Radiographic outcomes of lateral sinus floor elevation at sites without perforations and sites with perforations managed with a resorbable membrane: A retrospective study.

AIM: To evaluate the radiographic outcomes of lateral sinus floor elevation with simultaneous implant placement at sites without sinus membrane perforation (SMP) and sites with SMP managed with a resorbable membrane. MATERIALS AND METHODS: One hundred and thirty-nine patients and 170 implants (56 perforation, 114 non-perforation) were included. Cone-beam computed tomography (CBCT) images were taken before surgery (T0), immediately after surgery (T1) and 6 months after surgery (T2). Post-operative augmentation parameters, including endo-sinus bone gain (ESBG) along the implant axis, mean new bone height (NBH) surrounding the implant and augmentation volume (AV), were measured at T1 and T2. RESULTS: At T1, there were no significant differences in ESBG, NBH and AV between the two groups. At T2, although ESBG did not significantly differ between the two groups, NBH (8.50 ± 1.99 mm vs. 9.99 ± 2.52 mm, p = .039) and AV (519.37 ± 258.38 mm3 vs. 700.99 ± 346.53 mm3, p < .001) were significantly lower in the perforation group. The shrinkage of graft material from T1 to T2, including ΔESBG (p = .002), ΔNBH (p < .001) and ΔAV (p < .001), was higher in the perforation group. CONCLUSIONS: SMP during LSFE with simultaneous implant placement is associated with greater resorption of the grafted area at a 6-month follow-up.

The high-bone-mass phenotype of novel transgenic mice with LRP5 A241T mutation.

Gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) can cause high-bone-mass (HBM) phenotype, with 19 identified mutations so far. The A242T mutation in LRP5 has been found in 9 families, making it one of the most prevalent mutations. However, the correlation between the A242T mutation and HBM phenotype remains unverified in animal models. This study aimed to investigate the bone properties in a new transgenic mouse model carrying the LRP5 A241T missense mutation, equivalent to A242T in humans. Heterozygous Lrp5A241T mice were generated using CRISPR/Cas9 genome editing. Body weight increased with age from 4 to 16 weeks, higher in males than females, with no difference between Lrp5A241T mice and wild-type control. Micro-CT showed slightly longer femur and notably elevated trabecular bone mass of the femur and fifth lumbar spine with higher bone mineral density, bone volume fraction, and trabecular thickness in Lrp5A241T mice compared to wild-type mice. Additionally, increased cortical bone thickness and volume of the femur shaft and skull were observed in Lrp5A241T mice. Three-point bending tests of the tibia demonstrated enhanced bone strength properties in Lrp5A241T mice. Histomorphometry confirmed that the A241T mutation increased bone formation without affecting osteoblast number and reduced resorption activities in vivo. In vitro experiments indicated that the LRP5 A241T mutation enhanced osteogenic capacity of osteoblasts with upregulation of the Wnt signaling pathway, with no significant impact on the resorptive activity of osteoclasts. In summary, mice carrying the LRP5 A241T mutation displayed high bone mass and quality due to enhanced bone formation and reduced bone resorption in vivo, potentially mediated by the augmented osteogenic potential of osteoblasts. Continued investigation into the regulatory mechanisms of its bone metabolism and homeostasis may contribute to the advancement of novel therapeutic strategies for bone disorders.

The mediating role of sugar and lipid metabolism and systemic inflammation in the association between breakfast skipping and periodontitis: A population-based study.

BACKGROUND: This study investigated the association between breakfast skipping and periodontitis and the mediating role of sugar and lipid metabolism and systemic inflammation in this association using data from the Korea National Health and Nutrition Examination Survey 2016-2018. METHODS: This study included 11,953 participants, representing an estimated 33.9 million people. Complex sample logistic regression was used to assess the independent association between breakfast skipping and periodontitis. Subgroup analysis was conducted with modifiers including age, sex, body mass index (BMI), urban residence, education level, marital status, and diabetes. Structural equation modeling assessed potential mediation by biomarkers related to glucose and lipid metabolism along with systemic inflammation. RESULTS: The fully adjusted logistic regression model indicated a positive association between breakfast skipping and periodontitis (odds ratio [OR] = 1.234 (1.026-1.483), p = 0.025). This association was highlighted in middle-aged (40-60 years), female, highly educated, married individuals with BMI < 25 kg/m2, and those in urban areas without diabetes. Blood glucose (ß ± SE = 0.006 ± 0.002, p = 0.014), triglycerides (ß ± SE = 0.004 ± 0.002, p = 0.033), and white blood cell count (ß ± SE = 0.011 ± 0.003, p = 0.003) were identified as partial mediators. CONCLUSIONS: A new, independent association between breakfast skipping, and periodontitis has been discovered, which is partially mediated by sugar and lipid metabolism, and systemic inflammation. The findings provide new insights into the benefits of chrononutrition for periodontal health.

