N-glycosylation of SCAP exacerbates hepatocellular inflammation and lipid accumulation via ACSS2-mediated histone H3K27 acetylation.

Sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) is a widely expressed membrane glycoprotein that acts as an important modulator of lipid metabolism and inflammatory stress. N-glycosylation of SCAP has been suggested to modulate cancer development, but its role in nonalcoholic steatohepatitis (NASH) is poorly understood. In this study, the N-glycosylation of SCAP was analyzed by using sequential trypsin proteolysis and glycosidase treatment. The liver cell lines expressing wild-type and N-glycosylation sites mutated SCAP were constructed to investigate the N-glycosylation role of SCAP in regulating inflammation and lipid accumulation as well as the underlying mechanisms. The hepatic SCAP protein levels were significantly increased in C57BL/6J mice fed with Western diet and sugar water (WD + SW) and diabetic db/db mice, which exhibited typical liver steatosis and inflammation accompanied with hyperglycemia. In vitro, the enhanced N-glycosylation by high glucose increased the protein stability of SCAP and hence increased its total protein levels, whereas the ablation of N-glycosylation significantly decreased SCAP protein stability and alleviated lipid accumulation and inflammation in hepatic cell lines. Mechanistically, SCAP N-glycosylation increased not only the SREBP-1-mediated acetyl-CoA synthetase 2 (ACSS2) transcription but also the AMPK-mediated S659 phosphorylation of ACCS2 protein, causing the enhanced ACSS2 levels in nucleus and hence increasing the histone H3K27 acetylation (H3K27ac), which is a key epigenetic modification associated with NASH. Modulating ACSS2 expression or its location in the nuclear abolished the effects of SCAP N-glycosylation on H3K27ac and lipid accumulation and inflammation. In conclusion, SCAP N-glycosylation aggravates inflammation and lipid accumulation through enhancing ACSS2-mediated H3K27ac in hepatocytes.NEW & NOTEWORTHY N-glycosylation of SCAP exacerbates inflammation and lipid accumulation in hepatocytes through ACSS2-mediated H3K27ac. Our data suggest that SCAP N-glycosylation plays a key role in regulating histone H3K27 acetylation and targeting SCAP N-glycosylation may be a new strategy for treating nonalcoholic steatohepatitis (NASH).

Synthesis of X@DRHC (X=Co, Ni, Mn) catalyst from comprehensive utilization of waste rice husk and spent lithium-ion batteries for efficient peroxymonosulfate (PMS) activation.

Highly efficient resource recycling and comprehensive utilization play a crucial role in achieving the goal of reducing resource wasting, environmental protection, and achieving goal of sustainable development. In this work, the two kinds waste resources of agricultural rice husk and metal ions (Co, Ni, and Mn) from spent lithium-ion batteries have been skillfully utilized to synthesize novel Fenton-like catalysts. Desiliconized rice husk carbon (DRHC) with rich pore structure and large specific surface area from rice husk has been prepared and used as scalable carrier, and dandelion-like nanoparticles cluster could be grown in situ on the surface of the carrier by using metal ions contained waste water. The designed catalysts (X@DRHC) as well as their preparation process were characterized in detail by SEM, TEM, BET, XRD and XPS, respectively. Meanwhile, their catalytic abilities were also studied by activating potassium peroxomonosulfate (PMS) to remove methylene blue (MB). The results indicate X@DRHC displays excellent degradation efficiency on MB with wide pH range and stable reusability, which is suitable for the degradation of various dyes. This work has realized the recycling and high-value utilization of waste resources from biomass and spent lithium-ion batteries, which not only creates an efficient way to dispose waste resources, but also shows high economic benefits in large-scale water treatment.

Periodontal ligament fibroblasts-derived exosomes induced by PGE2 inhibit human periodontal ligament stem cells osteogenic differentiation via activating miR-34c-5p/SATB2/ERK.

