Self-Assembled Micelles Based on Ginsenoside Rg5 for the Targeted Treatment of PTX-Resistant Tumors.

Paclitaxel (PTX) is one of the first-line drugs for prostate cancer (PC) treatment. However, the poor water solubility, inadequate specific targeting ability, multidrug resistance, and severe neurotoxicity are far from being fully resolved, despite diverse PTX formulations in the market, such as the gold-standard PTX albumin nanoparticle (Abraxane) and polymer micelles (Genexol-PM). Some studies attempting to solve the multiple problems of chemotherapy delivery fall into the trap of an extremely complicated formulation design and sacrifice druggability. To better address these issues, this study designed an efficient, toxicity-reduced paclitaxel-ginsenoside polymeric micelle (RPM). With the aid of the inherent amphiphilic molecular structure and pharmacological effects of ginsenoside Rg5, the prepared RPM enhances the water solubility and active targeting of PTX, inhibiting chemotherapy resistance in cancer cells. Moreover, the polymeric micelles demonstrated favorable anti-inflammatory and neuroprotective effects, providing ideas for the development of new clinical anti-PC preparations.

Molecular insight into the vertical migration and degradation of dissolved organic matter in riparian soil profiles.

Due to the molecular complexity of dissolving organic matter (DOM), the vertical molecular distribution of riparian soil DOM (especially dissolved organic nitrogen (DON) and dissolved organic phosphorus (DOP)) in different land use types and their relationship with the bacterial community is still unclear. This study analyzed the spectral characteristics of riparian soil DOM from 0 to 100 cm in wild grassland, agricultural land, and bare land. The molecular distribution of DOM was revealed through Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and the specific relationship between DOM and bacterial community composition (BCC) was evaluated. The results showed that the DOM in the upper soil layer (0-40 cm) was mainly composed of recalcitrant macromolecular organics, while that in the lower layer (40-100 cm) was labile small molecular organics. In agricultural land, the total storage of DOM was lower than that in wild grassland, but with a higher abundance of recalcitrant organic carbon (lignin, etc.). At the same time, the bacterial community in agricultural land is shifting towards copiotrophs. In addition, the abundance of labile C degrading genes increases with nitrate as the main electron acceptor. However, sulfates are mainly used as electron acceptors in wild grasslands. Both DOP and DON were dominated by lignin and displayed higher chemical diversity in the upper soil. The bioavailability of DOP in three types of soil is higher than that of DON. DOM-BCC network analysis shows that the recalcitrant DON and DOP molecules in soil are positively correlated with phylum Actinobacteriota in agricultural land. These results emphasize that the DOM molecular characteristics were closely related to the function of the soil bacterial community.

Unveiling the repressive mechanism of a PPS-like regulator (PspR) in polyhydroxyalkanoates biosynthesis network.

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a type of polyhydroxyalkanoates (PHA) that exhibits numerous outstanding properties and is naturally synthesized and elaborately regulated in various microorganisms. However, the regulatory mechanism involving the specific regulator PhaR in Haloferax mediterranei, a major PHBV production model among Haloarchaea, is not well understood. In our previous study, we showed that deletion of the phosphoenolpyruvate (PEP) synthetase-like (pps-like) gene activates the cryptic phaC genes in H. mediterranei, resulting in enhanced PHBV accumulation. In this study, we demonstrated the specific function of the PPS-like protein as a negative regulator of phaR gene expression and PHBV synthesis. Chromatin immunoprecipitation (ChIP), in situ fluorescence reporting system, and in vitro electrophoretic mobility shift assay (EMSA) showed that the PPS-like protein can bind to the promoter region of phaRP. Computational modeling revealed a high structural similarity between the rifampin phosphotransferase (RPH) protein and the PPS-like protein, which has a conserved ATP-binding domain, a His domain, and a predicted DNA-binding domain. Key residues within this unique DNA-binding domain were subsequently validated through point mutation and functional evaluations. Based on these findings, we concluded that PPS-like protein, which we now renamed as PspR, has evolved into a repressor capable of regulating the key regulator PhaR, and thereby modulating PHBV synthesis. This regulatory network (PspR-PhaR) for PHA biosynthesis is likely widespread among haloarchaea, providing a novel approach to manipulate haloarchaea as a production platform for high-yielding PHA. KEY POINTS: • The repressive mechanism of a novel inhibitor PspR in the PHBV biosynthesis was demonstrated • PspR is widespread among the PHA accumulating haloarchaea • It is the first report of functional conversion from an enzyme to a trans-acting regulator in haloarchaea.

