ALPL regulates pro-angiogenic capacity of mesenchymal stem cells through ATP-P2X7 axis controlled exosomes secretion.

BACKGROUND: Early-onset bone dysplasia is a common manifestation of hypophosphatasia (HPP), an autosomal inherited disease caused by ALPL mutation. ALPL ablation induces prototypical premature bone ageing characteristics, resulting in impaired osteogenic differentiation capacity of human bone marrow mesenchymal stem cells (hBMMSCs). As angiogenesis is tightly coupled with osteogenesis, it also plays a necessary role in sustaining bone homeostasis. We have previously observed a decrease in expression of angiogenesis marker gene CD31 in the metaphysis of long bone in Alpl+/- mice. However, the role of ALPL in regulation of angiogenesis in bone has remained largely unknown. METHODS: Exosomes derived from Normal and HPP hBMMSCs were isolated and identified by ultracentrifugation, transmission electron microscopy, and nanoparticle size measurement. The effects of ALPL on the angiogenic capacity of hBMMSCs from HPP patients were assessed by immunofluorescence, tube formation, wound healing and migration assay. exo-ELISA and Western Blot were used to evaluate the exosomes secretion of hBMMSCs from HPP, and the protein expression of VEGF, PDGFBB, Angiostatin and Endostatin in exosomes respectively. RESULTS: We verified that ALPL ablation resulted in impaired pro-angiogenic capacity of hBMMSCs, accounting for reduced migration and tube formation of human umbilical vein endothelial cells, as the quantities and proteins composition of exosomes varied with ALPL expression. Mechanistically, loss of function of ALPL enhanced ATP release. Additional ATP, in turn, led to markedly elevated level of ATP receptor P2X7, which consequently promoted exosomes secretion, resulting in a decreased capacity to promote angiogenesis. Conversely, inhibition of P2X7 increased the angiogenic induction capacity by preventing excessive release of anti-angiogenic exosomes in ALPL deficient-hBMMSCs. CONCLUSION: The ALPL-ATP axis regulates the pro-angiogenic ability of hBMMSCs by controlling exosomes secretion through the P2X7 receptor. Thus, P2X7 may be proved as an effective therapeutic target for accelerating neovascularization in ALPL-deficient bone defects.

Spatiotemporally Coupled Electron-Hole Dynamics in Two Dimensional Heterostructures.

Coulomb interactions play a crucial role in low-dimensional semiconductor materials, e.g., 2D layered semiconductors, dictating their electronic and optical properties. However, fundamental questions remain as to whether and how Coulomb interactions affect the charge or energy flow in 2D heterostructures, which is essential for their light-electricity conversions. Herein, using ultrafast spectroscopy, we report real space coupled electron-hole dynamics in 2D heterostructures. We show in (WSe2/)WS2/MoTe2 with a controlled energy gradient for the hole and a near flat band for electron transfer, the fate of the electron is controlled by the hole in coupled dynamics. The interfacial electron transfer from WS2 to MoTe2 follows the hole closely and can be facilitated or suppressed by dynamic Coulomb interaction. In parallel to the band alignment, this study reveals the critical role of Coulomb interactions on the fate of photogenerated charges in 2D heterostructures, providing experimental evidence for coupled electron-hole dynamics and a new knob for steering nanoscale charge or energy transfer process.

ErbB4 processing is involved in OGD/R induced neuron injury.

OBJECTIVE: Our previous study found that ErbB4 gene expression was changed after oxygen-glucose deprivation/reperfusion (OGD/R). However, the exact role and mechanism of ErbB4 in brain ischemia are largely unknown. In this study, we explored the protective effects of ErbB4 and its possible mechanism after OGD/R. METHODS: Cerebral ischemia/reperfusion (I/R) injury model was established in vitro and in vivo. Cell viability, apoptosis, and ROS production were measured by MTT, TUNEL, and fluorescent probe 2', 7'-dichlorofluorescein diacetate (DCFH-DA). Infarct size was evaluated by TTC. We performed bioinformatics analyses to screen for novel key genes involved in ErbB4 changes. RNA-Seq was used to transcriptome analysis. RNA and protein expression were detected by quantitative RT‒PCR and western bloting. RESULTS: The expression of 80-kDa ErbB4 decreased after cerebral I/R injury in vitro and in vivo. Co-expression network analysis revealed that ErbB4 expression was correlated with the changes in Adrb1, Adrb2, Ldlr, and Dab2. Quantitative RT‒PCR revealed that the mRNA expression levels of Adrb1, Adrb2, and Dab2 were upregulated, and that of Ldlr was decreased after OGD/R. Activation of ErbB4 expression by neuregulin 1 (NRG1) significantly promoted cell survival, attenuated hippocampal apoptosis, and decreased ROS production after OGD/R. Furthermore, the elimination of ErbB4 using a specific siRNA reversed these beneficial effects. CONCLUSION: Our data revealed the neuroprotective effects of ErbB4 against OGD/R injury, and the action could be related to changes in the ErbB4 membrane-associated fragment and the expression of Adrb1, Adrb2, Ldlr, and Dab2.

