Putative pathogenic factors underlying Streptococcus oralis opportunistic infections.

Streptococcus oralis, belonging to the viridans group streptococci (VGS), has been considered a component of the normal flora predominantly inhabiting the oral cavity. In recent years, a growing body of literature has revealed that dental procedures or daily tooth brushing activities can cause the spread of S. oralis from the oral cavity into various body sites leading to life-threatening opportunistic infections such as infective endocarditis (IE) and meningitis. However, very little is currently known about the pathogenicity of S. oralis. Thus, the aim of this review is to update the current understanding of the pathogenic potential of S. oralis to pave the way for the prevention and treatment of S. oralis opportunistic infections.

RNA reading protein YTHDF2 mediates Benzo(k)fluoranthene induced male reproductive injury by regulating the stability of BCL2.

Benzo (k) fluoranthene (BkF) has adverse effects on male reproduction, but its specific mechanism of action is still unclear. This study focused on the role of RNA reading protein YTHDF2 and its mechanism in BkF induced male reproductive injury. Mouse GC-2 spermatocytes were exposed to 0, 40, 80, 160 µM BkF. It was found that BkF significantly increased the apoptosis of GC-2 cell and decreased its survival rate. BCL2 in spermatocytes decreased significantly, while the expression of P53 and BAX exhibited a notable increase. Interestingly, the expression of RNA reading protein YTHDF2 progressively rose in tandem with the escalating BkF exposure dosage. Overexpression of YTHDF2 significantly reduced the viability of cells and increased the apoptosis rate. Meanwhile, there was a substantial increase in the expression of P53 and BAX, BCL2 was significantly down-regulated. On the contrary, interfering with YTHDF2 increased cell proliferation and reduced cell apoptosis. Furthermore, YTHDF2 overexpression exacerbated the decrease in cell viability under BkF exposure, while YTHDF2 knockdown was the opposite. The results from the RIP assay demonstrated a significant enhancement in the interaction of YTHDF2 protein with BCL2 mRNA following the overexpression of YTHDF2. In addition, animal experiments showed that there was an increase in apoptosis and a decrease in proliferation of testicular cells in mice in the high-dose (30 mg/kg) BkF group by TUNEL staining and Ki67 staining. Immunohistochemical analysis showed that BCL2 levels were significantly lower in the high-dose group than in the control group, while YTHDF2, P53 and BAX were dramatically increased. In summary, our study suggests that YTHDF2 has been implicated in BkF-induced male reproductive injury by promoting the degradation of BCL2.

Dynamic changes in volatile profiles and bacterial communities during natural fermentation of Mei yu, traditional Chinese fermented fish pieces.

Microbial metabolism is important for the unique flavor formation of Mei yu, a kind of traditional Chinese fermented fish pieces. However, the interactive relationship between microorganisms and flavor components during fermentation is still unclear. In this study, electronic nose and headspace-solid-phase microextraction-gas chromatography-mass spectrometry analysis were performed to identify flavor components in Mei yu during the fermentation, and the absolute microbial quantification was conducted to identify the diversity and succession of microbial communities. During fermentation, there was an increase in the types of volatile compounds. Alcohols, aldehydes, aromatics and esters were the main flavor compounds and significantly increased in Mei yu, while hydrocarbon and aldehydes significantly decreased. The absolute abundances of Lactobacillus, Lactococcus and Weissella increased significantly after 3 days' fermentation, which were closely associated with the productions of 1-nonanol, 2-methoxy-4-vinylphenol, guaiacol, ethyl palmitate and ethyl caprylate that might though pathways related to fatty acid biosynthesis and amino acid metabolism. However, these genera were negatively correlated with the production of indole. Additionally, the total volatile basic nitrogen (TVB-N) levels of Mei yu fermented during 3 days were within the limits of 25 mg TVB-N/100 g fish, with the contents of free amino acids and lipoxygenase activities were significant lower than that of 4 days' fermentation. In view of food safety and flavor, it suggested that the natural fermented Mei yu at room temperature should be controlled within 3 days. This study highlights the application of absolute quantification to microbiome analysis in traditional fermented Mei yu and provides new insights into the roles of microorganisms in flavor formation during fermentation.

