Three-dimensional Reconstruction and Comparison of Temporomandibular Joint Space Volume Before and After Orthognathic Surgery in Patients with Skeletal Class III Malocclusion With Mandibular Deviation.

OBJECTIVE: To look into the association between the degree of deviation and the changing trend in the temporomandibular joint (TMJ) space volume after orthognathic surgery in patients with skeletal Class III malocclusion. METHODS: Twenty patients having combined orthodontic-orthognathic treatment for skeletal Class III malocclusions with mandibular deviation were chosen, and craniofacial spiral CT was performed before (T0), two weeks after (T1), and six months after (T2) surgery. Using 3D volume reconstruction, further partitioning, and analysis of each domain's volume changes over time, the TMJ space volume is to be obtained. The differences in changes between groups A (mild deviation group) and B (severe deviation group) were examined to examine the impact of the degree of deviation on the TMJ space volume. RESULTS: A statistically significant difference ( P <0.05) existed between the postoperative TMJ space volume in group A and the preoperative overall, anterolateral, and anteroinferior space volume; the same difference also existed between the postoperative TMJ space volume in the NDS and the preoperative posterolateral, posteroinferior space volume. In group B, the postoperative TMJ space volume was statistically significant ( P <0.05) compared with the preoperative total and anteroinferior space volume in the DS; the difference between the total volume of the T1 stage on the NDS and the total volume of the T0 stage was statistically significant ( P <0.05). The two groups showed substantial differences in the space volume changes between the T1-T0 phase and the T2-T1 period. CONCLUSION: Patients with skeletal Class III malocclusion and mandibular deviation after orthognathic surgery see a change in the TMJ space volume. All patient types experience a largely consistent space volume change trend two weeks after surgery, and the degree of mandibular deviation is correlated with the intensity and longevity of the alteration.

Advances in the natural history of urinary incontinence in adult females.

The aim of this review is to summarise the related characteristics of the natural history of female urinary incontinence (UI) using a narrative descriptive approach. PubMed, EMBASE and Web of Science were searched for articles published from 1 January 2010 to 1 January 2020 on the natural history of female UI, which including incidence, persistence, progression, remission, and regression of a single subtype of UI and the mutual influence of different UI subtypes. This literature review includes 15 articles published, indicates that UI is highly dynamic, with symptoms varying according to disease severity and subtype and influenced by multiple factors at different disease stages. Recent studies have increased our understanding of the natural history of UI. Future research should systematically analyse the progression of each subtype of UI and interactions between subtypes to prevent the progression of UI across females life course.

Association between Serum Oxytocin, Bone Mineral Density and Body Composition in Chinese Adult Females.

Background and Objectives: Oxytocin (OT) is a neuropeptide hormone which is known for its classical effects in pregnancy and lactation. Recently, growing evidence demonstrated a close relation between OT and bone. The present study aimed to explore the relationship between OT, bone and osteoporosis risk in Chinese adult females. Materials and Methods: in total, 149 adult females were enrolled. The serum OT levels were measured using ELISA kits. Bone mineral density (BMD) and body composition were measured by dual-energy X-ray absorptiometry (DXA). The study subjects were divided into two groups according to their menopause status and then divided into tertiles based on their serum OT level. Results: Serum OT, serum estradiol and BMD at three skeletal sites were significantly higher in the premenopausal group than in the postmenopausal group (p < 0.001, p = 0.008 and p < 0.001, respectively). In the tertile analysis, relative to tertile 1, significant associations were found for tertile 3 for OT levels and higher BMD in the femoral neck and total hip, in both pre- and postmenopausal groups. Using logistic regression analysis, tertile 3 appeared less likely to have low-BMD osteoporosis than tertile 1 (OR = 0.257, 95% CI = 0.073, 0.910). In multivariate stepwise regression analysis, OT and total lean mass were two positive determinants of BMD in the femoral neck and total hip in the premenopausal group (adjusted R2 for the model = 0.232 and 0.199, respectively; both p < 0.001). Conclusion: Our study demonstrated positive associations between serum OT levels and BMD in a Chinese (non-Caucasian) population. OT appeared to be more strongly associated with hip BMD in premenopausal females. These results may suggest a protective role and potential therapeutic use of OT in osteoporosis, especially for premenopausal women.

