Posterior default mode network is associated with the social performance in male children with autism spectrum disorder: A dynamic causal modeling analysis based on triple-network model.

The triple-network model has been widely applied in neuropsychiatric disorders including autism spectrum disorder (ASD). However, the mechanism of causal regulations within the triple-network and their relations with symptoms of ASD remains unclear. 81 male ASD and 80 well matched typically developing control (TDC) were included in this study, recruited from Autism Brain Image Data Exchange-I datasets. Spatial reference-based independent component analysis was used to identify the anterior and posterior part of default-mode network (aDMN and pDMN), salience network (SN), and bilateral executive-control network (ECN) from resting-state functional magnetic resonance imaging data. Spectral dynamic causal model and parametric empirical Bayes with Bayesian model reduction/average were adopted to explore the effective connectivity (EC) within triple-network and the relationship between EC and autism diagnostic observation schedule (ADOS) scores. After adjusting for age and site effect, ASD and TDC groups both showed inhibition patterns. Compared with TDC, ASD group showed weaker self-inhibition in aDMN and pDMN, stronger inhibition in pDMN→aDMN, weaker inhibition in aDMN→LECN, pDMN→SN, LECN→SN, and LECN→RECN. Furthermore, negative relationships between ADOS scores and pDMN self-inhibition strength, as well as with the EC of pDMN→aDMN were observed in ASD group. The present study reveals imbalanced effective connections within triple-networks in ASD children. More attentions should be focused at the pDMN, which modulates the core symptoms of ASD and may serve as an important region for ASD diagnosis and the target region for ASD treatments.

Enhancement of silicon vacancy fluorescence intensity in silicon carbide using a dielectric cavity.

Over the past decades, spin qubits in silicon carbide (SiC) have emerged as promising platforms for a wide range of quantum technologies. The fluorescence intensity holds significant importance in the performance of quantum photonics, quantum information process, and sensitivity of quantum sensing. In this work, a dual-layer Au/SiO2 dielectric cavity is employed to enhance the fluorescence intensity of a shallow silicon vacancy ensemble in 4H-SiC. Experimental results demonstrate an effective fourfold augmentation in fluorescence counts at saturating laser power, corroborating our theoretical predictions. Based on this, we further investigate the influence of dielectric cavities on the contrast and linewidth of optically detected magnetic resonance (ODMR). There is a 1.6-fold improvement in magnetic field sensitivity. In spin echo experiments, coherence times remain constant regardless of the thickness of dielectric cavities. These experiments pave the way for broader applications of dielectric cavities in SiC-based quantum technologies.

NLRP3 promotes radiation-induced brain injury by regulating microglial pyroptosis.

PURPOSE: Radiation-induced brain injury, one of the side effects of cranial radiotherapy in tumour patients, usually results in durable and serious cognitive disorders. Microglia are important innate immune-effector cells in the central nervous system. However, the interaction between microglia and neurons in radiation-induced brain injury remains uncharacterised. METHODS AND MATERIALS: We established a microglia-neuron indirect co-culture model to assess the interaction between them. Microglia exposed to radiation were examined for pyroptosis using lactate dehydrogenase (LDH) release, Annexin V/PI staining, SYTOX staining and western blot. The role of nucleotide-binding oligomerisation domain-like receptor family pyrin domain containing 3 (NLRP3) was investigated in microglia exposed to radiation and in mouse radiation brain injury model through siRNA or inhibitor. Mini-mental state examination and cytokines in blood were performed in 23 patients who had experienced cranial irradiation. RESULTS: Microglia exerted neurotoxic features after radiation in the co-culture model. NLRP3 was up-regulated in microglia exposed to radiation, and then caspase-1 was activated. Thus, the gasdermin D protein was cleaved, and it triggered pyroptosis in microglia, which released inflammatory cytokines. Meanwhile, treatment with siRNA NLRP3 in vitro and NLRP3 inhibitor in vivo attenuated the damaged neuron cell and cognitive impairment, respectively. What is more, we found that the patients after radiation with higher IL-6 were observed to have a decreased MMSE score. CONCLUSIONS: These findings indicate that radiation-induced pyroptosis in microglia may promote radiation-induced brain injury via the secretion of neurotoxic cytokines. NLRP3 was evaluated as an important mediator in radiation-induced pyroptosis and a promising therapeutic target for radiation-induced brain injury.

