[Efficacy and radiology evaluation of pulpotomy in mature permanent teeth].

OBJECTIVE: To observe the clinical efficacy of pulpotomy in patients of different ages and to explore the occurrence and characteristics of pulpal calcification. METHODS: A total of 77 patients who underwent pulpotomy for mature permanent premolars and molars with caries-derived pulp exposure in the Department of General Dentistry, Peking University School and Hospital of Stomatology from October 2019 to August 2022 were selected. Pulpotomies were performed in a single visit using iRoot BP Plus bioceramic material as pulp capping agent. The patients were divided into three groups according to age: 25 cases in the adolescent group (11-20 years old) with a mean age of (15.88±2.19) years; 27 cases in the middle-aged group (21-50 years old) with a mean age of (34.59±8.67) years; and 25 cases in the elder-aged group (51-83 years old) with a mean age of (63.84±7.40) years. The patients were reviewed 1 year after the operation to evaluate the clinical efficacy and to record the formation of calcified bridge, thickness of calcified bridge, and pulp calcification index (PCI). RESULTS: There was no statistically significant difference between the three groups in terms of gender, dentition, and tooth position (P > 0.05). The 1-year postoperative follow-up rate was 85.71% (66/77), including 88.00% (22/25) in the adolescent group, 85.19% (23/27) in the middle-aged group, and 84.00% (21/25) in the elder-aged group. The 1-year follow-up clinical success rates of the three groups were 95.45% (21/22), 91.30% (21/23), and 95.24% (20/21), respectively, with no statistically significant difference (P>0.05). Among the clinical success cases, calcified bridges appeared in 12 cases (57.14%, 12/21) in the adolescent group, 8 cases (38.10%, 8/21) in the middle-aged group, and 3 cases (15.00%, 3/20) in the elder-aged group, with statistically significant differences (χ2= 7.810, P = 0.020 < 0.05). The difference was statistically significant (F = 4.434, P = 0.020 < 0.05) when comparing the thickness of calcified bridges among the three groups. Calcified bridge thickness was negatively correlated with age (r = -0.516, P < 0.05). The changes in pulpal calcification index ΔPCI were 0.67 ± 0.58, 0.43 ± 0.51, and 0.25 ± 0.52, respectively, with statistically significant differences among the three groups (F = 3.404, P = 0.040 < 0.05). CONCLUSION: Pulpotomy for caries-derived pulp exposure in elderly patients could also achieve a high success rate. The incidence of calcified bri-dges after pulpotomy and the acceleration of pulpal calcification were age-related. The adolescent group was more likely to form calcified bridges and also showed more pronounced accelerated root canal calcification.

Primary membranous nephropathy in two siblings with one combined with anti-glomerular basement membrane disease: a case report.

BACKGROUND: The phospholipase A2 receptor (PLA2R) associated with membranous nephropathy (MN) is an organ-specific autoimmune disease associated with PLA2R and human leukocyte antigen (HLA) genes. Familial PLA2R-related MN is rarely reported. The combination of anti-GBM disease and MN has been well documented, though the mechanism behind it remains unclear. CASE PRESENTATION: We describe two siblings diagnosed with pathology-confirmed PLA2R-related MN 1 year apart. And one of the two siblings developed an anti-GBM disease. The high-resolution HLA typing showed identical alleles in both siblings, specifically heterozygotes of DRB1*15:01/*03:01. CONCLUSION: We describe a familial case of PLA2R-related MN supporting the role of genetic factors that HLA-DRB1*15:01 and DRB1*03:01 predispose patients in the development of PLA2R-related MN in the Han Chinese population. The combination of MN and anti-GBM disease may also partially be associated with the same susceptible HLA allele DRB1*15:01.

Treatment Durations and Whitening Outcomes of Different Tooth Whitening Systems.

