Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis.

Craniosynostosis results from premature fusion of the cranial suture(s), which contain mesenchymal stem cells (MSCs) that are crucial for calvarial expansion in coordination with brain growth. Infants with craniosynostosis have skull dysmorphology, increased intracranial pressure, and complications such as neurocognitive impairment that compromise quality of life. Animal models recapitulating these phenotypes are lacking, hampering development of urgently needed innovative therapies. Here, we show that Twist1+/- mice with craniosynostosis have increased intracranial pressure and neurocognitive behavioral abnormalities, recapitulating features of human Saethre-Chotzen syndrome. Using a biodegradable material combined with MSCs, we successfully regenerated a functional cranial suture that corrects skull deformity, normalizes intracranial pressure, and rescues neurocognitive behavior deficits. The regenerated suture creates a niche into which endogenous MSCs migrated, sustaining calvarial bone homeostasis and repair. MSC-based cranial suture regeneration offers a paradigm shift in treatment to reverse skull and neurocognitive abnormalities in this devastating disease.

Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate renal fibrosis in diabetic nephropathy by targeting Hedgehog/SMO signaling.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. Currently, there are no effective drugs for the treatment of DN. Although several studies have reported the therapeutic potential of mesenchymal stem cells, the underlying mechanisms remain largely unknown. Here, we report that both human umbilical cord MSCs (UC-MSCs) and UC-MSC-derived exosomes (UC-MSC-exo) attenuate kidney damage, and inhibit epithelial-mesenchymal transition (EMT) and renal fibrosis in streptozotocin-induced DN rats. Strikingly, the Hedgehog receptor, smoothened (SMO), was significantly upregulated in the kidney tissues of DN patients and rats, and positively correlated with EMT and renal fibrosis. UC-MSC and UC-MSC-exo treatment resulted in decrease of SMO expression. In vitro co-culture experiments revealed that UC-MSC-exo reduced EMT of tubular epithelial cells through inhibiting Hedgehog/SMO pathway. Collectively, UC-MSCs inhibit EMT and renal fibrosis by delivering exosomes and targeting Hedgehog/SMO signaling, suggesting that UC-MSCs and their exosomes are novel anti-fibrotic therapeutics for treating DN.

Odontogenic infections in the antibiotic era: approach to diagnosis, management, and prevention.

PURPOSE: The prevalence of odontogenic infections remains one of the highest in the world. If untreated, odontogenic infections can break through the limitation, disseminate to other organs or spaces, and cause high mortality rates. However, it is still difficult to rapidly target limited or disseminated infections in clinical practice. The type of disseminated odontogenic infections and the responsible bacteria have not been described in detail. METHODS: Search databases (e.g., PubMed, MEDLINE, Web of Science, Embase) for reports published from 2018.1 to 2022.9. Use search strategies: ("odontogenic infections" OR "pulpitis" OR "periapical lesions" OR "periodontal diseases") AND ("disseminated infections" OR "complication"). RESULTS: Fourteen different types of disseminated odontogenic infections, most of which are polymicrobial infections, can spread through the body either direct or through hematogenous diffusion. Multiple microbial infections can be more invasive in the transmission of infection. Secondary infections are commonly associated with bacteria like Fusobacterium spp., Streptococcus spp., Peptostreptococcus spp., Prevotella spp., and Staphylococcus spp. Antibiotics with broad-spectrum activity are fundamental as first-line antimicrobial agents based on the microorganisms isolated from disseminated infections. CONCLUSION: This review elaborates on the epidemiology, microorganisms, risk factors, and dissemination routes, and provides evidence-based opinions on the diagnosis, multidisciplinary management, and prevention of odontogenic infections for dentists and clinicians.

Clinical accuracy of partially guided implant placement in edentulous patients: A computed tomography-based retrospective study.

