Regeneration of the human segmentation clock in somitoids in vitro.

Each vertebrate species appears to have a unique timing mechanism for forming somites along the vertebral column, and the process in human remains poorly understood at the molecular level due to technical and ethical limitations. Here, we report the reconstitution of human segmentation clock by direct reprogramming. We first reprogrammed human urine epithelial cells to a presomitic mesoderm (PSM) state capable of long-term self-renewal and formation of somitoids with an anterior-to-posterior axis. By inserting the RNA reporter Pepper into HES7 and MESP2 loci of these iPSM cells, we show that both transcripts oscillate in the resulting somitoids at ~5 h/cycle. GFP-tagged endogenous HES7 protein moves along the anterior-to-posterior axis during somitoid formation. The geo-sequencing analysis further confirmed anterior-to-posterior polarity and revealed the localized expression of WNT, BMP, FGF, and RA signaling molecules and HOXA-D family members. Our study demonstrates the direct reconstitution of human segmentation clock from somatic cells, which may allow future dissection of the mechanism and components of such a clock and aid regenerative medicine.

Exploring flatfeet morphology in children aged 6-12 years: relationships with body mass and body height through footprints and three-dimensional measurements.

The aim of the study was to determine the relationship between flatfoot morphology and body mass and height in children aged 6-12 years. A total of 6471 Chinese children (mean age 9.0 ± 1.9 years, 41% female) were assessed for foot morphometry, body height, and body mass index. Foot morphology, including foot length, width, girth, arch height, hallux valgus angle, and rearfoot valgus angle, was measured using a 3D laser scanner. Flatfoot evaluations were conducted using the Sztriter-Godunov index (KY) from footprints. All measurements were analyzed by age and sex using the mean values of the left and right sides. Comparisons were performed between flatfoot groups, between body mass index (BMI) groups, and between body height groups. The study revealed a significant decrease in the incidence of bipedal flatfoot with age (p < 0.001), whereas the prevalence of obesity remained consistent (p > 0.05). Bipedal flatfoot was associated with distinct morphological changes, including lower arches, reduced instep height, diminished ankle heights and a greater rearfoot valgus angle (p < 0.05). When comparing the BMI groups, overweight children had larger and thicker feet (p < 0.05), but no differences were found in arch height and ankle height (p > 0.05). When comparing the body height groups, short-statured children had a shorter feet girth, shorter arches, and shorter ankle height (p < 0.05), but no differences were found in the rearfoot valgus angle (p > 0.05). CONCLUSION: The main characteristics of flat feet include lower arches and instep heights and ankle heights but higher rearfoot valgus angles. In general, overweight children's feet do not have the common features of flat feet. In contrast, short children had similar features of flatfoot except for rearfoot valgus. Assessment of posture, such as rearfoot valgus, can be critical in identifying children with flat feet. WHAT IS KNOWN: • The morphology of children's feet is associated with body growth, but the relationship between flatfeet and body mass and height remains controversial. WHAT IS NEW: • Three-dimensional foot measurement shows that body mass is generally not associated with flatfeet, while short children have lower arches but no rearfoot valgus.

Effects of manipulations of oblique pulling on the biomechanics of the sacroiliac joint: a cadaveric study.

