Responses of microRNA in digestive glands of mussel Mytilus galloprovincialis exposed to polystyrene nanoplastics.

Polystyrene nanoplastics (PS-NPs) are typical accumulated nanoplastics in the marine environment and organisms, and have strong potential risks to marine ecological environment and human health. MiRNAs could respond to and participate in the response process of environmental stressors. However, the response of miRNAs to nanoplastics has not been fully explored. In this study, miRNA responses of digestive glands in mussels Mytilus galloprovincialis treated by 200 nm PS-NPs (20, 200, 2000 µg/L) for 7 days were characterized by BGISEQ-500 deep sequencing and bioinformatics analysis, along with histopathological quantification with planimetric parameters on hematoxylin and eosin (H&E) staining. Results showed that one novel miRNA (novel_mir63) and seven known miRNAs (miR-34_2, miR-34_5, miR-281_8, let-7-5p_6, miR-10, miR-124, miR-29b-3p) were significantly (adjusted P-value < 0.05) differentially expressed after PS-NPs treatments, and most of them were down-regulated expect for novel_mir63 and miR-34_2. Function analysis of target genes corresponding to these differentially expressed miRNAs indicated that PS-NPs disturbed the process related to metabolism, aging, cardiac function, neural excitation, and repairment. Among them, acetyl-CoA C-acetyltransferase and purine metabolism pathway played vital connection roles. Meanwhile, significantly morphology changes of digestive tubes obtained from H&E stained sections also implied severely disrupted metabolic capability in digestive glands, reflected by significantly increased mean diverticular radius (MDR) and mean luminal radius (MLR) values and the ratio of MLR to mean epithelial thickness (MET), and significantly decreased MET value and MET/MDR. Overall, these findings have revealed new characterization of miRNAs and their target genes in mussel M. galloprovincialis under PS-NPs stress, and provide important clues to further elucidate the toxicity mechanisms of PS-NPs.

Mutations of PTCH1 gene in two pedigrees with bifid rib-basal cell nevus-jaw cyst syndrome. / 肋骨分叉-基底细胞痣-é¢Œéª¨å›Šè‚¿ç»¼åˆå¾ä¸¤å®¶ç³»åŸºå› åºåˆ—å˜å¼‚åˆ†æž.

Two male patients with bifid rib-basal cell nevus-jaw cyst syndrome (BCNS) were admitted to Department of Stomatology, the First Affiliated Hospital of Bengbu Medical College due to radiological findings of multiple low density shadows in the jaw. Clinical and imaging findings showed thoracic malformation, calcification of the tentorium cerebellum and falx cerebrum as well as widening of the orbital distance. Whole exon high-throughput sequencing was performed in two patients and their family members. The heterozygous mutations of c.C2541C>A(p.Y847X) and c.C1501C>T(p.Q501X) in PTCH1 gene were detected in both patients. Diagnosis of BCNS was confirmed. The heterozygous mutations of PTCH1 gene locus were also found in the mothers of the two probands. Proband 1 showed clinical manifestations of low intelligence, and heterozygous mutations of c.C2141T(p.P714L) and c.G3343A(p.V1115I) were detected in FANCD2 gene. Proband 2 had normal intelligence and no FANCD2 mutation. The fenestration decompression and curettage of jaw cyst were performed in both patients. Regular follow-up showed good bone growth at the original lesion, and no recurrence has been observed so far.

Crowding-Induced DNA Translocation through a Protein Nanopore.

A crowded cellular environment is highly associated with many significant biological processes. However, the effect of molecular crowding on the translocation behavior of DNA through a pore has not been explored. Here, we use nanopore single-molecule analytical technique to quantify the thermodynamics and kinetics of DNA transport under heterogeneous cosolute PEGs. The results demonstrate that the frequency of the translocation event exhibits a nonmonotonic dependence on the crowding agent size, while both the event frequency and translocation time increase monotonically with increasing crowder concentration. In the presence of PEGs, the rate of DNA capture into the nanopore elevates 118.27-fold, and at the same time the translocation velocity decreases from 20 to 120 µs/base. Interestingly, the impact of PEG 4k on the DNA-nanopore interaction is the most notable, with up to ΔΔG = 16.27 kJ mol-1 change in free energy and 764.50-fold increase in the binding constant at concentration of 40% (w/v). The molecular crowding effect will has broad applications in nanopore biosensing and nanopore DNA sequencing in which the strategy to capture analyte and to control the transport is urgently required.