Periodontitis-induced oral microbiome alterations provide clues on how periodontitis exacerbates colitis.

AIM: To evaluate whether and how microbiota-derived metabolites associated with periodontitis aggravate colitis in mice. MATERIALS AND METHODS: A mouse model of periodontitis and colitis was constructed. Unbiased transcriptomic analyses of the colon were performed to explore important pathways through which periodontitis exacerbated colitis. Oral and gut bacteria were analysed using 16S rRNA sequencing. Gas chromatography-mass spectrometry was used to observe the alterations of oral and gut metabolites. Isolated intestinal lamina propria lymphocytes were analysed by flow cytometry. Inflammasome pathway was detected using qRT-PCR, Western blotting or ELISA. RESULTS: Periodontitis activated the colonic inflammasome pathway and altered the gut microbial composition and metabolite profiles in mice with colitis. Notably, periodontitis induced increase of the faecal metabolite isoleucine (Ile) which was synthesized by microbiota and plants. Moreover, periodontitis upregulated the Ile levels in saliva, but not in serum, indicating that Ile might be an oral pathobiont-synthesizing metabolite that transited from the oral cavity to the gut. Ile triggered the inflammasome pathway, upregulated the number of inflammatory IL-1ßhigh MHCIIhigh Ly6Chigh monocytes in colonic lamina propria, and exacerbated colitis. Further studies found that the Ile metabolite acetyl-coenzyme A positively regulated NLRP3 inflammasome by KAT5-mediated acetylation of NLRP3. CONCLUSIONS: Our study revealed that alteration in periodontitis-induced microbial metabolites deteriorated colitis in a mouse model and that this was associated with Ile production.

Directional Water Transport Janus Composite Nanofiber Membranes for Comfortable Bioprotection.

The Janus membrane has a huge prospect for personal comfortable protection. However, there still is a huge imbalance between the comfort and protection of the existing Janus membrane. There is an urgent need to further improve the comprehensive performance of the protective membrane to realize both protection and comfort. Herein, we report the Janus membrane with directional water transport capacity and dust rejection performance by compounding the polyvinyl chloride hydrophobic nanofiber membrane and polyamide-6 blended polyvinyl pyrrolidone hydrophilic nanofiber membrane. This Janus composite nanofiber membrane exhibited an excellent dust rejection efficiency of 99.99%, air permeability of 42.15 mm/s, which was 76 times that of the commercial waterproof and breathable PTFE membrane, water vapor transmission rate of 4.89 kg/(m2 × 24 h), and accumulative one-way transport capacity of 888.7%. In addition, the breakthrough pressure of the Janus membrane in the reverse direction (i.e., hydrophilic layer to hydrophobic layer) was four times that in the positive direction (i.e., hydrophobic layer to hydrophilic layer), suggesting it to be a potential substrate for comfortable bioprotection with a comprehensive protection capability.

Efficacy of aromatherapy on dental anxiety: A systematic review of randomised and quasi-randomised controlled trials.