OBJECTIVES: This retrospective study was intended to evaluate the clinical accuracy of partially guided template in guiding implant placement in edentulous patients. METHODS: A total of 120 implants were placed in 24 patients with at least one completely edentulous arch with a partially guided system. Based on CBCT data, a repeatable method was used to measure linear and angular deviations of implants at 3D level in Mimics medical software. The influence of supporting tissue and implant region on the accuracy was assessed, followed by the evaluation of direction of linear deviations in biologically vital areas. RESULTS: Linear deviations of all implants were 1.91 ± 0.68 mm, 1.47 ± 0.68 mm, and 1.02 ± 0.69 mm at apical, apical lateral, and apical vertical levels. When at the cervical, cervical lateral, and cervical vertical levels, the linear deviations were 1.53 ± 0.65 mm, 0.98 ± 0.53 mm, and 1.01 ± 0.69 mm, respectively. Angular deviation of all implants was 7.14 ± 3.41°. Implants guided by mucosa + tooth-supported templates showed higher linear deviations at apical vertical level (1.21 ± 0.72 mm vs. 0.86 ± 0.63 mm, p < .05) and cervical vertical level (1.18 ± 0.72 mm vs. 0.87 ± 0.63 mm, p < .05) than mucosa-supported templates, and implants in maxilla were found higher angular deviation than mandible (7.89 ± 3.61° vs. 6.29 ± 2.97°, p < .05). CONCLUSIONS: The partially guided template served as clinically viable surgical assistance in implant placement in edentulous patients. When using mucosa + tooth-supported template or placing implants in maxilla, more caution was required, especially in biologically vital areas.

Comparative evaluation of transverse width indices for diagnosing maxillary transverse deficiency.

OBJECTIVES: This study aimed to compare and evaluate different transverse width indices for diagnosing maxillary transverse deficiency (MTD), a common malocclusion characterized by uncoordinated dental arches, crossbites, and tooth crowding. MATERIALS AND METHODS: Sixty patients aged 7-12 years were included in the study, with 20 patients diagnosed with MTD and 40 normal controls. Transverse width indices, including maxillary width at the buccal alveolar crest and lingual midroot level, as well as at the jugal process width, were measured. Differences between these indices and their corresponding mandibular indices were used as standardized transverse width indices. The reference range of these indices was determined and evaluated. Receiver operating characteristic (ROC) analysis was performed to evaluate their diagnostic ability. RESULTS: The transverse width indices and standardized transverse width indices of the MTD group were significantly smaller than those of the control group, except for the jugal process width. The evaluation of the reference range and ROC analysis revealed that the difference of the maxillomandibular width at buccal alveolar crest was the most accurate diagnostic method. CONCLUSIONS: The jugal point analysis method may not be suitable for diagnosing MTD. Instead, measuring the difference in maxillomandibular width at the buccal alveolar crest proves to be a more reliable and accurate diagnostic method for MTD.

Anatomy and function of the canalis sinuosus and its injury prevention and treatment strategies in implant surgery. / çª¦ç®¡çš„è§£å‰–ä¸ŽåŠŸèƒ½åŠå ¶åœ¨ç§æ¤æœ¯ä¸­æŸä¼¤çš„é˜²æ²»ç­–ç•¥.

The canalis sinuosus, a canal containing the anterior superior alveolar nerve bundle, originates from the infraorbital canal and extends along the maxillary sinus and nasal cavity edges to the anterior maxilla. It was once regarded as an anatomical variation. However, with the widespread application of cone beam computed tomography (CBCT), the detection rate of canalis sinuosus in the population has increased. The canalis sinuosus exhibits diverse courses, branching into multiple accessory canals and terminating at the nasal floor or the anterior tooth region, with the majority traversing the palatal side of the central incisor. The anterior superior alveolar nerve bundle within the canalis sinuosus not only innervates and nourishes the maxillary anterior teeth, their corresponding soft tissues, and the maxillary sinus mucosa, but also relates to the nasal septum, lateral nasal wall, and parts of the palatal mucosa. To minimize surgical complications, implantologists need to investigate strategies for preventing and treating canalis sinuosus injuries. Preoperatively, implantologists should use CBCT to identify the canalis sinuosus and virtually design implant placement at a distance of more than 2 mm from the canalis sinuosus. Intraoperatively, implantologists should assess bleeding and patient comfort, complemented by precision surgical techniques such as the use of implant surgical guide plates. Postoperatively, CBCT can be employed to examine the relationship between the implant and the canalis sinuosus, and treatment of canalis sinuosus injuries can be tailored based on the patient's symptoms. This review summarizes the detection of canalis sinuosus in the population, its anatomical characteristics, and its physiological functions in the anterior maxilla, and discusses strategies for effectively avoiding canalis sinuosus injuries during implant surgery, thereby enhancing implantologists' awareness and providing references for clinical decision-making.

