Synergistic acceleration of machine learning and molecular docking for prostate-specific antigen ligand design.

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.

Assessing bioartificial organ function: the 3P model framework and its validation.

The rapid advancement in the fabrication and culture of in vitro organs has marked a new era in biomedical research. While strides have been made in creating structurally diverse bioartificial organs, such as the liver, which serves as the focal organ in our study, the field lacks a uniform approach for the predictive assessment of liver function. Our research bridges this gap with the introduction of a novel, machine-learning-based "3P model" framework. This model draws on a decade of experimental data across diverse culture platform studies, aiming to identify critical fabrication parameters affecting liver function, particularly in terms of albumin and urea secretion. Through meticulous statistical analysis, we evaluated the functional sustainability of the in vitro liver models. Despite the diversity of research methodologies and the consequent scarcity of standardized data, our regression model effectively captures the patterns observed in experimental findings. The insights gleaned from our study shed light on optimizing culture conditions and advance the evaluation of the functional maintenance capacity of bioartificial livers. This sets a precedent for future functional evaluations of bioartificial organs using machine learning.

Cotyledon-Specific Flow Evaluation of Rhesus Macaque Placental Injury Using Ferumoxytol Dynamic Contrast-Enhanced MRI.

BACKGROUND: Recently, dynamic contrast-enhanced (DCE) MRI with ferumoxytol as contrast agent has recently been introduced for the noninvasive assessment of placental structure and function throughout. However, it has not been demonstrated under pathological conditions. PURPOSE: To measure cotyledon-specific rhesus macaque maternal placental blood flow using ferumoxytol DCE MRI in a novel animal model for local placental injury. STUDY TYPE: Prospective animal model. SUBJECTS: Placental injections of Tisseel (three with 0.5 mL and two with 1.5 mL), monocyte chemoattractant protein 1 (three with 100 µg), and three with saline as controls were performed in a total of 11 rhesus macaque pregnancies at approximate gestational day (GD 101). DCE MRI scans were performed prior (GD 100) and after (GD 115 and GD 145) the injection (term = GD 165). FIELD STRENGTH/SEQUENCE: 3 T, T1-weighted spoiled gradient echo sequence (product sequence, DISCO). ASSESSMENT: Source images were inspected for motion artefacts from the mother or fetus. Placenta segmentation and DCE processing were performed for the dynamic image series to measure cotyledon specific volume, flow, and normalized flow. Overall placental histopathology was conducted for controls, Tisseel, and MCP-1 animals and regions of tissue infarctions and necrosis were documented. Visual inspections for potential necrotic tissue were conducted for the two Tisseelx3 animals. STATISTICAL TESTS: Wilcoxon rank sum test, significance level P < 0.05. RESULTS: No motion artefacts were observed. For the group treated with 1.5 mL of Tisseel, significantly lower cotyledon volume, flow, and normalized flow per cotyledon were observed for the third gestational time point of imaging (day ~145), with mean normalized flow of 0.53 minute-1 . Preliminary histopathological analysis shows areas of tissue necrosis from a selected cotyledon in one Tisseel-treated (single dose) animal and both Tisseelx3 (triple dose) animals. DATA CONCLUSION: This study demonstrates the feasibility of cotyledon-specific functional analysis at multiple gestational time points and injury detection in a placental rhesus macaque model through ferumoxytol-enhanced DCE MRI. LEVEL OF EVIDENCE: NA TECHNICAL EFFICACY: Stage 2.

Hsa_circ_0005397 promotes hepatocellular carcinoma progression through EIF4A3.