Background and Objectives: Tooth whitening is a relatively conservative and effective option to treat discolored teeth. However, questions remain whether in-office or at-home tooth whitening products with short treatment durations are as effective and stable as products with longer treatment durations. Materials and Methods: Forty human third molars with intact enamel surfaces were divided into four groups of ten each, subjected to discoloration challenges with coffee for 60 h, and they were treated with four professional tooth whitening systems: two for take-home use-6% hydrogen peroxide for 30 min/d for a total of 7 h in 14 days (HP6), 10% carbamide peroxide for 10 h/d for 140 h in 14 days (CP10), as well as two for in-office use-35% HP for 10 min × 3 (HP35) for a total of 30 min and 40% HP for 20 min × 3 (HP40) for a total of 60 min. Teeth colors were assessed in the CIE L*a*b* color space with a spectrophotometer immediately and six months after whitening treatments. Surface roughness (Sa) for the treated and untreated enamel surfaces of the teeth in all groups were evaluated with a three-dimensional laser scanning microscope after six months. Results: No significant differences were found between HP6 and CP10 groups immediately after whitening (∆E 10.6 ± 1.6 vs. 11.4 ± 1.7, p > 0.05) and at six months after treatments (∆E 9.0 ± 1.9 vs. 9.2 ± 2.5, p > 0.05), or between HP35 and HP40 groups immediately after whitening (∆E 5.9 ± 1.2 vs. 5.3 ± 1.7, p > 0.05) and at six months after treatments (∆E 7.2 ± 1.6 vs. 7.7 ± 1.3, p > 0.05). The two at-home whitening systems achieved significantly better whitening outcomes than the two in-office products immediately after whitening (p < 0.05). However, at six months after treatments, the differences between at-home and in-office treatments had narrowed significantly (p > 0.05). There were no statistically significant differences with respect to the Sa values between the treated and untreated surfaces (p > 0.05). Conclusions: Tooth whitening products in the same product category have similar whitening efficacies, despite significant differences in treatment durations (7 vs. 140 h, and 30 min vs. 60 min, respectively). Take-home products achieved better whitening outcomes than in-office products, but they needed 14 to 280 times longer treatment durations.

RNA-seq characterization of histamine-releasing mast cells as potential therapeutic target of osteoarthritis.

OBJECTIVE: Mast cells in the osteoarthritis (OA) synovium correlate with disease severity. This study aimed to further elucidate the role of mast cells in OA by RNA-Seq analysis and pharmacological blockade of the activity of histamine, a key mast cell mediator, in murine OA. METHODS: We examined OA synovial tissues and fluids by flow cytometry, immunostaining, single-cell and bulk RNA-Seq, qPCR, and ELISA. Cetirizine, a histamine H1 receptor (H1R) antagonist, was used to treat the destabilization of the medial meniscus (DMM) mouse model of OA. RESULTS: Flow cytometry and immunohistology analysis of OA synovial cells revealed KIT+ FcεRI+ and TPSAB1+ mast cells. Single-cell RNA-Seq of OA synovial cells identified the expression of prototypical mast cell markers KIT, TPSAB1, CPA3 and HDC, as well as distinctive markers HPGD, CAVIN2, IL1RL1, PRG2, and CKLF, confirmed by bulk RNA-Seq and qPCR. A mast cell prototypical marker expression score classified 40 OA patients into three synovial pathotypes: mast cell-high, -medium, and -low. Additionally, we detected mast cell mediators including histamine, tryptase AB1, CPA3, PRG2, CAVIN2, and CKLF in OA synovial fluids. Elevated H1R expression was detected in human OA synovium, and treatment of mice with the H1 receptor antagonist cetirizine reduced the severity and OA-related mediators in DMM. CONCLUSION: Based on differential expression of prototypical and distinct mast cell markers, human OA joints can be stratified into mast cell-high, -medium, and -low synovial tissue pathotypes. Pharmacologic blockade of histamine activity holds the potential to improve OA disease outcome.

In situ determination of the extreme damage resistance behavior in stomatopod dactyl club.

