DeepGRNCS: deep learning-based framework for jointly inferring gene regulatory networks across cell subpopulations.

Inferring gene regulatory networks (GRNs) allows us to obtain a deeper understanding of cellular function and disease pathogenesis. Recent advances in single-cell RNA sequencing (scRNA-seq) technology have improved the accuracy of GRN inference. However, many methods for inferring individual GRNs from scRNA-seq data are limited because they overlook intercellular heterogeneity and similarities between different cell subpopulations, which are often present in the data. Here, we propose a deep learning-based framework, DeepGRNCS, for jointly inferring GRNs across cell subpopulations. We follow the commonly accepted hypothesis that the expression of a target gene can be predicted based on the expression of transcription factors (TFs) due to underlying regulatory relationships. We initially processed scRNA-seq data by discretizing data scattering using the equal-width method. Then, we trained deep learning models to predict target gene expression from TFs. By individually removing each TF from the expression matrix, we used pre-trained deep model predictions to infer regulatory relationships between TFs and genes, thereby constructing the GRN. Our method outperforms existing GRN inference methods for various simulated and real scRNA-seq datasets. Finally, we applied DeepGRNCS to non-small cell lung cancer scRNA-seq data to identify key genes in each cell subpopulation and analyzed their biological relevance. In conclusion, DeepGRNCS effectively predicts cell subpopulation-specific GRNs. The source code is available at https://github.com/Nastume777/DeepGRNCS.

Chromosome-scale genome assembly of Prunus pusilliflora provides novel insights into genome evolution, disease resistance, and dormancy release in Cerasus L.

Prunus pusilliflora is a wild cherry germplasm resource distributed mainly in Southwest China. Despite its ornamental and economic value, a high-quality assembled P. pusilliflora genome is unavailable, hindering our understanding of its genetic background, population diversity, and evolutionary processes. Here, we de novo assembled a chromosome-scale P. pusilliflora genome using Oxford Nanopore, Illumina, and chromosome conformation capture sequencing. The assembled genome size was 309.62 Mb, with 76 scaffolds anchored to eight pseudochromosomes. We predicted 33 035 protein-coding genes, functionally annotated 98.27% of them, and identified repetitive sequences covering 49.08% of the genome. We found that P. pusilliflora is closely related to Prunus serrulata and Prunus yedoensis, having diverged from them ~41.8 million years ago. A comparative genomic analysis revealed that P. pusilliflora has 643 expanded and 1128 contracted gene families. Furthermore, we found that P. pusilliflora is more resistant to Colletotrichum viniferum, Phytophthora capsici, and Pseudomonas syringae pv. tomato (Pst) DC3000 infections than cultivated Prunus avium. P. pusilliflora also has considerably more nucleotide-binding site-type resistance gene analogs than P. avium, which explains its stronger disease resistance. The cytochrome P450 and WRKY families of 263 and 61 proteins were divided into 42 and 8 subfamilies respectively in P. pusilliflora. Furthermore, 81 MADS-box genes were identified in P. pusilliflora, accompanying expansions of the SVP and AGL15 subfamilies and loss of the TM3 subfamily. Our assembly of a high-quality P. pusilliflora genome will be valuable for further research on cherries and molecular breeding.

Altered whole-brain gray matter volume in form-deprivation myopia rats based on voxel-based morphometry: A pilot study.

