External Field-Responsive Ternary Non-Noble Metal Oxygen Electrocatalyst for Rechargeable Zinc-Air Batteries.

Despite the increasing effort in advancing oxygen electrocatalysts for zinc-air batteries (ZABs), the performance development gradually reaches a plateau via only ameliorating the electrocatalyst materials. Herein, a new class of external field-responsive electrocatalyst comprising Ni0.5 Mn0.5 Fe2 O4 stably dispersed on N-doped Ketjenblack (Ni0.5 Mn0.5 Fe2 O4 /N-KB) is developed via polymer-assisted strategy for practical ZABs. Briefly, the activity indicator ΔE is significantly decreased to 0.618 V upon photothermal assistance, far exceeding most reported electrocatalysts (generally >0.680 V). As a result, the photothermal electrocatalyst possesses comprehensive merits of excellent power density (319 mW cm-2 ), ultralong lifespan (5163 cycles at 25 mA cm-2 ), and outstanding rate performance (100 mA cm-2 ) for liquid ZABs, and superb temperature and deformation adaptability for flexible ZABs. Such improvement is attributed to the photothermal-heating-enabled synergy of promoted electrical conductivity, reactant-molecule motion, active area, and surface reconstruction, as revealed by operando Raman and simulation. The findings open vast possibilities toward more-energy-efficient energy applications.

[Spatiotemporal Occurrence of Organophosphate Esters in the Surface Water and Sediment of Taihu Lake and Relevant Risk Assessment].

Aiming to explore the spatiotemporal occurrence of organophosphate esters (OPEs) in the aquatic environment of Taihu Lake and to assess the relevant ecological risk, monomeric and oligomeric OPEs in the surface water and sediment of Taihu Lake were determined using solid phase extraction and ultra-high performance liquid chromatography-tandem mass spectrometry. The target monomeric OPEs included chlorinated OPEs, alkyl OPEs, and aryl OPEs. There was no significant difference in the spatial distribution of OPEs in water and sediment between the pollutant-impacted and less-impacted zones. The average concentrations of OPEs in summer and winter were, respectively, 752.7 and 498.5 ng·L-1 in water and 124.0 and 54.5 ng·g-1 in sediment, indicating an obvious seasonal difference, especially for the monomeric OPEs. The OPEs levels in both the water and sediment were ranked in the order of chlorinated OPEs > alkyl OPEs > aryl OPEs≈oligomeric OPEs. The pseudo-partitioning coefficients (Kd) of OPEs between the sediment and surface water of Taihu Lake were much higher in summer (0.05-4.17 L·g-1) compared to those in winter (0.02-3.47 L·g-1) and were significantly positively correlated with the lg Kow values of OPEs. Based on the median concentrations of OPEs in the water of Taihu Lake, the ecological risk of OPEs was assessed by risk quotient (RQ) values, which indicated a medium risk at an RQ level of 0.34 during winter and 0.35 during summer. The assessment results showed that the risk ranking of OPEs was consistent with that of their concentrations, and the monomeric OPEs posed a higher ecological risk in summer compared to that in winter. Although the ecological risk of oligomeric OPEs in this study was not serious and was lower than that of monomeric OPEs, it is an urgent requirement to conduct ecotoxicology studies on oligomeric OPEs in the future since available data is highly limited at present.

Synthesis of spiropyrans via Ru(II)-catalyzed coupling of 3-aryl-2H-benzo[b][1,4]oxazines with benzoquinones.

An efficient Ru(II)-catalyzed C-H activation-based spiroannulation of benzoxazines with the easily available benzoquinone and N-sulfonyl quinone monoimine has been realized, providing a straightforward strategy to access NH-containing spiropyrans in moderate to good yields with good functional group compatibility. The procedure features atom- and step-economy, mild conditions, and excellent chemoselectivity. Moreover, a catalytically competent five-membered cycloruthenated complex has been isolated.

Identifying STRN3-RARA as a new fusion gene for acute promyelocytic leukemia.