Platelet count and clinical outcomes among ischemic stroke patients with endovascular thrombectomy in DIRECT-MT.

OBJECTIVES: The prognostic role of baseline platelet count (PLT) in acute ischemic stroke patients with large vessel occlusion undergoing endovascular thrombectomy is unclear. Whether PLT modifies alteplase treatment effect on clinical outcome in those patients is also uncertain. METHODS: We derived data from a multicenter randomized clinical trial (DIRECT-MT) comparing intravenous alteplase before endovascular treatment vs. endovascular treatment only. The 654 patients with available PLT data were included. Primary outcome was the ordinal modified Rankin Scale (mRS) score evaluated at 90 days. We also assessed various secondary and safety outcomes. RESULTS: After adjusting for confounding factors, patients in the top tertile of PLT had a significantly lower risk of a worse shift in the distribution of mRS score (Odds Ratio: 0.671, 95% Confidence Interval: 0.473-0.953, p for trend=0.025), major disability and death (Odds Ratio: 0.617, 95% Confidence Interval: 0.393-0.97, p for trend=0.037) as well as death (Odds Ratio: 0.544, 95% Confidence Interval: 0.313-0.947, p for trend=0.031), respectively, compared with the bottom one. Among patients in the bottom tertile of PLT, combination therapy was associated with a better imaging outcome of eTICI score of 2b, 2c or 3 on final angiogram (Odds Ratio: 3.23, 95% Confidence Interval: 1.49-7.002) with a marginally significant interaction effect. CONCLUSIONS: Participants with higher baseline PLT had a decreased risk of poor functional outcomes. Low baseline PLT modified alteplase treatment effect on the eTICI score on final angiogram. Combination therapy was beneficial for patients with low baseline PLT to have a better reperfusion status.

Traumatic temporomandibular joint bony ankylosis in growing rats.

BACKGROUND: The pathogenesis of traumatic temporomandibular joint (TMJ) bony ankylosis remains unknown. This study aimed to explore the pathogenesis of traumatic TMJ bony ankylosis in a rat model. METHODS: Twenty-four 3-week-old male Sprague-Dawley rats were used in this study. Excision of the whole disc, the fibrocartilage damage of the condyle and glenoid fossa, and narrowed joint space were performed in the left TMJ of the operation group to induce TMJ bony ankylosis (experimental side). The right TMJ underwent a sham operation (sham side). The control group did not undergo any operations. At 1, 4, and 8 weeks postoperatively, rats of the operation group were sacrificed and TMJ complexes were evaluated by gross observation, Micro-CT, histological examinations, and immunofluorescence microscopy. Total RNA of TMJ complexes in the operation group were analyzed using RNA-seq. RESULTS: Gross observations revealed TMJ bony ankylosis on the experimental side. Micro-CT analysis demonstrated that compared to the sham side, the experimental side showed a larger volume of growth, and a considerable calcified bone callus formation in the narrowed joint space and on the rougher articular surfaces. Histological examinations indicated that endochondral ossification was observed on the experimental side, but not on the sham side. RNA-seq analysis and immunofluorescence revealed that Matrix metallopeptidase 13 (MMP13) and Runt-related transcription factor 2 (RUNX2) genes of endochondral ossification were significantly more downregulated on the experimental side than on the sham side. The primary pathways related to endochondral ossification were Parathyroid hormone synthesis, secretion and action, Relaxin signaling pathway, and IL-17 signaling pathway. CONCLUSIONS: The present study provided an innovative and reliable rat model of TMJ bony ankylosis by compound trauma and narrowed joint space. Furthermore, we demonstrated the downregulation of MMP13 and RUNX2 in the process of endochondral ossification in TMJ bony ankylosis.

