Deletion of Tmem268 in mice suppresses anti-infectious immune responses by downregulating CD11b signaling.

Transmembrane protein 268 (TMEM268) is a novel, tumor growth-related protein first reported by our laboratory. It interacts with the integrin subunit ß4 (ITGB4) and plays a positive role in the regulation of the ITGB4/PLEC signaling pathway. Here, we investigated the effects and mechanism of TMEM268 in anti-infectious immune response in mice. Tmem268 knockout in mice aggravated cecal ligation and puncture-induced sepsis, as evidenced by higher bacterial burden in various tissues and organs, congestion, and apoptosis. Moreover, Tmem268 deficiency in mice inhibited phagocyte adhesion and migration, thus decreasing phagocyte infiltration at the site of infection and complement-dependent phagocytosis. Further findings indicated that TMEM268 interacts with CD11b and inhibits its degradation via the endosome-lysosome pathway. Our results reveal a positive regulatory role of TMEM268 in ß2 integrin-associated anti-infectious immune responses and signify the potential value of targeting the TMEM268-CD11b signaling axis for the maintenance of immune homeostasis and immunotherapy for sepsis and related immune disorders.

Pediatric sleep-disordered breathing in Shanghai: characteristics, independent risk factors and its association with malocclusion.

OBJECTIVES: This study aimed to determine the prevalence and independent risk factors of SDB, and explore its association with malocclusion among 6-11-year-old children in Shanghai, China. METHODS: A cluster sampling procedure was adopted in this cross-sectional study. Pediatric Sleep Questionnaire (PSQ) was applied to evaluate the presence of SDB. Questionnaires including PSQ, medical history, family history, and daily habits/environment were completed by parents under instruction, and oral examinations were implemented by well-trained orthodontists. Multivariable logistic regression was applied to identify independent risk factors for SDB. Chi-square tests and Spearman's Rank Correlation were used to estimate the relationship between SDB and malocclusion. RESULTS: A total of 3433 subjects (1788 males and 1645 females) were included in the study. The SDB prevalence was about 17.7%. Allergic rhinitis (OR 1.39, 95% CI 1.09-1.79), adenotonsillar hypertrophy (OR 2.39, 95% CI 1.82-3.19), paternal snoring (OR 1.97, 95% CI 1.53-2.53), and maternal snoring (OR 1.35, 95% CI 1.05-1.73) were independent risk factors for SDB. The SDB prevalence was higher in children with retrusive mandibles than in proper or excessive ones. No significant difference was observed in the correlation between SDB and lateral facial profile, mandible plane angle, constricted dental arch form, the severity of anterior overjet and overbite, degree of crowding and spacing, and the presence of crossbite and open bite. CONCLUSIONS: The prevalence of SDB in primary students in the Chinese urban population was high and highly associated with mandible retrusion. The independent risk factors included Allergic rhinitis, adenotonsillar hypertrophy, paternal snoring, and maternal snoring. More efforts should be made to enhance public education about SDB and related dental-maxillofacial abnormalities.

Cancer stem cell markers ALDH1 and Bmi1 expression in oral erythroplakia revisited: Implication for driving the process of field cancerization.

The correlation of ALDH1 and Bmi1 expression in potentially malignant oral erythroplakia (OE) with oral carcinoma development was reported in our earlier study. Interestingly, a model of field cancerization orchestrated by the cancer stem cells (CSC) was proposed and suggested the identification of CSC-specific markers is useful for prognosis and providing novel targets for prevention and treatment of field cancerization. We revisited the correlation of ALDH1 and Bmi1 expression in OE with the second and multiple carcinomas development. Strikingly, we observed that the expression of ALDH1 and Bmi1 within a single potentially malignant OE lesion significantly correlate with subsequently developing multiple and multifocal carcinomas, which parallels the process of oral field cancerization. Significantly, ALDH1 and Bmi1 are well-defined markers of CSC for head and neck cancer. Consequently, we provided a preliminary evidence for CSC driving the process of field cancerization.

Ad5-EMC6 mediates antitumor activity in gastric cancer cells through the mitochondrial apoptosis pathway.

