Oxidative stress-induced hypermethylation and low expression of ANXA2R: Novel insights into the dysfunction of melanocytes in vitiligo.

BACKGROUND: Vitiligo is a skin disorder with melanocyte destruction caused by complex interplay between multiple genetic and environmental factors. Recent studies have suggested DNA methylation is involved in the melanocyte damage, but the underlying mechanism remains unknown. OBJECTIVE: To explore the abnormal DNA methylation patterns in vitiligo lesional and nonlesional skin, and the mechanism of DNA methylation involved in vitiligo pathogenesis. METHODS: Initially, the genome-wide aberrant DNA methylation profiles in lesional and nonlesional skin of vitiligo were detect via Illumina methylation EPIC 850k Beadchip. Subsequently, a comprehensive analysis was conduct to investigate the genomic characteristics of differentially methylated regions (DMRs). Furthermore, the effects of key aberrant methylated genes on cell apoptosis and function of both melanocytes and keratinocytes were further identified and validated by western bloting, ELISA, and immunofluorescence. RESULTS: Compared with nonlesional skins, we discovered 79 significantly differentially methylated CpG sites in vitiligo lesions. These DMRs were mainly located in the gene body and the TS1500 region. Annexin A2 receptor (ANXA2R), a crucial gene in cell apoptosis, was hypermethylated in vitiligo lesions. Furthermore, we showed that ANXA2R displayed hypermethylation and low expression levels in both keratinocytes and melanocytes of vitiligo patients, and the hypermethylated-triggered downregulation of ANXA2R under oxidative stress induced melanocyte apoptosis, and inhibited the secretion of stem cell factor (SCF) from keratinocytes thus impaired the survival of melanocytes. CONCLUSIONS: Our study illustrates the DNA methylation modification in vitiligo, and further demonstrates the molecular mechanism of hypermethylated ANXA2R in the dysfunction of melanocytes under oxidative stress.

A synergistically antimicrobial and antioxidant hyaluronic acid hydrogel for infected wounds.

Bacterial infections during wound healing impede the healing process and trigger local or systemic inflammatory reactions. Consequently, there is an urgent need to develop a new material with antimicrobial and antioxidant properties to promote infected wound healing. A synergistically antimicrobial and antioxidant hyaluronic acid hydrogel (HMn) is prepared by employing MnO2 nanosheets into 4ARM-PEG5000-SH crosslinked methacrylated hyaluronic acid (HAMA) network. The coordination between sulfhydryl groups of 4ARM-PEG5000-SH and MnO2 nanosheets ensures entrapment of the nanosheets within the hydrogel, while the interaction between 4ARM-PEG5000-SH and HAMA results in facile gelation through thiol-ene click reaction. MnO2 nanosheets exhibit strong photothermal properties and reactive oxygen species (ROS) scavenging abilities, while hyaluronic acid promotes wound healing. When subjected to near-infrared (NIR) irradiation, the HMn achieves a bactericidal rate of 95.24 % for Staphylococcus aureus and nearly 100 % for Escherichia coli. In animal experiments, treatment with the HMn under NIR irradiation results in the best wound healing outcomes. Both in vitro and vivo biocompatible assays demonstrate that the HMn has rarely cell cytotoxicity and tissue damage. The HMn is easy to prepare and has good biocompatibility as well as efficient antibacterial and antioxidant properties, providing a novel method for the treatment of infected wounds.

Bimetallic Organic Gel for Effective Methyl Orange Dye Adsorption.