Highly Efficient Multiple Exciton Generation and Harvesting in Few-Layer Black Phosphorus and Heterostructure.

Multiple exciton generation (MEG) in semiconductors that yields two or more excitons by absorbing one high-energy photon has been proposed to break the Shockley-Queisser limit and boost photon-to-electron conversion efficiency. However, MEG performance in conventional bulk semiconductors or later colloidal nanocrystals is far from satisfactory. Here, we report efficient MEG in few-layer black phosphorus (BP), a direct narrow bandgap two-dimensional (2D) semiconductor with layer-tunable properties. MEG performance improves with decreasing layer number and reaches 2.09Eg threshold and 93% efficiency for two-layer BP, approaching energy conservation limit. The enhanced MEG can be attributed to strong Coulomb interaction and high density of states in 2D materials. Furthermore, MEG of BP shows negligible degradation in vertical heterostructure and multielectron can be extracted by interfacial transfer with near unity yield. These results suggest 2D semiconductors as an ideal system for next generation highly efficient light emission and charge transfer devices.

TMT-labelled quantitative proteomic analysis to predict the target promoting human odontogenic inflammatory granulation tissue transform into reparative granulation tissue.

OBJECTIVES: Odontogenic inflammatory diseases are main causes for alveolar bone breakdown and teeth loss, leaving great difficulties in denture restoration. Local inflammatory granulation tissue (IGT) is considered as pathological tissue and required to be removed. However, there are many evidences supporting that under appropriate intervention, IGT in alveolar bone maybe transformed into reparative granulation tissue (RGT), followed by ossification. Therefore, this study aimed to discover a specific target to promote this transformation. MATERIALS AND METHODS: After drawing out histological differences between IGT and RGT with haematoxylin and eosin (H&E) and immunohistochemical (IHC) assay staining, TMT-labelled quantitative proteomic analysis was applied to identify potential targets. RESULTS: The most striking histological property of RGT was found to be ECM deposition, which significantly decreased inflammatory cells, prominently increased fibroblasts as well as triggered changes of vascular types. Combined with histological findings and proteomic analysis, five KEGG pathways were associated with ECM, inflammation and angiogenesis and 49 pathways involved in differentially expressed proteins. COL1A1 was not only the most up-regulated protein, but also one of main hubs in protein-protein interaction regulatory network. Specific protease cathepsin K (CTSK) was identified. Level of CTSK in RGT was down-regulated to 69.10-76.97% (p < .05), with significantly up-regulated COL1A1, COL1A2, FN1 and TGFB1 included in focal adhesion, PI3K-Akt signalling pathways and angiogenesis. CTSK involved in transformation from IGT to RGT. CONCLUSIONS: CTSK might be a target to regulate transformation from IGT to RGT in alveolar bone through ECM, stem cells and angiogenesis mechanisms. However, further research is also clearly required.

Efficient hot-electron extraction in two-dimensional semiconductor heterostructures by ultrafast resonant transfer.

Energy loss from hot-carrier cooling sets the thermodynamic limit for the photon-to-power conversion efficiency in optoelectronic applications. Efficient hot-electron extraction before cooling could reduce the energy loss and leads to efficient next generation devices, which, unfortunately, is challenging to achieve in conventional semiconductors. In this work, we explore hot-electron transfer in two-dimensional (2D) layered semiconductor heterostructures, which have shown great potential for exploring new physics and optoelectronic applications. Using broadband micro-area ultrafast spectroscopy, we firmly established a type I band alignment in the WS2-MoTe2 heterostructure and ultrafast (∼60 fs) hot-electron transfer from photoexcited MoTe2 to WS2. The hot-electron transfer efficiency increases with excitation energy or excess energy as a result of a more favorable continuous competition between resonant electron transfer and cooling, reaching 90% for hot electrons with 0.3 eV excess energy. This study reveals exciting opportunities of designing extremely thin absorber and hot-carrier devices using 2D semiconductors and also sheds important light on the photoinduced interfacial process including charge transfer and generation in 2D heterostructures and optoelectronic devices.

Dentists' entrepreneurial intention and associated factors in public hospitals in major cities in Guangdong (South China): a cross-sectional study.