Highly Stable Silver Nanowire Plasmonic Electrodes for Flexible Polymer Light-Emitting Devices.

Silver nanowire (AgNW) transparent electrodes are considered as a promising candidate for applications in flexible optoelectronic devices. However, it remains a great challenge to obtain flexible AgNW electrodes with excellent optoelectrical properties and mechanical flexibility. Here, highly stable Ag nanoparticle (AgNP)-enhanced plasmonic AgNW electrodes are demonstrated via the controllable in situ growth of AgNPs at the AgNW junctions and introduction of an l-histidine (l-His) wrapping layer. The flexible transparent electrodes of AgNW-AgNP/l-His possess a low sheet resistance (Rsh) of ∼17.5 Ω sq-1, a high transmittance of ∼92.5% (550 nm), and a robust mechanical stability (100,000 bending cycles). Benefiting from plasmon-coupling effects, flexible polymer light-emitting devices (FPLEDs) with AgNW-AgNP/l-His electrodes present a current efficiency (CE) of ∼14.8 cd A-1 and an external quantum efficiency (EQE) of ∼5.6%, constituting ∼80% and ∼75% increases compared to those of the reference devices with AgNW electrodes, respectively. Additionally, the laminated flexible transparent PLEDs (FT-PLEDs) are demonstrated by integrating polydimethylsiloxane/AgNW-AgNP anodes by a soft lamination process. The FT-PLEDs present a CE of ∼7.1 cd A-1 (cathode side: ∼3.9 cd A-1; anode side: ∼3.2 cd A-1) and an EQE of ∼2.7% (cathode side: ∼1.5%; anode side: ∼1.2%). Furthermore, the FPLEDs and FT-PLEDs exhibit robust mechanical durability, maintaining ∼89% and ∼86% of their initial luminance after 1000 bending cycles at a bending radius of 2 mm, respectively. This work opens up a new avenue for the development of high performance and stable flexible optoelectronic devices.

Stomatal maturomics: hunting genes regulating guard cell maturation and function formation from single-cell transcriptomes.

Stomata play critical roles in gas exchange and immunity to pathogens. While many genes regulating early stomatal development up to the production of young guard cells (GCs) have been identified in Arabidopsis, much less is known about how young GCs develop into mature functional stomata. Here we perform a maturomics study on stomata, with "maturomics" defined as omics analysis of the maturation process of a tissue or organ. We develop an integrative scheme to analyze three public stomata-related single-cell RNA-seq datasets and identify a list of 586 genes that are specifically up-regulated in all three datasets during stomatal maturation and function formation. The list, termed sc_586, is enriched with known regulators of stomatal maturation and functions. To validate the reliability of the dataset, we selected two candidate G2-like transcription factor genes, MYS1 and MYS2, to investigate their roles in stomata. These two genes redundantly regulate the size and hoop rigidity of mature GCs, and the mys1 mys2 double mutatants cause mature GCs with severe defects in regulating their stomatal apertures. Taken together, our results provide a valuable list of genes for studying GC maturation and function formation.

Single-cell network analysis reveals gene expression programs for Arabidopsis root development and metabolism.

Single-cell RNA-seq (scRNA-seq) datasets of Arabidopsis roots have been generated, but related comprehensive gene co-expression network analyses are lacking. We conducted a single-cell gene co-expression network analysis with publicly available scRNA-seq datasets of Arabidopsis roots using a SingleCellGGM algorithm. The analysis identified 149 gene co-expression modules, which we considered gene expression programs (GEPs). By checking their spatiotemporal expression, we identified GEPs specifically expressed in major root cell types along their developmental trajectories. These GEPs defined gene programs regulating root cell development at different stages and are enriched with relevant developmental regulators. As examples, a GEP specific for quiescent center (QC) contains 20 genes regulating QC and stem cell niche homeostasis, and five GEPs are expressed in sieve elements (SEs) from early to late developmental stages, with the early-stage GEP containing 17 known SE developmental regulators. We also identified GEPs for metabolic pathways with cell type-specific expression, suggesting the existence of cell type-specific metabolism in roots. Using the GEPs, we discovered and verified a columella-specific gene, NRL27, as a regulator of auxin-related root gravitropism response. Our analysis thus systematically revealed GEPs regulating Arabidopsis root development and metabolism and provided candidate genes for root biology studies.