A bimetallic organic gel (MOG-Fe/Al) was synthesized through the solvothermal method. The gel state of the product obtained under optimized gel formation conditions is sufficient to carry 2 g of weight for a long time. Scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, Brunauer-Emmett-Teller (BET) technique, and X-ray photoelectron spectroscopy (XPS) analysis confirmed the structures and morphologies of the synthesized materials. MOG-Fe/Al, with good stability, excellent durability, and wide applicability, exhibited efficient MO adsorption capacity as high as 335.88 mg/g at 25 °C. Adsorption-influencing factors including solution pH, contact time, and temperature were investigated. The adsorption performance of the bimetallic organic gel was better than that of the monometallic organic gels (MOG-Fe and MOG-Al), and its adsorption processes were in accordance with the pseudo-second-order kinetic and Langmuir isothermal models. The excellent adsorption capacity of the MOG-Fe/Al is due to its surface structure, pore volume, π-π interactions, hydrogen bonds, and electrostatic interactions.

Bioactivity assessment of organophosphate flame retardants via a dose-dependent yeast functional genomics approach.

Organophosphate flame retardants (OPFRs) have been widely detected in multiple environment media and have many adverse effects with complex toxicity mechanisms. However, the early molecular responses to OPFRs have not been fully elucidated, thereby making it difficult to assess their risks accurately. In this work, we systematically explored the point of departure (POD) of biological pathways at genome-wide level perturbed by 14 OPFRs with three substituents (alkyl, halogen, and aryl) using a dose-dependent functional genomics approach in Saccharomyces cerevisiae at 24 h exposure. Firstly, our results demonstrated that the overall biological potency at gene level (PODDRG20) ranged from 0.013 to 35.079 µM for 14 OPFRs, especially the tributyl phosphate (TnBP) exhibited the strongest biological potency with the least PODDRG20. Secondly, we found that structural characteristics of carbon number and logKow were significantly negatively correlated with POD, and carbon number and logKow also significantly affected lipid metabolism associated processes. Thirdly, these early biological pathways of OPFRs toxification were found to be involved in lipid metabolism, oxidative stress, DNA damage, MAPK signaling pathway, and amino acid and carbohydrate metabolism, among which the lipid metabolism was the most sensitive molecular response perturbed by most OPFRs. More importantly, we identified one resistant mutant strain with knockout of ERG2 (YMR202W) gene participated in steroid biosynthesis pathway, which can serve as a key yeast strain of OPFRs toxification. Overall, our study demonstrated an effective platform for accurately assessing OPFRs risks and provided a basis for further green OPFRs development.

Discovery of a potent and highly selective inhibitor of SIRT6 against pancreatic cancer metastasis in vivo.

Pancreatic cancer, one of the most aggressive malignancies, has no effective treatment due to the lack of targets and drugs related to tumour metastasis. SIRT6 can promote the migration of pancreatic cancer and could be a potential target for antimetastasis of pancreatic cancer. However, highly selective and potency SIRT6 inhibitor that can be used in vivo is yet to be discovered. Here, we developed a novel SIRT6 allosteric inhibitor, compound 11e, with maximal inhibitory potency and an IC50 value of 0.98 ± 0.13 µmol/L. Moreover, compound 11e exhibited significant selectivity against other histone deacetylases (HADC1‒11 and SIRT1‒3) at concentrations up to 100 µmol/L. The allosteric site and the molecular mechanism of inhibition were extensively elucidated by cocrystal complex structure and dynamic structural analyses. Importantly, we confirmed the antimetastatic function of such inhibitors in four pancreatic cancer cell lines as well as in two mouse models of pancreatic cancer liver metastasis. To our knowledge, this is the first study to reveal the in vivo effects of SIRT6 inhibitors on liver metastatic pancreatic cancer. It not only provides a promising lead compound for subsequent inhibitor development targeting SIRT6 but also provides a potential approach to address the challenge of metastasis in pancreatic cancer.

Orchestrating Precision within the Tumor Microenvironment by Biomimetic Nanoprodrugs for Effective Tumor Therapy.