BACKGROUND: A rapid growth in private dentistry in China has been observed during recent years. Promoting the entrepreneurship of dentists has increasingly received attention in both dentistry and dental education worldwide. However, understanding about the unique features of entrepreneurial behaviors of dentists remains inadequate. METHODS: This study examines dentist's entrepreneurial intention (EI), which was represented by his/her intention of leaving the public hospital system to be engaged in the private sector. Through a snowball sampling method, a total of 336 questionnaires from public hospitals in five major cities in Guangdong Province (China) were collected. The association between the dentists' EI and their individual characteristics were analyzed using a logistic regression model. RESULTS: In the sample studied, 35.7% of the respondents reported to have EI. Female dentists are less likely to report EI (OR = 0.365, p = 0.001). Dentists in the age group of 36 to 45 years (OR = 14.205, p = 0.012) and those aged over 45 years (OR = 8.45, p = 0.066) reported respectively a much stronger EI than those in their 20s. Compared with intern dentists, attending dentists (OR = 7.812, p = 0.016) and associate/chief dentists (OR = 9.857, p = 0.021) were significantly more likely to report EI. Those with master level (OR = 0.221, p = 0.021) or doctorate degrees (OR = 0.118, p = 0.005) are much less likely to report EI. Meanwhile, those in mid-large hospitals (with 101-200 employees) (OR = 3.554, p = 0.036) and small hospitals (with < 50 employees) (OR = 2.398, p = 0.044) reported a stronger EI than those in large hospitals. Additionally, dentists' entrepreneurial behaviors, risk aversion attitudes and their family background all have significant associations. CONCLUSIONS: Since dentistry is a knowledge-intensive industry, dentists' entrepreneurial behaviors have their own features. The findings by this study suggest that, accumulation of practical skills in a dental career, as implied by age, professional qualifications and leadership skills, help to promote EI, whereas an academic oriented education degree per se does not. Dentists in mid-large and small hospitals, rather than in top large hospitals in China, have higher EI. Additionally, female dentists may need more social supports to develop a higher EI. These findings have practical implications for the promotion of EI among dentists.

FoxO3 transcription factor promotes autophagy after transient cerebral ischemia/reperfusion.

Aim: Autophagy was activated after cerebral ischemia reperfusion (I/R) injury. However, the molecular mechanisms underlying regulation of autophagy in cerebral I/R injury were not completely understood. Studies reported that Forked-box class O (FoxO) transcription factors involved in autophagy and might be the regulator of autophagy in multiple cells. In this study, we investigated the effects of FoxO3 on regulating autophagy after cerebral I/R injury. Materials and methods: Rats were subjected to MCAO for 2 h and reperfusion for different times, western blot was used to examine the expression of p-FoxO3, FoxO3 and the autophagic marker LC3 and Beclin-1 in penumbral region. Then rats were injected with WT-FoxO3 or TM-FoxO3 adenovirus by lateral cerebral ventricle to increase the function of FoxO3, western blot was used to examine the expression of LC3 and Beclin-1 in penumbral region. TTC and HE staining were used to evaluate the effects of increased FoxO3 activation on I/R induced brain damage. Results: Our studies showed that I/R injury resulted in induction of autophagy in penumbral brain tissue with concomitant dephosphorylation of FoxO3, consistent with increased activity of nuclear FoxO3 transcription factor. Increased FoxO3 activation led to autophagy significantly increased and had a protective effects on I/R injury. Conclusion: These data revealed an important role of FoxO3 in regulating autophagy in brain, and provided a new approach for further prevention and treatment of cerebral ischemia.

Investigation of Long Non-coding RNA Expression Profiles in the Substantia Nigra of Parkinson's Disease.

Genetics is considered as an important risk factor in the pathological changes of Parkinson's disease (PD). Substantia nigra (SN) is thought to be the most vulnerable area in this process. In recent decades, however, few related long non-coding RNAs (lncRNAs) in the SN of PD patients had been identified and the functions of those lncRNAs had been studied even less. In this study, we sought to investigate the lncRNA expression profiles and their potential functions in the SN of PD patients. We screened lncRNA expression profiles in the SN of PD patients using the lncRNA mining approach from the ArrayExpress database, which included GSE20295. The samples were from 11 of PD and 14 of normal tissue samples. We identified 87 lncRNAs that were altered significantly in the SN during the occurrence of PD. Among these lncRNAs, lncRNA AL049437 and lncRNA AK021630 varied most dramatically. AL049437 was up-regulated in the PD samples, while AK021630 was down-regulated. Based on the results, we focused on the potential roles of the two lncRNAs in the pathogenesis of PD by the knockdown of the expression of AL049437 or AK021630 in human neuroblastoma SH-SY5Y cell line. Results indicated that the reduction in AL049437 level increased cell viability, mitochondrial transmembrane potential (Δψm), mitochondrial mass, and tyrosine hydroxylase (TyrH) secretion. By contrast, the knockdown of AK021630 resulted in the opposite effect. Based on these results, we speculated that lncRNA AL049437 likely contributed to the risk of PD, while lncRNA AK021630 likely inhibited the occurrence of PD.

