Tool mark prediction on the surface of large-aperture mirrors via magnetorheological finishing.

The magnetorheological finishing (MRF) of surfaces often results in tool mark errors. A prediction model can effectively guide subsequent processing, necessitating thorough research. To address this issue, this paper introduces an enhanced continuous tool influence function method. This method involves sub dwell time convolution with varying tool influence functions, enabling tool mark prediction. Numerical simulations demonstrate the proposed method's effectiveness, while the data size is estimated to confirm its economic properties. Subsequently, a MRF experiment was conducted, affirming the practicability through power spectral density evaluation. A fast algorithm is given to guide tool mark predictions on large-aperture mirrors fabrication engineering subjected to sub-aperture polishing.

Evolution mechanism of scratch removal based on the implementation of magnetorheological finishing.

Scratches on optical components induce laser damage and limit the increase in laser power. Magnetorheological finishing (MRF) is a highly deterministic optical manufacturing technology that can improve the surface roughness of optical components. Although MRF has exhibited significant potential for reducing subsurface damage and removing scratches, the principle and mechanism behind the scratch removal are not sufficiently understood. In this study, the theory of fluid mechanics is used to analyze the pressure, velocity, and particle trajectory distribution near a scratch. A physical model was developed for the differential removal of scratches at the bottom and surface of the optical components. The morphological evolution of the scratch was predicted during removal, and detailed experiments were performed to verify the effectiveness of the proposed model. The results indicate that scratches expand laterally rather than being completely removed. Furthermore, scratch removal efficiency is greater when the removal direction is perpendicular to the scratch rather than being parallel. This study offers an intrinsic perspective for a comprehensive understanding of the MRF technique used for scratch removal, which can be beneficial for removing scratches from aspherical optical systems.

Dwell time for optical fabrication using the modified discrete convolution matrix method.

More accurate dwell time calculation methods are necessary to achieve superior error convergence in producing optically critical components. Although the discrete convolution matrix method finds widespread application, it still has approximate errors in the non-uniform discrete form of tool paths. To address this issue, this paper introduced a modified matrix elements method and presented the general Voronoi polygon area weight calculation forms under different tool path discretization forms. The mechanism is explained through analysis and the validity is verified by numerical simulation. The modified method significantly improved uniformity distribution and accuracy in computation of surface residuals. This improvement holds promise as a guiding principle for the fabrication of ultra-precision optical components.

An optimized filter design approach for enhancing imaging quality in industrial linear accelerator.

BACKGROUND: The polychromatic X-rays generated by a linear accelerator (Linac) often result in noticeable hardening artifacts in images, posing a significant challenge to accurate defect identification. To address this issue, a simple yet effective approach is to introduce filters at the radiation source outlet. However, current methods are often empirical, lacking scientifically sound metrics. OBJECTIVE: This study introduces an innovative filter design method that optimizes filter performance by balancing the impact of ray intensity and energy on image quality. MATERIALS AND METHODS: Firstly, different spectra under various materials and thicknesses of filters were obtained using GEometry ANd Tracking (Geant4) simulation. Subsequently, these spectra and their corresponding incident photon counts were used as input sources to generate different reconstructed images. By comprehensively comparing the intensity differences and noise in images of defective and non-defective regions, along with considering hardening indicators, the optimal filter was determined. RESULTS: The optimized filter was applied to a Linac-based X-ray computed tomography (CT) detection system designed for identifying defects in graphite materials within high-temperature gas-cooled reactor (HTR), with defect dimensions of 2 mm. After adding the filter, the hardening effect reduced by 22%, and the Defect Contrast Index (DCI) reached 3.226. CONCLUSION: The filter designed based on the parameters of Average Difference (AD) and Defect Contrast Index (DCI) can effectively improve the quality of defect images.

Comparison of the intraarticular osteotomy and the "window" osteotomy in the treatment of tibial plateau fracture involving depressed posterolateral fragments.

