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The carcinogenic function of zinc finger protein 479 (ZNF479) has been found in a few sorts of cancer. However, the part of ZNF479 in gastric cancer remains vague. In this study, the effect of ZNF479 on gastric cancer cell survival, metastasis and epithelial mesenchymal transition (EMT) was investigated using the Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays. Immunofluorescence assay and Western blot was carried out to evaluate the levels of cell cycle, EMT, and MEK/ERK/DNMT1 pathway-related proteins. A lung metastasis cancer mice model was constructed to evaluate the function of ZNF479 on tumor metastasis in vivo. We noticed that overexpression of ZNF479 promoted cell growth, cell cycle progression, invasion and EMT of gastric cancer cells, whereas ZNF479 knockdown appeared the inverse comes about. Moreover, downregulation of ZNF479 hindered tumor metastasis in mice. Advanced investigation implied that ZNF479 was engaged in the regulation of gastric cancer progression by affecting the MEK/ERK/DNMT1 pathway for that the MEK-specific inhibitor PD98059 reversed the impact of ZNF479 overexpression on gastric cancer cells and repressed MEK/ERK/DNMT1 signal. In conclusion, ZNF479 promotes gastric cancer cells by activating the MEK/ERK/DNMT1 pathway, ZNF479 may give a new and viable gene target for gastric cancer intercession.

To examine the difference in the topological properties of brain functional network between the children with obstructive sleep apnea (OSA) and healthy controls, and to explore the relationships between these properties and cognitive scores of OSA children. Twenty-four OSA children (6.5 ± 2.8 years, 15 males) and 26 healthy controls (8.0 ± 2.9 years, 11 males) underwent resting-state fMRI (rs-fMRI), based on which brain functional networks were constructed. We compared the global and regional topological properties of the network between OSA children and healthy controls. Partial correlation analysis was performed between topological properties and cognitive scores across OSA children. When comparing the OSA children with the healthy controls, lower full-scale intelligent quotient (FIQ) and verbal intelligent quotient (VIQ) were observed. Additionally, nodal degree centrality decreased in the bilateral anterior cingulate and paracingulate gyrus, but increased in the right middle frontal gyrus, the left fusiform gyrus, and the left supramarginal gyrus. Nodal efficiency decreased in the right precentral gyrus, and the bilateral anterior cingulate and paracingulate gyrus, but increased in the left fusiform gyrus. Nodal betweenness centrality increased in the dorsolateral part of the right superior frontal gyrus, the left fusiform gyrus, and the left supramarginal gyrus. Further, the nodal degree centrality in the left supramarginal gyrus was positively correlated with FIQ. In contrast, none of global topological properties showed difference between those two groups. The outcomes of OSA may impaired the regional topological properties of the brain functional network of OSA children, which may be potential neural mechanism underlying the cognitive declines of these patients.

Background Since dysregulation of total Interleukin (IL)-18 and IL-18 binding protein (IL-18BP) may participate in systemic lupus erythematosus (SLE) and contribute to the occurrence of non-autoimmune epilepsy, the aim of the current work is to investigate whether the interaction between IL-18 and IL-18BP plays any role in neuropsychiatric systemic lupus erythematosus related seizures. Methods Data from 137 SLE patients and 30 healthy controls (HC) were consecutively collected from 2020 to 2021. Serum levels of total IL-18 and IL-18BP for all patients and HC were measured by ELISA test. Free IL-18 was calculated based on the law of mass action. Results Among the 137 SLE patients, 103 had active disease and were classified into NPSLE ( n = 50) and Non-NPSLE ( n = 53) groups. Among the NPSLE patients, 16 had seizure disorders. Serum free IL-18 levels were increased in NPSLE (277.6 [150.9–428.8]pg/mL) and were correlated with disease activity (r = 0.268, p = 0.002). Moreover, serum free IL-18 levels in NPSLE patients with seizure disorders (350.9 [237.9–455.9]pg/mL) were significantly higher than the levels in those with other neuropsychiatric symptoms (237.7 [124.6–428.8] pg/mL). Conclusions The expression of free IL-18 was increased in neuropsychiatric systemic lupus erythematosus(NPSLE), especially in NPSLE related seizures. Also, serum levels of free IL-18 were significantly increased in active SLE patients. In this regard, free IL-18 may be involved in the pathogenesis of NPSLE related seizures and associated with disease activity.

Background: Papillary thyroid carcinoma (PTC) is one of the most common endocrine malignancies and has a favorable prognosis. However, optimal treatments and prognostic markers have not been clearly identified. Methods: Gene expression data from primary PTC were downloaded from the Gene Expression Omnibus database and subjected to two analyses of differentially expressed genes (DEGs), followed by intersecting individual and integrated DEGs analyses as well as gene set enrichment analysis. Analysis of data from Sequence Read Archive and The Cancer Genome Atlas, immunohistochemistry and qRT-PCR of TFF3 were performed to validate the results. Finally, the relationship between gene expression and disease-free survival as well as immune cell infiltration were investigated. Results: Six critical DEGs and several tumor-enriched signaling pathways were identified. Immunohistochemistry and qRT-PCR validated the low expression of TFF3 in PTC. TFF3 and FCGBP are coexpressed in PTC, and patients with lower gene expression had worse disease-free survival but higher immune cell infiltration. Conclusion: TFF3 was significantly underexpressed and may function with FCGBP synergistically in PTC.

Lin Mei,1,* Xiaodan Li,1,* Shengcai Wang,1,* Run Si,2 Tingting Ji,1 Zhifei Xu,3 Yun Peng,4 Yue Liu,4 Hongbin Li,1 Jie Zhang,1 Yongli Guo,5 Jinghong Tian,6 Guifei Zhou,2 Huifang Huang,2 Jun Tai,1,7,* Jiangang Liu,8,9 Xin Ni1 1Department of Otolaryngology, Head and Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2School of Computer and Information Technology, Beijing Jiaotong University, Beijing, People’s Republic of China; 3Department of Respiration, Beijing Children′s Hospital, Capital Medical University, National Center for Children′s Health, Beijing, People’s Republic of China; 4Department of Radiology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 5Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, People’s Republic of China; 6Department of Neurorehabilitation, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 7Department of Otorhinolaryngology, Children’s Hospital, Capital Institute of Pediatrics, Beijing, People’s Republic of China; 8Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, People’s Republic of China; 9Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of the People’s Republic of China, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiangang LiuBeijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, 100191, People’s Republic of ChinaEmail jgliu@buaa.edu.cnXin NiDepartment of Otolaryngology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56 Nanlishilu, Beijing, People’s Republic of ChinaTel +86-139-1011-1999Email nixin@bch.com.cnObjective: To investigate the impacts of obstructive sleep apnea (OSA) on white matter (WM) integrity and cognitive functions of pediatric patients with different levels of OSA severity.Methods: Fifty-eight children with OSA and thirty-four healthy controls (HC) were recruited. All participants underwent diffusion tensor imaging (DTI) examination, polysomnography (PSG), and neurocognitive assessments. Patients were divided into mild OSA (MG) and moderate-severe OSA (SG) groups. WM integrity, PSG data, and neurocognitive assessment scores were compared among those groups.Results: For apnea hypopnea index (AHI), obstructive apnea hypopnea index (OAHI), arousal index, SpO2 nadir, and attention, SG was worse than both MG and HC with MG worse than HC. For baseline SpO2 and intelligence, SG was worse than both MG and HC with no significant difference between MG and HC. Impaired WM integrity was observed in bilateral anterior thalamic radiation, bilateral inferior fronto-occipital fasciculus, bilateral inferior longitudinal fasciculus, right superior longitudinal fasciculus, right hippocampus, left cingulate gyrus, right uncinate fasciculus, callosum forceps major, and callosum forceps minor only for SG than for HC. WM integrity was significantly correlated with OSA severity and neurocognitive assessment scores only for SG, but not for MG.Conclusion: Decreased baseline SpO2, WM impairment, and intelligence decline were all observed only for SG, but not for MG, implying an associated relationship among decreased SpO2, WM impairment and WM impairment. Thus, for SG, additional assessments of brain damage and cognitive function decline are needed for prognostic evaluation of OSA.Keywords: diffusion tensor imaging, obstructive sleep apnoea, children, tract-based spatial statistics, white matter

Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in liver cancer. Circular RNA_0090049 (circ_0090049) has been shown to be involved in the advance of HCC. However, the interaction between circ_0090049 and microRNA (miRNA) in HCC has not been studied. Methods Quantitative real-time PCR was used to detect the expression of related genes. Through detection of cell proliferation, migration, invasion, and rate of tumor sphere formation, the capping experiment was carried out to verify the regulatory relationship between miRNA and circ_0090049 or circ_0090049 and ubiquitin-conjugating enzyme E2 T (UBE2T). The expression of related proteins was detected by Western blotting. The interaction of miRNA with circ_0090049 or UBE2T was notarized by Dual-luciferase reporter assay. Xenotransplantation experiments confirmed the function of circ_0090049 in vivo. Results Circ_0090049 and UBE2T were upregulated in liver cancer. Silencing circ_0090049 reduced the proliferation, migration, invasion, and tumor spheroid formation rate of Huh7 and HCCLM3 cells. MiR-605-5p and miR-548c-3p were identified as targets of circ_0090049, and UBE2T was the target of miR-605-5p and miR-548c-3p. Anti-miR-605-5p, anti-miR-548c-3p or UBE2T overexpression restored the inhibitory effect of circ_0090049 knockdown on HCC cells. Animal experiments confirmed the antitumor effect of silence circ_0090049. Conclusion Circ_0090049 regulates the expression of UBE2T by regulating miR-605-5p or miR-548c-3p, thereby promoting the development of HCC cells.

Ewing-like sarcomas (ELS) are round cell mesenchymal neoplasms that are highly aggressive to bone and/or soft tissue. However, they rarely occur in the nose, with no reported such cases in the medical literature to date. Here, we reported the case of a two-year-old Chinese boy who presented with a mass in the left nasal cavity. Surprisingly, the final histopathological diagnosis of the nasal mass was determined to be a subtype of ELS, BCOR-rearranged sarcoma. Therefore, we retrospectively analyzed the clinical data of this case and reviewed the relevant literature on ELS and BCOR-rearranged sarcoma. The purpose of this article is to provide new insights into the clinical characteristics of children with BCOR-rearranged Ewing-like sarcoma and to improve the understanding of this disease.

qRT-PCR is a common and key technical means to study gene expression in biological research. However, reliability and accuracy of quantification by qRT-PCR is entirely dependent on the identification of appropriate reference genes. Cucumber as an economical vegetable is widely cultivated worldwide and is subject to serious nematode infection, especially from

The profiling of small extracellular vesicle-associated microRNAs (sEV-miRNAs) plays a vital role in cancer diagnosis and monitoring. However, detecting sEV-miRNAs with low expression in clinical samples remains challenging. Herein, we propose a novel electrochemical biosensor using localized DNA tetrahedron-assisted catalytic hairpin assembly (LDT-CHA) for sEV-miRNA determination. The LDT-CHA contained localized DNA tetrahedrons with CHA substrates, leveraging an efficient localized reaction to enable sensitive and rapid sEV-miRNA measurement. Based on the LDT-CHA, the proposed platform can quantitatively detect sEV-miRNA down to 25 aM in 30 min with outstanding specificity. For accurate diagnosis of gastric cancer patients, a combination of LDT-CHA and a panel of four sEV-miRNAs (sEV-miR-1246, sEV-miR-21, sEV-miR-183-5P, and sEV-miR-142-5P) was employed in a gastric cancer cohort. Compared with diagnosis with single sEV-miRNA, the proposed platform demonstrated a higher accuracy of 88.3% for early gastric tumor diagnoses with higher efficiency (AUC: 0.883) and great potential for treatment monitoring. Thus, this study provides a promising method for the bioanalysis and determination of the clinical applications of LDT-CHA. Graphical Abstract

Restoration of damaged highway-bridge networks is critical to the recovery of the networks’ functionality in support of post-disaster recovery actions. Restoration-scheduling problems have traditio...

Objectives To investigate alterations in neurocognitive, attention, paediatric sleep questionnaire (PSQ) scores and whole brain white matter (WM) integrity between children with mild and severe obstructive sleep apnoea (OSA) according to sex and whether these changes are associated with OSA severity. Methods Fifty-seven children (36 males and 21 females) diagnosed with OSA were recruited for this study. Children of both sexes were divided into mild (male-MG, female-MG) and severe (male-SG, female-SG) groups according to OSA severity. Polysomnography (PSG), neurocognitive, attention and PSQ tests were compared between groups by one-way samples analysis of variance (ANOVA) F test. Diffusion tensor imaging (DTI) was scanned using a 3T GE MRI scanner and analysed by Tract-based Spatial Statistics (TBSS). Spearman correlation was calculated between DTI Eigenvalues and clinical characteristics. Results Compared to mild OSA patients, severe OSA patients presented greater severity of obstructive apnoea hypopnea index (OAHI), neurocognition, PSQ and attention tests in both male and female patients. Brain WM integrity in the male-SG, compared to the male-MG, demonstrated significantly reduced fractional anisotropy (FA) values in the right middle frontal gyrus and the right frontal sub-gyral regions and increased axial diffusivity (AD) values in the right inferior frontal gyrus, left parietal angular gyrus and sub-gyral regions, while no differences were found between the female-MG and female-SG. Alterations in male-SG brain regions were observably correlated with severity in male OSA patients. Conclusions The integrity of WM, which regulates autonomic, cognitive, and attention functions, is impaired in male, but not female, children with severe OSA.

Gastric cancer is the fifth most common malignancy and the third most deadly tumor in the world. Zinc finger protein 479 (ZNF479) has been demonstrated to play crucial roles in hepatocellular carcinoma. However, the function of ZNF479 in gastric cancer remains to be clarified. The current study aimed to investigate the role of ZNF479 in gastric cancer progression and elucidate the potential molecular mechanism. In this study, Cell Count Kit‐8 and colony formation assays demonstrated that knockdown of ZNF479 inhibited cell proliferation in AGS and SGC‐7901 cells. Of note, knockdown of ZNF479 hinders tumor growth of xenograft tumor mice. What is more, knockdown of ZNF479 inhibited glucose uptake, lactate production, adenosine triphosphate level, and extracellular acidification ratio; increased oxygen consumption ratio in gastric cancer cells; and decreased the expression of glycolytic proteins both in vitro and in vivo. Furthermore, analysis mechanism suggests that ZNF479 participated in the regulation of gastric cancer progression through affecting the β‐catenin/c‐Myc signaling pathway. Collectively, ZNF479 plays a role as an oncogene through modulating β‐catenin/c‐Myc signaling pathway in the development of gastric cancer, which provides a new research target for future studies.