Biodegradable Microelectrodes for Monitoring the Dynamics of Extracellular Ca2+ in Rat Brain.

In vivo electrochemical analysis is of great significance in understanding the dynamics of various physiological and pathological activities. However, the conventional microelectrodes for electrochemical analysis are rigid and permanent, which comes with increased risks for long-term implantation and secondary surgery. Here, we develop one biodegradable microelectrode for monitoring the dynamics of extracellular Ca2+ in rat brain. The biodegradable microelectrode is prepared by sputtering gold nanoparticles (AuNPs) on a wet-spun flexible poly(l-lactic acid) (PLLA) fiber for conduction and transduction and coating a Ca2+ ion-selective membrane (ISM) with a PLLA matrix on the PLLA/AuNPs fiber, forming PLLA/AuNPs/Ca2+ISME (ISME = ion-selective microelectrode). The prepared microelectrode shows excellent analytical properties including a near-Nernst linear response toward Ca2+ over the concentration range from 10 µM to 50 mM, good selectivity, and long-term stability for weeks as well as biocompatibility and biodegradability. The PLLA/AuNPs/Ca2+ISME can monitor the dynamics of extracellular Ca2+ following spreading depression induced by high potassium even if in the fourth day. This study provides a new design strategy for the biodegradable ISME and promotes the development of biodegradable microelectrodes for long-term monitoring of chemical signals in brain.

Biocompatible Microelectrode for In Vivo Sensing with Improved Performance.

In vivo sensing based on implantable microelectrodes has been widely used to monitor neurochemicals due to its high spatial and temporal resolution and engineering interface designability, which has become a powerful drive to decode the mysteries of degenerative diseases and regulate neural activity. Over the past few decades, with the development of a variety of advanced materials and technologies, encouraging progress has been made in quantifying various neurochemical transients. However, because of the complex chemical atmosphere including thousands of small and large biomolecules and the inherent low mechanical property of brain tissue, the design of a compatible microelectrode for the in vivo electrochemical tracking of neurochemicals with high selectivity and stability still faces great challenges. This Perspective presents a brief account of recent representative progress in the rational regulation of the microelectrode interface to resolve the questions of selectivity and sensitive decrease resulting from antiprotein adsorption, and how to decrease the mechanical mismatch of an implanted electrode with that of brain tissue. Possible future research directions on further addressing the above key issues and a more biocompatible microelectrode for in vivo long-time electrochemical analysis are also discussed.

Design and experimental study on closed-loop process of preparing chitosan from crab shells.

The purpose of this article is to design a green and comprehensive utilization process for preparing chitosan from crab shells. Glutamate acid was used as a decalcifying agent for crab shells, and the mixed solution of potassium hydroxide/isopropanol was used for deproteinization and deacetylation to prepare chitosan. Glutamic acid and isopropanol could be recovered for recycling. At the same time, calcium carbonate and protein in crab shells were converted into calcium hydrogen phosphate and compound fertilizer containing nitrogen, phosphorus, and potassium, respectively. The prepared chitosan was characterized by Fourier-transform infrared (FT-IR), differential scanning calorimetry (DSC), x-ray diffraction (XRD), and scanning electron microscopy (SEM), and its deacetylation degree and viscosity average molecular weight were 88.7% ± 0.68% and 792.1 ± 10.82 kDa, respectively. The recoveries of glutamic acid and isopropanol were 95.56% ± 1.39% and 88.14% ± 1.13%, respectively. The prepared chitosan has large molecular weight and deacetylation degree, controllable production cost, comprehensive utilization of crab shell components, and greatly reduced waste emissions.