Association between glucose levels of children with type 1 diabetes and parental economic status in mobile health application.

BACKGROUND: The glycemic control of children with type 1 diabetes (T1D) may be influenced by the economic status of their parents. AIM: To investigate the association between parental economic status and blood glucose levels of children with T1D using a mobile health application. METHODS: Data from children with T1D in China's largest T1D online community, Tang-TangQuan®. Blood glucose levels were uploaded every three months and parental economic status was evaluated based on annual household income. Children were divided into three groups: Low-income (< 30000 Yuan), middle-income (30000-100000 Yuan), and high-income (> 100000 yuan) (1 Yuan = 0.145 United States Dollar approximately). Blood glucose levels were compared among the groups and associations were explored using Spearman's correlation analysis and multivariable logistic regression. RESULTS: From September 2015 to August 2022, 1406 eligible children with T1D were included (779 female, 55.4%). Median age was 8.1 years (Q1-Q3: 4.6-11.6) and duration of T1D was 0.06 years (0.02-0.44). Participants were divided into three groups: Low-income (n = 320), middle-income (n = 724), and high-income (n = 362). Baseline hemoglobin A1c (HbA1c) levels were comparable among the three groups (P = 0.072). However, at month 36, the low-income group had the highest HbA1c levels (P = 0.036). Within three years after registration, glucose levels increased significantly in the low-income group but not in the middle-income and high-income groups. Parental economic status was negatively correlated with pre-dinner glucose (r = -0.272, P = 0.012). After adjustment for confounders, parental economic status remained a significant factor related to pre-dinner glucose levels (odds ratio = 13.02, 95%CI: 1.99 to 126.05, P = 0.002). CONCLUSION: The blood glucose levels of children with T1D were negatively associated with parental economic status. It is suggested that parental economic status should be taken into consideration in the management of T1D for children.

Single-pixel positron beam diagnosis via compressive sampling.

The morphology is a crucial indicator for diagnosing a low-energy, low-brightness particle beam. However, conventional positron beam diagnosis, based on the pixel scanning principle, is limited by physical constraints, such as the resolution of detector pixels. Here, we have presented a novel slow positron diagnosis method using compressive sampling. With a 100 × 100 pixel-sized mask, for example, the positron beam morphology can be significantly reconstructed with a peak signal-to-noise ratio of ∼40 dB, even at half the sampling rate compared to pixel scanning. It explores a promising approach for positron beam diagnosis with an ultra-high resolution and fast sampling rates.

Association between composite dietary antioxidant index and stroke among individuals with diabetes.

BACKGROUND: Recent research has underscored the potentially protective role of dietary antioxidants against chronic conditions, such as cardiovascular diseases and stroke. The composite dietary antioxidant index (CDAI), which reflects the overall intake of key dietary antioxidants, has been identified as a crucial metric for exploring this relationship. Although previous research has shown a negative correlation between CDAI levels and stroke risk in prediabetic individuals, there remains a substantial gap in understanding this association among individuals with dia-betes, who are at an inherently greater risk for cerebrovascular events. AIM: To investigate the association between CDAI and stroke risk in individuals with diabetes. METHODS: Using a cross-sectional study design, this investigation analyzed data from the National Health and Nutrition Examination Survey spanning from 2003 to 2018 that included 6735 participants aged over 20 years with diabetes. The CDAI was calculated from 24-h dietary recalls to assess intake of key antioxidants: Vitamins A, C, and E; carotenoids; selenium; and zinc. Multivariate logistic regression and restricted cubic spline analysis were used to rigorously examine the relationship between CDAI and stroke risk. RESULTS: The participant cohort, with an average age of 59.5 years and a slight male majority, reflected the broader demographic characteristics of individuals with diabetes. The analysis revealed a strong inverse relationship between CDAI levels and stroke risk. Remarkably, those in the highest quintile of CDAI demonstrated a 43% lower prevalence of stroke compared to those in the lowest quintile, even after adjustments for various confounders. This finding not only highlights the negative association between CDAI and stroke risk but also underscores the significant potential of antioxidant-rich diets in reducing stroke prevalence among patients with diabetes. CONCLUSION: Our findings suggested that CDAI was inversely associated with stroke prevalence among patients with diabetes. These results suggest incorporating antioxidant-rich foods into dietary regimens as a potential strategy for stroke prevention.