Endoplasmic reticulum membrane protein complex subunit 6 (EMC6), also known as transmembrane protein 93 (transmembrane protein 93, TMEM93), is an autophagy-related protein. EMC6 overexpression inhibits cancer cell growth and induces apoptosis, but the interaction partners of EMC6 and its cellular responsibilities remain incompletely understood. In this study, we report that adenovirus-mediated ectopic overexpression of EMC6 (Ad5-EMC6) in BGC823 and SGC7901 gastric cancer cells decreases the activity of ERK1/2, down-regulates the levels of BCL-2 protein and phosphorylated BCL-2, increases the expression of tBID and BAX, and decreases mitochondrial membrane potential and subsequently leading to cell apoptosis. In a xenograft tumor model, we found that Ad5-EMC6 impairs the tumorigenesis of SGC7901 gastric cancer cells in nude mice. Additionally, Ad5-EMC6 enhances the sensitivity of gastric cancer cells to the chemotherapeutic drug etoposide. Collectively, these results demonstrate that EMC6-induced apoptosis of gastric cancer cells occurs at least partially through the mitochondrial-mediated apoptosis pathway. Our study suggests a rational basis for the potential clinical application of Ad5-EMC6 in gastric cancer.

Prevalence and distribution of oral mucosal lesions: a cross-sectional study in Shanghai, China.

BACKGROUND: An epidemiological study on the oral mucosal lesions (OMLs) in general population from China was scarce. The objective of this study was to investigate the prevalence and distribution of OMLs in Shanghai, China and to evaluate their association with demographic factors and smoking/drinking habits based on a large scaled population on a wide spectrum. METHODS: In this population-based cross-sectional study, 11054 community-dwelling individuals (M/F: 5140/5914; age range, 1-96 years) were randomly selected and examined according to WHO criteria. RESULTS: The prevalence of OMLs was 10.8% in this study. A total of 1192 (M/F: 543/649; mean age, 56.9 years) individuals were presented with different types of OMLs. The most common type of OMLs was fissured tongue (prevalence of 3.15%), followed by recurrent aphthae (1.48%), traumatic ulcer (1.13%), and angular cheilitis (0.86%). The two most common potentially malignant disorders were oral lichen planus (0.81%) and leukoplakia (0.22%). Regression analysis revealed that the elderly age, smoking, and alcohol intake were statistically significant risk factors of OMLs with emphasis on leukokeratosis, leukoplakia, and lichen planus. CONCLUSION: The prevalence and distribution of OMLs were elucidated in an eastern area of China, and the importance of tobacco and alcohol in the pathogenesis of OMLs was evidenced. Our data have provided baseline information about epidemiologic aspects of OMLs that can be valuable in organized program targeting on oral health and hygiene.

Machine learning for predicting liver and/or lung metastasis in colorectal cancer: A retrospective study based on the SEER database.

OBJECTIVE: This study aims to establish a machine learning (ML) model for predicting the risk of liver and/or lung metastasis in colorectal cancer (CRC). METHODS: Using the National Institutes of Health (NIH)'s Surveillance, Epidemiology, and End Results (SEER) database, a total of 51265 patients with pathological diagnosis of colorectal cancer from 2010 to 2015 were extracted for model development. On this basis, We have established 7 machine learning algorithm models. Evaluate the model based on accuracy, and AUC of receiver operating characteristics (ROC) and explain the relationship between clinical pathological features and target variables based on the best model. We validated the model among 196 colorectal cancer patients in Beijing Electric Power Hospital of Capital Medical University of China to evaluate its performance and universality. Finally, we have developed a network-based calculator using the best model to predict the risk of liver and/or lung metastasis in colorectal cancer patients. RESULTS: 51265 patients were enrolled in the study, of which 7864 (15.3 %) had distant liver and/or lung metastasis. RF had the best predictive ability, In the internal test set, with an accuracy of 0.895, AUC of 0.956, and AUPR of 0.896. In addition, the RF model was evaluated in the external validation set with an accuracy of 0.913, AUC of 0.912, and AUPR of 0.611. CONCLUSION: In this study, we constructed an RF algorithm mode to predict the risk of colorectal liver and/or lung metastasis, to assist doctors in making clinical decisions.

Expression of cancer stem cell markers ALDH1 and Bmi1 in oral erythroplakia and the risk of oral cancer.