Several studies have confirmed that exosomes containing microRNAs (miRNAs) from the aseptic inflammatory microenvironment play an important role in bone remodeling. But the mechanism that induces changes in the osteogenic ability of periodontal ligament stem cells (PDLSCs) is still unclear. In the present study, the osteogenic function of periodontal ligament fibroblasts-derived exosomes induced by PGE2 on PDLSCs was detected by real-time PCR, alizarin red assay and alkaline phosphatase staining. High-throughput miRNAs sequencing was used to reveal that miR-34c-5p in exosomes-PGE2 was upregulated compared it in exosomes-normal. Real-time PCR and western blotting assay verified that overexpression of miR-34c-5p inhibited osteogenic differentiation, and reduced phosphorylation of ERK1/2. In addition, dual-luciferase reporter assay revealed that miR-34c-5p targeted special AT-rich sequence-binding protein 2 (SATB2). It was shown that exosomal miR-34c-5p inhibited osteogenic differentiation of PDLSCs via SATB2/ERK pathway.

MicroRNA-27a, downregulated in human obesity, exerts an antiapoptotic function in adipocytes.

Adipocyte apoptosis is a key initial event that contributes to macrophage infiltration into adipose tissue (AT) and thus triggers AT inflammation in obesity. MicroRNA-27a (miR-27a) was shown to mediate the pathological processes of many metabolic disorders; however, whether miR-27a is involved in adipocyte apoptosis of obese AT remains unknown. The present study aimed to investigate the alteration of miR-27a in obese individuals and its antiapoptotic function in adipocytes. In vivo, serum samples and omental adipose tissue from humans as well as epididymal fat pads from mice were collected to detect miR-27a expression. In vitro, 3T3-L1 preadipocytes and mature adipocytes were treated with TNF-α to induce apoptosis and transfected with a mimic for overexpressing miR-27a-3p. The results showed that miR-27a was markedly decreased in the serum and AT of obese human patients and in the AT of high-fat diet-fed mice. Regression analyses revealed that the serum level of miR-27a was correlated with metabolic parameters in human obesity. Notably, TNF-α induced cell apoptosis in both preadipocytes and mature adipocytes, as evidenced by the upregulation of cleaved caspase 3 and cleaved caspase 8 and the ratio of Bax to Bcl-2, while these effects were partly diminished by miR-27a overexpression. In addition, TUNEL and Hoechst 33258 staining verified that miR-27a overexpression markedly inhibited the apoptosis of adipocytes under TNF-α stimulation. Thus, miR-27a was downregulated in the AT of obese subjects with proapoptotic status, and overexpression of miR-27a exerted an antiapoptotic effect on preadipocytes, providing a novel potential target for preventing AT dysfunction.

Respiratory Fluid Mechanics of the Effect of Mouth Breathing on High-Arched Palate: Computational Fluid Dynamics Analyses.

Computational fluid dynamics (CFD) was introduced into the study of palate growth and development to explain the mechanisms by which mouth breathing affects palate descent from an aerodynamic perspective. Cone beam computed tomography (CBCT) data were used to reconstruct a 3-dimensional model during natural mouth breathing of a volunteer. The model was imported into CFX 19.0 for numerical simulation of nasal breathing, mouth-nasal breathing, and mouth breathing. The pressure in the oronasal cavity was analyzed, and the pressure difference between the oral and nasal surfaces of hard palate under different breathing patterns was calculated. CFD can be used to simulate the stress on the oral and nasal surfaces of the palate under different breathing patterns. The pressure differences and resultant force between the oral and nasal surfaces of the hard palate during nasal inspiration, nasal expiration, mouth-nasal inspiration, mouth-nasal expiration, mouth inspiration, and mouth expiration were 0 Pa, 4 Pa (upward), 9 Pa (upward), 3 Pa (downward), 474 Pa (upward), 263 Pa (downward), respectively, and 87.99 N (upward), 88.03 N (upward), 88.01 N (upward), 88.01 N (upward), 88.05 N (upward), 87.94 N (upward), respectively. Therefore, CFD can be used to investigate the growth and development of the palate. When the volunteer opened his mouth, the pressure difference between the oral and nasal surfaces of the hard palate was about 88 N upward regardless of whether there was airflow in the mouth. The reversal of the direction of the force on the hard palate may be one of the factors affecting its descent of it.