Malignant tumors are still one of the most deadly diseases that threaten human life and health. However, developing new drugs is challenging due to lengthy trials, funding constraints, and regulatory approval procedures. Consequently, researchers have devoted themselves to transforming some clinically approved old drugs into antitumor drugs with certain active ingredients, which have become an attractive alternative. Disulfiram (DSF), an antialcohol medication, can rapidly metabolize in the physiological environment into diethyldithiocarbamate (DTC) which can readily react with Cu2+ ions in situ to form the highly toxic bis(N,N-diethyldithiocarbamate)-copper(II) (CuET) complex. In this study, DSF is loaded into mesoporous dopamine nanocarriers and surface-chelated with tannin and Cu2+ to construct M-MDTC nanoprodrugs under the camouflage of K7 tumor cell membranes. After intravenous injection, M-MDTC nanoprodrugs successfully reach the tumor sites with the help of mediated cell membranes. Under slightly acidic pH and photothermal stimulation conditions, DSF and Cu2+ are simultaneously released, forming a highly toxic CuET to kill tumor cells in situ. The generated CuET can also induce immunogenic cell death of tumor cells, increase the proportion of CD86+ CD80+ cells, and promote dendritic cell maturation. In vitro and in vivo studies of M-MDTC nanoprodrugs have shown excellent tumor-cell-killing ability and solid tumor suppression. This approach enables in situ amplification of chemotherapy in the tumor microenvironment, achieving an effective antitumor treatment.

Synergistic reinforcement of immunogenic cell death and transformation of tumor-associated macrophages via an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform.

The immune system's role in tumor growth and spread has led to the importance of activating immune function in tumor therapy. We present a strategy using an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform (M1mDDTF) to synergistically reinforce immunogenic cell death (ICD) and transform tumor-associated macrophages (TAMs) against tumors. The M1mDDTF nanoparticles consist of doxorubicin-loaded dendritic mesoporous silica nanoparticles chelated with FeIII-tannic acid (FeIIITA) and coated with M1-type macrophage membranes. In the acidic tumor microenvironment, FeIIITA releases Fe2+ and generates ·OH, aided by near infrared irradiation for enhanced doxorubicin release. Furthermore, the M1mDDTF nanoplatform not only directly kills tumor cells but stimulates ICD, which can increase the proportion of CD86+ CD80+ cells and promote dendritic cell maturation. Particularly, the M1mDDTF nanoplatform can also promote the gradual polarization of TAMs into the M1-type and promote tumor cell killing. This study demonstrates the safety and multifunctionality of M1mDDTF nanoparticles, highlighting their potential for clinical tumor treatment. STATEMENT OF SIGNIFICANCE: Malignant tumors are a global concern and a major cause of death. Nanoparticles' passive targeting is ineffective and hindered by reticuloendothelial system clearance. Therefore, enhancing nanoparticle accumulation in tumors while minimizing toxicity is a challenge. Coating nanoparticles with cell membranes enhances biocompatibility, immune evasion, and specific targeting. This approach has led to the development of numerous cell membrane-mimicking nanomaterials with remarkable properties and functions. This study developed an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform, boosting immunogenic cell death and transforming tumor-associated macrophages. Tannic acid in the tumor microenvironment reduced Fe3+ to Fe2+, generating ·OH. M1mDDTF nanosystem induced M1-type macrophage polarization, inhibiting tumor growth and triggering immune cell death. Safe and versatile, these M1mDDTF nanoparticles hold promise for clinical tumor treatment.

Oxidative stress drives vascular smooth muscle cell damage in acute Stanford type A aortic dissection through HIF-1α/HO-1 mediated ferroptosis.