Here we report a new fusion gene, STRN3-RARA, in acute promyelocytic leukemia (APL). It cooperates with UTX deficiency to drive full-blown APL in mice. Although STRN3-RARA leukemia quickly relapses after all-trans retinoic acid treatment, it can be restrained by cepharanthine.

The effects of dimethyl fumarate on cytoplasmic LPS-induced noncanonical pyroptosis in periodontal ligament fibroblasts and dental pulp cells.

AIM: Pyroptosis is a type of inflammatory cell death and is related to pulpitis and apical periodontitis. In this study, the aim was to investigate how periodontal ligament fibroblasts (PDLFs) and dental pulp cells (DPCs) respond to pyroptotic stimuli and explore whether dimethyl fumarate (DMF) could block pyroptosis in PDLFs and DPCs. METHODOLOGY: Three methods (stimulation with lipopolysaccharide [LPS] plus nigericin, poly(dA:dT) transfection and LPS transfection) were used to induce pyroptosis in PDLFs and DPCs, two types of fibroblasts related to pulpitis and apical periodontitis. THP-1 cell was used as a positive control. Afterwards, PDLFs and DPCs were treated with or without DMF before inducing pyroptosis to examine the inhibitory effect of DMF. Pyroptotic cell death was measured by lactic dehydrogenase (LDH) release assays, cell viability assays, propidium iodide (PI) staining and flow cytometry. The expression levels of cleaved gasdermin D N-terminal (GSDMD NT), caspase-1 p20, caspase-4 p31 and cleaved PARP were examined by immunoblotting. Immunofluorescence analysis was used to detect the cellular distribution of GSDMD NT. RESULTS: Periodontal ligament fibroblasts and DPCs were more sensitive to cytoplasmic LPS-induced noncanonical pyroptosis than to canonical pyroptosis induced by stimulation with LPS priming plus nigericin or by poly(dA:dT) transfection. In addition, treatment with DMF attenuated cytoplasmic LPS-induced pyroptotic cell death in PDLFs and DPCs. Mechanistically, it was shown that the expression and plasma membrane translocation of GSDMD NT were inhibited in DMF-treated PDLFs and DPCs. CONCLUSIONS: This study indicates that PDLFs and DPCs are more sensitive to cytoplasmic LPS-induced noncanonical pyroptosis and that DMF treatment blocks pyroptosis in LPS-transfected PDLFs and DPCs by targeting GSDMD, suggesting DMF might be a promising drug for the management of pulpitis and apical periodontitis.

Management of Crown-root Fracture with 180-degree Rotation Replantation: a Report of 2 Cases.

Intentional replantation involves a combination of periodontics, endodontics, prosthodontics and oral surgery. Crown-root fracture management is still complicated nowadays. A fracture line extending longitudinally to the subgingival area and intruding bioogical width could affect infection control, gingival health and crown restoration. In the present study, we present two cases. Case 1 involved a 23-year-old man who presented at our hospital with crown-root fracture of the maxillary left central incisor. A radiographic image of the tooth revealed a fracture line under the alveolar crest. The fractured tooth was treated with intentional replantation with 180-degree rotation, root canal treatment and veneer restoration. The patient was followed up for 60 months. The replanted tooth functioned well, and no symptoms of resorption or ankylosis were observed by radiographic examination. Case 2 involved a 20-year-old woman who was referred to our hospital for crown-root fracture of her maxillary teeth. A radiographic examination revealed complicated crown-root fracture of the maxillary right lateral incisor and both maxillary central incisors. The central incisors were treated with intentional replantation with 180-degree rotation. At the 48-month follow-up, the fractured teeth were found to have regained normal function based on clinical and radiographic examination. Limited case reports are available on a long-term follow-up of intentional replantation with 180-degree rotation. These two cases, particularly case 2, presented optimal healing after 4 years with unideal crown-root ratios. This case report suggests that this old method of preserving teeth with crown-root fractures can be used as a last resort to save teeth owing to its timesaving and microinvasive procedure.

Flexible, Permeable, and Recyclable Liquid-Metal-Based Transient Circuit Enables Contact/Noncontact Sensing for Wearable Human-Machine Interaction.

