Multi-omics analysis of immune-related microbiome and prognostic model in head and neck squamous cell carcinoma.

OBJECTIVES: The aim of our study is to explore the transcriptional and microbial characteristics of head and neck cancer's immune phenotypes using a multi-omics approach. MATERIALS AND METHODS: Employing TCGA data, we analyzed head and neck squamous cell carcinoma (HNSCC) immune cells with CIBERSORT and identified differentially expressed genes using DESeq2. Microbial profiles, obtained from the TCMA database, were analyzed using LEfSe algorithm to identify differential microbes in immune cell infiltration (ICI) subgroups. Random Forest algorithm and deep neural network (DNN) were employed to select microbial features and developed a prognosis model. RESULTS: We categorized HNSCC into three immune subtypes, finding ICI-2 with the worst prognosis and distinct microbial diversity. Our immune-related microbiome (IRM) model outperformed the TNM staging model in predicting survival, linking higher IRM model scores with poorer prognosis, and demonstrating clinical utility over TNM staging. Patients categorized as low-risk by the IRM model showed higher sensitivity to cisplatin and sorafenib treatments. CONCLUSIONS: This study offers a comprehensive exploration of the ICI landscape in HNSCC. We provide a detailed scenario of immune regulation in HNSCC and report a correlation between differing ICI patterns, intratumor microbiome, and prognosis. This research aids in identifying prime candidates for optimizing treatment strategies in HNSCC. CLINICAL RELEVANCE: This study revealed the microbial signatures associated with immunophenotyping of HNSCC and further found the microbial signatures associated with prognosis. The prognostic model based on IRM microbes is helpful for early prediction of patient prognosis and assisting clinical decision-making.

Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma.

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes, leading to facial bone destruction and a high recurrence rate. However, the mechanisms governing tumor initiation and recurrence are poorly understood. Here, we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution. Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response (IR), bone remodeling (BR), tooth development (TD), epithelial development (ED), and cell cycle (CC) signatures. Of note, we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence, which was dominated by the EZH2-mediated program. Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids. These data described the tumor subpopulation and clarified the identity, function, and regulatory mechanism of CC ameloblastoma cells, providing a potential therapeutic target for ameloblastoma.

Fabrication of antimicrobial cationic hydrogels driven by physically and chemically crosslinking for wound healing.

The wound therapy based on antibiotic delivery inevitably leads to the emergence of drug resistance. Hydrogel biomaterials with inherent antibacterial activities have emerged as promising candidates for addressing this issue. However, developing an inherently antibacterial hydrogel through simple and facile strategies to promote localized wound infection healing remains a challenge. In this study, we successfully constructed antimicrobial cationic hydrogels with self-healing and injectable properties through physically and chemically dual-crosslinked networks. The networks were formed by the copolymers poly[(di(ethylene glycol) methyl ether methacrylate)-co-(4-formylphenyl methacrylate)-co-(2-(methacryloyloxy)ethyl]trimethylammonium chloride solution)] (PDFM) and poly[(di(ethylene glycol) methyl ether methacrylate)-co-(2-aminoethyl methacrylate hydrochloride)-co-(2-(((6-(6-methyl-4[1H]pyrimidionylureido) hexyl)carbamoyl)oxy)ethyl methacrylate)] (PDAU). The hydrogel systems effectively facilitate the regeneration and healing of infected wounds through the contact bactericidal feature of quaternary ammonium cations. The presence of Schiff base bonds in the injectable hydrogels imparts remarkable pH responsiveness and self-healing properties. In vitro experiments verified their intrinsic antibacterial activities along with their favorable cytocompatibility and hemocompatibility in both in vitro and in vivo. In addition, the hydrogel significantly accelerated the healing of bacterially infected in a full-thickness skin wound. This facilely prepared dual-crosslinked hydrogel, without antibiotics loading, holds significant prospects for treating infected wounds.

Codelivery of CuS and DOX into Deep Tumors with Size and Charge-Switchable PAMAM Dendrimers for Chemo-photothermal Therapy.