Nanopore sequencing for smear-negative pulmonary tuberculosis-a multicentre prospective study in China.

PURPOSE: In this prospective study, the diagnosis accuracy of nanopore sequencing-based Mycobacterium tuberculosis (MTB) detection was determined through examining bronchoalveolar lavage fluid (BALF) samples from pulmonary tuberculosis (PTB) -suspected patients. Compared the diagnostic performance of nanopore sequencing, mycobacterial growth indicator tube (MGIT) culture and Xpert MTB/rifampin resistance (MTB/RIF) assays. METHODS: Specimens collected from suspected PTB cases across China from September 2021 to April 2022 were tested then assay diagnostic accuracy rates were compared. RESULTS: Among the 111 suspected PTB cases that were ultimately diagnosed as PTB, the diagnostic rate of nanopore sequencing was statistically significant different from other assays (P < 0.05). Fleiss' kappa values of 0.219 and 0.303 indicated fair consistency levels between MTB detection results obtained using nanopore sequencing versus other assays, respectively. Respective PTB diagnostic sensitivity rates of MGIT culture, Xpert MTB/RIF and nanopore sequencing of 36.11%, 40.28% and 83.33% indicated superior sensitivity of nanopore sequencing. Analysis of area under the curve (AUC), Youden's index and accuracy values and the negative predictive value (NPV) indicated superior MTB detection performance for nanopore sequencing (with Xpert MTB/RIF ranking second), while the PTB diagnostic accuracy rate of nanopore sequencing exceeded corresponding rates of the other methods. CONCLUSIONS: In comparison with MGIT culture and Xpert MTB/RIF assays, BALF's nanopore sequencing provided superior MTB detection sensitivity and thus is suitable for testing of sputum-scarce suspected PTB cases. However, negative results obtained using these assays should be confirmed based on additional evidence before ruling out a PTB diagnosis.

Knockdown of LRP5 Promotes Proliferation and Invasion of Tongue Squamous Cell Carcinoma through Compensatory Activation of Akt Signaling.

The role of LRP5, a critical receptor in the Wnt signaling pathway, remains unexplored in tongue squamous cell carcinoma (TSCC). This study investigates the impact of LRP5 knockdown on the biological behaviors of TSCC cell lines both in vitro and in vivo. Our findings indicate that LRP5 knockdown significantly enhances cell proliferation, migration, and invasion in CAL27 and SCC25 cell lines. RNA-seq analysis reveals compensatory activation of the Akt pathway, with 119 genes significantly upregulated post-LRP5 knockdown. Elevated MMP1 expression suggests its potential involvement in TSCC progression. Western blot analysis demonstrates increased Akt phosphorylation, upregulated proliferation-related PCNA, and downregulated apoptosis-related caspase-3 after LRP5 knockdown. Down-regulation of E-cadherin and ß-Catenin, proteins associated with cell adhesion and invasion, further elucidates the molecular mechanism underlying increased cell migration and invasion. Our study concludes that compensatory Akt pathway activation is essential for the LRP5 knockdown-induced migration and proliferation of CAL27 and SCC25 cells. These results highlight LRP5 as a potential therapeutic target for TSCC. Simultaneous inhibition of Wnt and Akt signaling emerges as a promising approach for TSCC treatment.

Coupled processes involving ammonium inputs, microbial nitrification, and calcite dissolution control riverine nitrate pollution in the piedmont zone (Qingshui River, China).