BACKGROUND: Oral erythroplakia (OE) is a notoriously aggressive oral pre-malignant lesion with a high tendency to oral cancer development, but its biological behavior is largely unknown. The objective of this study was to determine the expression of cancer stem cell markers ALDH1 and Bmi1 in OE and their correlation with malignant transformation of OE. METHODS: In a retrospective case-control study, expression patterns of ALDH1 and Bmi1 were determined using immunohistochemistry in samples from 34 patients with OE, including patients with untransformed lesions (n=17) and patients with malignant transformed lesions (n=17). RESULTS: ALDH1 and Bmi1 expression was observed in 19 (55.9%) and 20 (58.8%) of 34 patients with OE, respectively. Multivariate analysis revealed that ALDH1 expression was significantly associated with increased risk of transformation (P<0.05), but Bmi1 expression was not a significant marker (P > 0.05). Notably, the coexpression of both ALDH1 and Bmi1 was a strong indicator associated with 8.56-fold (95% confidence interval [CI], 1.74-42.17; P<0.01) for malignant transformation. Point prevalence analysis revealed that 78.6% (95% CI, 54.0-100) of the patient with coexpression of both ALDH1 and Bmi1 developed oral cancer. CONCLUSION: Our data indicated that the expression patterns of ALDH1 and Bmi1 in OE were associated with malignant transformation, suggesting that they may be valuable predictors for evaluating the risk of oral cancer.

Immunoexpression of interleukin-22 and interleukin-23 in oral and cutaneous lichen planus lesions: a preliminary study.

Interleukin- (IL-) 22 is the signature cytokine of T-helper (Th) 22 cells, and IL-23 is required for IL-22 production. The objective of this study was to examine the immunoexpression of IL-22 and IL-23 in archival paraffin-embedded biopsy specimens from oral LP (n = 42) and cutaneous LP (n = 38) against normal control tissues. The results showed that the percentage of cells expressing IL-22 and IL-23 in LP were significantly higher in LP compared to controls, respectively (both P < 0.001). The correlation between IL-22 and IL-23 expression was significant (P < 0.05). Moreover, the percentage of cells expressing IL-22 and IL-23 in oral LP were significantly higher than cutaneous LP (P < 0.05). Collectively, our findings demonstrated that the increased expression of IL-22 and IL-23 in LP lesions could play roles in the pathogenesis of LP. Moreover, oral LP expressing IL-22 and IL-23 was higher than cutaneous LP, probably due to Th22 cells as an important component of oral mucosal host defense against oral microbiota and tissue antigens. This may be associated with the difference in clinical behaviour of the two variants of the disease.

Papillary squamous cell carcinoma of the oral mucosa: a clinicopathologic and immunohistochemical study of 12 cases and literature review.

Papillary squamous cell carcinoma (SCC) (PSCC) of the oral mucosa is a relatively rare but distinct variant of SCC of head and neck. The objectives of this study were to describe the clinicopathologic and immunohistochemical features of a series of patients with oral PSCC and to review the literature on this topic. Retrospective review of patients with clinical and pathologic diagnosis of PSCC (n = 12) between 2000 and 2008 in our institution was conducted. The outcome analysis in a mean follow-up of 56 months (range, 24-131 months) was performed. These patients were 7 women and 5 men, and the mean age at diagnosis was 72.9 years (range, 53-83 years). The cheek and the gingiva were the predominant sites of involvement. At the end of follow-up, 4 patients were found to have local recurrence, and 3 were dead of disease. The estimated 3- and 5-year survival was 91.7% and 76.4% for the whole series, respectively. Histopathologically, the papillary pattern consisted of multiple, thin, delicate filiform, finger-like papillary projections with fibrovascular cores. Besides, the exophytic pattern consisted of the broad-based bulbous to "cauliflower-like" exophytic growth with rounded projections. Immunohistochemically, positivity for CKpan, CKhmw (high molecular weight), and p53, yet negativity for CK8, vimentin, desmin, smooth muscle actin, and S-100 was observed in PSCC. In conclusion, 2 specific histopathologic growth patterns of oral PSCC were identified to separate from conventional SCC. Patients with PSCC have a favorable outcome in relation to exophytic nature and limited invasion of the tumor.