OBJECTIVES: The methods of reduction of depressed posterolateral fragments in tibial plateau fracture through anterolateral approaches remain controversial. This paper aimed to compare the intraarticular osteotomy technique and the "window" osteotomy technique for the reduction of depressed posterolateral fragments through anterolateral approach. METHOD: From January 2015 to January 2022, we retrospectively reviewed the data on patients with tibial plateau fracture involving depressed posterolateral fragments treated with the intraarticular osteotomy or the "window" osteotomy. 40 patients underwent the intraarticular osteotomy were divided into group A, while 36 patients underwent the "window" osteotomy were divided into group B. The operative time, bone grafting volume, fracture healing time, complication, reduction quality and postoperative functional results were compared between the two groups. RESULTS: The average follow-up duration was 16.6 ± 3.7 months. The average bone grafting volume for all patients in group B was essential larger than group A (p = 0.001). Compared to group B, patients in groups A had significantly shorter fracture healing time (p = 0.011). The depth of depressed articular surface, PSA and the radiographic evaluation at 2 days and 6 months after surgery in group A were significantly lower than group B (p<0.05). Based on the HSS knee-rating score, no significant difference in function results was found between the two groups (p>0.05). No significant difference was found in operation time and blood loss between the two groups (p>0.05). CONCLUSION: The intraarticular osteotomy could obtain satisfactory clinical results in tibial plateau fracture involving posterolateral fragments.

Integrated Analysis of Transcriptome Expression Profiles Reveals miRNA-326-NKX3.2-Regulated Porcine Chondrocyte Differentiation.

The porcine body length trait is an essential factor affecting meat production and reproductive performance. It is evident that the development/lengthening of individual vertebrae is one of the main reasons for increases in body length; however, the underlying molecular mechanism remains unclear. In this study, RNA-seq analysis was used to profile the transcriptome (lncRNA, mRNA, and miRNA) of the thoracic intervertebral cartilage (TIC) at two time points (1 and 4 months) during vertebral column development in Yorkshire (Y) and Wuzhishan pigs (W). There were four groups: 1- (Y1) and 4-month-old (Y4) Yorkshire pigs and 1- (W1) and 4-month-old (W4) Wuzhishan pigs. In total, 161, 275, 86, and 126 differentially expressed (DE) lncRNAs, 1478, 2643, 404, and 750 DE genes (DEGs), and 74,51, 34, and 23 DE miRNAs (DE miRNAs) were identified in the Y4 vs. Y1, W4 vs. W1, Y4 vs. W4, and Y1 vs. W1 comparisons, respectively. Functional analysis of these DE transcripts (DETs) demonstrated that they had participated in various biological processes, such as cellular component organization or biogenesis, the developmental process, the metabolic process, bone development, and cartilage development. The crucial bone development-related candidate genes NK3 Homeobox 2 (NKX3.2), Wnt ligand secretion mediator (WLS), gremlin 1 (GREM1), fibroblast growth factor receptor 3 (FGFR3), hematopoietically expressed homeobox (HHEX), (collagen type XI alpha 1 chain (COL11A1), and Wnt Family Member 16 (WNT16)) were further identified by functional analysis. Moreover, lncRNA, miRNA, and gene interaction networks were constructed; a total of 55 lncRNAs, 6 miRNAs, and 7 genes formed lncRNA-gene, miRNA-gene, and lncRNA-miRNA-gene pairs, respectively. The aim was to demonstrate that coding and non-coding genes may co-regulate porcine spine development through interaction networks. NKX3.2 was identified as being specifically expressed in cartilage tissues, and it delayed chondrocyte differentiation. miRNA-326 regulated chondrocyte differentiation by targeting NKX3.2. The present study provides the first non-coding RNA and gene expression profiles in the porcine TIC, constructs the lncRNA-miRNA-gene interaction networks, and confirms the function of NKX3.2 in vertebral column development. These findings contribute to the understanding of the potential molecular mechanisms regulating pig vertebral column development. They expand our knowledge about the differences in body length between different pig species and provide a foundation for future studies.

Third-Generation Dynamic Anterior Plate-Screw System for Quadrilateral Fractures: Digital Design Based on 834 Pelvic Measurements.