Rivers in agricultural countries widely suffer from diffuse nitrate (NO3-) pollution. Although pollution sources and fates of riverine NO3- have been reported worldwide, the driving mechanisms of riverine NO3- pollution associated with mineral dissolution in piedmont zones remain unclear. This study combined hydrogeochemical compositions, stable isotopes (δ18O-NO3-, δ15N-NO3-, δ18O-H2O, and δ2H-H2O), and molecular bioinformation to determine the pollution sources, biogeochemical evolution, and natural attenuation of riverine NO3- in a typical piedmont zone (Qingshui River). High NO3- concentration (37.5 ± 9.44 mg/L) was mainly observed in the agricultural reaches of the river, with ~15.38 % of the samples exceeding the acceptable limit for drinking purpose (44 mg/L as NO3-) set by the World Health Organization. Ammonium inputs, microbial nitrification, and HNO3-induced calcite dissolution were the dominant driving factors that control riverine NO3- contamination in the piedmont zone. Approximately 99.4 % of riverine NO3- contents were derived from NH4+-containing pollutants, consisted of manure & domestic sewage (74.0 % ± 13.0 %), NH4+-synthetic fertilizer (16.1 % ± 8.99 %), and soil organic nitrogen (9.35 % ± 4.49 %). These NH4+-containing pollutants were converted to HNO3 (37.2 ± 9.38 mg/L) by nitrifying bacteria, and then the produced HNO3 preferentially participated in the carbonate (mainly calcite) dissolution, which accounted for 40.0 % ± 12.1 % of the total riverine Ca2+ + Mg2+, also resulting in the rapid release of NO3- into the river water. Thus, microbial nitrification could be a new and non-negligible contributor of riverine NO3- pollution, whereas the involvement of HNO3 in calcite dissolution acted as an accelerator of riverine NO3- pollution. However, denitrification had lesser contribution to natural attenuation for high NO3- pollution. The obtained results indicated that the mitigation of riverine NO3- pollution should focus on the management of ammonium discharges, and the HNO3-induced carbonate dissolution needs to be considered in comprehensively understanding riverine NO3- pollution in piedmont zones.

Bone alteration and esthetics associated with implant-supported prostheses in the anterior maxilla under different implant placement timing: A retrospective clinical study of 1 to 3 years.

STATEMENT OF PROBLEM: Different factors influence alterations in facial bone thickness and esthetic outcomes after implant placement. Whether the timing of implant placement influences alterations in the bone dimensional and esthetic outcomes is unclear. PURPOSE: The purpose of this retrospective clinical study was to assess the influence of the timing of implant placement on alveolar bone alterations and esthetic outcome. MATERIAL AND METHODS: Data were collected from 40 patients who had received guided bone regeneration (GBR) performed simultaneously with immediate, early, or delayed single-tooth implant placement in the anterior maxilla. Facial and palatal horizontal bone thicknesses (FHBT, PHBT) and vertical bone level (FVBL, PVBL) immediately after surgery (T0), at 6 months after implant placement (T1), and at 1 to 3 years follow-up (T2) were measured, and the changes calculated. The pink esthetic score (PES) and white esthetic score (WES) were evaluated at the 1- to 3-year follow-up. The Kruskal-Wallis followed by the Dunn t test was applied to evaluate bone alteration among groups, and the Bonferroni method was used for adjusting multiple comparisons. The 1-way ANOVA test was used to determine any significance in the esthetic outcome in the 3 groups (α=.05). RESULTS: The reduction in the FHBT0 of the immediate, early, and delayed implant placement group (T2-T0) was -1.17 (-1.70, -0.61) mm, -1.53 (-1.69, -0.49) mm, and -1.47 (-2.30, -0.20) mm, respectively. The FHBT around the implant apices remained basically stable. No obvious changes in the PHBT around the implants of the immediate and delayed implant placement group were noted. The FVBL significantly decreased in each group during the follow-up period (-1.34 (01.88, -0.56) mm, immediate; -2.88 (-3.79, -1.07) mm, early; -1.26 (-2.52, -0.48) mm, delayed). The PVBL change in the early implant placement group (-2.18 (-3.26, -0.86) mm) was more significant than that in the immediate (-0.55 (-2.10, -0.17) mm) and delayed (-0.51 (-1.29, 0.02) mm) implantation groups (P =.013). The mean ±standard deviation PES/WES score of the immediate (15.6 ±1.84) and early (15.00 ±1.13) implant placement groups was higher than that of the delayed implant placement group (13.92 ±2.10) without significant difference. CONCLUSIONS: Similar bone changes and esthetic outcomes were found around implants of the immediate, early, and delayed implant placement groups.

