Genome Sequencing of Three Pathogenic Fungi Provides Insights into the Evolution and Pathogenic Mechanisms of the Cobweb Disease on Cultivated Mushrooms.

Fungal diseases not only reduce the yield of edible mushrooms but also pose potential threats to the preservation and quality of harvested mushrooms. Cobweb disease, caused primarily by fungal pathogens from the Hypocreaceae family, is one of the most significant diseases affecting edible mushrooms. Deciphering the genomes of these pathogens will help unravel the molecular basis of their evolution and identify genes responsible for pathogenicity. Here, we present high-quality genome sequences of three cobweb disease fungi: Hypomyces aurantius Cb-Fv, Cladobotryum mycophilum CB-Ab, and Cladobotryum protrusum CB-Mi, isolated from Flammulina velutipes, Agaricus bisporus, and Morchella importuna, respectively. The assembled genomes of H. aurantius, C. mycophilum, and C. protrusum are 33.19 Mb, 39.83 Mb, and 38.10 Mb, respectively. This is the first report of the genome of H. aurantius. Phylogenetic analysis revealed that cobweb disease pathogens are closely related and diverged approximately 17.51 million years ago. CAZymes (mainly chitinases, glucan endo-1,3-beta-glucosidases, and secondary metabolite synthases), proteases, KP3 killer proteins, lipases, and hydrophobins were found to be conserved and strongly associated with pathogenicity, virulence, and adaptation in the three cobweb pathogens. This study provides insights into the genome structure, genome organization, and pathogenicity of these three cobweb disease fungi, which will be a valuable resource for comparative genomics studies of cobweb pathogens and will help control this disease, thereby enhancing mushroom quality.

Network pharmacology and phytochemical composition combined with validation in vivo and in vitro reveal the mechanism of platycodonis radix ameliorating PM2.5-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Platycodonis radix (PR), the root of Platycodon grandiflorus (Jacq.) A. DC., is a traditional Chinese medicine recognized for its dual role as both a medicinal and dietary substance, exhibiting significant anti-inflammatory properties. It is frequently utilized in the treatment of lung diseases. However, the molecular mechanisms by which PR exerts its effects in the treatment of acute lung injury (ALI) remain unclear. AIM OF THE STUDY: This study presents a novel strategy that integrates network pharmacology, molecular docking, untargeted metabolomics analysis and experimental validation to investigate the molecular mechanisms through which PR treats ALI. MATERIALS AND METHOD: Initially, the bioactive components of PR, along with its targets and pathways in the treatment of ALI, were identified using network pharmacology. Following this, preliminary validation was conducted through molecular docking. The active ingredients in the aqueous extract of PR were characterized using HPLC-MS. Finally, in vivo and in vitro experiments were performed to further validate the findings from the network pharmacology. RESULTS: A total of 14 bioactive components and 156 effective targets were identified using the TCMSP, DisGeNET, Genecard, OMIM databases and Venny 2.1.0. Protein-protein interaction (PPI) analysis revealed 22 core targets including TP53, AKT1, STAT3 and JUN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these targets primarily participate in the regulation of cellular apoptosis, lung cancer and inflammatory pathways. Molecular docking demonstrated that four bioactive components exhibited strong affinities with their respective docking targets. LC-MS analysis confirmed that the aqueous extract of PR contained 87 components, including two active ingredients identified through network pharmacology and molecular docking. Preliminary validation was conducted in mice with ALI induced by acute PM2.5 exposure, revealing that the aqueous extract of PR reduced inflammatory factor levels in bronchoalveolar lavage fluid, enhanced antioxidant capacity in lung tissue, and decreased lung cell apoptosis in PM2.5-exposed mice. Notably, PR alleviated PM2.5-induced ALI through the STAT3, JUN, and AKT1 signaling pathways. Similarly, the results of in vitro intervention experiments further confirmed that the aqueous extract of PR protected pulmonary epithelial cells against PM2.5 exposure through activating AKT1 sinalling pathway, and inhibiting STAT3 and JUN signalling pathways. CONCLUSION: This study identifies the active components of PR and elucidates the molecular mechanisms by which PR alleviates ALI, specifically by inhibiting the phosphorylation levels of STAT3 and c-JUN, or by activating the phosphorylation level of AKT1. These results provide a foundational basis for the application of PR in the treatment or prevention of lung injuries induced by particulate matter.