[Testis-sparing microsurgery for benign testis tumor: A report of 16 cases].

OBJECTIVE: To investigate the safety and clinical effect of testis-sparing microsurgery (TSMS) in the treatment of benign testis tumor (BTT). METHODS: We retrospectively analyzed the clinical data on 16 cases of BTT treated in the Department of Andrology of the Affiliated Hospital of Qingdao University from October 2020 to February 2023. The median age of the patients was 23 years. All the tumors were unilateral, 7 in the left and 9 in the right side, with a median diameter of 1.85 cm (1.0－3.5 cm). The patients all underwent color Doppler flow imaging (CDFI), MRI, semen analysis and examination of serum T, alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH), followed by TSMS. The boundaries between the tumors and normal testis tissue were accurately identified under the microscope, and the tumors and the adjacent normal testis tissue 2 mm from their margins were excised completely. Bipolar coagulation forceps were used for wound hemostasis to maximally preserve the normal testis tissue. The resected specimens were subjected to fast frozen pathology intraoperatively, and the patients were followed up for 14－40 months by regular scrotal CDFI, MRI and examinations of serum T and semen parameters. RESULTS: The levels of serum T, AFP, HCG and LDH and semen parameters were all within the normal range preoperatively. TSMS were successfully completed in all the cases, and all were pathologically confirmed as BTT according to the latest edition of WHO Classification of Tumors: Urinary and Male Genital Tumors. CDFI showed normal blood supply within the testis tissue at 1 month after surgery. No signs of intra-testicular tumor residue, recurrence or metastasis, nor significant changes in the levels of serum T, AFP, HCG or LDH or semen parameters were observed during the follow-up as compared with the baseline. Natural conception was achieved in 2 cases at 16 and 18 months respectively after surgery. CONCLUSION: BTT can be differentially diagnosed by CDFI and MRI before surgery and confirmed by histopathology. TSMS can achieve complete excision of the tumor, maximal sparing of the normal testis tissue and thereby effective preservation of male fertility.

FTO mediates bisphenol F-induced blood-testis barrier impairment through regulating ferroptosis via YTHDF1/TfRc and YTHDF2/SLC7A11 signal axis.

Bisphenol F (BPF) has been extensively utilized in daily life, which brings new hazards to male reproductive health. However, the specific functional mechanism is still unclear. Both cell and animal models were utilized for exploring the role of RNA methylation and ferroptosis and its underlying mechanisms in male reproductive injury induced by BPF. In animal model, BPF severely destroyed the integrity of the blood-testis barrier (BTB) and induced ferroptosis. Furthermore, BPF significantly affected the barrier function of TM4 cells and promoted ferroptosis. Importantly, ChIP assays revealed that BPF inhibited AR transcriptional regulation of FTO and FTO expression was downregulated in TM4 cells. Overexpression of FTO prevented the impairment of BTB by inhibiting ferroptosis in TM4 cells. Mechanistically, FTO could significantly down-regulate the m6A modification level of TfRc and SLC7A11 mRNA through MeRIP experiment. RIP experiments showed that YTHDF1 can bind to TfRc mRNA and promote its translation while YTHDF2 could bind to SLC7A11 mRNA and reduce its mRNA stability. Therefore, our results suggest that FTO plays a key role in BPF induced male reproductive toxicity through YTHDF1-TfRc axis and YTHDF2-SLC7A11 axis and may provide new ideas and methods for the prevention and treatment of male reproductive diseases associated with environmental pollutants.

Benzo(a)pyrene promotes the malignant progression of malignant-transformed BEAS-2B cells by regulating YTH N6-methyladenosine RNA binding protein 1 to inhibit ferroptosis.