Accurate targeting of therapeutic agents to specific tumor tissues, especially via deep tumor penetration, has been an effective strategy in cancer treatments. Here, we described a flexible nanoplatform, pH-responsive zwitterionic acylsulfonamide betaine-functionalized fourth-generation PAMAM dendrimers (G4-AB), which presented multiple advantages for chemo-photothermal therapy, including template synthesis of ultrasmall copper sulfide (CuS) nanoparticles and further encapsulation of doxorubicin (DOX) (G4-AB-DOX/CuS), long-circulating performance by a relatively large size and zwitterionic surface in a physiological environment, combined size shrinkage, and charge conversions via pH-responsive behavior in an acidic tumor microenvironment (TME). Accordingly, high tumor penetration and positive cell uptake for CuS and DOX have been determined, which triggered an excellent combination treatment under near-infrared irradiation in comparison to the monochemotherapy system and irresponsive chemo-photothermal system. Our study represented great promise in constructing multifunctional carriers for the effective delivery of photothermal nanoparticles and drugs in chemo-photothermal therapy.

Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis.

Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.

Glycopolymer-based multifunctional antibacterial hydrogel dressings for accelerating cutaneous wound healing.

Antimicrobial hydrogel dressings have received extensive attention for their wide and promising applications in preventing infections associated with wound healing. However, the development of versatile antibacterial hydrogels inevitably leads to complex structures, which restricts their applications. In this work, a multifunctional antibacterial hydrogel based on a reversible diolborate bond crosslinked network was prepared via the interactions between the zwitterionic glycopolymer poly[(2-methacryloyloxyethyl phosphorylcholine)-co-(N,N-dimethylacrylamide)-co-(2-lactobionamidoethyl methacrylamide)] (PMDL) and borax in conjunction with a simple mixing of Ag NPs within 10 s. The obtained PMDL-12%/borax/Ag NP hydrogel displays a rapid self-healing ability and excellent injectability, as well as good adhesiveness to biological tissues and surfaces of various materials. Moreover, the hydrogels exhibit efficient antibacterial activities against Escherichia coli and Staphylococcus aureus, which could prevent bacterial infections in wound care. The multifunctional hydrogel also shows good cytocompatibility and hemocompatibility. Importantly, in vivo wound healing evaluation of a mouse full-thickness skin defect model confirms that the hydrogel effectively accelerates cutaneous regeneration and wound healing by regulating inflammation and promoting collagen deposition. This multifunctional wound dressing hydrogel prepared using a facile strategy has promising application in biomedical areas.

Tunable Nanoparticles with Aggregation-Induced Emission Heater for Precise Synergistic Photothermal and Thermodynamic Oral Cancer Therapy of Patient-Derived Tumor Xenograft.

The fluorophores in the second near-infrared (NIR-II) biological window (1000 - 1700 nm) show great application prospects in the fields of biology and optical communications. However, both excellent radiative transition and nonradiative transition cannot be achieved simultaneously for the majority of traditional fluorophores. Herein, tunable nanoparticles formulated with aggregation-induced emission (AIE) heater are developed rationally. The system can be implemented via the development of an ideal synergistic system that can not only produce photothermal from nonspecific triggers but also trigger carbon radical release. Once accumulating in tumors and subsequently being irradiated with 808 nm laser, the nanoparticles (NMB@NPs) encapsulated with NMDPA-MT-BBTD (NMB) are splitted due to the photothermal effect of NMB, leading to the decomposition of azo bonds in the nanoparticle matrix to generate carbon radical. Accompanied by second near-infrared (NIR-II) window emission from the NMB, fluorescence image-guided thermodynamic therapy (TDT) and photothermal therapy (PTT) which significantly inhibited the growth of oral cancer and negligible systemic toxicity is achieved synergistically. Taken together, this AIE luminogens-based synergistic photothermal-thermodynamic strategy brings a new insight into the design of superior versatile fluorescent NPs for precise biomedical applications and holds great promise to enhance the therapeutic efficacy of cancer therapy.

Synthesis of pH-responsive polyzwitterions for activated cellular uptake and tumor accumulation of gold nanoparticles at tumorous acidity.

