SNHG1 knockdown promotes osteogenic differentiation of hDFSCs through anti-oxidative stress mediated by autophagy.

The long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) plays a crucial role in tumorigenesis and is frequently employed as a prognostic biomarker. However, its involvement in the osteogenic differentiation of oral stem cells, particularly human dental follicle stem cells (hDFSCs), remains unclear. Our investigation revealed that the absence of SNHG1 enhances the osteogenic differentiation of hDFSCs. Furthermore, the downregulation of SNHG1 induces autophagy in hDFSCs, leading to a reduction in intracellular oxidative stress levels. Notably, this effect is orchestrated through the epigenetic regulation of EZH2. Our study unveils a novel function of SNHG1 in governing the osteogenic differentiation of hDFSCs, offering fresh insights for an in-depth exploration of the molecular mechanisms underlying dental follicle development. These findings not only provide a foundation for advancing the understanding of SNHG1 but also present innovative perspectives for promoting the repair and regeneration of periodontal supporting tissue, ultimately contributing to the restoration of periodontal health and tooth function.

Lhx6 deficiency causes human embryonic palatal mesenchymal cell mitophagy dysfunction in cleft palate.

BACKGROUND: Overconsumption of retinoic acid (RA) or its analogues/derivatives has been linked to severe craniomaxillofacial malformations, such as cleft palate and midface hypoplasia. It has been noted that RA disturbed the proliferation and migration of embryonic palatal mesenchymal (EPM) cells in these malformations, yet the exact mechanisms underlying these disruptions remained unclear. METHODS: A model of retinoic acid (RA)-induced cleft palate in fetal mice was successfully established. Histological alterations in the palate were evaluated using Hematoxylin and Eosin (H&E) staining and RNA in situ hybridization (RNAscope). Cellular proliferation levels were quantified via the Cell Counting Kit-8 (CCK-8) assay and EdU incorporation assay, while cell migration capabilities were investigated using wound healing and Transwell assays. Mitochondrial functions were assessed through Mito-Tracker fluorescence, mitochondrial reactive oxygen species (ROS) measurement, ATP level quantification, and mitochondrial DNA (mtDNA) copy number analysis. Differential gene expression and associated signaling pathways were identified through bioinformatics analysis. Alterations in the transcriptional and translational levels of Lhx6 and genes associated with mitophagy were quantified using quantitative PCR (qPCR) and Western blot analysis, respectively. Mitochondrial morphology and the mitochondrial autophagosomes within cells were examined through transmission electron microscopy (TEM). RESULTS: Abnormal palatal development in mice, along with impaired proliferation and migration of human embryonic palatal mesenchymal (HEPM) cells, was associated with RA affecting mitochondrial function and concomitant downregulation of Lhx6. Knockdown of Lhx6 in HEPM cells resulted in altered cell proliferation, migration, and mitochondrial function. Conversely, the aberrant mitochondrial function, proliferation, and migration observed in RA-induced HEPM cells were ameliorated by overexpression of Lhx6. Subsequent research demonstrated that Lhx6 ameliorated RA-induced dysfunction in HEPM cells by modulating PINK1/Parkin-mediated mitophagy, thereby activating the MAPK signaling pathways. CONCLUSION: Lhx6 is essential for mitochondrial homeostasis via tuning PINK1/Parkin-mediated mitophagy and MAPK signaling pathways. Downregulation of Lhx6 by RA transcriptionally disturbs the mitochondrial homeostasis, which in turn leads to the proliferation and migration defect in HEPM cells, ultimately causing the cleft palate.

Release Pattern of Light Aromatic Hydrocarbons during the Biomass Roasting Process.

Roasting is an important step in the pretreatment of biomass upgrading. Roasting can improve the fuel quality of biomass, reduce the O/C and H/C ratios in the biomass, and provide the biomass with a fuel quality comparable to that of lignite. Therefore, studying the structure and component evolution laws during biomass roasting treatment is important for the rational and efficient utilization of biomass. When the roasting temperature is 200-300 °C, the cellulose and hemicellulose in the biomass undergo a depolymerization reaction, releasing many monocyclic aromatic hydrocarbons with high reactivity. The proportion of monocyclic aromatic hydrocarbons in biomass roasting products can be effectively regulated by controlling the reaction temperature, residence time, catalyst, baking atmosphere, and other factors in the biomass roasting process. This paper focuses on the dissociation law of organic components in the pretreatment process of biomass roasting.