Compact supermode switch for photonic matrix processing.

A 2 × 2 switch based on differential effective thermo-optic (TO) coefficients of waveguide supermodes is proposed and experimentally demonstrated as a more compact alternative to Mach-Zehnder interferometer (MZI)-based switches used in coherent photonic matrix processing networks. The total waveguide width of the device is 1.335 µm. Using a novel, to the best of our knowledge, supermode coupler with a wideband 3-dB coupling ratio, the switch was engineered to have on-off extinction ratios (ERs) ranging from 24.1 to 38.9 dB for the two output ports over a 135 nm bandwidth. Insertion losses (ILs) of less than 0.3 and 0.4 dB over the 100 nm bandwidth were measured for bar and cross transmission, respectively. The waveguide width error tolerance is +/-30 nm. The proposed device has the potential to improve the scalability of a programmable coherent mesh for matrix processing by increasing the integration density without sacrificing the overall accuracy or limiting the operational wavelength range of the mesh.

High-visibility energy-time entanglement system enabled by a low-loss silicon-integrated platform.

Energy-time (E-T) entanglement is widely employed in long-distance quantum entanglement distribution due to its strong robustness against transmission fluctuations. In this Letter, we report what we believe to be the first silicon monolithically integrated E-T entanglement system, which integrates the photon sources, wavelength demultiplexers, and Franson interferometers on a single chip. Also, by utilizing low-loss multimode waveguides in Franson interferometers, we measured an on-chip quantum interference visibility of 99.66% (±0.47%), to our knowledge one of the highest values for integrated E-T entanglement systems reported to date. The quantum interference after 1- and 5-km fiber propagation shows visibilities of 96.72% (±0.78%) and 97.46% (±1.23%), respectively. These results demonstrate the potential of using silicon monolithic integration for advance E-T entanglement-based quantum communication networks.

Widespread 2013-2020 decreases and reduction challenges of organic aerosol in China.

High concentrations of organic aerosol (OA) occur in Asian countries, leading to great health burdens. Clean air actions have resulted in significant emission reductions of air pollutants in China. However, long-term nation-wide trends in OA and their causes remain unknown. Here, we present both observational and model evidence demonstrating widespread decreases with a greater reduction in primary OA than in secondary OA (SOA) in China during the period of 2013 to 2020. Most of the decline is attributed to reduced residential fuel burning while the interannual variability in SOA may have been driven by meteorological variations. We find contrasting effects of reducing NOx and SO2 on SOA production which may have led to slight overall increases in SOA. Our findings highlight the importance of clean energy replacements in multiple sectors on achieving air-quality targets because of high OA precursor emissions and fluctuating chemical and meteorological conditions.

Association among abnormal glycolipids, reproductive hormones, and cognitive dysfunction in female patients with bipolar disorder.

BACKGROUND: Patients with bipolar disorder (BD) show abnormalities in glucolipid metabolism and reproductive hormone levels, which are of concern in women with BD. This study was dedicated to investigating the glucolipid and reproductive hormone levels of female patients, and to preliminarily investigating their relationships with cognition. METHODS: A total of 58 unmedicated female BD patients, 61 stable-medicated female BD patients, and 63 healthy controls (HC) were recruited in this study. Serum glycolipid indexes and reproductive hormones were measured. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test). RESULTS: Patients with BD showed significant cognitive impairment (p < 0.05), which was not affected by medication. Triglycerides (TG), luteinizing hormone (LH), and high-density lipoprotein cholesterol (HDL-c) were altered in stable-medicated BD patients. In addition, regression analysis showed that progesterone (PRGE) and prolactin (PRL) were negatively associated with cognitive performance in stable-medicated BD patients. CONCLUSIONS: Female BD patients may have cognitive deficits and abnormal levels of glycolipids and reproductive hormones. And abnormal levels of glycolipids and reproductive hormones may be associated with cognitive dysfunction in female BD patients.