The response sensitivity of surface material plays an important role in adjustable nano-bio interactionin vivo. In this present, a zwitterionic polymer (polyzwitterion) containing quaternary ammonium cation and sulfonamide anion poly(4-((4-(3-(methacryloyloxy)propoxy)phenyl) sulfonamido)-N, N, N-trimethyl-4-oxobutan-1-aminium chloride) (PMPTSA) was synthesized by Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT) polymerization to explore the pH responsive behavior in tumors. The PMPTSA-coated gold nanoparticles (PMPTSA-@-Au NPs) showed zwitterionic nature such as antifouling ability, low cellular uptake and prolonged circulation time similar with common hydrophilic polymers, including polyethylene glycol (PEG), poly(carboxybetaine methacrylate) and poly(sulfobetaine methacrylate) functional gold nanoparticles in physiological environment (pH 7.4). A high sensitivity and reversible positive charge conversion of P(MPTSA)-@-Au NPs at tumor slight acidic microenvironment (∼pH 6.8) leaded to an enhanced cellular internalization than that at pH 7.4 and increased tumor accumulation compared with PEG, polycarboxybetaines and polymer sulphobetaine (PSB) functional gold nanoparticles. The highly pH responsive PMPTSA will provide the promising application in cancer nanomedicine.

Synergistic size and charge conversions of functionalized PAMAM dendrimers under the acidic tumor microenvironment.

Developing nanomedicine with highly adaptive behaviors has shown great effectiveness in cancer treatment. However, the multi-functional integration of nano-therapeutic systems inevitably leads to complexity in the structure and impairs the operational efficiency or performance. Herein, we describe a novel nano-therapeutic system, G4-AB, capable of simultaneous dual conversions of the size and charge while targeting the acidic tumor microenvironment. G4-AB, containing a hydrophobic inner cavity for doxorubicin (DOX) loading, was synthesized by modifying amine-terminated 4th-generation polyamidoamine (G4-PAMAM) dendrimers with acylsulfonamide betaine (AB). Due to the dipole-dipole interaction among the AB moieties, G4-AB self-assembles to form micellar clusters with a zwitterionic surface. Possessing an anti-fouling property and suitable size, G4-AB exhibits optimized blood circulation under physiological pH conditions. Moreover, the extracellular pH value of the tumor microenvironment (pH 6.5) can trigger the protonation of acylsulfonamide, resulting in the cationization of AB and dissociation of G4-AB into unimolecular micelles (∼12 nm) due to electrostatic repulsion. The synergistic dual conversions further ensure drug accumulation with enhanced tumor penetration and cell internalization. The in vitro and in vivo experiments demonstrate that the G4-AB-DOX nano-therapeutic system possesses better antitumor efficiency and lower toxicity than free DOX or PEGylated PAMAM.

Construction of antibacterial adhesion surfaces based on bioinspired borneol-containing glycopolymers.

Preparation of antibacterial coating materials is considered an effective strategy to prevent medical device-related infections. In the present study, by combining 2-lactobionamidoethyl methacrylamide with a uniquely structured borneol compound, new copolymers poly(2-lactobionamidoethyl methacrylamide-co-glycidyl methacrylate-co-isobornyl acrylate) (poly(LAEMA-co-GMA-co-BA)) were synthesized by a simple free-radical polymerization. An amine containing silane layer was first prepared on the substrate surface by a silanization reaction. The glycopolymers were grafted onto the silane layer through covalent bonding to obtain glycosylated coatings. X-ray photoelectron spectroscopy (XPS) confirmed the successful preparation of the APTES-functionalized surface and polymer layers. The surface wettability was measured by the contact angle (CA). The coated surfaces were relatively flat and smooth as confirmed by Atomic Force Microscopy (AFM). Moreover, the prepared coatings showed good antibacterial adhesion properties toward both E. coli and S. aureus. Furthermore, no significant cytotoxicity to the MRC-5 cells (lung fibroblasts) in vitro was observed, indicating the good biocompatibility of the antibacterial coatings. This study provides an excellent strategy for designing an antibacterial surface containing glycopolymers and natural antibacterial compounds, and these coatings may be suitable for medical devices.