In vitro and in vivo accuracy of autonomous robotic vs. fully guided static computer-assisted implant surgery.

OBJECTIVES: To assess the accuracy of autonomous robotic and fully guided static computer-assisted implant surgery (sCAIS) performed on models and patients. MATERIALS AND METHODS: This study was divided into in vitro and in vivo sections. In vitro, 80 operators were assigned to two groups randomly. Forty operators performed forty autonomous robotic implant (ARI group) surgeries and the remaining forty operators carried out forty fully guided sCAIS (FGI group) surgeries on maxillary models, respectively. Each operator placed an implant in one maxillary model. In vivo, 60 patients with 113 implants from 2019 to 2023 (ARI group: 32 patients, 58 implants; FGI group: 28 patients, 55 implants) receiving implant surgeries were incorporated in this retrospective research. The preoperative and postoperative cone beam computer tomographs (CBCTs) were utilized to estimate the linear deviations and angular deviations in two-dimensional (2D) and three-dimensional (3D) space. The Pearson's chi-square test, Shapiro-Wilk test, Student's t test, Mann-Whitney U test and mixed models were applied, and p <0.05 was considered statistically significant. RESULTS: In vitro, a total of 80 implants were enrolled and significant differences were found between the two groups (p < 0.001): The 3D deviation at the platform of ARI and FGI group was 0.58 ± 0.60 mm and 1.50 ± 1.46 mm, respectively, at the apex was 0.58 ± 0.60 mm and 1.78 ± 1.35 mm, respectively, and angle was 1.01 ± 0.87° and 2.93 ± 1.59°, respectively. Also, except for mesiodistal deviation at the implant platform, the rest linear and angular deviations in the ARI group were significantly lower than those in the FGI group in 2D space (p < 0.001). In vivo, a significantly lower mean of angular deviation (0.95 ± 0.50°, p < 0.001) and the linear deviation at both platform (0.45 ± 0.28 mm, p < 0.001) and apex (0.47 ± 0.28 mm, p < 0.001) were observed in ARI group when compared to the FGI group (4.31 ± 2.60°; 1.45 ± 1.27 mm; 1.77 ± 1.14 mm). CONCLUSIONS: The use of autonomous robotic technology showed significantly higher accuracy than the fully guided sCAIS.

Application of silk fibroin coatings for biomaterial surface modification: a silk road for biomedicine. / ä¸ç´ è›‹ç™½æ¶‚å±‚åœ¨ç”Ÿç‰©ææ–™è¡¨é¢ä¿®é¥°ä¸­çš„åº”ç”¨ï¼š 生物医学领域的丝绸之路.

Silk fibroin (SF) as a natural biopolymer has become a popular material for biomedical applications due to its minimal immunogenicity, tunable biodegradability, and high biocompatibility. Nowadays, various techniques have been developed for the applications of SF in bioengineering. Most of the literature reviews focus on the SF-based biomaterials and their different forms of applications such as films, hydrogels, and scaffolds. SF is also valuable as a coating on other substrate materials for biomedicine; however, there are few reviews related to SF-coated biomaterials. Thus, in this review, we focused on the surface modification of biomaterials using SF coatings, demonstrated their various preparation methods on substrate materials, and introduced the latest procedures. The diverse applications of SF coatings for biomedicine are discussed, including bone, ligament, skin, mucosa, and nerve regeneration, and dental implant surface modification. SF coating is conducive to inducing cell adhesion and migration, promoting hydroxyapatite (HA) deposition and matrix mineralization, and inhibiting the Notch signaling pathway, making it a promising strategy for bone regeneration. In addition, SF-coated composite scaffolds can be considered prospective candidates for ligament regeneration after injury. SF coating has been proven to enhance the mechanical properties of the substrate material, and render integral stability to the dressing material during the regeneration of skin and mucosa. Moreover, SF coating is a potential strategy to accelerate nerve regeneration due to its dielectric properties, mechanical flexibility, and angiogenesis promotion effect. In addition, SF coating is an effective and popular means for dental implant surface modification to promote osteogenesis around implants made of different materials. Thus, this review can be of great benefit for further improvements in SF-coated biomaterials, and will undoubtedly contribute to clinical transformation in the future.