Assessment of perineal body properties in women with stress urinary incontinence using Transperineal shear wave elastography.

Limited data on the correlation between the perineal body (PB) and stress urinary incontinence (SUI) are available. The objectives of this study were to quantify the PB using shear wave elastography (SWE) technology with a high-frequency linear array probe to evaluate the relationship between the properties of PB and stress urinary incontinence (SUI). This study included 64 women with SUI and 70 female control participants. The length, height, perimeter, and area of PB in all participants were calculated using transperineal ultrasound, and the elasticity of PB was assessed by SWE at rest and during the maximal Valsalva maneuver, respectively. In addition, the comparison of PB parameters between the patients with SUI and the healthy participants was conducted. The transperineal ultrasound and SWE examination was performed in 134 participants, and the elastic modulus values were significantly increased from participants at rest to those during the maximal Valsalva maneuver in all participants (Emax: 35.59 versus 53.13 kPa, P < 0.001; and Emean: 26.97 versus 40.25 kPa, P < 0.001). Emax and Emean of PB exhibited significant differences during the maximal Valsalva maneuver between the SUI group and the control group (47.73 versus 58.06 kPa, P < 0.001; and 35.78 versus 44.33 kPa, P < 0.001) and had a negative correlation with SUI. The BMI and PB height during the maximal Valsalva maneuver in the SUI group were found to be significantly higher than that in healthy volunteers. Emax and Emean of PB negatively correlated with BMI during the maximal Valsalva maneuver (r = -0.277, P = 0.001 and r = -0.211, P = 0.014). ROC curve analysis demonstrated that PB perimeter of less than 12.68mm was strongly associated with SUI during the maximal Valsalva maneuver, and an Emax of less than 55.76 kPa had a 100% specificity in predicting SUI. SWE can quantify the elasticity of PB, identifying a significant difference between participants at rest and during Valsalva maneuver. In addition, the stiffness of the PB was significantly lower in women with SUI than in healthy women, which may provide a noninvasive clinical practice in SUI prediction.

[Prediction model of Reduning Injection content based on near-infrared and mid-infrared technology combined with spectral fusion].

In this paper, a method for rapidly determining the content of chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, gardeniside, and strychnoside in Reduning Injection(RI) was established based on near-infrared spectroscopy(NIRS), midinfrared spectroscopy(MIRS), and spectral fusion technology. Six pretreatment methods and five variable screening methods were investigated, and the best method was selected to establish a partial least square(PLS) model of two single spectra. At the same time,the NIRS and MIRS were fused with equal weights and characteristic bands, and the PLS model was established. The prediction effect of the four models on the quality control components was compared: NIRS>characteristic band fusion>MIRS>equal weight fusion. The relative standard error of prediction(RSEP) of the NIRS models on the five quality control components was less than 2. 5%, and the ratio of performance to deviation(RPD) was greater than 9. 5. The results show that the single spectrum model of NIRS is the best quantitative detection method, and the model of NIRS combined with the PLS algorithm can be used for the rapid detection of Reduning Injection.

Dynamic contrast-enhanced and diffusion-weighted MRI of cervical carcinoma: Correlations with Ki-67 proliferation status.