Background and Objectives: To investigate the digital measurement method for the plate trajectory of dynamic anterior plate-screw system for quadrilateral plate (DAPSQ), and then design a third-generation DAPSQ plate that conforms to the needs of the Chinese population through collating a large sample anatomical data. Materials and Methods: Firstly, the length of the pubic region, quadrilateral region, iliac region, and the total length of the DAPSQ trajectory were measured by a digital measurement approach in 22 complete pelvic specimens. Then, the results were compared with the direct measurement of pelvic specimens to verify the reliability of the digital measurement method. Secondly, 504 cases (834 hemilateral pelvis) of adult pelvic CT images were collected from four medical centers in China. The four DAPSQ trajectory parameters were obtained with the digital measurement method. Finally, the third-generation DAPSQ plate was designed, and its applicability was verified. Results: There was no statistically significant difference in the four trajectory parameters when comparing the direct measurement method with the digital measurement method (p > 0.05). The average lengths of the pubic region, quadrilateral region, iliac region, and the total length in Chinese population were (60.96 ± 5.39) mm, (69.11 ± 5.28) mm, (84.40 ± 6.41) mm, and (214.46 ± 10.15) mm, respectively. Based on the measurement results, six models of the DAPSQ plate including small size (A1,A2), medium size (B1,B2), and the large size (C1,C2) were designed. The verification experiment showed that all these six type plates could meet the requirement of 94.36% cases. Conclusions: A reliable computerized method for measuring irregular pelvic structure was proposed, which not only provided an anatomical basis for the design of the third-generation DAPSQ plate, but also provided a reference for the design of other pelvic fixation devices.

A Cross-Species Reactive TIGIT-Blocking Antibody Fc Dependently Confers Potent Antitumor Effects.

The T cell immunoreceptor with Ig and ITIM domains (TIGIT) has been shown to exert inhibitory roles in antitumor immune responses. In this study, we report the development of a human mAb, T4, which recognizes both human and mouse TIGIT and blocks the interaction of TIGIT with its ligand CD155 in both species. The T4 Ab targets the segment connecting F and G strands of TIGIT's extracellular IgV domain, and we show in studies with mouse tumor models that the T4 Ab exerts strong antitumor activity and induces durable immune memory against various tumor types. Mechanistically, we demonstrate that the T4 Ab's antitumor effects are mediated via multiple immunological impacts, including a CD8+ T immune response and Fc-mediated effector functions, through NK cells that cause significant reduction in the frequency of intratumoral T regulatory cells (Tregs). Notably, this Treg reduction apparently activates additional antitumor CD8+ T cell responses, targeting tumor-shared Ags that are normally cryptic or suppressed by Tregs, thus conferring cross-tumor immune memory. Subsequent engineering for Fc variants of the T4 Ab with enhanced Fc-mediated effector functions yielded yet further improvements in antitumor efficacy. Thus, beyond demonstrating the T4 Ab as a promising candidate for the development of cancer immunotherapies, our study illustrates how the therapeutic efficacy of an anti-TIGIT Ab can be improved by enhancing Fc-mediated immune effector functions. Our insights about the multiple mechanisms of action of the T4 Ab and its Fc variants should help in developing new strategies that can realize the full clinical potential of anti-TIGIT Ab therapies.

Self-Trained Deep Forest with Limited Samples for Urban Impervious Surface Area Extraction in Arid Area Using Multispectral and PolSAR Imageries.

Impervious surface area (ISA) has been recognized as a significant indicator for evaluating levels of urbanization and the quality of urban ecological environments. ISA extraction methods based on supervised classification usually rely on a large number of manually labeled samples, the production of which is a time-consuming and labor-intensive task. Furthermore, in arid areas, man-made objects are easily confused with bare land due to similar spectral responses. To tackle these issues, a self-trained deep-forest (STDF)-based ISA extraction method is proposed which exploits the complementary information contained in multispectral and polarimetric synthetic aperture radar (PolSAR) images using limited numbers of samples. In detail, this method consists of three major steps. First, multi-features, including spectral, spatial and polarimetric features, are extracted from Sentinel-2 multispectral and Chinese GaoFen-3 (GF-3) PolSAR images; secondly, a deep forest (DF) model is trained in a self-training manner using a limited number of samples for ISA extraction; finally, ISAs (in this case, in three major cities located in Central Asia) are extracted and comparatively evaluated. The experimental results from the study areas of Bishkek, Tashkent and Nursultan demonstrate the effectiveness of the proposed method, with an overall accuracy (OA) above 95% and a Kappa coefficient above 0.90.