BACKGROUND: There are many reports on the treatment of sacroiliac joint dysfunction by manipulation of oblique pulling (MOP). However, the specific mechanism of MOP on the sacroiliac joint remains unclear. This study aimed to investigate the effect of MOP on the biomechanics of the sacroiliac joint and the effect of the anterior sacroiliac ligament on the stability of the sacroiliac joint. METHODS: First, MOP-F1 (F: force) and MOP-F2 were applied to nine cadaveric pelvises. Then, segmental resection of the anterior sacroiliac ligament was performed. The range of motion of the sacroiliac joint was observed in all procedures. RESULTS: Under MOP-F1 and F2, the average total angles were 0.84° ± 0.59° and 1.52° ± 0.83°, and the displacements were 0.61 ± 0.21 mm and 0.98 ± 0.39 mm, respectively. Compared with MOP-F1, MOP-F2 caused greater rotation angles and displacements of the sacroiliac joint (p = 0.00 and p = 0.01, respectively). In addition, the rotation angles and displacements of the sacroiliac joint significantly increased after complete resection of the anterior sacroiliac ligament (p = 0.01 and p = 0.02, respectively). The increase was mainly due to the transection of the upper part of the anterior sacroiliac ligament. CONCLUSIONS: MOP-F2 caused greater rotation angles and displacements of the sacroiliac joint and was a more effective manipulation. The anterior sacroiliac ligament played an important role in maintaining the stability of the sacroiliac joint; the upper part of the anterior sacroiliac ligament contributed more to the stability of the joint than the lower part.

A finite element analysis of sacroiliac joint displacements and ligament strains in response to three manipulations.

BACKGROUND: Clinical studies have found that manipulations have a good clinical effect on sacroiliac joint (SIJ) pain without specific causes. However, the specific mechanisms underlying the effect of manipulations are still unclear. The purpose of this study was to investigate the effects of three common manipulations on the stresses and displacements of the normal SIJ and the strains of the surrounding ligaments. METHODS: A three-dimensional finite element model of the pelvis-femur was developed. The manipulations of hip and knee flexion (MHKF), oblique pulling (MOP), and lower limb hyperextension (MLLH) were simulated. The stresses and displacements of the SIJ and the strains of the surrounding ligaments were analyzed during the three manipulations. RESULTS: MOP produced the highest stress on the left SIJ, at 6.6 MPa, while MHKF produced the lowest stress on the right SIJ, at 1.5 MPa. The displacements of the SIJ were all less than 1 mm during the three manipulations. The three manipulations caused different degrees of ligament strain around the SIJ, and MOP produced the greatest straining of the ligaments. CONCLUSION: The three manipulations all produced small displacements of the SIJ and different degrees of ligament strains, which might be the mechanism through which they relieve SIJ pain. MOP produced the largest displacement and the greatest ligament strains.

Up-regulation of microRNA-200c-3p inhibits invasion and migration of renal cell carcinoma cells via the SOX2-dependent Wnt/ß-catenin signaling pathway.

BACKGROUND: MicroRNA-200c-3p (miR-200c-3p) has been revealed to be related to renal cell carcinoma (RCC) progression, while the inner mechanisms remain unknown. In our study, we intend to unearth the capability of miR-200c-3p in RCC development via the Wnt/ß-catenin signaling pathway through binding to SOX2. METHODS: miR-200c-3p, SOX2, ß-catenin and GSK3ß expression in both tissues and cells of RCC were detected by RT-qPCR or western blot analysis. miR-200c-3p was restored or silenced to determine their biological functions of RCC cells. Expression of SOX2 and related proteins in the Wnt/ß-catenin signaling pathway were evaluated by RT-qPCR and western blot analysis. The effect of the combination of downregulated miR-200c-3p and downregulated SOX2 on cell biological behavior change was also determined. RESULTS: Initially, we found that miR-200c-3p was declined while SOX2, ß-catenin and GSK3ß was elevated in RCC tissues and cells. A498 cells with the largest difference in miR-200c-3p expression and OS-RC-2 cells with the smallest difference were selected for subsequent experiments. Additionally, upregulated miR-200c-3p and downregulated SOX2 was determined to suppress proliferation, migration, invasion and induce apoptosis of RCC cells. Furthermore, miR-200c-3p inhibited SOX2 to inactivate the Wnt/ß-catenin signaling pathway. CONCLUSION: Collectively, this study highlights that upregulated miR-200c-3p inhibits expression of SOX2, thereby inhibiting development of RCC cells via modulating the Wnt/ß-catenin signaling pathway activation.

Optimizing Performance in Supercapacitors through Surface Decoration of Bismuth Nanosheets.