The past several years have witnessed a rapid development of intelligent wearable devices. However, despite the splendid advances, the creation of flexible human-machine interfaces that synchronously possess multiple sensing capabilities, wearability, accurate responsivity, sensitive detectivity, and fast recyclability remains a substantial challenge. Herein, a convenient yet robust strategy is reported to craft flexible transient circuits via stencil printing liquid metal conductor on the water-soluble electrospun film for human-machine interaction. Due to the inherent liquid conductor within porous substrate, the circuits feature high-resolution, customized patterning viability, attractive permeability, excellent electroconductivity, and superior mechanical stability. More importantly, such circuits display appealing noncontact proximity capabilities while maintaining compelling tactile sensing performance, which is unattainable by traditional systems with compromised contact sensing. As such, the flexible circuit is utilized as wearable sensors with practical multifunctionality, including information transfer, smart identification, and trajectory monitoring. Furthermore, an intelligent human-machine interface composed of the flexible sensors is fabricated to realize specific goals such as wireless object control and overload alarm. The transient circuits are quickly and efficiently recycled toward high economic and environmental values. This work opens vast possibilities of generating high-quality flexible and transient electronics for advanced applications in soft and intelligent systems.

Pollutant impacts on bacteria in surface water and sediment: Conventional versus emerging pollutants in Taihu Lake, China.

Bacteria play a critical role in biogeochemical cycling, self-purification, and food web fueling in surface freshwater ecosystems. However, the comparison between the impacts of conventional and emerging pollutants on the bacteria in surface water and sediment remains unclear and requires for an in-depth understanding to assess ecological risk and select associated bioindicators. Taihu Lake, a typical shallow lake in China, was divided into pollutant impacted and less-impacted zones for sampling. Spatial distributions of conventional pollutants, emerging pharmaceuticals, and bacterial communities were investigated in surface water and sediment. The correlations of pollutants with bacterial communities and the variations in bacterial functions were analyzed to help assess the pollutant influences on bacteria. The results showed that the water quality index and trophic level index across the whole lake were at medium to good, and mesotropher to light eutropher grades, respectively, indicating a relatively good control on conventional pollutants in water. Target pharmaceuticals were at much higher concentrations in water of the impacted zone compared to the less-impacted zone, exhibiting close positive relationships with the bacterial phyla in the impacted water. The ratio of Firmicutes to Proteobacteria in surface water is suggested as a plausible bioindicator to evaluate the level of inflow pharmaceutical contamination and the risk of relevant bacterial resistance in the outflow. In sediment, no significant difference was observed for pharmaceuticals between the two zones, whereas total phosphorus and orthophosphate were substantially higher in the impacted zone. Phosphorus pollutants were tightly associated with the bacterial genera in the impacted sediment, likely relating to the increase in iron- or sulfate-reducing bacteria which implies the potential risk of phosphorus releasing from sediment to water.

Preparation of antioxidant peptides from Moringa oleifera leaves and their protection against oxidative damage in HepG2 cells.

Moringa oleifera leaves are a kind of new food raw materials, rich in functional factors, M. oleifera leaves aqueous extract have antioxidant activity and M. oleifera leave protein is an important active ingredient in the aqueous extract. Numerous studies have shown that peptides have strong antioxidant activity. To reveal the antioxidant effects of M. oleifera (MO) leaves peptides, MO leave antioxidant peptides were isolated and prepared to clarify their antioxidant activity. MLPH1 (<1 kDa), MLPH3 (1~3 kDa), MLPH5 (3~5 kDa), and MLPH10 (5~10 kDa) fractions were obtained by the membrane ultrafiltration classification of MO leaves proteolytic hydrolysate (MLPH). MLPH1 was further separated by centrifugal filters, and the fraction separated by <1 kDa (MLPH1-1) was identified and analyzed by LC-MS/MS. The purpose of this study was to investigate the effect of MO leaves antioxidant peptide pretreatment on H2O2-treated HepG2 cells and to refine the antioxidant activity. The results showed that MLPH1 had the strongest antioxidant activity, and three MO leaves antioxidant peptides (LALPVYN, LHIAALVFQ, and FHEEDDAKLF) were obtained. The peptide with the sequence LALPVYN and a molecular weight of 788.44 Da had the strongest antioxidant activity. After 24 h of LALPVYN pretreatment, the cell viability and the CAT, GSH-Px, and SOD enzyme activity were significantly increased, and the MDA, ROS, and apoptosis rates were significantly decreased. These results provide a theoretical basis for further research on the antioxidant mechanism of MO leaves peptides.