Background: Acute Stanford type A aortic dissection (ATAAD) is characterized by intimal tearing and false lumen formation containing large amounts of erythrocytes with heme. Heme oxygenase 1 (HO-1) is the key enzyme to degrade heme for iron accumulation and further ferroptosis. The current study aimed at investigating the role of HO-1 in the dissection progression of ATAAD. Methods: Bioinformatic analyses and experimental validation were performed to reveal ferroptosis and HO-1 expression in ATAAD. Human aortic vascular smooth muscle cell (HA-VSMC) was used to explore underlying molecular mechanisms and the role of HO-1 overexpression in ATAAD. Results: Ferroptosis was identified as a critical manner of regulated cell death in ATAAD. HO-1 was screened as a key signature of ferroptosis in ATAAD, which was closely associated with oxidative stress. Single cell/nucleus transcriptomic analysis and histological staining revealed that HO-1 and HIF-1α were upregulated in vascular smooth muscle cell (VSMC) of ATAAD. Further in vitro experiments showed that H2O2-induced oxidative stress increased VSMC ferroptosis with the overexpression of HO-1, which could be suppressed by HIF-1α inhibitor PX-478. HIF-1α could transcriptionally regulate the expression of HO-1 through binding to its promoter region. Pharmacological inhibition of HO-1 by zinc protoporphyrin (ZnPP) did not reduce H2O2-induced HA-VSMC damage without heme co-incubation. However, H2O2-induced HA-VSMC damage was worsened when heme was added into the medium, and ZnPP could reduce HA-VSMC damage in this condition. Conclusion: HO-1 is a key signature of VSMC ferroptosis in ATAAD. HIF-1α/HO-1 mediated ferroptosis might participate in oxidative stress induced VSMC damage.

A facile strategy to fabricate a skin-like hydrogel with adhesive and highly stretchable attributes through small molecule triggering toward flexible electronics.

Polyacrylamide hydrogel is a promising matrix in biomedical applications due to its biocompatibility, transparency and flexibility. However, its implementation in skin-attachable applications is impeded by its inherent deficiency in surface-adaptive adhesion and inadequate mechanical conformity to skin tissues. Herein, tris, a biocompatible small molecule with a triple hydrogen bonding cluster in its molecule structure, is introduced for the first time into a polyacrylamide hydrogel. This incorporation is achieved via a facile one-pot strategy, resulting in a highly stretchable hydrogel with an impressive strain capacity (2574.75 ± 28.19%), a human dermis tissue-compatible Young's modulus (27.89 ± 2.05 kPa) and an intrinsically universal adhesion capacity (16.66 ± 0.32 N). These superior properties are attributed to the elevated hydrogen bonding density and the plasticizing effect induced by tris, without compromising the hydrogel's excellent transparency (>90% transmittance). Moreover, by incorporating calcium ions into the resulting soft adhesive hydrogel, we demonstrate its utility in skin-like sensors, leading to a substantial enhancement in strain sensitivity and electrical conductivity, in conjunction with the plasticizing influence exerted by tris. This work offers a facile and environmentally friendly solution to fabricate ultra-stretchable adhesive polyacrylamide hydrogel matrixes for dynamic surfaces, even under large deformation, which can broaden their potential applications in integrated bioelectronics.

TMEM215 Prevents Endothelial Cell Apoptosis in Vessel Regression by Blunting BIK-Regulated ER-to-Mitochondrial Ca Influx.