Candidal infection in oral leukoplakia: a clinicopathologic study of 396 patients from eastern China.

Previous studies have suggested a link between the presence of Candida invasion and oral premalignant lesion. The objective of the current study was to investigate the clinicopathologic features of candidal infection in biopsies of a large retrospective cohort of patients with premalignant oral leukoplakia (n = 396) from eastern China and assess the clinical implications. Candidal hyphae were detected with periodic acid-Schiff staining of the biopsy samples. The results showed that 59 patients (15.9%) with oral leukoplakia were infected by Candida. The average age of the patients with candidal leukoplakia was 60.7 years with equal sex ratio. The tongue was the predominant site (66.1%). Epithelial hyperplasia and dysplasia were involved in 44.1% and 55.9% of patients, respectively. Multivariate analysis revealed that patient older than 60 years (odd ratio [OR], 2.28; P = .005), lesion located at the tongue (OR, 1.89; P = .038), and presence of dysplasia (OR, 2.02; P = .018) were significant risk factors of candidal infection in oral leukoplakia. Collectively, clinicopathologic features of candidal leukoplakia in eastern China were elucidated. A point to highlight was that we identified a subpopulation that was more liable to candidal infection. Elderly patients with oral tongue leukoplakia with epithelial dysplasia had much higher risk of candidal infection. Antifungal therapy was further recommended to be routine treatment of this subpopulation.

CD133 expression in oral lichen planus correlated with the risk for progression to oral squamous cell carcinoma.

Oral lichen planus (OLP) is a potentially malignant disorder associated with an increased risk for progression to oral squamous cell carcinoma (OSCC). The objective of this study to determine protein expression of cancer stem cell marker CD133 in tissue samples of patients with OLP and evaluate the correlation between CD133 expression and the risk of progression to OSCC. In this longitudinal case-control study, a total of 110 patients with OLP who received a mean follow-up of 56 months were enrolled, including 100 patients who did not progress to OSCC and 10 patients who had progressed to OSCC. CD133 expression was determined using immunohistochemistry in samples from these patients. Analysis of 10 cases of normal oral mucosa and 6 cases of postmalignant OSCC form previously diagnosed OLP was also performed. The results showed that CD133 expression was observed in 29% cases of nonprogressing OLP and in 80% cases of progressing OLP (P = .002). CD133 was not expressed in normal oral mucosa, but it positively expressed in the 100% cases of OSCC. Logistic regression analysis revealed that the risk of malignant progression in the patients with CD133-positive expression was significantly higher than those with CD133 negativity (odds ratio, 9.79; 95% confidence interval, 1.96-48.92; P = .005). Collectively, CD133 expression was significantly associated with malignant progression in a longitudinal series of patients with OLP. Our findings suggested that CD133 may serve as a novel candidate biomarker for risk assessment of malignant potential of OLP.

The Influence of Emotional Experience on Semantic Processing of Concrete Concepts.

Introduction: Parallel distributed processing theory (PDP theory) holds that all brain regions involved in conceptual representation perform a series of activities at the same time. However, the role of emotional experience information in concrete conceptual representation is still unknown. This study further explores whether the emotional experience will also affect the semantic processing of concrete concept representations. Methods: This study used the emotion priming paradigm and semantic judgment task to explore whether emotion priming impacts the processing of animal concepts with different emotional experiences through two experiments. In Experiments 1a and 1b, pleasant or disgusted faces were used as emotional priming stimuli to explore whether the explicit processing of emotions would affect the semantic processing of animal concepts. Experiments 2a and 2b used positive or negative scenery pictures as emotional priming stimuli to explore whether the implicit processing of emotions would affect the semantic processing of animal concepts. Results: The Experiment 1 results showed that the perception of faces promotes the processing of animal words, showing the "word-emotion congruence effect". Experiment 2a did not show the expected results, while Experiment 2b showed that the general negative perception of scenery pictures could significantly promote the processing of disgusted animal words. The results further proved the "word-emotion congruence effect" shown in the results of Experiment 1 from the perspective of implicit emotion processing. Combining the results of two experiments, it can be proven that emotional experience affects the semantic processing process of concrete concepts. Discussion: Both Experiment 1 and Experiment 2b of this study show the "word-emotion congruence effect". PDP theory believes that conceptual representation is represented by the activity patterns of billions of neurons distributed in many areas of the brain, and related semantic processing and sensory processing will occur simultaneously. The results of this experiment well support PDP theory.