Risk and resilience assessments have been both widely, but separately, used as tools for guiding policymakers to formulate disaster-risk reduction policies. On the one hand, risk assessment is utilized to estimate the risk associated with disasters in terms of operational metrics such as monetary or casualties’ loss; on the other hand, most resilience analysis assesses and represent community resilience as an index, without a specific unit metric, to gauge levels of disparity in community’s post-disaster recovery capability among the areas of interest. Although disaster-risk reduction policies should be best informed by both risk and resilience assessments, an informative integrated assessment approach accounting for both seems to be lacked in current research, insofar as the difficulty in properly integrating their distinct measurement metrics. This paper commences with a literature review of risk assessment and community resilience. It then proposes an integrated framework that can comprehensively assess both seismic risk and resilience, by taking into account the casualties and economic losses associated with earthquakes resulted from a risk assessment, and the infrastructure-system resilience and community socioeconomic–demographic resilience resulted from a resilience assessment. More specifically, an integrated tool, risk-based resilience-concentration curve, is proposed for assessing the inequality of given types of risk in the community’s infrastructure-system resilience, and socioeconomic–demographic resilience, respectively. A case study is presented using the data from a city in Israel: the first phase of the case study focused on the concentration of casualties’ risk in community’s infrastructure-system resilience, and the second on the concentration of economic risk in community’s socioeconomic–demographic resilience. The results show that unevenly distributed risk and community resilience can cause inequality of risk in resilience capacity in certain administrative tracts of the city. Based on these findings, the paper recommends a range of risk-reduction strategies for different administrative tracts based on their risk-based resilience concentration curves.

Data-driven housing-market segmentation has been given increasing prominence for its objectiveness in identifying submarkets based on the housing data’s underlying structures. However, when handling high-dimensionality housing dataset, traditional statistical-clustering methods have been found to tend to lose low-variance information of the dataset and be deficient in deriving the globally optimal number of submarkets. Accordingly, with the intention of achieving more rigorous high-dimensionality housing market segmentation, a swarm-inspired projection (SIP) algorithm is introduced by this study. Using a high-dimensionality Taipei city’s housing dataset in a case study, a comparison of the proposed SIP algorithm and a statistical-clustering method using the combination of principal component analysis (PCA) and K-means clustering is conducted in evaluating the predictive accuracy of hedonic price models of the housing submarkets. The results show that, as compared to the original single market, the segmented submarkets resulting from SIP algorithm are more homogenous and distinctive, where the resulted hedonic price models have high-level statistical explanation and disparate sets of hedonic prices for different submarkets. In addition, as compared to the use of a statistical-clustering method, SIP algorithm is found to obtain a more optimal number of submarkets, where the resulted hedonic price models are found to achieve greater improvement of statistical explanation and more stable reduction of prediction error. These findings highlight the advantages of our proposed SIP algorithm in high-dimensionality housing market segmentation, and thus it is hoped that the present research will serve as a practical tool to better inform further studies aimed at market-segmentation-related problems.

Obstructive sleep apnea (OSA) is a common sleep‐disordered breathing disease that often leads to many comorbidities (e.g., cognitive dysfunction), which adversely affect the quality of life for patients with OSA. Thus far, the underlying mechanisms of this dysfunction remain unclear. Many studies have focused on OSA‐related characteristics, including intermittent hypoxemia and sleep fragmentation. There is increasing emphasis on neuroimaging studies to explore underlying relationships between neuropathological changes and cognitive dysfunction. This article reviews recent research progress concerning cognitive dysfunction associated with OSA to reveal potential mechanisms that contribute to this dysfunction., Obstructive sleep apnea (OSA) often leads to cognitive dysfunction, however, the underlying mechanisms of this damage remain unclear. In previous studies, a various of researches have been showed that cognitive dysfunction was associated with OSA‐related characteristics and specific neuropathological changes, thus, these findings may provide specific insight into exploring the potential mechanisms.

Obstructive sleep apnea (OSA) is a common chronic sleep-related breathing disorder in children. Previous studies showed widespread alterations in white matter (WM) in children with OSA mainly by using diffusion tensor imaging (DTI), while diffusional kurtosis imaging (DKI) extended DTI and exhibited improved sensitivity in detecting developmental and pathological changes in neural tissues. Therefore, we conducted whole-brain DTI and DKI analyses and compared the differences in kurtosis and diffusion parameters within the skeleton between 41 children with OSA and 32 healthy children. Between-group differences were evaluated by tract-based spatial statistics (TBSS) analysis (p 0.05, TFCE corrected), and partial correlations between DKI metrics and sleep parameters were assessed considering age and gender as covariates. Compared with the controls, children with OSA showed significantly decreased kurtosis fractional anisotropy (KFA) mainly in white matter regions with a complex fibre arrangement including the posterior corona radiate (PCR), superior longitudinal fasciculus (SLF), and inferior fronto-occipital fasciculus (IFOF), while decreased FA in white matter regions with a coherent fibre arrangement including the posterior limb of internal capsule (PLIC), anterior thalamic radiation (ATR), and corpus callosum (CC). Notably, the receiver operating characteristic (ROC) curve analysis demonstrated the KFA value in complex tissue regions significantly (p 0.001) differentiated children with OSA from the controls. In addition, the KFA value in the left PCR, SLF, and IFOF showed significant partial correlations to the sleep parameters for children with OSA. Combining DKI derived kurtosis and diffusion parameters can provide complementary neuroimaging biomarkers for assessing white matter alterations, and reveal pathological changes and monitor disease progression in paediatric OSA.

The accumulation of macrophages and cholesterol crystals in atherosclerotic plaques is an important pathological feature of patients with the acute coronary syndrome (ACS). Decreased estrogen levels and estrogen receptors (ERs) lead to an increase in atherosclerosis in postmenopausal women. Whether estrogen prevents atherosclerosis by promoting macrophage cholesterol crystal metabolism via estrogen receptor alpha (ERα) is unknown. The ascending aorta of postmenopausal women decreased the fibrous cap around the plaque, increased the aggregation of CC and macrophages, and reduced the expression of ERα, and transcription factor EB (TFEB). Estrogen supplementation ameliorated atherosclerosis, and reduced CC and macrophages in the cardiac aorta and CC in primary peritoneal macrophages in OVX LDLR−/− mice. Silencing TFEB eliminated the effect of estrogen in enhancing lysosomal function, promoting CC internalization in lysosomes, and promoting reverse cholesterol transport (RCT) through APOA1, but did not affect triglyceride (TG) accumulation or RCT mediated by HDL in macrophages. Inhibition of hormone-sensitive lipase (HSL) decreased the effect of estrogen in increasing RCT through APOA1 and HDL and decreasing TG in macrophages. Inhibition of ERα weakened the effect of estrogen in reducing CC, TG, total cholesterol(TC), free cholesterol(FC), and cholesterol ester (CE) in macrophages. Silencing ERα eliminated the effect of estrogen in increasing lysosomal function and promoting the expression of TFEB, HSL, ABCA1/ABCG1 and inhibiting the expression of NLRP3 and IL-1β in macrophages. Our results provide evidence that estrogen promotes macrophage CC metabolism, which includes increasing the internalization of CC in lysosomes through rescuing the lysosomal biogenesis program by the ERα-TFEB pathway and promoting RCT via ERα-TFEB and HSL pathways to increase the cholesterol efflux.