Identification of potential therapeutic targets for plaque vulnerability based on an integrated analysis.

BACKGROUND AND AIMS: This study aimed to explore potential hub genes and pathways of plaque vulnerability and to investigate possible therapeutic targets for acute coronary syndrome (ACS). METHODS AND RESULTS: Four microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), weighted gene coexpression networks (WGCNA) and immune cell infiltration analysis (IIA) were used to identify the genes for plaque vulnerability. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology, Gene Ontology annotation and protein-protein interaction (PPI) network analyses were performed to explore the hub genes. Random forest and artificial neural networks were constructed for validation. Furthermore, the CMap and Herb databases were employed to explore possible therapeutic targets. A total of 168 DEGs with an adjusted P < 0.05 and approximately 1974 IIA genes were identified in GSE62646. Three modules were detected and associated with CAD-Class, including 891 genes that can be found in GSE90074. After removing duplicates, 114 hub genes were used for functional analysis. GO functions identified 157 items, and 6 pathways were enriched for the KEGG pathway at adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). Random forest and artificial neural network models were built based on the GSE48060 and GSE34822 datasets, respectively, to validate the previous hub genes. Five genes (GZMA, GZMB, KLRB1, KLRD1 and TRPM6) were selected, and only two of them (GZMA and GZMB) were screened as therapeutic targets in the CMap and Herb databases. CONCLUSION: We performed a comprehensive analysis and validated GZMA and GZMB as a target for plaque vulnerability, which provides a therapeutic strategy for the prevention of ACS. However, whether it can be used as a predictor in blood samples requires further experimental verification.

Remnant cholesterol trajectory and subclinical arteriosclerosis: a 10-year longitudinal study of Chinese adults.

We aimed to identify different trajectories of remnant cholesterol (RC) and investigate the association of RC trajectories with vascular endothelial function and atherosclerosis progression in a longitudinal cohort of the Chinese population. A total of 521 participants were included in the flow-mediated vasodilation (FMD) subcohort study, and 7775 participants were included in the brachial-ankle pulse wave velocity (baPWV) subcohort study. All participants had ≥ 3 medical examinations during the 10-year follow-up period. In the FMD subcohort study, three distinct RC trajectories were identified according to the RC range and changing pattern over time: "low" (57.58%), "moderate" (30.90%) and "high" (11.52%). The proportion of the three groups with vascular endothelial dysfunction (FMD < 7.0%) was 20.00%, 39.75% and 60.00% respectively. Taking the low group as a reference, participants in the moderate and high groups had over 1.88 and 2.94 times the odds of vascular endothelial dysfunction (P = 0.048). In the baPWV subcohort study, three distinct RC trajectories were also identified: "low" (54.29%), "moderate" (38.97%) and "high" (6.74%). The proportion of the three groups with atherosclerosis (baPWV > 1400 cm/s) was 38.79%, 51.26% and 59.01% respectively. Taking the low group as a reference, participants in the moderate and high groups had over 1.46 and 2.16 times the odds of atherosclerosis (P < 0.001). The findings indicated that distinct RC trajectories are significantly associated with vascular endothelial function and atherosclerosis. Regular monitoring to identify persistent increases in RC may be more helpful in identifying individuals with a high risk of cardiovascular disease.

Classification and functional characterization of regulators of intracellular STING trafficking identified by genome-wide optical pooled screening.