LncRNA HOTAIRM1 promotes dental follicle stem cell-mediated bone regeneration by regulating HIF-1α/KDM6/EZH2/H3K27me3 axis.

Large bone defect reconstruction undergoes hypoxia and remains a major practical challenge. Bone tissue engineering with a more promising stem cell source facilitates the development of better therapeutic outcomes. Human dental follicle stem cells (hDFSCs) with superior multipotency, osteogenic capacity, and accessibility have been proven a promising cell source for bone regeneration. We previously identified a novel long noncoding RNA (lncRNA), HOTAIRM1, to be highly expressed in hDFSCs. Here we found that HOTAIRM1 overexpressed hDFSCs promoted bone regeneration in rat critical-size calvarial defect model. Mechanically, HOTAIRM1 was induced in hDFSCs under hypoxic conditions and activated HIF-1α. RNA-sequencing analysis indicated that HOTAIRM1 upregulated oxygen-sensing histone demethylases KDM6A/B and suppressed methyltransferase EZH2 via targeting HIF-1α. The osteogenic differentiation of hDFSCs was accompanied with demethylation of H3K27, and HOTAIRM1 overexpression decreased the distribution of H3K27me3 in osteogenic genes, including ALP, M-CSF, Wnt-3a, Wnt-5a, Wnt-7a, and ß-catenin, thus promoted their transcription. Our study provided evidence that HOTAIRM1 upregulated KDM6A/B and inhibited EZH2 in a HIF-1α dependent manner to enhance the osteogenesis of hDFSCs. HOTAIRM1-mediated hDFSCs may serve as a promising therapeutic approach to promote bone regeneration in clinical practice.

Partitioning-Induced Isolation of Analyte and Analysis via Multiscaled Aqueous Two-Phase System.

Most fluorescence-based bioanalytical applications need labeling of analytes. Conventional labeling requires washing to remove the excess fluorescent labels and reduce the noise signals. These pretreatments are labor intensive and need specialized equipment, hindering portable applications in resource-limited areas. Herein, we use the aqueous two-phase system (ATPS) to realize the partitioning-induced isolation of labeled analytes from background signals without extra processing steps. ATPS is formed by mixing two polymers at sufficiently high concentrations. ATPS-based isolation is driven by intrinsic affinity differences between analytes and excess labels. To demonstrate the partitioning-induced isolation and analysis, fluorescein isothiocyanate (FITC) is selected as the interfering fluorophore, and a monoclonal antibody (IgG) is used as the analyte. To optimize ATPS compositions, different molecular weights and mass fractions of polyethylene glycol (PEG) and dextran and different phosphate-buffered saline (PBS) concentrations are investigated. Various operational scales of our approach are demonstrated, suggesting its compatibility with various bioanalytical applications. In centimeter-scale ATPS, the optimized distribution ratios of IgG and FITC are 91.682 and 0.998 using PEG 6000 Da and dextran 10,000 Da in 10 mM PBS. In millimeter-scale ATPS, the analyte is enriched to 6.067 fold using 15 wt % PEG 35,000 Da and 5 wt % dextran 500,000 Da in 10 mM PBS. In microscale ATPS, analyte dilutions are isolated into picoliter droplets, and the measured fluorescence intensities linearly correlated with the analyte concentrations (R2 = 0.982).

Hierarchically Structured Nanoparticle-Free Omniphobic Membrane for High-Performance Membrane Distillation.