PURPOSE: The purpose of this study was to explore the expression and potential mechanism of hsa_circ_0005397 in hepatocellular carcinoma progression. METHODS: Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) was used to measure the expression level of hsa_circ_0005397 and EIF4A3 from paired HCC tissues and cell lines. Western Blot (WB) and immunohistochemistry (IHC) were used to verify the protein level of EIF4A3. The specificity of primers was confirmed by agarose gel electrophoresis. Receiver Operating Characteristic (ROC) Curve was drawn to analyze diagnostic value. Actinomycin D and nuclear and cytoplasmic extraction assays were utilized to evaluate the characteristics of hsa_circ_0005397. Cell Counting kit-8 (CCK-8) and colony formation assays were performed to detect cell proliferation. Flow cytometry analysis was used to detect the cell cycle. Transwell assay was performed to determine migration and invasion ability. RNA-binding proteins (RBPs) of hsa_circ_0005397 in HCC were explored using bioinformatics websites. The relationship between hsa_circ_0005397 and Eukaryotic Translation Initiation Factor 4A3 (EIF4A3) was verified by RNA Binding Protein Immunoprecipitation (RIP) assays, correlation and rescue experiments. RESULTS: In this study, hsa_circ_0005397 was found to be significantly upregulated in HCC, and the good diagnostic sensitivity and specificity shown a potential diagnostic capability. Upregulated expression of hsa_circ_0005397 was significantly related to tumor size and stage. Hsa_circ_0005397 was circular structure which more stable than liner mRNA, and mostly distributed in the cytoplasm. Upregulation of hsa_circ_0005397 generally resulted in stronger proliferative ability, clonality, and metastatic potency of HCC cells; its downregulation yielded the opposite results. EIF4A3 is an RNA-binding protein of hsa_circ_0005397, which overexpressed in paired HCC tissues and cell lines. In addition, expression of hsa_circ_0005397 decreased equally when EIF4A3 was depleted. RIP assays and correlation assay estimated that EIF4A3 could interacted with hsa_circ_0005397. Knockdown of EIF4A3 could reverse hsa_circ_0005397 function in HCC progression. CONCLUSIONS: Hsa_circ_0005397 promotes progression of hepatocellular carcinoma through EIF4A3. These research findings may provide novel clinical value for hepatocellular carcinoma.

Plasma neurofilament light as a promising biomarker in neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder lacking reliable biomarkers. This study investigates plasma protein levels as potential biomarkers of disease severity and progression in NIID. In this study, we enrolled 30 NIID patients and 36 age- and sex-matched controls, following them for 1-2 years. Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and tau were measured using ultrasensitive single molecule array (Simoa) assays. Disease severity was evaluated with the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL), and CNS symptom counts, in addition to neuroimaging data. Our study revealed that NIID patients has significantly higher plasma NfL (median, 35.2 vs. 8.61 pg/mL, p < 0.001) and GFAP (102 vs. 79.0 pg/mL, p = 0.010) levels compared to controls, with NfL emerging as a robust diagnostic marker (AUC = 0.956). NfL levels were notably higher in acute-onset NIID (77.5 vs. 28.8 pg/mL, p = 0.001). NfL correlated strongly with disease severity, including MMSE (ρ = - 0.687, p < 0.001), MoCA (ρ = - 0.670, p < 0.001), ADL (ρ = 0.587, p = 0.001), CNS symptoms (ρ = 0.369, p = 0.045), and white matter hyperintensity volume (ρ = 0.620, p = 0.004). Higher baseline NfL (≥ 35.2 pg/mL) associated with increased ADL scores, CNS symptoms, and white matter hyperintensity at follow-up. UCH-L1 and total tau levels showed no significant differences. Our results suggested the potential of NfL as a promising biomarker of disease severity and progression in NIID.

Serum circPRDM5 as a novel diagnostic biomarker for acute myocardial infarction.

BACKGROUND: Circular RNA (CircRNA) is known to play an important role in cardiovascular diseases, but its use as a biomarker of acute myocardial infarction (AMI) has not been studied. This study explores the feasibility of circPRDM5 as a novel biomarker of AMI. METHODS: CircPRDM5 was screened by bioinformatics, the correct circPRDM5 primers were tested by agarose gel electrophoresis (AGE) and Sanger sequencing, and the expression level of serum circPRDM5 was detected by Quantitative Reverse Transcription-Polymerase Chain Reaction. (qRT-PCR), and the diagnostic value of circPRDM5 was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: The expression of circPRDM5 in serum of AMI patients was significantly decreased compared with that of healthy control group and angina group (P < 0.001). The area under ROC curve of serum circPRDM5 was 0.862 [95 % CI, 0.814-0.909]. The combined diagnosis of serum circPRDM5, cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB) could improve the sensitivity of diagnosing AMI. The expression level of serum circPRDM5 increased after percutaneous coronary intervention (PCI). CONCLUSIONS: CircPRDM5 can be used as a novel biomarker for AMI, and its combination with cTnT and CK-MB can improve diagnostic value.

Biosynthetic mechanism of the yellow pigments in the marine bacterium Pseudoalteromonas sp. strain T1lg65.

