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Abstract Background Prioritizing genes that underlie complex brain disorders poses a considerable challenge. Despite previous studies have found that they shared symptoms and heterogeneity, it remained difficult to systematically identify the risk genes associated with them. Methods By using the CAGE (Cap Analysis of Gene Expression) read alignment files for 439 human cell and tissue types (including primary cells, tissues and cell lines) from FANTOM5 project, we predicted enhancer-promoter interactions (EPIs) of 439 cell and tissue types in human, and examined their reliability. Then we evaluated the genetic heritability of 17 diverse brain disorders and behavioral-cognitive phenotypes in each neural cell type, brain region, and developmental stage. Furthermore, we prioritized genes associated with brain disorders and phenotypes by leveraging the EPIs in each neural cell and tissue type, and analyzed their pleiotropy and functionality for different categories of disorders and phenotypes. Finally, we characterized the spatiotemporal expression dynamics of these associated genes in cells and tissues. Results We found that identified EPIs showed activity specificity and network aggregation in cell and tissue types, and enriched TF binding in neural cells played key roles in synaptic plasticity and nerve cell development, i.e., EGR1 and SOX family. We also discovered that most neurological disorders exhibit heritability enrichment in neural stem cells and astrocytes, while psychiatric disorders and behavioral-cognitive phenotypes exhibit enrichment in neurons. Furthermore, our identified genes recapitulated well-known risk genes, which exhibited widespread pleiotropy between psychiatric disorders and behavioral-cognitive phenotypes (i.e., FOXP2), and indicated expression specificity in neural cell types, brain regions, and developmental stages associated with disorders and phenotypes. Importantly, we showed the potential associations of brain disorders with brain regions and developmental stages that have not been well studied. Conclusions Overall, our study characterized the gene-enhancer regulatory networks and genetic mechanisms in the human neural cells and tissues, and illustrated the value of reanalysis of publicly available genomic datasets.

BackgroundThe use of low-dose aspirin for women with twin pregnancies remains controversial. This study was to describe the frequency of preeclampsia and aspirin use in twin pregnancies in real practice.MethodsThis retrospective cohort study based on real-world data was conducted in the Obstetrics and Gynecology Hospital of Fudan University between 2013 and 2020. Women with twin pregnancies who received prenatal care before 20 weeks of gestational age were included. They were divided into those using low-dose aspirin (LDA group) and those not using aspirin group (N-LDA group). The primary outcome was the frequency of preeclampsia, and secondary outcomes included early-onset and preterm mild and severe preeclampsia.ResultsA total of 2,946 women had twin pregnancies, and 241 were excluded due to missing information. Of 2,705 eligible women, 291 (10.75%) were administered aspirin and the other 2,414 (89.25%) did not. The patients in the LDA group were significantly more likely to be older, have a higher rate of use of ART, have a previous history of hypertension, and have gestational diabetes (p < 0.05). In the LDA group, aspirin compliance ≥50% was relatively low (14.43%, 42/291). Preeclampsia occurred in 106 of 291 participants (36.43%) in the LDA group, as compared to 449 of 2,411 (18.62%) in the N-LDA group (OR: 2.15, 95% CI: 1.62–2.82; p < 0.01). The association was confirmed (OR: 1.74, 95% CI: 1.26–2.4; p < 0.01) in the 1:2 case-matched analysis. Higher odds of ratio in the LDA group were demonstrated (aORs > 1, p < 0.01), except for early-onset and preterm mild preeclampsia (p > 0.05). This association was confirmed in a subgroup analysis of methods of conception (aORs ≥ 1, p > 0.05).ConclusionAspirin prescription of 75 to 100 mg in twin pregnancies was associated with no significant reduction of preeclampsia, which may be due to poor compliance with the aspirin used. Further randomized controlled or prospective cohort studies are required.