The structure and mechanical properties of the stomatopod dactyl club have been studied extensively for its extreme impact tolerance, but a systematic in situ investigation on the multiscale mechanical responses under high-speed impact has not been reported. Here the full dynamic deformation and crack evolution process within projectile-impacted dactyl using combined fast 2D X-ray imaging and high-resolution ex situ tomography are revealed. The results show that hydration states can lead to significantly different toughening mechanisms inside dactyl under dynamic loading. A previously unreported 3D interlocking structural design in the impact surface and impact region is reported using nano X-ray tomography. Experimental results and dynamic finite-element modeling suggest this unique structure plays an important role in resisting catastrophic structural damage and hindering crack propagation. This work is a contribution to understanding the key toughening strategies of biological materials and provides valuable information for biomimetic manufacturing of impact-resistant materials in general.

Hydrothermal Synthesis and Formation Mechanism of Self-Assembled Strings of CoOOH Nanodiscs.

The formation and self-assembly mechanisms of nanomaterials are of great significance for the preparation and application of materials. In this study, the orientationally aggregated CoOOH nanosheets and the self-assembled strings of CoOOH nanodiscs were prepared by hydrothermal method. The formation and self-assembly mechanisms of CoOOH nanodiscs were investigated by XRD, XPS, DLS, TEM, and SEM techniques, as well as DFT calculations. The results show that the formation process of the stacked CoOOH nanodiscs was driven by surface energy and can be divided into four steps: nucleation and growth of CoOOH primary nanosheets; oriented attachment of CoOOH nanosheets; self-assembly of CoOOH nanodiscs; and aggregation of strings of CoOOH nanodiscs. This study contributes meaningfully to the controllable preparation of CoOOH nanomaterials.

Controlled Synthesis and Surface Engineering of Janus Chitosan-Gold Nanoparticles for Photoacoustic Imaging-Guided Synergistic Gene/Photothermal Therapy.

The unsymmetrical morphology and unique properties of Janus nanoparticles (JNPs) provide superior performances for biomedical applications. In this work, a general and facile strategy is developed to construct a series of symmetrical and unsymmetrical chitosan/gold nanoparticles. Taking advantage of the active motion derived from Janus structure, selective surface functionalization of polysaccharide domain, and photothermal effect of gold nanorods, Janus chitosan/gold nanoparticles (J-Au-CS) are selected as a model system to construct Janus-structured chitosan/gold nanohybrids (J-ACP). Near-infrared (NIR)-responsive J-ACP composed of polycationic chitosan nanospheres and PEGylated gold nanorods hold great potential to realize photoacoustic (PA) imaging-guided complementary photothermal therapy (PTT)/gene therapy for breast cancer. The morphology effect of chitosan/gold nanostructures on enhanced PTT, cellular uptake, and gene transfection is investigated. The feasibility of PA imaging to track the accumulation of J-ACP and guide PTT is also explored. Notably, synergistic therapy is achieved based on PTT-enhanced gene therapy. In addition, the loading function of chitosan/gold nanoparticles for fluorescence imaging is demonstrated. The current work extends the application of JNPs for imaging-guided synergistic cancer therapy and provides flexible candidates with distinct structures for diverse biomedical applications.

Versatile Types of Organic/Inorganic Nanohybrids: From Strategic Design to Biomedical Applications.

Organic/inorganic nanohybrids have attracted widespread interests due to their favorable properties and promising applications in biomedical areas. Great efforts have been made to design and fabricate versatile nanohybrids. Among different organic components, diverse polymers offer unique avenues for multifunctional systems with collective properties. This review focuses on the design, properties, and biomedical applications of organic/inorganic nanohybrids fabricated from inorganic nanoparticles and polymers. We begin with a brief introduction to a variety of strategies for the fabrication of functional organic/inorganic nanohybrids. Then the properties and functions of nanohybrids are discussed, including properties from organic and inorganic parts, synergistic properties, morphology-dependent properties, and self-assembly of nanohybrids. After that, current situations of nanohybrids applied for imaging, therapy, and imaging-guided therapy are demonstrated. Finally, we discuss the prospect of organic/inorganic nanohybrids and highlight the challenges and opportunities for the future investigations.