OBJECTIVES: To investigate the association of quantitative parameter (apparent diffusion coefficient [ADC]) from diffusion-weighted imaging (DWI) and various quantitative and semiquantitative parameters from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) with Ki-67 proliferation index (PI) in cervical carcinoma (CC). METHODS: A total of 102 individuals with CC who received 3.0 T MRI examination (DWI and DCE MRI) between October 2016 and December 2022 were enrolled in our investigation. Two radiologists separately assessed the ADC parameter and various quantitative and semiquantitative parameters including (volume transfer constant [Ktrans], rate constant [kep], extravascular extracellular space volume fraction [ve], volume fraction of plasma [vp], time to peak [TTP], maximum concentration [MaxCon], maximal slope [MaxSlope] and area under curve [AUC]) for each tumor. Their association with Ki-67 PI was analyzed by Spearman association analysis. The discrepancy between low-proliferation and high-proliferation groups was subsequently analyzed. The receiver operating characteristic (ROC) curve analysis utilized to identify optimal cut-off points for significant parameters. RESULTS: Both ADC (ρ = -0.457, p < 0.001) and Ktrans (ρ = -0.467, p < 0.001) indicated a strong negative association with Ki-67 PI. Ki-67 PI showed positive correlations with TTP, MaxCon, MaxSlope and AUC (ρ = 0.202, 0.231, 0.309, 0.235, respectively; all p values<0.05). Compared with the low-proliferation group, high-Ki-67 group presented a significantly lower ADC (0.869 ± 0.125 × 10-3 mm2/s vs. 1.149 ± 0.318 × 10-3 mm2/s; p < 0.001) and Ktrans (1.314 ± 1.162 min-1vs. 0.391 ± 0.390 min-1; p < 0.001), also significantly higher MaxCon values (0.756 ± 0.959 vs. 0.422 ± 0.341; p < 0.05) and AUC values (2.373 ± 3.012 vs. 1.273 ± 1.000; p < 0.05). The cut-offs of ADC, Ktrans, MaxCon and AUC for discrimating low- and high-Ki-67 groups were 0.920 × 10-3 mm2/s, 0.304 min-1, 0.209 and 1.918, respectively. CONCLUSIONS: ADC, Ktrans, TTP, MaxCon, MaxSlope and AUC are associated with Ki-67 PI. ADC and Ktrans exhibited high performance to discriminate low and high Ki-67 status of CC.

The efficacy of levonorgestrelintrauterine system, drospirenone & ethinylestradiol tablets (II) and dydrogesterone in preventing the recurrence of endometrial polyps.

OBJECTIVE: To analyze the efficacy of levonorgestrelintrauterine system, Drospirenone & ethinylestradiol tablets (II), and dydrogesterone in preventing the recurrence of endometrial polyps after hysteroscopic endometrial polypectomy. METHODS: One hundred seventy patients who underwent hysteroscopic endometrial polypectomy in the Gynecology Department of Tianmen First People's Hospital in Hubei Province from January 2022 to June 2023 were randomly divided into the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, dydrogesterone group, and a control group. The recurrence rates, endometrial thickness, and menstrual volume changes at 6 and 12 months post-operation were compared among these four groups. RESULTS: The recurrence rates in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group were lower than the control group, with statistical significance (P < 0.01), with the levonorgestrelintrauterine system group having the lowest recurrence rate. The endometrial thickness at 6 and 12 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was thinner than that of the control group and thinner than pre-operation, with statistical significance (P < 0.01). The menstrual volume at 3 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was significantly less than the control group, and less than the pre-operation volume. CONCLUSION: Dydrogesterone, drospirenone & ethinylestradiol tablets (II), and levonorgestrelintrauterine system all play a role in preventing the recurrence of endometrial polyps, but levonorgestrelintrauterine system is significantly better than dydrogesterone and Drospirenone & ethinylestradiol tablets (II) in terms of postoperative recurrence rate, endometrial thickness, menstrual changes, and compliance, and is worth promoting in clinical application.

White matter integrity of right frontostriatal circuit predicts internet addiction severity among internet gamers.

Excessive use of the internet, which is a typical scenario of self-control failure, could lead to potential consequences such as anxiety, depression, and diminished academic performance. However, the underlying neuropsychological mechanisms remain poorly understood. This study aims to investigate the structural basis of self-control and internet addiction. In a cohort of 96 internet gamers, we examined the relationships among grey matter volume and white matter integrity within the frontostriatal circuits and internet addiction severity, as well as self-control measures. The results showed a significant and negative correlation between dACC grey matter volume and internet addiction severity (p < 0.001), but not with self-control. Subsequent tractography from the dACC to the bilateral ventral striatum (VS) was conducted. The fractional anisotropy (FA) and radial diffusivity of dACC-right VS pathway was negatively (p = 0.011) and positively (p = 0.020) correlated with internet addiction severity, respectively, and the FA was also positively correlated with self-control (p = 0.036). These associations were not observed for the dACC-left VS pathway. Further mediation analysis demonstrated a significant complete mediation effect of self-control on the relationship between FA of the dACC-right VS pathway and internet addiction severity. Our findings suggest that the dACC-right VS pathway is a critical neural substrate for both internet addiction and self-control. Deficits in this pathway may lead to impaired self-regulation over internet usage, exacerbating the severity of internet addiction.

