Multifunctional biomimetic hydrogel dressing provides anti-infection treatment and improves immunotherapy by reprogramming the infection-related wound microenvironment.

The advancement of biomaterials with antimicrobial and wound healing properties continues to present challenges. Macrophages are recognized for their significant role in the repair of infection-related wounds. However, the interaction between biomaterials and macrophages remains complex and requires further investigation. In this research, we propose a new sequential immunomodulation method to enhance and expedite wound healing by leveraging the immune properties of bacteria-related wounds, utilizing a novel mixed hydrogel dressing. The hydrogel matrix is derived from porcine acellular dermal matrix (PADM) and is loaded with a new type of bioactive glass nanoparticles (MBG) doped with magnesium (Mg-MBG) and loaded with Curcumin (Cur). This hybrid hydrogel demonstrates controlled release of Cur, effectively eradicating bacterial infection in the early stage of wound infection, and the subsequent release of Mg ions (Mg2+) synergistically inhibits the activation of inflammation-related pathways (such as MAPK pathway, NF-κB pathway, TNF-α pathway, etc.), suppressing the inflammatory response caused by infection. Therefore, this innovative hydrogel can safely and effectively expedite wound healing during infection. Our design strategy explores novel immunomodulatory biomaterials, offering a fresh approach to tackle current clinical challenges associated with wound infection treatment.

Shell-Sheddable Polymeric Micelles Alleviate Oxidative Stress and Inflammation for Enhanced Ischemic Stroke Therapy.

As a ROS scavenger, resveratrol exerts a neuroprotective effect by polarizing the M1 microglia to the anti-inflammatory M2 phenotype for ischemic stroke treatment. However, the obstruction of the blood-brain barrier (BBB) seriously impairs the efficacy of resveratrol. Herein, we develop a stepwise targeting nanoplatform for enhanced ischemic stroke therapy, which is fabricated by pH-responsive poly(ethylene glycol)-acetal-polycaprolactone-poly(ethylene glycol) (PEG-Acetal-PCL-PEG) and modified with cRGD and triphenylphosphine (TPP) on a long PEG chain and a short PEG chain, respectively. The as-designed micelle system features effective BBB penetration through cRGD-mediated transcytosis. Once entering the ischemic brain tissues and endocytosed by microglia, the long PEG shell can be detached from the micelles in the acidic lysosomes, subsequently exposing TPP to target mitochondria. Thus, the micelles can effectively alleviate oxidative stress and inflammation by enhanced delivery of resveratrol to microglia mitochondria, reversing the microglia phenotype through the scavenging of ROS. This work offers a promising strategy to treat ischemia-reperfusion injury.

A comparative study of the use of digital technology in the anterior smile experience.

OBJECTIVES: this study aims to compare the clinical outcomes of traditional and digital crown extension guides in the aesthetic restoration of anterior teeth. Additionally, the study will analyze the differences in the results of various digital crown extension guides in anterior aesthetic restorations. METHODS: Sixty-two patients who required aesthetic restoration of their anterior teeth were selected for this study. The patients had a total of 230 anterior teeth and were randomly divided into three groups: a control group of 22 cases who received diagnostic wax-up with pressure film, an experimental group 1 of 20 cases who received 3D printed digital models with pressure film, and an experimental group 2 of 20 patients who received digital dual-positioning guides. The control group had a total of 84 anterior teeth, experimental group 1 had 72 anterior teeth, and experimental group 2 had 74 anterior teeth. The study compared three methods for fabricating crown extension guides: the control group used the diagnostic wax-up plus compression film method, while experimental group 1 used compression film on 3D printed models and experimental group 2 used 3D printed digital dual-positioning crown extension guides. After the crown lengthening surgery, the control group patients wore DMG resin temporary crown material for gingival contouring, while the experimental group patients wore 3D printed resin temporary crowns for the same purpose. The patients were followed up in the outpatient clinic after wearing temporary crowns for 1 month, 3 months, and 6 months, respectively. The clinical results were evaluated in terms of marginal fit, red aesthetic index, and white aesthetic index. RESULTS: Based on the statistical analysis, the experimental group required significantly fewer follow-up visits and less time for guide design and fabrication compared to the control group. Additionally, the surgical time for the experimental group was significantly shorter than that of the control group. During the postoperative period between the 1st and 3rd month, the PES index scores for the marginal gingival level, proximal, and distal mesiodistal gingival papillae of the experimental group showed a trend of superiority over those of the control group. By the 6th month, the marginal gingival level exhibited a significant difference between the experimental and control groups. The experimental group demonstrated superior results to the control group in terms of shape, contour, and volume of the teeth, color, surface texture, and transparency of the restorations, and features during the 1st and 3rd postoperative months. In the 6th month, the comparative results indicated that the experimental group continued to exhibit superior outcomes to the control group in terms of the shape, color, surface texture, and transparency of the restorations, as well as the characteristics of the teeth. Additionally, the experimental group demonstrated significantly fewer gingival alterations than the control group at 1 month, 3 months, and 6 months post-procedure, with this difference being statistically significant. Furthermore, the combination of 3D printing technology and restorative techniques was utilized, resulting in consistent patient satisfaction. CONCLUSION: Digitalisation plays an important role in anterior aesthetic restorations. The use of digital technology to manage the entire process of anterior cosmetic restorations can improve restorative results, reduce the number of follow-up appointments, shorten consultation time, and achieve better patient satisfaction.