The Effect of Intranasal Dexmedetomidine on Emergence Delirium Prevention in Pediatric Ambulatory Dental Rehabilitation Under General Anesthesia: A Randomized Clinical Trial.

Purpose: Sevoflurane is the preferred anesthetic agent for induction and maintenance of ambulatory surgery due to its property of fast onset and recovery. However, it has been recognized as one of the major contributors of emergence delirium. The aim of this study was to evaluate the preventive effect of intranasal dexmedetomidine on the occurrence of emergence delirium in pediatric patients under general anesthesia with sevoflurane. Patients and Methods: Ninety pediatric patients undergoing dental rehabilitation under sevoflurane anesthesia were enrolled in this study. The patients were divided into three groups (n=30 each in the 2 µg/kg dexmedetomidine, 1 µg/kg dexmedetomidine, and control with saline groups). The same volume (0.02mL/kg) of the mixed solution was dropped into the nasal cavity of the children 30 minutes before surgery. We used the Pediatric Anesthesia Emergence Delirium Scale (PAED) to assess the level and incidence of delirium in the post-anesthesia care unit. Results: Compared with the control group, prophylactic use of different dosages of intranasal dexmedetomidine significantly reduces the incidence of ED and severe ED in PACU (P<0.001). Intranasal administration of 2 µg/kg dexmedetomidine was associated with a better acceptance of mask induction and a better tolerance of separation with parents. Conclusion: Both 2 µg/kg and 1 µg/kg intranasal dexmedetomidine can achieve ED preventive effects in PACU in dental rehabilitation under general anesthesia. A dosage of 2 µg/kg is more effective in preventing severe ED and providing better mask acceptance.

RNF115/BCA2 deficiency alleviated acute liver injury in mice by promoting autophagy and inhibiting inflammatory response.

The E3 ubiquitin ligase RING finger protein 115 (RNF115), also known as breast cancer-associated gene 2 (BCA2), has been linked with the growth of some cancers and immune regulation, which is negatively correlated with prognosis. Here, it is demonstrated that the RNF115 deletion can protect mice from acute liver injury (ALI) induced by the treatment of lipopolysaccharide (LPS)/D-galactosamine (D-GalN), as evidenced by decreased levels of alanine aminotransaminase, aspartate transaminase, inflammatory cytokines (e.g., tumor necrosis factor α and interleukin-6), chemokines (e.g., MCP1/CCL2) and inflammatory cell (e.g., monocytes and neutrophils) infiltration. Moreover, it was found that the autophagy activity in Rnf115-/- livers was increased, which resulted in the removal of damaged mitochondria and hepatocyte apoptosis. However, the administration of adeno-associated virus Rnf115 or autophagy inhibitor 3-MA impaired autophagy and aggravated liver injury in Rnf115-/- mice with ALI. Further experiments proved that RNF115 interacts with LC3B, downregulates LC3B protein levels and cell autophagy. Additionally, Rnf115 deletion inhibited M1 type macrophage activation via NF-κB and Jnk signaling pathways. Elimination of macrophages narrowed the difference in liver damage between Rnf115+/+ and Rnf115-/- mice, indicating that macrophages were linked in the ALI induced by LPS/D-GalN. Collectively, for the first time, we have proved that Rnf115 inactivation ameliorated LPS/D-GalN-induced ALI in mice by promoting autophagy and attenuating inflammatory responses. This study provides new evidence for the involvement of autophagy mechanisms in the protection against acute liver injury.

Two stem cell markers, ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1, predict the transformation of oral leukoplakia to cancer: a long-term follow-up study.