Purified desulphated glucosinolates (GSLs) were subjected to thermal treatment in model systems without interference to investigate the formation of volatile components derived from GSLs only. Desulphated progoitrin (PRO), desulphated gluconapin (GNA), and desulphated glucobrassicanapin (GBN) were isolated from rapeseed (Brassica napus L.). Their structures were identified via spectroscopic data. According to the final thermal degradation compounds of the desulphated GSLs, the thermal degradation pathways of the GSLs identified herein in rapeseed during roasting were speculated. PRO degradation formed 2,4-pentadienenitrile by eliminating the hydroxyl group of the R group to generate the double bond at C-2. GNA degradation produced 4-isothiocyanato-1-butene. Two degradation pathways were possibly involved in the degradation of GNA and GBN. The main precursors that produce the pungent flavour of rapeseed oil were obtained by exploring the relationship between the degradation of the GSLs and the volatile flavour of this vegetable oil during roasting.

Circulating tumor cells (CTCs) in cancer patients’ peripheral blood have been demonstrated to be a significant biomarker for metastasis detection, disease prognosis, and therapy response. Due to their extremely low concentrations, efficient enrichment and non-destructive release are needed. Herein, an FTO chip modified with multifunctional gelatin nanoparticles (GNPs) was designed for the specific capture and non-destructive release of CTCs. These nanoparticles share a similar dimension with the microvilli and pseudopodium of the cellular surface; thus, they can enhance adhesion to CTCs, and then GNPs can be degraded by the enzyme matrix metalloproteinase (MMP-9), gently releasing the captured cells. In addition, the transparency of the chip makes it possible for fluorescence immunoassay identification in situ under a microscope. Our chip attained a high capture efficiency of 89.27%, a release efficiency of 91.98%, and an excellent cellular viability of 96.91% when the concentration of MMP-9 was 0.2 mg/mL. Moreover, we successfully identified CTCs from cancer patients’ blood samples. This simple-to-operate, low-cost chip exhibits great potential for clinical application.

Abstract The utilization of an inorganic hole‐transport layer (HTL) is one of the most effective methods to improve the stability and reduce the cost of perovskite solar cells (PSCs). However, achieving high‐quality inorganic HTL films, especially HTL films in n‐i‐p structures, via solution processes remains a big challenge. Here, a simple surface modification strategy for low‐cost and stable cuprous oxide (Cu2O) quantum dots is proposed, which utilizes a silane coupling agent. The modified Cu2O can be directly deposited on the perovskite film as the top HTL without decomposing the perovskite to maintain an n‐i‐p structure. The efficiency (18.9%) of PSCs with surface‐modified Cu2O as the HTL is significantly higher than that (11.9%) of PSCs with unmodified Cu2O, which is also the record efficiency for a Cu2O‐based perovskite solar cell in n‐i‐p structure. The enhanced performance of PSCs is attributed to the remarkably enhanced film properties achieved through surface modification. Moreover, because of the dopant‐free technology and hydrophobic surface, the Cu2O‐based PSCs have distinctly better stability than 2,2′,7,7′‐tetrakis[N,N‐di(4‐methoxyphenyl)amino]‐9,9′‐spiro‐bifluorene‐based PSCs.

In this study, we developed fluorescent dual pH and oxygen sensors loaded in multi-well plates for in-situ and high-throughput monitoring of oxygen respiration and extracellular acidification during microbial cell growth for understanding metabolism. Biocompatible PHEMA-co-PAM materials were used as the hydrogel matrix. A polymerizable oxygen probe (OS2) derived from PtTFPP and a polymerizable pH probe (S2) derived from fluorescein were chemically conjugated into the matrix to solve the problem of the probe leaching from the matrix. Gels were allowed to cure directly on the bottom of 96-well plates at room-temperature via redox polymerization. The influence of matrix’s composition on the sensing behaviors was investigated to optimize hydrogels with enough robustness for repeatable use with good sensitivity. Responses of the dual sensing hydrogels to dissolved oxygen (DO) and pH were studied. These dual oxygen-pH sensing plates were successfully used for microbial cell-based screening assays, which are based on the measurement of fluorescence intensity changes induced by cellular oxygen consumption and pH changes during microbial growth. This method may provide a real-time monitoring of cellular respiration, acidification, and a rapid kinetic assessment of multiple samples for cell viability as well as high-throughput drug screening. All of these assays can be carried out by a conventional plate reader.