STING is an innate immune sensor that traffics across many cellular compartments to carry out its function of detecting cyclic di-nucleotides and triggering defense processes. Mutations in factors that regulate this process are often linked to STING-dependent human inflammatory disorders. To systematically identify factors involved in STING trafficking, we performed a genome-wide optical pooled screen and examined the impact of genetic perturbations on intracellular STING localization. Based on subcellular imaging of STING protein and trafficking markers in 45 million cells perturbed with sgRNAs, we defined 464 clusters of gene perturbations with similar cellular phenotypes. A higher-dimensional focused optical pooled screen on 262 perturbed genes which assayed 11 imaging channels identified 73 finer phenotypic clusters. In a cluster containing USE1, a protein that mediates Golgi to ER transport, we found a gene of unknown function, C19orf25. Consistent with the known role of USE1, loss of C19orf25 enhanced STING signaling. Other clusters contained subunits of the HOPS, GARP and RIC1-RGP1 complexes. We show that HOPS deficiency delayed STING degradation and consequently increased signaling. Similarly, GARP/RIC1-RGP1 loss increased STING signaling by delaying STING exit from the Golgi. Our findings demonstrate that genome-wide genotype-phenotype maps based on high-content cell imaging outperform other screening approaches, and provide a community resource for mining for factors that impact STING trafficking as well as other cellular processes observable in our dataset.

Modified respiratory-triggered SPACE sequences for magnetic resonance cholangiopancreatography.

Background: Respiratory-triggered (RT) and breath-hold are the most common acquisition modalities for magnetic resonance cholangiopancreatography (MRCP). The present study compared the three different acquisition modalities for optimizing the use of MRCP in patients with diseases of the pancreatic and biliary systems. Materials and methods: Three MRCP acquisition modalities were used in this study: conventional respiratory-triggered sampling perfection with application-optimized contrasts using different flip evolutions (RT-SPACE), modified RT-SPACE, and breath-hold (BH)-SPACE. Fifty-eight patients with clinically suspected pancreatic and biliary system disease were included. All image data were acquired on a 1.5 T MR. Scan time and image quality were compared between the three acquisition modalities. Friedman test, which was followed by post-hoc analysis, was performed among triple-scan protocol. Results: There was a significant difference in the mean acquisition time among conventional RT-SPACE, modified RT-SPACE, and BH-SPACE (167.41±32.11 seconds vs 50.84±73.78 seconds vs 18.00 seconds, P <0.001). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were also significantly different among the three groups (P <0.001). The SNR and CNR were higher in the RT-SPACE group than in the BH-SPACE group (P <0.05). However, there were no statistically significant differences (P >0.05) among the 3 groups regarding quality of overall image, image clarity, background inhibition, and visualization of the pancreatic and biliary system. Conclusions: MRCP acquisition with the modified RT-SPACE sequence greatly shortens the acquisition time with comparable quality images. The MRCP acquisition modality could be designed based on the patient's situation to improve the examination pass rate and obtain excellent images for diagnosis.

CROPseq-multi: a versatile solution for multiplexed perturbation and decoding in pooled CRISPR screens.

Forward genetic screens seek to dissect complex biological systems by systematically perturbing genetic elements and observing the resulting phenotypes. While standard screening methodologies introduce individual perturbations, multiplexing perturbations improves the performance of single-target screens and enables combinatorial screens for the study of genetic interactions. Current tools for multiplexing perturbations are incompatible with pooled screening methodologies that require mRNA-embedded barcodes, including some microscopy and single cell sequencing approaches. Here, we report the development of CROPseq-multi, a CROPseq1-inspired lentiviral system to multiplex Streptococcus pyogenes (Sp) Cas9-based perturbations with mRNA-embedded barcodes. CROPseq-multi has equivalent per-guide activity to CROPseq and low lentiviral recombination frequencies. CROPseq-multi is compatible with enrichment screening methodologies and optical pooled screens, and is extensible to screens with single-cell sequencing readouts. For optical pooled screens, an optimized and multiplexed in situ detection protocol improves barcode detection efficiency 10-fold, enables detection of recombination events, and increases decoding efficiency 3-fold relative to CROPseq. CROPseq-multi is a widely applicable multiplexing solution for diverse SpCas9-based genetic screening approaches.

[Screening of place cell and analysis of its influencing factors for pigeons].