Clinical features and markers to identify pulmonary lesions caused by infection or vasculitis in AAV patients.

OBJECTIVES: Pulmonary lesion is frequently seen in ANCA-associated vasculitis (AAV) patients primarily due to AAV lung involvement or infection, which are hard to differentiate due to their high similarity in clinical manifestations. We aimed to analyze the clinical features of pulmonary lesions consequent to AAV involvement or infection in AAV patients and further identify the markers for differential diagnosis. METHODS: 140 AAV patients who admitted to the Renmin Hospital of Wuhan University from January 2016 to July 2021 were included in this study. According to the nature of lung conditions, these patients were divided into the non-pulmonary lesion group, the lung infection group and the non-pulmonary infection group, and their demographics, clinical symptoms, imaging features, as well as laboratory findings were compared. A receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of single biomarker and composite biomarkers on pulmonary infection was then evaluated. RESULTS: The patients in the lung infection group were significantly older than those in the no lesion group (63.19 ± 14.55 vs 54.82 ± 15.08, p = 0.022). Patients in the lung infection group presented more frequent symptoms and more obvious pulmonary image findings. Compared with patients in the non-pulmonary infection group, patients in the lung infection group showed a higher symptom incidence of fever, chest tightness, cough and expectoration, and hemoptysis (52.94% vs 16.00%, 61.76% vs 40.00%, 72.06% vs 46.00%, 27.94% vs 8.00%, p < 0.05, respectively), and more changes in pulmonary CT scanning images in terms of patched/striped compact opacity, alveolar hemorrhage, bronchiectasis, pleural effusion, as well as mediastinal lymphadenopathy (89.71% vs 52.00%, 11.76% vs 2.00%, 22.06% vs 8.00%, 50.00% vs 20.00%, 48.53% vs 24.00%, p < 0.05, respectively). In addition, patients in the lung infection group had significantly higher levels of serum pro-calcitonin (PCT), C-reactive protein (CRP), amyloid A (SAA), blood neutrophil-to-lymphocyte ratio (NLCR), erythrocyte sedimentation rate (ESR), as well as Birmingham vasculitis activity score (BVAS) than patients in the other two groups (p < 0.05). Among all biomarkers, PCT exhibited the highest diagnostic efficacy (0.928; 95%CI 0.89-0.97) for pulmonary infected AAV patients at a cut-off score of 0.235 ng/ml with 85.3% sensitivity and 84% specificity. Moreover, the composite biomarker of PCT-CRP-NLCR showed more diagnostic efficacy (0.979; 95% CI 0.95-1.00) in distinguishing the infectious and non-infectious lung injuries in AAV patients. CONCLUSIONS: AAV patients with lung infection manifested more clinical symptoms and prominent lung image changes. The PCT and composite biomarker PCT-CRP-NLCR showed high diagnostic efficacy for a lung infection in AAV patients. Pulmonary lesion caused by either infection or AAV involvement is commonly seen and difficult to distinguish. We aim to identify the biomarkers that can be applied in the differentiation diagnosis of pulmonary lesions in AAV patients.

Research progress in effect of chewing-side preference on temporomandibular joint and its relationship with temporo-mandibular disorders. / åä¾§å’€åš¼å¯¹é¢žä¸‹é¢Œå ³èŠ‚ç»“æž„çš„å½±å“åŠå ¶ä¸Žé¢žä¸‹é¢Œå ³èŠ‚ç´Šä¹±çš„å ³ç³».