Clinical effects of maxillary protraction in different stages of dentition in skeletal class III children: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the effectiveness of using maxillary protraction during different stages of the dentition by assessing changes in the jaws and inclination of incisors. MATERIALS AND METHODS: MEDLINE (PubMed), Embase, Cochrane, Web Of Science, China National Knowledge Infrastructure and Wanfang Databases were searched without time limitations up to 15 January 2022. Google Scholar was used to search grey literature. We included cohort studies that compared the effect of maxillary protraction by analysing primary outcomes and were grouped in age-related conditions. Mean differences and 95% confidence intervals were used for statistical analysis, followed by Grading of Recommendations Assessment, Development and Evaluation analysis. RESULTS: Six studies were finally included. The heterogeneity test showed P ≥ .1 and I2  ≤ 50%, and a fixed-effect model was applied. Patients in the early treatment group (ETG) were mainly in the early-mixed dentition stage, while patients in the late treatment group (LTG) were in the late-mixed and early-permanent dentition stage. Meta-analysis showed that there were no statistical differences (P > .05) between the ETG and LTG groups in terms of SNA (the angle composed by point Sella-Nasion-Subspinale), SNB (the angle composed by point Sella-Nasion-Supramentale), ANB (the angle composed by point Subspinale-Nasion-Supramentale), Wits, U1/SN (the angle composed by the axis of upper incisors and Sella-Nasion plane) and L1/MP (the angle composed by the axis of lower incisors and the mandibular plane). CONCLUSION: Our analysis showed that maxillary protraction applied in the late-mixed or early-permanent dentition stage did not cause different effects on the maxillary growth, the correction of the intermaxillary relationship, the inhibition of mandibular growth and dental tipping of skeletal class III patients when compared to that in the early-mixed dentition stage. Collectively, these data provide a theoretical basis for widening the applicable age period of maxillary protraction and choosing the best treatment opportunity for children patients after a comprehensive assessment.

Prognostic analysis and nomogram establishment in patients with head and neck myoepithelial carcinoma.

PURPOSE: To further explore the clinicopathological characteristics and determinants of survival of patients with HNMC. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to collect the data of patients diagnosed with HNMC from 1975 to 2016. Kaplan-Meier analysis and log-rank testing compared the survival difference. Cox hazard regression models analyzed the survival outcome and prognostic factors. Concordance index (C-index) verified the nomogram. RESULTS: A total of 322 eligible cases were retrieved. The mean age at diagnosis was 61 years old and the male to female ratio was 1:1. The major salivary gland was the most common primary site (72.5%). Patients with adjuvant radiation showed better overall survival (OS) (P < 0.05). Advanced grade, N, M stage and nonsurgery contributed independently to shorter OS, while the advanced N, M stage and nonsurgery contributed independently to shorter disease-specific survival (DSS) (P < 0.05). The C-index of OS-specific nomogram was 0.768 (95% CI 0.726-0.810). CONCLUSIONS: HNMC usually appears in elderly patients and has no gender difference. The 5-year OS and DSS rates are 70% and 79.8%, respectively. Grade, N, M stage and surgery are independent prognostic factors for OS, while N, M stage and surgery are independent prognostic factors for DSS. Compared with the surgery alone, adjuvant radiation appears to offer a significant OS benefit for patients with stage III or IV.

Novel Prediction Models for Patients With Oral Squamous Cell Carcinoma at Different Anatomical Sites.