ß-Glucan from Lentinula edodes prevents cognitive impairments in high-fat diet-induced obese mice: involvement of colon-brain axis.

BACKGROUND: Long-term high fat (HF) diet intake can cause neuroinflammation and cognitive decline through the gut-brain axis. (1, 3)/(1, 6)-ß-glucan, an edible polysaccharide isolated from medical mushroom, Lentinula edodes (L. edodes), has the potential to remodel gut microbiota. However, the effects of L. edodes derived ß-glucan against HF diet-induced neuroinflammation and cognitive decline remain unknown. This study aimed to evaluate the neuroprotective effect and mechanism of dietary L edodes ß-glucan supplementation against the obesity-associated cognitive decline in mice fed by a HF diet. METHODS: C57BL/6J male mice were fed with either a lab chow (LC), HF or HF with L. edodes ß-glucan supplementation diets for 7 days (short-term) or 15 weeks (long-term). Cognitive behavior was examined; blood, cecum content, colon and brain were collected to evaluate metabolic parameters, endotoxin, gut microbiota, colon, and brain pathology. RESULTS: We reported that short-term and long-term L. edodes ß-glucan supplementation prevented the gut microbial composition shift induced by the HF diet. Long-term L. edodes ß-glucan supplementation prevented the HF diet-induced recognition memory impairment assessed by behavioral tests (the temporal order memory, novel object recognition and Y-maze tests). In the prefrontal cortex and hippocampus, the ß-glucan supplementation ameliorated the alteration of synaptic ultrastructure, neuroinflammation and brain-derived neurotrophic factor (BDNF) deficits induced by HF diet. Furthermore, the ß-glucan supplementation increased the mucosal thickness, upregulated the expression of tight junction protein occludin, decreased the plasma LPS level, and inhibited the proinflammatory macrophage accumulation in the colon of mice fed by HF diet. CONCLUSIONS: This study revealed that L. edodes ß-glucan prevents cognitive impairments induced by the HF diet, which may occur via colon-brain axis improvement. The finding suggested that dietary L. edodes ß-glucan supplementation may be an effective nutritional strategy to prevent obesity-associated cognitive decline.

Dicyanamide Anion-Based Ionic Liquid-Functionalized Graphene-Supported Pt Catalysts for Boosting Methanol Electrooxidation.

As an environmentally friendly energy technology, direct methanol fuel cells (DMFCs) meet the needs of sustainable development. Herein, novel dicyanamide anion-based (N(CN)2-) ionic liquid (IL)-functionalized reduced graphene oxide (rGO)-supported Pt catalysts are synthesized via a facile one-pot room temperature reduction method, which show a boost in methanol oxidation performance compared with Pt/rGO. The mass activities of the as-prepared Pt/emimN(CN)2/rGO (863.6 mA mg-1Pt) and Pt/epyN(CN)2/rGO (524.9 mA mg-1Pt) are about five and three times higher than that of Pt/rGO (178.6 mA mg-1Pt), and about six and four times higher than that of Pt/C (140.2 mA mg-1Pt), respectively. The participation of ILs significantly improves the CO poisoning resistance, stability, and activity for methanol oxidation of catalysts. The relationship between the structures and conductivities of diverse ILs and the performance of Pt catalysts are studied systematically. These findings may offer a promising prospect of ILs in DMFCs.

Serum concentrations of oxytocin, DHEA and follistatin are associated with osteoporosis or sarcopenia in community-dwelling postmenopausal women.