Surveillance for severe hand, foot, and mouth disease from 2009 to 2015 in Jiangsu province: epidemiology, etiology, and disease burden.

BACKGROUND: Severe hand, foot, and mouth disease (HFMD) is a common childhood illness caused by various enteroviruses. The disease has imposed increased burden on children younger than 5 years old. We aimed to determine the epidemiology, CNS complication, and etiology among severe HFMD patients, in Jiangsu, China. METHODS: Epidemiological, clinical, and laboratory data of severe HFMD cases were extracted from 2009 to 2015. The CNS complication, annually severe illness rates, mortality rates, severity-PICU admission rates, severity-hospitalization rates, and so on were analyzed to assess the disease burden of severe HFMD. All analyses were stratified by time, region, population, CNS involvement and serotypes. The VP1 gene from EV-A71, CV-A16, CV-A6, CV-A10 and other enteroviruses isolates was amplified. Phylogenetic analysis was performed using MEGA5.0. RESULTS: Seven thousand nine hundred ninety-four severe HFMD cases were reported, of them, 7224 cases were inpatients, 611 were PICU inpatients, and 68 were fatal. The average severe illness rate, mortality rate, severity-fatality rate, severity-PICU admission rate, and severity-hospitalization rate were 14.54, 0.12,8506, 76,430, and 903,700 per 1 million, respectively. The severe illness rate was the highest in the 12-23 months age group, and the greatest mortality rate was in the 6-11 months age group. Geographical difference in severe illness rate and mortality were found. Patients infected with EV-A71 were at a higher proportion in different CNS involvement even death. EV-A71, CV-A16 and other enteroviruses accounted for 79.14, 6.49, and 14.47%, respectively. A total of 14 non-EV-A71/ CV-A16 genotypes including CV-A2, CV-A4, CV-A 6, CV-A9, CV-A10, CV-B1, CV-B2, CV-B3, CV-B4, CV-B5, E-6, E-7, E-18, and EV-C96 were identified. Phylogentic analyses demonstrated that EV-A71 strains belonged to subgenotype C4a, while CV-A16 strains belonged to sub-genotype B1a and sub-genotype B1b of genotype B1. CV-A6 strains were assigned to genogroup F, and CV-A10 strains belonged to genogroup D. CONCLUSIONS: Future mitigation policies should take into account the age, region heterogeneities, CNS conditions and serotype of disease. Additional a more rigorous study between the mild and severe HFMD should be warranted to elucidate the difference epidemiology, pathogen spectrum and immunity patterns and to optimize interventions in the following study.

Fluorescence Lifetime-Resolved Ion-Selective Nanospheres for Simultaneous Imaging of Calcium Ion in Mitochondria and Lysosomes.

In this paper, novel calcium-selective nanospheres incorporating Pluronic F127 and (4-carboxybutyl) triphenylphosphonium bromide (TPP) as shell layers were designed to monitor the level of free calcium ion in mitochondria and lysosomes at living cells simultaneously. TPP as a target for mitochondria drove the nanospheres to bind intracellular mitochondria, while the lipophilic F127 layer resulted in the partial accumulation of nanospheres in lysosomes. This dual feature of the shell layer led to the colocation of nanospheres in both mitochondria and lysosomes. Chromoionophore III (ETH 5350) was chosen as the chromoionophore in the nanospheres that had different fluorescence lifetimes in either mitochondria or lysosomes, and therefore, the locations of the nanospheres at these two cellular compartments were identified. After the stimulation of cells using ionomycin, a burst of calcium concentration in mitochondria was observed that was associated with almost constant calcium concentration in lysosomes. The simultaneous recording of calcium ions in both of the compartments using fluorescence lifetime-solved nanospheres offered a special strategy to spatially monitor subcellular fluctuation of ions in living cells.

PTD modified paclitaxel anti-resistant liposomes for treatment of drug-resistant non-small cell lung cancer.

