2,5,11,14-Tetra­oxa-8-aza­dispiro­[13.4.0]nona­deca-15,17,19-triene

The title compound, C14H21NO4, has been synthesized from o-dihydroxy­benzene by a three-step reaction. There are two chemically equal but crystallographically independent mol­ecules in the asymmetric unit. The crystal packing is governed by C—H⋯O hydrogen bonds and C—H⋯π inter­actions, forming an infinite network

Examining associations of folic acid supplements administered to mothers during pre-conceptional and prenatal periods with autism spectrum disorders in their offspring: insights from a multi-center study in China

ObjectiveTo investigate the relationship between maternal folic acid (FA) supplementation during the pre-conceptional and prenatal periods and the subsequent risk of autism spectrum disorder (ASD) in offspring.MethodsA total of 6,049 toddlers aged 16–30 months were recruited from August 2016 to March 2017 for this cross-sectional study conducted in China. The parents of the enrolled toddlers provided information on maternal supplemental FA, socio-demographic information, and related covariates. Standard diagnostic procedures were implemented to identify toddlers with ASD.ResultsAmong the 6,049 children included in the study, consisting of 3,364 boys with an average age of 22.7 ± 4.1 months, a total of 71 children (1.2%) were diagnosed with ASD. Mothers who did not consume FA supplements during the prenatal period were found to have a significantly increased risk of having offspring with ASD, in comparison to those who were exposed to FA supplements (odds ratio [OR] = 2.47). However, we did not find a similar association during the pre-conceptional period. Compared to mothers who consistently used FA supplements from pre-conception to the prenatal period, those who never used FA supplements were statistically significantly associated with a higher risk of ASD in their offspring (OR = 2.88).ConclusionThis study indicated that providing continuous maternal FA supplementation during the pre-conceptional and prenatal periods may decrease the risk of ASD in offspring. The prenatal period is considered to be the most crucial time for intervention

A Review of Biomarkers and Their Clinical Impact in Resected Early-Stage Non-Small-Cell Lung Cancer

The postoperative survival of early-stage non-small-cell lung cancer (NSCLC) patients remains unsatisfactory. In this review, we examined the relevant literature to ascertain the prognostic effect of related indicators on early-stage NSCLC. The prognostic effects of the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), mesenchymal–epithelial transition (MET), C-ros oncogene 1 (ROS1), or tumour protein p53 (TP53) alterations in resected NSCLC remains debatable. Kirsten rat sarcoma viral oncogene homologue (KRAS) alterations indicate unfavourable outcomes in early-stage NSCLC. Meanwhile, adjuvant or neoadjuvant EGFR-targeted agents can substantially improve prognosis in early-stage NSCLC with EGFR alterations. Based on the summary of current studies, resected NSCLC patients with overexpression of programmed death-ligand 1 (PD-L1) had worsening survival. Conversely, PD-L1 or PD-1 inhibitors can substantially improve patient survival. Considering blood biomarkers, perioperative peripheral venous circulating tumour cells (CTCs) and pulmonary venous CTCs predicted unfavourable prognoses and led to distant metastases. Similarly, patients with detectable perioperative circulating tumour DNA (ctDNA) also had reduced survival. Moreover, patients with perioperatively elevated carcinoembryonic antigen (CEA) in the circulation predicted significantly worse survival outcomes. In the future, we will incorporate mutated genes, immune checkpoints, and blood-based biomarkers by applying artificial intelligence (AI) to construct prognostic models that predict patient survival accurately and guide individualised treatment

The Profile and Clinical Significance of ITGB2 Expression in Non-Small-Cell Lung Cancer

