Single Mo Atoms Stabilized on High-Entropy Perovskite Oxide: A Frontier for Aerobic Oxidative Desulfurization.

The design and preparation of catalysts with both excellent stability and maximum exposure of catalytic active sites is highly desirable; however, it remains challenging in heterogeneous catalysis. Herein, a entropy-stabilized single-site Mo catalyst via a high-entropy perovskite oxide LaMn0.2Fe0.2Co0.2Ni0.2Cu0.2O3 (HEPO) with abundant mesoporous structures was initiated by a sacrificial-template strategy. The presence of electrostatic interaction between graphene oxide and metal precursors effectively inhibits the agglomeration of precursor nanoparticles in a high-temperature calcination process, thereby endowing the atomically dispersed Mo6+ coordinated with four O atoms on the defective sites of HEPO. The unique structure of single-site Mo atoms' random distribution with an atomic scale greatly enriches the oxygen vacancy and increases surface exposure of the catalytic active sites on the Mo/HEPO-SAC catalyst. As a result, the obtained Mo/HEPO-SAC exhibits robust recycling stability and ultra-high oxidation activity (turnover frequency = 3.28 × 10-2) for the catalytic removal of dibenzothiophene (DBT) with air as the oxidant, which represents the top level and is strikingly higher than the state-of-the-art oxidation desulfurization catalysts reported previously under the same or similar reaction conditions. Therefore, the finding here for the first time expands the application of single-atom Mo-supported HEPO materials into the field of ultra-deep oxidative desulfurization.

The interaction of CD300lf and ceramide reduces the development of periodontitis by inhibiting osteoclast differentiation.

AIM: The regulation of osteoclasts (OCs) by inhibitory immunoreceptors maintains bone homeostasis and is considered an important determinant of the extent of periodontal pathology. The aim of this study was to investigate the role of the inhibitory immunoreceptor CD300lf and its ligand ceramide in osteoclastogenesis in periodontitis. MATERIALS AND METHODS: The expression of CD300lf was measured in vitro and in a ligature-induced periodontitis model. The effect of CD300lf ablation on osteoclastogenesis was examined in ligature-retained and ligature removal periodontitis models. The effect of ceramide, the ligand of CD300lf, was examined in osteoclastogenesis in vitro and in vivo by smearing 20 µg of ceramide dissolved in carboxymethylcellulose on teeth and gingiva every other day in an experimental periodontitis model and ligature removal model. RESULTS: CD300lf expression was downregulated during osteoclastogenesis. Ablation of CD300lf in the ligature-induced periodontitis model increased the number of OCs and exacerbated bone damage. Bone resorption caused by CD300lf ablation was reversible following ligature removal. CD300lf-ceramide binding suppressed osteoclastogenesis in vitro and inhibited alveolar bone loss in a mouse periodontitis model. CONCLUSIONS: Our findings reveal that CD300lf-ceramide binding plays a critical negative role in alveolar bone loss in periodontitis by inhibiting OCs differentiation.

Comparison of Piezosurgery and Conventional Osteotomy for Orbital Hypertelorism Surgical Correction.

The purpose of this study was to compare the safety and effect of piezosurgery with conventional osteotomy in a box-shifting procedure for orbital hypertelorism (ORH) correction surgery. This study retrospectively analyzed the clinical record of 10 ORH patients aged from 5 to 12 years, and they were second-degree ORH with an interorbital distance (IOD) of 35 to 37.8 mm. Three of them received the osteotomy with piezosurgery (the piezosurgery group), whereas the other 7 patients received osteotomy with the conventional osteotomy method (the control group). They were compared with age and preoperative IOD. All the patients' IOD was effectively improved to normal range after the surgery. The results showed that the application of piezosurgery did not prolong the surgery time (piezosurgery group: 8.3±0.5 hours; control group: 8.7±1.4 hours, P =0.68). Furthermore, the patients in the piezosurgery group had less drainage volume (piezosurgery group: 79.1±12 mL; the control group: 170±41.3 mL, P =0.0065) and shorter postoperative hospital stay (piezosurgery group: 8.3±2.0 d; control group: 12.43±2.29 d, P =0.029). There were 2 patients who had wound infections, 1 in the piezosurgery group and 1 in the control group, respectively. However, 1 patient in the control group suffered from cerebrospinal fluid leakage. On the basis of the results, the application of piezosurgery benefited the patients on a better and smoother recovery course with less drainage and shorter hospital stays. The advantages of piezosurgery are the fine and precise osteotomy and the protection for soft tissue, which make it a comparatively safe and effective tool for craniofacial surgery, especially for young patients.