Objectives: The objectives of this study were to explore the clinical heterogeneity of differentiated thyroid cancer (DTC) between prepubertal children and adolescents and guide clinical treatment. Methods: A retrospective study included patients with DTC aged ≤19 years in Beijing Children’s Hospital from June 2014 to June 2019. All patients were enrolled and divided into 2 subgroups based on the threshold age of 10 years, namely the childhood group (CG) (≤10 years old); and the adolescent group (AG) (between 10 and 19 years old). The χ2 test and Fisher’s exact test were used to estimate the effect of risk factors in the 2 age groups. Multivariate binary logistic regression models were conducted to assess the recurrent risk factors. Results: Seventy cases of DTC were included with an average age of 9.94 ± 2.88 years, including 35 in CG and 35 in AG. The most common clinical manifestation was a painless mass in the neck, accounting for 77.1% (54/70) of patients. Compared with the AG, the CG was more likely to have lymph node metastasis (p = 0.022) and distant metastasis (p = 0.041). The CG was more likely to have extrathyroidal extension (p = 0.012) and had a significantly higher recurrence rate than the AG (p = 0.040). Age was an independent variable predictive of recurrence (p = 0.0347). Conclusion: Regional invasiveness, cervical lymph node metastasis, and distant metastasis of DTC were more likely to occur in children ≤10 years old. Meanwhile, children ≤10 years old with DTC were more likely to have recurrence than adolescent’s postsurgical treatment. Thus, children younger than 10 years of age with DTC should be treated more aggressively.

Purpose: Gastric cancer (GC) is one of the most frequent tumors with high mortality rate, worldwide. A proper understanding of the mechanism underlying its progression is required for its diagnosis and development of novel treatment option. MicroRNAs are associated with the development and advancement of different types of cancer, including GC. The current research was aimed at investigating the molecular and biological function of miR-148a-3p in GC development.Methods: A human normal gastric epithelial cell line, GES-1 (control) as well as four GC cell lines (NUGC-4, SNU-520, STKM-2 and MKN-74) were employed for the study. MiR-148a-3p and ATP6AP2 expression levels in GC cell lines were examined by RT-qPCR technique. Transfection procedure was used to upregulate miR-148a-3p expression in the MKN-45 cell line. MTT assay was utilized to evaluate cell viability in GC cell lines. The molecular interaction between miR-148a-3p and ATP6AP2 was predicted using bioinformatics system and the prediction was then validated by luciferase reporter assay.Results: Expression levels of miR-148-3p was low, whilst that of ATP6AP2 was high in GC cell lines. MiR-148a-3p overexpression resulted in the reduction of cell viability in GC cell lines. More so, it was confirmed that miR-148-3p, as a post-transcriptional regulator inhibited ATP6AP2 expression by having a negative association with it in GC cells. More so, ATP6AP2 was found to be a direct target of miR-148a-3p.Conclusion: Our results revealed that miR-148a-3p plays a crucial function in GC development through targeting ATP6AP2. This finding could be explored in the discovery of new therapeutic approaches for GC treatment. Keywords: ATP6AP2, Cell viability, Gastric cancer, miR-148a-3p, Progression

Gastric cancer (GC) is a common malignancy with a poor prognosis. Tripartite motif-containing 50 (TRIM50) belongs to the TRIM family and is reported to be related to numerous cancers. This study aimed to investigate the function of TRIM50 in GC.Three microarray datasets (GSE13911, GSE79973, and GSE19826) containing GC and adjacent nontumor tissues were used for bioinformatics analysis to screen GC-related genes and assess the associations between GC development and TRIM50 expression. Then, TRIM50 expression in GC cells was detected at mRNA and protein levels. After TRIM50 was knockdown or overexpressed, the effect of TRIM50 on the proliferation and metastasis of GC cells was analyzed using Cell Counting Kit-8 (CCK-8), flow cytometry, scratch, and Transwell assays. The interaction between TRIM50 andBioinformatics revealed that TRIM50 expression was decreased in GC samples and associated with GC development.TRIM50 overexpression may inhibit cell proliferation and metastasis in GC via

Background: It calls great attention of the leadership competency status of medical students as it is believed that their good leadership ability can improve the clinical practice or research outcome. It is believed to be among the most important competency of a doctor or a scientist. Meanwhile, the leadership competency status of the medical graduate freshmen and the influencing factors of it had been rarely researched. Methods: From July to September in 2020 and 2021, 851 medical graduate freshmen from seven teaching hospitals of the Capital Medical University (CMU) participated in a survey including three 5-point Likert scales based on different models and in which they implied their leadership abilities. The scales included Socially Responsible Leadership Scale (SRLS), Emotionally Intelligent Leadership for students Inventory (EILI) and the Student Leadership Practices Inventory-Self Instrument(SLPI). After self-scoring of these three scales, four questions were asked about the attitude of the cultivation of leadership and scored by the 5-point Likert scale. The data were then analyzed by two independent samples t-test or one-way ANOVA and multiple linear regressions. Results: The scores of all dimensions of the SRLS were at the medium level except for controversy with civility. The scores of the dimensions of consciousness of context, self and others of EILI and the dimensions of enable others to act and encourage the heart of SLPI were at the medium level.And the scores of the dimensions of model the way, inspire a shared vision and challenge the process of SLPI were at the high level. The leadership abilities of medical graduate freshmen were affected by the demographics, participation of social activities and leadership learning. Multiple linear regression analysis showed that the scores of SLPI were jointly affected by the scores of SRLS and EILI ((F=2674.44, PR2=0.86).Conclusions: Chinese medical graduate freshmen had a medium to high level of leadership abilities except for controversy with civility according to the survey. Leadership ability can be affected by demographic characteristics, social activities and leadership learning situations. Leadership practice is influenced by both personal responsibility and emotional intelligence. Themed series of activities especially with a service theme could be involved in the cultivation of their leadership abilities in practice aspect.

Myositis ossificans (MO) is a benign, self-limiting, and nonneoplastic lesion involving the skeletal muscle or soft tissue, rarely occurring in the head and neck. It is relatively rare in clinical practice, and it is difficult to distinguish specific cases from musculoskeletal conditions, which poses unique challenges for clinical diagnosis and treatment. We reported that a 9-year-old boy suffered from local and nontraumatic MO of the trapezius muscle. Given the rarity of this case, the present article detailed the diagnosis and treatment of this rare case and reviewed the relevant literature on MO, focusing on the clinical, pathological, and radiographic characteristics of MO. Notably, these investigations aimed to enhance clinicians’ understanding of the disease and improve diagnostic accuracy.

As a common malignant tumor, colorectal cancer (CRC) has a high incidence. Recent investigations have suggested that although great improvement has been achieved in the survival rate of early-stage CRC patients, the overall survival rate remains low. Mounting reports have proved that lncRNAs take part in the development of various cancers and possess the regulatory functions in cancers. For example, ASB16 antisense RNA 1 (ASB16-AS1) is a poorly researched novel lncRNA whose specific functions in CRC are still unknown. In our research, we discovered that ASB16-AS1 was with high expression in CRC cells. In addition, ASB16-AS1 silencing restrained the proliferation, migration, invasion, and stemness while accelerating cell apoptosis of CRC cells. Mechanism experiments were applied to explore the regulatory mechanism of ASB16-AS1. It turned out that miR-185-5p could interact with ASB16-AS1 and inhibited the progression of CRC cells. TEAD1 (TEA domain transcription factor1) - a major effector of the Hippo signaling was proved to serve as the target of miR-185-5p and promote CRC development. In short, ASB16-AS1 drove the progression of CRC through the regulation of miR-185-5p/TEAD1 axis.