Integrins are involved in extracellular and intracellular signaling and are often aberrantly expressed in tumors. Integrin beta 2 (ITGB2) has previously been demonstrated to be correlated with the host defense. However, the expression profile and role of ITGB2 in non-small-cell lung cancer (NSCLC) remain unclear. Here, we found that the genetic alterations in ITGB2 was predominated by gene mutation and copy number deletion using cBioPortal analysis, and its expression was downregulated in the NSCLC tissues, as validated by the UALCAN, TCGA, and GEO databases and our tissue samples. Kaplan–Meier (KM) plotter analysis revealed that patients with a lower ITGB2 expression had a shorter overall survival (OS) time (p = 0.01). Moreover, 1089 differentially expressed genes (DEGs) in the NSCLC tissues were screened using the TCGA database. The GO and KEGG enrichment analysis showed that the DEGs were closely associated with immune processes and cell adhesion. The protein–protein interaction (PPI) network revealed that 10 of 15 EMT-related genes among the DEGs might lead to the metastasis of NSCLC. Concomitantly, the expression of ITGB2 was positively correlated with the infiltration of Treg cells and Myeloid-derived suppressor cells (MDSC). Biologically, the ectopic expression of ITGB2 significantly inhibited the proliferation and metastasis of NSCLC cells. Mechanistically, we demonstrated that ITGB2 suppressed the expression of N-cadherin, Vimentin, Slug, Snail, and Twist, while it promoted E-cadherin expression, according to gain-of-function studies. In conclusion, ITGB2 can inhibit the proliferation and migration of NSCLC cells, leading to a poor prognosis, via epithelial–mesenchymal transition (EMT) signaling

Cognitive behavioural therapy attenuates the enhanced early facial stimuli processing in social anxiety disorders: an ERP investigation

Abstract Background Previous studies of patients with social anxiety have demonstrated abnormal early processing of facial stimuli in social contexts. In other words, patients with social anxiety disorder (SAD) tend to exhibit enhanced early facial processing when compared to healthy controls. Few studies have examined the temporal electrophysiological event-related potential (ERP)-indexed profiles when an individual with SAD compares faces to objects in SAD. Systematic comparisons of ERPs to facial/object stimuli before and after therapy are also lacking. We used a passive visual detection paradigm with upright and inverted faces/objects, which are known to elicit early P1 and N170 components, to study abnormal early face processing and subsequent improvements in this measure in patients with SAD. Methods Seventeen patients with SAD and 17 matched control participants performed a passive visual detection paradigm task while undergoing EEG. The healthy controls were compared to patients with SAD pre-therapy to test the hypothesis that patients with SAD have early hypervigilance to facial cues. We compared patients with SAD before and after therapy to test the hypothesis that the early hypervigilance to facial cues in patients with SAD can be alleviated. Results Compared to healthy control (HC) participants, patients with SAD had more robust P1–N170 slope but no amplitude effects in response to both upright and inverted faces and objects. Interestingly, we found that patients with SAD had reduced P1 responses to all objects and faces after therapy, but had selectively reduced N170 responses to faces, and especially inverted faces. Interestingly, the slope from P1 to N170 in patients with SAD was flatter post-therapy than pre-therapy. Furthermore, the amplitude of N170 evoked by the facial stimuli was correlated with scores on the interaction anxiousness scale (IAS) after therapy. Conclusions Our results did not provide electrophysiological support for the early hypervigilance hypothesis in SAD to faces, but confirm that cognitive-behavioural therapy can reduce the early visual processing of faces. These findings have potentially important therapeutic implications in the assessment and treatment of social anxiety. Trial registration HEBDQ201402

The enhanced x-ray timing and polarimetry mission – eXTP: an update on its scientific cases, mission profile and development status

The enhanced x-ray timing and polarimetry mission (eXTP) is a flagship observatory for x-ray timing, spectroscopy and polarimetry developed by an international consortium. Thanks to its very large collecting area, good spectral resolution and unprecedented polarimetry capabilities, eXTP will explore the properties of matter and the propagation of light in the most extreme conditions found in the universe. eXTP will, in addition, be a powerful x-ray observatory. The mission will continuously monitor the x-ray sky, and will enable multi-wavelength and multi-messenger studies. The mission is currently in phase B, which will be completed in the middle of 2022