Knockdown the moyamoya disease susceptibility gene, RNF213, upregulates the expression of basic fibroblast growth factor and matrix metalloproteinase-9 in bone marrow derived mesenchymal stem cells.

Moyamoya disease (MMD) is a chronic, progressive cerebrovascular occlusive disease. Ring finger protein 213 (RNF213) is a susceptibility gene of MMD. Previous studies have shown that the expression levels of angiogenic factors increase in MMD patients, but the relationship between the susceptibility gene RNF213 and these angiogenic mediators is still unclear. The aim of the present study was to investigate the pathogenesis of MMD by examining the effect of RNF213 gene knockdown on the expression of matrix metalloproteinase-9 (MMP-9) and basic fibroblast growth factor (bFGF) in rat bone marrow-derived mesenchymal stem cells (rBMSCs). Firstly, 40 patients with MMD and 40 age-matched normal individuals (as the control group) were enrolled in the present study to detect the levels of MMP-9 and bFGF in serum by ELISA. Secondly, Sprague-Dawley male rat BMSCs were isolated and cultured using the whole bone marrow adhesion method, and subsequent phenotypic analysis was performed by flow cytometry. Alizarin red and oil red O staining methods were used to identify osteogenic and adipogenic differentiation, respectively. Finally, third generation rBMSCs were transfected with lentivirus recombinant plasmid to knockout expression of the RNF213 gene. After successful transfection was confirmed by reverse transcription-quantitative PCR and fluorescence imaging, the expression levels of bFGF and MMP-9 mRNA in rBMSCs and the levels of bFGF and MMP-9 protein in the supernatant of the culture medium were detected on the 7th and 14th days after transfection. There was no significant difference in the relative expression level of bFGF among the three groups on the 7th day. For the relative expression level of MMP-9, there were significant differences on the 7th day and 14th day. In addition, there was no statistically significant difference in the expression of bFGF in the supernatant of the RNF213 shRNA group culture medium, while there was a significant difference in the expression level of MMP-9. The knockdown of the RNF213 gene affects the expression of bFGF and MMP-9. However, further studies are needed to determine how they participate in the pathogenesis of MMD. The findings of the present study provide a theoretical basis for clarifying the pathogenesis and clinical treatment of MMD.

Mental Health and Quality of Life in Chronic Kidney Disease Patients with Mild-to-Moderate Depression: A Retrospective Cohort Study of Mindfulness-Based Stress Reduction Therapy.

BACKGROUND: Chronic kidney disease (CKD) patients may experience pessimism, and even despair, due to long-term nature of the condition, which increases the risk of depression. Mindfulness-based stress reduction (MBSR) can relieve depression. This retrospective cohort study aimed to investigate the effects of MBSR on mental health and quality of life in CKD patients with mild-to-moderate depression, so as to provide guidance for clinical nursing programs. METHODS: The clinical data of 100 CKD patients with mild-to-moderate depression who were treated in Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences from January 2021 to March 2023 were retrospectively analyzed. Based on nursing method received, the patients were divided into the conventional group (conventional management) and the MBSR group (MBSR therapy was implemented in addition to conventional management). After matching, there were 35 cases in each group. The scores for the self-rating depression scale (SDS), Connor-Davidson Resilience Scale (CD-RISC), Five-factor Mindfulness Questionnaire (FFMQ), Pittsburgh Sleep Quality Index (PSQI), and 36-item Short Form Health Survey (SF-36) were compared between the two groups. RESULTS: After management, the SDS and PSQI scores of the MBSR group were lower than those of the conventional group, and the CD-RISC, FFMQ and SF-36 scores were higher than those of the conventional group (p < 0.05). CONCLUSION: MBSR can improve the mental health, sleep quality, and quality of life of CKD patients with mild-to-moderate depression, and improve psychological resilience and mindfulness.