Effects of whitening toothpaste and bleaching treatment on resin composite discoloration caused by cigarette smoke and electronic vapor aerosol.

PURPOSE: To compare the effects of whitening toothpaste and bleaching with 6% hydrogen peroxide (H2O2) on discoloration of dental resin composite caused by cigarette smoke (CS) and electronic vapor product (EVP) aerosol. METHODS: 40 resin composite discs were divided into three groups: 15 each for CS and EVP aerosol exposure and 10 for air exposure (control). Exposures were performed for 15 days, with daily brushing with regular toothpaste. Two whitening sessions, including 21 days of brushing with whitening toothpaste and 3 days of treatments with take-home bleaching (6% H2O2), were performed after the exposure. Color and gloss were assessed before exposure, at every 5 days of exposure, and after each whitening session. RESULTS: After 15 days of exposure, marked discoloration of resin composite was observed in the CS group (ΔE = 23.66 ± 2.31), minimal color change in the EVP group ((ΔE = 2.77 ± 0.75), and no color change in the control group. Resin composites exposed to CS did not recover their original color after treatment with whitening toothpaste ((ΔE = 20.17 ± 2.68) or take-home bleaching ((ΔE = 19.32 ± 2.53), but those exposed to EVP aerosol reverted to baseline after treatment with whitening toothpaste ((ΔE = 0.98 ± 0.37), and no further change in color was observed following take-home bleaching. The gloss of resin composites exposed to CS, EVP aerosol, and air decreased equally with exposure time. Brushing with whitening toothpaste recovered the gloss similarly in all groups, but no further change was observed following take-home bleaching. CLINICAL SIGNIFICANCE: Aerosol from electronic vapor products induced minimal discoloration of resin composites that can be completely reverted by brushing with whitening toothpaste alone. Bleaching with 6% H2O2 did not revert discoloration caused by cigarette smoke. Whitening toothpaste could help revert the decreased gloss of resin composites.

Effects of desensitizing dentifrices on dentin tubule occlusion and resistance to erosive challenges.

BACKGROUND: Many studies have demonstrated efficacy of casein phosphopeptide (CPP) containing products for dentin tubule occlusion for treatment of dentin sensitivity, but their effectiveness under dynamic erosive challenges remains to be elucidated. The purpose of the present study was to investigate the effectiveness of a desensitizing dentifrice containing CPP in occluding dentin tubules and resisting erosive challenges in comparison to that containing polyvinyl methyl ether/maleic acid (PVM/MA) copolymers. METHODS: A total of 33 dentin discs were prepared from coronal sections of human third molars and divided into 3 groups: a toothpaste containing CPP; a toothpaste containing PVM/MA and submicron silica; and a regular toothpaste (Controls). A soft-bristle toothbrush was used to brush the dentin discs with the dentifrices for 45 strokes in 30 s at a force of approximately 200 g. The brushing cycle was repeated after immersion of the dentin discs in artificial saliva overnight. The dentin discs were then challenged in orange juice for 10 min in an incubator rocking at 120 rpm. Three fields were randomly selected on each dentin disk surface to assess dentin tubule occlusions after each brushing cycle and after orange juice challenge with a 3D laser scanning microscope. Specimen cross sections were examined with a scanning electron microscope equipped with energy dispersive spectroscopy (SEM/EDS). RESULTS: After the first and second cycles of brushing, dentin tubules were occluded on average by 56.3% and 85.7% in CPP group, 66.2% and 88.1% in PVM/MA group, and 0.0 and 13.0% in the controls, respectively. There were no statistically significant differences in dentin tubule occlusions between the CPP and PVM/MA groups after two cycles of brushing (p>0.05). After dynamic erosive challenges with orange juice, 20.3% of the dentin tubules in the CPP group, 79.1% in the PVM/MA group and none in the control remained occluded (P<0.05). SEM/EDS imaging showed that dentin tubules were blocked with plugs containing dentifrice substances in CPP and PVM/MA groups after treatments, but none in the controls. CONCLUSIONS: Desensitizing dentifrices containing CPP or PVM/MA could effectively occlude dentin tubules after two cycles of brushing. PVM/MA in combination with submicron silicon dioxide exhibited stronger resistance to dynamic erosive challenges by acidic beverages. Inorganic fillers that can enter dentin tubules and resist erosive challenges may be key for desensitizing dentifrices.