Open reduction and internal fixation of quadrilateral plate fractures in the elderly: association between initial fracture pattern and outcomes.

BACKGROUND: Acetabular fractures with medial displacement of the quadrilateral plate (QLP) are common in the elderly. The presence of QLP fractures greatly increase the surgical difficulty of acetabular fractures. This study aims to evaluate the clinical radiological outcomes of open reduction and internal fixation (ORIF) in QLP fractures in elderly patients and to investigate factors potentially affecting the result. METHODS: We conducted a retrospective study. A series of 37 consecutive patients with acetabular fracture involving the QLP aged 60 years and older who received ORIF between January 2010 and May 2019 were included. QLP fractures were classified according to Walid's classification system. Radiological outcomes were evaluated using Matta criteria and functional outcomes were assessed using the modified Merle d'Aubigné score. The relationships between Walid's classification and radiological or functional outcomes were analyzed. RESULTS: According to Walid's classification, 18, 13, 6 were classified as QLP1, QLP2 and QLP3, respectively. The average follow-up was 35.5 ± 10.7 months. We obtained anatomic reduction in 48.6 % (18/37) of cases, imperfect reduction in 40.5 % (15/37) of cases, and poor reduction in 10.8 % (4/37) of cases. Excellent-good functional scores were found in 83.7 % (modified Merle d'Aubigné). There were no cases of screw entering the hip, pull-out and loosening or implant failure during the follow-up. Walid's classification was positively correlated with radiological outcomes of reduction (r = 0.661; P < 0.001), and functional outcomes (r = 0.478; P = 0.003). Unsatisfactory reduction was demonstrated a correlation with the development of post-traumatic arthritis (r =-0.410; P = 0.012). CONCLUSIONS: ORIF may be suggested for quadrilateral plate fractures in the elderly. Walid's classification system is associated with the reduction quality and functional recovery.

Modified mini-incision "internal splinting" versus percutaneous repair technique of acute Achilles tendon rupture: five year retrospective case-controlled study.

PURPOSE: Several kinds of minimally invasive surgical techniques are applied to acute Achilles tendon rupture. The risks of sural never injury and re-ruptures are still major issues. The purpose of this study was to compare the middle-term results of two different minimally invasive repair techniques for acute Achille tendon rupture. METHODS: Twenty-four cases underwent the modified mini-incision "internal splinting" repair technique in group A, and 29 cases underwent a percutaneous repair technique in group B and were evaluated. The intra-operative data, complications, the time of recovery, and the post-operative magnetic resonance imaging were analyzed. At the final follow-up, the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Thermann score were evaluated. RESULTS: The mean follow-up time was 59.96 ± 4.16 months (range 48-67). At the final follow-up, the AOFAS score and Thermann score in both groups had similar feedback. No nerve injury, infection, or re-rupture was encountered in group A, except two cases with anchor irritation. One case with sural nerve injury and one with a re-rupture were recorded in group B, respectively. The final MRI showed thicker regeneration of the tendon in both groups. CONCLUSIONS: The middle-term results indicated the modified mini-incision "internal splinting" technique for acute Achilles tendon rupture is similar to the percutaneous repair technique. A lower risk of sural nerve injury and re-rupture may be advantages.

Novel Abs targeting the N-terminus of fibroblast growth factor 19 inhibit hepatocellular carcinoma growth without bile-acid-related side-effects.