Ultrasonic-Cellulase Synergistic Extraction of Crude Polysaccharides from Moringa oleifera Leaves and Alleviation of Insulin Resistance in HepG2 Cells.

Moringa oleifera leaves (MOL) are a new food resource, rich in functional factors. MOL polysaccharides are important active macromolecules within MOL. However, there are problems, such as low extraction rates and lack of evidence for functional activity. Therefore, in this experiment, single-factor experiments were carried out using MOL powder as the raw material, and the Plackett-Burman test was used to screen the significantly influential test factors. The extraction process of MOL polysaccharide was optimized by response surface methodology. The insulin resistance alleviating activity of MOLP polysaccharides was initially explored. The results showed that the extraction of Moringa oleifera leaves crude polysaccharides (MOLP) by ultrasonic assisted cellulase enzymatic digestion was (17.03 ± 1.03)%, and the obtained MOLP was a crude polysaccharide with an average molecular weight (Mw) of 279.48 kDa, consisting of fucose, rhamnose, arabinose, galactose, glucose, xylose, mannose, galacturonic acid, and glucuronic acid. MOLP had an IC50 value of 8.02 mg/mL for α-glucosidase and scavenging activity against free radicals such as ABTS, DPPH, hydroxyl radicals, and superoxide anion with an IC50 value of 0.21 mg/mL 0.31 mg/mL 0.97 mg/mL 0.49 mg/mL. At the same time, MOLP significantly enhanced the glucose consumption, glycogen synthesis, CAT, SOD, GSH-Px activity, and reduced the MDA and ROS content in high glucose-induced insulin-resistant HepG2 (IR-HepG2) cells. This experiment improved the extraction rate of MOLP and demonstrated that MOLP has antioxidant activity and α-glucosidase inhibitory activity, which can alleviate the insulin resistance of high glucose-induced HepG2 cells. It provides partial data support for the possible hypoglycemic effect of MOLP by alleviating oxidative stress, and also provides new ideas for the in-depth study of basic research and industrial application of MOLP.

Defect-Engineered Co3 O4 @Nitrogen-Deficient Graphitic Carbon Nitride as an Efficient Bifunctional Electrocatalyst for High-Performance Metal-Air Batteries.

The ability to craft high-efficiency and non-precious bifunctional oxygen catalysts opens an enticing avenue for the real-world implementation of metal-air batteries (MABs). Herein, Co3 O4 encapsulated within nitrogen defect-rich g-C3 N4 (denoted Co3 O4 @ND-CN) as a bifunctional oxygen catalyst for MABs is prepared by graphitizing the zeolitic imidazolate framework (ZIF)-67@ND-CN. Co3 O4 @ND-CN possesses superb bifunctional catalytic performance, which facilitates the construction of high-performance MABs. Concretely, the rechargeable zinc-air battery based on Co3 O4 @ND-CN shows a superior round-trip efficiency of ≈60% with long-term durability (over 340 cycles), exceeding the battery with the state-of-the-art noble metals. The corresponding lithium-oxygen battery using Co3 O4 @ND-CN exhibits an excellent maximum discharge/charge capacity (9838.8/9657.6 mAh g-1 ), an impressive discharge/charge overpotential (1.14 V/0.18 V), and outstanding cycling stability. Such compelling electrocatalytic processes and device performances of Co3 O4 @ND-CN originate from concurrent compositional (i.e., defect-engineering) and structural (i.e., wrinkled morphology with abundant porosity) elaboration as well as the well-defined synergy between Co3 O4 and ND-CN, which produce an advantageous surface electronic environment corroborated by theoretical modeling. By extension, a rich diversity of other metal oxides@ND-CN with adjustable defects, architecture, and enhanced activities may be rationally designed and crafted for both scientific research on catalytic properties and technological development in renewable energy conversion and storage systems.

