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Competing endogenous RNA (ceRNA)-mediated signaling pathway dysregulation provides great insight into comprehensively understanding the molecular mechanism and combined targeted therapy for glioblastoma. circRNA is characterized by high stability, tissue/developmental stage-specific expression and abundance in brain and plays significant roles in the initiation and progression of cancer. Our previous published data have demonstrated that RPN2 was significantly upregulated in glioma and promoted tumor progression via the activation of the Wnt/β-catenin pathway. Furthermore, we proved that miR-422a regulated the Wnt/β-catenin signaling pathway by directly targeting RPN2. In this study, based on the glioblastoma microarray profiles, we identified the upstream circTOP2A, which completely bound to miR-422a and was co-expressed with the RPN2. circTOP2A was significantly overexpressed in glioma and conferred a poor prognosis. circTOP2A could regulate RPN2 expression by sponging miR-422a, verified by western blot, dual-luciferase reporter gene assay, and RNA pull-down assay. Functional assays including CCK8, transwell and FITC-annexin V were performed to explore the RPN2-mediated role of the circTOP2A effect on the glioma malignant phenotype. Additionally, TOP/FOP and immunofluorescence analysis were used to confirm that sh-circTOP2A could suppress the Wnt/β-catenin pathway partly through RPN2. Finally, a tumor xenograft model was applied to validate the biological function of circTOP2A in vivo. Taken together, our findings reveal the critical role of circTOP2A in promoting glioma proliferation and invasion via a ceRNA mechanism and provide an exploitable biomarker and therapeutic target for glioma patients.

Background Crizotinib is associated with a favorable survival benefit in patients with ALK‐positive non‐small cell lung cancer (NSCLC); however, a subset of patients harboring ALK rearrangement shows a poor response. Methods We collected the clinical features and survival outcomes of 28 primary‐resistant responders (PRR) with progression‐free survival (PFS) of < 3 months on crizotinib and compared these with 78 long‐term responders (LTR) that achieved > 24 months PFS (control). Results Primary resistance was observed in 6.5% of the patients. The median PFS of the PRR and LTR groups was 1.2 months (95% confidence interval [CI] 0.70–1.73) and 47.0 months (95% CI 34.39–59.64), respectively. A better Eastern Cooperative Oncology Group performance status score was significantly associated with longer PFS (odds ratio 0.06, 95% CI 0.01–0.33; P = 0.001). The median overall survival (OS) of the PRR group was 8.4 months (95% CI 3.47–13.42) and crizotinib as first‐line treatment was an independent predictive factor for survival outcome (P = 0.005). Patients administered ALK‐tyrosine kinase inhibitors after crizotinib progression had significantly longer survival than the PRR group treated with best supportive care (P = 0.007), but no significant difference was found between ALK‐tyrosine kinase inhibitor treatment and single chemotherapy (P = 0.944). Conclusion Patients with primary resistance to crizotinib displayed unfavorable survival outcomes and the underlying mechanism cannot be identified in clinical features. Nevertheless, next‐generation ALK inhibitors and chemotherapy after crizotinib progression could confer a therapeutic and survival benefit in this population.

The CAPTRA-Lung study (NCT03334864) is a prospective observational study that will capture real-world data of patients with advanced or metastatic non-small cell lung cancer (NSCLC) across China. The study aims to complement the results from current therapeutic regimens to improve the standard of diagnosis and treatment, evaluate the effectiveness and safety of systemic therapy, and determine the factors influencing the outcomes and responses to treatment. From January 2018 to December 2023, eligible patients with advanced or metastatic NSCLC who are receiving treatment and participating in follow-up at 16 institutions in China, will be enrolled. The demographic, clinical, laboratory, and treatment characteristics and responses to treatment will be recorded in a case report form and transcribed into an electronic data capture system. Overall survival, progression-free survival, overall response rate, and incidence of adverse events will be calculated from the time of initial enrolment until progression evaluated by physicians, last contact, date of death, or analysis cutoff date, respectively. Based on the disease characteristics and treatment strategies, four sub-cohorts will also be established. This study cohort could serve as a pool of patients with advanced or metastatic NSCLC to support further research.