Transcriptome and metabolite analysis reveal the drought tolerance of foxtail millet significantly correlated with phenylpropanoids-related pathways during germination process under PEG stress.

BACKGROUND: Foxtail millet [Setaria italica (L.) P. Beauv.] is an excellent crop known for its superior level of drought tolerance across the world. Especially, less water is needed during its germination period than the other cereal crops. However, the knowledge of the mechanisms underlying the abiotic stress effects on seed germination of foxtail millet is largely unknown. RESULTS: The water uptake pattern of foxtail millet seeds was ploted during germination period, according to which the germination time course of millet was separated into three phases. We sequenced the transcriptome of foxtail millet seeds, which were treated by PEG during different germination phases after sowing. The transcriptional studies revealed that more DEGs were identified during the further increase in water uptake period (phase III) than during the rapid initial uptake period (phase I) and the plateau period (phase II) under PEG stress. The pathway analysis of DEGs showed that the highly enriched categories were related to phenylpropanoid biosynthesis, plant hormone signal transduction and phenylalanine metabolism during phase III. The 20 phenylpropanoids-related genes of germinating foxtail millet were found to be down-regulated during the further increase in water uptake period under PEG stress. Further expression analysis identified 4 genes of phenylalanine ammonia-lyase, 4-coumarate-CoA ligase 3, cinnamoyl-CoA reductase 1, cationic peroxidase SPC4 in phenylpropanoids-related pathway, which played important roles in foxtail millet in response to PEG stress during different germination periods. The studies of metabolites in phenylpropanoid biosynthesis pathway revealed that higher amount of cinnamic acid was accumulated in germinating seeds under PEG stress, while the contents of p-coumaric acid, caffeic acid, ferulic acid and sinapic acid were decreased. And the effects of five phenolic compounds on germination and growth of foxtail millet showed that 1 mM concentration of cinnamic acid inhibited shoot and root growth, especially root development. Ferulic acid, caffeic acid, sinapic acid and p-coumaric acid could increase the root length and root/sprout in lower concentration. CONCLUSIONS: These findings suggest that key genes and metabolites of foxtail millet related with phenylpropanoids pathway may play prominent roles in the regulation of resistance to drought during germination. Foxtail millet can probably avoid drought by regulating the levels of endogenous allelochemicals.

Non-Tacky Fluorinated and Elastomeric STEM Networks.

Soft, elastomeric, non-tacky polymer networks are synthesized by reversible deactivation radical polymerization (RDRP). First, the pristine, structurally tailored and engineered macromolecular (STEM) networks are synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization and incorporated an atom transfer radical polymerization (ATRP) inimer into the network. Subsequently, poly(n-butyl acrylate) (PBA) and/or poly(octafluoropentyl acrylate) (POFPA) side chains are grafted from the network by photo-induced ATRP. These low glass transition temperature side chains produced soft materials (E = 104-178 kPa). However, only the POFPA-containing networks are also non-tacky. The fluorine content and material properties are investigated by dynamic mechanical analysis, elemental analysis, spectroscopy, and contact angle measurements.