Hepatocellular carcinoma (HCC) is a common and particularly fatal form of cancer for which very few drugs are effective. The fibroblast growth factor 19 (FGF19) has been viewed as a driver of HCC development and a potential Ab target for developing novel HCC therapy. However, a previously developed anti-FGF19 Ab disrupted FGF19's normal regulatory function and caused severe bile-acid-related side-effects despite of having potent antitumor effects in preclinical models. Here, we developed novel human Abs (G1A8 and HS29) that specifically target the N-terminus of FGF19. Both Abs inhibited FGF19-induced HCC cell proliferation in vitro and significantly suppressed HCC tumor growth in mouse models. Importantly, no bile-acid-related side effects were observed in preclinical cynomolgus monkeys. Fundamentally, our study demonstrates that it is possible to target FGF19 for anti-HCC therapies without adversely affecting its normal bile acid regulatory function, and highlights the exciting promise of G1A8 or HS29 as potential therapy for HCC.

Protein expression profiles in Meishan and Duroc sows during mid-gestation reveal differences affecting uterine capacity, endometrial receptivity, and the maternal-fetal Interface.

BACKGROUND: Embryonic mortality is a major concern in the commercial swine industry and primarily occurs early in gestation, but also during mid-gestation (~ days 50-70). Previous reports demonstrated that the embryonic loss rate was significant lower in Meishan than in commercial breeds (including Duroc). Most studies have focused on embryonic mortality in early gestation, but little is known about embryonic loss during mid-gestation. RESULTS: In this study, protein expression patterns in endometrial tissue from Meishan and Duroc sows were examined during mid-gestation. A total of 2170 proteins were identified in both breeds. After statistical analysis, 70 and 114 differentially expressed proteins (DEPs) were identified in Meishan and Duroc sows, respectively. Between Meishan and Duroc sows, 114 DEPs were detected at day 49, and 98 DEPs were detected at day 72. Functional enrichment analysis revealed differences in protein expression patterns in the two breeds. Around half of DEPs were more highly expressed in Duroc at day 49 (DUD49), relative to DUD72 and Meishan at day 49 (MSD49). Many DEPs appear to be involved in metabolic process such as arginine metabolism. Our results suggest that the differences in expression affect uterine capacity, endometrial matrix remodeling, and maternal-embryo cross-talk, and may be major factors influencing the differences in embryonic loss between Meishan and Duroc sows during mid-gestation. CONCLUSIONS: Our data showed differential protein expression pattern in endometrium between Meishan and Duroc sows and provides insight into the development process of endometrium. These findings could help us further uncover the molecular mechanism involved in prolificacy.

An improved mouse model of Graves disease by once immunization with Ad-TSHR289.

The novel Graves disease (GD) model was established in BALB/c mice with recombinant adenovirus expressing the full-length human TSHR (Ad-TSHR289) by three times immunizations for nearly three months. Reducing the frequency of immunizations may shorten the modeling time to improve the efficiency of the study. In this study, female BALB/c mice were immunized one time with an adenovirus expressing the autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). At the 3, 6, 12, 17 weeks after the immunization, mice were sacrificed. The blood was collected and thyroids were removed. T3, T4, TRAB and thyroid weight/body weight (TW/BW) were tested. Compared with the Normal control (NC) group, the incidence of hyperthyroidism at 3, 6, 12 and 17 weeks after immunization were about 66.67%, 100%, 100%, and 100%. Meanwhile, the incidences of goiter were nearly 50%, 83.33%, 100% and 100% at the same stages. Therefore, modeling rates of GD were about 50%, 83.33%, 100%, 100% at 3, 6, 12 and 17 weeks after immunization. T3 in serum continues to increase from 3 weeks to 17 weeks after immunization. Serum TRAb reached to peak at 6 weeks and remained from 12 weeks after immunization, while T4 and TW/BW had kept steady from 6 weeks. There are positive correlations between T3, T4 and TRAb, TRAb and TW/BW, as well as T3, T4 and TW/BW. GD model can be constructed by primary immunization with Ad-TSHR289, which could be detected at 3 weeks and at least until the 17 weeks after primary immunization. It would improve the efficiency of GD research.

Synthesis of manganese dioxide with different morphologies for thallium removal from wastewater.