OBJECTIVES: To evaluate the efficacy of aromatherapy on dental anxiety. METHODS: A detailed protocol was registered a priori (PROSPERO: CRD42019141093). PubMed, EMBASE, CDSR, CENTRAL, CNKI and grey literature databases were searched from inception to 10 January 2020. Randomised controlled trials (RCTs) and quasi-randomised controlled trials (CCTs) that examined the effects of aromatherapy on dental anxiety, compare to either negative control (i.e. no aromatherapy) or other positive control approaches (e.g. music), were included. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration's tool and ROBINS-I, while the certainty of evidence was assessed using GRADE. A narrative synthesis was performed, rather than meta-analysis, due to the high level of heterogeneity across studies. RESULTS: Eleven RCTs and six CCTs were included. The risk of bias was identified as either high or unclear in RCTs, and moderate to serious in CCTs. Performance bias and detection bias were the most prevalent in RCTs, followed by selection bias and reporting bias. As to CCTs, greater risk of bias was found in the selection of participants into the study and in the measurement of outcomes. Based on the selected studies, the most commonly used aromatherapy for dental anxiety management was lavender fragrance, followed by orange. Compared to the negative control condition, aromatherapy might reduce the anxiety-related physiological parameters and psychometric rating, pain, and mood, alertness, and calmness compared to the negative control condition; and there might be no intergroup difference in such outcomes between aromatherapy and music. However, GRADEs of the relevant evidence were judged as low to very low. CONCLUSIONS: Compared to the negative control condition, aromatherapy is more effective to reduce dental anxiety and has comparable effects on dental anxiety compared to music intervention; however, the certainty of evidence is relatively limited. Further high-quality randomised trials with robust study design and large sample size are warranted to confirm our findings and to confirm the role of aromatherapy in relieving dental anxiety.

Influence of pontic design on speech with an anterior fixed dental prosthesis: A clinical study and finite element analysis.

STATEMENT OF PROBLEM: Patients may experience disturbed articulation after treatment with a fixed dental prosthesis. However, studies that assess the relationship between fixed dental prosthesis design and the accuracy of speech sound production are lacking. PURPOSE: The purpose of this clinical and finite element analysis (FEA) study was to examine the influence of pontic design on speech with anterior fixed dental prostheses. MATERIAL AND METHODS: First, an articulation test was carried out in which a partially edentulous participant was required to pronounce 4 Chinese words containing the voiceless fricative/s/while wearing fixed dental prostheses with 2 types of pontic designs. The oral morphology was obtained by cone beam computed tomography (CBCT) scanning while the participant, wearing the 2 fixed dental prosthesis designs, was pronouncing the voiceless fricative/s/sound. The geometry of the oral cavity was then reconstructed by an image processing software program. Finally, a finite element model for sound wave propagation inside the oral cavity was developed within the framework of the finite element analysis software program. By using this model, the sound pressure level of the 2 types of pontic design was characterized and quantified under different fundamental frequencies (F0). The data were analyzed with 1-way ANOVA (α=.05). RESULTS: The experimental articulation test reported that the pontic design of fixed dental prostheses affected the speech production of the/s/sound (P<.001). The numerical study reported that the sound pressure level values were different under various fundamental frequencies. In addition, the pontic design of fixed dental prostheses affected the sound pressure level values, and the differences varied significantly from 420 to 1300 Hz (P<.05); however, the differences were not significant between 120 and 420 Hz (P>.05). Moreover, further comparisons of low F0 (120 to 500 Hz), medium F0 (520 to 900 Hz), and high F0 (920 to 1300 Hz) reported that the differences in the medium F0 area were most obvious (P<.001 for maximum sound pressure level value and P=.001 for sound pressure level value at Point Q). CONCLUSIONS: Both the fixed dental prosthesis pontic design and the fundamental frequency could affect the sound field distribution.

Deletion of the pps-like gene activates the cryptic phaC genes in Haloferax mediterranei.