BACKGROUND: In developmental and pathological tissues, nascent vessel networks generated by angiogenesis require further pruning/regression to delete nonfunctional endothelial cells (ECs) by apoptosis and migration. Mechanisms underlying EC apoptosis during vessel pruning remain elusive. TMEM215 (transmembrane protein 215) is an endoplasmic reticulum-located, 2-pass transmembrane protein. We have previously demonstrated that TMEM215 knockdown in ECs leads to cell death, but its physiological function and mechanism are unclear. METHODS: We characterized the role and mechanism of TMEM215 in EC apoptosis using human umbilical vein endothelial cells by identifying its interacting proteins with immunoprecipitation-mass spectrometry. The physiological function of TMEM215 in ECs was assessed by establishing a conditional knockout mouse strain. The role of TMEM215 in pathological angiogenesis was evaluated by tumor and choroidal neovascularization models. We also tried to evaluate its translational value by delivering a Tmem215 small interfering RNA (siRNA) using nanoparticles in vivo. RESULTS: TMEM215 knockdown in ECs induced apoptotic cell death. We identified the chaperone BiP as a binding partner of TMEM215, and TMEM215 forms a complex with and facilitates the interaction of BiP (binding immunoglobin protein) with the BH (BCL-2 [B-cell lymphoma 2] homology) 3-only proapoptotic protein BIK (BCL-2 interacting killer). TMEM215 knockdown triggered apoptosis in a BIK-dependent way and was abrogated by BCL-2. Notably, TMEM215 knockdown increased the number and diminished the distance of mitochondria-associated endoplasmic reticulum membranes and increased mitochondrial calcium influx. Inhibiting mitochondrial calcium influx by blocking the IP3R (inositol 1,4,5-trisphosphate receptor) or MCU (mitochondrial calcium uniporter) abrogated TMEM215 knockdown-induced apoptosis. TMEM215 expression in ECs was induced by physiological laminar shear stress via EZH2 downregulation. In EC-specific Tmem215 knockout mice, induced Tmem215 depletion impaired the regression of retinal vasculature characterized by reduced vessel density, increased empty basement membrane sleeves, and increased EC apoptosis. Moreover, EC-specific Tmem215 ablation inhibited tumor growth with disrupted vasculature. However, Tmem215 ablation in adult mice attenuated lung metastasis, consistent with reduced Vcam1 expression. Administration of nanoparticles carrying Tmem215 siRNA also inhibited tumor growth and choroidal neovascularization injury. CONCLUSIONS: TMEM215, which is induced by blood flow-derived shear stress via downregulating EZH2, protects ECs from BIK-triggered mitochondrial apoptosis mediated by calcium influx through mitochondria-associated ER membranes during vessel pruning, thus providing a novel target for antiangiogenic therapy.

Characterizing temporal variability and repeatability of dose-dependent functional genomics approach for evaluating triclosan toxification.

Dose-dependent functional genomics approach has shown great advantage in identifying the molecular initiating event (MIE) of chemical toxification and yielding point of departure (POD) at genome-wide scale. However, POD variability and repeatability derived from experimental design (settings of dose, replicate number, and exposure time) has not been fully determined. In this work, we evaluated POD profiles perturbed by triclosan (TCS) using dose-dependent functional genomics approach in Saccharomyces cerevisiae at multiple time points (9 h, 24 h and 48 h). The full dataset (total 9 concentrations with 6 replicates per treatment) at 9 h was subsampled 484 times to generate subsets of 4 dose groups (Dose A - Dose D with varied concentration range and spacing) and 5 replicate numbers (2 reps - 6 reps). Firstly, given the accuracy of POD and the experimental cost, the POD profiles from 484 subsampled datasets demonstrated that the Dose C group (space narrow at high concentrations and wide dose range) with three replicates was best choice at both gene and pathway levels. Secondly, the variability of POD was found to be relatively robustness and stability across different experimental designs, but POD was more dependent on the dose range and interval than the number of replicates. Thirdly, MIE of TCS toxification was identified to be the glycerophospholipid metabolism pathway at all-time points, supporting the ability of our approach to accurately recognize MIE of chemical toxification at both short- and long-term exposure. Finally, we identified and validated 13 key mutant strains involved in MIE of TCS toxification, which could serve as biomarkers for TCS exposure. Taken together, our work evaluated the repeatability of dose-dependent functional genomics approach and the variability of POD and MIE of TCS toxification, which will benefit the experimental design for future dose-dependent functional genomics study.

A multifunctional polymeric coating with self-adsorbed, antifouling and in situ remineralization properties for caries management.