CONTEXT: Non-small cell lung carcinoma (NSCLC) is a type of epithelial lung cancer that accounts for approximately 80-85% of lung carcinoma cases. Chemotherapy for the NSCLC is unsatisfactory due to multidrug resistance, nonselectively distributions and the accompanying side effects. OBJECTIVE: The objective of this study was to develop a kind of PTD modified paclitaxel anti-resistant liposomes to overcome these chemotherapy limitations. METHOD: The studies were performed on LLT cells and resistant LLT cells in vitro and on NSCLC xenograft mice in vivo, respectively. RESULTS AND DISCUSSION: In vitro results showed that the liposomes with suitable physicochemical characteristics could significantly increase intracellular uptake in both LLT cells and resistant LLT cells, evidently inhibit the growth of cancer cells, and clearly induce the apoptosis of resistant LLT cells. Studies on resistant LLT cells xenograft mice demonstrated that the liposomes magnificently enhanced the anticancer efficacy in vivo. Involved action mechanisms were down-regulation of adenosine triphosphate binding cassette transporters on resistant LLT cells, and activation of the apoptotic enzymes (caspase 8/9/3). CONCLUSION: The PTD modified paclitaxel anti-resistant liposomes may provide a promising strategy for treatment of the drug-resistant non-small cell lung cancer.

[Comparative study on pharmacokinetics and tissue distribution of a novel microemulsion based on the paclitaxel/L-OH lipid complex and paclitaxel injection in cremophor].

The pharmacokinetics and tissue distributions of the novel paclitaxel microemulsion based on the L-OH lipid complex made in our laboratory were studied in this article with the commercial paclitaxel injection in cremophor as reference preparation by injected intravenously with single dose of 5 mg x kg(-1) in rats. LC-MS/MS method was used to determine the drug concentration in plasma and calculate the pharmacokinetic parameters. [3H]-paclitaxel was used to reveal the tissue distributions of different organs in 0.5 h, 3 h, 24 h and 120 h. The results indicated that the AUC of the emulsion group descended to 42.55%, with the CLz and Vz increased by 2.27 times and 3.81 times respectively. Tissue distribution results revealed that the emulsion showed a significantly increase in liver and spleen with a peak concentration up to 5 times; a slightly increase was observed in lung with no statistical differences; a significantly decrease in heart, kidney, gastrointestinal tract, bone marrow, aorta, thymus, pancreas, fat, muscle, skin, seminal vesicle, reproductive organs and brain with a drop of 40%-80%. These results indicated that paclitaxel microemulsion based on L-OH lipid complexes can remarkably reduced the blood exposure, accelerate plasma clearance rate and increase distribution volume. The fact that paclitaxel microemulsion tended to be uptake by reticuloendothelial system (RES) contributed to the target in liver, spleen and lung, and help to reduce the toxicity in blood, heart, kidney and gastrointestinal tract.

Association between Periodontitis and Aortic Calcification: A Cohort Study.

The present study investigated the association between the presence of periodontitis and aortic calcification (AC) risk among Chinese adults. A total of 6059 individuals who underwent regular health check-ups and received a diagnosis of periodontitis between 2009 and 2016 were included. The outcome was AC, assessed by a chest low-dose spiral CT scan. Cox proportional hazards regression analysis was used to assess the association between periodontitis and AC risk after adjusting for several confounders. After a median follow-up period of 2.3 years (interquartile range: 1.03-4.97 years), 843 cases of AC were identified, with 532 (12.13%) and 311 (18.59%) patients in the non-periodontitis group and periodontitis group, respectively. Multivariate analyses demonstrated that, compared with those without periodontitis, the hazard ratio and 95% confidence interval for AC risk in participants with periodontitis was 1.18 (1.02-1.36) (P = .025) in the fully adjusted model. Stratified analyses showed that the positive relationship between periodontitis and AC was more evident in males and participants <65 years of age (pinteraction = .005 and .004, respectively). Our results show that the presence of periodontitis was positively associated with AC among Chinese adults, especially among males and younger participants.

[Application of personalized guide plate combined with real-time navigation in repairing mandibular defect using fibula muscle flap].