Advances in Robot-Assisted Surgery for Facial Bone Contouring Surgery.

Since our team reported the application of robot-assisted surgery in facial contouring surgery in 2020, further clinical trials with large samples have been conducted. This paper will report the interim results of a single-center, large-sample randomized controlled trial of the first robot developed by our team for facial contouring surgery. Meanwhile, this research field will be systematically reviewed and prospected.

Virtual reality used in undergraduate orthodontic education.

INTRODUCTION: Undergraduate dental students frequently have reduced clinical experience which presents a challenge for their dental education. Previously, we developed a virtual reality (VR) simulating the whole clinical treatment process of a patient with angle Class II division 1 malocclusion, and the VR also helped to explain some important orthodontic concepts. As a novel teaching tool, this study aims to compare the effects of VR versus traditional case analysis by Power Point (PPT) in inspiring student learning motivation and evaluating learning experience. MATERIALS AND METHODS: A randomized, cross-over, stratified sampling method was taken to divide the fourth-year undergraduate dental students equally into two groups. The two groups were crossed over to use VR and PPT. RESULTS: For the whole study, results indicated that students in the VR group showed higher learning motivation (including attention, relevance, confidence and satisfaction) than in the PPT group, but the differences between VR and PPT groups were not very big, and the median of the differences located at 0. For learning experience, students thought VR to be more useful, more enjoyable and more engaging, but the median of differences also located at 0. Notably, the majority of students had higher recommendations for VR than PPT, and the median difference located at 1. However, when the two phases were analysed separately, some items showed no significant differences between VR and PPT learning. CONCLUSION: VR is a very useful adjunct to education compared to traditional case analysis by PPT, but we cannot exaggerate its benefits. Educators should make good use of VR to solve the difficult problems in education.

Amyloid peptides with antimicrobial and/or microbial agglutination activity.

Microbe (including bacteria, fungi, and virus) infection in brains is associated with amyloid fibril deposit and neurodegeneration. Increasing findings suggest that amyloid proteins, like Abeta (Aß), are important innate immune effectors in preventing infections. In some previous studies, amyloid peptides have been linked to antimicrobial peptides due to their common mechanisms in membrane-disruption ability, while the other mechanisms of bactericidal protein aggregation and protein function knockdown are less discussed. Besides, another important function of amyloid peptides in pathogen agglutination is rarely illustrated. In this review, we summarized and divided the different roles and mechanisms of amyloid peptides against microbes in antimicrobial activity and microbe agglutination activity. Besides, the range of amyloids' antimicrobial spectrum, the effectiveness of amyloid peptide states (monomers, oligomers, and fibrils), and cytotoxicity are discussed. The good properties of amyloid peptides against microbes might provide implications for the development of novel antimicrobial drug. KEY POINTS: • Antimicrobial and/or microbial agglutination is a characteristic of amyloid peptides. • Various mechanisms of amyloid peptides against microbes are discovered recently. • Amyloid peptides might be developed into novel antimicrobial drugs.

ARID1B/SUB1-activated lncRNA HOXA-AS2 drives the malignant behaviour of hepatoblastoma through regulation of HOXA3.