Haloferax mediterranei, a poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) producing haloarchaeon, possesses four PHA synthase encoding genes, phaC, phaC1, phaC2, and phaC3. In the wild-type strain, except phaC, the other three genes are cryptic and not transcribed under PHA-accumulating conditions. The PhaC protein together with PhaE subunit forms the active PHA synthase and catalyzes PHBV polymerization. Previously, it was observed that the deletion of a gene named pps-like significantly enhanced PHBV accumulation probably resulted from the upregulation of pha cluster genes (phaR-phaP-phaE-phaC). The present study demonstrated the influence of pps-like gene deletion on the cryptic phaC genes. As revealed by qRT-PCR, the expression level of the three cryptic genes was upregulated in the ΔEPSΔpps-like geneΔphaC mutant. Sequential knockout of the cryptic phaC genes and fermentation experiments showed that PhaC1 followed by PhaC3 had the ability to synthesize PHBV in ΔEPSΔpps-like geneΔphaC mutant. Both PhaC1 and PhaC3 could complex with PhaE to form functionally active PHA synthase. However, the expression of phaC2 did not lead to PHBV synthesis. Moreover, PhaC, PhaC1, and PhaC3 exhibited distinct substrate specificity as the 3HV content in PHBV copolymers was different. The EMSA result showed that PPS-like protein might be a negative regulator of phaC1 gene by binding to its promoter region. Taken together, PhaC1 had the most pronounced effect on PHBV synthesis in ΔEPSΔpps-like geneΔphaC mutant and deletion of pps-like gene released the negative effect from phaC1 expression and thereby restored PHBV accumulating ability in ΔphaC mutant. KEY POINTS: • Cryptic phaC genes were activated by pps-like gene deletion. • PPS-like protein probably regulated phaC1 expression by binding to its promoter. • Both PhaC1 and PhaC3 formed active PHA synthase with PhaE.

Unusual Phosphoenolpyruvate (PEP) Synthetase-Like Protein Crucial to Enhancement of Polyhydroxyalkanoate Accumulation in Haloferax mediterranei Revealed by Dissection of PEP-Pyruvate Interconversion Mechanism.

Phosphoenolpyruvate (PEP)/pyruvate interconversion is a major metabolic point in glycolysis and gluconeogenesis and is catalyzed by various sets of enzymes in different Archaea groups. In this study, we report the key enzymes that catalyze the anabolic and catabolic directions of the PEP/pyruvate interconversion in Haloferax mediterranei The in silico analysis showed the presence of a potassium-dependent pyruvate kinase (PYKHm [HFX_0773]) and two phosphoenol pyruvate synthetase (PPS) candidates (PPSHm [HFX_0782] and a PPS homolog protein named PPS-like [HFX_2676]) in this strain. Expression of the pykHm gene and ppsHm was induced by glycerol and pyruvate, respectively; whereas the pps-like gene was not induced at all. Similarly, genetic analysis and enzyme activities of purified proteins showed that PYKHm catalyzed the conversion from PEP to pyruvate and that PPSHm catalyzed the reverse reaction, while PPS-like protein displayed no function in PEP/pyruvate interconversion. Interestingly, knockout of the pps-like gene led to a 70.46% increase in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) production. The transcriptome sequencing (RNA-Seq) and quantitative reverse transcription-PCR (qRT-PCR) results showed that many genes responsible for PHBV monomer supply and for PHBV synthesis were upregulated in a pps-like gene deletion strain and thereby improved PHBV accumulation. Additionally, our phylogenetic evidence suggested that PPS-like protein diverged from PPS enzyme and evolved as a distinct protein with novel function in haloarchaea. Our findings attempt to fill the gaps in central metabolism of Archaea by providing comprehensive information about key enzymes involved in the haloarchaeal PEP/pyruvate interconversion, and we also report a high-yielding PHBV strain with great future potentials.IMPORTANCEArchaea, the third domain of life, have evolved diversified metabolic pathways to cope with their extreme habitats. Phosphoenol pyruvate (PEP)/pyruvate interconversion during carbohydrate metabolism is one such important metabolic process that is highly differentiated among Archaea However, this process is still uncharacterized in the haloarchaeal group. Haloferax mediterranei is a well-studied haloarchaeon that has the ability to produce polyhydroxyalkanoates (PHAs) under unbalanced nutritional conditions. In this study, we identified the key enzymes involved in this interconversion and discussed their differences with their counterparts from other members of the Archaea and Bacteria domains. Notably, we found a novel protein, phosphoenolpyruvate synthetase-like (PPS-like), which exhibited high homology to PPS enzyme. However, PPS-like protein has evolved some distinct sequence features and functions, and strikingly the corresponding gene deletion helped to enhance poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) synthesis significantly. Overall, we have filled the gap in knowledge about PEP/pyruvate interconversion in haloarchaea and reported an efficient strategy for improving PHBV production in H. mediterranei.