Objective: To explore the application of personalized guide plate combined with intraoperative real-time navigation in repairing of mandibular defect using fibula muscle flap, providing the basis for the precise repair and reconstruction of mandible. Methods: The clinical data of 12 patients (9 males and 3 females) aged from 23 to 71 years (mean, 55.5 years) between July 2019 and December 2021 were recorded. These patients were diagnosed as benign or malignant mandibular tumors, including 2 cases of ameloblastoma, 6 cases of squamous cell carcinoma, 2 cases of osteosarcoma, 1 case of adenoid cystic carcinoma, and 1 case of squamous carcinoma. All patients were treated with mandibular amputation, and then repaired by double-stacked three-segment fibula muscle flap. Preoperative virtual design scheme and guide plate were performed. During the operation, personalized guide plate combined with real-time navigation was used for fibular osteotomy and shaping. Thin-slice CT examination was performed at 2-3 weeks after operation, and was fitted with the preoperative virtual design scheme. The difference between the distance of bilateral mandibular angles relative to the reference plane in three-dimensional directions (left-right, vertical, and anterior-posterior) and the difference of the medial angle of the lower edge of the mandible reconstructed by fibula were measured, and the mean error of chromatographic fitting degree was calculated. Results: The guide plate and navigation were applied well, and the fibula shaping and positioning were accurate. The fibula muscle flap survived, the incision healed well, and the occlusal relationship was good. All 12 patients were followed up 1-29 months, with an average of 17 months. There was no significant difference on the distance of bilateral mandibular angles relative to the reference plane in the left-right [(-0.24±1.35) mm; t=-0.618, P=0.549], vertical [-0.85 (-1.35, 1.40) mm; Z=-0.079, P=0.937], and anterior-posterior [(-0.46±0.78) mm; t=-2.036, P=0.067] directions. The difference of the medial angle of the lower edge of the mandible reconstructed by fibula was also not significant [(-1.35±4.34)°; t=-1.081, P=0.303)]. Postoperative CT and preoperative virtual design fitting verified that there was no significant difference in the change of the mandibular angle on both sides, and the average error was (0.47±1.39) mm. Conclusion: The personalized guide combined with intraoperative real-time navigation improves the accuracy of peroneal muscle flap reconstruction of the mandible, reduces the complications, and provides a preliminary basis for the application of visual intraoperative navigation in fibula muscle flap reconstruction of the mandible.

Self-Adjuvanting Lipoprotein Conjugate αGalCer-RBD Induces Potent Immunity against SARS-CoV-2 and its Variants of Concern.

Safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants are the best approach to successfully combat the COVID-19 pandemic. The receptor-binding domain (RBD) of the viral spike protein is a major target to develop candidate vaccines. α-Galactosylceramide (αGalCer), a potent invariant natural killer T cell (iNKT) agonist, was site-specifically conjugated to the N-terminus of the RBD to form an adjuvant-protein conjugate, which was anchored on the liposome surface. This is the first time that an iNKT cell agonist was conjugated to the protein antigen. Compared to the unconjugated RBD/αGalCer mixture, the αGalCer-RBD conjugate induced significantly stronger humoral and cellular responses. The conjugate vaccine also showed effective cross-neutralization to all variants of concern (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). These results suggest that the self-adjuvanting αGalCer-RBD has great potential to be an effective COVID-19 vaccine candidate, and this strategy might be useful for designing various subunit vaccines.

Formulation, characterization and hypersensitivity evaluation of an intravenous emulsion loaded with a paclitaxel-cholesterol complex.

