Forecasting and analyzing influenza activity in Hebei Province, China, using a CNN-LSTM hybrid model.

BACKGROUND: Influenza, an acute infectious respiratory disease, presents a significant global health challenge. Accurate prediction of influenza activity is crucial for reducing its impact. Therefore, this study seeks to develop a hybrid Convolution Neural Network-Long Short Term Memory neural network (CNN-LSTM) model to forecast the percentage of influenza-like-illness (ILI) rate in Hebei Province, China. The aim is to provide more precise guidance for influenza prevention and control measures. METHODS: Using ILI% data from 28 national sentinel hospitals in the Hebei Province, spanning from 2010 to 2022, we employed the Python deep learning framework PyTorch to develop the CNN-LSTM model. Additionally, we utilized R and Python to develop four other models commonly used for predicting infectious diseases. After constructing the models, we employed these models to make retrospective predictions, and compared each model's prediction performance using mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE), and other evaluation metrics. RESULTS: Based on historical ILI% data from 28 national sentinel hospitals in Hebei Province, the Seasonal Auto-Regressive Indagate Moving Average (SARIMA), Extreme Gradient Boosting (XGBoost), Convolution Neural Network (CNN), Long Short Term Memory neural network (LSTM) models were constructed. On the testing set, all models effectively predicted the ILI% trends. Subsequently, these models were used to forecast over different time spans. Across various forecasting periods, the CNN-LSTM model demonstrated the best predictive performance, followed by the XGBoost model, LSTM model, CNN model, and SARIMA model, which exhibited the least favorable performance. CONCLUSION: The hybrid CNN-LSTM model had better prediction performances than the SARIMA model, CNN model, LSTM model, and XGBoost model. This hybrid model could provide more accurate influenza activity projections in the Hebei Province.

Harnessing spin effects for heterogeneous single-atom spin catalysis.

This perspective explores detailed structural design and strategies for spin regulation in single-atom spin catalysis, enabling unparalleled efficiency in chemical transformations through the harnessing of spin effects combined with atomic precision of active sites.

Coordination and Hydrogen Bond Chemistry in Tungsten Oxide@Polyaniline Composite toward High-Capacity Aqueous Ammonium Storage.

Aqueous ammonium ion batteries (AAIBs) have garnered significant attention due to their unique energy storage mechanism. However, their progress is hindered by the relatively low capacities of NH4 + host materials. Herein, the study proposes an electrodeposited tungsten oxide@polyaniline (WOx@PANI) composite electrode as a NH4 + host, which achieves an ultrahigh capacity of 280.3 mAh g-1 at 1 A g-1, surpassing the vast majority of previously reported NH4 + host materials. The synergistic interaction of coordination chemistry and hydrogen bond chemistry between the WOx and PANI enhances the charge storage capacity. Experimental results indicate that the strong interfacial coordination bonding (N: →W6+) effectively modulates the chemical environment of W atoms, enhances the protonation level of PANI, and thus consequently the conductivity and stability of the composites. Spectroscopy analysis further reveals a unique NH4 +/H+ co-insertion mechanism, in which the interfacial hydrogen bond network (N-H···O) accelerates proton involvement in the energy storage process and activates the Grotthuss hopping conduction of H+ between the hydrated tungsten oxide layers. This work opens a new avenue to achieving high-capacity NH4 + storage through interfacial chemistry interactions, overcoming the capacity limitations of NH4 + host materials for aqueous energy storage.

Dietary human milk oligosaccharides reduce allergic airway inflammation by modulating SCFAs level and ILC2 activity.