Benzo[a]pyrene (BaP) is associated with the development of lung cancer, but the underlying mechanism has not been completely clarified. Here, we used 10 µM BaP to induce malignant transformation of human bronchial epithelial BEAS-2B cells, named BEAS-2B-T. Results indicated that BaP (6.25, 12.5 and 25 µM) treatment significantly promoted the migration and invasion of BEAS-2B-T cells. Meanwhile, BaP exposure inhibited ferroptosis in BEAS-2B-T, ferroptosis-related indexes Fe2+, malondialdehyde (MDA), lipid peroxidation (LPO) and reactive oxygen species (ROS) decreased significantly. The protein level of ferroptosis-related molecule transferrin receptor (TFRC) decreased significantly, while solute carrier family 7 membrane 11 (SLC7A11), ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) increased significantly. The intervention of ferroptosis dramatically effected the migration and invasion of BEAS-2B-T induced by BaP. Furthermore, the expression of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) was markedly increased after BaP exposure. YTHDF1 knockdown inhibited BEAS-2B-T migration and invasion by promoting ferroptosis. In the meantime, the contents of Fe2+, MDA, LPO and ROS increased significantly, TFRC was markedly increased, and SLC7A11, FTH1, and GPX4 were markedly decreased. Moreover, overexpression of YTHDF1 promoted BEAS-2B-T migration and invasion by inhibiting ferroptosis. Importantly, knockdown of YTHDF1 promoted ferroptosis and reduced BEAS-2B-T migration and invasion during BaP exposure, and overexpression of YTHDF1 increased migration and invasion of BEAS-2B-T by inhibiting ferroptosis during BaP exposure. RNA immunoprecipitation assays indicated that the binding of YTHDF1 to SLC7A11 and FTH1 markedly increased after YTHDF1 overexpression. Therefore, we concluded that BaP promotes the malignant progression of BEAS-2B-T cells through YTHDF1 upregulating SLC7A11 and FTH1 to inhibit ferroptosis. This study reveals new epigenetic and ferroptosis markers for preventing and treating lung cancer induced by environmental carcinogens.

Clinical phenotype and laboratory characteristics of 93 patients with congenital fibrinogen disorders from unrelated 36 families.

Background: Congenital fibrinogen disorders (CFDs) are rare bleeding disorders (RBDs) caused by mutations in 1 of the 3 fibrinogen genes (FGA, FGB, and FGG). Objectives: To investigate the clinical phenotype, laboratory features, diagnosis, treatment, and prognosis of CFDs. Methods: Clinical data of 93 subjects with CFDs identified from June 2018 to December 2023 were retrospectively analyzed. Results: Among the 93 patients, there were 46 males (49.5%) and 47 females (50.5%), with a median age of 23 years. Fifty-three of 93 (57%) subjects experienced bleeding, 3/93 (3.2%) experienced thrombosis, and 37/93 (39.8%) were asymptomatic. Females were more prone to experience bleeding (P < .0001). The 93 patients exhibited prolonged thrombin time, significantly decreased fibrinogen activity (Fg:C), and normal or decreased fibrinogen antigen. The 93 patients included 3 with hypofibrinogenemia, 16 with hypodysfibrinogenemia, and 74 with dysfibrinogenemia. Among the 53 patients with bleeding, bleeding episodes were identified in 3.8% (2/53), 20.8% (11/53), and 75.5% (40/53) patients with hypofibrinogenemia, hypodysfibrinogenemia, and dysfibrinogenemia, respectively. Genetic analysis was performed on 22 cases from 8 pedigrees, revealing 10 mutations, including 1 novel splice mutation. Twenty-eight (30.1%) subjects received replacement therapy to treat or prevent bleeding, consisting of 8 fresh frozen plasma transfusions, 3 packing and suture treatment, and 61 fibrinogen infusions. Conclusion: Most patients with CFDs have mild or no bleeding symptoms. Fg:C combined with fibrinogen antigen and pedigree investigation can improve the feasibility and accuracy of diagnosis of CFDs. The severity of bleeding symptoms was negatively correlated with Fg:C.