Background: Myopia is one of the major public health problems worldwide. However, the exact pathogenesis of myopia remains unclear. This study proposes using voxel-based morphometry (VBM) to investigate potential morphological alterations in gray matter volume (GMV) in form-deprivation myopia (FDM) rats. Methods: A total of 14 rats with FDM (FDM group) and 15 normal controls (NC group) underwent high-resolution magnetic resonance imaging (MRI). Original T2 brain images were analyzed using VBM method to identify group differences in GMV. Following MRI examination, all rats were perfused with formalin, and immunohistochemical analysis of NeuN and c-fos levels was performed on the visual cortex. Results: In the FDM group, compared to the NC group, significantly decreased GMVs were found in the left primary visual cortex, left secondary visual cortex, right subiculum, right cornu ammonis, right entorhinal cortex and bilateral molecular layer of the cerebellum. Additionally, significantly increased GMVs were found in the right dentate gyrus, parasubiculum, and olfactory bulb. Conclusions: Our study revealed a positive correlation between mGMV and the expression of c-fos and NeuN in the visual cortex, suggesting a molecular relationship between cortical activity and macroscopic measurement of visual cortex structural plasticity. These findings may help elucidate the potential neural pathogenesis of FDM and its relationship to changes in specific brain regions.

Effectiveness of micro-implant in vertical control during orthodontic extraction treatment in class II adults and adolescents after pubertal growth peak: a systematic review and meta-analysis.

OBJECTIVE: To compare the effectiveness of micro-implant (MI) and conventional anchorage (CA) in vertical control during orthodontic extraction treatment of class II adults and adolescents after pubertal growth peak. MATERIALS AND METHODS: Literature search was conducted through Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP, China Biology Medicine (CBM), and other sources, from inception to December 2021. Randomized clinical trials (RCTs) and controlled clinical trials (CCTs) were included. Mean differences (MDs) with 95% confidence intervals (CIs) were conducted. A meta-analysis concerning change of mandibular plane, vertical change of upper and lower molar, change of occlusal plane, SNB, chin position, and profile was carried out. RESULTS: A total of 10,669 records were identified in the database search, and 19 studies (10 RCTs and 9 CCTs) were included in the final analysis. Compared with CA, MI significantly decreased mandibular plane angle and intruded upper molars. No significant difference was found in vertical change of lower molars, occlusal plane, SNB, chin position, and profile. CONCLUSION: MI seems to be more effective than CA in vertical control during orthodontic extraction treatment of class II adults and adolescents after pubertal growth peak. CLINICAL RELEVANCE: MI should be given priority when considering the vertical control of class II patients, which is beneficial to the counterclockwise rotation of mandible or at least prevention of deterioration of the profile.

Identification of hub genes and pathways of ferroptosis in Fusarium keratitis by bioinformatics methods.

Background: Fungal keratitis is a common blinding eye disease, and Fusarium is one of the main species that cause fungal keratitis. As is well known, oxidative stress plays an important role in Fusarium keratitis and it is also a significant initiating factor of ferroptosis. But the relationship between Fusarium keratitis and ferroptosis is currently unclear. This study aimed to speculate and validate potential ferroptosis-related genes in Fusarium keratitis using bioinformatics analysis, which provided ideas for further research on its specific mechanism and new targets for its treatment. Methods: The microarray expression profiling dataset (GSE58291) came from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were obtained by the limma package of the R software. The DEGs were performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Then, the DEGs were intersected with the genes in the ferroptosis database. The top 5 hub genes were obtained by the protein-protein interaction (PPI) network analysis and the cytoHubba plug-in of Cytoscape software. The hub genes were subjected to GSEA analysis. Then we analyzed the immune infiltration of the samples by CIBERSORT and ssGSEA algorithm. Finally, we validated the mRNA of hub genes by qPCR. Results: A total of 1,368 DEGs were identified and 26 ferroptosis-related DEGs were obtained. At the same time, ferroptosis-related pathways were enriched by GO and KEGG using DEGs. HMOX1, CYBB, GPX2, ALOX5 and SRC were obtained by the PPI network analysis and the cytoHubba plug-in of Cytoscape software. The iron metabolism and immune response related pathways were enriched using GSEA. They included hematopoietic cell lineage, lysosome and FC gamma R mediated phagocytosis. T cells follicular helper, monocytes, macrophages and mast cells might play an important role in Fusarium keratitis using analysis of immune infiltration. Finally, qPCR confirmed that the expression of HMOX1, CYBB, ALOX5 mRNA in the DON group was significantly elevated, while the expression of GPX2 were significantly decreased. Conclusions: Ferroptosis may play an important role in Fusarium keratitis. HMOX1, CYBB, ALOX5 and GPX2 may be key ferroptosis-related genes in the pathogenesis of Fusarium keratitis.