It has been becoming increasingly evident that long non-coding RNAs (lncRNAs) play important roles in various human cancers. However, the biological processes and clinical significance of most lncRNAs in hepatoblastoma (HB) remain unclear. In our previous study, genome-wide analysis with a lncRNA microarray found that lncRNA HOXA-AS2 was up-regulated in HB. Stable transfected cell lines with HOXA-AS2 knockdown or overexpression were constructed in HepG2 and Huh6 cells, respectively. Our data revealed knockdown of HOXA-AS2 increased cell apoptosis and inhibited cell proliferation, migration and invasion in HB. Up-regulation of HOXA-AS2 promoted HB malignant biological behaviours. Mechanistic investigations indicated that HOXA-AS2 was modulated by chromatin remodelling factor ARID1B and transcription co-activator SUB1, thereby protecting HOXA3 from degradation. Therefore, HOXA-AS2 positively regulates HOXA3, which might partly demonstrate the involvement of HOXA3 in HOXA-AS2-mediated HB carcinogenesis. In conclusion, HOXA-AS2 is significantly overexpressed in HB and the ARID1B/HOXA-AS2/HOXA3 axis plays a critical role in HB tumorigenesis and development. These results might provide a potential new target for HB diagnosis and therapy.

Dysfunctional role of elevated TIGIT expression on T cells in oral squamous cell carcinoma patients.

OBJECTIVE: This study was aimed to analyze the role of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) expression on T cells in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TILs) were collected from OSCC patients. The correlation between TIGIT expression and clinicopathologic features was analyzed by chi-square test. Phenotypic and functional study of TIGIT+ T cells were performed by flow cytometry. RESULTS: TIGIT was highly expressed on T cells from PBMC and TILs. High expression of TIGIT on CD4+ T cells (19.0%) and CD8+ T cells (35.9%) was also associated with higher T stage and nodal invasion. Moreover, TIGIT+ CD4+ and TIGIT+ CD8+ T cells sorted from OSCC patients showed a dysfunctional phenotype (low cell proliferation and low secretion of IL-2, TNF-α and IFN-γ), and TIGIT+ CD4+ T cells exhibited inhibitory function (high expression of Foxp3 and high amounts of IL-10). Importantly, TIGIT blockade can enhance the proliferation ability and effective cytokine production (IL-2, TNF-α, and IFN-γ) of CD4+ and CD8+ T cells from OSCC patients in vitro. CONCLUSIONS: TIGIT-expressing T cells exhibit a lower effector cytokine-releasing phenotype in OSCC patients.

Berberine attenuates septic cardiomyopathy by inhibiting TLR4/NF-κB signalling in rats.

CONTEXT: Berberine (Ber) can increase the survival rate of septic mice and inhibit inflammation, but whether it has a protective effect on septic cardiomyopathy (SCM) is unclear. OBJECTIVE: To investigate whether Ber ameliorates SCM in a rat model and its potential mechanism. MATERIALS AND METHODS: Male SD rats were randomly divided into three groups: control (Con, n = 6) (DD H2O, 2 mL/100 g, ig, qd × 3 d, then saline, 10 mg/kg, ip); sepsis [LPS (lipopolysaccharide), n = 18] (LPS 10 mg/kg instead of saline, ip); and berberine intervention (Ber, n = 18) (Ber, 50 mg/kg instead of DD H2O, ig, qd × 3 d, LPS instead of saline, ip). Hemodynamics, HE staining, ELISA and western blot were performed at 6, 24, and 48 h after intraperitoneal injection of LPS to evaluate the effect of berberine in septic rats. RESULT: Berberine could recover myocardial injury by partially increased ± dp/dt max (1151, 445 mmHg/s) and LVEDP levels (1.49 mmHg) with LPS-induced rats, as well as an ameliorated increase of cTnT (217.53 pg/mL) in the Ber group compared with that in the LPS group (at 24 h). In addition, HE staining results showed that berberine attenuated the myocardial cell swelling induced by LPS. In contrast to the LPS group, the up-regulation of TLR4, p65 TNF-α, and IL-1ß were attenuated in the Ber group. DISCUSSION AND CONCLUSIONS: Berberine showed a protective effect on septic cardiomyopathy rats possibly through inhibiting the activation of TLR4/NF-κB signalling pathway. Whether it improves SCM through other mechanisms is our ongoing research.

