Immune Checkpoint in Glioblastoma: Promising and Challenging

Glioblastoma (GBM) is a severe malignant brain cancer with poor overall survival. Conventional intervention remains dismal to prevent recurrence and deterioration of GBM cell. Recent years have witnessed exciting breakthroughs in novel immune strategies, especially checkpoint inhibitors, some of which have become adjuvant setting after standard of care in melanoma. Several clinical trials of checkpoint inhibitors are ongoing in glioblastoma and other brain carcinomas. Plus, synergistic combinations of checkpoint inhibitors with conventional therapy strategies—radiotherapy, temozolomide, bevacizumab, and corticosteroids are now being exploited and applied in clinical settings. This review highlights the recent developments of checkpoints in GBM immunotherapy to provide a brief and comprehensive review of current treatment options. Furthermore, we will discuss challenges remained, such as unique immune system of central nervous system (CNS), immune-related toxicities, synergies, and adverse interactions of combination therapies

Tunable nonlinear optical bistability based on Dirac semimetal in photonic crystal Fabry-Perot cavity

In this paper, we study the nonlinear optical bistability (OB) in a symmetrical multilayer structure. This structure is constructed by embedding a nonlinear three-dimensional Dirac semimetal (3D DSM) into a solution filled one-dimensional photonic crystal Fabry-Perot cavity. OB stems from the third order nonlinear conductivity of 3D DSM and the local field of resonance mode could enhance the nonlinearity and reduce the thresholds of OB. This structure achieves the tunability of OB due to that the transmittance could be modulated by the Fermi energy. OB threshold and threshold width could be remarkably reduced by increasing the Fermi energy. Besides, it is found that the OB curve depends heavily on the angle of incidence of the incoming light, the structural parameters of the Fabry-Perot cavity, and the position of 3D DSM inside the cavity. After parameter optimization, we obtained OB with a threshold of 106 V/m. We believe this simple structure provides a reference idea for realizing low threshold and tunable all optical switching devices. Keywords: Optical bistability, Dirac semimetal, Fabry-Perot cavity

Central and Peripheral Changes in FOS Expression in Schizophrenia Based on Genome-Wide Gene Expression

Schizophrenia is a chronic, debilitating neuropsychiatric disorder. Multiple transcriptomic gene expression profiling analysis has been used to identify schizophrenia-associated genes, unravel disease-associated biomarkers, and predict clinical outcomes. We aimed to identify gene expression regulation, underlying pathways, and their roles in schizophrenia pathogenesis. We searched the Gene Expression Omnibus (GEO) database for microarray studies of fibroblasts, lymphoblasts, and post-mortem brains of schizophrenia patients. Our analysis demonstrated high FOS expression in non-neural peripheral samples and low FOS expression in brain tissues of schizophrenia patients compared with healthy controls. FOS exhibited predictive value for schizophrenia patients in these datasets. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that “amphetamine addiction” was among the top 10 significantly enriched KEGG pathways. FOS and FOSB, which are implicated in the amphetamine addiction pathway, were up-regulated in schizophrenia fibroblast samples. Protein–protein interaction (PPI) network analysis revealed that proteins closely interacting with FOS-encoded protein were also involved in the amphetamine addiction pathway. Pearson correlation test indicated that FOS showed positive correlation with genes in the amphetamine pathway. The results revealed that FOS was acceptable as a biomarker for schizophrenia and may be involved in schizophrenia pathogenesis

The effect of parenting styles on Chinese undergraduate nursing students’ academic procrastination: the mediating role of causal attribution and self-efficacy