Group 2 innate lymphoid cells (ILC2s) play a crucial role in the progression of asthma, yet the regulatory mechanisms modulating ILC2 responses in asthma remain underexplored. Human milk oligosaccharides (HMOs), vital non-nutritive components of breast milk, are known to significantly shape immune system development and influence the incidence of allergic diseases. However, their impact on ILC2-driven asthma is not fully understood. Our research reveals that dietary HMOs act as potent inhibitors of ILC2 responses and allergic airway inflammation. Treatment with 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL) significantly reduced ILC2-related airway inflammation induced by papain or Alternaria alternata in mice, evidenced by decreased eosinophil (EOS) infiltration and lower IL-5 and IL-13 levels in BALF. Notably, while ILC2 expresses HMO receptors, HMO did not act directly on ILC2 but potentially modulated their activity through alterations in gut microbiota derived SCFAs. HMO treatments alleviated airway inflammation in SCFA-dependent manners, with SCFA depletion or receptor blocking reversing these beneficial effects. This study reveals the potential of dietary HMOs in managing asthma through modulation of ILC2 activity and the gut-lung axis, proposing a new therapeutic avenue that utilises the immunomodulatory capacities of nutritional components to combat respiratory diseases.

Contributions of Surface Oxidizing Species and Cu+ to the Antibacterial Activities of Cu2O with Different Crystalline Structures.

Although precise regulation of the crystalline structures of metal oxides is an effective method to improve their antibacterial activities, the corresponding mechanisms involved in this process are still unclear. In this study, three kinds of cuprous oxide (Cu2O) samples with different structures of cubes, octahedra, and rhombic dodecahedra (c-Cu2O, o-Cu2O, and r-Cu2O) have been successfully synthesized and their antibacterial activities are compared. The antibacterial activities follow the order of r-Cu2O > o-Cu2O > c-Cu2O, revealing the significant dependence of the antibacterial activities on the crystalline structures of Cu2O. Quenching experiments, as well as the NBT and DPD experiments indicate that ≡CuII─OO• superoxo and ≡CuII─OOH peroxo, instead of •OH, O2•-, and H2O2, are the primary oxidizing species in the oxidative damage to E. coli. Raman analysis further confirms the presence of both ≡CuII─OO• superoxo and ≡CuII─OOH peroxo on the surface of r-Cu2O. On the other hand, the NCP experiment reveals that Cu+, instead of Cu2+, also contributes to the antibacterial process. This study provides new insight into the antibacterial mechanisms of Cu2O.

Composition Modulation-Mediated Band Alignment Engineering from Type I to Type III in 2D vdW Heterostructures.

Band alignment engineering is crucial for facilitating charge separation and transfer in optoelectronic devices, which ultimately dictates the behavior of Van der Waals heterostructures (vdWH)-based photodetectors and light emitting diode (LEDs). However, the impact of the band offset in vdWHs on important figures of merit in optoelectronic devices has not yet been systematically analyzed. Herein, the regulation of band alignment in WSe2/Bi2Te3- xSex vdWHs (0 ≤ x ≤ 3) is demonstrated through the implementation of chemical vapor deposition (CVD). A combination of experimental and theoretical results proved that the synthesized vdWHs can be gradually tuned from Type I (WSe2/Bi2Te3) to Type III (WSe2/Bi2Se3). As the band alignment changes from Type I to Type III, a remarkable responsivity of 58.12 A W-1 and detectivity of 2.91×1012 Jones (in Type I) decrease in the vdWHs-based photodetector, and the ultrafast photoresponse time is 3.2 µs (in Type III). Additionally, Type III vdWH-based LEDs exhibit the highest luminance and electroluminescence (EL) external quantum efficiencies (EQE) among p-n diodes based on Transition Metal Dichalcogenides (TMDs) at room temperature, which is attributed to band alignment-induced distinct interfacial charge injection. This work serves as a valuable reference for the application and expansion of fundamental band alignment principles in the design and fabrication of future optoelectronic devices.

Effect of astragalus injection on left ventricular remodeling in HFmrEF: a systematic review and meta-analysis.