The sustainable combined location-inventory-routing problem (CLIRP) based on demand forecasting is studied in this paper. Based on the construction of a multi-stage demand forecasting model, five parts of total logistics costs: the costs of trunk transportation and regional transportation, the fixed costs of distribution center construction, the inventory holding costs, shortage costs, and salvage, are comprehensively considered. The existing CLIRP model does not consider the environmental influence. Thus, a sustainable CLIRP model considering carbon emission is established with minimum logistics costs and emission as the objective function. A heuristic algorithm gives the initial solution, and then a hybrid heuristic algorithm combining the tabu search algorithm with the simulated annealing algorithm is proposed to find the global near-optimal solution. Finally, a numerical example of a garment chain enterprise is given to illustrate the solving process of the model. The results show that using the proposed algorithm determines the optimal locations of RDCs, and the transportation routes with each region are obtained with the minimum total logistics costs and carbon emission. The model realizes the combination of location, inventory, and routing problems of the large garment enterprises and finally realizes the goal of optimizing the sustainable logistics distribution network of the garment industry, which verifies the effectiveness of the model. Moreover, a comparison is made to show the efficiency of the proposed algorithm; the results show that the proposed algorithm in this paper optimizes the route and selections of RDCs.

Lay abstract Thyroid cancers are some of the most common endocrine malignancies. However, the optimal treatments and prognostic markers have not been clearly identified. We identified six critical differentially expressed genes and several tumor-enriched signaling pathways in papillary thyroid carcinoma, and found that

Previous research has revealed that microRNA-361 (miR-361) functions as a fundamental modulator in non-small-cell lung cancer and esophageal carcinoma. However, its involvement in pancreatic cancer (PC) is yet to be elucidated. Therefore, the present study aimed to examine the mechanism and function of miR-361 during the regulation of PC cell migration and viability. It was demonstrated that miR-361 expression decreased in PC cell lines and tissues, and the overexpression of miR-361 suppressed in vivo PC cell proliferation in mice. Moreover, flow cytometry and MTT assays indicated that the miR-361 mimic decreased the viability and increased the apoptosis of PC cells. Both Transwell migration and wound healing assays identified that miR-361 ameliorated the migratory ability of PC cells. Using dual-luciferase reporter assays, it was found that miR-361 targeted mitogen-activated protein kinase (MAPK)/JNK 3'-untranslated regions, inducing the downregulation of this gene. In PC cells, overexpression of MAPK/JNK diminished the pro-apoptotic effect of the miR-361 mimic, while restoring the migratory activity of PC cells. Collectively, the present results suggested novel molecular mechanisms underlying PC progression and development.

This letter proposes a simple and effective method to remove haze from a single input foggy or underwater image. The algorithm is originated from the physically valid description of the transmission of the scattering light during the volumetric scattering medium, interpreting the formation of the haze with the layered transmission model. We establish the explicit expression of the transmittance with respect to statistics of the back scattered light in front of the scene. The parameters for the evaluation of the transmittance can be estimated by the second order statistics of the back scattered light both with and without the scene. Since the transmittance map is evaluated for each RGB channel respectively, the color recovery by the proposed method is wavelength dependent and physically valid. Experimental results on both terrestrial and underwater images are given, which show the effectiveness and advantage of the proposed method.

Long non-coding RNAs (lncRNAs) play vital roles in diabetic nephropathy (DN). This research aimed to study the potential role and underlying molecular mechanisms of long non-coding RNA MEG3 in DN. We found that MEG3 was upregulated in DN in vivo and in vitro and could enhance cell fibrosis and inflammatory response in DN. MEG3 functioned as an endogenous sponge for miR-181a in mesangial cells (MCs) via direct targeting and in an Ago2-dependent manner. MiR-181a inhibition promoted MC fibrosis and inflammatory response. In addition, Egr-1 was confirmed as a target gene of miR-181a. Further investigations verified that MEG3 promotes fibrosis and inflammatory response via the miR-181a/Egr-1/TLR4 axis in vitro and in vivo. These results provide new insights into the regulation between MEG3 and the miR-181a/Egr-1/TLR4 signaling pathway during DN progression.

The definition of large-volume pathologic N1 metastases has been changed in the 2017 version 2 of the National Comprehensive Cancer Network guidelines, leading to a controversy over the optimal surgical approach selection for patients with biopsy-proven papillary thyroid carcinoma (PTC). The aim of this study was to investigate the therapeutic efficacy of total thyroidectomy (TT) and thyroid lobectomy (TL) for these patients.Retrospective population-based database analysis.A total of 906 consecutive PTC patients with pathologic N1 metastases (5 involved nodes with metastases ≤5 mm in the largest dimension) were retrieved from the Surveillance, Epidemiology, and End Results database, and divided into two groups (≤2 mm,2-5 mm) based on the size of the extent of disease. Overall survival (OS) was then compared between patients treated with TT and TL, followed by Cox proportional hazards regression analysis to explore multiple prognostic factors.OS favored TT compared with TL in patients with more than five involved nodes and metastases2 to 5 mm in the largest dimension (P .05). Cox analysis showed that the TL was not an independent factor associated with poorer OS than TT in these patients (P .05).TT showed better survival than TL for patients with more than five involved nodes and metastases2 to 5 mm in the largest dimension. For patients with more than five involved nodes and metastases ≤2 mm in the largest dimension, either TT or TL can be recommended because there was no difference in survival.NA Laryngoscope, 130:269-273, 2020.

High salt intake (HS) is an important factor in the development of many metabolic diseases. The liver is the metabolic center in the body. However, the effect of short-term HS on the liver mitochondria and its mechanism are still unclear. In this study, we investigated the effects of short-term HS on liver mitochondrial function. We found that HS reduced Sirtuin3 (SIRT3) protein level, increasing protein carbonylation in mice liver. HS intake decreased ATP production, mitochondrial transcription factor A (TFAM), and complex I level. SIRT3 knockout (SKO) mice exhibited similar results with HS-treated wild-type mice but with a less extent of carbonylation and ATP reduction. Our study shows that short-term HS led to increased hepatic oxidative state, impaired mitochondrial biosynthesis, and bioenergetics. HS-treated mice could still maintain hepatic glucose homeostasis by compensatory activation of Adenosine 5'-monophosphate-activated protein kinase (AMPK). However, in HS-treated SKO mice, AMPK was not activated, instead, the glycogen synthase activity increased, which caused an exceptionally increased glycogen accumulation. This study provides evidence that short-term HS intake could cause the early hepatic metabolic changes, highlighting the importance of controlling salt intake especially in those patients with defects in SIRT3. Highlights High salt intake down-regulates SIRT3 protein level and increases oxidation. High salt intake activates AMPK via AMP-dependent pathway. High salt intake impairs energy metabolism. High salt combined with SIRT3 knockout results in glycogen accumulation.