The functional loss of membranes caused by pore wetting, mineral scaling, or structural instability is a critical challenge in membrane distillation (MD), which primarily hinders its practical applications. Herein, we propose a novel and facile strategy to fabricate omniphobic membranes with exceptionally robust MD performance. Specifically, a substrate with a hierarchical re-entrant architecture was constructed via spray-water-assisted non-solvent-induced phase separation (SWNIPS), followed by a direct fluorinated surface decoration via "thiol-ene" click chemistry. Deionized (DI) water contact angle measurements revealed an ultrahigh surface water contact angle (166.8 ± 1.8°) and an ultralow sliding angle (3.6 ± 1.1°) of the resultant membrane. Destructive abrasion cycle and ultrasonication tests confirmed its structural robustness. Moreover, the membrane possessed excellent wetting resistance, as evidenced by the prevention of membrane pore penetration by all low-surface-tension testing liquids, allowing stable long-term MD operation to treat brine wastewater with a surfactant content of 0.6 mM. In a desalination experiment using shale gas wastewater, the omniphobic membrane exhibited robust MD performance, achieving a high water recovery ratio of ∼60% without apparent changes in water flux and permeate conductivity over the entire membrane process. Overall, our study paves the way for a nanoparticle-free methodology for the scalable fabrication of high-performance MD membranes with surface omniphobicity and structural robustness in hypersaline wastewater treatment.

The interaction of CD300lf and ceramide reduces the development of periodontitis by inhibiting osteoclast differentiation.

AIM: The regulation of osteoclasts (OCs) by inhibitory immunoreceptors maintains bone homeostasis and is considered an important determinant of the extent of periodontal pathology. The aim of this study was to investigate the role of the inhibitory immunoreceptor CD300lf and its ligand ceramide in osteoclastogenesis in periodontitis. MATERIALS AND METHODS: The expression of CD300lf was measured in vitro and in a ligature-induced periodontitis model. The effect of CD300lf ablation on osteoclastogenesis was examined in ligature-retained and ligature removal periodontitis models. The effect of ceramide, the ligand of CD300lf, was examined in osteoclastogenesis in vitro and in vivo by smearing 20 µg of ceramide dissolved in carboxymethylcellulose on teeth and gingiva every other day in an experimental periodontitis model and ligature removal model. RESULTS: CD300lf expression was downregulated during osteoclastogenesis. Ablation of CD300lf in the ligature-induced periodontitis model increased the number of OCs and exacerbated bone damage. Bone resorption caused by CD300lf ablation was reversible following ligature removal. CD300lf-ceramide binding suppressed osteoclastogenesis in vitro and inhibited alveolar bone loss in a mouse periodontitis model. CONCLUSIONS: Our findings reveal that CD300lf-ceramide binding plays a critical negative role in alveolar bone loss in periodontitis by inhibiting OCs differentiation.

Genetically engineered CXCR4-modified exosomes for delivery of miR-126 mimics to macrophages alleviate periodontitis.

Biofilm-related diseases are a group of diseases that tolerate antimicrobial chemotherapies and therefore are refractory to treatment. Periodontitis, a non-device chronic biofilm disease induced by dental plaque, can serve as an excellent in vivo model to study the important effects of host factors on the biofilm microenvironment. Macrophage activity is one of the key factors that modulate the progression of inflammation-driven destruction in periodontitis; therefore it is an important host immunomodulatory factor. In this study, the reduction of microRNA-126 (miR-126) with the recruitment of macrophages in periodontitis was confirmed in clinical samples, and a strategy for targeted delivery of miR-126 to macrophages was explored. Exosomes overexpressing the C-X-C motif chemokine receptor 4 (CXCR4) loaded with miR-126 (CXCR4-miR126-Exo) was successfully constructed, which reduced off-target delivery to macrophages and regulated macrophages toward the anti-inflammatory phenotype. In vivo local injection of CXCR4-miR126-Exo into sites of periodontitis in rats effectively reduced bone resorption and osteoclastogenesis and inhibited the progression of periodontitis. These results provide new insights for designing novel immunomodulatory factor targeted delivery systems to treat periodontitis and other biofilm-related diseases.

Sonosensitive Phase-Changeable Nanoparticle Mediated Enhanced Chemotherapy in Prostate Cancer by Low-Intensity Focused Ultrasound.