Chewing-side preference is one of the risk factors for temporomandibular disorders (TMD), and people with chewing-side preference is more prone to have short and displaced condyles, increased articular eminence inclination and glenoid fossa depth. The proportion of TMD patients with chewing-side preference is often higher than that of the normal subjects. Clinical studies have shown a strong correlation between chewing-side preference and TMD symptoms and signs; and animal studies have shown that chewing-side preference can affect the growth, development, damage and repair of the mandible. After long-term unilateral mastication, changes in the stress within the joint cause the imbalance of temporomandibular joint (TMJ) structural reconstruction, the transformation and even destruction of the fiber structure of masticatory muscle, resulting in uncoordinated movement of bilateral muscles. The joint neurogenic diseases caused by the increase of neuropeptide substance P and calcitonin-gene-related-peptide (CGRP) released locally by TMJ may be the mechanism of TMD. This article reviews the research progress of the influence of chewing-side preference on the structure of TMJ, the relationship between chewing-side preference and TMD, and the related mechanisms.

Correlating Oxidation State and Surface Ligand Motifs with the Selectivity of CO2 Photoreduction to C2 Products.

The design for non-Cu-based catalysts with the function of producing C2+ products requires systematic knowledge of the intrinsic connection between the surface state as well as the catalytic activity and selectivity. In this work, photochemical in situ spectral surface characterization techniques combined with the first principle calculations (DFT) were applied to investigate the relationships between the composition of surface states, coordinated motifs, and catalytic selectivity of a titanium oxynitride catalyst. When the catalyst mediates CO2 photoreduction, C2 product selectivity is positively correlated with the surface Ti2+ /Ti3+ ratio and the surface oxidation state is regulated and controlled by coordinated motifs of N-Ti-O/V[O], which can reduce the potential dimerization energy barriers of *CO-CO* and promote spontaneous formation of the subsequent *CO-CH2 * intermediate. This phenomenon provides a new perspective for the design of heterogeneous catalysts for photoreduction of CO2 into useful products.

Pathogenic variant of DYNC2H1 associated with lingual hamartoma in a Chinese pedigree.

BACKGROUND: Molecular etiology of lingual hamartoma is poorly understood. This study aims to identify potentially deleterious mutations for lingual hamartoma and analyze its molecular profile by a combination of whole-exome sequencing and RNA-sequencing. METHODS: Whole-exome sequencing was conducted on the proband presenting lingual hamartoma and patient's unaffected family members. Potentially pathogenic mutations were identified after filtration. The pathogenicity of the identified variants was predicted by in silico algorithms and conservative analysis. RNA-sequencing was performed to further explore the molecular profile of lingual hamartoma. RESULTS: Whole-exome sequencing of the proband and patients' unaffected brother and parents identified a de novo mutation c.931C>T_p.Pro311Ser in the DYNC2H1 gene (NM_001080463.2). The DYNC2H1 mutation was predicted to be disease-causing for affecting highly conserved amino acid by PolyPhen2 and Mutation Taster. RNA-sequencing analysis showed that the DYNC2H1 gene was significantly down-regulated in lingual hamartoma. Gene set enrichment analysis revealed cilium assembly and Hedgehog signaling pathway were significantly affected. CONCLUSION: The study expanded our knowledge on the clinical and genetic spectrum of lingual hamartoma by identifying causal variants in a Chinese pedigree. DYNC2H1 is likely to participate in tongue development and its pathologic mutation may underlie the etiology of lingual hamartoma.

Shikonin enhances chemosensitivity of oral cancer through ß-catenin pathway.

OBJECTIVES: This study concentrates on exploring the synergistic effect of shikonin on cisplatin against oral cancer. METHODS: To analyze the IC50 value of shikonin, gradient concentrations of shikonin were added to the oral cancer cell culture medium. After the cisplatin-resistant cell line was established, the effects of cisplatin and shikonin on the survival rate, proliferation, apoptosis and related pathway protein expression of common/drug-resistant oral cancer cells were compared through MTT, clone formation, flow cytometry, and Western blot experiments. ß-catenin, which had the most significant expression changes, was overexpressed and silenced, and used to design a reverse validation. RESULTS: Shikonin inhibited the viability of oral cancer cells. Although cisplatin killed some cancer cells, its effect on drug-resistant cancer cells was significantly reduced. The addition of shikonin enhanced the sensitivity of drug-resistant cells to cisplatin. Shikonin regulated key proteins in cell proliferation and apoptosis-related pathways. Among them, shikonin generated the most evident inhibitory effect on ß-catenin. Therefore, ß-catenin overexpression plasmid/siß-catenin was transfected into the cells. Silenced ß-catenin was found to reinforce the damaging effect of cisplatin on cancer cells, and overexpressed ß-catenin reversed the effect of shikonin. CONCLUSION: By down-regulating ß-catenin expression, shikonin improves the sensitivity of drug-resistant oral cancer cells to cisplatin.