Uric acid and evaluate the coronary vascular stenosis gensini score correlation research and in gender differences.

BACKGROUND AND AIMS: Recent studies have shown that the negative effect of uric acid (UA) on coronary arteries determines the severity of atherosclerotic disease. This study aims to explore the relationship between serum UA level and Gensini score, which reflects the severity of coronary artery disease. METHODS: A total of 860 patients with suspected coronary heart disease who were admitted to hospital due to angina pectoris or myocardial ischemia related symptoms and received coronary angiography were selected. Based on the findings of the angiography, they were categorized into two groups: the coronary heart disease (CHD) group (n = 625) and the control group (n = 235). The uric acid levels and other clinical data were compared between these groups. Additionally, the prevalence of coronary heart disease and Gensini score were compared between the groups, considering gender-specific quartiles of uric acid levels. The clinical baseline data were analyzed using appropriate statistical methods, and multivariate logistic regression analysis was conducted to identify independent risk factors for coronary heart disease. RESULTS: Of 860 patients (mean age, 63.97 ± 11.87 years), 528 were men (mean age, 62.06 ± 11.5 years) and 332 were women (mean age, 66.99 ± 10.11 years). The proportion of smoking, diabetes, hypertension, and hyperlipidemia in the coronary heart disease group was higher than that in the control group (P < 0.05). HbA1C, Gensini score, BMI, TG and hsCRP in the coronary heart disease group were higher than those in the control group (P < 0.05), and HDL-C was lower than that in the control group (P < 0.05). There were no significant differences in age, heart rate, Cr, TC and LDL-C between the two groups (P > 0.05).Multivariate logistic regression analysis showed that age, hypertension, hsCRP and SUA levels increased the risk of coronary heart disease, and the difference was statistically significant(OR = 1.034,95%CI 1.016-1.052, P = 0.001; OR = 1.469,95%CI 1.007-2.142, P = 0.046;OR = 1.064,95%CI 1.026-1.105, P = 0.001; OR = 1.011,95%CI 1.008-1.014, P < 0.001). CONCLUSION: Serum uric acid is positively correlated with Gensini score in patients with coronary heart disease, which is an independent factor for evaluating the degree of coronary artery stenosis and has a predictive effect.

Type H vessels in osteogenesis, homeostasis, and related disorders.

The vascular system plays a crucial role in bone tissue. Angiogenic and osteogenic processes are coupled through a spatial-temporal connection. Recent studies have identified three types of capillaries in the skeletal system. Compared with type L and E vessels, type H vessels express high levels of CD31 and endomucin, and function to couple angiogenesis and osteogenesis. Endothelial cells in type H vessels interact with osteolineage cells (e.g., osteoblasts, osteoclasts, and osteocytes) through cytokines or signaling pathways to maintain bone growth and homeostasis. In imbalanced bone homeostases, such as osteoporosis and osteoarthritis, it may be a new therapeutic strategy to regulate the endothelial cell activity in type H vessels to repair the imbalance. Here, we reviewed the latest progress in relevant factors or signaling pathways in coupling angiogenesis and osteogenesis. This review would contribute to further understanding the role and mechanisms of type H vessels in coupling angiogenic and osteogenic processes. Furthermore, it will facilitate the development of therapeutic approaches for bone disorders by targeting type H vessels.

Biomaterials derived from hard palate mucosa for tissue engineering and regenerative medicine.

Autologous materials have superior biosafety and are widely used in clinical practice. Due to its excellent trauma-healing ability, the hard palate mucosa (HPM) has become a hot spot for autologous donor area research. Multiple studies have conducted an in-depth analysis of the healing ability of the HPM at the cellular and molecular levels. In addition, the HPM has good maneuverability as a donor area for soft tissue grafts, and researchers have isolated various specific mesenchymal stem cells (MSCs) from HPM. Free soft tissue grafts obtained from the HPM have been widely used in the clinic and have played an essential role in dentistry, eyelid reconstruction, and the repair of other specific soft tissue defects. This article reviews the advantages of HPM as a donor area and its related mechanisms, classes of HPM-derived biomaterials, the current status of clinical applications, challenges, and future development directions.