Single-cell RNA-seq analysis identifies meniscus progenitors and reveals the progression of meniscus degeneration.

OBJECTIVES: The heterogeneity of meniscus cells and the mechanism of meniscus degeneration is not well understood. Here, single-cell RNA sequencing (scRNA-seq) was used to identify various meniscus cell subsets and investigate the mechanism of meniscus degeneration. METHODS: scRNA-seq was used to identify cell subsets and their gene signatures in healthy human and degenerated meniscus cells to determine their differentiation relationships and characterise the diversity within specific cell types. Colony-forming, multi-differentiation assays and a mice meniscus injury model were used to identify meniscus progenitor cells. We investigated the role of degenerated meniscus progenitor (DegP) cell clusters during meniscus degeneration using computational analysis and experimental verification. RESULTS: We identified seven clusters in healthy human meniscus, including five empirically defined populations and two novel populations. Pseudotime analysis showed endothelial cells and fibrochondrocyte progenitors (FCP) existed at the pseudospace trajectory start. Melanoma cell adhesion molecule ((MCAM)/CD146) was highly expressed in two clusters. CD146+ meniscus cells differentiated into osteoblasts and adipocytes and formed colonies. We identified changes in the proportions of degenerated meniscus cell clusters and found a cluster specific to degenerative meniscus with progenitor cell characteristics. The reconstruction of four progenitor cell clusters indicated that FCP differentiation into DegP was an aberrant process. Interleukin 1ß stimulation in healthy human meniscus cells increased CD318+ cells, while TGFß1 attenuated the increase in CD318+ cells in degenerated meniscus cells. CONCLUSIONS: The identification of meniscus progenitor cells provided new insights into cell-based meniscus tissue engineering, demonstrating a novel mechanism of meniscus degeneration, which contributes to the development of a novel therapeutic strategy.

Identifying the pulsed neuron networks' structures by a nonlinear Granger causality method.

BACKGROUND: It is a crucial task of brain science researches to explore functional connective maps of Biological Neural Networks (BNN). The maps help to deeply study the dominant relationship between the structures of the BNNs and their network functions. RESULTS: In this study, the ideas of linear Granger causality modeling and causality identification are extended to those of nonlinear Granger causality modeling and network structure identification. We employed Radial Basis Functions to fit the nonlinear multivariate dynamical responses of BNNs with neuronal pulse firing. By introducing the contributions from presynaptic neurons and detecting whether the predictions for postsynaptic neurons' pulse firing signals are improved or not, we can reveal the information flows distribution of BNNs. Thus, the functional connections from presynaptic neurons can be identified from the obtained network information flows. To verify the effectiveness of the proposed method, the Nonlinear Granger Causality Identification Method (NGCIM) is applied to the network structure discovery processes of Spiking Neural Networks (SNN). SNN is a simulation model based on an Integrate-and-Fire mechanism. By network simulations, the multi-channel neuronal pulse sequence data of the SNNs can be used to reversely identify the synaptic connections and strengths of the SNNs. CONCLUSIONS: The identification results show: for 2-6 nodes small-scale neural networks, 20 nodes medium-scale neural networks, and 100 nodes large-scale neural networks, the identification accuracy of NGCIM with the Gaussian kernel function was 100%, 99.64%, 98.64%, 98.37%, 98.31%, 84.87% and 80.56%, respectively. The identification accuracies were significantly higher than those of a traditional Linear Granger Causality Identification Method with the same network sizes. Thus, with an accumulation of the data obtained by the existing measurement methods, such as Electroencephalography, functional Magnetic Resonance Imaging, and Multi-Electrode Array, the NGCIM can be a promising network modeling method to infer the functional connective maps of BNNs.

The efficacy and safety of thalidomide on the recurrence interval of continuous recurrent aphthous ulceration: A randomized controlled clinical trial.