The Past, Present, and Future of Dentoalveolar Surgery in China.

Dentoalveolar surgery, formerly known as dental surgery or oral surgery, is one of the basic branches of oral and maxillofacial surgery. While it has a long history; however, there are great differences in its evolution globally. This article presents a brief review on the development of dentoalveolar surgery internationally. Furthermore, a systematic review on its development in China, is detailed in 6 stages. However, while its development in China since 2005 has been most profound, improvements are still needed in treatment concepts, instruments, treatment processes, attention to high-risk populations and cooperation with other dental/medical disciplines. Future projections based on present standards of care are also presented.

Influence of the lateral pterygoid muscle on traumatic temporomandibular joint bony ankylosis.

BACKGROUND: The pathogenesis of traumatic TMJ ankylosis remains unclear. This study aimed to verify the role of the lateral pterygoid muscle in the pathogenesis of traumatic temporomandibular joint (TMJ) bony ankylosis. METHODS: Eight 6-month-old male sheep were used in this study. Bilateral TMJ osteotomies were performed to induce sagittal fractures of the mandibular condyle. The lateral one-fourth segment of the disc was removed to establish a model of TMJ bony ankylosis. Subsequently, the function of the left and right lateral pterygoid muscles was blocked (experimental group) or maintained (control group), respectively. At 12 weeks postoperatively, animals were sacrificed and TMJ complex samples were evaluated by gross observation, spiral computed tomography (CT), micro-CT, and histological examinations. RESULTS: Gross observation revealed bony ankylosis in the control TMJs and fibrous adhesions in the experimental TMJs. Spiral CT and micro-CT demonstrated that, compared to the experimental group, the control group showed calcified callus formation in the joint space and roughened articular surfaces after new bone formation, which protruded into the joint space. Maximum mediolateral and anteroposterior condylar diameters were significantly larger in the control group than in the experimental group. Micro-CT also showed that the primary growth orientation of new trabeculae was consistent with the direction of lateral pterygoid traction in the control group, but not in the experimental group. Histological examination showed fibro-osseous ankylosis in the control group, but not in the experimental group. CONCLUSIONS: The lateral pterygoid simulates the effects of distraction osteogenesis, which is an important factor in the pathogenesis of TMJ bony ankylosis during the healing of sagittal condylar fractures.

Observational Study of Surgical Treatment of Sagittal Fractures of Mandibular Condyle.

OBJECTIVE: This study was conducted to investigate the complications that occur after surgical treatment of sagittal fracture of the mandibular condyle (SFMC). METHODS: A retrospective study was conducted on patients in whom SFMC was treated using surgical methods (87 patients, 105 sides) between January 1995 and December 2011 (79 sides were treated by rigid internal fixation and the remaining 26 sides were removed the condylar fragments). The longest follow-up was 17 years, and the shortest was 2 years. Follow-ups were conducted to assess mandibular activity, mouth opening, and computed tomography scans of condylar morphologic alterations. The postoperative complications were evaluated and the causes were analyzed. RESULTS: We observed 3 patients with joint ankylosis (all of them were removed the condylar fragments); 8, mouth opening less than 30 mm; 23, deviation on mouth opening at 6 months. At 4 weeks, 19 patients had facial nerve weakness, which was resolved within 6 months. The radiological investigation showed complete remodeling in 56.2% of the condyles (in the 59 sides, 57 sides were treated by rigid internal fixation and 2 sides were removed the condylar fragments); partial remodeling 27.6% condyles (in the 29 sides, 20 sides were treated by rigid internal fixation and 9 sides were removed the condylar fragments); poor remodeling, 16.2% condyles (in the 17 sides, 2 sides were treated by rigid internal fixation and 15 sides were removed the condylar fragments). CONCLUSIONS: Surgical treatment of SFMC is not perfect. There were some complications that occurred after the surgical treatment of SFMC. The findings also indicate that condylar anatomic reduction is the basis for functional recovery and, therefore, rigid fixation should be implemented. Furthermore, the removal of condylar fragments should be performed with caution, and if used, the fragments should be removed entirely.