PURPOSE: The individualized prediction of oral cavity squamous cell carcinoma (OC-SCC) is essential and should be as comprehensive as possible. The aim of this study was to identify new risk factors and develop nomograms comparing all anatomic sites of the oral cavity. MATERIALS AND METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. All patients with OC-SCC diagnosed from 2004 to 2015 were selected and divided into the training cohort and the validation cohort. Age, gender, race, marital status, primary site, tumor grade, American Joint Committee on Cancer (AJCC) stage, TNM stage, surgical treatment, radiotherapy and chemotherapy were identified as predictor variables. The overall survival (OS) and disease specific survival (DSS) were identified as outcome variables. Kaplan-Meier method with log-rank test, univariate and multivariate cox regression analysis were performed. Independent prognostic factors were used to develop 3- and 5-year nomograms. Hazard ratio (HR) and corresponding 95% confidence interval (CI) showed the influence of each factor on OS or DSS. Concordance indexes (C-indexes) and calibration curves verified the nomograms internally and externally. RESULTS: A total of 12,346 patients were included. Marital status and chemotherapy were independent prognostic factors (P < .05). Tumors occurring on the cheek mucosa had the highest risk in OS (HR, 2.0, 95% CI, 1.7-2.3) and DSS (HR, 4.7, 95% CI, 3.6-6.0), while tumors occurring on the lip had the lowest risk in OS (HR, 1.0) and DSS (HR,1.0). The C-indexes for OS in the training and validation sets were 0.767 and 0.770, respectively, and for DSS were 0.800 and 0.799, respectively. CONCLUSION: Marital status and chemotherapy independently affect OC-SCC patients' survival. The prognosis is least favorable for tumors occurring on the cheek mucosa and most favorable for tumors occurring on the lip.

Low torque is a risk factor for non-carious cervical lesions (NCCLs) in maxillary premolars.

PURPOSE: To determine the prevalence of non-carious cervical lesions (NCCLs) in maxillary premolars of different torques and simulated cervical stress profiles of the premolars under coincident loadings using finite element analysis (FEA). METHODS: The CBCT scans of 616 maxillary premolars from 154 subjects were retrospectively evaluated. The premolars were ascribed into low torque group (LTG) <-10.9°, medium torque group (MTG) -10.9° to -3.9°, and high torque group (HTG) >-3.9°, when the torque was referring to the occlusion plane. The prevalence of NCCLs in each group was evaluated. Then finite element models of a maxillary first premolar, its adjacent teeth and alveolar bone were established. The models were prepared with ANSYS software generating the premolars presenting different torques. The mastication scenario for the premolars in maximum intercuspation position was simulated. RESULTS: The prevalence of NCCLs was 15.7% in LTG, 7.9% in MTG and 5.5% in HTG. The prevalence of LTG was significantly higher than that of MTG (P< 0.05) and HTG (P< 0.01). As for FEA, the stresses at the buccal necks of the premolars basically increased with decrease of the torque. The tensile stress peaks were in the cemento-enamel junction in most premolars of the LTG, while in the middle of the crowns in premolars of MTG and HTG. CLINICAL SIGNIFICANCE: Low torque with excessive lingual inclination is a risk factor for NCCLs of maxillary premolars, and excessive tensile stress concentration in buccal necks during mastication may be responsible for that.

Bisphenol A promotes hyperuricemia via activating xanthine oxidase.

The prevalence of hyperuricemia has increased rapidly over the past decades. Bisphenol A (BPA) is an environmental endocrine disruptor. We investigated the effects of BPA on uric acid metabolism and its potential mechanisms. Experiments were performed in different animal models, cell cultures, and humans. In 3 different animal models, BPA exposure increased serum and hepatic uric acid with enhanced activity of xanthine oxidase (XO) in liver, whereas the excretion of uric acid was unchanged. Both in vivo and in vitro, BPA-induced uric acid production was decreased after treatment with allopurinol, which is a XO inhibitor. XO led to the accumulation of uric acid after xanthine was added, with the enzyme-catalyzed reaction, which was enhanced by BPA. Altered secondary structures of XO were found by circular dichroism analysis in the conditions of different BPA concentrations. Molecular docking portrayed Asp360 and Lys422 of XO to be the preferred binding sites for BPA. Mutation of both sites significantly blocked the effect of BPA on XO activity. In humans, patients with hyperuricemia exhibited higher levels of serum BPA than subjects without hyperuricemia. These findings demonstrate BPA promotes hyperuricemia by increasing hepatic uric acid synthesis via the activation of XO, probably through direct binding.-Ma, L., Hu, J., Li, J., Yang, Y., Zhang, L., Zou, L., Gao, R., Peng, C., Wang, Y., Luo, T., Xiang, X., Qing, H., Xiao, X., Wu, C., Wang, Z., He, J. C., Li, Q., Yang, S. Bisphenol A promotes hyperuricemia via activating xanthine oxidase.