BACKGROUND: Recurrent aphthous ulceration (RAU) is the most common oral mucosal disease. Some patients have almost continuous oral ulcers which influence the quality of life. The aim of this study was to observe the efficacy and safety of thalidomide on the recurrence interval of continuous RAU. METHODS: A randomized controlled clinical trial was designed, and 60 continuous RAU patients were randomly assigned to the experimental group (n = 32, taking thalidomide before bed at a dose of 100 mg/d for 10 days, then 50 mg/d for 10 days, and 25 mg/d for 10 days) and the control group (n = 28, taking 0.4 mg/kg/d prednisone every morning for 15 days and then 0.2 mg/kg/d for 15 days). The clinical outcomes consisted of the primary outcome (recurrence interval) and the secondary outcomes (pain level, number of ulcers, and days for ulcer healing), and they were measured at every visit. Adverse reactions were recorded. RESULTS: A total of 54 and 51 patients presented at the first and second return visit, respectively. After 1 month, the increase in the recurrence interval was not shown to differ between the two groups (P = .12). However, the improvement in the recurrence interval was significantly greater in the experimental group (P < .001) at the second return visit. The improvement in the secondary outcomes was identical between two groups at each return visit (P > .05). The incidence of adverse reactions was similar between two groups (P = .50). CONCLUSIONS: Thalidomide had a long-term effect of extending the recurrence interval of continuous RAU.

Organic/inorganic nanohybrids as multifunctional gene delivery systems.

In this review, we summarize the rational design and versatile application of organic/inorganic hybrid gene carriers as multifunctional delivery systems. Organic/inorganic nanohybrids with both organic and inorganic components in one nanoparticle have attracted intense attention because of their favorable properties. Particularly, nanohybrids comprising cationic polymers and inorganic nanoparticles are considered to be promising candidates as multifunctional gene delivery systems. In this review, we begin with an introduction of gene delivery and gene carriers to demonstrate the incentive for fabricating nanohybrids as multifunctional carriers. Next, the construction strategies and morphology effects of organic/inorganic hybrid gene carriers are summarized and discussed. Both sections provide valuable information for the design and synthesis of hybrid gene carriers with superior properties. Finally, an overview is provided of the application of nanohybrids as multifunctional gene carriers. Diverse therapies and versatile imaging-guided therapies have been achieved via the rational design of nanohybrids. In addition to a simple combination of the functions of organic and inorganic components, the performances arising from the synergistic effects of both components are considered to be more intriguing. In summary, this review might offer guidance for the understanding of organic/inorganic nanohybrids as multifunctional gene delivery systems.

Survey of non-physiotherapy department medical staff in China and their understanding of physiotherapy in comprehensive management of haemophilia.

INTRODUCTION: Physiotherapy plays a very important role in comprehensive care of patients with haemophilia. Due to limited resources and a lack of understanding among medical personnel, physiotherapy has not become a standard component of comprehensive management of haemophilia in China. AIM: To investigate the understanding and practice of physiotherapy in the comprehensive management of haemophilia by non-physiotherapy department medical staff engaged in haemophilia work in China. METHODS: A specifically designed questionnaire was used to investigate the medical staff who participated in the 10th World Federation of Hemophilia-Hemophilia Conference China held in Xi'an, China, from 14 October to 16 October 2016. RESULTS: Among all respondents, 97.2% believed that haemophilia patients needed physiotherapy. However, only 17.5% of the respondents were found to have a very accurate understanding of the timing of physiotherapeutic interventions for haemophilia patients; 83.9% of the respondents worried that physiotherapy would increase the incidence of new haemorrhagic episodes in haemophilia patients, and 11.1% of the respondents never recommended physiotherapy for haemophilia patients. Factors that independently affected the respondents' knowledge of the timing of physiotherapy in haemophilia patients were their professional rank and participation in continuing education that included haemophilia physiotherapy. One factor that independently affected respondents' recommendation of physiotherapy to patients was participation in continuing education that included haemophilia physiotherapy. CONCLUSION: Haemophilia continuing education covering physiotherapy should be strengthened for new non-physiotherapy medical staff in the haemophilia field.