Alveolar ridge preservation with deproteinized bovine bone graft and collagen membrane and delayed implants.

To evaluate clinically and radiographically an alveolar ridge, preservation technique with deproteinized bovine bone graft and absorbable collagen membrane and then restoration with delayed implants were done. The study included 30 patients. The trial group's sockets were filled with deproteinized bovine bone graft (Bio-Oss) and covered with absorbable collagen membrane (Bio-Gide). The control group's sockets healed without any treatment. Panoramic radiograph and computed tomography were taken immediately after graft and 3 and 6 months later to evaluate the height, width, and volume change of the alveolar ridge bone. Dental implants were inserted in all sockets at 6 months, and osseointegration condition was evaluated in the following 12 months. All sockets healed uneventfully. In the trial group, the mean (SD) height reduction of the alveolar ridge bone was 1.05 (0.24) mm at 3 months and 1.54 (0.25) mm at 6 months. The width reduction was 1.11 (0.13) mm at 3 months and 1.84 (0.35) mm at 6 months. Bone volume reduction was 193.79 (21.47) mm at 3 months and 262.06 (33.08) mm at 6 months. At the same trend, in the control group, the bone height reduction was 2.12 (0.15) mm at 3 months and 3.26 (0.29) mm at 6 months. The width reduction was 2.72 (0.19) mm at 3 months and 3.56 (0.28) mm at 6 months. Bone volume reduction was 252.19 (37.21) mm at 3 months and 342.32 (36.41) mm at 6 months. There was a significant difference in alveolar ridge bone height, width, and volume reduction in the 2 groups. The osseointegration condition had no significant difference between the 2 groups. This study suggested that the deproteinized bovine bone graft and absorbable collagen membrane were beneficial to preserve the alveolar ridge bone and had no influence on the osseointegration of delayed implant.

Ultrafast Interlayer Charge Transfer Outcompeting Intralayer Valley Relaxation in Few-Layer 2D Heterostructures.

While 2D transition metal dichalcogenides (TMDs) feature interesting layer-tunable multivalley band structures, their preeminent role in determining the photoexcitation charge transfer dynamics in 2D heterostructures (HSs) is yet to be unraveled, as previous charge transfer studies on TMD HSs have been mostly focused on monolayers with a direct bandgap at the K valley. By ultrafast transient absorption spectroscopy and deliberately designed few-layer WSe2/WS2 HSs, we have observed an ultrafast interlayer electron transfer from photoexcited few-layer WSe2 to WS2, prior to intralayer relaxation to lower lying dark valleys. More interestingly, we have identified an unconventional ∼0.5 ps electron back-transfer process after the initial interlayer electron transfer in HSs with WSe2 layers ≥ 3, regenerating indirect intralayer excitons. The result reveals an ielectron and valley relaxation pathway mediated by interlayer charge transfer in 2D HSs, faster than intralayer relaxation. It also sheds light on the origin of generally observed robust ultrafast interlayer charge transfer in TMD HSs and provides guidance toward optoelectronic and valleytronic devices using few-layer TMDs.

Neuroprotective effect of 2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxy-ß-D-pyranoside against sodium nitroprusside-induced neurotoxicity in HT22 cells.

2-(4-Methoxyphenyl) ethyl-2-acetamido-2-deoxy-ß-D-pyranoside (GlcNAc-Sal), the salidroside analog was synthesized and shown to inhibit hypoglycemia and serum limitation induced apoptosis in PC12 cells. This study investigated the protective effects of GlcNAc-Sal on sodium nitroprusside (SNP)-induced cytotoxicity in HT22 cells. Cell viability tests and Hoechst 33342 staining comfirmed that GlcNAc-Sal pretreatment attenuated SNP-stimulated apoptotic cell death in HT22 cells in a concentration-dependent manner. The measurements of reactive oxygen species (ROS), nitric oxide (NO) production and apoptosis-related gene and protein expression suggest that the protection of GlcNAc-Sal, shown in this study, might be mediated by inhibiting intracellular ROS and NO production, and regulating apoptosis-related gene and protein expression during SNP stimulation. Perhaps, this study might contribute to the development of GlcNAc-Sal as an agent for preventing and/or treating a variety of NO-induced brain diseases.

Phase-pure 2D tin halide perovskite thin flakes for stable lasing.