Application of Opposing Triangle Flaps in Three Different Kinds of Conjoined Twins.

BACKGROUND: Conjoined twins are a rare congenital anomaly. If separation of the conjoined organs is feasible, reconstruction of the skin and tissue defects is a challenge for the plastic surgeon. This article describes the use of opposing triangle flaps in the separation of three different kinds of conjoined twins. METHODS: Plastic surgeons measured each conjoined area and designated the vertical length as a and the width as b. The length of the base of the opposing triangle flap was calculated to match a, and the height of the triangle to match b. RESULTS: After detailed calculations and careful surgery, the area of the opposing triangle flaps nearly covered the areas exposed after separation, and the three conjoined twins achieved primary closure of their wounds. The pygopagus and ischiopagus twins recovered uneventfully. The omphalopagus twins developed a wound infection, but after daily wound care, the twins recovered within a week. CONCLUSIONS: With precise calculations, the opposing triangle flap is a feasible and effective method for defect closure after separation of conjoined twins in certain cases. Clinicians may prefer this technique because it avoids the complications and second surgery necessitated by tissue expanders.

Thrombomodulin (TM) in tumor cell differentiation and periphery blood immune microenvironment in oral squamous cell carcinoma.

Thrombomodulin (TM, also known as CD141), which functions as an anticoagulant, is widely expressed on cell surface of a variety of cell types, including human blood cells as well as certain immune cells. To determine whether TM could be a potential marker for OSCC diagnosis as well as a molecular target for OSCC therapy, we examined the expression of TM in an oral cancer tissue microarray with 153 oral cancer tissues. Further, we also analyzed the expression of TM on DCs of 36 OSCC patients and 36 healthy donors. The expression of TM was determined using standard immunohistochemistry on a tissue microarray of 153 OSCC patients. Flow cytometric analyses were performed to determine the proportions of CD141+ DCs in the PBMC of 36 OSCC patients and 36 healthy donors. Clinicopathological correlations were performed based on the available clinical data. Our results showed that in the univariate analysis, high TM expression was significantly associated with well differentiation of tumor cells (P=.001), but not correlated with overall survival and disease-free survival (P>.05). In addition, CD141+ DCs were both present in OSCC patients and healthy donors with about 0.04%. There was no significant difference with the percentages of CD141+ DCs in the PBMC of OSCC patients and that of the normal control group (P>.05). This study indicates that TM expression might play the most critical role in the differentiation of OSCC tumors. Functional distinctions of CD141+ DCs in OSCC patients deserve further investigation to provide important therapeutic understandings for future immunotherapy.

Expression Profiling Identifies Circular RNA Signature in Hepatoblastoma.

BACKGROUND/AIMS: Hepatoblastoma is the most common malignant pediatric liver cancer. circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of circRNAs in hepatoblastoma is still unknown. METHODS: Circular RNA microarray was conducted to identify hepatoblastoma-related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in hepatoblastoma. MTT assays, Ki67 staining, and Transwell assays were conducted to clarify the role of circRNA in hepatoblastoma in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in hepatoblastoma cell. RESULTS: 869 differentially expressed circRNAs were identified between hepatoblastoma and adjacent normal liver samples, including 421 up-regulated circRNAs and 448 down-regulated circRNAs. The significant enriched GO term of hepatoblastoma-related circRNAs in biological process, cellular component, and molecular function were "chromosome organization", "cytoplasm", and "organic cyclic compound binding". Tight junction signaling pathway was ranked the Top 1 potentially affected by circRNA-mediated regulatory network. circ_0015756 was significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. circ_0015756 silencing decreased hepatoblastoma cell viability, proliferation, and invasion in vitro. circ_0015756 acted as miR-1250-3p sponge to regulate hepatoblastoma cell function. CONCLUSIONS: circRNAs are involved in the pathogenesis of hepatoblastoma. circ_0015756 is a promising target for the prognosis, diagnosis, and treatment of hepatoblastoma.