Prostate cancer (PCa) is one of the most common cancer types. Early detection of PC offers the best chance of successful treatment. A noninvasive, image-guided therapy mediated by targeted nanoparticles (NPs) has the potential to improve the efficacy and safety of cancer therapies. Herein, we report a sonosensitive nanoparticle modified with anti-PSMA (prostate-specific membrane antigen) antibodies to activate target prostate tumors. These nanoparticles (PFP@IR780@PTX@liposome NPs) were co-loaded with the chemotherapeutic agent docetaxel and the sonosensitizer IR780, as well as phase-changeable perfluorocarbon (PFC) liquids. The liquid-gas phase change could be induced by low-intensity focused ultrasound (LIFU) in vitro. We found that the PFP@IR780@PTX@liposome NPs can specifically accumulate in prostate tumors after LIFU irradiation, as monitored by ultrasound and photoacoustic imaging. Meanwhile, docetaxel was controllably released from the nanoparticles to achieve enhanced chemotherapeutic therapy in vivo. These sonosensitive phase-changeable NPs can visually treat prostate cancers effectively and have a clinical potential.

Dual Role of Interleukin-20 in Different Stages of Osteoclast Differentiation and Its Osteoimmune Regulation during Alveolar Bone Remodeling.

Osteoimmunology mediators are critical to balance osteoblastogenesis and osteoclastogenesis to maintain bone homeostasis. A lot of the osteoimmunology mediators are regulated by interleukin-20 (IL-20). However, little is known about the role of IL-20 in bone remodeling. Here, we showed that IL-20 expression was correlated with osteoclast (OC) activity in remodeled alveolar bone during orthodontic tooth movement (OTM). Ovariectomize (OVX) in rats promoted OC activity and enhanced IL-20 expression, while blocking OC inhibited IL-20 expression in osteoclasts. In vitro, IL-20 treatment promoted survival, inhibited apoptosis of the preosteoclast at the early stages of osteoclast differentiation, and boosted the formation of osteoclasts and their bone resorption function at the late stages. More importantly, anti-IL-20 antibody treatment blocked IL-20-induced osteoclastogenesis and the subsequent bone resorption function. Mechanistically, we showed that IL-20 synergistically acts with RANKL to activate the NF-κB signaling pathway to promote the expression of c-Fos and NFATc1 to promote osteoclastogenesis. Moreover, we found that local injection of IL-20 or anti-IL-20 antibody enhanced osteoclast activity and accelerated OTM in rats, while blocking IL-20 reversed this phenomenon. This study revealed a previously unknown role of IL-20 in regulating alveolar bone remodeling and implies the application of IL-20 to accelerated OTM.

FGF8 and BMP2 mediated dynamic regulation of dental mesenchyme proliferation and differentiation via Lhx8/Suv39h1 complex.

The homeobox gene, LIM-homeobox 8 (Lhx8), has previously been identified as an essential transcription factor for dental mesenchymal development. However, how Lhx8 itself is regulated and regulates odontogenesis remains poorly understood. In this study, we employed an RNAscope assay to detect the co-expression pattern of Lhx8 and Suv39h1 in the dental mesenchyme, which coincided with the dynamic expression profiles of the early epithelium signal of Fibroblast Growth Factor 8 (FGF8) and the later mesenchymal signal Bone Morphogenetic Protein 2 (BMP2). Moreover, FGF8 activated Lhx8, whereas BMP2 repressed Lhx8 expression at the transcriptional level. The high expression of Lhx8 in the early dental mesenchyme maintained the cell fate in an undifferentiated status by interacting with Suv39h1, a histone-lysine N-methyltransferase constitutively expressed in the dental mesenchyme. Further in the ex vivo organ culture model, the knockdown of Suv39h1 significantly blocked the function of Lhx8 and FGF8. Mechanistically, Lhx8/Suv39h1 recognized the odontoblast differentiation-related genes and repressed gene expression via methylating H3K9 on their promoters. Taken together, our data here suggest that Lhx8/Suv39h1 complex is inversely regulated by epithelium-mesenchymal signals, balancing the differentiation and proliferation of dental mesenchyme via H3K9 methylation.

All-Organic Flexible Ferroelectret Nanogenerator with Fabric-Based Electrodes for Self-Powered Body Area Networks.