Ruddlesden-Popper tin halide perovskites are a class of two-dimensional (2D) semiconductors with exceptional optoelectronic properties, high carrier mobility, and low toxicity. However, the synthesis of phase-pure 2D tin perovskites is still challenging, and the fundamental understanding of their optoelectronic properties is deficient compared to their lead counterparts. Here, we report the synthesis of a series of 2D tin perovskite bulk crystals with high phase purity via a mixed-solvent strategy. By engineering the quantum-well thickness (related to n value) and organic ligands, the optoelectronic properties, including photoluminescence emission, exciton-phonon coupling strength, and exciton binding energy, exhibit a wide tunability. In addition, these 2D tin perovskites exhibited excellent lasing performance. Both high-n value tin perovskite (n > 1) and n = 1 tin perovskite thin flakes were successfully optically pumped to lase. Furthermore, the lasing from 2D tin perovskites could be maintained up to room temperature. Our findings highlight the tremendous potential of 2D tin perovskites as promising candidates for high-performance lasers.

Umbilical cord mesenchymal stem cell-derived apoptotic extracellular vesicles ameliorate cutaneous wound healing in type 2 diabetic mice via macrophage pyroptosis inhibition.

BACKGROUND: Delayed healing of diabetic cutaneous wounds is one of the most common complications of type 2 diabetes mellitus (T2DM), which can bring great distress to patients. In diabetic patients, macrophages accumulate around skin wounds and produce NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasomes, which in turn undergo pyroptosis and produce inflammatory factors such as interleukin-1ß that affect wound healing. Although our previous study revealed that apoptotic extracellular vesicles (ApoEVs) produced from mesenchymal stem cells (MSCs) improve cutaneous wound healing in normal C57BL/6 mice, whether ApoEVs can also improve diabetic wound healing remains unclear. METHODS: Umbilical cord mesenchymal stem cells (UCMSCs) were cultured in vitro and apoptosis was induced. ApoEVs were extracted and identified and used in a T2DM mouse cutaneous wound model to evaluate the efficacy. The inhibitory effect of ApoEVs on macrophage pyroptosis was verified in vivo and in vitro, and the level of oxidative stress in macrophages was assessed to explore the mechanism by which ApoEVs play a role. RESULTS: UCMSC-derived ApoEVs improved skin defect healing in T2DM mice. Moreover, UCMSC-derived ApoEVs inhibited macrophage pyroptosis in T2DM mice in vivo as well as in vitro under high-glucose culture conditions. In addition, we demonstrated that ApoEVs reduce oxidative stress levels, which is a possible mechanism by which they inhibit macrophage pyroptosis. CONCLUSIONS: Our study confirmed that local application of UCMSC-derived ApoEVs improved cutaneous wound healing in T2DM mice. ApoEVs, as products of MSC apoptosis, can inhibit macrophage pyroptosis and regulate the death process by decreasing the level of oxidative stress.

Secondary healing after removal of large keratocystic odontogenic tumor in the mandible: enucleation followed by open packing of iodoform gauze.

PURPOSE: The aim of this retrospective study was to present the findings of an open packing method after enucleation of large keratocystic odontogenic tumors (KCOTs) in the mandible. PATIENTS AND METHODS: We performed a retrospective case series study of 27 patients with KCOTs larger than 5 cm treated at our institution between September 2003 and September 2008. A conservative surgical treatment was applied, which involved enucleation of the primary lesion and open packing of the residual osseous defect with iodoform gauze for secondary healing. Bone regeneration, tumor recurrence, and surgical complications were observed and analyzed. We used the χ(2) test and Pearson correlation coefficient for statistical analysis. RESULTS: The postoperative follow-up time was 52.3 months on average (range, 24 to 84 months). The packing gauze was changed every 2 weeks after enucleation, and the total duration for packing was 10.2 months on average (range, 7-15 months). Bone regeneration and satisfactory secondary healing were observed clinically and radiographically after treatment. Only 1 case had a recurrence 6 months after initial treatment, which was attributed to insufficient bony unroofing during enucleation. The recurrent lesion was re-treated by the same method, and no recurrence occurred in the following 6 years. No serious complications from this method of treatment were observed. No significant variables were found to be related to the recurrence. CONCLUSIONS: Enucleation with subsequent open packing was shown to be a conservative and comfortable treatment for patients and appears to be an effective choice for the management of large KCOTs in the mandible.