BACKGROUND: Osteoporosis and sarcopenia are major health issues in postmenopausal women due to their high prevalence and association with several adverse outcomes. However, no biomarkers may be used for screening and diagnosis. The current study investigated potential biomarkers for osteoporosis and/or sarcopenia in postmenopausal women. METHODS: A cross-sectional study on 478 healthy community-dwelling postmenopausal women aged 50-90 years was performed. Osteoporosis and sarcopenia were defined according to the World Health Organization (WHO) and Asian Working Group for Sarcopenia (AWGS). RESULTS: Dehydroepiandrosterone (DHEA) was related to muscle strength (ß = 0.19, p = 0.041) and function (ß = 0.58, p = 0.004). Follistatin (ß = - 0.27, p = 0.01) was related to muscle mass. Oxytocin (ß = 0.59, p = 0.044) and DHEA (ß = 0.51, p = 0.017) were related to bone mass. After adjusting for age, oxytocin (odds ratio (OR) 0.75; 95% confidence intervals (CI) 0.63-0.98; p = 0.019) was associated with osteoporosis, and DHEA (OR 0.73; 95% CI 0.51-0.96; p = 0.032) and follistatin (OR 1.66; 95% CI 1.19-3.57; p = 0.022) were associated with sarcopenia. CONCLUSIONS: Postmenopausal women with sarcopenia were more likely to have lower DHEA levels and higher follistatin levels, and postmenopausal women with osteoporosis were more likely to have lower oxytocin levels.

Supplement of microbiota-accessible carbohydrates prevents neuroinflammation and cognitive decline by improving the gut microbiota-brain axis in diet-induced obese mice.

BACKGROUND: Western pattern diets induce neuroinflammation and impair cognitive behavior in humans and animals. Neuroinflammation and cognitive impairment have been associated with microbiota dysbiosis, through the gut-brain axis. Furthermore, microbiota-accessible carbohydrates (MACs) found in dietary fiber are important in shaping the microbial ecosystem and have the potential to improve the gut-brain-axis. However, the effects of MACs on neuroinflammation and cognition in an obese condition have not yet been investigated. The present study aimed to evaluate the effect of MACs on the microbiota-gut-brain axis and cognitive function in obese mice induced by a high-fat and fiber deficient (HF-FD) diet. METHODS: C57Bl/6 J male mice were fed with either a control HF-FD or a HF-MAC diet for 15 weeks. Moreover, an additional group was fed with the HF-MAC diet in combination with an antibiotic cocktail (HF-MAC + AB). Following the 15-week treatment, cognitive behavior was investigated; blood, cecum content, colon, and brain samples were collected to determine metabolic parameters, endotoxin, gut microbiota, colon, and brain pathology. RESULTS: We report MACs supplementation prevented HF-FD-induced cognitive impairment in nesting building and temporal order memory tests. MACs prevented gut microbiota dysbiosis, including increasing richness, α-diversity and composition shift, especially in Bacteroidetes and its lower taxa. Furthermore, MACs increased colonic mucus thickness, tight junction protein expression, reduced endotoxemia, and decreased colonic and systemic inflammation. In the hippocampus, MACs suppressed HF-FD-induced neuroglia activation and inflammation, improved insulin IRS-pAKT-pGSK3ß-pTau synapse signaling, in addition to the synaptic ultrastructure and associated proteins. Furthermore, MACs' effects on improving colon-cognitive parameters were eliminated by wide spectrum antibiotic microbiota ablation. CONCLUSIONS: These results suggest that MACs improve cognitive impairments via the gut microbiota-brain axis induced by the consumption of an HF-FD. Supplemental MACs to combat obesity-related gut and brain dysfunction offer a promising approach to prevent neurodegenerative diseases associated with Westernized dietary patterns and obesity.

Self-Replication-Assisted Rapid Preparation of DNA Nanowires at Room Temperature and Its Biosensing Application.

A rapid room-temperature DNA nanowires preparation strategy on the basis of self-replicating catalyzed hairpin assembly (SRCHA) was reported. In this system, three hairpin probes (P1, P2, and P3) were well-designed and partially hybridize to each other, and two split trigger DNA sequences were integrated into P1 and P3, respectively. When the SRCHA was initiated by the trigger DNA, a series of DNA assembly steps based on the toehold-mediated DNA strand displacement were activated, and the Y shaped DNA (P1-P2-P3) was formed. In that case, the two split trigger DNA sequences will come into close-enough proximity to form the trigger DNA replicas, which can initiate the additional SRCHA reaction cycles for DNA nanowire preparation, and eventually a rapid room-temperature DNA nanowires preparation strategy without need of fuel strands was successfully developed. Furthermore, the prepared DNA nanowires have been used to develop a rapid and signal amplified sensing platform for sensitive adenosine triphosphate (ATP) detection.

A new approach for reducing beam hardening artifacts in polychromatic X-ray computed tomography using more accurate prior image.

