Capsaicin Reduces Cancer Stemness and Inhibits Metastasis by Downregulating SOX2 and EZH2 in Osteosarcoma.

Metastasis of osteosarcoma is an important adverse factor affecting patients' survival, and cancer stemness is the crucial cause of distant metastasis. Capsaicin, the main component of pepper, has been proven in our previous work to inhibit osteosarcoma proliferation and enhance its drug sensitivity to cisplatin at low concentrations. This study aims to further explore the anti-osteosarcoma effect of capsaicin at low concentrations (100[Formula: see text][Formula: see text]M, 24[Formula: see text]h) on stemness and metastasis. The stemness of human osteosarcoma (HOS) cells was decreased significantly by capsaicin treatment. Additionally, the capsaicin treatment's inhibition of cancer stem cells (CSCs) was dose-dependent on both sphere formation and sphere size. Meanwhile, capsaicin inhibited invasion and migration, which might be associated with 25 metastasis-related genes. SOX2 and EZH2 were the most two relevant stemness factors for capsaicin's dose-dependent inhibition of osteosarcoma. The mRNAsi score of HOS stemness inhibited by capsaicin was strongly correlated with most metastasis-related genes of osteosarcoma. Capsaicin downregulated six metastasis-promoting genes and up-regulated three metastasis-inhibiting genes, which significantly affected the overall survival and/or disease-free survival of patients. In addition, the CSC re-adhesion scratch assay demonstrated that capsaicin inhibited the migration ability of osteosarcoma by inhibiting its stemness. Overall, capsaicin exerts a significant inhibitory effect on the stemness expression and metastatic ability of osteosarcoma. Moreover, it can inhibit the migratory ability of osteosarcoma by suppressing its stemness via downregulating SOX2 and EZH2. Therefore, capsaicin is expected to be a potential drug against osteosarcoma metastasis due to its ability to inhibit cancer stemness.

Hypoxia-induced miR-9 expression promotes ovarian cancer progression via activating PI3K/AKT/mTOR/GSK3ß signaling pathway.

Ovarian cancer (OC) is one of the most prevalent malignant tumors affecting women's life and health. Since OC has a poor prognosis due to extensive metastasis, there is a need to explore a new mechanism of OC metastasis. microRNAs (miRs) are single-stranded, non-coding RNAs. miR-9 has been reported to promote cancer and may provide a new strategy for OC diagnosis. The purpose of this study was to examine the function and underlying mechanism of miR-9 in OC. RT-qPCR was used to assess miR-9 expression levels. Transwell assays were used to determine the number of migrating and invading OC cells. The protein expression levels of the PI3K/AKT/mTOR/GSK3ß signaling pathway were examined using western blotting. The results informed that, when compared to normal ovarian tissues, miR-9 was remarkably expressed in OC tissues, and hypoxia might lead to overexpression of miR-9-5p while inhibiting miR-9 notably suppressed the migrating and invading cell numbers in OC cells. In vivo, miR-9-5p knockdown inhibited tumor growth in a subcutaneous nude mice model of SKOV3 cells. Our findings suggest that miR-9 could be an underlying oncogene in OC, opening up new avenues for OC diagnosis and treatment of OC by targeting miR-9.

Parental involvement in postoperative pain management among children in a urology ward: A best practice implementation project.

AIM: Postoperative pain has adverse effects on children with urological problems, including sleep disturbances, incision dehiscence, bleeding and delayed recovery. Accurate parental assessment of children's behaviours and responses could help to manage postoperative pain. We aimed to implement evidence-based practice for parental involvement in a urology ward, to increase parents' participation in children's postoperative pain management. DESIGN: The project was conducted in a paediatric urology ward using the framework and methods of the Fudan University Evidence-Based Nursing Center's Evidence-based Continuous Quality Improvement Model. METHODS: Fifteen audit criteria were used to represent best practice recommendations for parental involvement in postoperative pain management. A pre-implementation audit was conducted with 211 randomly sampled children and parents. Obstacles, promoting factors and key strategies were analysed, and evidence-based interventions implemented to improve compliance. A follow-up audit using the same audit criteria was conducted with 202 children and parents to assess the effect of targeted strategies on compliance with best practice. The SQUIRE guidelines were followed. RESULTS: At the baseline audit, compliance with the evidence-based criteria was 0%-71.5%; only five audit criteria achieved a compliance rate > 60%. After best practice implementation, the follow-up audit showed compliance improvements for all criteria; compliance for three criteria improved to 100%. PATIENT OR PUBLIC CONTRIBUTION: This best practice implementation project improved parents' participation in children's postoperative pain management. The findings demonstrate how audits can promote best practice in postoperative pain management for children. Additional studies will be conducted to address children's postoperative life quality based on best practice.