A Potential Complication After Drainage in Odontogenic Descending Necrotizing Mediastinitis: Chyle Leakage.

ABSTRACT: Descending necrotizing mediastinitis is a serious complication of odontogenic infections. Incision and drainage of the maxillofacial infection with mediastinal drainage represent the principal management. However, chyle leakage after drainage in descending necrotizing mediastinitis is rare and has not been reported. Here the authors present a case of a 74-year-old man with chyle leakage after mediastinal drainage, which is successfully treated.

circSLC41A1 Resists Porcine Granulosa Cell Apoptosis and Follicular Atresia by Promoting SRSF1 through miR-9820-5p Sponging.

Ovarian granulosa cell (GC) apoptosis is the major cause of follicular atresia. Regulation of non-coding RNAs (ncRNAs) was proved to be involved in regulatory mechanisms of GC apoptosis. circRNAs have been recognized to play important roles in cellular activity. However, the regulatory network of circRNAs in follicular atresia has not been fully validated. In this study, we report a new circRNA, circSLC41A1, which has higher expression in healthy follicles compared to atretic follicles, and confirm its circular structure using RNase R treatment. The resistant function of circSLC41A1 during GC apoptosis was detected by si-RNA transfection and the competitive binding of miR-9820-5p by circSLC41A1 and SRSF1 was detected with a dual-luciferase reporter assay and co-transfection of their inhibitors or siRNA. Additionally, we predicted the protein-coding potential of circSLC41A1 and analyzed the structure of circSLC41A1-134aa. Our study revealed that circSLC41A1 enhanced SRSF1 expression through competitive binding of miR-9820-5p and demonstrated a circSLC41A1-miR-9820-5p-SRSF1 regulatory axis in follicular GC apoptosis. The study adds to knowledge of the post-transcriptional regulation of follicular atresia and provides insight into the protein-coding function of circRNA.

Necroptosis in pathogenesis of osteoarthritis and its therapeutic implications.

Osteoarthritis is a progressive degenerative joint disease induced by many causes, for which there is no radical cure currently. Necroptosis is a newly reported programmed cell death, and its related factors are also inseparable from the progress of osteoarthritis. For examples, damage-associated molecular pattern promotes the release of various inflammatory factors, so as to recruit macrophages and promote local inflammation of the joint; inhibition of receptor-interacting protein kinase can reduce the death of cell and the expression of inflammatory factors, so as to reduce cartilage damage. Therefore, in-depth study of the regulatory mechanism of necroptosis in osteoarthritis will help to further reveal the pathogenesis of osteoarthritis, so as to provide potential targets for the treatment of osteoarthritis.

Anemia is associated with severe illness in COVID-19: A retrospective cohort study.