NASP gene contributes to autism by epigenetic dysregulation of neural and immune pathways.

BACKGROUND: Epigenetics makes substantial contribution to the aetiology of autism spectrum disorder (ASD) and may harbour a unique opportunity to prevent the development of ASD. We aimed to identify novel epigenetic genes involved in ASD aetiology. METHODS: Trio-based whole exome sequencing was conducted on ASD families. Genome editing technique was used to knock out the candidate causal gene in a relevant cell line. ATAC-seq, ChIP-seq and RNA-seq were performed to investigate the functional impact of knockout (KO) or mutation in the candidate gene. RESULTS: We identified a novel candidate gene NASP (nuclear autoantigenic sperm protein) for epigenetic dysregulation in ASD in a Chinese nuclear family including one proband with autism and comorbid atopic disease. The de novo likely gene disruptive variant tNASP(Q289X) subjects the expression of tNASP to nonsense-mediated decay. tNASP KO increases chromatin accessibility, promotes the active promoter state of genes enriched in synaptic signalling and leads to upregulated expression of genes in the neural signalling and immune signalling pathways. Compared with wild-type tNASP, tNASP(Q289X) enhances chromatin accessibility of the genes with enriched expression in the brain. RNA-seq revealed that genes involved in neural and immune signalling are affected by the tNASP mutation, consistent with the phenotypic impact and molecular effects of nasp-1 mutations in Caenorhabditis elegans. Two additional patients with ASD were found carrying deletion or deleterious mutation in the NASP gene. CONCLUSION: We identified novel epigenetic mechanisms mediated by tNASP which may contribute to the pathogenesis of ASD and its immune comorbidity.

The Critical Role of Leadership in Patient Safety Culture: A Mediation Analysis of Management Influence on Safety Factors.

Purpose: This research aims to investigate the role of management leadership in promoting a culture of patient safety within healthcare organizations. Through a comprehensive mediation analysis of the Chinese version of the safety attitudes questionnaire (CSAQ) and patient safety culture, the study examines the interplay between these critical factors and their combined influence on healthcare outcomes. Patients and Methods: In a medical center located in Taiwan, a cross-sectional survey was carried out utilizing the CSAQ. Among the 1500 distributed surveys, 1037 were returned and deemed valid, resulting in a return rate of 69.13%. To investigate the main measures, Structural Equation Modeling with mediation analysis was employed to scrutinize the direct and indirect effects of factors including teamwork climate, job satisfaction, stress recognition, perceptions of management, working conditions, and emotional exhaustion on safety climate. Results: The findings reveal that effective management leadership plays a pivotal role in shaping safety attitudes and fostering a robust patient safety culture. The study identifies three critical facets of patient safety that are entirely mediated by management perceptions: teamwork climate, working conditions, and stress recognition. The results highlight the importance of enhancing these dimensions to advance the patient safety culture within healthcare organizations. Moreover, stress recognition is identified as a critical factor influencing the organizational culture of patient safety. Conclusion: This research offers valuable insights for healthcare organizations seeking to prioritize patient safety and improve overall quality of care. By enhancing our understanding of the critical factors that shape safety attitudes and patient safety culture, this study provides a roadmap for effective management leadership and a culture of patient safety within healthcare organizations. The study underscores the significance of management leadership in promoting patient safety culture and highlights the importance of enhancing teamwork climate, working conditions, and stress recognition to advance patient safety culture.

Effects of Designed Herbal Formula on Growth Performance, Blood Indices, Organ Traits, and Cecum Microbiology in Broilers.