Due to their electrically polarized air-filled internal pores, optimized ferroelectrets exhibit a remarkable piezoelectric response, making them suitable for energy harvesting. Expanded polytetrafluoroethylene (ePTFE) ferroelectret films are laminated with two fluorinated-ethylene-propylene (FEP) copolymer films and internally polarized by corona discharge. Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS)-coated spandex fabric is employed for the electrodes to assemble an all-organic ferroelectret nanogenerator (FENG). The outer electret-plus-electrode double layers form active device layers with deformable electric dipoles that strongly contribute to the overall piezoelectric response in the proposed concept of wearable nanogenerators. Thus, the FENG with spandex electrodes generates a short-circuit current which is twice as high as that with aluminum electrodes. The stacking sequence spandex/FEP/ePTFE/FEP/ePTFE/FEP/spandex with an average pore size of 3 µm in the ePTFE films yields the best overall performance, which is also demonstrated by the displacement-versus-electric-field loop results. The all-organic FENGs are stable up to 90 °C and still perform well 9 months after being polarized. An optimized FENG makes three light emitting diodes (LEDs) blink twice with the energy generated during a single footstep. The new all-organic FENG can thus continuously power wearable electronic devices and is easily integrated, for example, with clothing, other textiles, or shoe insoles.

A novel targeted multifunctional nanoplatform for visual chemo-hyperthermia synergy therapy on metastatic lymph nodes via lymphatic delivery.

BACKGROUND: Distant metastasis to vital organs is the major contributor to breast cancer mortality, and regional lymph node metastasis is an important facilitator of distant metastasis and recurrence in this cancer. The early diagnosis and precise treatment of lymph node metastasis are crucial for staging and prognosis in breast cancer. Herein, we report a visualized precision medicine nanoplatform of metastatic lymph nodes for ultrasonic/photoacoustic (US/PA) dual modal imaging-guided in situ targeted hyperthermia-combined chemotherapy. RESULTS: Carbon nanoparticles (CNs), approved by the China Food and Drug Administration, were loaded with docetaxel and rationally combined with anti-hypoxia-inducible factor 1α antibody-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles to achieve the combination of passive targeting at the lymph nodes and intracellular targeting at HIF 1α factor. The accumulation and retention of nanoparticles in metastatic lymph nodes via lymphatic delivery were enhanced. Docetaxel could be effectively offloaded by CNs that have active carbon nanoparticles, and the PLGA membrane prevented drug leakage. The nanoparticles exhibited excellent photothermal performance with a photothermal conversion efficiency of 28.9%, killing tumor cells in metastatic lymph nodes through hyperthermia. In vitro and in vivo systematic evaluations revealed that hyperpyrexia triggered the rupture of nanoparticles caused by the phase transition of perfluorohexane, resulting in docetaxel release for achieving in situ hyperthermia-combined chemotherapy. CONCLUSIONS: The laser-triggered highly efficient in situ chemotherapy nanosystem achieves targeted synergistic chemo-hyperthermia treatment of metastatic lymph nodes, and lymphatic delivery represents a strategy to avoid additional injury caused by drugs entering the blood circulation.

Cancer cell membrane-coated nanoparticles for bimodal imaging-guided photothermal therapy and docetaxel-enhanced immunotherapy against cancer.

BACKGROUND: Mono-therapeutic modality has limitations in combating metastatic lesions with complications. Although emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. The rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer. RESULTS: Poly lactic-co-glycolic acid (PLGA, 50 mg) nanospheres were constructed with photothermal transduction agents (PTAs)-Prussian blue (PB, 2.98 mg) encapsulated in the core and chemotherapeutic docetaxel (DTX, 4.18 mg)/ immune adjuvant-imiquimod (R837, 1.57 mg) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated "M@P-PDR"), which acted as "Nano-targeted cells" to actively accumulate in tumor sites, and were guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by the immune adjuvant R837, the maturation rate of DCs increased by 4.34-fold compared with that of the control. In addition, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving the immunosuppressive TME. The proportion of M2-TAMs decreased from 68.57% to 32.80%, and the proportion of M1-TAMs increased from 37.02% to 70.81%. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased from 17.33% (control) to 35.5%. Primary tumors and metastasis were significantly inhibited when treated with "Nano-targeted cells"-based cocktail therapy. CONCLUSION: "Nano-targeted cells"-based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/recurrence.

The evaluation of stomatology English education in China based on 'Guanghua cup' international clinical skill exhibition activity.