The Pseudoalteromonas genus marine bacteria have attracted increasing interest because of their abilities to produce bioactive metabolites. The pigmented Pseudoalteromonas group encodes more secondary metabolite biosynthetic gene clusters (BGCs) than the non-pigmented group. Here, we report a yellow pigmented bacterium Pseudoalteromonas sp. strain T1lg65, which was isolated from a mangrove forest sediment. We showed that the yellow pigments of T1lg65 belong to the group of lipopeptide alterochromides. Further genetic analyses of the alterochromide BGC revealed that the yellow pigments are biosynthesized by aryl-polyene synthases and nonribosomal peptide synthases. Within the gene cluster, altA encodes a tyrosine ammonia acid lyase, which catalyzes synthesis of the precursor 4-hydroxycinnamic acid (4-HCA) from tyrosine in the alterochromide biosynthetic pathway. In addition, altN, encoding a putative flavin-dependent halogenase, was proven to be responsible for the bromination of alterochromides based on gene deletion, molecular docking, and site mutagenesis analyses. In summary, the biosynthetic pathway, precursor synthesis, and bromination mechanism of the lipopeptide alterochromides were studied in-depth. Our results expand the knowledge on biosynthesis of Pseudoalteromonas pigments and could promote the development of active pigments in the future.IMPORTANCEThe marine bacteria Pseudoalteromonas spp. are important biological resources because they are producers of bioactive natural products, including antibiotics, pigments, enzymes, and antimicrobial peptides. One group of the microbial pigments, alterochromides, holds a great value for their novel lipopeptide structures and antimicrobial activities. Previous studies were limited to the structural characterization of alterochromides and genome mining for the alterochromide biosynthesis. This work focused on the biosynthetic mechanism for alterochromide production, especially revealing functions of two key genes within the gene cluster for the alterochromide biosynthesis. On the one hand, our study provides a target for metabolic engineering of the alterochromide biosynthesis; on the other hand, the 4-HCA synthase AltA and brominase AltN show potential in the biocatalyst industry.

CircRNA and ferroptosis in human disease: Insights for new treatments.

Circular RNA (circRNA), classified as a type of non-coding RNA, has gained significant attention in the field of biology due to its distinctive ring structure and functional properties. Recent research has provided evidence that specific circRNAs have the ability to modulate disease progression through diverse mechanisms, one of which is by regulating cellular ferroptosis. Ferroptosis is a form of regulated cell death that is driven by iron dependency and lipid peroxidation, and extensive investigations have revealed a relationship between ferroptosis and disease development. In addition to evidence that both circRNAs and ferroptosis exert critical roles in disease progression, circRNAs have also been shown to actively mediate the process of ferroptosis. The relationship between circRNAs and ferroptosis therefore influences disease progression and offers novel targets for disease treatment. By directly or indirectly modulating the expression of circRNAs that regulate the expression of ferroptosis-related proteins, it may be possible to impact disease progression by promoting or inhibiting ferroptosis. Current research indicates such approaches may hold significant value in a wide variety of common diseases across physiological systems. This review comprehensively summarizes the findings of recent studies investigating the roles of circRNAs in the regulation of ferroptosis in various diseases.

Comprehensive characterization and expression analysis of enzymatic antioxidant gene families in passion fruit (Passiflora edulis).

Passion fruit, a valuable tropical fruit, faces climate-related growth challenges. Antioxidant enzymes are vital for both stress protection and growth regulation in plants. We first provided systemic analysis of enzymatic antioxidant gene families in passion fruit, identifying 90 members including 11 PeSODs, 45 PeAPXs, 8 PeCATs, 7 PeGPXs, 6 PeMDHARs, 8 PeDHARs, and 5 PeGRs. Gene members in each gene family with same subcellular localization showed closer phylogenetic relationship. Many antioxidant genes exhibited tissue- or developmental stage-specific expression patterns during floral and fruit development, with some widely expressed. Their co-expressed genes were linked to photosynthesis and energy metabolism, suggesting roles in protecting highly proliferating tissues from oxidative damage. Potential genes for enhancing temperature stress resistance were identified. The involvement of diverse regulatory factors including miRNAs, transcription factors, and CREs might contribute to the complex roles of antioxidant genes. This study informs future research on antioxidant genes and passion fruit breeding.

Direct alkylation of quinoxalinones with electron-deficient alkenes enabled by a sequential paired electrolysis.