The objective of this paper was to develop a novel Cremophor-free, autoclave stable, intravenous emulsion for paclitaxel (PACE). A paclitaxel-cholesterol complex was used as the drug carrier to improve the solubility of paclitaxel in the oil phase of emulsions. The complex and PACE were prepared by rotary evaporation and high-pressure homogenization, respectively. Effects of oil phases, emulsifiers and pH values on the characteristics of PACE were investigated. PACE was characterized with regard to its appearance, morphology, osmolality, pH value, particle size, zeta potential, encapsulation efficiency and stability. Hypersensitivity was evaluated by guinea pig hypersensitivity reaction. The final formulation was composed of the complex, soybean oil, medium-chain triglyceridel, soybean lecithin, poloxamer 188 and glycerol. The resulting PACE had an encapsulation efficiency of 97.3% with a particle size of 135 nm and a zeta potential of -38.3 mV. Osmolality and pH of the formulation were 383 mOsmol/kg and 4.5, respectively. The formulation survived autoclaving at 115 °C for 30 min and remained stable for at least 12 months at 6 °C. PACE also exhibited a better tolerance than an equal dose of Cremophor-based paclitaxel injection in guinea pigs, as no obvious hypersensitivity reaction was observed. These results suggested that PACE has a great potential for industrial-scale production and clinical applications.

Bilateral Necrotizing Retinitis following Encephalitis Caused by the Pseudorabies Virus Confirmed by Next-Generation Sequencing.

Purpose: The objective of this study was to report a case of bilateral necrotizing retinitis following viral encephalitis caused by the pseudorabies virus.Case report: A 49-year-old male had decreased bilateral visual acuity after the recovery of consciousness for one month. He had been in an unconsciousness status due to encephalitis for two months before the ocular symptoms developed. He was a pig slaughterer. Ocular ultrasound showed bilateral vitreous haze and retinal detachment. A vitrectomy and silicone oil tamponade were performed on the left eye. During surgery, massive periphery retinal necrosis appearing as a tattered fish net, and multiple retinal holes were observed. The pseudorabies virus was detected by next-generation sequencing in the vitreous specimen.Conclusion: The pseudorabies virus may cause bilateral necrotizing retinitis following viral encephalitis among those with close contact to pigs. Intraocular fluid provides a greater selection of samples and a longer time window for pathogenic detection.

Responsive Carbonized Polymer Dots for Optical Super-resolution and Fluorescence Lifetime Imaging of Nucleic Acids in Living Cells.

The rapid development of advanced optical imaging methods including stimulated emission depletion (STED) and fluorescence lifetime imaging microscopy (FLIM) has provided powerful tools for real-time observation of submicrometer biotargets to achieve unprecedented spatial and temporal resolutions. However, the practical imaging qualities are often limited by the performance of fluorescent probes, leading to unsatisfactory results. In particular, long-term imaging of nucleic acids in living cells with STED and FLIM remained desirable yet challenging due to the lack of competent probes combining targeting specificity, biocompatibility, low power requirement, and photostability. In this work, we rationally designed and synthesized a nanosized carbonized polymer dot (CPD) material, CPDs-3, with highly efficient and photostable emission for the super-resolution and fluorescence lifetime imaging of nucleic acids in living cells. The as-fabricated nanoprobe showed responsive emission properties upon binding with nucleic acids, providing an excellent signal-to-noise ratio in both spatial and temporal dimensions. Moreover, the characteristic saturation intensity value of CPDs-3 was as low as 0.68 mW (0.23 MW/cm2), allowing the direct observation of chromatin structures with subdiffraction resolution (90 nm) at very low excitation (<1 µW) and depletion power (<5 mW). Owing to its low toxicity, high photonic efficiency, and outstanding photostability, CPDs-3 was capable of performing long-term imaging both with STED and FLIM setups, demonstrating great potential for the dynamic study of nucleic acid functionalities in the long run.

Short-time deep eutectic solvents pretreatment enhanced production of fermentable sugars and tailored lignin nanoparticles from abaca.

Deep eutectic solvents (DES) pretreatment is a promising approach to decrease "biomass recalcitrance" and boost the cellulose bioconversion as well as lignin valorization. In this study, a short-time DES pretreatment strategy was performed to enhance the production of high-yield fermentable sugars and tailored lignin nanoparticles (LNPs) from abaca. The glucose yield reached 92.4% under the optimal pretreatment condition (110 °C, 30 min), which was dramatically increased in comparison with that (9.5%) of control abaca. Simultaneously, nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) techniques indicated that the removed and regenerated DES lignin fractions displayed depolymerized structures and have relatively low molecular weight with relatively homogeneous morphology and narrow size distribution. Transmission electron microscope (TEM) analysis indicated that these lignin fractions are LNPs and the size of the optimal LNPs fraction is ranged from 30 nm to 50 nm. Moreover, all the DES lignin exhibited excellent antioxidant activities as compared to the commercial antioxidant butylated hydroxytoluene (BHT), which can be used as a promising natural antioxidant in industry. In short, this study demonstrated that the short-time DES pretreatment will improve the enzymatic digestibility and facilitate the controllable production and valorization of LNPs from abaca biomass, which will further promote the economic and overall benefits of biorefinery.