A Facile Strategy for Self-Healing Polyurethanes Containing Multiple Metal-Ligand Bonds.

A metal-ligand crosslinked internal self-healing polyurethane is developed using low-cost and commercially available compounds. The mechanical, photoluminescent, and self-healing properties can be governed by incorporating multiple metal-ligand crosslinks with weak and strong coordination bonds and varying the metal ion. In-situ attenuated total reflectance Fourier transform infrared spectroscopy reveals that the metal-ligand bond is cleaved during the damage process while metal ion is still coordinated with the ligand by stronger metal-pyridyl interaction. The multiple metal-ligand coordination facilitates the crosslinks to be fully reformed during the repairing process, leading to the superior self-healing property.

Superior intratumoral penetration of paclitaxel nanodots strengthens tumor restriction and metastasis prevention.

Recently discovered intratumoral diffusion resistance, together with poor solubility and nontargeted distribution of chemotherapeutic drugs, has significantly impaired the performance of cancer treatments. By developing a well-designed droplet-confined/cryodesiccation-driven crystallization approach, we herein report the successful preparation of nanocrystallites of insoluble chemotherapeutic drug paclitaxel (PTX) in forms of nanodots (NDs, ≈10 nm) and nanoparticles (NPs, ≈70 nm) with considerably high drug loading capacity. Superficially coated Pluronic F127 is demonstrated to endow the both PTX nanocrystallites with excellent water solubility and prevent undesired phagocyte uptake. Further decoration with tumor-penetrating peptide iRGD, as expected, indiscriminatively facilitates tumor cell uptake in traditional monolayer cell culture model. On the contrary, distinctly enhanced performances in inward penetration and ensuing elimination of 3D multicellular tumor spheroids are achieved by iRGD-NDs rather than iRGD-NPs, revealing the significant influence of particle size variation in nanoscale. In vivo experiments verify that, although efficient tumor enrichment is achieved by all nanocrystallites, only the iRGD-grafted nanocrystallites of ultranano size realize thorough intratumoral delivery and reach cancer stem cells, which are concealed inside the tumor core. Consequently, much strengthened restriction on progress and metastasis of orthotopic 4T1 mammary adenocarcinoma is achieved in murine model, in sharp contrast to commercial PTX formulation Taxol.

High intensity focused ultrasound responsive metallo-supramolecular block copolymer micelles.

The metal-supramolecular diblock copolymer containing mechano-labile bis(terpyridine)-Cu(II) complex linkage in the junction point was synthesized. These metal-ligand containing amphiphilic copolymers are able to self-assemble in aqueous solution to form spherical micelles with poly(propylene glycol) block forming the hydrophobic core. It is found that high intensity focused ultrasound can open the copolymer micelles and trigger the release of the payload in the micelle. The micellar properties and release kinetics of encapsulated guest molecule in response to ultrasound stimuli were investigated. The weak Cu(II)-terpyridine dynamic bond in the copolymer chain can be cleaved under ultrasound and thus leads to the disruption of the copolymer micelle and the release of loaded cargo. This study will open up a new way for the molecular design of ultrasound modulated drug delivery systems.

Historic changes of polychlorinated biphenyls (PCBs) in juvenile and adult cetaceans from the Pearl River estuary from 2003 to 2020.