The association between nutritive, non-nutritive sucking habits and primary dental occlusion.

BACKGROUND: The development of primary dentition can be affected by oral sucking habits. Therefore, this study aims to investigate the association of nutritive and non-nutritive sucking habits with primary dentition development. METHODS: One thousand one hundred and fourteen children aged 2 to 5 years old in Hong Kong were recruited in a cross-sectional study. Information on their nutritive (e.g. breastfeeding and bottle feeding) and non-nutritive sucking habits (e.g. pacifier use and thumb/digit sucking) was collected via questionnaires. The children's primary occlusions were examined in three dimensions. RESULTS: Children who were breastfed for more than 6 months had a lower proportion of daily pacifier use (p < 0.05). Children who used pacifiers daily had a higher proportion of thumb/digit sucking (p < 0.05). Children who used pacifiers daily for more than one year had higher chances of developing an anterior open bite (p < 0.05) and a reduced overbite (p < 0.05). Those exhibiting daily thumb/digit sucking for more than one year had higher chances of developing Class II incisor and Class II canine relationships, an increased overjet and anterior open bite (p < 0.05). CONCLUSION: Pure breastfeeding for more than 6 months is inversely associated with daily pacifier use and daily pacifier use is positively associated with daily thumb/digit sucking. Children with more than one year of daily pacifier use and thumb/digit sucking have higher chances of developing abnormal dental relationships in the sagittal (i.e. Class II incisor and Class II canine relationships and increased overjet) and vertical (i.e. anterior open bite) dimensions, respectively.

Association of breastfeeding and three-dimensional dental arch relationships in primary dentition.

BACKGROUND: The benefits of breastfeeding on oral health are still inconclusive, especially the association on occlusion. This study aimed to investigate the association of breastfeeding and the development of primary dentition. METHODS: A cross-sectional study was conducted with 851 Asian children aged 2-5 years old in Hong Kong. Questionnaires were completed by the parents to collect information on breastfeeding and the non-nutritive sucking habits. The children's dental arch relationships were examined in the sagittal, vertical, and transverse dimensions by an experienced examiner. RESULTS: Children who experienced pure breastfeeding for more than 6 months had a lower chance of developing a class II incisal relationship (P < 0.05) or an increased overjet (P < 0.05), and had wider intercanine (P < 0.05) and intermolar widths (P < 0.05). Vertically, no association on the extent of overbite or openbite was found (P > 0.05). CONCLUSIONS: Pure breastfeeding for more than 6 months is positively associated with primary dental arch development in the anterior sagittal dental segment and on the horizontal arch width in primary dentition. Therefore, pure breastfeeding for more than 6 months is recommended, as it is associated with lower chance of the development of abnormal dental relationships. The results will be valuable for education and promotion of maternal breastfeeding.

The role of traditional Chinese medicines in osteogenesis and angiogenesis.