Intense pulsed light (IPL) therapy for meibomian gland dysfunction (MGD)-related dry eye disease (DED): a systematic review and meta-analysis.

To compare the effect of intense pulsed light (IPL) therapy and conventional treatments in meibomian gland dysfunction (MGD)-related dry eye disease (DED). A literature search was conducted in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP, and China Biology Medicine (CBM) up to January 2022. Randomized controlled trials (RCTs) were included. Mean differences (MDs) and their 95% confidence intervals (CIs) were calculated. A meta-analysis concerning changes in tear break-up time (BUT), changes in Ocular Surface Disease Index (OSDI) scores, changes in non-invasively measured tear break-up time (NIBUT), changes in corneal and conjunctival fluorescein staining (CFS) scores, and changes in Standard Patient Evaluation of Eye Dryness (SPEED) scores was carried out. The initial search identified a total of 1842 records in the databases, and 11 studies were included in the final analysis. Compared to conventional therapies, IPL therapy was associated with significantly reduced OSDI (MD, - 7.49; 95% CI, - 12.47 to - 2.5) and SPEED (MD, - 3.28; 95% CI, - 5.64 to - 0.93) scores, while BUT (MD, 1.94; 95% CI, 1.19 ~ 2.69) and NIBUT (MD, 2.55; 95% CI, 1.07 ~ 4.04) significantly increased. No significant difference was found in the change in CFS between the two groups. Both IPL treatment and traditional treatments are effective in the treatment of MGD-related DED. IPL application seems to be superior to traditional treatments.

Whole-genome resequencing reveals the origin of tea in Lincang.

Phylogeographic, population genetics and diversity analysis are crucial for local tea resource conservation and breeding programs. Lincang in Yunnan has been known as the possible place of domestication for tea worldwide, yet, its genetic makeup and unique Lincang origin are little understood. Here, we reported a large-scale whole-genome resequencing based population genomic analysis in eight main tea-producing areas of Lincang in Yunnan (1,350 accessions), and the first comprehensive map of tea genome variation in Lincang was constructed. Based on the population structure, tea sample in Lincang was divided into three subgroups, and inferred Xigui and Nahan Tea Mountain in Linxiang, Baiying Mountain Ancient Tea Garden in Yun, and Jinxiu Village of Xiaowan Town in Fengqing, which belong to the birthplace of the three subgroups, were all likely to be the origin center of Lincang tea. Meanwhile, the history population sizes analysis show that similar evolutionary patterns were observed for the three subgroups of Lincang. It also was observed that the hybrid among eight areas of Lincang was noticeable, resulting in insignificant genetic differentiation between geographical populations and low genetic diversity. The findings of this study clarified the genetic make-up and evolutionary traits of the local population of tea, which gave some insight into the development of Lincang tea.

Influencing factors for peripheral and posterior lesions in mild non-proliferative diabetic retinopathy-the Kailuan Eye Study.