Trimming Crystallizable Fragment (Fc) Glycans Enables the Direct Enzymatic Transfer of Biomacromolecules to Antibodies as Therapeutics.

Glycoengineering has provided powerful tools to construct site-specific antibody conjugates. However, only small-molecule payloads can be directly transferred to native or engineered antibodies using existing glycoengineering strategies. Herein, we demonstrate that reducing the complexity of crystallizable fragment (Fc) glycans could dramatically boost the chemoenzymatic modification of immunoglobulin G (IgG) via an engineered fucosyltransferase. In this platform, antibodies with Fc glycans engineered to a simple N-acetyllactosamine (LacNAc) disaccharide are successfully conjugated to biomacromolecules, such as oligonucleotides and nanobodies, in a single step within hours. Accordingly, we synthesized an antibody-conjugate-based anti-human epidermal growth factor receptor 2 (HER2)/ cluster of differentiation 3 (CD3) bispecific antibody and used it to selectively destroy patient-derived cancer organoids by reactivating endogenous T lymphocyte cells (T cells) inside the organoid. Our results highlight that this platform is a general approach to construct antibody-biomacromolecule conjugates with translational values.

Survival analysis of implants placed simultaneously with lateral sinus floor elevation in severely atrophic maxilla: A 3- to 12-year retrospective cohort study.

OBJECTIVES: To retrospectively evaluate whether implants placed simultaneously with lateral sinus floor elevation (LSFE) in severely atrophic maxilla (residual bone height [RBH] ≤3 mm) could achieve long-term survival and comprehensively analyze the factors influencing their survival rates. MATERIALS AND METHODS: A total of 123 patients receiving LSFE and simultaneous implant placement from 2010 to 2019 and their 123 implants in sites with RBH ≤3 mm were included in this study. Basic characteristics of patients and implants were collected from the medical record system and cone-beam computed tomography (CBCT) images. Kaplan-Meier survival curves were applied to estimate cumulative survival rates (CSRs) and Cox proportional hazards regression models were used to detect factors influencing implant survival. RESULTS: The 6-year and 12-year CSR of implants placed in sites with RBH ≤3 mm were 95.7% (95% confidence interval [CI]: 92.1%-99.5%) and 76.6% (95% CI: 58.1%-100%), respectively. Eight patients presented late implant failure. Univariate and multivariate Cox regression analyses demonstrated that RBH ≤2 mm (hazard ratio [HR]: 20.63, p = 0.000) and smoking habit (HR: 6.055, p = 0.024) were significantly associated with long-term implant survival. Specifically, the 10-year CSR of implants in sites with RBH ≤2 mm (53.3%, 95% CI: 27.5%-100%) was dramatically lower than those in sites with RBH >2 mm (92.9%, 95% CI: 81.7%-100%, p = 0.000). CONCLUSIONS: Implants placed simultaneously with LSFE in sites with RBH ≤3 mm can achieve long-term survival. However, caution is required especially for implantation in sites with RBH ≤2 mm. Besides, the smoking habit is also considered a risk factor jeopardizing long-term implant survival.

Effect of mitophagy in the formation of osteomorphs derived from osteoclasts.

Osteoclasts are specialized multinucleated giant cells with unique bone-destroying capacities. A recent study revealed that osteoclasts undergo an alternative cell fate by dividing into daughter cells called osteomorphs. To date, no studies have focused on the mechanisms of osteoclast fission. In this study, we analyzed the alternative cell fate process in vitro and, herein, reported the high expression of mitophagy-related proteins during osteoclast fission. Mitophagy was further confirmed by the colocalization of mitochondria with lysosomes, as observed in fluorescence images and transmission electron microscopy. We investigated the role played by mitophagy in osteoclast fission via drug stimulation experiments. The results showed that mitophagy promoted osteoclast division, and inhibition of mitophagy induced osteoclast apoptosis. In summary, this study reveals the role played by mitophagy as the decisive link in osteoclasts' fate, providing a new therapeutic target and perspective for the clinical treatment of osteoclast-related diseases.

Role and Mechanism of BMP4 in Regenerative Medicine and Tissue Engineering.