The metal-free alkylation of N-heterocycles with alkenes has remained a synthetic challenge. We report here the successful implementation of metal-free alkylation of quinoxalinones with electron-deficient alkenes enabled by a sequential paired electrolysis. This protocol provides a mechanistically distinct approach to prepare a variety of C-3 alkylated quinoxalinones that are otherwise quite difficult to synthesize by other means.

Revealing Further Insights into Astringent Seeds of Chinese Fir by Integrated Metabolomic and Lipidomic Analyses.

Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.) stands as one of the pivotal afforestation tree species and timber resources in southern China. Nevertheless, the occurrence of seed abortion and a notably high proportion of astringent seeds significantly curtail the yield and quality of elite seeds, resulting in substantial economic losses. The development of astringent seeds is accompanied by significant physiological and biochemical alterations. Here, the first combined lipidomic and metabolomic analysis was performed to gain a comprehensive understanding of astringent seed traits. A total of 744 metabolites and 616 lipids were detected, of which 489 differential metabolites and 101 differential lipids were identified. In astringent seeds, most flavonoids and tannins, as well as proline and γ-aminobutyric acid, were more accumulated, along with a notable decrease in lipid unsaturation, indicating oxidative stress in the cells of astringent seeds. Conversely, numerous elemental metabolites were less accumulated, including amino acids and their derivatives, saccharides and alcohols, organic acids and nucleotides and their derivatives. Meanwhile, most lipid subclasses, mainly associated with energy storage (triglyceride and diglyceride) and cell membrane composition (phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine), also exhibited significant reductions. These results reflected a disruption in the cellular system or the occurrence of cell death, causing a reduction in viable cells within astringent seeds. Furthermore, only one lipid subclass, sphingosine phosphate (SoP), was more accumulated in astringent seeds. Additionally, lower accumulation of indole-3-acetic acid and more accumulation of salicylic acid (SA) were also identified in astringent seeds. Both SA and SoP were closely associated with the promotion of programmed cell death in astringent seeds. Collectively, our study revealed significant abnormal changes in phytohormones, lipids and various metabolites in astringent seeds, allowing us to propose a model for the development of astringent seeds in Chinese fir based on existing research and our findings. This work enriches our comprehension of astringent seeds and presents valuable bioindicators for the identification of astringent seeds.

Reorganization of the structural connectome during vision recovery in pituitary adenoma patients post-transsphenoidal surgery.

Pituitary adenomas (PAs) can exert pressure on the optic apparatus, leading to visual impairment. A subset of patients may observe a swift improvement in their vision following surgery. Nevertheless, the alterations in the structural connectome during the early postoperative period remain largely unexplored. The research employed probabilistic tractography, graph theoretical analysis, and statistical methods on preoperative and postoperative structural magnetic resonance imaging and diffusion tensor images from 13 PA patients. Postoperative analysis revealed an increase in global and local efficiency, signifying improved network capacity for parallel information transfer and fault tolerance, respectively. Enhanced clustering coefficient and reduced shortest path length were also observed, suggesting a more regular network organization and shortened communication steps within the brain network. Furthermore, alterations in node graphical properties were detected, implying a restructuring of the network's control points, possibly contributing to more efficient visual processing. These findings propose that rapid vision recovery post-surgery may be associated with significant reorganization of the brain's structural connectome, enhancing the efficiency and adaptability of the network, thereby facilitating improved visual processing.

Integrating single-nucleus sequence profiling to reveal the transcriptional dynamics of Alzheimer's disease, Parkinson's disease, and multiple sclerosis.