Does Digital Inclusive Finance Effectively Promote Agricultural Green Development?-A Case Study of China.

Agricultural green development is increasingly being discussed in sustainable development. This paper constructs agricultural green development from four dimensions: resource savings, environmental protection, ecological conservation, and quality industrialization. We apply the entropy-weighted Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) method to measure agricultural green development and employ a panel dataset of provinces in China from 2011-2019. Then, the dynamic spatial Durbin model is adopted to estimate the spatial effect of digital inclusive finance on agricultural green development. The main findings are as follows: (1) digital inclusive finance effectively promotes agricultural green development, and the promotional effect shows temporary and spatial spillover; (2) regional heterogeneity exists in the spatial effect in the short and long term; and (3) education, digital infrastructure, and traditional finance are important factors influencing this spatial effect of digital inclusive finance on agricultural green development.

Circulating small extracellular vesicles from patients with periodontitis contribute to development of insulin resistance.

BACKGROUND: Epidemiological studies have identified the role of periodontitis in the pathogenesis of type 2 diabetes, but the underlying mechanism is poorly understood. It is well-known that small extracellular vesicles are lipid bilayer vesicles derived from cells with a diameter around 30 to 200 nm. The purpose of this study was to investigate whether periodontitis induced or exacerbated insulin resistance via circulating small extracellular vesicles. METHODS: Plasma small extracellular vesicles from control and periodontitis rats were intravenously injected into type 2 diabetic rats. Insulin tolerance tests, glucose tolerance tests, and the activation of the insulin signaling pathway were measured to detect the effect of the plasma small extracellular vesicles on insulin sensitivity. In addition, circulating small extracellular vesicles from patients with periodontitis with or without diabetes were isolated and co-cultured with HepG2 cells. The ability of glucose uptake was assessed using the fluorescence of 2-NBDG via flow cytometry. The activation of insulin signaling pathway was examined via Western blotting. Real time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of enzyme related to glycolysis and gluconeogenesis. RESULTS: Small extracellular vesicles derived from the plasma of periodontitis rats further impaired glucose tolerance and insulin tolerance in diabetic rats and significantly reduced the activation of the insulin signaling pathway in liver tissues, as evidenced by the decreased levels of p-AKT and p-GSK3ß and the reduced hepatic glycogen content. For small extracellular vesicles isolated from human plasma, the concentration of small extracellular vesicles in patients with type 2 diabetes combined with periodontitis was higher than that of the healthy control and periodontitis alone. Moreover, circulating small extracellular vesicles from patients with periodontitis significantly inhibited the glucose uptake capacity and inhibited insulin signaling of HepG2 cells. CONCLUSION: Periodontitis acted as a contributing factor to exacerbate insulin resistance of type 2 diabetic rats. Plasma small extracellular vesicles played a critical role in periodontitis aggravating insulin resistance.

Controllable and Scale-Up Synthesis of Nickel-Cobalt Boride@Borate/RGO Nanoflakes via Reactive Impingement Mixing: A High-Performance Supercapacitor Electrode and Electrocatalyst.

Large-scale synthesis of graphene-based nanomaterials in stirred tank reactor (STR) often results in serious agglomeration because of the poor control during micromixing process. In this work, reactive impingement mixing is conducted in a two-stage impinging jet microreactor (TS-IJMR) for the controllable and scale-up synthesis of nickel-cobalt boride@borate core-shell nanostructures on RGO flakes (NCBO/RGO). Benefiting from the good process control and improved micromixing efficiency of TS-IJMR, NCBO/RGO nanosheet provides a large BET surface area, abundant of suitable mesopores (2-5 nm), fast ion diffusion, and facile electron transfer within the whole electrode. Therefore, NCBO/RGO electrode exhibits a high specific capacitance of 2383 F g-1 at 1 A g-1, and still retains 1650 F g-1 when the current density is increased to 20 A g-1, much higher than those of nickel boride@borate/RGO (NBO/RGO) and cobalt boride@borate/RGO (CBO/RGO) synthesized in TS-IJMR, as well as NCBO/RGO-S synthesized in STR. In addition, an asymmetric supercapacitor (NCBO/RGO//AC) is constructed with NCBO/RGO and activated carbon (AC), which displays a high energy density of 53.3 W h kg-1 and long cyclic lifespan with 91.8% capacitance retention after 5000 charge-discharge cycles. Finally, NCBO/RGO is used as OER electrocatalyst to possess a low overpotential of 309 mV at a current density of 10 mA cm-2 and delivers a good long-term durability for 10 h. This study opens up the potential of controllable and scale-up synthesis of NCBO/RGO nanosheets for high-performance supercapacitor electrode materials and OER catalysts.