The article aims to review various Traditional Chinese Medicines (TCMs) with both osteogenic and angiogenic effects, alone and in combination, and to consider whether these TCMs promote osteogenesis via angiogenesis and vascular endothelial growth factor (VEGF). Each of the TCMs involving in osteogenesis was searched through PubMed and CBMdisc using its Latin name and English name, and keywords such as 'osteogenesis', 'bone', 'osteoblast', 'angiogenesis', 'VEGF' were used. A total of 241 articles were screened from PubMed and CBMdisc. The articles were only chosen if they discussed the relationship of the TCMs with bone formation and/or angiogenesis. Twenty-seven articles were chosen, of which 16 were in English and 11 were in Chinese with English abstract. As a result, the TCMs (Danshen or Salvia miltiorrhiza Bunge, Danggui or Angelica sinensis, Astragalus membranaceus Bunge or Huangqi, and Ge Gan or Puerarin radix) that have a relationship with both osteogenesis and angiogenesis were screened out. It is found that the aforementioned TCMs enhance angiogenesis and osteogenesis. They show a positive effect on bone formation, and the possible mechanisms may be related to their ability to promote angiogenesis via an effect on substances such as VEGF.

Periodontal ligament cells-derived exosomes promote osteoclast differentiation via modulating macrophage polarization.

Several studies have demonstrated that exosomes (Exos) are involved in the regulation of macrophage polarization and osteoclast differentiation. However, the characteristics as well as roles of exosomes from human periodontal ligament cells (hPDLCs-Exos) in M1/M2 macrophage polarization and osteoclast differentiation remain unclear. Here, periodontal ligament cells were successfully extracted by method of improved Type-I collagen enzyme digestion. hPDLCs-Exos were extracted by ultracentrifugation. hPDLCs-Exos were identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting (WB). Osteoclast differentiation was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR), WB and tartrate-resistant acid phosphatase (TRAP) staining. M1/M2 macrophage polarization were evaluated by RT-qPCR and WB. The results showed hPDLCs-Exos promoted osteoclast differentiation and M2 macrophage polarization, but inhibited M1 macrophage polarization. Moreover, M1 macrophages inhibited osteoclast differentiation, whereas M2 macrophages promoted osteoclast differentiation. It has shown that hPDLCs-Exos promoted osteoclast differentiation by inhibiting M1 and promoting M2 macrophage polarization.

Effect of Mechanical Loading on Bone Regeneration in HA/ß-TCP/SF Scaffolds Prepared by Low-Temperature 3D Printing In Vivo.

It has been well demonstrated that a dynamic culture environment improves tissue-engineered bone formation in vitro, but little is known about how cyclical mechanical loading induced bone formation in scaffolds in situ. To mimic the organic and inorganic components and multilevel structure of a bony microenvironment, hydroxyapatite/ß tricalcium phosphate/silk fibroin(HA/ß-TCP/SF) composite scaffolds with macro- and micropores were fabricated in this study. The mechanical properties and structure of the scaffolds were adjusted based on the ratio of organic and inorganic components and three-dimensional (3D) printing parameters. Dynamic sinusoidal loading with different frequencies was applied to the composite scaffold. Mouse bone precursor cells MC3T3-E1 were seeded on the scaffolds, and the cell compatibility of the scaffolds was investigated by MTT, SEM, and HE. The effect of the loading on bone formation in the scaffold in situ was investigated in a rabbit tibia defect model. The scaffold showed viscoelasticity and hysteresis under dynamic sinusoidal loading with different frequencies. With an increase in HA/ß-TCP, the stress and modulus of the scaffolds increased. MTT, SEM, and HE results showed that MC3T3-E1 cells could adhere and proliferate on the composite scaffolds. After loading in vivo, the quantity of newly formed bone and the bone volume fraction increased. Micro-CT, undecalcified Van Gieson (VG) staining, and fluorescent double-labeling results suggested that appropriate cyclical mechanical loading at frequencies of 1 and 10 Hz had positive effects on bone formation in situ and it may play a role in clinical bone defect repair.

Hepatocyte CD36 protects mice from NASH diet-induced liver injury and fibrosis via blocking N1ICD production.