PURPOSE: Metal artifacts severely degrade CT image quality in clinical diagnosis, which are difficult to removed, especially for the beam hardening artifacts. The metal artifact reduction (MAR) based on prior images are the most frequently-used methods. However, there exists a lot misclassification in most prior images caused by absence of prior information such as the spectrum distribution of X-ray beam source, especially many or big metal included. The purpose of this work is to find a more accurate prior image to improve image quality. METHODS: The proposed method comprise of following four steps. First, the metal image is segmented by thresholding an initial image, where the metal traces are identified in the initial projection data using the forward projection of the metal image. Second, the accurate absorbent model of certain metal image is calculated according to the spectrum distribution of certain X-ray beam source and energy-dependent attenuation coefficients of metal. Then, a new metal image is reconstructed by the general analytical reconstruction algorithm such as filtered back projection (FPB). The prior image is obtained by segmenting the difference image between the initial image and the new metal image into air, tissue and bone. Finally, the initial projection data are normalized by dividing the projection data of prior image pixel to pixel, the corrected image is obtained by interpolation, denormalization and reconstruction. RESULTS: Some clinical images with dental fillings and knee prostheses are used to evaluate the proposed algorithm and normalized metal artifact reduction (NMAR) and linear interpolation (LI) method. The results demonstrate the artifacts can be reduced efficiently by the proposed method. CONCLUSIONS: The proposed method could obtain an exact prior image using the prior information about X-ray beam source and energy-dependent attenuation coefficients of metal. As a result, the better performance of reducing beam hardening artifacts can be improved, even though there were many or big implants. Moreover, the process of the proposed method is rather simple and little extra calculation burden is necessary. It has superiorities over other algorithms when include big or many implants.

Reduce beam hardening artifacts of polychromatic X-ray computed tomography by an iterative approximation approach.

BACKGROUND: The beam hardening artifact is one of most important modalities of metal artifact for polychromatic X-ray computed tomography (CT), which can impair the image quality seriously. OBJECTIVE: An iterative approach is proposed to reduce beam hardening artifact caused by metallic components in polychromatic X-ray CT. METHODS: According to Lambert-Beer law, the (detected) projections can be expressed as monotonic nonlinear functions of element geometry projections, which are the theoretical projections produced only by the pixel intensities (image grayscale) of certain element (component). With help of a prior knowledge on spectrum distribution of X-ray beam source and energy-dependent attenuation coefficients, the functions have explicit expressions. Newton-Raphson algorithm is employed to solve the functions. The solutions are named as the synthetical geometry projections, which are the nearly linear weighted sum of element geometry projections with respect to mean of each attenuation coefficient. In this process, the attenuation coefficients are modified to make Newton-Raphson iterative functions satisfy the convergence conditions of fixed pointed iteration(FPI) so that the solutions will approach the true synthetical geometry projections stably. The underlying images are obtained using the projections by general reconstruction algorithms such as the filtered back projection (FBP). The image gray values are adjusted according to the attenuation coefficient means to obtain proper CT numbers. RESULTS: Several examples demonstrate the proposed approach is efficient in reducing beam hardening artifacts and has satisfactory performance in the term of some general criteria. In a simulation example, the normalized root mean square difference (NRMSD) can be reduced 17.52% compared to a newest algorithm. CONCLUSIONS: Since the element geometry projections are free from the effect of beam hardening, the nearly linear weighted sum of them, the synthetical geometry projections, are almost free from the effect of beam hardening. By working out the synthetical geometry projections, the proposed approach becomes quite efficient in reducing beam hardening artifacts.

Histological image segmentation using fast mean shift clustering method.