BACKGROUND: Although oral leukoplakia (OL) is the best-known potentially malignant disorder, the risk of OL malignant transformation is difficult to assess. ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1 are stem cell markers that have been found to be associated with head and neck tumorigenesis. The objective of the current study was to evaluate the usefulness of ABCG2 and BMI-1 in predicting OL transformation. METHODS: In a retrospective cohort of 135 patients with OL from the study institution who had a mean follow-up of 5.5 years, 32 developed cancer between 1985 and 2008. The expression of ABCG2 and BMI-1 was determined using immunohistochemistry in samples from these patients, and included untransformed OL (n = 103) and malignant-transformed OL (n = 32). The association between protein expression and clinicopathological parameters and transformation was analyzed. RESULTS: Expression of ABCG2 and BMI-1 was observed in 58 (43.0%) and 44 (32.6%) of 135 patients, respectively. The correlation between ABCG2 and BMI-1 expression was significant (P = .024). Kaplan-Meier analysis revealed that 37.9% of patients with ABCG2 positivity developed cancer compared with 13.0% of patients with ABCG2 negativity (P = .014, log-rank test). Approximately 40.9% of patients with BMI-1 positivity developed cancer compared with 15.4% of patients with BMI-1 negativity (P = .029, log-rank test). Multivariate analysis revealed that ABCG2 and BMI-1 expression was associated with a 3.24-fold (95% confidence interval [95% CI], 1.31-7.98; P = .011) and 4.03-fold (95% CI, 1.59-10.26; P = .003) increased the risk of transformation, respectively. CONCLUSIONS: ABCG2 and BMI-1 expression was found to be associated with the development of oral cancer in a large cohort of patients with OL for whom long-term follow-up was available, which suggests that ABCG2 and BMI-1 may be used as predictors of OL transformation.

Clinicopathologic features of oral squamous papilloma and papillary squamous cell carcinoma: a study of 197 patients from eastern China.

Oral squamous papilloma and papillary squamous cell carcinoma are 2 clinicopathologically distinctive papillary epithelial tumors. The current study aims to compare the clinical and pathologic features of these oral papillary lesions in a patient population from eastern China. A retrospective review in a series of patients with clinical and pathologic diagnosis of oral squamous papilloma (n = 141) and papillary squamous cell carcinoma (n = 56) was conducted. The average age of oral squamous papilloma was 51.0 years (male-to-female ratio, 1.82), with the palate being the predominant site. The average age of oral papillary squamous cell carcinoma was 63.3 years (male-to-female ratio, 1.67), with the gingiva being the predominant site. Multivariate analysis revealed that the elderly patient with papillary lesion (≥60 years) was associated with 3.09-fold (95% confidence interval, 1.59-6.03) increased carcinoma risk compared with the nonelderly patient. The lesion located on the gingiva was associated with 4.98-fold (95% confidence interval, 1.96-12.63) increased carcinoma risk compared with other oral sites. Collectively, clinicopathologic features of oral squamous papilloma and papillary squamous cell carcinoma in eastern China were elucidated. Elderly patients with oral papillary lesions located on the gingiva correlate with higher carcinoma risk. It highlights the importance of using a histologic examination to confirm the clinical diagnosis for any suspicious papillary lesions.

A retrospective clinicopathological study on oral lichen planus and malignant transformation: analysis of 518 cases.

OBJECTIVE: To investigate the epidemiological and clinical characteristics of a relatively large cohort of patients with oral lichen planus (OLP) from eastern China. STUDY DESIGN: A total of 518 patients with histologically confirmed OLP in a long-term follow-up period (6 months-21.5 years) were retrospectively reviewed in our clinic. RESULTS: Of the 518 patients, 353 females and 165 males were identified. The average age at diagnosis was 46.3 years (range 9-81 years) with the buccal mucosa being the most common site (87.8%). At initial presentation, white lichen and red lichen was seen in 52.3% and 47.7% patients, respectively. Of these, 5 (0.96%) patients previously diagnosed clinically and histopathologically as OLP developed oral cancer. All of them were the females with no a history of smoking or alcohol use. CONCLUSIONS: Clinical features of eastern Chinese OLP patients were elucidated. Notably, approximately 1% of OLP developed into cancer, which provides further evidence of potentially malignant nature of OLP.

Efficacy of orthodontic treatment versus adenotonsillectomy in children with moderate obstructive sleep apnoea and mandibular retrognathia: study design and protocol for a non-inferiority randomised controlled trial.