Objectives: The aim of this meta-analysis is to evaluate the effect of astragalus injection (AI) on left ventricular remodeling (LVR) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Methods: The randomized controlled trials (RCTs) of AI in treating HFmrEF were retrieved from 8 major English and Chinese electronic databases, up until November 30, 2023. To evaluate the methodological quality of the included studies, the Cochrane bias risk tool and the Modified Jadad Scale were employed. Stata 17.0 software was utilized for statistical analysis, sensitivity analysis, and assessment of publication bias. Results: Ten RCTs with 995 patients (562 males and 433 females) were identified. Meta-analysis indicated that compared to conventional treatment (CT), AI significantly improved LVR, specifically increasing left ventricular ejection fraction (LVEF, MD = 4.56, 95% CI: 3.68-5.44, p < 0.00001), decreasing left ventricular end-diastolic volume (LVEDV, MD = -7.89, 95% CI: -11.13 to -4.64, p < 0.00001), left ventricular end-diastolic diameter (LVEDD, MD = -4.18, 95% CI: -5.79 to -2.56, p < 0.00001), left ventricular end-systolic volume (LVESV, MD = -8.11, 95% CI: -11.79 to -4.43, p < 0.00001), and left ventricular end-systolic diameter (LVESD, MD = -3.42, 95% CI: -4.90 to -1.93, p < 0.00001). AI also improved clinical efficacy (RR = 4.62, 95% CI: 3.11-6.88, p < 0.00001), reduced N-terminal pro-brain natriuretic peptide (NT-pro BNP, MD = -27.94, 95% CI: -43.3 to -12.36) level, without increasing the incidence of adverse reactions (RR = 1.60, 95% CI: 0.59-4.29, p = 0.35). Sensitivity analysis confirmed the reliability of the merged results, and Begg's and Egger's tests showed no significant publication bias. Conclusion: The systematic review and meta-analysis revealed that combining AI with CT improves LVR without increasing adverse events in HFmrEF patients. However, caution is needed in interpreting the results due to limited evidence. Future high-quality RCTs are needed to support these conclusions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO [CRD42022347248].

Water temperature and salt ions respectively drive the community assembly of bacterial generalists and specialists in diverse plateau lakes.

Plateau lakes (e.g., freshwater and saltwater lakes) are formed through intricate processes and harbor diverse microorganisms that mediate aquatic ecosystem functions. The adaptive mechanisms of lake microbiota to environmental changes and the ecological impacts of such changes on microbial community assembly are still poorly understood in plateau regions. This study investigated the structure and assembly of planktonic bacterial communities in 24 lakes across the Qinghai-Tibetan and Inner Mongolia Plateaus, with particular focus on habitat generalists, opportunists, and specialists. High-throughput sequencing of the 16S ribosomal RNA genes revealed that bacterial generalists had a lower species number (2196) but higher alpha diversity than the specialist and opportunist counterparts. Taxonomic dissimilarity and phylogenetic diversity analyses unraveled less pronounced difference in the community composition of bacterial generalists compared to the specialist and opportunist counterparts. Geographical scale (14.4 %) and water quality (12.6 %) emerged as major ecological variables structuring bacterial communities. Selection by water temperature and related variables, including mean annual temperature, elevation, longitude, and latitude, mainly shaped the assembly of bacterial generalists. Ecological drift coupled with selection by salt ions and related variables, including total phosphorus, chlorophyll a, and salinity, predominantly drove the assembly of bacterial specialists and opportunists. This study uncovers distinct bacterial responses to interacting ecological variables in diverse plateau lakes and the ecological processes structuring bacterial communities across various lake habitats under anthropogenic disturbance or climate change.

Automatic reorientation to generate short-axis myocardial PET images.

BACKGROUND: Accurately redirecting reconstructed Positron emission tomography (PET) images into short-axis (SA) images shows great significance for subsequent clinical diagnosis. We developed a system for automatic redirection and quantitative analysis of myocardial PET images. METHODS: A total of 128 patients were enrolled for 18 F-FDG PET/CT myocardial metabolic images (MMIs), including 3 image classifications: without defects, with defects, and excess uptake. The automatic reorientation system includes five modules: regional division, myocardial segmentation, ellipsoid fitting, image rotation and quantitative analysis. First, the left ventricular geometry-based canny edge detection (LVG-CED) was developed and compared with the other 5 common region segmentation algorithms, the optimized partitioning was determined based on partition success rate. Then, 9 myocardial segmentation methods and 4 ellipsoid fitting methods were combined to derive 36 cross combinations for diagnostic performance in terms of Pearson correlation coefficient (PCC), Kendall correlation coefficient (KCC), Spearman correlation coefficient (SCC), and determination coefficient. Finally, the deflection angles were computed by ellipsoid fitting and the SA images were derived by affine transformation. Furthermore, the polar maps were used for quantitative analysis of SA images, and the redirection effects of 3 different image classifications were analyzed using correlation coefficients. RESULTS: On the dataset, LVG-CED outperformed other methods in the regional division module with a 100% success rate. In 36 cross combinations, PSO-FCM and LLS-SVD performed the best in terms of correlation coefficient. The linear results indicate that our algorithm (LVG-CED, PSO-FCM, and LLS-SVD) has good consistency with the reference manual method. In quantitative analysis, the similarities between our method and the reference manual method were higher than 96% at 17 segments. Moreover, our method demonstrated excellent performance in all 3 image classifications. CONCLUSION: Our algorithm system could realize accurate automatic reorientation and quantitative analysis of PET MMIs, which is also effective for images suffering from interference.