BACKGROUND: Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) are three nervous system diseases that partially overlap clinically and genetically. However, bulk RNA-sequencing did not accurately detect the core pathogenic molecules in them. The availability of high-quality single cell RNA-sequencing data of post-mortem brain collections permits the generation of a large-scale gene expression in different cells in human brain, focusing on the molecular features and relationships between diseases and genes. We integrated single-nucleus RNA-sequencing (snRNA-seq) datasets of human brains with AD, PD, and MS to identify transcriptomic commonalities and distinctions among them. METHODS: The snRNA-seq datasets were downloaded from Gene Expression Omnibus (GEO) database. The Seurat package was used for snRNA-seq data processing. The uniform manifold approximation and projection (UMAP) were utilized for cluster identification. The FindMarker function in Seurat was used to identify the differently expressed genes. Functional enrichment analysis was carried out using the Gene Set Enrichment Analysis (GSEA) and Gene ontology (GO). The protein-protein interaction (PPI) analysis of differentially expressed genes (DEGs) was analyzed using STRING database ( http://string-db.org ). SCENIC analysis was performed using utilizing pySCENIC (v0.10.0) based on the hg19-tss-centered-10 kb-10species databases. The analysis of potential therapeutic drugs was analyzed on Connectivity Map ( https://clue.io ). RESULTS: The gene regulatory network analysis identified several hub genes regulated in AD, PD, and MS, in which HSPB1 and HSPA1A were key molecules. These upregulated HSP family genes interact with ribosome genes in AD and MS, and with immunomodulatory genes in PD. We further identified several transcriptional regulators (SPI1, CEBPA, TFE3, GRHPR, and TP53) of the hub genes, which has important implications for uncovering the molecular crosstalk among AD, PD, and MS. Arctigenin was identified as a potential therapeutic drug for AD, PD, and MS. CONCLUSIONS: Together, the integrated snRNA-seq data and findings have significant implications for unraveling the shared and unique molecular crosstalk among AD, PD, and MS. HSPB1 and HSPA1A as promising targets involved in the pathological mechanisms of neurodegenerative diseases. Additionally, the identification of arctigenin as a potential therapeutic drug for AD, PD, and MS further highlights its potential in treating these neurological disorders. These discoveries lay the groundwork for future research and interventions to enhance our understanding and treatment of AD, PD, and MS.

Single-nucleus transcriptional profiling uncovers the reprogrammed metabolism of astrocytes in Alzheimer's disease.

Astrocytes play an important role in the pathogenesis of Alzheimer's disease (AD). It is widely involved in energy metabolism in the brain by providing nutritional and metabolic support to neurons; however, the alteration in the metabolism of astrocytes in AD remains unknown. Through integrative analysis of single-nucleus sequencing datasets, we revealed metabolic changes in various cell types in the prefrontal cortex of patients with AD. We found the depletion of some important metabolites (acetyl-coenzyme A, aspartate, pyruvate, 2-oxoglutarate, glutamine, and others), as well as the inhibition of some metabolic fluxes (glycolysis and tricarbocylic acid cycle, glutamate metabolism) in astrocytes of AD. The abnormality of glutamate metabolism in astrocytes is unique and important. Downregulation of GLUL (GS) and GLUD1 (GDH) may be the cause of glutamate alterations in astrocytes in AD. These results provide a basis for understanding the characteristic changes in astrocytes in AD and provide ideas for the study of AD pathogenesis.

Endoscope-Assisted Keyhole Surgery for Traumatic Subacute Subdural Hematoma Evacuation in Emergencies.

OBJECTIVE: This study aimed to investigate whether a simple endoscopic method was effective for the evacuation of traumatic subacute subdural hematomas. METHODS: A total of 51 patients with subacute subdural hematomas requiring surgery were enrolled in this study. An endoscopic hematoma evacuation was performed through a small bone window for 22 patients. Hematoma evacuation by open surgery was performed for 29 patients. The postoperative Glasgow Coma Scale scores improvement, surgery times, displacement of midline measurements, and intraoperative blood loss were recorded and analyzed for each patient. RESULTS: The average time from the initial incision to suture completion was 38.41 ± 6.97 minutes for the endoscopic surgery group and 74.66 ± 9.54 minutes for the open-surgery group (P < 0.01). The average total blood loss was 41.36 ± 10.82 ml for the endoscopic group and 250.00 ± 58.25 ml for the open-surgery group (P < 0.01). No postoperative bleeding occurred in either group. The midline displacement measurement showed significant improvement on the day after surgery, with 5.21 ± 1.98 mm in the study group versus 6.75 ± 1.37 mm in the control group (P < 0.01). At the 1-month follow-up appointment, the midline measurement was normal in both groups. Computed tomography scans revealed almost no residual hematomas, representing an average evacuation rate of 100% in both groups. The average Glasgow Coma Scale scores improvement on the day after surgery were 1.77 ± 1.93 in the endoscopic surgery group and 1.66 ± 0.77 in the open-surgery group (P = 0.766). CONCLUSION: Endoscopic subacute subdural hematoma removal through a small bone window achieved satisfactory hematoma removal using a minimally invasive method when compared with an open-surgery method.

MR Imaging, MGMT Promoter Methylation Features and Prognostic Analysis of Subventricular Zone Contacting IDH Wild-type Glioblastoma.