Experimental Study on the Performance of Hydraulic Vibration Assisted Broaching (HVAB) Based on Piezoelectric Sensors.

In order to improve the keyway broaching process and verify the feasibility of vibration-assisted broaching process, an experimental study on a novel hydraulic vibration assisted broaching (HVAB) system with double-valve electro-hydraulic exciter (DVEHE) is proposed in this paper. The performances of HVAB at different excitation frequencies were compared from three aspects: (a) the cutting force under the different vibration frequencies, (b) the surface roughness of the workpiece, and (c) the flank face wear of the tool. For precision on-line measurement of larger broaching forces, four piezoelectric sensors were fixed on the broaching machine. The experimental results show that HVAB can effectively improve the performance of the broaching process, approximately reduce the broaching force by as much as 9.7% compared to conventional broaching (CB) and improve the surface quality of workpiece. Some explanations are offered to support the observations.

Prognostic significance of tumor infiltrating immune cells in oral squamous cell carcinoma.

BACKGROUND: Prognostic factors aid in the stratification and treatment of cancer. This study evaluated prognostic importance of tumor infiltrating immune cell in patients with oral squamous cell carcinoma. METHODS: Profiles of infiltrating immune cells and clinicopathological data were available for 78 OSCC patients with a median follow-up of 48 months. The infiltrating intensity of CD8, CD4, T-bet, CD68 and CD57 positive cells were assessed by immunohistochemistry. Chi-square test was used to compare immune markers expression and clinicopathological parameters. Univariate and multivariate COX proportional hazard models were used to assess the prognostic discriminator power of immune cells. The predictive potential of immune cells for survival of OSCC patients was determined using ROC and AUC. RESULTS: The mean value of CD8, CD4, T-bet, CD68 and CD57 expression were 28.99, 62.06, 8.97, 21.25 and 15.75 cells per high-power field respectively. The patient cohort was separated into low and high expression groups by the mean value. Higher CD8 expression was associated with no regional lymph node metastasis (p = 0.033). Patients with more abundant stroma CD57+ cells showed no metastasis into regional lymph node (p = 0.005), and early clinical stage (p = 0.016). The univariate COX regression analyses showed that no lymph node involvement (p < 0.001), early clinical stage (TNM staging I/II vs III/IV, p = 0.007), higher CD8 and CD57 expression (p < 0.001) were all positively correlated with longer overall survival. Multivariate COX regression analysis showed that no lymph node involvement (p = 0.008), higher CD8 (p = 0.03) and CD57 (p < 0.001) expression could be independent prognostic indicators of better survival. None of CD4, T-bet or CD68 was associated with survival in ether univariate or multivariate analysis. ROC and AUC showed that the predictive accuracy of CD8 and CD57 were all superior compared with TNM staging. CD57 (AUC = 0.868; 95% CI, 0.785-0.950) and CD8 (AUC = 0.784; 95% CI, 0.680-0.889) both provided high predictive accuracy, of which, CD57 was the best predictor. CONCLUSION: Tumor stroma CD57 and CD8 expression was associated with lymphnode status and independently predicts survival of OSCC patients. Our results suggest an active immune microenvironment in OSCC that may be targetable by immune drugs.

Treatment of Children With Congenital Severe Blepharoptosis by Frontalis Aponeurosis Flap Advancement Under General Anesthesia in a Single Incision.