APC c.4621C>T variant causing Gardner's syndrome in a Han Chinese family may be inherited through maternal mosaicism.

Gardner's syndrome is a rare autosomal dominant hereditary disease that is characterized by multiple colorectal polyps combined with extra-colonic presentation (such as osteoma or desmoid tumors) of familial adenomatous polyposis syndrome. Gardner's syndrome is caused by the mutation of the adenomatous polyposis coli (APC) gene, which is located at 5q21. The aim of the current study was to investigate the APC gene mutations present in a Han Chinese family diagnosed with Gardner's syndrome. The 38-year-old proband presented with clinical symptoms, and was later diagnosed with Gardner's syndrome. Genomic DNA was extracted from the peripheral venous blood of 150 normal controls as well as the family members of the proband. Analysis of the respective APC gene sequences was performed using PCR amplification and Sanger sequencing. Pathogenesis associated with the APC mutation was investigated using reverse-transcription quantitative PCR and determined through bioinformatics approaches. Haplotype analysis was performed to identify the genetic source of the mutation(s). In the initial screening for APC variants, the APC c.4621C>T variant was detected in the proband and his son, but was not detected in the proband's affected mother. The mRNA expression changed significantly according to age and the presence of the mutation in the blood of the patients. Haplotype analysis suggested the presence of maternal mosaicism for this mutation. Haplotype analysis revealed that the APC c.4621C>T variant in a patient with Gardner's syndrome was most likely derived from his mother through mosaicism. These results indicate the necessity to verify the possibility of gonadal mosaicism when a proband diagnosed with Gardner's syndrome appears to exhibit a de novo mutation.

The gain-of-function FAM83H mutation caused hypocalcification amelogenesis imperfecta in a Chinese family.

OBJECTIVES: Autosomal-dominant hypocalcification amelogenesis imperfecta (ADHCAI) is a hereditary disease characterized by enamel defects. ADHCAI is mainly caused by nonsense mutations in a gene called family with sequence similarity 83 member H (FAM83H). To study the pathogenesis of ADHCAI, a Chinese ADHCAI family was investigated. MATERIALS AND METHODS: The ultrastructure of enamel was analyzed by micro-CT and scanning electron microscopy. Whole-exome sequencing (WES) was performed to identify the pathogenic gene. The function of the mutant FAM83H was studied by real-time PCR, western blotting, subcellular localization, and protein degradation pathway analyses. RESULTS: WES identified a known nonsense mutation (c.1915A > T) in exon 5 of the FAM83H gene, causing a truncated protein (p.Lys639*). However, the cases reported herein exhibited significant differences in the clinical phenotype compared with that the previously reported case. An abnormal enamel rod head structure was observed in affected teeth. In vitro functional studies showed altered protein localization and a decreased protein degradation rate for mutant FAM83H. CONCLUSIONS: We verified the FAM83H p.Lys639* protein as a gain-of-function variant causing ADHCAI. Abnormal enamel rod head structure was observed in teeth with mutant FAM83H proteins. We also investigated the molecular pathogenesis and presented data on the abnormal degradation of mutant FAM83H proteins. CLINICAL RELEVANCE: This study helped the family members to understand the disease progression and provided new insights into the pathogenesis of ADHCAI. Due to the large heterogeneity of ADHCAI, this study also provided a genetic basis for individuals who exhibit similar clinical phenotypes.

Promote anti-inflammatory and angiogenesis using a hyaluronic acid-based hydrogel with miRNA-laden nanoparticles for chronic diabetic wound treatment.