Bismuth (Bi) exhibits a high theoretical capacity, excellent electrical conductivity properties, and remarkable interlayer spacing, making it an ideal electrode material for supercapacitors. However, during the charge and discharge processes, Bi is prone to volume expansion and pulverization, resulting in a decline in the capacitance. Deposition of a nonmetal on its surface is considered an effective way to modulate its morphology and electronic structure. Herein, we employed the chemical vapor deposition technique to fabricate Se-decorated Bi nanosheets on a nickel foam (NF) substrate. Various characterizations indicated that the deposition of Se on Bi nanosheets regulated their surface morphology and chemical state, while sustaining their pristine phase structure. Electrochemical tests demonstrated that Se-decorated Bi nanosheets exhibited a 51.1% improvement in capacity compared with pristine Bi nanosheets (1313 F/g compared to 869 F/g at a current density of 5 A/g). The energy density of the active material in an assembled asymmetric supercapacitor could reach 151.2 Wh/kg at a power density of 800 W/kg. These findings suggest that Se decoration is a promising strategy to enhance the capacity of the Bi nanosheets.

Manipulations of Oblique Pulling Affect Sacroiliac Joint Displacements and Ligament Strains: A Finite Element Analysis.

Objective: Clinical studies have found that manipulation of oblique pulling has a good clinical effect on sacroiliac joint pain. However, there is no uniform standard for manipulation of oblique pulling at present. The purpose of this study was to investigate the effects of four manipulations of oblique pulling on sacroiliac joint and surrounding ligaments. Methods: A three-dimensional finite element model of the pelvis was established. Four manipulations of oblique pulling were simulated. The stresses and displacements of sacroiliac joint and the strains of surrounding ligaments were analyzed under four manipulations of oblique pulling. Results: Manipulation of oblique pulling F2 and F3 caused the highest and lowest stress on the pelvis, at 85.0 and 52.6 MPa, respectively. Manipulation of oblique pulling F3 and F1 produced the highest and lowest stress on the left sacroiliac joint, at 6.6 and 5.6 MPa, respectively. The four manipulations of oblique pulling mainly produced anterior-posterior displacement. The maximum value was 1.21 mm, produced by manipulation of oblique pulling F2, while the minimal value was 0.96 mm, produced by manipulation of oblique pulling F3. The four manipulations of oblique pulling could all cause different degrees of ligament strain, and manipulation of oblique pulling F2 produced the greatest ligament strain. Conclusions: The four manipulations of oblique pulling all produced small displacements of sacroiliac joint. However, they produced different degrees of ligament strain. Manipulation of oblique pulling F2 produced the largest displacement of sacroiliac joint and the greatest ligament strain, which could provide a certain reference for physiotherapists.

Sustentaculum tali in Chinese population: anatomy and clinical significance.

BACKGROUND: Previous studies lacked adequate quantitative data on sustentaculum tali (ST), especially in Chinese population. The aims of this study are to explore the quantitative morphology of ST in dried bone specimens, and to discuss its implications related to ST screw fixation, talar articular facet variation, as well as subtalar coalitions. METHODS: A total of 965 dried intact calcanei from Chinese adult donors were evaluated. All linear parameters were measured by two observers with a digital sliding vernier caliper. RESULTS: Most parts of ST body can accommodate a commonly-used 4-mm-diameter screw, but the minimum height of anterior ST is only 4.02 mm. The shapes of the STs are slightly affected by left-right, subtalar facet, but the subtalar coalition may potentially increase the sizes of STs. The incidence of tarsal coalition is 14.09%. Among the osseous connection, there are 58.8% of type A articular surface and 76.5% of middle and posterior talar facet (MTF and PTF) involvement. ROC curve shows that subtalar coalition will be detected when ST length is greater than 16.815 mm. CONCLUSIONS: Theoretically, all the STs can accommodate 4 mm diameter screw, but a 3.5 mm diameter screw is recommended to be placed in the middle or posterior of the small ST for safety. The shapes of the STs are greatly influenced by the subtalar coalition, while they are less affected by left-right, subtalar facet. The osseous connection is common in type A articular surface and always involved in the MTF and PTF. The cut-off value of the length of STs was confirmed as 16.815 mm for predicting subtalar coalition.