The objective of this study was to investigate the effect of the designed herbal formula (DHF) on growth performance, blood indices, organ traits, and cecum microbiology in broilers. A total of 96 male broilers of 1 d were selected and randomly assigned to two groups with six replicates of eight broilers each. The control (CON) and the basal diet containing 1.0% DHF (Astragali radix, Atractylodes macrocephala Koidz., Isatis tinctoria Linnaeus, and Citri reticulatae pericarpium, 2:1:1:2) were fed separately. The experiment was conducted for 35 days. The results showed that the DHF diet increased body weight and decreased the feed conversion ratio (FCR) (p < 0.05). At 21 days, the spleen, thymus, lymphocytes, and thrombocytes were increased (p < 0.05), and pancreas, duodenum, heterophils, and mean corpuscular hemoglobin (MCH) were decreased (p < 0.05). At 35 days, the heart, pancreas, white blood cell, heterophils, hemoglobin, MCH and mean corpuscular hemoglobin concentration (MCHC) were decreased, while lymphocytes and middle cells were increased (p < 0.05). The results of microbial diversity analysis showed that the DHF diet decreased the microbial diversity of the cecum. Firmicutes and Bacteroidetes were the dominant phyla, where the DHF diet increased the relative abundances of Bacteroides uniformis, Bacteroides vulgatus, and Faecalibacterium prausnitzii, and then decreased the relative abundance of Shigella sonnei. In conclusion, DHF played a positive role in improving the growth performance, immune performance, and relative abundance of Bacteroides uniformis, Bacteroides vulgatus, and Faecalibacterium prausnitzii in cecum microbiology in broilers, and has the potential to be used as a novel feed additive.

Revealing novel genomic insights and therapeutic targets for juvenile idiopathic arthritis through omics.

BACKGROUND: The genetic architecture of JIA remains only partially comprehended. There is a clear imperative for continued endeavours to uncover insights into the underlying causes of JIA. METHODS: This study encompassed a comprehensive spectrum of endeavours, including conducting a JIA genome-wide association study (GWAS) meta-analysis that incorporated data from 4550 JIA cases and 18 446 controls. We employed in silico and genome-editing approaches to prioritizing target genes. To investigate pleiotropic effects, we conducted phenome-wide association studies. Cell-type enrichment analyses were performed by integrating bulk and single-cell sequencing data. Finally, we delved into potential druggable targets for JIA. RESULTS: Fourteen genome-wide significant non-HLA loci were identified, including four novel loci, each exhibiting pleiotropic associations with other autoimmune diseases or musculoskeletal traits. We uncovered strong genetic correlation between JIA and BMD traits at 52 genomic regions, including three GWAS loci for JIA. Candidate genes with immune functions were captured by in silico analyses at each novel locus, with additional findings identified through our experimental approach. Cell-type enrichment analysis revealed 21 specific immune cell types crucial for the affected organs in JIA, indicating their potential contribution to the disease. Finally, 24 known or candidate druggable target genes were prioritized. CONCLUSIONS: Our identification of four novel JIA-associated genes, CD247, RHOH, COLEC10 and IRF8, broadens the novel potential drug repositioning opportunities. We established a new genetic link between COLEC10, TNFRSF11B and JIA/BMD. Additionally, the identification of RHOH underscores its role in positive thymocyte selection, thereby illuminating a critical facet of JIA's underlying biological mechanisms.

Effects of Heat Stress on Breast Muscle Metabolomics and Lipid Metabolism Related Genes in Growing Broilers.