Chronic diabetic wound causes serious threat to human health due to its long inflammatory phase and the reduced vascularization. Herein, we develop a hydrogel system for the treatment of diabetic wound, which can short the inflammatory stage (through the use of ori) and promote the angiogenesis (through the addition of siRNA-29a gene). Based on the Schiff base bonds, the Gel/Alg@ori/HA-PEI@siRNA-29a hydrogel was prepared by mixing oxidized hydroxymethyl propyl cellulose (OHMPC), adipic dihydrazide-modified hyaluronic acid (HA-ADH), oridonin (ori) loaded alginate microspheres (Alg@ori) and siRNA-29a gene-loading hyaluronic acid-polyethyleneimine complex HA-PEI@siRNA-29a (HA-PEI@siRNA-29a) under physiological conditions, which had moderate mechanical strength, appropriate swelling property, impressive stability, and slow release ability of ori and siRNA-29a. Excellent biocompatibility of the prepared hydrogel was also confirmed by in vitro mouse fibroblasts L929 cells culture study. Moreover, in vivo experiments further demonstrated that the prepared Gel/Alg@ori/HA-PEI@siRNA-29a hydrogel not only significantly accelerated the diabetic wound healing, angiogenesis factors (α-SMA and CD31) production, but also inhibited pro-inflammatory factors (IL-6 and TNF-α). In summary, we believe that the prepared hydrogels exhibit great potential for the treatment of chronic diabetic wound.

Hectogram-scale green synthesis of hierarchical 4A zeolite@CuO x (OH)(2-2x) (0 ≤ x < 1) nanosheet assemblies core-shell nanoarchitectures with Superb Congo red adsorption performance.

Delicate design of hierarchical nanoarchitectures has become a highly effective strategy to develop novel adsorbents with improved adsorption capacity. Herein, hectogram-scale green fabrication of hierarchical 4A zeolite@CuO x (OH)(2-2x) (0 ≤ x < 1) nanosheet assemblies core-shell nanoarchitectures (4A-Cu-T, T was the calcination temperature) with terrific Congo red (CR) dye adsorption performance was achieved through a simple, template-free and surfactant-free hydrothermal approach. A series of characterization techniques, including scanning electron microscopy, transmission electron microscopy, X-ray diffraction and photoelectron spectroscopy demonstrated that all resultant adsorbents featured a core-shell structure with 4A zeolite as core ingredients and CuO x (OH)(2-2x) (0 ≤ x < 1) nanosheet assemblies as shell components. The adsorption experimental results pointed out that 4A-Cu-300 with a maximum adsorption capacity of 512.987 mg g-1 showed the best adsorption performance amongst all as-prepared adsorbents, and the adsorption capacity of shell component-CuO x Cu(OH)(2-2x) (0 ≤ x < 1) nanosheet assemblies was calculated up to 3685.500 mg g-1. The shell thickness and phase ratio of CuO and Cu(OH)2 in CuO x (OH)(2-2x) (0 ≤ x < 1) nanosheet assemblies played key roles in improving the adsorption capacity. The successive tests suggested that the "carbon deposition" resulted in the decreased adsorption capacity of first-regenerated adsorbents, but little variance in adsorption performance among regenerated samples demonstrated the good stability of such adsorbents. This work unlocks a method for the rational design of high-performance adsorbents via delicate decoration of poor-performance materials with nanosheet assemblies, which will endow the non-active materials with enhanced adsorption properties.

Expert consensus on marsupialization of cystic lesions of the jaw / 口腔疾病防治

@#Marsupialization is effective in the treatment of cystic lesions of the jaw. It is a simple operation that can result in minimal trauma, the reduction of postoperative recurrence, and maximum preservation of the surrounding tissue structure and function. However, there is a certain failure rate in clinical treatment due to the improper grasp of indications and nonstandard operation. The highest failure rate reported in the literature is 32.6%. To further standardize the clinical application of marsupialization and improve the success rate of treatment, we put forward an expert consensus of marsupialization in the treatment of jaw cystic lesions by reviewing the domestic and foreign literature and summarizing the experience in marsupialization from some famous domestic experts. In this consensus, we propose three elements of marsupialization: the establishment of the opening, the maintenance of cyst plugs and regular washing. The scope of application of marsupialization includes jaw cysts and cystic ameloblastomas. It is necessary to standardize the position of the opening, the size of the opening and the manufacture of the cyst plug, and a panoramic film or cone beam computed tomography(CBCT) should be used to observe the changes in the cystic cavity before and after operation. A second-stage operation should be performed when the lesion is significantly reduced by more than 50% or at least 5 mm from important structures; furthermore, the teeth of focus should be treated according to the relationship between the lesion and tooth and the type of tooth.