Teleost-specific TLR23 in Takifugu rubripes recruits MyD88 to trigger ERK pathway and promotes antibacterial defense.

Takifugu rubripes is a highly valued cultured fish in Asia, while pathogen infections can result in severe diseases and lead to substantial economic losses. Toll-like receptors (TLRs), as pattern recognition receptors, play a crucial role on recognition pathogens and initiation innate immune response. However, the immunological properties of teleost-specific TLR23 remain largely unknown. In this study, we investigated the biological functions of TLR23 (TrTLR23) from T. rubripes, found that TrTLR23 existed in various organs. Following bacterial pathogen challenge, the expression levels of TrTLR23 were significantly increased in immune related organs. TrTLR23 located on the cellular membrane and specifically recognized pathogenic microorganism. Co-immunoprecipitation and antibody blocking analysis revealed that TrTLR23 recruited myeloid differentiation primary response protein (MyD88), thereby mediating the activation of the ERK signaling pathway. Furthermore, in vivo showed that, when TrTLR23 is overexpressed in T. rubripes, bacterial replication in fish tissues is significantly inhibited. Consistently, when TrTLR23 expression in T. rubripes is knocked down, bacterial replication is significantly enhanced. In conclusion, these findings suggested that TrTLR23 played a critical role on mediation TLR23-MyD88-ERK axis against bacterial infection. This study revealed that TLR23 involved in the innate immune mechanism, and provided the foundation for development disease control strategies in teleost.

Challenges and Suggestions of Ethical Review on Clinical Research Involving Brain-Computer Interfaces.

Brain-computer interface (BCI) technology is rapidly advancing in medical research and application. As an emerging biomedical engineering technology, it has garnered significant attention in the clinical research of brain disease diagnosis and treatment, neurological rehabilitation, and mental health. However, BCI also raises several challenges and ethical concerns in clinical research. In this article, the authors investigate and discuss three aspects of BCI in medicine and healthcare: the state of international ethical governance, multidimensional ethical challenges pertaining to BCI in clinical research, and suggestive concerns for ethical review. Despite the great potential of frontier BCI research and development in the field of medical care, the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in BCI. To ensure "responsible innovation" in BCI research in healthcare and medicine, the creation of an ethical global governance framework and system, along with special guidelines for cutting-edge BCI research in medicine, is suggested.

Analytical and experimental analysis of concrete temperature and energy considering open-air environmental variations.

Longwave radiation is an important open-air environmental factor that can significantly affect the temperature of concrete, but it has often been ignored in the temperature analysis of open-air concrete structures. In this article, an improved analytical model of concrete temperature was proposed by considering solar radiation, thermal convection, thermal conduction and especially longwave radiation. Temperature monitoring of an open-air concrete block was carried out to verify the proposed model and analyze the heat energy characteristics of open-air concrete. As demonstrated by the open-air experiment, under the influence of longwave radiation, the temperature at the top of the concrete block could decrease rapidly at night and even become lower than the minimum temperature at its bottom. Compared with the analytical model that ignores longwave radiation, the improved model that includes it better matches the measured temperature. According to the energy analysis, although solar radiation controls the transient variation in heat energy, the heat exchange caused by longwave radiation were more than that caused by convection on sunlit surfaces, which indicates the importance of considering longwave radiation.

Cloud inversion analysis of surrounding rock parameters for underground powerhouse based on PSO-BP optimized neural network and web technology.

Aiming at the shortcomings of the BP neural network in practical applications, such as easy to fall into local extremum and slow convergence speed, we optimized the initial weights and thresholds of the BP neural network using the particle swarm optimization (PSO). Additionally, cloud computing service, web technology, cloud database and numerical simulation were integrated to construct an intelligent feedback analysis cloud program for underground engineering safety monitoring based on the PSO-BP algorithm. The program could conveniently, quickly, and intelligently carry out numerical analysis of underground engineering and dynamic feedback analysis of surrounding rock parameters. The program was applied to the cloud inversion analysis of the surrounding rock parameters for the underground powerhouse of the Shuangjiangkou Hydropower Station. The calculated displacement simulated with the back-analyzed parameters matches the measured displacement very well. The posterior variance evaluation shows that the posterior error ratio is 0.045 and the small error probability is 0.999. The evaluation results indicate that the intelligent feedback analysis cloud program has high accuracy and can be applied to engineering practice.