Polychlorinated biphenyls (PCBs), as a type of legacy persistent organic pollutants, pose significant health threats to wildlife. However, long-term residue changes and profiles of PCBs in cetaceans have not been extensively studied in the Pearl River Estuary (PRE), an important marine mammal area in China. Here, the body burdens, spatiotemporal trends, and health risks of 21 chlorobiphenyl congeners (∑21CBs) were analyzed in blubber samples collected from twelve cetacean species (n = 172) in the PRE from 2003 to 2020. Our results revealed medium levels of PCBs (316-96,233 ng g-1 lipid) compared to those reported for cetaceans elsewhere (70-370,000 ng g-1 lipid). Clear differences in PCB distribution patterns between inshore and offshore cetaceans and between odontocetes and mysticetes were also found. Both the coastal Indo-Pacific humpback dolphins (Sousa chinensis) and Indo-Pacific finless porpoises (Neophocaena phocaenoides) displayed similarly fine-scale spatial distribution patterns of PCBs, suggesting that the two cetaceans could serve as bioindicators of PCB pollution in the PRE. Additionally, both cetaceans exhibited decreasing trends in their blubber PCB concentrations over the past 20 years, likely reflecting the effective regulation of PCBs in the PRE Delta. Nevertheless, the relatively high and stable PCB-toxic equivalent (TEQ) levels detected in calf humpback dolphins during the sampling period suggested that the calves are still under the stresses of high PCB-related health risks. Our results highlight the need for more efforts to eliminate PCB contamination to prevent these cetaceans from continuous population decline and further extinction.

[Clinical comparative study on aesthetic effect of all-ceramic micro-veneer and minimally invasive ultra-thin veneer in repairing deformed anterior teeth].

PURPOSE: To compare the aesthetic effects of all-ceramic micro-veneer and minimally invasive ultra-thin veneer in repairing deformed anterior teeth. METHODS: One hundred and twenty patients with deformed anterior teeth were selected for aesthetic restoration. According to the patient's personal condition, a suitable repair protocol was selected. Patients in the experimental group (60 cases) were repaired with all-ceramic micro-adhesive surface, while patients in the control group (60 cases) were treated with minimally invasive ultra-thin veneer. The US Public Health Administration's Evaluation Criteria (USPHS) scores were recorded and compared 6 months, 12 months, and 24 months after restoration. Statistical analysis was performed using SPSS 25.0 software package. RESULTS: There was no significant difference in the integrity, color, marginal closeness, translucency and marginal staining of the restorations between the two groups 24 months after operation (P>0.05). The satisfaction rate of the aesthetics of the experimental group was significantly lower than that of the control group (71.60% vs 93.83%, P<0.05). The incidence of complications such as broken, detached and secondary caries during the follow-up period was significantly lower in the experimental group than in the control group (1.23% vs 11.11%, P<0.05). CONCLUSIONS: The results showed that there is no significant difference in the success rate between the two methods. All-ceramic micro-veneer technique has good long-term effect, fewer complications, easy to collapse and stain the lip margin, but it has a small amount of teeth preparation and a low incidence of pulpitis in the later period. Minimally invasive super-thin veneer has high aesthetic value, so it is necessary to choose appropriate aesthetic repair methods according to the patients' needs.

One-pot synthesis of multi-functional and environmental friendly tannic acid polymer with Fe3+ and formaldehyde as double crosslinking agents for selective removal of cation pollutants.

A novel multi-functional and environmental friendly tannic acid polymer (Fe3+-TA-HCHO) with Fe3+ and formaldehyde as double crosslinking agents together with cysteine as heteroatom source was prepared by a one-pot hydrothermal method. Characterization with transmission electron microscope (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectrometer (FT-IR), and elemental analysis demonstrated that the Fe3+-TA-HCHO possessed uniform structure and particle size as well as plentiful functional groups. The resulted Fe3+-TA-HCHO material as a adsorbent to remove methylene blue, sunset yellow, Pb2+, Hg2+, and AsO33- from water. The results suggested that Fe3+-TA-HCHO polymer (pHpzc is 2.33) showed different adsorption properties for anionic pollutants (sunset yellow and AsO33-) and cationic pollutants (methylene blue, Pb2+, and Hg2+). The material exhibited remarkable selectivity for adsorption and separation of pollutants. The maximum adsorption capacities calculated from Langmuir model for methylene blue, Pb2+, and Hg2+ were 154.32, 819.67, and 699.30 mg g-1, respectively. This is the first time that tannic acid polymer is synthesized by double crosslinking method, which not only developed a promising adsorbent for selective removal of cation pollutants, but also opened up a new avenue for synthesis and application of tannic acid polymer.

Water-dispersible pH/thermo dual-responsive microporous polymeric microspheres as adsorbent for dispersive solid-phase extraction of fluoroquinolones from environmental water samples and food samples.