AIM: To explore the influencing factors of diabetes type 2 patients with mild non-proliferative diabetic retinopathy (NPDR) in the Kailuan area of Tangshan, Hebei Province, China. METHODS: In this non-interventional, retrospective study, 683 patients with type 2 diabetes were included in the Kailuan Diabetic Retinopathy Study involving participants with diabetes in the community-based longitudinal Kailuan Study. Based on the undilated ultra-wide field (200°; UWF) images and partial dilated digital fundus images, the diabetic retinopathy (DR) of the surveyed population was graded. Interobserver agreement was estimated by using Cohen's Kappa statistics. The main outcome indicators included gender, age, weight, height, body mass index, blood pressure, circumferences of neck, waist and hip, current smoking, levels of fasting plasma glucose (FPG), hypersensitive C-reactive protein, creatinine, and cholesterol, etc. According to different lesions' locations of patients with mild NPDR, logistic regression models were used to estimate the odds ratios (ORs) and their 95%CIs of each risk factor. RESULTS: The study group of 683 patients included 570 males and 113 females. The mean age of the patients was 62.18±9.41y. Compared with dilated fundus examinations, there was fair agreement with the level of DR identified on UWF images in 63.91% of eyes (k=0.369, 95%CI, 0.00-0.00). Detected by UWF images, there were 98 patients with mild NPDR having peripheral retinal lesions, 35 patients with mild NPDR having posterior lesions, 44 patients with mild NPDR whose lesions were detected both in and out the standard two fields area, and 336 patients with non obvious DR. Parameters that conferred a statistically significant increased risks for mild NPDR with having peripheral retinal lesions were neck circumstance (OR, 1.124; 95%CI, 1.044-1.211), and with posterior lesions were FPG (OR, 1.052; 95%CI, 1.007-1.099). CONCLUSION: UWF is an effectiveness means of DR screening. Moreover, it is necessary to evaluate peripheral diabetic retinal lesions which can help to estimate the severity of DR. The phenomenon that nonuniform and inhomogeneous distribution of DR lesions has been found. And the influencing factors in mild NPDR are differing by different lesions' locations.

Passive Detection of Ship-Radiated Acoustic Signal Using Coherent Integration of Cross-Power Spectrum with Doppler and Time Delay Compensations.

Passive sonar is widely used for target detection, identification and classification based on the target radiated acoustic signal. Under the influence of Doppler, generated by relative motion between the moving target and the sonar array, the received ship-radiated acoustic signals are non-stationary and time-varying, which has a negative effect on target detection and other fields. In order to reduce the influence of Doppler and improve the performance of target detection, a coherent integration method based on cross-power spectrum is proposed in this paper. It can be concluded that the frequency shift and phase change in the cross-power spectrum obtained by each pair of data segments can be corrected with the compensations of time scale (Doppler) factor and time delay. Moreover, the time scale factor and time delay can be estimated from the amplitude and phase of the original cross-power spectrum, respectively. Therefore, coherent integration can be implemented with the compensated cross-power spectra. Simulation and experimental data processing results show that the proposed method can provide sufficient processing gains and effectively extract the discrete spectra for the detection of moving targets.

In Design of an Ocean Bottom Seismometer Sensor: Minimize Vibration Experienced by Underwater Low-Frequency Noise.

Ocean Bottom Seismometers (OBS) placed on the seafloor surface are utilized for measuring the ocean bottom seismic waves. The vibration of OBS excited by underwater noise on its surface may interfere with its measured results of seismic waves. In this particular study, an OBS was placed on the seabed, while ray acoustic theory was used to deduce the sound field distribution around the OBS. Then using this information, the analytical expression for the OBS vibration velocity was obtained in order to find various factors affecting its amplitude. The finite element computing software COMSOL Multiphysics® (COMSOL) was used to obtain the vibration response model of the OBS which was exposed to underwater noise. The vibration velocity for the OBS calculated by COMSOL agreed with the theoretical result. Moreover, the vibration velocity of OBS with different densities, shapes, and characters were investigated as well. An OBS with hemispherical shape, consistent average density as that of the seafloor, and a physical structure of double tank has displayed minimum amplitude of vibration velocity. The proposed COMSOL model predicted the impact of underwater noise while detecting the ocean bottom seismic waves with the OBS. In addition, it provides significant help for the design and optimization of an appropriate OBS.

Sparse estimation of backscattered echoes from underwater object using integrated dictionaries.