Concurrent of compound heterozygous variant of a novel in-frame deletion and the common hypomorphic haplotype in TBX6 and inherited 17q12 microdeletion in a fetus.

BACKGROUND: TBX6, a member of the T-box gene family, encodes the transcription factor box 6 that is critical for somite segmentation in vertebrates. It is known that the compound heterozygosity of disruptive variants in trans with a common hypomorphic risk haplotype (T-C-A) in the TBX6 gene contribute to 10% of congenital scoliosis (CS) cases. The deletion of chromosome 17q12 is a rare cytogenetic abnormality, which often leads to renal cysts and diabetes mellitus. However, the affected individuals often exhibit clinical heterogeneity and incomplete penetrance. METHODS: We here present a Chinese fetus who was shown to have CS by ultrasound examination at 17 weeks of gestation. Trio whole-exome sequencing (WES) was performed to investigate the underlying genetic defects of the fetus. In vitro functional experiments, including western-blotting and luciferase transactivation assay, were performed to determine the pathogenicity of the novel variant of TBX6. RESULTS: WES revealed the fetus harbored a compound heterozygous variant of c.338_340del (p.Ile113del) and the common hypomorphic risk haplotype of the TBX6 gene. In vitro functional study showed the p.Ile113del variant had no impact on TBX6 expression, but almost led to complete loss of its transcriptional activity. In addition, we identified a 1.85 Mb deletion on 17q12 region in the fetus and the mother. Though there is currently no clinical phenotype associated with this copy number variation in the fetus, it can explain multiple renal cysts in the pregnant woman. CONCLUSIONS: This study is the first to report a Chinese fetus with a single amino acid deletion variant and a T-C-A haplotype of TBX6. The clinical heterogeneity of 17q12 microdeletion poses significant challenges for prenatal genetic counseling. Our results once again suggest the complexity of prenatal genetic diagnosis.

Nanoscale Visualization of Symmetry-Breaking Electronic Orders and Magnetic Anisotropy in a Kagome Magnet YMn6Sn6.

A kagome lattice hosts a plethora of quantum states arising from the interplay between nontrivial topology and electron correlations. The recently discovered kagome magnet RMn6Sn6 (R represents a rare-earth element) is believed to showcase a kagome band closely resembling textbook characteristics. Here, we report the characterization of local electronic states and their magnetization response in YMn6Sn6 via scanning tunneling microscopy measurements under vector magnetic fields. Our spectroscopic maps reveal a spontaneously trimerized kagome electronic order in YMn6Sn6, where the 6-fold rotational symmetry is disrupted while translational symmetry is maintained. Further application of an external magnetic field demonstrates a strong coupling of the YMn6Sn6 kagome band to the field, which exhibits an energy shift discrepancy under different field directions, implying the existence of magnetization-response anisotropy and anomalous g factors. Our findings establish YMn6Sn6 as an ideal platform for investigating kagome-derived orbital magnetic moment and correlated magnetic topological states.

Liquid Gallium-Assisted Pyrolysis of MOF Affording CNT Non-Hollow Frameworks in High Yields for High-Performance Sodium-Ion Battery Anode.