PURPOSE: This study aimed to investigate the effect of frontalis aponeurosis flap advancement in children with congenital severe blepharoptosis. METHODS: A total of 23 cases (25 eyes) of children who had congenital severe blepharoptosis and poor levator function (≤4 mm) and received frontalis aponeurosis flap advancement treatment in the Plastic Surgery Department of the Children's Hospital of Fudan University from January 1, 2013, to January 1, 2015, were retrospectively analyzed to evaluate the postoperative effects. RESULTS: All patients (age range, 6-27 months) were followed up for an average duration of 15.3 months. Twenty eyes (80%) had excellent effects, 2 eyes (8%) had good effects, and 3 eyes (12%) had poor effects. The average preoperative marginal reflex distance was 0.2 mm (-2 to 2 mm), and the postoperative average marginal reflex distance was 3.1 mm (1-4 mm). None of the patients showed hematoma, infection, keratohelcosis, symblepharon separation, ectropion, trichiasis, or other postoperative complications. CONCLUSION: Frontalis aponeurosis flap advancement could be used to treat congenital severe blepharoptosis with good short-term effects.

Neck observation versus elective neck dissection in management of clinical T1/2N0 oral squamous cell carcinoma: a retrospective study of 232 patients.

OBJECTIVE: The management of early-stage (cT1/2N0) oral squamous cell carcinoma (OSCC) remains a controversial issue. The aim of this study was to compare the clinical outcomes of neck observation (OBS) and elective neck dissection (END) in treating patients with cT1/2N0 OSCC. METHODS: A total of 232 patients with cT1/2N0 OSCC were included in this retrospective study. Of these patients, 181 were treated with END and 51 with OBS. The survival curves of 5-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates were plotted using the Kaplan-Meier method for each group, and compared using the Log-rank test. RESULTS: There was no significant difference in 5-year OS and DSS rates between END and OBS groups (OS: 89.0% vs. 88.2%, P=0.906; DSS: 92.3% vs. 92.2%, P=0.998). However, the END group had a higher 5-year RFS rate than the OBS group (90.1% vs. 76.5%, P=0.009). Patients with occult metastases in OBS group (7/51) had similar 5-year OS rate (57.1% vs. 64.1%, P=0.839) and DSS rate (71.4% vs. 74.4%, P=0.982) to those in END group (39/181). In the regional recurrence patients, the 5-year OS rate (57.1% vs. 11.1%, P=0.011) and DSS rate (71.4% vs. 22.2%, P=0.022) in OBS group (7/51) were higher than those in END group (9/181). CONCLUSIONS: The results indicated that OBS policy could obtain the same 5-year OS and DSS as END. Under close follow-up, OBS policy may be an available treatment option for patients with clinical T1/2N0 OSCC.

Foxp3 overexpression in tumor cells predicts poor survival in oral squamous cell carcinoma.

BACKGROUND: Forkhead Box P3 (Foxp3) is a regulatory T cells marker, and its expression correlates with prognosis in a number of malignancies. The aim of this study is to determine the relationship of Foxp3 expression with clinicopathological parameters and prognosis in oral squamous cell carcinoma (OSCC). METHODS: Foxp3 expression was examined using immunohistochemistry (IHC) in paraffin-embedded tissue samples from 273 OSCC patients. Statistical analysis was performed to evaluate the associations between Foxp3 expression, the clinicopathologic characteristics and prognostic factors in OSCC. RESULTS: Foxp3 protein expression was significantly associated with lymph node metastasis (P <0.01). Both univariate and multivariate analyses revealed that Foxp3 was an independent factor for both 5 years overall survival (OS) and relapse-free survival (RFS) (both P <0.01). Patients with Foxp3 overexpression had shorter OS and RFS. CONCLUSIONS: Our results determined that elevated Foxp3 protein expression was a predictive factor of outcome in OSCC and could act as a promising therapeutic target.

Selective Versus Comprehensive Neck Dissection in Patients With T1 and T2 Oral Squamous Cell Carcinoma and cN0pN(+) Neck.