BACKGROUND: Colour image segmentation is fundamental and critical for quantitative histological image analysis. The complexity of the microstructure and the approach to make histological images results in variable staining and illumination variations. And ultra-high resolution of histological images makes it is hard for image segmentation methods to achieve high-quality segmentation results and low computation cost at the same time. METHODS: Mean Shift clustering approach is employed for histological image segmentation. Colour histological image is transformed from RGB to CIE L*a*b* colour space, and then a* and b* components are extracted as features. To speed up Mean Shift algorithm, the probability density distribution is estimated in feature space in advance and then the Mean Shift scheme is used to separate the feature space into different regions by finding the density peaks quickly. And an integral scheme is employed to reduce the computation cost of mean shift vector significantly. Finally image pixels are classified into clusters according to which region their features fall into in feature space. RESULTS: Numerical experiments are carried on liver fibrosis histological images. Experimental results demonstrate that Mean Shift clustering achieves more accurate results than k-means but is computational expensive, and the speed of the improved Mean Shift method is comparable to that of k-means while the accuracy of segmentation results is the same as that achieved using standard Mean Shift method. CONCLUSIONS: An effective and reliable histological image segmentation approach is proposed in this paper. It employs improved Mean Shift clustering, which is speed up by using probability density distribution estimation and the integral scheme.

Purification of a Pd20-TNFα fusion protein that prevents liver metastasis of gastric cancer.

The specific binding peptide pd20 of gastric cancer cells with a high potential for liver metastasis was fused with human tumour necrosis factor (TNF) α, and a prokaryotic expression vector was established to express the pd20-TNFα fusion protein. After purification and identification, the preventive effects of the fusion protein on liver metastasis of gastric cancer were observed in mice. The whole gene synthesis method was used for pd20-TNFα fusion gene preparation, and a pd20-TNFα prokaryotic expression vector was constructed. The vector was induced and expressed in Escherichia coli BL21. The expression products were analysed and verified by SDS-PAGE electrophoresis and Western blot analysis. The Ni-NTA column method was used to purify the fusion protein, and the L929 cytotoxicity method was used to detect biological activity. Flow cytometry apoptosis experiments and invasion assays were performed to observe the effects of the fusion protein on apoptosis and metastasis of gastric cancer cells with high potential for liver metastasis. Thirty nude mice with liver metastasis of gastric cancer were established and then randomly divided into three groups of ten mice each. The Pd20-TNFα recombinant protein (1.2 × 10(6) U/kg day) or standard TNFα (1.2 × 10(6) U/kg day) saline was administered via tail vein injection for 7 consecutive days. The pathological changes in various organs of nude mice were observed 4 weeks later. The size of the gastric cancer, the incidence of liver metastasis and the number of liver metastases were measured and calculated. We successfully constructed a Pd20-TNFα recombinant plasmid and prepared the fusion protein. Detection of the pd20-TNFα protein by immunofluorescence showed a very strong expression in liver tissue, suggesting a targeting of the fusion protein to the liver. The L929 cytotoxicity assays showed that the pd20-TNFα fusion purified protein had a significant lethal effect on L929 cells, with a killing activity of up to 7.6 × 10(6) IU/ml. The apoptosis experiments showed that as the concentration of the fusion protein increased, the early gastric cancer cell apoptosis also increased, with the early apoptosis rate increasing from 5.99 % to 9.04 %. Cell invasion experiments showed that the purified pd20-TNFα fusion protein significantly inhibited the in vitro invasion of XGC9811-L cells, with the penetrating cells being significantly decreased compared with the control group per unit time (P < 0.01). Vector experiments showed that the pd20-TNFα recombinant protein group had significantly reduced cancer lesions and liver metastasis in nude mice compared with the control group. We successfully purified a pd20-TNFα fusion protein and confirmed that it had significant biological activity promoting early gastric cancer cell apoptosis, thereby inhibiting gastric cancer cell invasion.

Emphysema early diagnosis using X-ray diffraction enhanced imaging at synchrotron light source.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide, and emphysema is a common component of COPD. Currently, it is very difficult to detect early stage emphysema using conventional radiographic imaging without contrast agents, because the change in X-ray attenuation is not detectable with absorption-based radiography. Compared with the absorption-based CT, phase contrast imaging has more advantages in soft tissue imaging, because of its high spatial resolution and contrast. METHODS: In this article, we used diffraction enhanced imaging (DEI) method to get the images of early stage emphysematous and healthy samples, then extract X-ray absorption, refraction, and ultra-small-angle X-ray scattering (USAXS) information from DEI images using multiple image radiography (MIR). We combined the absorption image with the USAXS image by a scatter plot. The critical threshold in the scatter plot was calibrated using the linear discriminant function in the pattern recognition. RESULTS: USAXS image was sensitive to the change of tissue micro-structure, it could show the lesions which were invisible in the absorption image. Combined with the absorption-based image, the USAXS information enabled better discrimination between healthy and emphysematous lung tissue in a mouse model. The false-color images demonstrated that our method was capable of classifying healthy and emphysematous tissues. CONCLUSION: Here we present USAXS images of early stage emphysematous and healthy samples, where the dependence of the USAXS signal on micro-structures of biomedical samples leads to improved diagnosis of emphysema in lung radiographs.