Multifunctional polymeric microspheres were prepared using hyper-cross-linking chemistry combined with surface-initiated atom transfer radical polymerization. The synthesized microspheres exhibited good water dispersibility, a high surface area, and pH/thermo dual-responsiveness. Fluoroquinolones (FQs), which contains a hydrophilic piperazine ring and hydrophobic fluorine atoms, were used as target analytes to assess the performance of the microspheres as a sorbent for dispersive solid-phase extraction (d-SPE). The d-SPE experimental parameters, including extraction time, amount of microspheres, extraction temperature, and sample solution pH, as well as the desorption conditions, were systematically studied. Coupled with LCMS/MS, an analytical method for analysis of trace-level FQs in water samples was developed and validated. Under optimal conditions, linearity with correlation coefficients (r) of >0.99 was achieved in the concentration range of 0.02-10 µg L-1. The limits of detection and quantification for the selected FQs were 5.0-6.7 and 12-20 ng L-1, respectively. High recovery values (93.1%-97.2%), a high enrichment factor (˜180), and good precision (RSD < 8%, n = 6) were obtained for FQ determination in spiked purified water samples. It was proposed that hydrophilic-hydrophobic transition induced by stretching and shrinking of polymer chains under different pH and temperature conditions offered good control of the surface wettability and altered the extraction behavior. The developed method was validated and was successfully applied to the analysis of FQs in environmental water samples, meat and milk samples. These results demonstrated that the water-dispersible polymeric microspheres have good potential for use in separation and extraction techniques.

Novel 3D Neuron Regeneration Scaffolds Based on Synthetic Polypeptide Containing Neuron Cue.

Neural tissue engineering has become a potential technology to restore the functionality of damaged neural tissue with the hope to cure the patients with neural disorder and to improve their quality of life. This paper reports the design and synthesis of polypeptides containing neuron stimulate, glutamic acid, for the fabrication of biomimetic 3D scaffold in neural tissue engineering application. The polypeptides are synthesized by efficient chemical reactions. Monomer γ-benzyl glutamate-N-carboxyanhydride undergoes ring-opening polymerization to form poly(γ-benzyl-l-glutamate), then hydrolyzes into poly(γ-benzyl-l-glutamate)-r-poly(glutamic acid) random copolymer. The glutamic acid amount is controlled by hydrolysis time. The obtained polymer molecular weight is in the range of 200 kDa for good quality of fibers. The fibrous 3D scaffolds of polypeptides are fabricated using electrospinning techniques. The scaffolds are biodegradable and biocompatible. The biocompatibility and length of neurite growth are improved with increasing amount of glutamic acid in scaffold. The 3D scaffold fabricated from aligned fibers can guide anisotropic growth of neurite along the fiber and into 3D domain. Furthermore, the length of neurite outgrowth is longer for scaffold made from aligned fibers as compared with that of isotropic fibers. This new polypeptide has potential for the application in the tissue engineering for neural regeneration.

Human heart valve-derived scaffold improves cardiac repair in a murine model of myocardial infarction.

Cardiac tissue engineering using biomaterials with or without combination of stem cell therapy offers a new option for repairing infarcted heart. However, the bioactivity of biomaterials remains to be optimized because currently available biomaterials do not mimic the biochemical components as well as the structural properties of native myocardial extracellular matrix. Here we hypothesized that human heart valve-derived scaffold (hHVS), as a clinically relevant novel biomaterial, may provide the proper microenvironment of native myocardial extracellular matrix for cardiac repair. In this study, human heart valve tissue was sliced into 100 µm tissue sheet by frozen-sectioning and then decellularized to form the hHVS. Upon anchoring onto the hHVS, post-infarct murine BM c-kit+ cells exhibited an increased capacity for proliferation and cardiomyogenic differentiation in vitro. When used to patch infarcted heart in a murine model of myocardial infarction, either implantation of the hHVS alone or c-kit+ cell-seeded hHVS significantly improved cardiac function and reduced infarct size; while c-kit+ cell-seeded hHVS was even superior to the hHVS alone. Thus, we have successfully developed a hHVS for cardiac repair. Our in vitro and in vivo observations provide the first clinically relevant evidence for translating the hHVS-based biomaterials into clinical strategies to treat myocardial infarction.