Cementodentinal Tear Associated with a Periodontal- Endodontic Combined Lesion: A Case Report with a 14-Month Follow-up.

This case report describes the diagnosis and multidisciplinary treatment of a clinically indiscoverable cementodentinal tear associated with a periodontal-endodontic combined lesion. The tear site was located at the palatal root surface of the maxillary left canine. Due to its position and concomitant periapical periodontitis, it was not noticed at the initial visit until a 3D CBCT examination was conducted. Through combined endodontic-periodontal therapy (which included root canal therapy, root debridement, and periodontal flap surgery), the tear fragment was removed, and the periapical lesion healed gradually. A histologic examination confirmed the definitive diagnosis of a cementodentinal tear. After 14 months, the periodontal and endodontic status of the maxillary left canine were stable. According to these results, CBCT examination and multidisciplinary cooperation seem to be effective and necessary for the diagnosis and treatment of such clinically indiscoverable cementodentinal/cemental tears.

Mesenchymal Mycn participates in odontoblastic lineage commitment by regulating Krüppel-like Factor 4 (Klf4) in mice.

BACKGROUND: Commitment of mouse dental papilla cells (mDPCs) to the odontoblast lineage is critical for dentin formation, and this biological process is regulated by a complex transcription factor network. The transcription factor Mycn is a proto-oncogene that plays an important role in tumorigenesis and normal embryonic development. An early study revealed that Mycn is exclusively expressed in dental mesenchymal cells at E15.5, which implies a potential role of Mycn in dentinogenesis. However, the role of Mycn in dentin formation remains elusive. Thus, it is of considerable interest to elucidate the role of Mycn in dentin formation. METHODS: Mycnfl/fl; Osr2IresCre (MycnOsr2) and Mycnfl/fl; K14Cre (MycnK14) transgenic mice were generated, and micro-CT scans were performed to quantitatively analyse the volumetric differences in the molars and incisors of the mutants and their littermates. Mycn was also knocked down in vitro, and alkaline phosphatase (ALP) and alizarin red staining (ARS) were conducted. Cleavage under targets and tagmentation (CUT&Tag) analysis and dual luciferase assays were performed to identify direct downstream targets of Mycn. Immunofluorescence and immunochemistry staining and western blotting (WB) were performed to analyse the expression levels of potential targets. Quantitative PCR, WB, ALP and ARS were performed to test the rescue efficiency. RESULTS: Mesenchymal ablation of Mycn (MycnOsr2) led to defective dentin formation, while epithelial deletion (MycnK14) had no obvious effects on tooth development. ALP and ARS staining revealed that the commitment capacity of mDPCs to the odontoblast lineage was compromised in MycnOsr2 mice. CUT&Tag analysis identified Klf4 as a potential direct target of Mycn, and a dual luciferase reporter assay verified that Mycn could bind to the promotor region of Klf4 and directly activate its transcription. Reciprocally, forced expression of Klf4 partially recovered the odontoblastic differentiation capacity of mDPCs with Mycn knockdown. CONCLUSIONS: Our results elucidated that mesenchymal Mycn modulates the odontoblastic commitment of dental papilla cells by directly regulating Klf4. Our study illustrated the role of Mycn in dentin development and furthers our general comprehension of the transcription factor networks involved in the dentinogenesis process. Thus, these results may provide new insight into dentin hypoplasia and bioengineered dentin regeneration.