UV-Protective, Self-Cleaning, and Antibacterial Nanofiber-Based Triboelectric Nanogenerators for Self-Powered Human Motion Monitoring.

Equipping wearable electronics with special functions will endow them with more additional values and more comprehensive practical performance. Here, we report an ultraviolet (UV)-protective, self-cleaning, antibacterial, and self-powered all-nanofiber-based triboelectric nanogenerator (TENG) for mechanical energy harvesting and self-powered sensing, which is fabricated with Ag nanowires (NWs)/TPU nanofibers and the TiO2@PAN networks through a facile electrospinning method. Due to the added TiO2 nanoparticles (NPs), the TENG presents excellent UV-protective performance, including the ultraviolet protection factor (UPF) of ∼204, the transmittance of UVA (TUVA) of ∼0.0574%, and the transmittance of UVB (TUVB) ∼0.107%. Furthermore, under solar lighting for 25 min, most surface contamination can be degraded, and the decreased power output would be recovered. Owing to the coupled effects of TiO2 NPs and Ag NWs, the TENG shows excellent antibacterial activity against Staphylococcus aureus. Due to the micro-to-nano hierarchical porous structure, the all-nanofiber-based TENG can serve as self-powered pedometers for detecting and tracking human motion behaviors. As a multifunctional self-powered device, the TENG prompts various applications in the fields of micro/nanopower sources, human movement monitoring, and human-machine interfaces, potentially providing an alternative energy solution and a multifunctional interactive platform for the next-generation wearable electronics.

Macular Perfusion Changes and Ganglion Cell Complex Loss in Patients with Silicone Oil-related Visual Loss.

OBJECTIVE: The aim of this study was to investigate macular perfusion changes and ganglion cell complex (GCC) loss in patients with unexplained visual loss following vitrectomy and silicone oil (SO) tamponade, and to evaluate the correlation between retinal blood flow and GCC loss using optical coherence tomography angiography (OCTA) and optical coherence tomography (OCT). METHODS: This retrospective study included seven eyes (seven patients) with unexpected visual loss after vitrectomy and SO tamponade. OCTA was used to evaluate the alterations in retinal vessel density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and radial peripapillary capillary plexus (RPCP). OCT was used to measure the thickness of GCC and retinal nerve fiber layer (RNFL). Medical records of patients were reviewed. RESULTS: Quantitative analysis of OCTA images revealed a significant reduction in SCP VD in the affected eyes compared with the controls (all sections P < 0.05). No difference was found in GCC thickness, but FLV (focal loss volume) and GLV (global loss volume) were significantly higher in the affected eyes (both P < 0.001). SCP VD was inversely correlated with FLV and GLV. CONCLUSIONS: Silicone oil-related severe visual loss was associated with superficial retinal microvasculature damage and ganglion cell apoptosis.

A breathable, biodegradable, antibacterial, and self-powered electronic skin based on all-nanofiber triboelectric nanogenerators.

Mimicking the comprehensive functions of human sensing via electronic skins (e-skins) is highly interesting for the development of human-machine interactions and artificial intelligences. Some e-skins with high sensitivity and stability were developed; however, little attention is paid to their comfortability, environmental friendliness, and antibacterial activity. Here, we report a breathable, biodegradable, and antibacterial e-skin based on all-nanofiber triboelectric nanogenerators, which is fabricated by sandwiching silver nanowire (Ag NW) between polylactic-co-glycolic acid (PLGA) and polyvinyl alcohol (PVA). With micro-to-nano hierarchical porous structure, the e-skin has high specific surface area for contact electrification and numerous capillary channels for thermal-moisture transfer. Through adjusting the concentration of Ag NW and the selection of PVA and PLGA, the antibacterial and biodegradable capability of e-skins can be tuned, respectively. Our e-skin can achieve real-time and self-powered monitoring of whole-body physiological signal and joint movement. This work provides a previously unexplored strategy for multifunctional e-skins with excellent practicability.