Draft genome sequence of Bacillus atrophaeus TL401, a biocontrol bacterium with plant growth-promoting properties.

Bacillus atrophaeus strain TL401 exhibits biocontrol activity against Botrytis cinerea on tomato and plant growth promotion. Here, we present the draft genome sequence of strain ITL401, which includes a circular chromosome with 4,213,034 bp and a guanine-cytosine content of 43.39%.

A novel scheme to design the filter for CT reconstruction using FBP algorithm.

BACKGROUND: The Filtered Back-Projection (FBP) algorithm is the most important technique for computerized tomographic (CT) imaging, in which the ramp filter plays a key role. FBP algorithm had been derived using the continuous system model. However, it has to be discretized in practical applications, which necessarily produces distortion in the reconstructed images. METHODS: A novel scheme is proposed to design the filters to substitute the standard ramp filter to improve the reconstruction performance for parallel beam tomography. The design scheme is presented under the discrete image model and discrete projection environment. The designs are achieved by constrained optimization procedures. The designed filter can be regarded as the optimal filter for the corresponding parameters in some ways. RESULTS: Some filters under given parameters (such as image size and scanning angles) have been designed. The performance evaluation of CT reconstruction shows that the designed filters are better than the ramp filter in term of some general criteria. CONCLUSIONS: The 2-D or 3-D FBP algorithms for fan beam tomography used in most CT systems, are obtained by modifying the FBP algorithm for parallel beam tomography. Therefore, the designed filters can be used for fan beam tomography and have potential applications in practical CT systems.

Dimethyl itaconate ameliorates cognitive impairment induced by a high-fat diet via the gut-brain axis in mice.

BACKGROUND: Gut homeostasis, including intestinal immunity and microbiome, is essential for cognitive function via the gut-brain axis. This axis is altered in high-fat diet (HFD)-induced cognitive impairment and is closely associated with neurodegenerative diseases. Dimethyl itaconate (DI) is an itaconate derivative and has recently attracted extensive interest due to its anti-inflammatory effect. This study investigated whether intraperitoneal administration of DI improves the gut-brain axis and prevents cognitive deficits in HF diet-fed mice. RESULTS: DI effectively attenuated HFD-induced cognitive decline in behavioral tests of object location, novel object recognition, and nesting building, concurrent with the improvement of hippocampal RNA transcription profiles of genes associated with cognition and synaptic plasticity. In agreement, DI reduced the damage of synaptic ultrastructure and deficit of proteins (BDNF, SYN, and PSD95), the microglial activation, and neuroinflammation in the HFD-fed mice. In the colon, DI significantly lowered macrophage infiltration and the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) in mice on the HF diet, while upregulating the expression of immune homeostasis-related cytokines (IL-22, IL-23) and antimicrobial peptide Reg3γ. Moreover, DI alleviated HFD-induced gut barrier impairments, including elevation of colonic mucus thickness and expression of tight junction proteins (zonula occludens-1, occludin). Notably, HFD-induced microbiome alteration was improved by DI supplementation, characterized by the increase of propionate- and butyrate-producing bacteria. Correspondingly, DI increased the levels of propionate and butyrate in the serum of HFD mice. Intriguingly, fecal microbiome transplantation from DI-treated HF mice facilitated cognitive variables compared with HF mice, including higher cognitive indexes in behavior tests and optimization of hippocampal synaptic ultrastructure. These results highlight the gut microbiota is necessary for the effects of DI in improving cognitive impairment. CONCLUSIONS: The present study provides the first evidence that DI improves cognition and brain function with significant beneficial effects via the gut-brain axis, suggesting that DI may serve as a novel drug for treating obesity-associated neurodegenerative diseases. Video Abstract.