Silencing of LINC01116 suppresses the development of oral squamous cell carcinoma by up-regulating microRNA-136 to inhibit FN1.

BACKGROUND: Oral squamous cell carcinoma (OSCC), one of the most common cancers worldwide with a high mortality rate, is accompanied by poor prognosis, highlighting the significance of early diagnosis and effective treatment. Long non-coding RNAs (lncRNAs) have been linked with the development and progression of various cancers. In this study, aberrantly expressed lncRNA LINC01116, microRNA-136 (miR-136), and fibronectin1 (FN1) were identified in OSCC using a microarray analysis. Therefore, this study aimed to investigate the role of LINC01116/miR-136/FN1 regulatory axis in OSCC. METHODS: The gain-of-function and loss-of-function experiments in vitro were performed to alter the expression of LINC01116 and miR-136 in OSCC cells to elucidate their effects on cellular processes, including epithelial-mesenchymal transition (EMT), viability, invasion, and migration. In addition, the interaction among LINC01116, miR-136, and FN1 was identified. Additionally, the tumorigenicity and lymph node metastasis (LNM) affected by LINC01116 were observed through xenograft tumor in nude mice. RESULTS: LINC01116 and FN1 were abundant in both OSCC tissues and cells, while miR-136 was poorly expressed. LINC01116 could competitively bind to miR-136, which targets and negatively regulates FN1. Moreover, in response to LINC01116 silencing or miR-136 over-expression, OSCC cells exhibited diminished EMT process and inhibited cell viability, invasion, and migration in vitro, coupling with impaired tumorigenicity and LNM in vivo. CONCLUSION: The fundamental findings in this study collectively demonstrate that LINC01116 silencing may inhibit the progression of OSCC via the miR-136-mediated FN1 inhibition, highlighting a promising therapeutic strategy for OSCC treatment.

Two-dimensional Acetate-based Light Lanthanide Fluoride Nanomaterials (F-Ln, Ln = La, Ce, Pr, and Nd): Morphology, Structure, Growth Mechanism, and Stability.

Discovery of novel two-dimensional (2D) materials is of fundamental importance but remains challenging. In this work, we design a simple and facile bottom-up approach to fabricate a new family of 2D acetate-based light lanthanide fluoride nanomaterials (F-Ln, Ln = La, Ce, Pr, Nd) at room temperature and atmosphere pressure, for the first time. Various characterization techniques confirm that as-synthesized F-Ln exhibit an ultrathin morphology with thickness up to 1.45 nm and lateral dimensions up to several hundred nanometers. Microstructure analysis demonstrates that F-Ln are a series of defect-rich 2D nanomaterials, which consist of nanocrystals with sub-10 nm domains. Structure characterization of F-Ce, a typical example, infers that BN-like F-Ce one-atom-layers sandwiched by intercalated acetate anions stack alternately along [001] direction to form nanocrystal building blocks of F-Ce. The study of growth mechanism suggests that three procedures are involved in the formation of F-Ce: hydrolysis reaction of cerium(III) acetate, structure transformation induced by fluorine ions, and assembly process guided by acetate anions. The as-prepared nanosheets show excellent stability with respect to environment stimuli such as air, heat, solvent, and high-energy electron beam. This study enriches the library of 2D materials and paves the way for future application of such 2D materials in areas such as catalysis, adsorption, separation, and energy storage/conversion.

Mixed matrix membrane contactor containing core-shell hierarchical Cu@4A filler for efficient SO2 capture.