Gadolinium-doped mesoporous calcium silicate/chitosan scaffolds enhanced bone regeneration ability.

Chitosan (CTS) and mesoporous calcium silicate (MCS) have been developed for bone defect healing; however, their bone regeneration capacity still does not satisfy the patients with bone diseases. Gadolinium (Gd) is accumulated in human bones, and plays a beneficial role in regulating cell performance and bone regeneration. We firstly constructed Gd-doped MCS/CTS (Gd-MCS/CTS) scaffolds by a lyophilization technology. The interconnected arrangement of CTS films lead to forming macropores by using ice crystals as templates during the lyophilization procedure, and the Gd-MCS nanoparticles dispersed uniformly on the macropore walls. The biocompatible chemical components and hierarchical pores facilitated the attachment and spreading of rat bone marrow-derived mesenchymal stem cells (rBMSCs). Interestingly, the Gd dopants in the scaffolds effectively activated the Wnt/ß-catenin signaling pathway, resulting in excellent cell proliferation and osteogenic differentiation capacities. The osteogenic-related genes such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and collagen type1 (COL-1) were remarkably up-regulated by Gd-MCS scaffolds as compared with MCS scaffolds, and their expression levels increased in a positive correlation with Gd doping amounts. Moreover, in vivo rat cranial defect tests further confirmed that Gd-MCS/CTS scaffolds significantly stimulated collagen deposition and new bone formation. The exciting finding suggested the beneficial effects of Gd3+ ions on osteogenic differentiation and new bone regeneration, and Gd-MCS/CTS scaffolds can be employed as a novel platform for bone defect healing.

Mature Human White Adipocytes Cultured under Membranes Maintain Identity, Function, and Can Transdifferentiate into Brown-like Adipocytes.

White adipose tissue (WAT) is a central factor in the development of type 2 diabetes, but there is a paucity of translational models to study mature adipocytes. We describe a method for the culture of mature white adipocytes under a permeable membrane. Compared to existing culture methods, MAAC (membrane mature adipocyte aggregate cultures) better maintain adipogenic gene expression, do not dedifferentiate, display reduced hypoxia, and remain functional after long-term culture. Subcutaneous and visceral adipocytes cultured as MAAC retain depot-specific gene expression, and adipocytes from both lean and obese patients can be cultured. Importantly, we show that rosiglitazone treatment or PGC1α overexpression in mature white adipocytes induces a brown fat transcriptional program, providing direct evidence that human adipocytes can transdifferentiate into brown-like adipocytes. Together, these data show that MAAC are a versatile tool for studying phenotypic changes of mature adipocytes and provide an improved translational model for drug development.

CONGENITAL CONTRACTILE PERIPAPILLARY STAPHYLOMA WITH RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To describe the occurrence of a congenital contractile peripapillary staphyloma in association with a rhegmatogenous retinal detachment. METHODS: The clinical course of a 17-year-old patient with a contractile peripapillary staphyloma and undergoing pars plana vitrectomy for repair of an associated retinal detachment was studied. RESULTS: The left eye showed a peripapillary staphyloma which during the ophthalmoscopical examination revealed contractile movements after the presentation of a light stimulus to either eye. The contraction of the peripapillary staphyloma was not correlated with a Valsalva maneuver, neck venous compression, forced lid closure, or respiratory movements. Because of a retinal detachment involving the inferior, nasal, and temporal retina, best-corrected visual acuity was 20/100. During pars plana vitrectomy under systemic anesthesia, the contractions of the peripapillary staphyloma subsided in the early phase of surgery, and reoccurred at approximately 80 minutes after the start of general anesthesia, when the posterior pole was touched with an aspiration syringe. CONCLUSION: The etiology of the movements of the congenital peripapillary staphyloma in our patient may include a misbalance between intraocular pressure and orbital cerebrospinal fluid pressure or contractions of extraocular muscles. The observations may give information about the physiology and pathophysiology of the optic nerve head.