of infection-triggered bactericidal and in vivo-proven osteogenic activities without causing bacterial resistance still remains a formidable challenge. Herein, antimicrobial peptides (AMPs) with osteogenic fragments were designed and complexed on the surface of silver nanoparticle (AgNP) through hydrogen bonding, and the collagen structure-bionic silk fibroin (SF) was applied to carry AgNPs@ AMPs to achieve infection-triggered antibacterial and osteointegration. As verified by TEM, AMPs contributed to the dispersion and size-regulation of AgNPs, with a particle size of about 20 nm, and a clear protein corona structure was observed on the particle surface. The release curve of silver ion displayed that the SF-based coating owned sensitive pH-responsive properties. In the antibacterial test against S.aureus for up to 21 days, the antibacterial rate had always remained above 99%. Meanwhile, the underlying mechanism was revealed, originating from the destruction of the bacterial cell membranes and ROS generation. The SF-based coating was conducive to the adhesion, diffusion, and proliferation of bone marrow stem cells (BMSCs) on the surface, and promoted the expression of osteogenic genes and collagen secretion. The in vivo implantation results showed that compared with the untreated Ti implants, SF-based coating enhanced osseointegration at week 4 and 8. Overall, the AgNPs@AMPs-loaded SF-based coating presented the ability to synergistically inhibit bacteria and promote osseointegration, possessing tremendous potential application prospects in bone defects and related-infection treatments.