Current landscape of primary small bowel leiomyosarcoma: cases report and a decade of insights.

The incidence of leiomyosarcoma (LMS) is about 4-5/100,000 individuals per year. LMSs occurring in the small bowel are even rarer, and their preoperative diagnosis is very difficult. We described two patients with pathologically confirmed small bowel LMS and analyzed their clinical and medical imaging features. Similar cases reported in English in Pubmed database over the past decade were reviewed and summarized. These tumors were categorized by the growth direction and relationship with the intestinal lumen into three types: intraluminal (n = 10), intermural (n = 3), and extraluminal (n = 7). Notably, among the three types of LMS, the intramural leiomyosarcoma stands out as a noteworthy subtype. Emerging evidence suggests that smaller tumor size (< 5 cm) and the intraluminal type may serve as favorable prognostic indicators, while the extraluminal type is associated with relatively poor prognosis. Furthermore, the integration of imaging features with CA125 and LDH biomarkers holds promise for potential diagnostic value in LMS.

Current understanding of ELF4 deficiency: a novel inborn error of immunity.

BACKGROUND: ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity (IEIs), specifically categorized as a "disease of immune dysregulation." Cases of this condition, reported by our team and others, are very limited worldwide. As such, our current knowledge of this new disease remains preliminary. This review aims to provide a brief overview of the clinical manifestations, pathogenesis, and treatment strategies for this novel IEI. DATA SOURCES: A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 deficiency. Our search strategy was "ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor" as of the time of manuscript submission. RESULTS: The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer, abdominal pain, and diarrhea in pediatric males. In some cases, immunodeficiency and autoimmunity can also be prominent. Targeted Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 gene. Western blotting for ELF4 expression of the patient's cells can confirm the pathogenic effect of the variant. To fully confirm the pathogenicity of the variant, further functional test is strongly advised. Glucocorticoid and biologics are the mainstream management of ELF4 deficiency disorder. CONCLUSIONS: Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of DEX. When atypical presentations are prominent, variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 function. Experience of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study.

Elimination of Intragrain Defect to Enhance the Performance of FAPbI3 Perovskite Solar Cells by Ionic Liquid.

Ionic liquids have been widely used to improve the efficiency and stability of perovskite solar cells (PSCs), and are generally believed to passivate defects on the grain boundaries of perovskites. However, few studies have focused on the relevant effects of ionic liquids on intragrain defects in perovskites which have been shown to be critical for the performance of PSCs. In this work, the effect of ionic liquid 1-hexyl-3-methylimidazolium iodide (HMII) on intragrain defects of formamidinium lead iodide (FAPbI3) perovskite is investigated. Abundant {111}c intragrain planar defects in pure FAPbI3 grains are found to be significantly reduced by the addition of the ionic liquid HMII, shown by using ultra-low-dose selected area electron diffraction. As a result, longer charge carrier lifetimes, higher photoluminescence quantum yield, better charge carrier transport properties, lower Urbach energy, and current-voltage hysteresis are achieved, and the champion power conversion efficiency of 24.09% is demonstrated. These observations suggest that ionic liquids significantly improve device performance resulting from the elimination of {111}c intragrain planar defects.

Validation of the "obturator functioning scale" for Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy.