An alarming number of students drop out of junior high school in developing countries. In this study, we examine the impacts of providing a social–emotional learning (SEL) program on the dropout behavior and learning anxiety of students in the first two years of junior high. We do so by analyzing data from a randomized controlled trial involving 70 junior high schools and 7,495 students in rural China. After eight months, the SEL program reduces dropout by 1.6 percentage points and decreases learning anxiety by 2.3 percentage points. Effects are no longer statistically different from zero after 15 months, perhaps due to decreasing student interest in the program. However, we do find that the program reduces dropout among students at high risk of dropping out (older students and students with friends who have already dropped out), both after eight and 15 months of exposure to the SEL program.

Human proteasomes are validated targets in oncology and are promising targets in immune related diseases. A number of peptide-based proteasome inhibitors have reached the clinic and several others are currently investigated in clinical trials. Despite these achievements, peptide-based inhibitors may be susceptible to protease-mediated degradation. In this paper, we report on our results on the introduction of 5-methylpyridin-2-one moiety in peptide vinyl sulfone and peptide epoxy ketone-based proteasome inhibitors. Pyridin-2-ones have previously been used as constrained peptide isosteres capable to act as a hydrogen-bond acceptor. Our results demonstrate that 5-methylpyridin-2-one can be introduced into proteasome inhibitors, but that the activity of the resulting compounds is compromised compared to their parent peptide vinyl sulfones and peptide epoxy ketones.

Nivolumab prolonged disease control in a patient with advanced squamous lung cancer that was refractory to multiple treatments. The rapid eradication of cancer after the administration of nivolumab caused hemoptysis and repeated infection. Six months after immunotherapy, mediastinal lymph node metastasis developed and afatinib effectively relieved dysphonia associated with nerve paralysis.

Proteasomes are therapeutic targets for various cancers and autoimmune diseases. Constitutively expressed proteasomes have three active sites, β1c, β2c, and β5c. Lymphoid tissues also express the immunoproteasome subunits β1i, β2i, and β5i. Rapid and simultaneous measurement of the activity of these catalytic subunits would assist in the discovery of new inhibitors, improve analysis of proteasome inhibitors in clinical trials, and simplify analysis of subunit expression. In this work, we present a cocktail of activity-based probes that enables simultaneous gel-based detection of all six catalytic human proteasome subunits. We used this cocktail to develop specific inhibitors for β1c, β2c, β5c, and β2i, to compare the active-site specificity of clinical proteasome inhibitors, and to demonstrate that many hematologic malignancies predominantly express immunoproteasomes. Furthermore, we show that selective and complete inhibition of β5i and β1i is cytotoxic to primary cells from acute lymphocytic leukemia (ALL) patients.

The Rh(II)-catalyzed sulfur ylide [1,2]-rearrangement of carbenoids generated from aryldiazoacetates has been realized via N–S bond insertion, generating tertiary sulfides in moderate to excellent yields. This demonstrates the first use of the sulfur ylide [1,2]-rearrangement undergoing N–S bond insertion. This protocol could proceed smoothly with high regioselectivity, low catalyst loading (0.1 mol% Rh2(OAc)4), gram-scale reaction and broad substrate scope. And the product could be converted into glycine derivatives through simple procedures.

Asian Americans are commonly perceived as the diligent and high-achieving “model minority.” This positive stereotype has negative consequences for this ethnic minority group because it trivializes their social and mental health problems. This image of success has made many overlook the true nature of the struggles many Asian American families have to face in the United States. Scientific literature suggests that Asian American children experience major adjustment problems in school including loneliness, isolation, withdrawal, rejection, anxiety, low self-esteem, and interpersonal distress. Cultural barriers exist between the Asian and the dominant society and influence Asian Americans' cognitive appraisal and coping choices when personal and emotional problems arise. These barriers also prevent clinicians from identifying and subsequently providing effective mental health services for Asian American children and their families. In this article, the authors examine the Asian cultural conceptions of mental health and various cultural barriers in an attempt to promote cultural understanding and competence among clinicians working with Asian American children and their families. Recommendations for clinical practice and future research directions are provided. © 2009 Wiley Periodicals, Inc.