Achieving high flux membrane contactor is significantly important for hazardous gas removal. In this study, we prepared poly(vinylidene fluoride) (PVDF)-based mixed matrix membrane contactor (MMMC) that contained a core-shell hirarchical Cu@4A composite filler (Cu@4A). On one hand, the Cu@4A regulated the physical structure of MMMC, which enhanced gas permeation and thus resulted in the increment of physical SO2 absorption flux. On the other hand, Cu@4A changed the chemical environment of MMMC by remarkably increased SO2 facilitated transport sites, which elevated SO2 concentration around Cu@4A by the enhancement of adsorption and oxidation of SO2, resulting in the increase of chemical SO2 absorption flux. Moreover, the copper nanosheets on 4A helped to construct facilitated transport pathways along the Cu@4A fillers at polymer-filler interface. The results showed that Cu@4A loaded MMMC exhibited increased SO2 removal efficiency and SO2 absorption flux compared with PVDF control membrane. Specifically, the M1040 MMMC loaded with 40 wt% Cu@4A and PVDF concentration 10 wt% exhibited the highest SO2 removal efficiency and SO2 absorption flux, which was up to 73.6% and 9.1 × 10-4 mol·m-2·s-1 at the liquid flow rate of 30 L/h. Besides, the overall SO2 mass transfer coefficient (Ko) and membrane mass transfer resistance (H/Km) were investigated.

[Adenoid cystic carcinoma cells produce exosomes that promote tumor cell proliferation].

OBJECTIVE: To observe the effect of exosomes released by adenoid cystic carcinoma (ACC) cell line SACC-83 on the proliferation of ACC cells. METHODS: Exosomes were isolated from SACC-83 cell culture supernatants using total exosome isolation reagents. The whole-mount exosomes were characterized using transmission electron microscope and Western blotting. The exosomes were labeled with green fluorescent dye PKH67 and co-cultured with SACC-83 cells for 48 h, followed by staining with Alexa Fluor 594 phalloidin and DAPI to observe exosome uptake by the cells using laser scanning confocal microscopy (LSCM). The cell proliferation was assessed using MTT assay and wound healing assay, and the expressions of ERK and P-ERK in the co-cultured SACC-83 cells were detected using Western blotting. RESULTS: The exosomes isolated from SACC-83 cells showed a size range of 30-100 nm and expressed the exosomal markers CD9, CD63 and TSG101. LSCM showed exosome uptake by SACC-83 cells, which exhibited accelerated proliferation and significantly enhanced P-ERK expression (P < 0.05) without significant changes in ERK expression. CONCLUSIONS: SACC-83 cells produce exosomes that promote the tumor cell proliferation and enhances the cellular expression of P-ERK, suggesting a potential role of MAPK/ERK pathway activation in exosome-mediated acceleration of ACC cell proliferation.

Whole exome sequencing identifies an AMBN missense mutation causing severe autosomal-dominant amelogenesis imperfecta and dentin disorders.

Tooth development is a complex process that involves precise and time-dependent orchestration of multiple genetic, molecular, and cellular interactions. Ameloblastin (AMBN, also named "amelin" or "sheathlin") is the second most abundant enamel matrix protein known to have a key role in amelogenesis. Amelogenesis imperfecta (AI [MIM: 104500]) refers to a genetically and phenotypically heterogeneous group of conditions characterized by inherited developmental enamel defects. The hereditary dentin disorders comprise a variety of autosomal-dominant genetic symptoms characterized by abnormal dentin structure affecting either the primary or both the primary and secondary teeth. The vital role of Ambn in amelogenesis has been confirmed experimentally using mouse models. Only two cases have been reported of mutations of AMBN associated with non-syndromic human AI. However, no AMBN missense mutations have been reported to be associated with both human AI and dentin disorders. We recruited one kindred with autosomal-dominant amelogenesis imperfecta (ADAI) and dentinogenesis imperfecta/dysplasia characterized by generalized severe enamel and dentin defects. Whole exome sequencing of the proband identified a novel heterozygous C-T point mutation at nucleotide position 1069 of the AMBN gene, causing a Pro to Ser mutation at the conserved amino acid position 357 of the protein. Exfoliated third molar teeth from the affected family members were found to have enamel and dentin of lower mineral density than control teeth, with thinner and easily fractured enamel, short and thick roots, and pulp obliteration. This study demonstrates, for the first time, that an AMBN missense mutation causes non-syndromic human AI and dentin disorders.