Stimuli-Responsive Polymers with Room-Temperature Phosphorescence.

Taking advantages of the impressing behaviors of room-temperature phosphorescence (RTP), the explorations in RTP materials are not only limited to efficient emission and ultralong lifetime of phosphorescence. The discovery and creation of stimuli-responsive properties have become the major pursuit, which will lay a solid foundation for future applications in RTP materials. Based on this, a review centered on recent progress of stimuli-responsive RTP materials is summarized to show frontier development in polymer systems. Different kinds of stimuli-responsive factors including light, oxygen, temperature, mechanical force and pH regulations are investigated in this review. Many potential applications and promising strategies are deeply discussed with the hope to assist future studies in this area.

Mycn deficiency underlies the development of orofacial clefts in mice and humans.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common subphenotype of non-syndromic orofacial clefts arising from genetic and/or environmental perturbations during embryonic development. We previously identified 2p24.2 as a risk locus associated with NSCL/P in the Chinese Han population, and MYCN is a candidate risk gene in this region. To understand the potential function of MYCN in craniofacial development, we generated Wnt1-Cre;Mycnflox/flox mice that exhibited cleft palate, microglossia and micrognathia, resembling the Pierre Robin sequence (PRS) in humans. Further analyses indicated that the cleft palate was secondary to the delayed elevation of palatal shelves caused by micrognathia. The micrognathia resulted from impaired chondrogenic differentiation in Merkel's cartilage, which limited tongue development, leading to microglossia. In terms of mechanism, Mycn deficiency in cranial neural crest cells (CNCCs) downregulated Sox9 expression by inhibiting Wnt5a in a CNCC-derived chondrogenic lineage in Merkel's cartilage. To investigate whether MYCN deficiency contributed to NSCL/P, we performed direct sequencing targeting all exons and exon-intron boundaries of MYCN in 104 multiplex families with Mendelian NSCL/P and identified a novel pathogenic variant in MYCN. Taken together, our data indicate that ablation of Mycn in mouse CNCCs could resemble PRS by suppressing the Wnt5a-Sox9 signaling pathway in Merkel's cartilage and that mutations in MYCN may be novel potential causes of NSCL/P.

Visually Monitoring the Compactness of Polymer Matrixes Coded by Disparate Luminescence.

The intrinsic property disclosure of polymer systems by visual monitoring of photoluminescence behaviors is of great value in fundamental interest and promising applications. Three novel polymer films were obtained by simply doping methyl 9,14-diphenyl-9,14-dihydrodibenzo[a,c]phenazine-11-carboxylate (DPC) with three polymer materials. The photoluminescence behaviors of these films represented diverse fluorescence emissions from light orange to blue, especially room-temperature phosphorescence (RTP) emissions with ultralong lifetime, attributing to various configurations of DPC molecules provided by distinct microscopic environments in three polymer systems. The rigidity and regularity of polymer systems would be visually reflexed by luminescence regulation and temperature responses. In addition, irregular distribution of distinct polymer systems could be specifically monitored by both fluorescence and phosphorescence behaviors when doping different polymer materials into one blend film.

Polymer-free corticosteroid dimer implants for controlled and sustained drug delivery.

Polymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have benefitted from their use for the treatment of inflammatory-mediated conditions. However, these polymer-based systems often have limited drug-loading capacity, suboptimal release kinetics, and/or promote adverse inflammatory responses. This manuscript investigates and describes a strategy for achieving controlled delivery of corticosteroids, based on a discovery that low molecular weight corticosteroid dimers can be processed into drug delivery implant materials using a broad range of established fabrication methods, without the use of polymers or excipients. These implants undergo surface erosion, achieving tightly controlled and reproducible drug release kinetics in vitro. As an example, when used as ocular implants in rats, a dexamethasone dimer implant is shown to effectively inhibit inflammation induced by lipopolysaccharide. In a rabbit model, dexamethasone dimer intravitreal implants demonstrate predictable pharmacokinetics and significantly extend drug release duration and efficacy (>6 months) compared to a leading commercial polymeric dexamethasone-releasing implant.