MicroRNAs in Serum Exosomes as Circulating Biomarkers for Postmenopausal Osteoporosis.

Postmenopausal osteoporosis (PMOP) is the most common skeletal disease in postmenopausal women and has become a global public health issue. Emerging evidence demonstrated the important relationship between microRNAs and PMOP. However, miRNAs have not yet been reported in PMOP. Hence, the present study aimed to investigate the differences in miRNA expression profiles in PMOP with fragility fractures to identify the key circulating miRNAs in serum exosomes and to validate these molecules as potential biomarkers. Postmenopausal women with osteoporotic fracture and normal bone mass were enrolled. Serum exosomes were isolated by traditional differential ultracentrifugation from participants. Isolated exosomes were identified by electron microscopy, western blotting and nanoparticle-tracking analysis and then examined for exosomal small RNA sequencing. The expression of miRNAs was compared by sRNA deep sequencing and bioinformatics analysis. Three miRNAs (mir-324-3p, mir-766-3p and mir-1247-5p) were found to be associated with BMD of L1-L4, FN (femur neck) and TH (total hip), while mir-330-5p and mir-3124-5p were associated with BMD of FN and TH. Furthermore, mir-330-5p was found to promote the ALP activity of hBMSCs, while mir-3124-5p showed the opposite result. The results showed that serum exosomal miRNAs were differentially expressed in postmenopausal osteoporosis patients with fragility fractures. Our study provides the first evidence that exosomal miRNA profiling revealed aberrant circulating miRNA in postmenopausal osteoporosis. Mir-324-3p, mir-766-3p, mir-1247-5p, mir-330-5p and mir-3124-5p, which were associated with bone mineral density (BMD), may serve as candidate diagnostic biomarkers as well as potentially contribute to pathophysiology of PMOP.

Identification of VdASP F2-interacting protein as a regulator of microsclerotial formation in Verticillium dahliae.

Verticillium dahliae, a notorious phytopathogenic fungus, causes vascular wilt diseases in many plant species. The melanized microsclerotia enable V. dahliae to survive for years in soil and are crucial for its disease cycle. In a previous study, we characterized the secretory protein VdASP F2 from V. dahliae and found that VdASP F2 deletion significantly affected the formation of microsclerotia under adverse environmental conditions. In this study, we clarified that VdASP F2 is localized to the cell wall. However, the underlying mechanism of VdASP F2 in microsclerotial formation remains unclear. Transmembrane ion channel protein VdTRP was identified as a candidate protein that interacts with VdASP F2 using pull-down assays followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and interaction of VdASP F2 and VdTRP was confirmed by bimolecular fluorescence complementary and coimmunoprecipitation assays. The deletion mutant was analysed to reveal that VdTRP is required for microsclerotial production, but it is not essential for stress resistance, carbon utilization and pathogenicity of V. dahliae. RNA-seq revealed some differentially expressed genes related to melanin synthesis and microsclerotial formation were significantly downregulated in the VdTRP deletion mutants. Taken together, these results indicate that VdASP F2 regulates the formation of melanized microsclerotia by interacting with VdTRP.

ZEB1 Mediates Bone Marrow Mesenchymal Stem Cell Osteogenic Differentiation Partly via Wnt/ß-Catenin Signaling.

Zinc finger E-box-binding homebox 1 (ZEB1) is a zinc-finger transcription factor best known for its role in promoting the epithelial-mesenchymal transition, which is also related to osteogenesis. Here, ZEB1 was investigated for its role in the commitment of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts. In vitro, ZEB1 expression decreased following osteogenic differentiation. Furthermore, silencing of ZEB1 in BMSCs promoted osteogenic activity and mineralization. The increase in osteogenic differentiation induced by si-ZEB1 could be partly rescued by the inhibition of Wnt/ß-catenin (si-ß-catenin). In vivo, knockdown of ZEB1 in BMSCs inhibited the rapid bone loss of ovariectomized (OVX) mice. ZEB1 expression has also been negatively associated with bone mass and bone formation in postmenopausal women. In conclusion, ZEB1 is an essential transcription factor in BMSC differentiation and may serve as a potential anabolic strategy for treating and preventing postmenopausal osteoporosis (PMOP).