Speech and orthodontic appliances: a systematic literature review.

Background: Various types of orthodontic appliances can lead to speech difficulties. However, speech difficulties caused by orthodontic appliances have not been sufficiently investigated by an evidence-based method. Objectives: The aim of this study is to outline the scientific evidence and mechanism of the speech difficulties caused by orthodontic appliances. Search methods and selection criteria: Randomized-controlled clinical trials (RCT), controlled clinical trials, and cohort studies focusing on the effect of orthodontic appliances on speech were included. A systematic search was conducted by an electronic search in PubMed, EMBASE, and the Cochrane Library databases, complemented by a manual search. Data collection and analysis: The types of orthodontic appliances, the affected sounds, and duration period of the speech disturbances were extracted. The ROBINS-I tool was applied to evaluate the quality of non-randomized studies, and the bias of RCT was assessed based on the Cochrane Handbook for Systematic Reviews of Interventions. No meta-analyses could be performed due to the heterogeneity in the study designs and treatment modalities. Results: Among 448 screened articles, 13 studies were included (n = 297 patients). Different types of orthodontic appliances such as fixed appliances, orthodontic retainers and palatal expanders could influence the clarity of speech. The /i/, /a/, and /e/ vowels as well as /s/, /z/, /l/, /t/, /d/, /r/, and /ʃ/ consonants could be distorted by appliances. Although most speech impairments could return to normal within weeks, speech distortion of the /s/ sound might last for more than 3 months. The low evidence level grading and heterogeneity were the two main limitations in this systematic review. Conclusions: Lingual fixed appliances, palatal expanders, and Hawley retainers have an evident influence on speech production. The /i/, /s/, /t/, and /d/ sounds are the primarily affected ones. The results of this systematic review should be interpreted with caution and more high-quality RCTs with larger sample sizes and longer follow-up periods are needed. Registration: The protocol for this systematic review (CRD42017056573) was registered in the International Prospective Register of Systematic Reviews (PROSPERO).

A Systematic Review of the Survival and Complication Rates of All-Ceramic Resin-Bonded Fixed Dental Prostheses.

PURPOSE: The aim of this systematic review was to investigate the survival and complication rates of all-ceramic resin-bonded fixed dental prostheses (RBFDPs). MATERIALS AND METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied. A systematic search was conducted by an electronic search in PubMed, EMBASE, Cochrane Library, and CNKI databases complemented by a manual search. Only clinical studies on all-ceramic RBFDPs with a mean follow-up period of at least 3 years qualified for data analyses. RESULTS: Among 1503 screened articles, one randomized controlled trial (RCT) and seven prospective or retrospective cohort studies were included in this study. The estimated 5-year survival rate of all-ceramic RBFDPs was 91.2%. Debonding and framework fracture were the two most frequent technical complications, and the estimated 5-year debonding rate and fracture rate were 12.2% and 4.8%, respectively. Additionally, cantilevered all-ceramic RBFDPs had a higher survival rate (p < 0.01), lower debonding rate, (p < 0.05), and fracture rate (p < 0.01) compared with two-retainer all-ceramic RBFDPs. Zirconia ceramic RBFDPs had a lower incidence of failure but a higher debonding rate compared with glass-ceramic RBFDPs (p < 0.01). CONCLUSION: Within the limitations of this systematic review, although all-ceramic RBFDPs have a favorable 5-year survival rate, this rate cannot represent the complete success of the treatment, since it may include typical complications such as debonding and fractures. There is an urgent need for long-term clinical studies, especially for well-designed RCTs on all-ceramic RBFDPs.

Environmental biodegradation of haloarchaea-produced poly(3-hydroxybutyrate-co-3-hydroxyvalerate) in activated sludge.