Carbon materials have great potential for applications in energy, biology, and environment due to their excellent chemical and physical properties. Their preparation by carbonization methods encounters limitations and the carbon loss during pyrolysis in the form of gaseous molecules results in low yield of carbon materials. Herein a low-energy (600 °C) and high-yield (82 wt.%) carbonization strategy is developed using liquid gallium-assisted pyrolysis of metal-organic frameworks (MOFs) affording the N-doped carbon nanotube (CNT) non-hollow frameworks encapsulating Co nanoparticles. The liquid gallium layer offers protection against air, promotes heat transfer, and limits the escape of small carbonaceous gaseous molecules, which greatly improve the yields of the pyrolysis reaction. Experimental and theoretical results reveal that the synergistic interaction between CNTs and N/O-containing groups gives a non-hollow framework composed of N/O-enriched and open CNTs (NOCNTF-15, 15 denotes the 15 mm thickness of the liquid gallium layer during the pyrolysis) with high specific capacity (185 mAh g-1 at 10 A g-1) and ultra-stable cyclability (stable operation at 10 A g-1 and 50 °C for 20 000 cycles). This study provides a unique approach to carbonization that facilitates the practical application of low-cost CNTs and other MOFs-derived carbon materials in high-performance sodium-ion batteries (SIBs).

Pharmacophore-based virtual screening of commercial databases against ß-secretase 1 for drug development against Alzheimer's disease.

ß-secretase 1, one of the most important proteins, is an aspartate protease. This membrane-associated protein is used for treating Alzheimer's disease (AD). Several inhibitors have been pursued against ß-secretase 1, but they still have not resulted effectively. Virtual screening based on pharmacophores has been shown to be useful for lead optimization and hit identification in the preliminary phase of developing a new drug. Here, we screen the commercially available databases to find the hits against ß-secretase 1 for drug discovery against AD. Virtual screening for 200,000 compounds was done using the database from the Vitas-M Laboratory. The phase screen score was utilized to assess the screened hits. Molecular docking was performed on compounds with phase scores >1.9. According to the study, the 66H ligand of the crystal structure has the maximum performance against ß-secretase 1. The redocking of the co-crystal ligand showed that the docked ligand was seamlessly united with the crystal structure. The reference complex had three hydrogen bonds with Asp93, Asp289, and Gly291; one van der Waals interaction with Gly74; and three hydrophobic interactions. After equilibration, the RMSD of the reference compound sustained a value of ∼1.5 Å until 30 ns and then boosted to 2.5 Å. On comparison, the RMSD of the S1 complex steadily increased to ∼2.5 Å at 15 ns, displayed slight aberrations at approximately ∼2.5-3 Å until 80 ns, and then achieved steadiness toward the end of the simulation. The arrangements of proteins stayed condensed during the mockup when bonded to these complexes as stable Rg values showed. Furthermore, the MM/GBSA technique was employed to analyze both compounds' total binding free energies (ΔGtotal). Our research study provides a new understanding of using 66H as anti-ß-secretase 1 for drug development against AD.

Phylogenomic data resolved the deep relationships of Gymnogynoideae (Selaginellaceae).

The unresolved phylogenetic framework within the Selaginellaceae subfamily Gymnogynoideae (ca. 130 species) has hindered our comprehension of the diversification and evolution of Selaginellaceae, one of the most important lineages in land plant evolution. Here, based on plastid and nuclear data extracted from genomic sequencing of more than 90% species of all genera except two in Gymnogynoideae, a phylogenomic study focusing on the contentious relationships among the genera in Gymnogynoideae was conducted. Our major results included the following: (1) Only single-copy region (named NR) and only one ribosomal operon was firstly found in Afroselaginella among vascular plants, the plastome structure of Gymnogynoideae is diverse among the six genera, and the direct repeats (DR) type is inferred as the ancestral state in the subfamily; (2) The first strong evidence was found to support Afroselaginella as a sister to Megaloselaginella. Alternative placements of Ericetorum and Gymnogynum were detected, and their relationships were investigated by analyzing the variation of phylogenetic signals; and (3) The most likely genus-level relationships in Gymnogynoideae might be: ((Bryodesma, Lepidoselaginella), (((Megaloselaginella, Afroselaginella), Ericetorum), Gymnogynum)), which was supported by maximum likelihood phylogeny based on plastid datasets, maximum likelihood, and Bayesian inference based on SCG dataset and concatenated nuclear and plastid datasets and the highest proportion of phylogenetic signals of plastid genes.