Anemia commonly aggravates the severity of respiratory diseases, whereas thus far, few studies have elucidated the impact of anemia on coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the clinical characteristics of patients with anemia, and to further explore the relationship between anemia and the severity of COVID-19. In this single-center, retrospective, observational study, a total of 222 confirmed patients admitted to Wuhan Ninth Hospital from 1 December 2019 to 20 March 2020 were recruited, including 79 patients with anemia and 143 patients without anemia. Clinical characteristics, laboratory findings, disease progression and prognosis were collected and analyzed. Risk factors associated with the severe illness in COVID-19 were established by univariable and multivariable logistic regression models. In our cohort, compared to patients without anemia, patients with anemia were more likely to have one or more comorbidities and severe COVID-19 illness. More patients demonstrated elevated levels of C-reactive protein (CRP), procalcitonin (PCT) and creatinine in anemia group. Levels of erythrocyte sedimentation rate, D-dimer, myoglobin, T-pro brain natriuretic peptide (T-pro-BNP) and urea nitrogen in patients with anemia were significantly higher than those without. In addition, the proportion of patients with dyspnea, elevated CRP, and PCT was positively associated with the severity of anemia. The odd ratio of anemia related to the severe condition of COVID-19 was 3.47 (95% confidence interval [CI]: 1.02-11.75; P = .046) and 3.77 (95% CI: 1.33-10.71; P = .013) after adjustment for baseline date and laboratory indices, respectively. Anemia is an independent risk factor associated with the severe illness of COVID-19, and healthcare professionals should be more sensitive to the hemoglobin levels of COVID-19 patients on admission. Awareness of anemia as a risk factor for COVID-19 was of great significance.

KLF2+ stemness maintains human mesenchymal stem cells in bone regeneration.

Mesenchymal stem cells (MSCs), which are undifferentiated stem cells with the property of stemness and the potential to differentiate into multiple lineages, including osteoblasts, have attracted a great deal of attention in bone tissue engineering. Consistent with the heterogeneity of MSCs, various surface markers have been used. However, it is still unclear which markers of MSCs are best for cell amplification in vitro and later bone regeneration in vivo. Krüppel-like Factor 2 (KLF2) is an important indicator of the stemness of human MSCs (hMSCs) and as early vascularization is also critical for bone regeneration, we used KLF2 as a novel in vitro marker for MSCs and investigated the angiogenesis and osteogenesis between KLF2+ MSCs and endothelial cells (ECs). We found a synergistic interaction between hMSCs and human umbilical vein ECs (HUVECs) in that KLF2+ stemness-maintained hMSCs initially promoted the angiogenesis of HUVECs, which in turn more efficiently stimulated the osteogenesis of hMSCs. In fact, KLF2+ hMSCs secreted angiogenic factors initially, with some of the cells then differentiating into pericytes through the PDGF-BB/PDGFR-ß signaling pathway, which improved blood vessel formation. The matured HUVECs in turn synergistically enhanced the osteogenesis of KLF2+ hMSCs through upregulated vascular endothelial growth factor. A three-dimensional coculture model using cell-laden gelatin methacrylate (GelMA) hydrogel further confirmed these results. This study provides insight into the stemness-directed synergistic interaction between hMSCs and HUVECs, and our results will have a profound impact on further strategies involving the application of KLF2+ hMSC/HUVEC-laden GelMA hydrogel in vascular network bioengineering and bone regeneration.

A Retrospective Study of 158 Cases on the Risk Factors for Recurrence in Ameloblastoma.

Background: Ameloblastoma is an odontogenic tumor occurring in jaws, with local aggressiveness and postoperative recurrence. This study was aim to investigate the clinical and radiographic risk factors for recurrence in ameloblastoma. Methods: Patients diagnosed with ameloblastoma between March 2009 and March 2019 were retrospectively analyzed. Clinical and Radiological data and follow-up records were collected. Survival analyses were performed by Kaplan-Meier and log-rank tests, as well as Cox proportional hazards model. Results: One hundred and fifty-eight patients (104 males and 54 females were enrolled. The overall recurrence rate for ameloblastoma was 13.29%, and 10.76% recurred within 5 years. Most of the tumors were located in mandible (86.71%), while the rest 21 cases were in maxilla (13.29%). More than half cases (55.06%) showed multilocular radiolucency, 61 cases (38.61%) showed unilocular radiolucency. Significant differences were found with amelobastoma recurrence rate related to treatment modality, impacted tooth and root resorption (P =0.002, 0.022 and 0.007 respectively). Conclusions: Treatment modality, impacted tooth and root resorption all showed statistically significant associations with the recurrence rate in ameloblastoma. However, due to the limitation of this study, further studies are needed to reveal the true mechanism of ameloblastoma recurrence.