BACKGROUND: English education in professional areas has become more and more important with the increasing internationalization of health profession education in countries around the world. In this study, we aimed to evaluate current Chinese stomatology English education based on Chinese participants' ability to apply stomatology English during an international stomatology skill competition called the 'Guanghua Cup activity'. METHODS: The registration rate of English and Chinese volunteers and the answer rate and accuracy of Chinese and international contestants on the English knowledge quiz were statistically described. A five-point Likert scale questionnaire was delivered to all participants. The data were analyzed using the Spearman test, Kruskal-Wallis rank sum test and Mann-Whitney U test. RESULTS: Among the 194 students, the English and Chinese volunteer registration rate was 7.73 and 30.93%, respectively. The answer rate of Chinese contestants and international contestants in the English quiz was 25 and 75%, with an accuracy rate of 50 and 66.70%, respectively. The questionnaire was graded by Likert five-level classification. There was a positive correlation between the use of English textbooks in classes and the communication with international teachers and students in the competition (Rs = 0.348, p = 0.016). English volunteers had more preparation in English before the competition, more opportunities to communicate with international peers, and greater improvement in English ability than the contestants and Chinese volunteers (p < 0.001). After the competition, all participants paid more attention to stomatology English (p < 0.001). CONCLUSIONS: Chinese stomatology students have difficulty in stomatology English application. The 'Guanghua Cup' helps to improve English proficiency of English volunteers and arouses the interest of stomatology English for all participants. Chinese stomatology school needs to strengthen and reach a consensus in stomatology English education.

Porphyromonas gingivalis induces depression via downregulating p75NTR-mediated BDNF maturation in astrocytes.

Many cross-sectional epidemiological studies have shown the incidence of periodontitis is positive correlated with that of depression. However, their causal relationship and underlying mechanism are largely unknown. Porphyromonas gingivalis (Pg) is the main pathogen for periodontitis. Employing female mice treated with Pg every other day for 4 weeks, we found that Pg-mice showed obvious depression-like behavior, an increased number of activated astrocytes and decreased levels of mature brain derived neurotrophic factor (BDNF) and astrocytic p75NTR in the hippocampus. Both hippocampal injection of BDNF and overexpression of p75NTR in astrocytes alleviated Pg-induced depression-like behavior in mice. Moreover, Pg-lipopolysaccharides (LPS) generated similar phenotypes, which were reversed by the TLR-4 inhibitor TAK242. Our results suggest that Pg-LPS decreases the level of astrocytic p75NTR and then downregulates BDNF maturation, leading to depression-like behavior in mice. Our study provides the first evidence that Pg is a modifiable risk factor for depression and uncovers a novel therapeutic target for the treatment of depression.

Construction of a Polypyrrole-Based Multifunctional Nanocomposite for Dual-Modal Imaging and Enhanced Synergistic Phototherapy against Cancer Cells.

Design and construction of multifunctional theranostic nanoplatforms are still desired for cancer-effective treatment. Herein, a kind of polypyrrole (PPy)-based multifunctional nanocomposite was designed and successfully constructed for dual-model imaging and enhanced synergistic phototherapy against cancer cells. Through graphene oxide (GO) sheet coating, PPy nanoparticles (NPs) were effectively combined with polyethylene glycol chains, Au NPs, and IR820 molecules. The obtained PGPAI NPs showed promising ability for photoacoustic/computed tomography imaging. Under near-infrared light irradiation, the PPy core and IR820 molecule effectively generated heat and reactive oxygen species (ROS), respectively. Furthermore, the loaded Au NPs owning catalase-like activity produced oxygen by decomposing H2O2 (up-regulated in tumor region), enhancing the oxygen-dependent photodynamic therapy efficacy. The formed PGPAI NPs were also proved to own desirable photothermal conversion efficiency, photothermal stability, colloidal stability, cytocompatibility, and cellular internalization behaviors. Furthermore, cell assay demonstrated that PGPAI NPs displayed enhanced synergistic phototherapy efficacy against cancer cells. These developed multifunctional nanoplatforms are promising for effective cancer theranostic applications.

Enhanced Photoacoustic and Photothermal Effect of Functionalized Polypyrrole Nanoparticles for Near-Infrared Theranostic Treatment of Tumor.