Manganese dioxide (MnO2) with different morphologies (tube-, wire-, rod-, and flower-like) was synthesized via hydrothermal method and then applied for thallium (Tl) removal from wastewater. During material synthesis, short reaction time (6 h) and low temperature (110 °C) were prone to form polycrystalline flower-like birnessite type MnO2, while long reaction time (24 h) and high temperature (240 °C) were inclined to produce polycrystalline wire-like birnessite type MnO2. Moderate reaction time (12 h) with low temperature at 120 °C/140 °C led to formation of mono-crystalline rod- and tube-like α-MnO2, respectively. Wire-like MnO2 was the most effective adsorbent for Tl(I) removal from both the synthetic and industrial wastewaters. The MnO2 of four morphologies exhibited similarly high Tl(III) removal owing to the precipitation of Tl(III) as Tl2O3. Effective Tl(I)/Tl(III) removal (99%) was achieved with wire-like MnO2 at an initial pH of 6 and an adsorbent dosage of 0.25 g/L. The Tl(I)/Tl(III) adsorption can be described with the pseudo-second-order kinetic. The Tl(I) removal was best fitted with the Freundlich model, with a maximum adsorption capacity of 450 mg/g. While the Tl(III) removal was best fitted with the Langmuir model, with an extremely high capacity of 6250 mg/g. Based on the results from XRD, SEM-EDS, FT-IR, and XPS analyses, the mechanisms of Tl removal using wire-like MnO2 are primarily surface complexation and oxidative precipitation. Overall, wire-like MnO2 is a highly effective adsorbent for Tl removal from both synthetic and actual wastewaters.

Profiling the RNA editomes of wild-type C. elegans and ADAR mutants.

RNA editing increases transcriptome diversity through post-transcriptional modifications of RNA. Adenosine deaminases that act on RNA (ADARs) catalyze the adenosine-to-inosine (A-to-I) conversion, the most common type of RNA editing in higher eukaryotes. Caenorhabditis elegans has two ADARs, ADR-1 and ADR-2, but their functions remain unclear. Here, we profiled the RNA editomes of C. elegans at different developmental stages of wild-type and ADAR mutants. We developed a new computational pipeline with a "bisulfite-seq-mapping-like" step and achieved a threefold increase in identification sensitivity. A total of 99.5% of the 47,660 A-to-I editing sites were found in clusters. Of the 3080 editing clusters, 65.7% overlapped with DNA transposons in noncoding regions and 73.7% could form hairpin structures. The numbers of editing sites and clusters were highest at the L1 and embryonic stages. The editing frequency of a cluster positively correlated with the number of editing sites within it. Intriguingly, for 80% of the clusters with 10 or more editing sites, almost all expressed transcripts were edited. Deletion of adr-1 reduced the editing frequency but not the number of editing clusters, whereas deletion of adr-2 nearly abolished RNA editing, indicating a modulating role of ADR-1 and an essential role of ADR-2 in A-to-I editing. Quantitative proteomics analysis showed that adr-2 mutant worms altered the abundance of proteins involved in aging and lifespan regulation. Consistent with this finding, we observed that worms lacking RNA editing were short-lived. Taken together, our results reveal a sophisticated landscape of RNA editing and distinct modes of action of different ADARs.

Digital radiography image denoising using a generative adversarial network.

Statistical noise may degrade the x-ray image quality of digital radiography (DR) system. This corruption can be alleviated by extending exposure time of detectors and increasing the intensity of radiation. However, in some instances, such as the security check and medical imaging examination, the system demands rapid and low-dose detection. In this study, we propose and test a generative adversarial network (GAN) based x-ray image denoising method. Images used in this study were acquired from a digital radiography (DR) imaging system. Promising results have been obtained in our experiments with x-ray images for the security check application. The Experiment results demonstrated that the proposed new image denoising method was able to effectively remove the statistical noise from x-ray images, while kept sharp edge and clear structure. Thus, comparing with the traditional convolutional neural network (CNN) based method, the proposed new method generates more plausible-looking images, which contains more details.

Interaction between ribosome assembly factors Krr1 and Faf1 is essential for formation of small ribosomal subunit in yeast.