Gastric cancer (GC) is a prevalent and heterogeneous malignancy in the digestive system. Increasing studies have suggested that circular RNAs are implicated in GC pathogenesis. This study aimed to explore the biological role and underlying mechanism of circRNA zinc finger protein 131 (circZNF131) in GC. The expression pattern of circZNF131, microRNA-186-5p (miR-186-5p), and 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 (PFKFB2) mRNA in GC tissues and cells was detected by quantitative real-time polymerase chain reaction. The stability of circZNF131 was verified using ribonuclease R assay. Functional experiments were performed by colony formation assay for cloning ability analysis, transwell assay and wounding healing assay for cell metastasis, and flow cytometry for cell apoptosis. Glycolysis metabolism was investigated by determining the levels of glucose uptake and lactate production. The protein detection of apoptosis- or glycolysis-associated markers, PFKFB2, and Ki-67 was implemented by western blot or immunohistochemistry. Dual-luciferase reporter assay was conducted to identify the interaction between miR-186-5p and circZNF131 or PFKFB2. The role of circZNF131 on tumor growth in nude mice was investigated via xenograft tumor assay. Expression analysis indicated that circZNF131 was upregulated in GC tissues and cells in a stable structure. Functional analyses showed that circZNF131 knockdown suppressed GC cell colony formation ability, migration, invasion and glycolysis metabolism, and induced cell apoptosis. Mechanically, miR-186-5p was a target of circZNF131, and miR-186-5p could bind to PFKFB2. Rescue experiments presented that miR-186-5p inhibition reversed the effects of circZNF131 knockdown on GC cell growth and glycolysis, and PFKFB2 overexpression abolished the impacts of miR-186-5p restoration on GC cell progression. Moreover, circZNF131 could positively modulate PFKFB2 expression via sponging miR-186-5p. In vivo, circZNF131 knockdown hindered GC tumor growth by regulating the miR-186-5p/PFKFB2 axis. circZNF131 could exert an oncogenic role in GC malignant development through the miR-186-5p/PFKFB2 axis, which might provide novel targets for GC treatment.

This cross-sectional study assesses the recent epidemiological trend of pulmonary tuberculosis in mainland China based on national surveillance data., Key Points Question Have the incidence and epidemiological characteristics of pulmonary tuberculosis (PTB) changed in China from 2005 to 2016? Findings In this cross-sectional study of the Chinese population, a total of 10 582 903 patients with PTB were reported from 2005 to 2016. The annual incidence ranged from 72.95 per 100 000 population in 2005 to 52.18 per 100 000 population in 2016, with a mean incidence of 66.61 per 100 000 population; the median patient age was 46 years, and 70.1% were farmers and herders. Meaning These findings suggest that preventive measures for PTB should be based on the results of epidemiological investigation., Importance The World Health Organization End TB (Tuberculosis) Strategy aims to decrease the global incidence and mortality of TB by 90% and 95%, respectively, as of 2035. Objective To characterize the recent epidemiological trend of pulmonary TB (PTB) in mainland China based on the national surveillance data. Design, Setting, and Participants This cross-sectional study collected demographic and clinical data of all patients reported in the national Tuberculosis Information Management System of China from January 1, 2005, to November 21, 2016. Data were analyzed from December 1, 2019, to July 31, 2020. Exposures Pulmonary TB was defined as bacteriologically confirmed or clinically diagnosed TB in the lung parenchyma or the tracheobronchial tree. Main Outcomes and Measures Temporal and spatial variation of annual incidence and demographic features of PTB in mainland China. Results In total, 10 582 903 patients with PTB were reported in mainland China from 2005 to 2016. The median age of patients with PTB was 46 (interquartile range [IQR], 30-61) years, and 28.53% were 60 years or older. Most patients with PTB were male (69.8%) and farmers or herders (70.0%). The mean (SD) incidence of PTB was 66.61 (8.09) per 100 000 population. The annual incidence decreased from 72.95 per 100 000 population in 2005 to 52.18 per 100 000 population in 2016, and the reduction was greater in the eastern and central regions (31.6%; from 69.43 to 47.48 per 100 000 population) than in the western region (21.0%; from 82.06 to 64.82 per 100 000 population). Xinjiang Uygur Autonomous Region (135.03 per 100 000 population), Guizhou Province (115.98 per 100 000 population), and the Tibet Autonomous Region (101.98 per 100 000 population) had the highest mean annual incidences. The median time from onset of illness to diagnosis decreased from 36 (IQR, 16-92) days from 2005 to 2007 to 31 (IQR, 15-63) days in 2008 and later (P

To evaluate the efficacy of Liuwei Dihuang formula ( LWDHF) on endothelial cells, and to study the mechanism behind the action of modulating expression of estrogen receptors.Hydrogen peroxide (H2O2) was applied to induce the apoptosis of human umbilical vein endothelial cells (HUVECs). The concentration of nitric oxide (NO), endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) were measured by assay kits. Western blot and real-time polymerase chain reaction (RT-PCR) were used to detect the expression of iNOS, eNOS, b-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), estrogen receptor (ER) α and ERβ. Also, small interfering RNA (siRNA) was involved to confirm whether the protective effects of LWDHF was medicated by ERs. In vivo, the female rats were ovariectomized to establish postmenopausal vascular injury model. Then the model rats were divided into three groups and treated with saline, estradiol and LWDHF respectively. The concentration of NO and NOS in serum were measured by assay kits, and the expression of Bax, Bcl-2, ERα and ERβ were detected by western blot and immunohistochemistry.In vitro study, LWDHF significantly protected HUVECs from H2O2-induced apoptosis, with the increase of Bcl-2 and the decrease of Bax. The treatment with LWDHF inhibited concentration of NO and iNOS, and upregulated the expression of eNOS, ERα and ERβ. In addition, ERα siRNA could block the protective effects of LWDHF, while ERβ siRNA showed little influence. In vivo, the treatment with LWDHF suppressed the vascular injury and reduced the level of NO and NOS. LWDHF increased the expression of Bcl-2, ERα and ERβ, as well as inhibiting the Bax expression.LWDHF could improve endothelial function and protect HUVECs from apoptosis via increasing the expression of ERα.

The quantum search on the graph is a very important topic. In this work, we develop a theoretic method on searching of single vertex on the graph [Phys. Rev. Lett. 114 110503 (2015)], and systematically study the search of many vertices on one low-connectivity graph, the joined complete graph. Our results reveal that, with the optimal jumping rate obtained from the theoretical method, we can find such target vertices at the time O ( N ) , where N is the number of total vertices. Therefore, the search of many vertices on the joined complete graph possessing quantum advantage has been achieved.

Atherosclerosis (AS) is exacerbated in the perimenopausal period, which significantly increases the incidence rate of cardiovascular disease. The disruption of the gut microbiota has been associated with AS or menopause, but the specific changes of AS-associated gut microbiota in the perimenopausal period remain largely unknown. As lipid abnormalities are mainly responsible for AS, the relationship between lipid metabolism abnormalities and gut microbiota disruptions during menopause is rarely reported hitherto. In the present study, ApoE−/- mice fed with a high-fat diet (HFD) were subjected to ovariectomy and supplemented with estrogen. The ovariectomized HFD-fed ApoE−/- mice underwent significant AS damage, hepatic lipid damage, hyperlipidemia, and changes of lipid metabolism- and transport-related enzymes. There was significantly higher abundance of some lipid metabolites in the plasma of ovariectomized HFD-fed ApoE−/- mice than in non-ovariectomized ones, including cholesterol esters, triglycerides, phospholipids, and other types of lipids (free fatty acids, acylcarnitine, sphingomyelins, and ceramides). The administration of estrogen significantly reduced the contents of most lipid metabolites. The diversity and composition of gut microbiota evidently changed in ovariectomized HFD-fed ApoE−/- mice, compared to HFD-fed ApoE−/- mice without ovariectomy. In contrast, with estrogen supplementation, the diversity and composition of gut microbiota were restored to approach that of non-ovariectomized HFD-fed ApoE−/- mice, and the relative abundances of some bacteria were even like those of C57BL/6 mice fed with a normal diet. On the other hand, the transplantation of feces from C57BL/6 mice fed with normal diet to ovariectomized HFD-fed ApoE−/- mice was sufficient to correct the hyperlipidemia and AS damage, and to reverse the characteristics changing of lipid metabolomics in ovariectomized HFD-fed ApoE−/- mice. These phenomena were also been observed after transplantation of feces from estrogen-treated ovariectomized HFD-fed ApoE−/- mice to ovariectomized HFD-fed ApoE−/- mice. Moreover, the gut microbiota and lipid metabolites were significantly correlated, demonstrating that the changes of serum lipids may be associated with the gut microbiota disruptions in the perimenopausal period. In conclusion, the gut microbiota during the progression of AS in the perimenopausal period showed specific compositional changes and significant correlations with circulating lipid metabolites. Estrogen supplementation may exert beneficial effects on gut bacteria and lipid metabolism.