Exploration of Mutated Genes and Prediction of Potential Biomarkers for Childhood-Onset Schizophrenia Using an Integrated Bioinformatic Analysis.

Childhood-onset schizophrenia (COS) is an unusual severe neurodevelopmental disorder of unknown etiology. In this study, we aimed to survey the missense variants in new cases of COS and also identify possible pathology biomarkers for COS. We found one list of mutated genes such as TTN, MUC12, and MUC2, which are the candidates to be involved in the etiology of COS. Next, we used WGSNA to predict COS disease-related genes and identified differential DNA methylation among COS disease groups, COS dangerous groups, and normal groups and found eight methylation sites that can be used as the diagnostic biomarkers. A total of six key genes are obtained through the intersection analysis between weighted correlation network analysis (WGCNA) mode, methylation-related genes, and differentially expressed genes (DGenes). These genes may play important roles in the progression of COS and serve as the potential biomarkers for future diagnosis. Our results might help to design the molecule or gene-targeted drugs for COS.

Analysis of hospitalization costs related to fall injuries in elderly patients.

BACKGROUND: With the aging world population, the incidence of falls has intensified and fall-related hospitalization costs are increasing. Falls are one type of event studied in the health economics of patient safety, and many developed countries have conducted such research on fall-related hospitalization costs. However, China, a developing country, still lacks large-scale studies in this area. AIM: To investigate the factors related to the hospitalization costs of fall-related injuries in elderly inpatients and establish factor-based, cost-related groupings. METHODS: A retrospective study was conducted. Patient information and cost data for elderly inpatients (age ≥ 60 years, n = 3362) who were hospitalized between 2016 and 2019 due to falls was collected from the medical record systems of two grade-A tertiary hospitals in China. Quantile regression (QR) analysis was used to identify the factors related to fall-related hospitalization costs. A decision tree model based on the chi-squared automatic interaction detector algorithm for hospitalization cost grouping was built by setting the factors in the regression results as separation nodes. RESULTS: The total hospitalization cost of fall-related injuries in the included elderly patients was 180479203.03 RMB, and the reimbursement rate of medical benefit funds was 51.0% (92039709.52 RMB/180479203.03 RMB). The medical material costs were the highest component of the total hospitalization cost, followed (in order) by drug costs, test costs, treatment costs, integrated medical service costs and blood transfusion costs The QR results showed that patient age, gender, length of hospital stay, payment method, wound position, wound type, operation times and operation type significantly influenced the inpatient cost (P < 0.05). The cost grouping model was established based on the QR results, and age, length of stay, operation type, wound position and wound type were the most important influencing factors in the model. Furthermore, the cost of each combination varied significantly. CONCLUSION: Our grouping model of hospitalization costs clearly reflected the key factors affecting hospitalization costs and can be used to strengthen the reasonable control of these costs.

The proportion and associated factors of anxiety in Chinese adolescents with depression during the COVID-19 outbreak.

BACKGROUND: Given the serious impact of the COVID-19 outbreak on the mental health of Chinese adolescents, this study aimed to examine the proportion of anxiety and its correlates among Chinese adolescents with depression during the pandemic. METHODS: This cross-sectional online survey was conducted from February 20th to February 27, 2020 in China. Symptoms of depression and anxiety were assessed by the 20-item Center for Epidemiological Studies-Depression (CES-D) and 7-item Generalized Anxiety Disorder (GAD-7), respectively. RESULTS: In this study, 3,498 adolescents with depression were identified. Of them, the proportion of anxiety was 45.1% (95% confidence interval [CI]=43.5%-46.8%). Multiple logistic regression analysis revealed that being concerned about graduation (OR=1.25, P=0.002, 95% CI=1.09-1.43), sleep duration <6hr/day (OR=1.80, P<0.001, 95% CI=1.38-2.34), study duration >8hr/day (OR=1.21, P=0.02, 95% CI=1.03-1.42), and quantity of homework higher than before (OR=1.68, P<0.001, 95% CI=1.40-2.02) were positively associated with anxiety; the number of confirmed COVID-19 cases at a provincial level of 100-999 (OR=0.70, P<0.001, 95% CI=0.59-0.83) and 1,000-9,999 (OR=0.69, P=0.001, 95% CI=0.55-0.87) were negatively related to anxiety in adolescents with depression. LIMITATIONS: Because this was a cross-sectional online study, the causality between variables and anxiety could not be examined among depressed adolescents. The use of self-reported scales may lead to an underestimation of the proportion of anxiety among adolescents with depression. CONCLUSIONS: The symptoms of anxiety were common in adolescents with depression during the COVID-19 outbreak. Timing screening and targeted interventions are necessary to mitigate the risks of mental illness of adolescents.

Up-regulation of SOCS4 promotes cell proliferation and migration in esophageal squamous cell carcinoma.