Place cell with location tuning characteristics play an important role in brain spatial cognition and navigation, but there is relatively little research on place cell screening and its influencing factors. Taking pigeons as model animals, the screening process of pigeon place cell was given by using the spike signal in pigeon hippocampus under free activity. The effects of grid number and filter kernel size on the place field of place cells during the screening process were analyzed. The results from the real and simulation data showed that the proposed place cell screening method presented in this study could effectively screen out place cell, and the research found that the size of place field was basically inversely proportional to the number of grids divided, and was basically proportional to the size of Gaussian filter kernel in the overall trend. This result will not only help to determine the appropriate parameters in the place cell screening process, but also promote the research on the neural mechanism of spatial cognition and navigation of birds such as pigeons.

Exclusion of HDAC1/2 complexes by oncogenic nuclear condensates.

Nuclear condensates have been shown to regulate cell fate control, but its role in oncogenic transformation remains largely unknown. Here we show acquisition of oncogenic potential by nuclear condensate remodeling. The proto-oncogene SS18 and its oncogenic fusion SS18-SSX1 can both form condensates, but with drastically different properties and impact on 3D genome architecture. The oncogenic condensates, not wild type ones, readily exclude HDAC1 and 2 complexes, thus, allowing aberrant accumulation of H3K27ac on chromatin loci, leading to oncogenic expression of key target genes. These results provide the first case for condensate remodeling as a transforming event to generate oncogene and such condensates can be targeted for therapy. One sentence summary: Expulsion of HDACs complexes leads to oncogenic transformation.

Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping.

Hyaluronan and proteoglycan link protein 1 (Hapln1) supports active cardiomyogenesis in zebrafish hearts, but its regulation in mammal cardiomyocytes is unclear. This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) and an adult mouse model of myocardial infarction. HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models, respectively. Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration. The results showed that recombinant human Hapln1 (rhHapln1) promotes the proliferation of hiPSC-CMs in a dose-dependent manner. As a physical binding protein of Hapln1, versican interacted with Nodal growth differentiation factor (NODAL) and growth differentiation factor 11 (GDF11). GDF11, but not NODAL, was expressed by hiPSC-CMs. GDF11 expression was unaffected by rhHapln1 treatment. However, this molecule was required for rhHapln1-mediated activation of the transforming growth factor (TGF)-ß/Drosophila mothers against decapentaplegic protein (SMAD)2/3 signaling in hiPSC-CMs, which stimulates cell dedifferentiation and proliferation. Recombinant mouse Hapln1 (rmHapln1) could induce cardiac regeneration in the adult mouse model of myocardial infarction. In addition, rmHapln1 induced hiPSC-CM proliferation. In conclusion, Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-ß/SMAD2/3 signaling pathway. Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts.

SIRT2-mediated deacetylation of ACLY promotes the progression of oesophageal squamous cell carcinoma.

ATP citrate lyase (ACLY), as a key enzyme in lipid metabolism, plays an important role in energy metabolism and lipid biosynthesis of a variety of tumours. Many studies have shown that ACLY is highly expressed in various tumours, and its pharmacological or gene inhibition significantly inhibits tumour growth and progression. However, the roles of ACLY in oesophageal squamous cell carcinoma (ESCC) remain unclear. Here, our data showed that ACLY inhibitor significantly attenuated cell proliferation, migration, invasion and lipid synthesis in different ESCC cell lines, whereas the proliferation, migration, invasion and lipid synthesis of ESCC cells were enhanced after ACLY overexpression. Furthermore, ACLY inhibitor dramatically suppressed tumour growth and lipid metabolism in ESCC cells xenografted tumour model, whereas ACLY overexpression displayed the opposite effect. Mechanistically, ACLY protein harboured acetylated modification and interacted with SIRT2 protein in ESCC cells. The SIRT2 inhibitor AGK2 significantly increased the acetylation level of ACLY protein and inhibited the proliferation and migration of ESCC cells, while overexpression of ACLY partially reversed the inhibitory effect of AGK2 on ESCC cells. Overall, these results suggest that targeting the SIRT2/ACLY signalling axis may be a potential therapeutic strategy for ESCC patients.