Modulating the Hydrothermal Synthesis of Co3O4 and CoOOH Nanoparticles by H2O2 Concentration.

The formation process and product control are very important in material synthesis. In this study, a facile one-pot hydrothermal method was used to prepare Co3O4 and CoOOH. H2O2 was used to modulate the formation process and control the final product by changing its concentration. The crystalline structures and morphologies of the as-prepared products were characterized by X-ray diffraction (XRD), Raman spectra, and scanning electron microscopy (SEM) techniques. It was found that the concentration of H2O2 influenced not only the phase of the final products but also their morphologies. The influences of H2O2 concentration on the precursor formation and the reaction path have been revealed. At a low concentration of H2O2 (5 wt %), the formed precursor is Co(CO3)0.5(OH)·0.11H2O, which can be directly transformed into Co3O4 upon increasing the hydrothermal time. At a medium concentration (15-20 wt %), the formed precursor and the final product are all CoOOH. At a high concentration (30 wt %), the formed precursor is CoOOH, and the final product is Co3O4. H2O2 plays the role of oxidant agent at the initial stage or reducing agent at the subsequent stage. This study offers a H2O2-concentration modulating method for the formation of Co3O4 and CoOOH.

High resolution mapping of nitrogen dioxide with TROPOMI: First results and validation over the Canadian oil sands.

TROPOMI, on-board the Sentinel-5 Precursor satellite is a nadir-viewing spectrometer measuring reflected sunlight in the ultraviolet, visible, near-infrared, and shortwave infrared spectral range. From these spectra several important air quality and climate-related atmospheric constituents are retrieved at an unprecedented high spatial resolution, including nitrogen dioxide (NO2). We present the first retrievals of TROPOMI NO2 over the Canadian Oil Sands, contrasting them with observations from the OMI satellite instrument, and demonstrate its ability to resolve individual plumes and highlight its potential for deriving emissions from individual mining facilities. Further, the first TROPOMI NO2 validation is presented, consisting of aircraft and surface in-situ NO2 observations, as well as ground-based remote-sensing measurements between March and May 2018. Our comparisons show that the TROPOMI NO2 vertical column densities are highly correlated with the aircraft and surface in-situ NO2 observations, and the ground-based remote-sensing measurements with a low bias (15-30 %) over the Canadian Oil Sands. PLAIN LANGUAGE SUMMARY: Nitrogen dioxide (NO2) is a pollutant that is linked to respiratory health issues and has negative environmental impacts such as soil and water acidification. Near the surface the most significant sources of NO2 are fossil fuel combustion and biomass burning. With a recently launched satellite instrument (TROPOspheric Monitoring Instrument; TROPOMI) NO2 can be measured with an unprecedented combination of accuracy, spatial coverage, and resolution. This work presents the first TROPOMI NO2 measurements near the Canadian Oil Sands and shows that these measurements have an outstanding ability to detect NO2 on a very high horizontal resolution that is unprecedented for satellite NO2 observations. Further, these satellite measurements are in excellent agreement with aircraft and ground-based measurements.

Locostatin Alleviates Liver Fibrosis Induced by Carbon Tetrachloride in Mice.