Predictive Significance of the Preoperative Neutrophil-lymphocyte Ratio for Recurrence in Idiopathic Granulomatous Mastitis Patients.

BACKGROUND: To investigate and assess the correlation between inflammatory markers, such as the preoperative neutrophil-lymphocyte ratio (NLR), and the recurrence of idiopathic granulomatous mastitis (IGM). METHODS: All patients with IGM who were free of malignancy or inflammatory diseases were included in this retrospective analysis between January 2013 and December 2019. On the basis of the presence or absence of recurrence, the patients were split into two groups. After collecting retrospective data, the relationship between patient characteristics, hematological markers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), NLR, platelet-lymphocyte ratio (PLR), and white blood cell count (WBC), and their connection with postoperative recurrence were assessed utilizing univariate and multivariate analyses, receiver operating characteristic curves (ROC curves), and logistic regression. RESULTS: Recurrences occurred in 40.0% (32/80) of the 80 patients over a median follow-up duration of 35.5 months (22.0-47.8 months). The recurrent group showed higher NLR and CRP than the non-recurrent group (PNLR = .003, PCRP = .02). Neutrophil-lymphocyte ratio and postoperative recurrence were associated (correlation coefficient r = .436, P = .01). The ROC curve's ideal threshold, which had predictive value for IGM recurrence, was 2.18 (sensitivity: 46.9%; specificity: 14.6%). CONCLUSION: The preoperative NLR is a simple and affordable way to predict IGM relapse, which is important for directing clinical work.

Associations of systemic inflammation markers with myocardial enzymes in pediatric adenotonsillar hypertrophy: A cross-sectional study.

Objective: The present study aimed to investigate the relationship between systemic inflammation markers and myocardial enzymes in children with adenotonsillar hypertrophy (ATH). Methods: The levels of myocardial enzymes were detected and the systemic inflammatory biomarkers including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and systemic immune inflammation index (SII) were calculated. Regression analyses were performed and a prediction model for screening myocardial injury was established by receiver operating characteristic (ROC) curve. Results: Finally, a total of 804 children with ATH were included. After adjusting for age, BMI, fasting blood glucose and lipid profiles, both NLR and SII were significantly associated with CK-MB (p = 0.041 and 0.034, respectively) and LDH (p = 0.002 and 0.001, respectively), and PLR was associated with CK-MB (p = 0.008). In addition, NLR, SII were independently associated with hyper-LDH [OR = 1.447, 95%CI (1.063, 1.968); OR = 1.001, 95%CI (1.000, 1.002), respectively] and the associations were more significant in girls. A prediction model for hyper-LDH based on SII was developed with the area under the ROC curve of 0.715 (0.682, 0.746). Conclusion: Systemic inflammation markers were only independently associated with serum hyper-LDH in children with ATH, especially in girls. Further investigation was needed to determine the relationship between systemic inflammation with myocardial enzymes in ATH children.

Absence of associations with prefrontal cortex and cerebellum may link to early language and social deficits in preschool children with ASD.