EMG-YOLO: road crack detection algorithm for edge computing devices.

Introduction: Road cracks significantly shorten the service life of roads. Manual detection methods are inefficient and costly. The YOLOv5 model has made some progress in road crack detection. However, issues arise when deployed on edge computing devices. The main problem is that edge computing devices are directly connected to sensors. This results in the collection of noisy, poor-quality data. This problem adds computational burden to the model, potentially impacting its accuracy. To address these issues, this paper proposes a novel road crack detection algorithm named EMG-YOLO. Methods: First, an Efficient Decoupled Header is introduced in YOLOv5 to optimize the head structure. This approach separates the classification task from the localization task. Each task can then focus on learning its most relevant features. This significantly reduces the model's computational resources and time. It also achieves faster convergence rates. Second, the IOU loss function in the model is upgraded to the MPDIOU loss function. This function works by minimizing the top-left and bottom-right point distances between the predicted bounding box and the actual labeled bounding box. The MPDIOU loss function addresses the complex computation and high computational burden of the current YOLOv5 model. Finally, the GCC3 module replaces the traditional convolution. It performs global context modeling with the input feature map to obtain global context information. This enhances the model's detection capabilities on edge computing devices. Results: Experimental results show that the improved model has better performance in all parameter indicators compared to current mainstream algorithms. The EMG-YOLO model improves the accuracy of the YOLOv5 model by 2.7%. The mAP (0.5) and mAP (0.9) are improved by 2.9% and 0.9%, respectively. The new algorithm also outperforms the YOLOv5 model in complex environments on edge computing devices. Discussion: The EMG-YOLO algorithm proposed in this paper effectively addresses the issues of poor data quality and high computational burden on edge computing devices. This is achieved through optimizing the model head structure, upgrading the loss function, and introducing global context modeling. Experimental results demonstrate significant improvements in both accuracy and efficiency, especially in complex environments. Future research can further optimize this algorithm and explore more lightweight and efficient object detection models for edge computing devices.

Changes on Cognition and Brain Network Temporal Variability After Pediatric Neurosurgery.

BACKGROUND AND OBJECTIVES: Pediatric intracranial space-occupying lesions are common, with prognoses improving markedly in recent years, significantly extending survival. As such, there is an imperative to pay increased attention to the postoperative cognitive functions and brain network alterations in these children because these factors significantly influence their quality of life. Temporal variability (TV) analysis of brain networks captures the full extent of resting-state activities, reflecting cognitive functions and rehabilitation potential. However, previous research rarely uses TV analyses and most focus on adults or children after multidisciplinary treatments, not reflecting the combined effect caused by neurosurgery only and self-repair. This study gives our insights into this field from a holistic perspective. METHODS: We studied 35 children with intracranial space-occupying lesions, analyzing pre- and postsurgery MRI and cognitive tests. We used TV analysis to assess changes and correlated imaging indicators with cognitive performance. RESULTS: We observed a tendency for cognitive recovery after about 3 months postsurgery, primarily in the domains of social cognition and nonverbal reasoning. TV analysis of brain networks indicated increased nodal variability within systems such as the visual and sensorimotor networks, which are integral to external interactions. Correlative analysis showed that alterations in certain occipital regions were associated with changes in social cognition and nonverbal reasoning. CONCLUSION: These findings suggest significant intrinsic repair in cognitive functions and brain networks at around 3 months postneurosurgery in children. This study not only enriches our comprehension of postoperative cognitive and brain network self-repair processes in children but also furnishes potential therapeutic targets for rehabilitation interventions and establishes a theoretical foundation for proactive surgical interventions.

Predictive value of bile acids as metabolite biomarkers for gallstone disease: A systematic review and meta-analysis.