INTRODUCTION: Orthodontic treatment and adenotonsillectomy (AT) are both conventional treatments for paediatric obstructive sleep apnoea (OSA). Each approach has distinct treatment advantages; however, there is currently a lack of solid evidence to support their efficacy comparison. We hypothesise that the objective effect of orthodontic treatment is not inferior to AT in children with moderate OSA and mandibular retrognathia, but orthodontic treatment has the advantage of promoting dentofacial growth. METHODS AND ANALYSIS: This is a randomised, open-label, parallel-group, active controlled trial that will study the efficacy of orthodontic treatment versus AT in children with moderate OSA accompanied by tonsillar adenoid hypertrophy and mandibular retrognathia. A total of 98 patients will be enrolled and randomised in a 2:1 ratio to either orthodontic treatment or AT group. Participants will be recruited at Shanghai Stomatological Hospital, Shanghai Children's Hospital of Shanghai Jiaotong University and Children's Hospital of Fudan University, which are all located in Shanghai, China. The primary endpoint is the per cent change in the obstructive apnoea-hypopnoea index from baseline (month 0) to the primary endpoint (month 7), and the mean reduction in A point, nasion and B point angle on cephalometric measurements by lateral X-ray films. Important secondary efficacy endpoints include sleep duration with oxygen saturation below 90% according to polysomnography and subjective symptoms (assessed by the OSA-20 questionnaire), etc. Safety endpoints will also be evaluated. ETHICS AND DISSEMINATION: The study was approved by the ethics committees of Shanghai Stomatological Hospital (approval no. (2021)002), Shanghai Children's Hospital of Shanghai Jiaotong University (approval no. 2021R046-F01) and Children's Hospital of Fudan University (approval no. (2021)136). Before enrolment, a qualified clinical research assistant will obtain written informed consent from both the participants and their guardians after full explanation of this study. The results will be presented at national or international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000037288.

TMEM189 negatively regulates the stability of ULK1 protein and cell autophagy.

ULK1 is crucial for initiating autophagosome formation and its activity is tightly regulated by post-translational modifications and protein-protein interactions. In the present study, we demonstrate that TMEM189 (Transmembrane protein 189), also known as plasmanylethanolamine desaturase 1 (PEDS1), negatively regulates the proteostasis of ULK1 and autophagy activity. In TMEM189-overexpressed cells, the formation of autophagesome is impaired, while TMEM189 knockdown increases cell autophagy. Further investigation reveals that TMEM189 interacts with and increases the instability of ULK1, as well as decreases its kinase activities. The TMEM189 N-terminal domain is required for the interaction with ULK1. Additionally, TMEM189 overexpression can disrupt the interaction between ULK1 and TRAF6, profoundly impairs K63-linked polyubiquitination of ULK1 and self-association, leading to the decrease of ULK1 stability. Moreover, in vitro and in vivo experiments suggest that TMEM189 deficiency results in the inhibition of tumorigenicity of gastric cancer. Our findings provide a new insight into the molecular regulation of autophagy and laboratory evidence for investigating the physiological and pathological roles of TMEM189.

The Effect of the Quantity and Distribution of Teammates' Tendency Toward Self-Interest and Altruism on Individual Decision-Making.

Previous studies have explored the impact of the cost ratio of individual solutions versus collective solutions on people's cooperation tendency in the presence of individual solutions. This study further explored the impact of team credibility on people's propensity to cooperate in the presence of individual solutions. Study 1 investigated the influence of different level of altruistic tendencies or the self-interest tendencies of teammates on participants' decision-making. Study 2 explored the influence of the distribution of altruistic tendencies or self-interest tendencies on participants' decision-making. The results of Study 1 showed that the proportion of participants who chose the collective solution increased with an increase in the altruistic tendencies of the team. When the altruistic tendencies of the teammates reached a certain value, the proportion of participants taking the collective solution showed a trend to stabilize. Furthermore, the proportion of participants who chose the individual solution increased with the increase in the self-interest tendencies of the team. When the self-interest tendencies of the teammates reached a certain value, the individual solution was stably adopted. The results of Study 2 showed that with the total altruistic tendency remaining unchanged, the more altruistic group members that altruistic tendencies were allocated to, the higher a participant's level of trust in the team would be, which showed the decentralized effect of altruistic tendencies. In the case that the total self-interest tendency was unchanged, the fewer self-interest group members the self-interest tendencies were allocated to, the higher a participant's level of trust in the team would be, which showed the convergent effect of self-interest tendencies.