BackgroundAcademic procrastination is common among college students, but there is a lack of research on the influencing mechanism of academic procrastination among nursing students. The purpose of this study was to explore the influence of parental rearing patterns on academic procrastination of nursing students, and the mediating role of causal attribution and self-efficacy.MethodsUsing Parental Bonding Instrument, Aitken Procrastination Inventory, Multidimensional Multi-Attribution Causality Scale and General Self-Efficiency Scale, the data of 683 nursing undergraduates from two universities in China were collected. Moreover, path analysis for structural equation modeling via AMOS 26.0 to evaluate mediation path model.ResultsPositive parenting style was negatively associated with academic procrastination (r = –0.350) and negative parenting style was positively associated with academic procrastination (r = 0.402). Positive parenting style directly or indirectly predicted academic procrastination through the mediating effect of internal attributional style (β = –0.10, 95% CI: –0.18 to –0.04) and self-efficacy (β = –0.07, 95% CI: –0.11 to –0.03), and this mediating effect accounted for 41.46% of the total effect. Positive parenting style directly or indirectly predicted academic delay through the mediating effect of external attributional style (β = 0.12, 95% CI: 0.07 to 0.17) and self-efficacy (β = 0.05, 95% CI: 0.03 to 0.08), and this mediating effect accounted for 42.5% of the total effect. In addition, causal attribution and self-efficacy of nursing students play a chain intermediary role between parenting style and academic procrastination.ConclusionParents should give students more care and autonomy and reduce control. In addition, educators should give students attribution training, which is helpful to improve students’ self-efficacy and reduce academic procrastination

Twelve-year outcomes of bedside laser photocoagulation for severe retinopathy of prematurity

PurposeThe purpose of this study is to evaluate the 12-year outcomes of bedside laser photocoagulation (LP) for severe retinopathy of prematurity (ROP) under sedation combined with ocular surface anesthesia in neonatal intensive care units (NICU).DesignThe study is a retrospective case series.MethodsInfants treated with bedside LP for severe ROP from April 2009 to September 2021 were included. All LP treatments were performed under sedation and surface anesthesia at the bedside in NICU. Data were recorded for clinical and demographic characteristics, total laser spots, duration of treatment, proportion of total regression of ROP, proportion of recurrence, and adverse events.ResultsA total of 364 infants (715 eyes) were included, with a mean gestational age of 28.6 ± 2.4 weeks (range: 22.6–36.6 weeks) and a mean birth weight of 1,156.0 ± 339.0 g (range: 480–2,200 g). The mean number of laser spots was 832 ± 469, and the mean duration of treatment was 23.5 ± 5.3 min per eye. Of all the eyes, 98.3% responded to LP with complete regression of ROP. ROP recurred in 15 (2.1%) eyes after the initial LP. Additional LP was performed in seven (1.0%) eyes. No patient exhibited mistaken LP of other ocular tissues, and there were no serious ocular adverse effects. None of them needed endotracheal intubation.ConclusionsBedside LP treatment is effective and safe for premature infants with severe ROP under sedation and surface anesthesia in NICU, especially for infants whose general condition is unstable and not suitable for transport

Exploring a novel seven-gene marker and mitochondrial gene TMEM38A for predicting cervical cancer radiotherapy sensitivity using machine learning algorithms

BackgroundRadiotherapy plays a crucial role in the management of Cervical cancer (CC), as the development of resistance by cancer cells to radiotherapeutic interventions is a significant factor contributing to treatment failure in patients. However, the specific mechanisms that contribute to this resistance remain unclear. Currently, molecular targeted therapy, including mitochondrial genes, has emerged as a new approach in treating different types of cancers, gaining significant attention as an area of research in addressing the challenge of radiotherapy resistance in cancer.MethodsThe present study employed a rigorous screening methodology within the TCGA database to identify a cohort of patients diagnosed with CC who had received radiotherapy treatment. The control group consisted of individuals who demonstrated disease stability or progression after undergoing radiotherapy. In contrast, the treatment group consisted of patients who experienced complete or partial remission following radiotherapy. Following this, we identified and examined the differentially expressed genes (DEGs) in the two cohorts. Subsequently, we conducted additional analyses to refine the set of excluded DEGs by employing the least absolute shrinkage and selection operator regression and random forest techniques. Additionally, a comprehensive analysis was conducted in order to evaluate the potential correlation between the expression of core genes and the extent of immune cell infiltration in patients diagnosed with CC. The mitochondrial-associated genes were obtained from the MITOCARTA 3.0. Finally, the verification of increased expression of the mitochondrial gene TMEM38A in individuals with CC exhibiting sensitivity to radiotherapy was conducted using reverse transcription quantitative polymerase chain reaction and immunohistochemistry assays.ResultsThis process ultimately led to the identification of 7 crucial genes, viz., GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2, which were strongly associated with radiotherapy sensitivity. The enrichment analysis has unveiled a significant association between these 7 crucial genes and prominent signaling pathways, such as the p53 signaling pathway, KRAS signaling pathway, and PI3K/AKT/MTOR pathway. By utilizing these 7 core genes, an unsupervised clustering analysis was conducted on patients with CC, resulting in the categorization of patients into three distinct molecular subtypes. In addition, a predictive model for the sensitivity of CC radiotherapy was developed using a neural network approach, utilizing the expression levels of these 7 core genes. Moreover, the CellMiner database was utilized to predict drugs that are closely linked to these 7 core genes, which could potentially act as crucial agents in overcoming radiotherapy resistance in CC.ConclusionTo summarize, the genes GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2 were found to be closely correlated with the sensitivity of CC to radiotherapy. Notably, TMEM38A, a mitochondrial gene, exhibited the highest degree of correlation, indicating its potential as a crucial biomarker for the modulation of radiotherapy sensitivity in CC