Introduction: Autism spectrum disorder (ASD) is a complex developmental disorder, characterized by language and social deficits that begin to appear in the first years of life. Research in preschool children with ASD has consistently reported increased global brain volume and abnormal cortical patterns, and the brain structure abnormalities have also been found to be clinically and behaviorally relevant. However, little is known regarding the associations between brain structure abnormalities and early language and social deficits in preschool children with ASD. Methods: In this study, we collected magnetic resonance imaging (MRI) data from a cohort of Chinese preschool children with and without ASD (24 ASD/20 non-ASD) aged 12-52 months, explored group differences in brain gray matter (GM) volume, and examined associations between regional GM volume and early language and social abilities in these two groups, separately. Results: We observed significantly greater global GM volume in children with ASD as compared to those without ASD, but there were no regional GM volume differences between these two groups. For children without ASD, GM volume in bilateral prefrontal cortex and cerebellum was significantly correlated with language scores; GM volume in bilateral prefrontal cortex was significantly correlated with social scores. No significant correlations were found in children with ASD. Discussion: Our data demonstrate correlations of regional GM volume with early language and social abilities in preschool children without ASD, and the absence of these associations appear to underlie language and social deficits in children with ASD. These findings provide novel evidence for the neuroanatomical basis associated with language and social abilities in preschool children with and without ASD, which promotes a better understanding of early deficits in language and social functions in ASD.

Single-cell RNA sequencing reveals the developmental program underlying proximal-distal patterning of the human lung at the embryonic stage.

The lung is the primary respiratory organ in human, in which the proximal airway and the distal alveoli are responsible for air conduction and gas exchange, respectively. However, the regulation of proximal-distal patterning at the embryonic stage of human lung development is largely unknown. Here we investigated the early lung development of human embryos at weeks 4-8 post fertilization (Carnegie stages 12-21) using single-cell RNA sequencing, and obtained a transcriptomic atlas of 169,686 cells. We observed discernible gene expression patterns of proximal and distal epithelia at week 4, upon the initiation of lung organogenesis. Moreover, we identified novel transcriptional regulators of the patterning of proximal (e.g., THRB and EGR3) and distal (e.g., ETV1 and SOX6) epithelia. Further dissection revealed various stromal cell populations, including an early-embryonic BDNF+ population, providing a proximal-distal patterning niche with spatial specificity. In addition, we elucidated the cell fate bifurcation and maturation of airway and vascular smooth muscle progenitor cells at the early stage of lung development. Together, our study expands the scope of human lung developmental biology at early embryonic stages. The discovery of intrinsic transcriptional regulators and novel niche providers deepens the understanding of epithelial proximal-distal patterning in human lung development, opening up new avenues for regenerative medicine.

Anatomical parameters of sustentaculum Tali screw placement in the Asian population: A retrospective radio-anatomical study.

Purpose: This study aimed to determine the anatomical parameters of successful Sustentaculum Tali (ST) screw placement in the Asian population. Method: CT scans of unilateral feet of 110 participants were reviewed, retrospectively. The 3 D reconstruction of the calcaneus and morphometric measurements were performed by Mimics Research 19.0 and 3-Matic Research 11.0. Finally, six cadaveric feet were used for verification of the accuracy of the measurements. Results: We discovered a method to help place ST screw successfully: (1) The entry point located at the middle section of the lateral wall of posterior talar articular surface (PTAS), and the perpendicular distance from the entry point to the lateral edge of PTAS (PDEL) was 10.78 mm, (2) Screw was perpendicular to the z-axis, 66.98° to the y-axis (the longitudinal axis of the foot), (3) The length of the ST screw should be approximately 44.74 mm in male and 41.14 mm in female, and (4) The diameter of the ST screw should be approximately 4.0 mm in male and 3.5 mm in female. With this new method, all screws in six cadaveric feet were placed successfully into the middle of ST. Conclusions: In this study, we discovered a general approach to safely place ST screws in the Asian population, which may potentially help surgeons improve their success rate in surgical practice.

Melatonin Accelerates Osteoporotic Bone Defect Repair by Promoting Osteogenesis-Angiogenesis Coupling.