BACKGROUND: The profiles of bile acids (BAs) in patients with gallstone disease (GSD) have been found to be altered markedly though in an inconsistent pattern. This study aims to characterize the variation of the BA profiles in GSD patients, thereby to discover the potential metabolite biomarkers for earlier detection of GSD. METHODS: Literature search of eight electronic database in both English and Chinese was completed on May 11, 2023. The qualitative and quantitative reviews were performed to summarize the changes of BA profiles in GSD patients compared with healthy subjects. The concentrations of BAs were adopted as the primary outcomes and the weighted mean differences (WMDs) and 95% confidence interval (CI) were generated by random-effects meta-analysis models. RESULTS: A total of 30 studies were enrolled which included 2313 participants and reported the 39 BAs or their ratios. Qualitative review demonstrated serum Taurocholic Acid (TCA), Glycochenodeoxycholic acid (GCDCA), Glycocholic acid (GCA), Taurochenodeoxycholic acid (TCDCA), Glycodeoxycholic acid (GDCA) and Deoxycholic acid (DCA) were significantly increased in GSD patients compared with healthy subjects. Meta analysis was performed in 16 studies and showed that serum Total BAs (TBA) (WMD = 1.36µmol/L, 95%CI = 0.33; 2.4) was elevated however bile TBA (WMD = -36.96mmol/L, 95%CI = -52.32; -21.6) was declined in GSD patients. GCA (WMD = 0.83µmol/L, 95%CI = 0.06; 1.6) and TCA (WMD = 0.51µmol/L; 95%CI = 0.18; 0.85) were both increased in serum sample; TCDCA (WMD = 2.64mmol/L, 95%CI = 0.16; 5.12) was rising, however GCDCA (WMD = -13.82mmol/L, 95%CI = -21.86; -5.78) was falling in bile sample of GSD patients. The level of serum DCA in the GSD patients was found to be increased by using chromatography, yet decreased by chromatography mass spectrometry. CONCLUSION: The profiles of BAs demonstrated distinctive changes in GSD patients compared with healthy control subjects. Serum GCA, TCA and GCDCA, as the typically variant BAs, presented as a potential marker for earlier diagnosis of GSD, which could facilitate early prophylactic intervention. Yet, further validation of these biomarkers by longitudinal studies is still warranted in the future. PROSPERO registration number CRD42022339649.

Transcriptional regulation of transcription factor genes WRI1 and LAFL during Brassica napus seed development.

The WRINKLED1 (WRI1) and LAFL [LEAFY COTYLEDON1 (LEC1), ABSCISIC ACID INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and LEC2] transcription factors play essential roles in governing seed development and oil biosynthesis. To gain a comprehensive understanding of the transcriptional regulation of WRI1 and LAFL, we conducted genome-wide association studies for the expression profiles of WRI1 and LAFL in developing seeds at 20 and 40 days after flowering (DAF) using 302 rapeseed (Brassica napus) accessions. We identified a total of 237 expression quantitative trait nucleotides (eQTNs) and 51 expression QTN-by-environment interactions (eQEIs) associated with WRI1 and LAFL. Around these eQTNs and eQEIs, we pinpointed 41 and 8 candidate genes with known transcriptional regulations or protein interactions with their expression traits, respectively. Based on RNA-seq and ATAC-seq data, we employed the XGBoost and Basenji models which predicted 15 candidate genes potentially regulating the expression of WRI1 and LAFL. We further validated the predictions via tissue expression profile, haplotype analysis, and expression correlation analysis, and verified the transcriptional activation activity of BnaC03.MYB56 (R2R3-MYB transcription factor 56) on the expression of BnaA09.LEC1 by dual-luciferase reporter and yeast one-hybrid assays. BnaA10.AGL15 (AGAMOUS-LIKE 15), BnaC04.VAL1 (VIVIPAROUS1/ABSCISIC ACID INSENSITIVE3-LIKE 1), BnaC03.MYB56, and BnaA10.MYB56 were co-expressed with WRI1 and LAFL at 20 DAF in M35, a key module for seed development and oil biosynthesis. We further validated the positive regulation of MYB56 on seed oil accumulation using Arabidopsis (Arabidopsis thaliana) mutants. This study not only delivers a framework for future eQEI identification but also offers insights into the developmental regulation of seed oil accumulation.