Atherosclerosis can be regarded as a chronic disease derived from the interaction between disordered lipoproteins and an unsuitable immune response. The evolution of foam cells is not only a significant pathological change in the early stage of atherosclerosis but also a key stage in the occurrence and development of atherosclerosis. The formation of foam cells is mainly caused by the imbalance among lipids uptake, lipids treatment, and reverse cholesterol transport. Although a large number of studies have summarized the source of foam cells and the mechanism of foam cells formation, we propose a new idea about foam cells in atherosclerosis. Rather than an isolated microenvironment, the macrophage multiple lipid uptake pathways, lipid internalization, lysosome, mitochondria, endoplasmic reticulum, neutral cholesterol ester hydrolase (NCEH), acyl-coenzyme A-cholesterol acyltransferase (ACAT), and reverse cholesterol transport are mutually influential, and form a dynamic process under multi-factor regulation. The macrophage takes on different uptake lipid statuses depending on multiple uptake pathways and intracellular lipids, lipid metabolites versus pro-inflammatory factors. Except for NCEH and ACAT, the lipid internalization of macrophages also depends on multicellular organelles including the lysosome, mitochondria, and endoplasmic reticulum, which are associated with each other. A dynamic balance between esterification and hydrolysis of cholesterol for macrophages is essential for physiology and pathology. Therefore, we propose that the foam cell in the process of atherosclerosis may be dynamic under multi-factor regulation, and collate this study to provide a holistic and dynamic idea of the foam cell.

Breast cancer is responsible for high morbidity and mortality across the globe. Studies are focusing to develop novel systemic therapies for the treatment of this disease. The present study was designed to examine the anticancer effects of Shionone against human breast cancer cells along with the underlying mechanism of its action.The breast cancer SK-BR-3 and normal breast MB-157 cell lines were used in the study. CCK8 assay was used for cell viability assessment. DAPI was used for the assessment of nuclear morphology. Acridine orange (AO)/ ethidium bromide (EB) and annexin V/propidium iodide (PI) assays were used for detection of apoptosis. Cell cycle analysis was done by flow cytometry. Protein expression was examined by western blot analysis.The results showed that in vitro administration of Shionone led to decline of proliferation of breast cancer cells. The reduction of proliferative rates was attributed to the induction of apoptosis of breast cancer cells. Shionone caused cleavage of caspase-3 and 9. The expression of Bax was increased and that of Bcl-2 was decreased upon Shionone treatment. The transwell assays showed that Shionone suppressed the migration and invasion of breast cancer cells in a dose-dependent manner. Finally, western blot analysis showed that Shionone blocked the Ras/Raf/MEK/ERK and STAT3 signaling pathways in breast cancer cells.Taken all together, the study established the anticancer role of triterpenoid Shionone in restricting the growth and proliferation of human breast cancer cells.

BRASSINOSTEROID INSENSITIVE1-EMS-suppressor 1 (BES1) is an essential regulator downstream of brassinosteroid signaling and plays important roles in plant stress response, growth, and development. To date, the regulation mechanisms of BES1 transcription factors have been identified and elucidated in model plants Arabidopsis and rice. However, little information is available regarding the BES1 family in Cucumis sativus. Therefore, this study conducted a genome-wide analysis of BES1 genes in cucumber. In cucumber, a total of six CsBES1 genes were identified, and their phylogenetic relationships, gene structures, and cis-elements in promoters were studied. CsBES1 genes were distributed on four of seven chromosomes. Gene structure analysis showed that the intron–exon model of CsBES1 genes was conserved and the CsBES1 protein contained a DUF822-conserved motif. Promoter cis-element prediction showed that plenty of developmental and stress- and hormone-related elements have been found in promoter regions of CsBES1 genes. Meanwhile, BES1 was divided into three groups (I, II, and III) on the basis of phylogenetic relationship analysis in six plant species. In addition, CsBES1 gene expression patterns were confirmed by transcription database and qRT-PCR analysis; the results showed that the expression of CsBES1 genes had not only tissue-specific expression but also different types of CsBES1 isoform which might respond to specific plant stresses. In summary, genome-wide identification, phylogeny, gene structure, and expression profile analysis of CsBES1 genes in cucumber provided a referable theoretical information for further functional study of CsBES1 genes and further facilitated the molecular breeding of cucumber.

Objective To explore the neural difference between children with obstructive sleep apnea (OSA) and healthy controls, together with the relation between this difference and cognitive dysfunction of children with OSA. Methods Twenty children with OSA (7.2 ± 3.1 years, apnea hypopnea index (AHI): 16.5 ± 16.6 events/h) and 29 healthy controls (7.7 ± 2.8 years, AHI: 1.7 ± 1.2 events/h) were recruited and matched with age, gender, and handedness. All children underwent resting-state fMRI (rs-fMRI) and T1-wighted imaging. Some children were sedated for MRI scanning. We compared amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) of children with OSA with those of healthy controls. During resting-state, the former reflects the intensity of the spontaneous neural activities, whereas the latter reflects temporal similarity of the spontaneous neural activities within a local brain region. Pearson correlation analysis was performed between these features of rs-fMRI and cognitive scores among children with OSA. Results Compared with controls, children with OSA showed decreased ALFF in the left angular gyrus but increased ALFF in the right insula, and decreased ReHo in the left medial superior frontal gyrus, right lingual gyrus, and left precuneus. Additionally, among children with OSA, the ReHo value in the right lingual gyrus was negatively correlated with FIQ and VIQ, whereas that in the left medial superior frontal gyrus was positively correlated with VIQ. Conclusions Children with OSA presented abnormal neural activities in some brain regions and impaired cognitive functions with the former possibly being the neural mechanism of the latter.

BRASSINOSTEROID INSENSITIVE1-EMS-suppressor 1 (BES1) is an essential regulator downstream of brassinosteroid signaling and plays important roles in plant stress response, growth, and development. To date, the regulation mechanisms of BES1 transcription factors have been identified and elucidated in model plants Arabidopsis and rice. However, little information is available regarding the BES1 family in Cucumis sativus. Therefore, this study conducted a genome-wide analysis of BES1 genes in cucumber. In cucumber, a total of six CsBES1 genes were identified, and their phylogenetic relationships, gene structures, and cis-elements in promoters were studied. CsBES1 genes were distributed on four of seven chromosomes. Gene structure analysis showed that the intron–exon model of CsBES1 genes was conserved and the CsBES1 protein contained a DUF822-conserved motif. Promoter cis-element prediction showed that plenty of developmental and stress- and hormone-related elements have been found in promoter regions of CsBES1 genes. Meanwhile, BES1 was divided into three groups (I, II, and III) on the basis of phylogenetic relationship analysis in six plant species. In addition, CsBES1 gene expression patterns were confirmed by transcription database and qRT-PCR analysis; the results showed that the expression of CsBES1 genes had not only tissue-specific expression but also different types of CsBES1 isoform which might respond to specific plant stresses. In summary, genome-wide identification, phylogeny, gene structure, and expression profile analysis of CsBES1 genes in cucumber provided a referable theoretical information for further functional study of CsBES1 genes and further facilitated the molecular breeding of cucumber.