Novel poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) copolymers produced by haloarchaea are excellent candidate biomaterials. However, there is no report hitherto focusing on the biodegradation of PHBHV synthesized by haloarchaea. In this study, an environmental biodegradation of haloarchaea-produced PHBHV films, with 10~60 mol% 3-hydroxyvalerate (3HV) composition and different microchemical structures, was studied in nutrition-depleted activated sludge. The changes in mass, molar mass, chemical composition, thermal properties, and surface morphology were monitored. The mass and molar mass of each film decreased significantly, while the PHA monomer composition remained unchanged with time. Interestingly, the sample of random copolymer PHBHV-2 (R-PHBHV-2) (3HV, 30 mol%) had the lowest crystallinity and was degraded faster than R-PHBHV-3 containing the highest 3HV content or the higher-order copolymer PHBHV-1 (O-PHBHV-1) possessing the highest surface roughness. The order of biodegradation rate was in the opposite trend to the degree of crystallizability of the films. Meanwhile, thermal degradation temperature of most films decreased after biodegradation. Additionally, the surface erosion of films was confirmed by scanning electron microscopy. The dominant bacteria probably responsible for the degradation process were identified in the activated sludge. It was inferred that the degradation rate of haloarchaea-produced PHBHV films mainly depended on sample crystallinity, which was determined by monomer composition and microchemical structure and in turn strongly influenced surface morphology.

The development of magnesium-based biomaterials in bone tissue engineering: A review.

Bone regeneration is a vital clinical challenge in massive or complicated bone defects. Recently, bone tissue engineering has come to the fore to meet the demand for bone repair with various innovative materials. However, the reported materials usually cannot satisfy the requirements, such as ideal mechanical and osteogenic properties, as well as biocompatibility at the same time. Mg-based biomaterials have considerable potential in bone tissue engineering owing to their excellent mechanical strength and biosafety. Moreover, the biocompatibility and osteogenic activity of Mg-based biomaterials have been the research focuses in recent years. The main limitation faced in the applications of Mg-based biomaterials is rapid degradation, which can produce excessive Mg2+ and hydrogen, affecting the healing of the bone defect. In order to overcome the limitations, researchers have explored several ways to improve the properties of Mg-based biomaterials, including alloying, surface modification with coatings, and synthesizing other composite materials to control the degradation rate upon implantation. This article reviewed the osteogenic mechanism and requirement for appropriate degradation rate and focused on current progress in the biomedical use of Mg-based biomaterials to inspire more clinical applications of Mg in bone regeneration in the future.

Robust and self-lubricating polyvinyl alcohol tubes with a mucosa-like hierarchical architecture for endotracheal intubation.

Mechanical mismatch between interventional intubation tubes and human tissues often triggers inevitable friction and causes secondary injury to patients during interventional therapy. Herein, we propose a fabrication strategy of a self-lubricating polyvinyl alcohol (PVA) tube by industrial extrusion technology followed by simple infiltration with water. First, biocompatible glycerin was introduced to weaken the intrinsic hydrogen interaction of PVA by new molecular complexation, broadening the gap between the melting and decomposition temperatures and enabling the stable extrusion of the PVA tube. Subsequently, the as-prepared PVA tube was infiltrated with an aqueous solution to construct a strong hydrogen bonding network between PVA and water molecules, forming a soft hydration layer similar to the upper epithelium layer of mucosa. Benefiting from the solid and liquid properties of the hydration layer as well as the small proportion relative to the whole, the infiltrated PVA tube exhibited excellent hydration lubrication behavior and robust mechanical property. The friction coefficient, tensile strength and elongation at break were measured to be 0.05, 26.2 MPa and 654%, respectively, surpassing the values of 0.5, 16.4 MPa and 240% observed in a commercial polyvinyl chloride tube. In vitro, the PVA intubation tube demonstrated significant biocompatibility, and short-term exposure exhibited minimal impacts on the morphology and proliferation of L929 cells. Ultimately, the potential of the infiltrated PVA tube for interventional intubation was demonstrated successfully using an in vivo rabbit model, providing a new idea for the follow-up development of interventional intubation tubes.