Ribosome formation in Saccharomyces cerevisiae requires a large number of transiently associated assembly factors that coordinate processing and folding of pre-rRNA and binding of ribosomal proteins. Krr1 and Faf1 are two interacting proteins present in early 90 S precursor particles of the small ribosomal subunit. Here, we determined a co-crystal structure of the core domain of Krr1 bound to a 19-residue fragment of Faf1 at 2.8 Å resolution. The structure reveals that Krr1 consists of two packed K homology (KH) domains, KH1 and KH2, and resembles archaeal Dim2-like proteins. We show that KH1 is a divergent KH domain that lacks the RNA-binding GXXG motif and is involved in binding another assembly factor, Kri1. KH2 contains a canonical RNA-binding surface and additionally associates with an α-helix of Faf1. Specific disruption of the Krr1-Faf1 interaction impaired early 18 S rRNA processing at sites A0, A1, and A2 and caused cell lethality, but it did not prevent incorporation of the two proteins into pre-ribosomes. The Krr1-Faf1 interaction likely maintains a critical conformation of 90 S pre-ribosomes required for pre-rRNA processing. Our results illustrate the versatility of KH domains in protein interaction and provide insight into the role of Krr1-Faf1 interaction in ribosome biogenesis.

The role of Pin1 protein in aging of human tendon stem/progenitor cells.

Aging of tendon stem/progenitor cells (TSPCs) can lead to tissue degeneration and subsequent injury. However, the molecular mechanisms controlling TSPC aging are not completely understood. In the present study, we investigated the role of Pin1 in aging of human TSPCs. Pin1 mRNA and protein expression levels were significantly decreased during prolonged in vitro culture of human TSPCs. Furthermore, overexpression of Pin1 delayed the progression of cellular senescence, as confirmed by downregulation of senescence-associated ß-galactosidase, increased telomerase activity and decreased levels of the senescence marker, p16(INK4A). Conversely, Pin1 siRNA transfection promoted senescence in TSPCs. In addition, miR-140-5p regulated Pin1 expression at the translational level via directly targeting its 3'UTR. Our results collectively demonstrate that Pin1 acts as an important regulator of TSPC aging.

Tendon derived stem cells promote platelet-rich plasma healing in collagenase-induced rat achilles tendinopathy.

BACKGROUND/AIMS: Tendon injuries are common, difficult to cure and usually healed with fibrosis and scar tissue. The aim of this study was to evaluate tendon derived stem cells (TDSCs) and platelet rich plasma (PRP) in the treatment of collagenase induced Achilles tendinopathy in rat. METHODS: Four and 8 weeks (n=18) after TDSCs, PRP, PRP with TDSC or PBS (control) injection into collagenase or saline (sham) injected rat Achilles tendon, tendon tissue was harvested and tendon quality was evaluated by histology and biomechanical testing. TDSCs were cultured and treated by 10% PRP, and the FAK/ERK1/2 signaling pathway and tenocyte-related genes were detected by western blot analysis. RESULTS: Compared to the control, PRP treatment resulted in better healing of injured tendons with improved histological outcomes and biomechanical functions. The addition of TDSCs to PRP treatment significantly enhanced the effects of PRP treatment alone. TDSC injection alone had little effect on tendon healing. PRP and PRP with TDSC treatments of collagenase induced tendon injuries also increased the mRNA and protein expression of tenocyte-related genes (type I collagen, SCX, Tenascin C) and activated the focal adhesion kinase (FAK) and extracellular-regulated kinase (ERK) 1/2 signaling pathways. Treatment of TDSCs in vitro with 10% PRP significantly increased the phosphorylation levels of FAK and ERK1/2 and the protein levels of tenocyte-related genes (Col I, SCX and Tenascin C). Inhibition of the FAK and ERK1/2 signaling pathways abolished the effect of PRP. CONCLUSION: This study concludes that PRP combined with TDSCs is potentially effective for the treatment of tendinopathy. The PRP induced, FAK and ERK1/2 dependent activation of tenocyte related genes in TDSCs in vitro suggests that the beneficial healing effect of the PRP with TDSC combination might occur by means of an improved TDSC differentiation toward the tenocyte lineage. Thus, a PRP with TDSC combination therapy may be clinically useful.