Previous studies have revealed that melatonin could play a role in anti-osteoporosis and promoting osteogenesis. However, the effects of melatonin treatment on osteoporotic bone defect and the mechanism underlying the effects of melatonin on angiogenesis are still unclear. Our study was aimed to investigate the potential effects of melatonin on angiogenesis and osteoporotic bone defect. Bone marrow mesenchymal stem cells (BMSCs) were isolated from the femur and tibia of rats. The BMSC osteogenic ability was assessed using alkaline phosphatase (ALP) staining, alizarin red S staining, qRT-PCR, western blot, and immunofluorescence. BMSC-mediated angiogenic potentials were determined using qRT-PCR, western blot, enzyme-linked immunosorbent assay, immunofluorescence, scratch wound assay, transwell migration assay, and tube formation assay. Ovariectomized (OVX) rats with tibia defect were used to establish an osteoporotic bone defect model and then treated with melatonin. The effects of melatonin treatment on osteoporotic bone defect in OVX rats were analyzed using micro-CT, histology, sequential fluorescent labeling, and biomechanical test. Our study showed that melatonin promoted both osteogenesis and angiogenesis in vitro. BMSCs treated with melatonin indicated higher expression levels of osteogenesis-related markers [ALP, osteocalcin (OCN), runt-related transcription factor 2, and osterix] and angiogenesis-related markers [vascular endothelial growth factor (VEGF), angiopoietin-2, and angiopoietin-4] compared to the untreated group. Significantly, melatonin was not able to facilitate human umbilical vein endothelial cell angiogenesis directly, but it possessed the ability to promote BMSC-mediated angiogenesis by upregulating the VEGF levels. In addition, we further found that melatonin treatment increased bone mineralization and formation around the tibia defect in OVX rats compared with the control group. Immunohistochemical staining indicated higher expression levels of osteogenesis-related marker (OCN) and angiogenesis-related markers (VEGF and CD31) in the melatonin-treated OVX rats. Then, it showed that melatonin treatment also increased the bone strength of tibia defect in OVX rats, with increased ultimate load and stiffness, as performed by three-point bending test. In conclusion, our study demonstrated that melatonin could promote BMSC-mediated angiogenesis and promote osteogenesis-angiogenesis coupling. We further found that melatonin could accelerate osteoporotic bone repair by promoting osteogenesis and angiogenesis in OVX rats. These findings may provide evidence for the potential application of melatonin in osteoporotic bone defect.

Appropriate Exogenous Expression Stoichiometry of GATA4 as an Important Factor for Cardiac Reprogramming of Human Dermal Fibroblasts.

Reprogramming of human dermal fibroblasts (HDFs) into induced cardiomyocyte-like cells (iCMs) represents a promising strategy for human cardiac regeneration. Different cocktails of cardiac transcription factors can convert HDFs into iCMs, although with low efficiency and immature phenotype. Here, GATA4, MEF2C, TBX5, MESP1, and MYOCD (GMTMeMy for short) were used to reprogram HDFs by retrovirus infection. We found that the exogenous expression stoichiometry of GATA4 (GATA4 stoichiometry) significantly affected reprogramming efficiency. When 1/8 dosage of GATA4 virus (GATA4 dosage) plus MTMeMy was used, the reprogramming efficiency was obviously improved compared with average pooled virus encoding each factor, which measured, by the expression level of cardiac genes, the percentage of cardiac troponin T and alpha-cardiac myosin heavy-chain immunopositive cells and the numbers of iCMs showing calcium oscillation or beating synchronously in co-culture with mouse CMs. In addition, we prepared conditioned maintenance medium (CMM) by CM differentiation of H9 human embryonic stem cell line. We found that compared with traditional maintenance medium (TMM), CMM made iCMs show well-organized sarcomere formation and characteristic calcium oscillation wave earlier. These findings demonstrated that appropriate GATA4 stoichiometry was essential for cardiac reprogramming and some components in CMM were important for maturation of iCMs.

MYOCD is Required for Cardiomyocyte-like Cells Induction from Human Urine Cells and Fibroblasts Through Remodeling Chromatin.