Manufacturing biodegradable lignocellulosic films with tunable properties from spent coffee grounds: A sustainable alternative to plastics.

Manufacturing biodegradable lignocellulosic films from spent coffee grounds (SCG) as an alternative to commercial plastics is a viable solution to address plastic pollution. Here, the biodegradable lignocellulosic films from SCG were fabricated via a sequential alkaline treatment and ionic liquid-based dissolution process. The alkaline treatment process could swell the cell wall of SCG, change its carbohydrates and lignin contents, and enhance its solubility in ionic liquids. The prepared SCG films with different lignin contents exhibited outstanding UV blocking capability (42.07-99.99 % for UVB and 20.96-99.99 % for UVA) and light scattering properties, good surface hydrophobicity (water contact angle = 63.2°-88.7°), enhanced water vapor barrier property (2.28-6.79 × 10-12 g/m·s·Pa), and good thermal stability. Moreover, the SCG films exhibit excellent mechanical strength (50.10-81.56 MPa, tensile strength) and biodegradability (fully degraded within 30 days when buried in soil) compared to commercial plastic. The SCG films represent a promising alternative that can replace non-biodegradable plastics.

Development of a rapid-shaping and user-friendly membrane with long-lasting space maintenance for guided bone regeneration.

The success of guided bone regeneration (GBR) surgery depends largely on the use of GBR membranes to maintain space for bone regeneration and prevent soft tissue ingrowth. However, currently available commercial degradable GBR membranes are often limited by poor space maintenance ability and require additional suture or nail for fixation. To overcome these limitations, we developed a rapid-shaping, adhesive, and user-friendly GBR membrane (PLGA film-PGN) with long-lasting space maintenance by immersing an electrospun poly(lactide-co-glycolic acid) film in a photo-crosslinkable hydrogel composed of polyethylene glycol diacrylate, gelatin methacryloyl, and nanosilicate (PGN). The PGN hydrogel significantly improved the mechanical strength of the PLGA film-PGN and endowed it with plasticity and adhesive properties, making it more maneuverable. The maximum bending force that the PLGA film-PGN could withstand was over 55 times higher than that of the HEAL ALL film (a commonly used commercial GBR membrane). PLGA film-PGN also promoted the proliferation and osteogenic differentiation of rBMSCs. According to a critical-size rat calvarial defect model, PLGA film-PGN maintained the space within the defect area and significantly enhanced bone formation 4 weeks after the surgery. To conclude, the study provided a novel perspective on GBR membrane design and the multifunctional PLGA film-PGN membrane demonstrated great potential for bone defect reconstruction.

Battery-free optoelectronic patch for photodynamic and light therapies in treating bacteria-infected wounds.

Light therapy is an effective approach for the treatment of a variety of challenging dermatological conditions. In contrast to existing methods involving high doses and large areas of illumination, alternative strategies based on wearable designs that utilize a low light dose over an extended period provide a precise and convenient treatment. In this study, we present a battery-free, skin-integrated optoelectronic patch that incorporates a coil-powered circuit, an array of microscale violet and red light emitting diodes (LEDs), and polymer microneedles (MNs) loaded with 5-aminolevulinic acid (5-ALA). These polymer MNs, based on the biodegradable composite materials of polyvinyl alcohol (PVA) and hyaluronic acid (HA), serve as light waveguides for optical access and a medium for drug release into deeper skin layers. Unlike conventional clinical photomedical appliances with a rigid and fixed light source, this flexible design allows for a conformable light source that can be applied directly to the skin. In animal models with bacterial-infected wounds, the experimental group with the combination treatment of metronomic photodynamic and light therapies reduced 2.48 log10 CFU mL-1 in bactericidal level compared to the control group, indicating an effective anti-infective response. Furthermore, post-treatment analysis revealed the activation of proregenerative genes in monocyte and macrophage cell populations, suggesting enhanced tissue regeneration, neovascularization, and dermal recovery. Overall, this optoelectronic patch design broadens the scope for targeting deep skin lesions, and provides an alternative with the functionality of standard clinical light therapy methods.