Heavy Metal Resistances and Chromium Removal of a Novel Cr(VI)-Reducing Pseudomonad Strain Isolated from Circulating Cooling Water of Iron and Steel Plant.

Three bacterial isolates, GT2, GT3, and GT7, were isolated from the sludge and water of a circulating cooling system of iron and steel plant by screening on Cr(VI)-containing plates. Three isolates were characterized as the members of the genus Pseudomonas on the basis of phenotypic characteristics and 16S rRNA sequence analysis. All isolates were capable of resisting multiple antibiotics and heavy metals. GT7 was most resistant to Cr(VI), with a minimum inhibitory concentration (MIC) of 6.5 mmol L-1. GT7 displayed varied rates of Cr(VI) reduction in M2 broth, which was dependent on pH, initial Cr(VI) concentration, and inoculating dose. Total chromium analysis revealed that GT7 could remove a part of chromium from the media, and the maximum rate of chromium removal was up to 40.8 %. The Cr(VI) reductase activity of GT7 was mainly associated with the soluble fraction of cell-free extracts and reached optimum at pH 6.0∼8.0. The reductase activity was apparently enhanced by external electron donors and Cu(II), whereas it was seriously inhibited by Hg(II), Cd(II), and Zn(II). The reductase showed a K m of 74 µmol L-1 of Cr(VI) and a V max of 0.86 µmol of Cr(VI) min-1 mg-1 of protein. The results suggested that GT7 could be a promising candidate for in situ bioremediation of Cr(VI).

Chuanminshen violaceum polysaccharides improve the immune responses of foot-and-mouth disease vaccine in mice.

Water-soluble polysaccharides from Chuanminshen violaceum (CVPS) were evaluated for their physicochemical properties, monosaccharide composition, and adjuvant potential to specific cellular and humoral immune responses in a mouse model of foot-and-mouth disease virus (FMDV) vaccination. The average molecular weight (Mw) of the CVPS was 968.31 kDa. The monosaccharide components of the CVPS was rhamnose, arabinose, fucose, mannose, glucose, and galactose with a relative mass of 6.29%, 21.87%, 16.59%, 12.54%, 13.07%, and 28.05%, respectively. Administering CVPS as an adjuvant significantly enhanced the phagocytic capacity of peritoneal macrophages, splenocyte proliferation, and the activity of NK cells and CTL as well as increased FMDV-specific IgG and IgG subclass antibody titers. Moreover, CVPS increased the expression of IL-2, IFN-γ, and IL-4 in CD4(+) T cells and IFN-γ expression in CD8(+) T cells. Additionally, CVPS enhanced CD40(+), CD80(+), and CD86(+) expression on DCs. Moreover, CVPS upregulated MHC-I/II, TLR-2/4 mRNA levels. In contrast, CVPS downregulated TGF-ß mRNA expression and the frequency of CD4(+)CD25(+)Foxp3(+) Treg cells. Taken together, these results indicate that administering CVPS as an adjuvant enhances both cellular and humoral immune responses via the TLR-2 and TLR-4 signalling pathways, thereby promoting DC maturation and suppressing TGF-ß expression and Treg frequency.

[Microflora on mucosa under different pontics of fixed partial bridge].

OBJECTIVE: To investigate the influence of three pontic types on alveolar ridge mucosal microecosystem. METHODS: Sixty patients ready to accept three unit metal ceramic bridges were selected. The bacterial type and the cultivable flora were counted and the proportions of bacteria detected on the top of alveolar ridge mucosal contact area before tooth preparation and three months after bridge insertion. RESULTS: Type and CFU of bacteria on the alveolar ridge mucosa under modified base-type pontics and modified ridge lap pontics increased significantly (P < 0.05); while there was no significant change under the ovata pontics (P > 0.05). Before tooth preparation and 3 months after fixed prosthesis insertion, the percentages of oral Streptococci and Neisseriae changed significantly (P < 0.05). CONCLUSIONS: The ovata pontic had less influence on mucosal microecosystem than the other two pontics and is the appropriate pontic design for clinical dentist.