BACKGROUND & AIMS: Fatty acid translocase CD36 (CD36/FAT) is a widely expressed membrane protein with multiple immuno-metabolic functions. Genetic CD36 deficiency is associated with increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in patients. Liver fibrosis severity mainly affects the prognosis in patients with MAFLD, but the role of hepatocyte CD36 in liver fibrosis of MAFLD remains unclear. METHODS: A high-fat high-cholesterol diet and a high-fat diet with high-fructose drinking water were used to induce nonalcoholic steatohepatitis (NASH) in hepatocyte-specific CD36 knockout (CD36LKO) and CD36flox/flox (LWT) mice. Human hepG2 cell line was used to investigate the role of CD36 in regulating Notch pathway in vitro. RESULTS: Compared to LWT mice, CD36LKO mice were susceptible to NASH diet-induced liver injury and fibrosis. The analysis of RNA-sequencing data revealed that Notch pathway was activated in CD36LKO mice. LY3039478, an inhibitor of γ-secretase, inhibited Notch1 protein S3 cleavage and Notch1 intracellular domain (N1ICD) production, alleviating liver injury and fibrosis in CD36LKO mice livers. Likewise, both LY3039478 and knockdown of Notch1 inhibited the CD36KO-induced increase of N1ICD production, causing the decrease of fibrogenic markers in CD36KO HepG2 cells. Mechanistically, CD36 formed a complex with Notch1 and γ-secretase in lipid rafts, and hence CD36 anchored Notch1 in lipid rafts domains and blocked Notch1/γ-secretase interaction, inhibiting γ-secretase-mediated cleavage of Notch1 and the production of N1ICD. CONCLUSIONS: Hepatocyte CD36 plays a key role in protecting mice from diet-induced liver injury and fibrosis, which may provide a potential therapeutic strategy for preventing liver fibrogenesis in MAFLD.

Hepatocyte CD36 modulates UBQLN1-mediated proteasomal degradation of autophagic SNARE proteins contributing to septic liver injury.

Macroautophagy/autophagy plays a protective role in sepsis-induced liver injury. As a member of class B scavenger receptors, CD36 plays important roles in various disorders, such as atherosclerosis and fatty liver disease. Here we found that the expression of CD36 in hepatocytes was increased in patients and a mouse model with sepsis, accompanied by impaired autophagy flux. Furthermore, hepatocyte cd36 knockout (cd36-HKO) markedly improved liver injury and the impairment of autophagosome-lysosome fusion in lipopolysaccharide (LPS)-induced septic mice. Ubqln1 (ubiquilin 1) overexpression (OE) in hepatocyte blocked the protective effect of cd36-HKO on LPS-induced liver injury in mice. Mechanistically, with LPS stimulation, CD36 on the plasma membrane was depalmitoylated and distributed to the lysosome, where CD36 acted as a bridge molecule linking UBQLN1 to soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and hence promoting the proteasomal degradation of SNARE proteins, resulting in fusion impairment. Overall, our data reveal that CD36 is essential for modulating the proteasomal degradation of autophagic SNARE proteins in a UBQLN1-dependent manner. Targeting CD36 in hepatocytes is effective for improving autophagic flux in sepsis and therefore represents a promising therapeutic strategy for clinical treatment of septic liver injury.Abbreviations: AAV8: adeno-associated virus 8; AOSC: acute obstructive suppurative cholangitis; ATP1A1: ATPase, Na+/K+ transporting, alpha 1 polypeptide; CASP3: caspase 3; CASP8: caspase 8; CCL2: chemokine (C-C motif) ligand 2; cd36-HKO: hepatocyte-specific cd36 knockout; Co-IP: co-immunoprecipitation; CQ: chloroquine; Cys: cysteine; GOT1: glutamic-oxaloacetic transaminase 1, soluble; GPT: glutamic-pyruvic transaminase, soluble; IL1B: interleukin 1 beta; IL6: interleukin 6; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LDH, lactate dehydrogenase; LPS: lipopolysaccharide; LYPLA1: lysophospholipase 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; OE: overexpression; qPCR: quantitative polymerase chain reaction; SNAP29: synaptosome associated protein 29; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TNF: tumor necrosis factor; TRIM: tripartite motif-containing; UBA: ubiquitin-associated; UBL: ubiquitin-like; UBQLN: ubiquilin; VAMP8: vesicle associated membrane protein 8; WT: wild-type.