Dental caries is a biofilm-induced bacterial infectious oral disease, where the early attachment of proteins and pathogenic bacteria to tooth surfaces has been known as the main cause of biofilm formation. Typically, dental caries is commonly accompanied by mineral depletion of enamels, thus causing dental demineralization. Multifunctional materials are highly attractive candidates for treating dental caries. Herein, we successfully synthesized diblock copolymers poly(ethylene glycol)-b-poly(aspartic acid) (PEG-PAsp) and modified them with alendronate sodium (ALN) to serve as bioactive bifunctional coatings (PEG-PAsp-ALN) on teeth. The PEG segments are employed for inhibiting proteins and bacterial adhesion. In addition, due to the presence of both PAsp and ALN, a synergistically strong binding capacity could be achieved with the tooth surface, thus promoting rapid and thorough remineralization in situ, while maintaining excellent safety. The combination treatment can significantly suppress the biofilm formation, which is beneficial for alleviating the demineralization of enamels caused by bacteria, and further, facilitate remineralization in situ. This approach thus demonstrates the potential of the copolymer PEG-PAsp-ALN coating as a multifunctional protecting layer on the tooth surface for high-efficiency prevention and treatment of dental caries.

The use of immobilised bacteria cross-linked within magnetic alginate beads enhances the treatment of benzophenone-type UV filter chemicals by the SBR system.

Benzophenone-n compounds (BPs) are applied in a broad spectrum of commercial products, one of which is sunscreen. These chemicals are frequently detected in a variety of environmental matrices worldwide, especially water bodies. BPs are defined as emerging contaminants as well as endocrine-disrupting contaminants; thus, it has become necessary to develop aggressive and green treatments to remove BPs. In this study, we used immobilised BP-biodegrading bacteria linked to reusable magnetic alginate beads (MABs). The MABs were added to a sequencing batch reactor (SBR) system to enhance the removal of 2,4-dihydroxybenzophenone (BP-1) and oxybenzone (BP-3) from sewage. The BP-1 and BP-3 biodegrading bacteria in the MABs consisted of strains from up to three genera to allow for efficient biodegradation. The strains used were Pseudomonas spp., Gordonia sp., and Rhodococcus sp. The optimal composition of the MABs consisted of 3% (w/v) alginate and 10% (w/v) magnetite. The MABs resulted in 60.8%-81.7% recovery by weight after 28 days, and there was a continuous release of bacteria. Moreover, the biological treatment of the BPs sewage improved after adding 100 g of BP1-MABs (1:27) and also 100 g BP3-MABs (1:27) into the SBR system at a hydraulic retention time (HRT) of 8 h. Compared with the SBR system without MABs, the removal rates of BP-1 and BP-3 increased from 64.2% to 71.5% and from 78.1% to 84.1%, respectively. Furthermore, the COD removal increased from 36.1% to 42.1%, and total nitrogen increased from 30.5% to 33.2%. Total phosphorus remained constant at 29%. The bacterial community analysis showed that the Pseudomonas population was <2% before the MAB addition, but increased to 56.1% by day 14. In contrast, the Gordonia sp. And Rhodococcus sp. Populations (<2%) remained unchanged throughout the 14-day treatment period.

Recent advances in adhesive materials used in the biomedical field: adhesive properties, mechanism, and applications.

Adhesive materials are natural or synthetic polymers with the ability to adhere to the surface of luminal mucus or epithelial cells. They are widely used in the biomedical field due to their unique adhesion, biocompatibility, and excellent surface properties. When used in the human body, they can adhere to an accessible target and remain at the focal site for a longer period, improving the therapeutic effect on local disease. An adhesive material with bacteriostatic properties can play an antibacterial role at the focal site and the adhesive properties of the material can prevent the focal site from being infected by bacteria for a period. In addition, some adhesive materials can promote cell growth and tissue repair. In this review, the properties and mechanism of natural adhesive materials, organic adhesive materials, composite adhesive materials, and underwater adhesive materials have been introduced systematically. The applications of these adhesive materials in drug delivery, antibacterials, tissue repair, and other applications are described in detail. Finally, we have discussed the prospects and challenges of using adhesive materials in the field of biomedicine.