BACKGROUND: As the largest concentration of neural stem cells in adult brain, the subventricular zone (SVZ) is considered to be a potential source of glioblastoma (GBM) occurrence in recent years. METHODS: In this study, 116 patients with glioblastoma treated at PLA General Hospital were retrospectively reviewed. The features of SVZ contacting glioblastoma were analyzed in terms of MR imaging and MGMT promoter methylation. We also evaluated the prognostic value of SVZ contacting in GBM patients. RESULTS: GBM with SVZ involvement on MRI is more likely to grow across the midline (36.8% vs. 6.9%, P=0.002), more often multifocal lesion (35.6% vs. 6.9%, P=0.003) and have a lower proportion of MGMT promoter methylation (36.8% vs. 69.0%, P=0.003). The median overall survival and progression- free survival of patients in the SVZ contacting group were 12 months and 7 months, while 25 months and 17 months in the non-contacting group (P<0.001, respectively). There was no significant difference in overall survival (P=0.229) and progression-free survival (P=0.808) between patients with different SVZ contacting regions. Multivariate survival analysis indicated that patients with MRI SVZ involvement showed worse overall survival (HR=2.060, 95%CI 1.195-3.550，P=0.009) and progression- free survival (HR=3.021, 95%CI 1.788-5.104，P＜0.001). CONCLUSION: This study suggested that MRI SVZ involvement at diagnosis is an independent risk factor for overall survival and progression-free survival in IDH wild-type glioblastoma patients. Based on MR imaging, we also found that SVZ contacting glioblastomas had a larger proportion of crossing midline tumors and multifocal lesions. In addition, patients with SVZ contact in our research presented a lower proportion of MGMT promoter methylation.

Genome-wide identification and expression analysis of the bHLH gene family in passion fruit (Passiflora edulis) and its response to abiotic stress.

Passion fruit is a tropical fruit crop with significant agricultural, economic and ornamental values. The growth and development of passion fruit are greatly affected by climatic conditions. In plants, the basic helix-loop-helix (bHLH) gene family plays essential roles in the floral organ and fruit development, as well as stress response. However, the characteristics and functions of the bHLH genes of passion fruit remain unclear. Here, 138 passion fruit bHLH members were identified and classified into 20 subfamilies. The structural analysis illustrated that PebHLH proteins of the specific subfamily are relatively conserved. Collinearity analysis indicated that the expansion of the PebHLH gene family mainly took place by segmental duplication, and the structural diversity of duplicated genes might contribute to their functional diversity. PebHLHs, which potentially regulate different floral organ and fruit development, were further screened out, and many of these genes were differentially expressed under various stress treatments. The co-presence of different cis-regulatory elements involved in developmental regulation, hormone and stress responses in the promoter regions of PebHLHs might be closely related to their diverse regulatory roles. Overall, this study will be helpful for further functional investigation of PebHLHs and provides clues for improvement of the passion fruit breeding.

PeHVA22 gene family in passion fruit (Passiflora edulis): initial characterization and expression profiling diversity.

Passion fruit, an economically valuable fruit crop, is highly vulnerable to adverse climate conditions. The HVA22 genes, recognized as abscisic acid (ABA) and stress-inducible, play vital roles in stress response and growth regulation in diverse eukaryotic organisms. Here, six HVA22 genes were firstly identified in passion fruit genome and all predicted to be localized within the endoplasmic reticulum. Phylogenetic analyses showed that all PeHVA22s were divided into four subgroups. The gene structural features of PeHVA22 genes clustered in the same subgroup were relatively conserved, while the gene structure characteristics of PeHVA22s from different subgroups varied significantly. PeHVA22A and PeHVA22C closely clustered with barley HVA22 in Group II, were also induced by ABA and drought stress treatment, suggesting conserved roles similar to barley HVA22. Meanwhile, most PeHVA22s exhibited induced expression post-drought treatment but were suppressed under salt, low and high-temperature conditions, indicating a unique role in drought response. Additionally, PeHVA22s displayed tissue-specific expression patterns across diverse tissues, except for PeHVA22B which maybe a pseudogene. Notably, PeHVA22C, PeHVA22E, and PeHVA22F predominantly expressed in fruit, indicating their involvement in fruit development. Almost all PeHVA22s showed variable expression at different developmental stages of stamens or ovules, implying their roles in passion fruit's sexual reproduction. The intricate roles of PeHVA22s may result from diverse regulatory factors including transcription factors and CREs related to plant growth and development, hormone and stress responsiveness. These observations highlighted that PeHVA22s might play conserved roles in ABA response and drought stress tolerance, and also be participated in the regulation of passion fruit growth and floral development.