BACKGROUND: Suppressors of cytokine signaling family member 4 (SOCS4) was shown to serve critical and multifaceted roles in the progression of numerous cancers, including hepatocellular carcinoma, thyroid cancer, breast cancer, and lung adenocarcinoma. While, the expression and the roles of SOCS4 in esophageal squamous cell carcinoma (ESCC) remain elusive. The current study is aimed to investigate the expression pattern and functions of SOCS4 in ESCC. METHODS: The relationship between SOCS4 and the clinicopathological features of ESCC was analyzed. SOCS4 expression in ESCC tissues was measured by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemical (IHC) staining. The roles of SOCS4 in modulating ESCC cell behaviors were examined using a series of assays, including cell proliferation assay, cell counting kit-8 (CCK-8) assay, cell cycle analysis, and wound-healing assay. RESULTS: In human ESCC tissues, SOCS4 expression was up-regulated and correlated with tumor size and lymph node metastasis, however was not correlated with the overall survival (OS) of patients. SOCS4 silencing in ESCC cells resulted in the suppression of cell growth, which was related to the cell cycle. SOCS4 knockdown also inhibited nuclear factor-kappa B (NF-κB) signaling and decreased the migratory potential of ESCC cells. CONCLUSIONS: These findings revealed that increased expression of SOCS4 in ESCC may promote the progression, proliferation, and migration by NF-κB signaling. Inhibition of SOCS4 may be a promising therapeutic strategy for ESCC.

Genome-wide Identification, Classification and Expression Analysis of the Mildew Resistance Locus O ( MLO ) Gene Family in Sweet Orange ( Citrus sinensis )

ABSTRACT Mildew resistance Locus O (MLO), a gene family specific to plants, plays significant roles in the resistance to powdery mildew (PM) and response to a variety of abiotic stresses, plant growth and development. Despite their importance as barley, rice, wheat, few studies are reported in dicots except Arabidopsis; no global analysis has been performed in the burgeoning model fruit plant sweet orange (Citrus sinensis). The recent release of the genome sequences of C. sinensis provides an opportunity to conduct a comprehensive overview the evolution and features of the MLO gene family in sweet orange. In this study, amount to 14 members of the Citrus sinensis MLO gene (CisMLO) family according to their gene structures, conserved motifs, and similitude among their presumptive Arabidopsis and rice orthologs were identified in silico. Based on these analyses, all CisMLOs were grouped into six clades and expanded partly due to one tandem duplication and two segmental duplication events. Survey of their chromosomal distributions uncovered that 14 CisMLOs are localized across 6 chromosomes. Multiple-sequence alignments showed that 11 of them shared seven highly conserved transmembrane domains (TMs), while all of the sweet orange MLO proteins except CisMLO4/14 had a calmodulin-binding domain for MLO function. Expression analysis demonstrated that the MLO gene family has a diverse tissue-specific expression profiles in the sweet orange development and plays potential critical roles in stress responses. These findings will facilitate further studies of evolutionary pattern and biological functions of MLO genes in sweet orange.

[Expression profiles of brain-derived neurotrophic factor in the spinal dorsal horn of young rats with visceral hypersensitivity].

OBJECTIVE: To explore the relationship between the expression of brain-derived neurotrophic factor (BDNF) in the spinal dorsal horn and the increase in visceral hypersensitivity in young rats by establishing a young rat model of visceral hypersensitivity by neonatal maternal separation (NMS). METHODS: Thirty-two newborn Sprague-Dawley rats were randomly and equally divided into four groups by a 2×2 factorial design: control, NMS, colorectal distension (CRD), and NMS+CRD. The newborn rats in the NMS and NMS+CRD groups were subjected to 3-hour daily maternal separation from days 2 to 14 after birth to establish a model of visceral hypersensitivity, while the rats in the control and CRD groups received no treatment after birth. At 6 weeks after birth, the CRD and CRD+NMS groups received CRD stimulation. The streptavidin-biotin complex immunohistochemical method was used to determine the expression of BDNF in the spinal dorsal horn. The immunohistochemical score (IHS) was calculated based on the percentage of BDNF-positive cells and color intensity. The percentage of BDNF-positive cells in the spinal dorsal horn and IHS were analyzed by factorial analysis of variance. RESULTS: The expression of BDNF was detected bilaterally in the spinal dorsal horn at different levels in the four groups. The percentage of BDNF-positive cells and IHS were significantly higher in the NMS and NMS+CRD groups than in the control group (P<0.05). The results of factorial analysis of variance indicated that NMS significantly increased the percentage of BDNF-positive cells in the spinal dorsal horn and IHS; a single CRD stimulation had no effects on the IHS of BDNF-positive cells in the spinal dorsal horn; there was no interaction between NMS and a single CRD stimulation. CONCLUSIONS: The over-expression of BDNF in the spinal dorsal horn may be involved in high visceral hypersensitivity in young rats induce by NMS.