Objective The efficacy and safety of montelukast in children with obstructive sleep apnea (OSA) remain controversial. Therefore, the aims of this systemic review and meta-analysis are to verify this issue and further provide reference for clinical practice. Methods Seven databases were searched for randomized controlled trials (RCTs) up to September 30, 2019. The literature screening and data extraction were performed by two independent researchers. Adverse reactions from trials were also recorded. Meta-analysis was performed and analyzed heterogeneity. Methodological and evidence quality were followed by to evaluate according to Cochrane handbook. Results A total of 4 RCTs including 305 children with mild to moderate OSA were involved. Compared with placebo, we found that oral montelukast (OM) significantly improved polysomnography (PSG) monitoring parameters, typical and relevant symptoms including snoring and mouth breathing, and adenoid morphology in children with OSA. When compared with routine drugs, not only PSG monitoring parameters and adenoid morphology, but also sleep-disordered breathing (SDB)-related questionnaire scores were improved in patients with OSA treated by combination of OM and routine drugs. In addition, compared with single nasal spray of mometasone furoate, the present study also showed that OM combined with nasal spray of mometasone furoate significantly improved PSG monitoring parameters, symptoms of snoring and mouth breathing and reduced tonsil morphology in pediatric OSA. In terms of treatment safety, one study reported adverse reactions of OM such as headache, nausea and vomiting, while no adverse events were reported after OM treatment in another study. Conclusion As a classic leukotriene receptor antagonist, montelukast can be used to treat children with mild to moderate OSA in the short term and improve clinical characteristics. The promotion and application of OM in clinic is considered to be a noninvasive option to avoid surgical treatment.

The mechanism of the characteristic intermittent hypoxia (IH) of obstructive sleep apnea syndrome (OSAS) on monocyte remain unclear. Our study found that OSAS children had a significantly upregulated expression in circulating proinflammatory cytokines IL-6 and IL-12, and endothelial injury markers VEGF and ICAM1. Association analysis revealed that the plasma TNFα, IL-1β, IL-6, IL-10 and IL-12 concentration were negatively associated with the minimal SpO2, a negative index for disease severity. OSAS monocytes presented an inflammatory phenotype with higher mRNA levels of inflammatory cytokines. Importantly, we noted a significant decrease in T-cell immunoglobulin and mucin domain (Tim)-3 expression in OSAS monocytes with the increase of the plasma proinflammatory cytokines. In vitro assay demonstrated that IH induced THP-1 cell overactivation via NF-κB dependent pathway was inhibited by the Tim-3 signal. Our results indicated that activation of monocyte inflammatory responses is closely related to OSAS-induced IH, and negatively mediated by a Tim-3 signaling pathway.

The current study aimed to investigate the role and underlying mechanisms of circ_LARP4 in diabetic nephropathy (DN). Here, mouse mesangial cells (SV40‐MES13) were cultured with 30 mM glucose to establish a DN cellular model. The qRT-PCR results indicated that circ_LARP4 expression was downregulated in the DN cellular model compared to that in the control cells. As determined by an MTT assay, circ_LARP4 overexpression via the circ_LARP4 overexpression (OE) plasmids inhibited the cell proliferation rate. As determined by an Annexin V/PI kit and flow cytometry, circ_LARP4 overexpression increased the cell apoptosis rate. As measured by Western blot, circ_LARP4 overexpression enhanced BAX expression but reduced Bcl-2 expression, also suggesting an enhancement of cell apoptosis. Moreover, regarding cell fibrosis, circ_LARP4 overexpression reduced the mRNA levels of fibrosis markers, including fibronectin, collagen I and collagen IV. Interestingly, miR-424 was found to be reduced in the DN cellular model after transfection with the circ_LARP4 OE plasmids. In addition, restoration of miR-424 expression with the miR-424 mimics reversed the negative effects of circ_LARP4 overexpression on cell proliferation and fibrosis. In conclusion, circ_LARP4 was lower in the DN cellular model than in normal cells, and circ_LARP4 overexpression resulted in decreased cell proliferation and cell fibrosis but increased cell apoptosis in the DN cellular model by sponging miR-424.

Early non-pharmaceutical interventions (NPIs) are crucial to prevent and control of COVID-19 pandemic. We established a stochastic non-classical SEIR NPIs model (ScEIQRsh) which can quantify the three kinds of NPIs measures simultaneously to mimic the clustered intra-family or intra-acquaintance spreading pattern of COVID-19 under the effective integrated NPIs in Mainland China. Model simulation demonstrated that measures to diminish contactable susceptible (Sc), such as home confinement, travel constraint, social distancing etc. and measures to avoid delay of diagnosis and hospitalized isolation (η) were more effective but consumptive than contact tracing (κ, ρ). From fitted model by MCMC method, the proportion of asymptomatic infectors was 14.88% (IQR 8.17%, 25.37%). The association between air temperature and the fitted transmission rate (β) of COVID-19 suggests that COVID-19 pandemic would be seasonal with the optimal temperature range of 5°C-14°C and peak of 10°C for spreading, and vaccine is indispensable to ultimate prevention COVID-19.

Background Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Although dysfunction of renal tubule, also exhibited as epithelial-mesenchymal transition (EMT) and fibrosis, is closely associated with DN, the mechanism underlying renal tubule dysfunction still remains obscure. Methods Here, we identify that miR-199b-3p protect renal tubule from diabetic- induced injury by repressing KDM6A, a histone lysine demethylase reinforcing diabetic renal tubule dysfunction through regulating E-cadherin expression. We investigated the relationship between KDM6A, E-cadherin and miR-199b-3p with a series of gain- and loss- function assay in different cell models and animal models. The expression of KDM6A, E-cadherin and miR-199b-3p was tested by qPCR, western bolt or IHC. The EMT was measured by wound healing assay. The dysfunction of renal tubule were observed through HE and PAS stain and the kidney functions were monitored through several pathological signs detection assay, such as albumin to creatinine ratio (ACR), blood urea nitrogen (BUN), creatinine (Cr), proteinuria. Results Lower expression of E-cadherin was related to a higher level of KDM6A, while E-cadherin was increased with KDM6A-inhibitor GSK-J4 treatment both in HG-induced HK-2 cells and STZ-induced kidney. However, the variable expression of E-cadherin caused by overexpression or silence RNA was failed to alter the KDM6A expression. The target prediction and dual-luciferase assay results showed miR-199b-3p is a new miRNA targeting KDM6A. Overexpression of miR-199b-3p increased E-cadherin expression and prevented EMT through repressing KDM6A expression in HG-induced HK-2 cells, whereas miR-199b-3p knockdown by inhibitor displayed opposite results with lower E-cadherin and worse EMT accompanying with higher level of KDM6A. In addition, the miR-199b-3p knockout mice exhibited more dysfunctional renal tubule and more serious damage in kidney tissue treated with STZ. Conclusions These results demonstrate that miR-199b-3p improve E-cadherin expression and prevent the progression of DN through targeting KDM6A. MiR-199b-3p could be a potential biomarker or target for the diagnosis and treatment of diabetic nephropathy in the future.