Astragalus polysaccharides protect against inactivated Vibrio alginolyticus-induced inflammatory injury in macrophages of large yellow croaker.

As an effective immunostimulant, Astragalus polysaccharides (APS) have been widely used in fish aquaculture, however, their action mechanisms remain poorly understood. In the present paper, the inflammatory macrophage model of large yellow croaker (Larimichthys crocea) was constructed by using formalin-inactivated Vibrio alginolyticus. Inactivated V. alginolyticus could cause cellular damage of primary head kidney macrophages (PKM) by decreasing cell activity and inducing reactive oxygen species (ROS) production and cell apoptosis. When PKM were pretreated with APS, the depressed cell activity induced by inactivated V. alginolyticus was significantly improved, and ROS overproduction and cell apoptosis were inhibited. Then the protection mechanism of APS was investigated by transcriptome analysis. After treated with inactivated V. alginolyticus, the expression of immune-related genes (TLR5s, TLR13, Clec4e, IKK, IκB, BCL-3, NF-κB2, REL, IL-1ß, and IL-6) and pyroptosis-related genes (caspase-1, NLRP3, and NLRC3) in PKM were significantly up-regulated. However, APS pretreatment reversed the up-regulation of most of the above-mentioned genes, where TLR5s, BCL-3, REL, caspase-1, NLRP12, IL-1ß, and IL-6 were significantly down-regulated compared with inactivated V. alginolyticus-treated group. These results suggested that APS could protect large yellow croaker PKM against inactivated V. alginolyticus-induced inflammatory injury, and may exert their protection effects by activating NF-κB and pyroptosis signaling pathways. These findings therefore advance our understanding of the immune regulation mechanism of APS in fish, and facilitate the application of APS in prevention and control of fish bacteriosis.

The imaging features and prognosis of gliomas involving the subventricular zone: An MRI study.

RATIONALE AND OBJECTIVES: As the largest concentrated region of neural stem cells in the adult brain, the subventricular zone (SVZ) is considered to have a close relationship with the origin of gliomas. An in-depth study of the characteristic manifestations associated with SVZ involvement in glioma may provide new ideas for individualized diagnosis and treatment of this fatal disease. MATERIALS AND METHODS: All 279 patients with glioma who underwent surgical treatment in our department from January 2016 to December 2021 were included. Clinical and imaging data were collected, and telephonic follow-up was conducted to analyze the overall survival and progression-free survival. Prognostic factors including SVZ involvement on glioblastoma patients' survival were analyzed. Next, the relationship between SVZ involvement, a set of unique imaging features and gene status were determined respectively. The chi-squared test, logistics regression, and Cox regression were used for statistical analysis. RESULTS: The patients were divided into the SVZ involvement group (n = 198, 70.97 %) and SVZ non-involvement group (n = 81, 29.03 %). The median overall survival and progression-free survival were 13 months and 7 months for the SVZ involvement group, but 25 months and 17 months for the SVZ non-involvement group, respectively. In multivariate Cox survival analysis, MRI SVZ involvement proved an independent risk factor for the survival of patients with glioblastoma. The patients with SVZ involvement sign had a lower rate of cystic lesion (32.32 % vs. 48.48 %, p = 0.029), and a larger mean maximum diameter (5.88 ± 1.28 vs. 3.28 ± 1.65 cm). Compared with high grade gliomas (HGG), T1 enhancement (25.25 % vs. 10.42 %, p = 0.041) and homogeneous signal on T2WI (14.14 % vs. 43.75 %, p = 0.025) were independently associated with SVZ involvement in WHO grade 2 gliomas(LGG). In the gene status analysis, the SVZ involvement group showed the lower rate of MGMT promoter methylation (57.58 % vs. 79.17 %, p = 0.017). CONCLUSION: SVZ involvement in MRI at diagnosis is an independent negative prognostic indicator for the survival of glioblastoma patients. Some image signs are associated with SVZ involvement in HGG and LGG respectively. The unique imaging and gene features of gliomas with SVZ involvement indicate that this kind of tumor maybe a unique subgroup of gliomas.