Bone morphogenetic protein 4 (BMP4) is emerging as a promising cytokine for regenerative medicine and tissue engineering. BMP4 has been shown to promote the regeneration of teeth, periodontal tissue, bone, cartilage, the thymus, hair, neurons, nucleus pulposus, and adipose tissue, as well as the formation of skeletal myotubes and vessels. BMP4 can also contribute to the formation of tissues in the heart, lung, and kidney. However, there are certain deficiencies, including the insufficiency of the mechanism of BMP4 in some fields and an appropriate carrier of BMP4 for clinical use. There has also been a lack of in vivo experiments and orthotopic transplantation studies in some fields. BMP4 has great distance from the clinical application. Therefore, there are many BMP4-related studies waiting to be explored. This review mainly discusses the effects, mechanisms, and applications of BMP4 in regenerative medicine and tissue engineering over the last 10 years in various domains and possible improvements. BMP4 has shown great potential in regenerative medicine and tissue engineering. The research of BMP4 has broad development space and great value.

The association of work physical activity and recreational physical activity with periodontitis in the NHANES (2009-2014).

BACKGROUND: The aim of this study was to investigate the association between different types and intensity of physical activities (PA) and periodontitis in a nationally representative sample of adults in the United States. METHODS: The data of periodontal condition and PA of 10,714 individuals were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014 and the Global Physical Activity Questionnaire (GPAQ). The association between the prevalence of periodontitis and two PAs (work PA and recreational PA) was respectively analyzed and adjusted by uni- and multi-variable logistic regression models. The odd ratios (ORs), adjusted odd ratios (ORad ), and 95% confidence interval (95% CI) were calculated as the main outcome indicators. RESULTS: After adjusted by age, sex, race, poverty-income ratio (PIR), diabetes, smoking status, alcohol use, and floss frequency, moderate and vigorous work PAs were significantly correlated with higher odds of periodontitis (ORad  = 1.22, 95% CI = 1.02-1.46; ORad  = 1.40, 95% CI = 1.04-1.89, respectively) while moderate and vigorous recreational PAs were correlated with lower odds of periodontitis (ORad  = 0.81, 95% CI = 0.69-0.95; ORad  = 0.55, 95% CI = 0.43-0.71, respectively). CONCLUSIONS: Work PAs and recreational PAs have opposite associations on the prevalence of developing periodontitis and their aggravating or protective associations enhance with the increase of intensity.

Light-controlled scaffold- and serum-free hard palatal-derived mesenchymal stem cell aggregates for bone regeneration.

Cell aggregates that mimic in vivo cell-cell interactions are promising and powerful tools for tissue engineering. This study isolated a new, easily obtained, population of mesenchymal stem cells (MSCs) from rat hard palates named hard palatal-derived mesenchymal stem cells (PMSCs). The PMSCs were positive for CD90, CD44, and CD29 and negative for CD34, CD45, and CD146. They exhibited clonogenicity, self-renewal, migration, and multipotent differentiation capacities. Furthermore, this study fabricated scaffold-free 3D aggregates using light-controlled cell sheet technology and a serum-free method. PMSC aggregates were successfully constructed with good viability. Transplantation of the PMSC aggregates and the PMSC aggregate-implant complexes significantly enhanced bone formation and implant osseointegration in vivo, respectively. This new cell resource is easy to obtain and provides an alternative strategy for tissue engineering and regenerative medicine.

Genetically modified cell spheroids for tissue engineering and regenerative medicine.

Cell spheroids offer cell-to-cell interactions and show advantages in survival rate and paracrine effect to solve clinical and biomedical inquiries ranging from tissue engineering and regenerative medicine to disease pathophysiology. Therefore, cell spheroids are ideal vehicles for gene delivery. Genetically modified spheroids can enhance specific gene expression to promote tissue regeneration. Gene deliveries to cell spheroids are via viral vectors or non-viral vectors. Some new technologies like CRISPR/Cas9 also have been used in genetically modified methods to deliver exogenous gene to the host chromosome. It has been shown that genetically modified cell spheroids had the potential to differentiate into bone, cartilage, vascular, nerve, cardiomyocytes, skin, and skeletal muscle as well as organs like the liver to replace the diseased organ in the animal and pre-clinical trials. This article reviews the recent articles about genetically modified spheroid cells and explains the fabrication, applications, development timeline, limitations, and future directions of genetically modified cell spheroid.