The problem of time-delays estimation of backscattered echoes from underwater targets is presented using a sparse reconstruction framework employing an integrated dictionary. To achieve high resolution, the used dictionary is usually defined over a finely spaced grid over the region of interest. Such a procedure may result in problems of being computational cumbersome or suffering from basis mismatch. In addition, the shape of the backscattered echoes may differ significantly from the expected waveforms used to form the dictionary, causing further mismatch problems. To alleviate such problems, the use of an integrated dictionary framework is introduced. Unlike traditional dictionaries that are defined over a set of grid points, the elements in an integrated dictionary are formed by integrating the expected waveform over bands of the parameter space. The resulting dictionary may be used to find initial regions of the parameters of interest using a smaller dictionary than otherwise required, without suffering a loss of performance. The elements can also better match with the backscattered echoes, even if these differ from their expected shape. Simulated results of the backscattered echoes from a cylindrical shell, as well as results from experimental measurements, illustrate the performance of the proposed method.

[One-hour post-load plasma glucose: a better indicator of glucose metabolism for obstructive sleep apnea?]

OBJECTIVE: To assess the value of blood glucose at different time points in oral glucose tolerance test (OGTT), particularly one?hour post load plasma glucose (1 hPG), in evaluating glucose metabolism in adult patients with obstructive sleep apnea (OSA). METHODS: Eighty nine adultswith newly diagnosed OSA were analyzed retrospectively for sleep architecture assessed using polysomnography and glucose metabolism assessed by OGTT at different time points (0, 30, 60, 120, and 180 min). Pearson's correlatives and multiple linear regression models were established to investigate the correlations between glucose metabolism and other indices including sleep architecture, apnea hypopnea index (AHI), mean and lowest oxygen saturation (MSO2 and LSO2) and obesity measurements. RESULTS: The majority (67.4%) of the patients had abnormal 1 hPG, and 41.6% had abnormal 2 hPG. 1 hPG was positively correlated with neck circumference (r=0.245), abdomen circumference (r=0.231), systolic blood pressure (r=0.213), diastolic blood pressure (r=0.276) and AHI (r=0.324), and was negatively associated with MSO2 (r=-0.341) and LSO2 (r=-0.387) (all P<0.05). After controlling for age, BMI, neck and abdomen circumferences, 1 hPG was found to inversely correlated with MSO2 (r=-0.253, P=0.032) and LSO2 (r=-0.311, P=0.008). In non-obese OSA subgroup, 1 hPG was significantly associated with OSA-related indices, and regression models showed that LSO2 and N2 were the two most important contributors to 1 hPG (adjusted R2=0.349, P<0.001); plasma glucose at other time points did not show such correlations. CONCLUSIONS: 1 hPG abnormality occurs earlier than 2 hPG in OSA patients. 1 hPG is significantly associated with OSA independent of obesity and may serve as a better index for measuring OSA-related glucose disorder.

iSuc-PseAAC: predicting lysine succinylation in proteins by incorporating peptide position-specific propensity.

Lysine succinylation in protein is one type of post-translational modifications (PTMs). Succinylation is associated with some diseases and succinylated sites data just has been found in recent years in experiments. It is highly desired to develop computational methods to identify the candidate proteins and their sites. In view of this, a new predictor called iSuc-PseAAC was proposed by incorporating the peptide position-specific propensity into the general form of pseudo amino acid composition. The accuracy is 79.94%, sensitivity 51.07%, specificity 89.42% and MCC 0.431 in leave-one-out cross validation with support vector machine algorithm. It demonstrated by rigorous leave-one-out on stringent benchmark dataset that the new predictor is quite promising and may become a useful high throughput tool in this area. Meanwhile a user-friendly web-server for iSuc-PseAAC is accessible at http://app.aporc.org/iSuc-PseAAC/. Users can easily obtain their desired results without the need to understand the complicated mathematical equations presented in this paper just for its integrity.