Effects of Hyperlipidemia on Osseointegration of Dental Implants and Its Strategies.

Hyperlipidemia refers to the abnormal increase in plasma lipid level exceeding the normal range. At present, a large number of patients require dental implantation. However, hyperlipidemia affects bone metabolism, promotes bone loss, and inhibits the osseointegration of dental implants through the mutual regulation of adipocytes, osteoblasts, and osteoclasts. This review summarized the effects of hyperlipidemia on dental implants and addressed the potential strategies of dental implants to promote osseointegration in a hyperlipidemic environment and to improve the success rate of dental implants in patients with hyperlipidemia. We summarized topical drug delivery methods to solve the interference of hyperlipidemia in osseointegration, which were local drug injection, implant surface modification and bone-grafting material modification. Statins are the most effective drugs in the treatment of hyperlipidemia, and they also encourage bone formation. Statins have been used in these three methods and have been found to be positive in promoting osseointegration. Directly coating simvastatin on the rough surface of the implant can effectively promote osseointegration of the implant in a hyperlipidemic environment. However, the delivery method of this drug is not efficient. Recently, a variety of efficient methods of simvastatin delivery, such as hydrogels and nanoparticles, have been developed to boost bone formation, but few of them were applied to dental implants. Applicating these drug delivery systems using the three aforementioned ways, according to the mechanical and biological properties of materials, could be promising ways to promote osseointegration under hyperlipidemic conditions. However, more research is needed to confirm.

Serum metabolomics provides clues in understanding colitis exacerbating experimental periodontitis in female mice.

OBJECTIVES: To evaluate the pathogenic role of colitis in experimental periodontitis and explore the potential serum metabolites of colitis exacerbating experimental periodontitis in mice model. DESIGN: C57BL/6 mice were divided into four groups (five mice in each group), including control, periodontitis, colitis and colitis+periodontitis group. Mice treated with 1.5 % dextran sulfate sodium for 14 days to induce colitis. On the seventh to fourteenth days, the experimental periodontitis model was established by installing a bacterially retentive ligature between two molars. Histological alteration of periodontium and colon was observed by hematoxylin and eosin staining. Tartrate-resistant acid phosphatase staining and micro-computed tomography was applied to evaluate alveolar bone loss. Gas chromatography-mass spectrometry was used to characterize serum metabolic profiles. RESULTS: Mice in colitis+periodontitis group displayed increased periodontal inflammation and alveolar bone loss when compared with the mice of periodontitis group, suggesting colitis aggravated periodontitis. Metabolomics analysis combined with enrichment analysis showed that colitis significantly (P＜0.05) altered the content of compounds associated with five metabolic pathways (e.g. fatty acid biosynthesis) of periodontitis mice. Notably, colitis significantly reduced the level of serum metabolites that inhibited the formation of osteoclasts (e.g. oleic acid) or anti-inflammatory metabolites (e.g. palmitoleic acid, palmitelaidic acid and chlorogenic acid) of periodontitis mice. CONCLUSIONS: Our findings showed that colitis might aggravate periodontitis and this might be associated with alteration of serum metabolic profiles.

Alginate-based biomaterial-mediated regulation of macrophages in bone tissue engineering.

Many studies in the bone tissue engineering field have focused on the interactions between materials and bone marrow stem cells. With the development of osteoimmunology, the immune cells' essential role in biomaterial-mediated osteogenesis has increasingly been recognized. As a promising therapeutic candidate for bone defects due to their prominent biocompatibility, tuneability, and versatility, it is necessary to develop alginate-based biomaterials that can regulate immune cells, especially macrophages. Moreover, modified alginate-based biomaterials may facilitate better regulation of macrophage phenotypes by the newly endowed physicochemical properties, including stiffness, porosity, hydrophilicity, and electrical properties. This review summarizes the role of macrophages in bone regeneration and the recent research progress related to the effects of alginate-based biomaterials on macrophages applied in bone tissue engineering. This review also emphasizes the strategies adopted by material design to regulate macrophage phenotypes, the corresponding macrophage responses, and their contribution to osteogenesis.