Despite direct reprogramming of human cardiac fibroblasts into induced cardiomyocytes (iCM) holds great potential for heart regeneration, the mechanisms are poorly understood. Whether other human somatic cells could be reprogrammed into cardiomyocytes is also unknown. Here, we report human urine cells (hUCs) could be converted into CM-like cells from different donors and the related chromatin accessibility dynamics (CAD) by assay for transposase accessible chromatin(ATAC)-seq. hUCs transduced by MEF2C, TBX5, MESP1 and MYOCD but without GATA4 expressed multiple cardiac specific genes, exhibited Ca2+ oscillation potential and sarcomeric structures, and contracted synchronously in coculture with mouse CM. Additionally, we found that MYOCD is required for both closing and opening critical loci, mainly by hindering the opening of loci enriched with motifs for the TEAD and AP1 family and promoting the closing of loci enriched with ETS motifs. These changes differ partially from CAD observed during iCM induction from human fibroblasts. Collectively, our study offers one practical platform for iCM generation and insights into mechanisms for iCM fate determination.

Biomechanical testing of three coracoclavicular ligament reconstruction techniques with a 3D printing navigation template for clavicle-coracoid drilling.

BACKGROUND: The identification and precise clavicle-coracoid drilling during coracoclavicular (CC) ligament reconstruction for acromioclavicular (AC) joint dislocation require a high level of experience and surgical skills. Furthermore, the improvement of flexible fixation, such as Endobutton techniques for CC ligament reconstructions is ongoing. We have developed a 3D printing technique navigation template for clavicle-coracoid drilling and a novel implant for the reconstruction. This study aimed to determine the efficiency of the navigation template for clavicle-coracoid drilling and to evaluate the biomechanical performance of the novel CC ligament reconstruction technique. METHODS: A total of 24 fresh-frozen human cadaveric shoulders were randomly assigned to 1 of 3 reconstruction groups or a control group: TightRope, Triple Endobutton, and the Adjustable Closed-Loop Double Endobutton technique. Computed tomography scans, navigation template designs, and 3D printing were performed for the shoulders. Then, AC joint dislocation was simulated in the reconstruction groups, and 3 CC ligament reconstruction techniques were operated via the 3D printing template separately. Furthermore, biomechanical protocols including the translation test (load from 5 to 70 N) and the load-to-failure test were performed to characterize the behaviors and strengths. One-way ANOVA test analyzed differences in displacement under the translation load and the load at failure. RESULTS: CC ligament reconstructions were performed successfully along with the 3D printing navigation template in the 3 reconstruction groups. During the translation test, no significant difference was found in displacements among the 4 groups. Meanwhile, the mean load of all reconstruction groups at failure (Adjustable Closed-Loop Double Endobutton, 722.1620 N; TightRope, 680.4020 N; Triple Endobutton, 868.5762 N) was significantly larger than the control group (564.6264 N, P<0.05). The Triple Endobutton group had the maximum load at failure (P<0.05), however, no significant difference was noticed between the other 2 reconstruction groups (P>0.05). CONCLUSIONS: The 3D printing navigation template may become helpful and reliable for AC joint dislocation surgery. Among the 3 CC ligament reconstruction techniques, the Triple Endobutton technique has the best strength in terms of biomechanics, while the biomechanical strength of the Adjustable Closed-Loop Double Endobutton technique is reliable in comparison with the TightRope technique.

Forkhead box family transcription factors as versatile regulators for cellular reprogramming to pluripotency.

Forkhead box (Fox) transcription factors play important roles in mammalian development and disease. However, their function in mouse somatic cell reprogramming remains unclear. Here, we report that FoxD subfamily and FoxG1 accelerate induced pluripotent stem cells (iPSCs) generation from mouse fibroblasts as early as day4 while FoxA and FoxO subfamily impede this process obviously. More importantly, FoxD3, FoxD4 and FoxG1 can replace Oct4 respectively and generate iPSCs with germline transmission together with Sox2 and Klf4. On the contrary, FoxO6 almost totally blocks reprogramming through inhibiting cell proliferation, suppressing the expression of pluripotent genes and hindering the process of mesenchymal to epithelial transition (MET). Thus, our study uncovers unexpected roles of Fox transcription factors in reprogramming and offers new insights into cell fate transition.