PURPOSE: There is still no consensus on the oncologic safety of selective neck dissection (SND) in the management of pathologically positive neck in patients with oral squamous cell carcinoma (OSCC). This study compared the clinical outcome between SND and comprehensive neck dissection (CND) for patients with T1 and T2 OSCC and a clinically negative but pathologically positive neck. MATERIALS AND METHODS: Retrospective study of medical records of patients with T1 and T2 OSCC and clinical N0 but pathologic N(+) disease from March 2000 through March 2011 was performed. Thirty-seven patients underwent SND or CND. Median follow-up was 51 months. Regional control and disease-specific survival rates were statistically analyzed. RESULTS: No significant differences in 3-year ipsilateral neck control rate (81.8 vs 91.7%; P = .590 by log-rank test) and overall regional control rate (72.7 vs 86.8%; P = .424 by log-rank test) were found between the SND and CND groups. Three-year disease-specific survival rates of the SND and CND groups were 72.7 and 82.1%, respectively. No significant difference was found between these 2 groups by log-rank test (P = .428). CONCLUSIONS: The results indicate that SND in conjunction with postoperative radiotherapy is effective in the management of patients with T1 and T2 OSCC and cN0pN(+) neck.

P53 Alleviates the Progression of Periodontitis by Reducing M1-type Macrophage Differentiation.

Our objective is to explore the effect of P53 on the progression of periodontitis by regulating macrophages differentiation both in vitro and in vivo. Eighteen normal and periodontitis gingival tissues were collected for detecting P53 expression and macrophages infiltration by immunofluorescence, real-time PCR (qPCR) and western-blot. The differentiation and the inflammatory cytokines (TNF-α and IL-6) expression of THP-1, RAW264.7 and bone marrow derived macrophage (BMDM) cells, treating with Pifithrin-α (P53 inhibitor) or Nutlin-3a (P53 activator) under lipopolysaccharide (LPS) stimulation, were observed by flow cytometry, qPCR and ELISA. The severity of periodontitis, inflammatory cytokines expression and macrophages infiltration were measured in experimental periodontitis wild-type mice and p53 gene conditional knocked-out (p53-CKO) mice, which were established by ligation and LPS injection. A higher number of P53-positive macrophages was found infiltrated in periodontitis tissues. In vitro experiments showed that compared with Nutlin-3a, the proportion of M1-type macrophages and the expression of TNF-α and IL-6 were higher in Pifithrin-α treated cells under LPS stimulation. In vivo experimental periodontitis mice, the Pifithrin-α intraperitoneal injection group showed greater alveolar bone loss, higher levels of TNF-α and IL-6 secretion and more M1-type macrophages infiltration, while the Nutlin-3a intraperitoneal injection group were observed mild symptoms compared with mice in the periodontitis group. P53-CKO mice exhibited more severe periodontitis and more M1-type macrophages infiltrated in local tissues compared with wild-type mice. The activation of p53 gene could alleviate periodontitis by reducing M1-type macrophage polarization. P53 may serve as keeper in the progression of periodontitis, providing new insights into periodontitis treatment.

Bioengineering and vascularization strategies for islet organoids: advancing toward diabetes therapy.

Diabetes presents a pressing healthcare crisis, necessitating innovative solutions. Organoid technologies have rapidly advanced, leading to the emergence of bioengineering islet organoids as an unlimited source of insulin-producing cells for treating insulin-dependent diabetes. This advancement surpasses the need for cadaveric islet transplantation. However, clinical translation of this approach faces two major limitations: immature endocrine function and the absence of a perfusable vasculature compared to primary human islets. In this review, we summarize the latest developments in bioengineering functional islet organoids in vitro and promoting vascularization of organoid grafts before and after transplantation. We highlight the crucial roles of the vasculature in ensuring long-term survival, maturation, and functionality of islet organoids. Additionally, we discuss key considerations that must be addressed before clinical translation of islet organoid-based therapy, including functional immaturity, undesired heterogeneity, and potential tumorigenic risks.