Functionalized nanomaterials with near-infrared (NIR) responsive capacity are quite promising for theranostic treatment of tumors, but formation of NIR responsive nanomaterials with enhanced theranostic ability and excellent biocompatibility is still very challenging. Herein, PEGylated indocyanine green (ICG)-loaded polypyrrole nanoparticles (PPI NPs) were designed and successfully formed through selecting polydopamine as the linkage between each component, demonstrating enhanced NIR responsive theranostic ability against tumor. By combining in vitro cell study with in vivo assay, the formed PPI NPs were proven to be fantastically biocompatible while effectively internalization in HeLa cells and retention in HeLa tumor were demonstrated by in vitro flow cytometry/confocal measurement and in vivo photoacoustic imaging assay. With the guidance of photoacoustic imaging, successful photothermal ablation of tumor was achieved by treatment with PPI NPs plus laser, which was much more effective than the group treated with NPs free of ICG. The combined enhanced photoacoustic and photothermal effect is mainly ascribed to the functionalized polypyrrole nanoparticles, which could accumulate in the tumor site more effectively with a relatively longer retention time taking advantage of the nanomaterial-induced endothelial leakiness phenomenon. All these results demonstrating that this designed PPI NPs possessing enhanced NIR responsive property hold great promise for tumor NIR theranostic applications.

Sn-Polyester/Polyimide Hybrid Flexible Free-Standing Film as a Tunable Dielectric Material.

Flexible films having high dielectric constants with low dielectric loss have promising application in the emerging area of high-energy-density materials. Here, for the first time, an organometallic, Sn-polyester-containing hybrid free-standing film in polyimide matrix is reported. Polyimide, pBTDA-HDA, is used with poly(dimethyltin glutarate) and poly(dimethyltin-3,3-dimethyglutarate) (pDMTDMG) for having a processable film with tunable dielectric properties. Hybrid film with 60% pDMTDMG and 40% PI (HB2) is found to have improved dielectric features over previously synthesized organic polyimide and organometallic Sn-polyester homopolymers. These novel organometallic-organic hybrid systems expanded a new area of dielectrics for next-generation electronics with superior overall electrical performance.

NOVEL MUTATIONS IN THE WNT1, TMEM38B, P4HB, AND PLS3 GENES IN FOUR UNRELATED CHINESE FAMILIES WITH OSTEOGENESIS IMPERFECTA.

OBJECTIVE: Osteogenesis imperfecta (OI) is a group of heritable fragile bone diseases, and the majority are caused by pathogenic variants in the COL1A1 and COL1A2 genes. We sought to identify the genetic causes and phenotypes of OI in Chinese patients without COL1A1 or COL1A2 mutations. METHODS: Twenty-three patients who were diagnosed with sporadic OI but did not carry COL1A1/2 mutations were recruited, and their genomic DNA was analyzed using targeted next-generation sequencing of rare OI-related genes. The resulting damaging mutations in the probands and their parents were verified using Sanger sequencing. Moreover, the efficacy of long-term bisphosphonate treatment was evaluated in proband 1. RESULTS: Compound heterozygous variants in the WNT1 and TMEM38B genes were identified in proband 1 and proband 2, respectively. A heterozygous mutation in the P4HB gene was identified in proband 3, and a hemizygous mutation in PLS3 was identified in proband 4. The unaffected parents of the probands (except the father of proband 4) with mutations in the WNT1, TMEM38B, and PLS3 genes were heterozygous carriers of each of the variants, respectively. Notably, proband 3 had the characteristic exophthalmos, flat nasal bridge and flat, wide forehead. None of the patients presented with dentinogenesis imperfecta or hearing loss. Furthermore, bisphosphonates exerted beneficial effects on proband 1, who carried the WNT1 mutations, by increasing bone mineral density Z-score, reshaping the compressed vertebrae and decreasing the fracture risk. CONCLUSION: We identified novel mutations and expanded the spectrum of phenotypes and genotypes of the extremely rare disorder OI. ABBREVIATIONS: BMD = bone mineral density; MIM = Mendelian Inheritance in Man; OI = osteogenesis imperfecta; PDI = protein disulfide isomerase.