Changes in the mental health status of the general Chinese population during the COVID-19 pandemic: A longitudinal study

The study is based on a longitudinal evaluation of the public, during the initial COVID-19 outbreak in China and 8 months after. It aimed to explore the changes in the mental health of the public at the beginning of the pandemic and during the regular epidemic prevention and control. An online survey questionnaire was used to collect data during the initial COVID-19 outbreak (February 10, 2020–February 18, 2020; T1) and 8 months after the outbreak (October 21, 2020–December 29, 2020; T2). Psychological distress was assessed using the Patient Health Questionnaire-9 (PHQ-9), Self-rating Anxiety Scale (SAS), and Post-traumatic Stress Disorder Checklist (PCL-5). A chi-square test was used to compare the changes in the depression and anxiety scores at T1 and T2, and the correlation between symptoms was analyzed through Spearman's rank correlation. In T1, 1,200 people were recruited, while 168 people responded in T2. Depression (48.2–31.0%; p=0.001) and anxiety (17.9–9.5%; p = 0.026) symptoms decreased over time; two participants developed post-traumatic stress disorder (PTSD) in T2. The scores of the PHQ-9 scale and the SAS scale were both positively correlated with the score of the PCL-5 scale and negatively correlated with sleep time. During the COVID-19 pandemic, part of the general population's anxiety and depression significantly reduced with time, and they rarely developed PTSD. PTSD occurrence was related to severe depression and anxiety

Study on condition prediction and influencing factors of manganese carbonate recovery by high gradient pulse magnetic separation

Manganese carbonate ore belongs to weakly magnetic minerals, and its co-associated minerals are mainly non-magnetic minerals, which can be separated from gangue minerals at high magnetic field intensity. However, manganese grade and recovery of magnetic separation concentrate of manganese carbonate ore are low in actual production. Therefore, the influences of manganese carbonate particle size, magnetic field intensity, volume susceptibility, pulse stroke, pH, and other factors were studied. The optimal test conditions for manganese carbonate ore recovery by high-gradient magnetic separation were predicted through the calculation results. The results show that the particle radius of manganese carbonate is 0.020 mm, the pulse impulse time is 200 r/min, and the magnetic field intensity is 0.9 T. The optimum condition test was carried out with Qianbei manganese carbonate ore as the material. The test results show that the optimum conditions are the particle radius of 0.074-0.019 mm, pulse impulse time of 200 r/min, and magnetic field intensity of 1.2 T. The reason for the deviation is that the actual ore has a fine distribution particle size, many associative bodies, complex composition, and serious agglomeration, resulting in variable particle volume susceptibility. The capture yield increases with the increase of magnetic field intensity and volume susceptibility but decreases with the increase of pulse. The lower the surface potential of manganese carbonate, the higher the recovery of manganese carbonate. The grade of manganese concentrate was 19.06% and the recovery was 76.85%. Mixed manganese concentrate with a grade of 18.04% and recovery of 87.14% was obtained by adding drugs and changing the grinding method