Nickel (Ni) performs its biological or toxic functions in nickel-protein coordination form. Novel Ni-binding peptides were isolated from a random dodecapeptide library displayed on the flagella of Escherichia coli against immobilized ions. On the basis of isolated sequences rich in histidine residues, two secondary libraries were constructed respectively. By consequent selection, more Ni-chelating peptides were identified and the consensus motif RHXHR (where X was always H) was deduced. The result suggested that not only histidine, but also arginine, play an important role in Ni-binding. Furthermore, two selected clones (1035 and 2022) were chosen for further identification. They exhibited similar relative binding affinity, which was about nine times that of the original library derived clones and statistically much more significant than the positive control with polyhistidine insert. Free nickel ions could almost completely inhibit the binding of the clones 1035 and 2022 to immobilized nickel, implicating that the peptides were able to chelate nickel ions. These studies reveal that bacterial surface displayed peptide libraries may have promising future potential for the development of metal bioadsorbents. Furthermore, novel Ni-binding peptides may provide lead molecules for Ni-chelation and applications thereof.

Guided by Perry and Weinstein's (1998) conceptual model of school adjustment, first-generation Chinese-American adolescents' school adjustment was compared with that of Mainland Chinese and European American adolescents in two domains of functioning, academic (attitudes to school and teacher; their sense of academic adequacy) and behavioral (depression, anxiety and social stress), using the Behavioral Assessment System for Children (BASC). Results indicated that Chinese-American adolescents reported more negative attitudes toward teachers than European American and Mainland Chinese students, had more negative perceptions of the school environment than students in Mainland China, and reported more feelings of inadequacy in academics than European American students. Chinese-American adolescents reported higher levels of depression and social stress than the other two groups, and more anxiety than Mainland Chinese students. Feelings of academic inadequacy were related to depression, anxiety and social stress for all three cultural groups. In addition, Chinese-American adolescents reported that they did not trust their teachers and their peers who were not Chinese-American, and felt that adults at school and home did not understand them. This feeling coupled with their fear, anger and frustration at being bullied frequently in school could be related to Chinese-American adolescents' negative perception of school and teachers. Implications of the study are discussed. © 2003 Wiley Periodicals, Inc. Psychol Schs 40: 71–84, 2003.

This study examined the structure of self-reported problem behaviors in Mainland Chinese children. Third grade (n = 3011) and fifth grade (n = 3708) students completed a 20-item Problem Behavior Frequency Checklist (PBFC). Findings suggested that among the four factors studied (physical aggression, substance use, delinquency, and self-centered behaviors), self-centered behaviors and physical aggression were reported most frequently by the Chinese elementary school children. Furthermore, boys had higher prevalence rates of problem behaviors than girls. Developmental differences were also present. Confirmatory factor analyses supported a model that included specific factors related to substance use, physical aggression, delinquency, and self-centered behaviors. Therefore, the single factor conceptualization in which different types of problem behaviors are hypothesized to reflect a single underlying common factor may not hold for this population. © 2003 Wiley Periodicals, Inc. Psychol Schs 40: 19–33, 2003.

In a furtherance of our SAR study on the C-6 position of quinolone antibacterials, a series of 6-desfluoro-8-methylquinolones were synthesized and evaluated for their in vitro antimicrobial activity. As a result of this study, compounds with strong activity against Gram-positive bacteria, including ciprofloxacin-resistant and methicillin-resistant Staphylococcus aureus, were identified. The best Gram-positive antibacterial activity was exhibited by piperidinyl derivative 6c, which was 17 times more potent than ciprofloxacin and displayed extremely high activity against Streptococcus pneumoniae with an MIC value of ≤0.016 μg/mL. Thus, we have shown that substituent combinations in the quinolone ring, excluding the C-6 fluorine atom, might produce powerful antibacterial agents.