Self-Adaptive Antibacterial Scaffold with Programmed Delivery of Osteogenic Peptide and Lysozyme for Infected Bone Defect Treatment.

Bone defects caused by disease or trauma are often accompanied by infection, which severely disrupts the normal function of bone tissue at the defect site. Biomaterials that can simultaneously reduce inflammation and promote osteogenesis are effective tools for addressing this problem. In this study, we set up a programmed delivery platform based on a chitosan scaffold to enhance its osteogenic activity and prevent implant-related infections. In brief, the osteogenic peptide sequence (YGFGG) was modified onto the surface of cowpea chlorotic mottle virus (CCMV) to form CCMV-YGFGG nanoparticles. CCMV-YGFGG exhibited good biocompatibility and osteogenic ability in vitro. Then, CCMV-YGFGG and lysozyme were loaded on the chitosan scaffold, which exhibited a good antibacterial effect and promoted bone regeneration for infected bone defect treatment. As a delivery platform, the scaffold showed staged release of lysozyme and CCMV-YGFGG, which facilitates the regeneration of infected bone defects. Our study provides a novel and promising strategy for the treatment of infected bone defects.

Multifunctional epoxy resin-based composites with excellent flexural strength and X-ray imaging capacity using micro/nano structured QF-Bi2SiO5 fillers.

Composites have been widely applied in various industries and are beneficial in attaining complicated functionalities. Particularly, for dental fiber posts or orthopedic implants, the composites should have excellent mechanical properties and good imaging effects for visualization in vivo. The traditional method to improve mechanical strength and visibility by adding reinforcing fillers and radiopacifiers is complicated and has poor distributions and long production times. Hence, fabricating an integrated reinforced filler with radiopacity is of considerable economic and social significance. After ball-milling and sintering quartz fiber (QF) and bismuth trioxide (Bi2O3), a multifunctional filler (QF-Bi2SiO5) is fabricated to impart excellent flexural strengths and high X-ray imaging qualities to the composites. A composite made of epoxy resin (EP) and QF-Bi2SiO5 has a high bending strength (126.87 ± 6.78 MPa) and bending modulus (3649.31 ± 343.87 MPa), which are attributed to the tight mechanical interlock between EP and micro/nano structures of QF-Bi2SiO5. The QF-Bi2SiO5/EP composite shows good X-ray imaging quality owing to the Bi2SiO5 crystal. Furthermore, the mechanical and imaging performances of various composites with commercial fillers were compared with that of the QF-Bi2SiO5/EP composite. No filler was found that can perform both functions as well as QF-Bi2SiO5. Hence, the fabricated composites containing micro/nano structured QF-Bi2SiO5 fillers have the potential to be used in a variety of fields requiring mechanical strength and X-ray imaging capability.

Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy.

Chemodynamic therapy (CDT), a noninvasive strategy, has emerged as a promising alternative to conventional chemotherapy for treating tumors. However, its therapeutic effect is limited by the amount of H2O2, pH value, the hypoxic environment of tumors, and it has suboptimal tumor-targeting ability. In this study, tumor cell membrane-camouflaged mesoporous Fe3O4 nanoparticles loaded with perfluoropentane (PFP) and glucose oxidase (GOx) are used as a tumor microenvironment-adaptive nanoplatform (M-mFeP@O2-G), which synergistically enhances the antitumor effect of CDT. Mesoporous Fe3O4 nanoparticles are selected as inducers for photothermal and Fenton reactions and as nanocarriers. GOx depletes glucose within tumor cells for starving the cells, while producing H2O2 for subsequent ·OH generation. Moreover, PFP, which can carry O2, relieves hypoxia in tumor cells and provides O2 for the cascade reaction. Finally, the nanoparticles are camouflaged with osteosarcoma cell membranes, endowing the nanoparticles with homologous targeting and immune escape abilities. Both in vivo and in vitro evaluations reveal high synergistic therapeutic efficacy of M-mFeP@O2-G, with a desirable tumor-inhibition rate (90.50%), which indicates the great potential of this platform for clinical treating cancer.