BACKGROUND AND AIMS: Liver fibrosis is featured with excessive deposition of extracellular matrix and fibrous connective tissue hyperplasia. The specific inhibitor of Raf-1 kinase inhibitor protein, locostatin, inhibits the migration of hepatic stellate cells. In this study, we investigated the effect of locostatin on liver fibrosis and its underlying mechanism. METHODS: Carbon tetrachloride (CCl4) was used to induce liver fibrosis in mice, and locostatin was injected intraperitoneally. Liver fibrosis was assessed by Masson and Sirius red staining, hydroxyproline (HYP) assay, and collagen percentage area. Collagen I, collagen III, and α-SMA were detected by RT-PCR and western blot. The levels of MMP-13, MMP-2, TIMP-1, and TIMP-2 were estimated by ELISA. Liver inflammation was evaluated by HE staining and immunohistochemistry; liver myeloperoxidase (MPO), superoxide dismutase, and malondialdehyde were measured by ELISA; and cytokines were by Mouse Cytokine Array Q4000. RESULTS: Compared to the CCl4 group, HYP (208.56 ± 6.12) µg/g, percentage of total collagen at overall region (1.91 ± 0.13), MMP-13/TIMP-1 (0.19 ± 0.01), MPO (1.45 ± 0.04) U/g, TGF-ß (2652 ± 91.20), PDGF-AA (3897 ± 290.69), and E-selectin (1569 ± 66.48) in the liver tissues were decreased significantly in the locostatin-treated group. CONCLUSIONS: Locostatin mitigated liver fibrosis and inflammation induced by CCl4. The mechanism is via inhibition inflammatory cytokines, TGF-ß, PDGF-AA, and E-selectin.

Exosomal miR-95-5p regulates chondrogenesis and cartilage degradation via histone deacetylase 2/8.

MicroRNAs play critical roles in the pathogenesis of osteoarthritis, the most common chronic degenerative joint disease. Exosomes derived from miR-95-5p-overexpressing primary chondrocytes (AC-miR-95-5p) may be effective in treating osteoarthritis. Increased expression of HDAC2/8 occurs in the tissues and chondrocyte-secreted exosomes of patients with osteoarthritis and mediates cartilage-specific gene expression in chondrocytes. We have been suggested that exosomes derived from AC-miR-95-5p (AC-miR-95-5p-Exos) would enhance chondrogenesis and prevent the development of osteoarthritis by directly targeting HDAC2/8. Our in vitro experiments showed that miR-95-5p expression was significantly lower in osteoarthritic chondrocyte-secreted exosomes than in normal cartilage. Treatment with AC-miR-95-5p-Exos promoted cartilage development and cartilage matrix expression in mesenchymal stem cells induced to undergo chondrogenesis and chondrocytes, respectively. In contrast, co-culture with exosomes derived from chondrocytes transfected with an antisense inhibitor of miR-95-5p (AC-anti-miR-95-5p-Exos) prevented chondrogenic differentiation and reduced cartilage matrix synthesis by enhancing the expression of HDAC2/8. MiR-95-5p suppressed the activity of reporter constructs containing the 3'-untranslated region of HDAC2/8, inhibited HDAC2/8 expression and promoted cartilage matrix expression. Our results suggest that AC-miR-95-5p-Exos regulate cartilage development and homoeostasis by directly targeting HDAC2/8. Thus, AC-miR-95-5p-Exos may act as an HDAC2/8 inhibitor and exhibit potential as a disease-modifying osteoarthritis drug.

Highly Dispersed Fullerenols Hamper Osteoclast Ruffled Border Formation by Perturbing Ca2+ Bundles.

Osteoporosis, a common and serious bone disorder affecting aged people and postmenopausal women, is characterized by osteoclast overactivity. One therapeutic strategy is suppressing the bone resorption function of hyperactive osteoclasts, but there is no effective drug in clinical practice so far. Herein, it is demonstrated that fullerenols suppress the bone resorption of osteoclasts by inhibiting ruffled borders (RBs) formation. The RBs formation, which is supported by well-aligned actin bundles (B-actins), is a critical event for osteoclast bone resorption. To facilitate this function, osteoclast RBs dynamics is regulated by variable microenvironments to bundle F-actins, protrude cell membrane, and so on. B-actin perturbation by fullerenols is determined here, offering an opportunity to regulate osteoclast function by destroying RBs. In vivo, the therapeutic effect of fullerenols on overactive osteoclasts is confirmed in a mouse model of lipopolysaccharide-induced bone erosion. Collectively, the findings suggest that fullerenols adhere to F-actin surfaces and inhibit RBs formation in osteoclasts, mainly through hampering Ca2+ from bundling F-actins, and this is likely due to the stereo-hindrance effect caused by adherent fullerenols.