Dynamic 3D images fusion of the temporomandibular joints: A novel technique.

OBJECTIVES: To demonstrate a procedure for fusing images from cone-beam computed tomography (CBCT), magnetic resonance imaging (MRI) and optical positioning tracking system to dynamically evaluate the relative motion of the temporomandibular joint (TMJ) for the diagnosis of temporomandibular disorders (TMD). METHODS: CBCT data was collected from a patient wearing a fixation device with markers in the intercuspal position. The patient's mandibular movements were recorded using an optical positioning tracking system. The CBCT data were imported into a virtual simulation system to reproduce the mandibular movement. Five jaw positions were selected for 3D printing of the occlusal plate that the patient wore to undergo MRI. MRI scans were registered with the CBCT image for fusion and reconstruction. RESULTS: The anatomical structures of the articular fossa, articular disc, and condyle were clearly displayed in the CBCT-MRI fused images. The spatial posture and relative position of the fossa-disc-condyle during mandibular movement could be reproduced dynamically using the 3D reconstruction model. CONCLUSIONS: This method can visually display mandibular motion trajectories and the relative TMJ positions. Virtual reproduction provides a comprehensive understanding of the articular disc's morphology and position in different states from a 3D perspective. CLINICAL SIGNIFICANCE: This method can be used in clinical studies of TMJ as an adjunct to the 3D dynamic diagnosis and assessment for complex patients with TMD and provide relevant data for doctors.

Clinical effectiveness of different types of bone-anchored maxillary protraction devices for skeletal Class III malocclusion: Systematic review and network meta-analysis.

Objective: This study aimed to estimate the clinical effects of different types of bone-anchored maxillary protraction devices by using a network meta-analysis. Methods: We searched seven databases for randomized and controlled clinical trials that compared bone-anchored maxillary protraction with tooth-anchored maxillary protraction interventions or untreated groups up to May 2021. After literature selection, data extraction, and quality assessment, we calculated the mean differences, 95% confidence intervals, and surface under the cumulative ranking scores of eleven indicators. Statistical analysis was performed using R statistical software with the GeMTC package based on the Bayesian framework. Results: Six interventions and 667 patients were involved in 18 studies. In comparison with the tooth-anchored groups, the bone-anchored groups showed significantly more increases in Sella-Nasion-Subspinale (°), Subspinale-Nasion-Supramentale(°) and significantly fewer increases in mandibular plane angle and the labial proclination angle of upper incisors. In comparison with the control group, Sella-Nasion-Supramentale(°) decreased without any statistical significance in all treated groups. IMPA (angle of lower incisors and mandibular plane) decreased in groups with facemasks and increased in other groups. Conclusions: Bone-anchored maxillary protraction can promote greater maxillary forward movement and correct the Class III intermaxillary relationship better, in addition to showing less clockwise rotation of mandible and labial proclination of upper incisors. However, strengthening anchorage could not inhibit mandibular growth better and the lingual inclination of lower incisors caused by the treatment is related to the use of a facemask.

Effect of placement angle on the stability of loaded titanium microscrews: a microcomputed tomographic and biomechanical analysis.

INTRODUCTION: The aim of this study was to evaluate the impact of the placement angle on the stability of loaded microscrews. METHODS: Forty-eight microscrews were placed at 4 angles ( 30°, 50°, 70°, and 90°) into the tibiae of 12 beagles, loaded with a force of 2 N immediately, and maintained for 8 weeks. Microcomputed tomography and pullout tests were used for morphometric and biomechanical analyses, respectively. RESULTS: All microcomputed tomography parameters and the peak loads at extraction of the microscrews were influenced by the placement angles of the microscrews. The higher microcomputed tomography parameters and the peak load at extraction were measured at angles from 50° to 70°. Oblique and vertical placement angles resulted in reduced stability of the loaded microscrews (P <0.05). CONCLUSIONS: To achieve the best stability of microscrews, a placement angle of 50° to 70° is advisable.