Association between Tourette syndrome and the dopamine D3 receptor gene rs6280.

BACKGROUND: Tourette syndrome (TS) is a complex, heterozygous genetic disorder. The number of molecular genetic studies have investigated several candidate genes, particularly those implicated in the dopamine system. The dopamine D3 receptor (DRD3) gene has been considered as a candidate gene in TS. There was not any report about the association study of TS and DRD3 gene in Han Chinese population. We combined a case-control genetic association analysis and nuclear pedigrees transmission disequilibrium test (TDT) analysis to investigate the association between DRD3 gene rs6280 single nucleotide polymorphisms (SNPs) and TS in a Han Chinese population. METHODS: A total of 160 TS patients was diagnosed by the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The DRD3 gene rs6280 SNPs were genotyped by TaqMan SNP genotyping assay technique in all subjects. We used a case-control genetic association analysis to compare the difference in genotype and allele frequencies between 160 TS patients and 90 healthy controls. At the same time, we used TDT analysis to identify the DRD3 gene rs6280 transmission disequilibrium among 101 nuclear pedigrees. RESULTS: The genotype and allele frequency of DRD3 gene rs6280 SNPs had no statistical difference between control group (90) and TS group (160) (χ2 = 3.647, P = 0.161; χ2 = 0.643, P = 0.423) using Chi-squared test. At the basis of the 101 nuclear pedigrees, TDT analysis showed no transmission disequilibrium of DRD3 gene rs6280 SNPs (χ2 = 0; P = 1). CONCLUSIONS: Our findings provide no evidence for an association between DRD3 gene rs6280 and TS in the Han Chinese population.

Utilisation of adsorption and desorption for simultaneously improving protein crystallisation success rate and crystal quality.

High-quality protein crystals of suitable size are an important prerequisite for applying X-ray crystallography to determine the 3-dimensional structure of proteins. However, it is often difficult to obtain protein crystals of appropriate size and quality because nucleation and growth processes can be unsuccessful. Here, we show that by adsorbing proteins onto porous polystyrene-divinylbenzene microspheres (SDB) floating on the surface of the crystallisation solution, a localised high supersaturation region at the surface of the microspheres and a low supersaturation region below the microspheres can coexist in a single solution. The crystals will easily nucleate in the region of high supersaturation, but when they grow to a certain size, they will sediment to the region of low supersaturation and continue to grow. In this way, the probability of crystallisation and crystal quality can be simultaneously increased in a single solution without changing other crystallisation parameters.

In vitro and in vivo CT imaging using bismuth sulfide modified with a highly biocompatible Pluronic F127.

Probe bismuth sulfide modified with Pluronic F127 (Bi2S3-PF127), which has high biocompatibility and dispersibility, is synthesized using triblock copolymer Pluronic F127 to modify hydrophobic Bi2S3 nanoparticles that are prepared by a hot injection method. TEM results show that most of the probe has a length of about 14.85 ± 1.70 nm and a breadth of about 4.79 ± 0.63 nm. After injected into the tail vein of a mouse, the probe has obvious CT contrast enhancement capability from x-ray CT imaging results. Meanwhile, the probe's in vivo toxicity is also studied. It is found that hematoxylin and eosin stains of major organs have no change. A biochemical analysis (alanine aminotransferase and aspartate aminotransferase) prove the probe has no adverse effects. The results of a blood analysis (white blood cell count, red blood cell count, hemoglobin, and platelet count) are also normal. The biological distribution of Bi by ICP-AES shows that most of nanoparticles are cleaned out after injection 48 h, and the circulation half-life of the probe is 5.0 h, suggesting that Bi2S3-PF127 has a long circulation and indicating that the Bi2S3-PF127 probe has good biocompatibility and safety.

Evaporation rate of water as a function of a magnetic field and field gradient.

The effect of magnetic fields on water is still a highly controversial topic despite the vast amount of research devoted to this topic in past decades. Enhanced water evaporation in a magnetic field, however, is less disputed. The underlying mechanism for this phenomenon has been investigated in previous studies. In this paper, we present an investigation of the evaporation of water in a large gradient magnetic field. The evaporation of pure water at simulated gravity positions (0 gravity level (ab. g), 1 g, 1.56 g and 1.96 g) in a superconducting magnet was compared with that in the absence of the magnetic field. The results showed that the evaporation of water was indeed faster in the magnetic field than in the absence of the magnetic field. Furthermore, the amount of water evaporation differed depending on the position of the sample within the magnetic field. In particular, the evaporation at 0 g was clearly faster than that at other positions. The results are discussed from the point of view of the evaporation surface area of the water/air interface and the convection induced by the magnetization force due to the difference in the magnetic susceptibility of water vapor and the surrounding air.