Natural Small Biological Molecule Based Supramolecular Bioadhesives with Innate Photothermal Antibacterial Capability for Nonpressing Hemostasis and Effective Wound Healing.

Bioadhesives with immediate wound closure, efficient hemostasis, and antibacterial properties that can well integrate with tissue are urgently needed in wound management. Natural small biological molecule based bioadhesives hold great promise for manipulating wound healing by taking advantage of integrated functionalities, synthetic simplification, and accuracy, cost efficiency and biosafety. Herein, a natural small biological molecule based bioadhesive, composed of natural small biological molecules (α-lipoic acid and tannic acid) and a small amount of ferric chloride, was prepared via an extremely simple and green route for wound management. In this system, covalent and noncovalent interactions between each component resulted in the self-healing supramolecular bioadhesive. It possessed appropriate wet-tissue adhesion, efficient nonpressing hemostasis and free radical scavenging abilities. More importantly, the interaction between tannic acid and Fe3+ endowed the bioadhesive with innate and steady photothermal activity, which showed excellent photothermal bactericidal activity to both E. coli and S. aureus. The bioadhesive promoted wound healing for linear and circular wounds in vivo, especially for infectious wounds under near-infrared (NIR) irradiation. This bioadhesive will have promising value as a safe and effective antimicrobial adhesive for infectious wound management.

Inspired by the Periodontium: A Universal Bacteria-Defensive Hydrogel for Preventing Percutaneous Device-Related Infection.

Percutaneous device-related infection has greatly shortened the service period of devices and seriously reduced the quality of life of patients. Bacteria are one of the main pathogenic factors and cannot be effectively and conveniently eradicated by traditional strategies (e.g., construct coatings and introduce antibiotics), due to the complex interface among medical devices, surrounding tissue, and colonizing bacteria. Inspired by the periodontium, a universal bacteria-defensive hydrogel adapting to the complicated interface is fabricated by introducing phenol-amine chemistry to a polymeric matrix of N-hydroxyethyl acrylamide (HPC hydrogels). The HPC hydrogels with excellent toughness (2.1 MJ/m3), adhesion (10.2 and 13.2 kPa for pigskin and Ti-6Al-4V alloy, respectively), and antibacterial property (up to 99.9% for both Escherichia coli and Staphylococcus aureus) contributed to the innate microbe barrier via sealing the tissue-device interface and adaptive defense to eradicate bacteria. Meanwhile, bacterial invasion experiments demonstrate HPC hydrogels possess both a bacteria-defensive property (up to 24 h) and cell-protecting function at the same time. Furthermore, the biocompatibility of HPC hydrogels is verified in tests for in vitro cytotoxicity and in vivo irritation. Hence, the designed HPC hydrogels are considered as an emerging and universal candidate for preventing bacterial infection and can protect the deep tissue around a percutaneous device.

Pooled image-base screening of mitochondria with microraft isolation distinguishes pathogenic mitofusin 2 mutations.

Most human genetic variation is classified as variants of uncertain significance. While advances in genome editing have allowed innovation in pooled screening platforms, many screens deal with relatively simple readouts (viability, fluorescence) and cannot identify the complex cellular phenotypes that underlie most human diseases. In this paper, we present a generalizable functional genomics platform that combines high-content imaging, machine learning, and microraft isolation in a method termed "Raft-Seq". We highlight the efficacy of our platform by showing its ability to distinguish pathogenic point mutations of the mitochondrial regulator Mitofusin 2, even when the cellular phenotype is subtle. We also show that our platform achieves its efficacy using multiple cellular features, which can be configured on-the-fly. Raft-Seq enables a way to perform pooled screening on sets of mutations in biologically relevant cells, with the ability to physically capture any cell with a perturbed phenotype and expand it clonally, directly from the primary screen.