Objective: The Obturator Functioning Scale (OFS) is a scale without formal measures of validity in any language. This study aimed to translate and adapt the OFS from English to Chinese and check its reliability and validity in Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy. Methods: The 15-item Chinese preversion of the OFS was completed by 133 patients in three tertiary stomatological hospitals. Of these, 41 completed it again one week after the first measurement. The patients also completed the Chinese version of the University of Washington quality of life scale (UW-QOL, Version 4). Results: Item 12 ("upper lip feels numb") was deleted to achieve a better statistical fit. The 14-item Chinese version of the OFS (OFS-Ch) demonstrated high internal consistency (Cronbach's alpha = 0.908). The test-retest reliability coefficients for most items exceeded 0.90, indicating substantial reproducibility. Confirmatory factor analysis found that the scale consisted of three correlated factors: 1) eating (four items), 2) speech (five items), and 3) other problems (five items). This explained 70.2 % of the total variance using exploratory factor analysis. The scale was significantly convergent and discriminant and could validly discriminate between patients with Brown I and IId maxillary defects. Conclusions: Our results showed that the OFS-Ch scale is a valid tool for evaluating oral dysfunction and satisfaction with appearance for patients with the obturator prosthesis and identifying those at risk of poor obturator function in clinical settings.

Integrated Bioinformatics and Machine Learning Analysis Identify ACADL as a Potent Biomarker of Reactive Mesothelial Cells.

Mesothelial cells with reactive hyperplasia are difficult to distinguish from malignant mesothelioma cells based on cell morphology. This study aimed to identify and validate potential biomarkers that distinguish mesothelial cells from mesothelioma cells through machine learning combined with immunohistochemistry. It integrated the gene expression matrix from three Gene Expression Omnibus data sets (GSE2549, GSE12345, and GSE51024) to analyze the differently expressed genes between normal and mesothelioma tissues. Then, three machine learning algorithms, least absolute shrinkage and selection operator, support vector machine recursive feature elimination, and random forest were used to screen and obtain four shared candidate markers, including ACADL, EMP2, GPD1L, and HMMR. The receiver operating characteristic curve analysis showed that the area under the curve for distinguishing normal mesothelial cells from mesothelioma was 0.976, 0.943, 0.962, and 0.956, respectively. The expression and diagnostic performance of these candidate genes were validated in two additional independent data sets (GSE42977 and GSE112154), indicating that the performances of ACADL, GPD1L, and HMMR were consistent between the training and validation data sets. Finally, the optimal candidate marker ACADL was verified by immunohistochemistry assay. Acyl-CoA dehydrogenase long chain (ACADL) was stained strongly in mesothelial cells, especially for reactive hyperplasic mesothelial cells, but was negative in malignant mesothelioma cells. Therefore, ACADL has the potential to be used as a specific marker of reactive hyperplasic mesothelial cells in the differential diagnosis of mesothelioma.

SOX4 regulates proliferation and apoptosis of human ovarian granulosa-like tumor cell line KGN through the Hippo pathway.

The proliferation and apoptosis of ovarian granulosa cells are important for folliculogenesis. As a transcription factor, SRY-box transcription factor 4 (SOX4) has important roles in regulating cellular proliferation and apoptosis. Nonetheless, the regulatory mechanisms of SOX4 on proliferation and apoptosis of granulosa cells remain elusive. Therefore, a stably overexpressed SOX4 ovarian granulosa cell line KGN was generated by lentivirus encapsulation. We observed that overexpression of SOX4 inhibits apoptosis, promotes proliferation and migration of KGN cells. Comparative analysis of the transcriptome revealed 868 upregulated and 696 downregulated DEGs in LV-SOX4 in comparison with LV-CON KGN cell lines. Afterward, further assessments were performed to explore the possible functions about these DEGs. The data showed their involvement in many biological processes, particularly the Hippo signaling pathway. Moreover, the expression levels of YAP1, WWTR1, WTIP, DLG3, CCN2, and AMOT, which were associated with the Hippo signaling pathway, were further validated by qRT-PCR. In addition, the protein expression levels of YAP1 were markedly elevated, while p-YAP1 were notably reduced after overexpression of SOX4 in KGN cells. Thus, these results suggested that SOX4 regulates apoptosis, proliferation and migration of KGN cells, at least partly, through activation of the Hippo signaling pathway, which might be implicated in mammalian follicle development.