With global warming and worsening climatic conditions, heat stress (HS) has become a significant challenge affecting the development of poultry production. In this study, we aimed to determine the effects of HS on breast muscle metabolomics and lipid metabolism-related genes in growing broilers. One hundred twenty 29-day-old Arbor Acres broilers were randomly divided into normal temperature (NT; 21 ± 1 °C) and heat stress (HS; 31 ± 1 °C) groups, with six replicates (ten birds in each replicate) in each group, raised for 14 days in two environment chambers at 60 ± 7% relative humidity. Compared with the broilers in the NT group, the average daily food intake, average daily gain and breast muscle yield in the HS group were significantly lower (p < 0.05). The feed conversion ratio was significantly higher in the HS group (p < 0.05). The concentrations of serum corticosterone, free fatty acids and cholesterol and the percentage of abdominal fat of broilers in the HS group were significantly higher (p < 0.05) than the values of the broilers in the NT group. Untargeted breast muscle metabolome analysis revealed 14 upregulated differential metabolites, including glycerophosphocholine, and 27 downregulated differential metabolites, including taurine, in the HS group compared to the NT group; the HS group also displayed significant effects on six metabolic pathways compared to the NT group (p < 0.05). The mRNA expression levels of peroxisome proliferator-activated receptor gamma coactivator-1-alpha, peroxisome proliferator-activated receptor alpha (PPARα) and ATP-binding cassette transporter A1 in the liver and breast muscles were significantly decreased in the HS group compared with the NT group (p < 0.05). The collective findings reveal that HS can cause disorders in breast muscle lipid metabolism in broilers. The PPARα gene might be the key gene in the mechanism of the lipid metabolism that is induced by HS in breast muscle of broilers. These findings provide novel insights into the effects of HS on chicken growth.

Target genes regulated by CLEC16A intronic region associated with common variable immunodeficiency.

BACKGROUND: CLEC16A intron 19 has been identified as a candidate locus for common variable immunodeficiency (CVID). OBJECTIVES: This study sought to elucidate the molecular mechanism by which variants at the CLEC16A intronic locus may contribute to the pathogenesis of CVID. METHODS: The investigators performed fine-mapping of the CLEC16A locus in a CVID cohort, then deleted the candidate functional SNP in T-cell lines by the CRISPR-Cas9 technique and conducted RNA-sequencing to identify target gene(s). The interactions between the CLEC16A locus and its target genes were identified using circular chromosome conformation capture. The transcription factor complexes mediating the chromatin interactions were determined by proteomic approach. The molecular pathways regulated by the CLEC16A locus were examined by RNA-sequencing and reverse phase protein array. RESULTS: This study showed that the CLEC16A locus is an enhancer regulating expression of multiple target genes including a distant gene ATF7IP2 through chromatin interactions. Distinct transcription factor complexes mediate the chromatin interactions in an allele-specific manner. Disruption of the CLEC16A locus affects the AKT signaling pathway, as well as the molecular response of CD4+ T cells to immune stimulation. CONCLUSIONS: Through multiomics and targeted experimental approaches, this study elucidated the underlying target genes and signaling pathways involved in the genetic association of CLEC16A with CVID, and highlighted plausible molecular targets for developing novel therapeutics.

Long Non-Coding RNAs: Discoveries, Mechanisms, and Research Strategies in Seeds.

Seeds provide nutrients for the embryo and allow for dormancy in stressed environments to better adapt the plant to its environment. In addition, seeds are an essential source of food for human survival and are the basis for the formation of food production and quality. Therefore, the research on the genetic mechanism of seed development and germination will provide a theoretical basis and technical support for the improvement of crop yield and quality. Recent studies have shown that long non-coding RNAs (lncRNAs) occupy a pivotal position in seed development and germination. In this review, we describe the key processes in seed biology and examine discoveries and insights made in seed lncRNA, with emphasis on lncRNAs that regulate seed biology through multiple mechanisms. Given that thousands of lncRNAs are present in the seed transcriptome, characterization has lagged far behind identification. We provide an overview of research strategies and approaches including some exciting new techniques that may uncover the function of lncRNAs in seed. Finally, we discuss the challenges facing the field and the opening questions. All in all, we hope to provide a clear perspective on discoveries of seed lncRNA by linking discoveries, mechanisms, and technologies.

The Effect of Preventing Oxidative Stress and Its Mechanisms in the Extract from Sonchus brachyotus DC. Based on the Nrf2-Keap1-ARE Signaling Pathway.

As the organ with the largest contact area with the outside world, the intestine is home to a large number of microorganisms and carries out the main functions of food digestion, absorption, and metabolism. Therefore, there is a very active metabolism of substances and energy in the gut, which is easily attacked by oxygen free radicals. What is more, oxidative stress can gradually and slowly cause very serious damage to the gut. Hence, maintaining redox balance is essential for maintaining environmental balance in the gut. Our previous studies have demonstrated that the extract of Sonchus brachyotus DC. (SBE) has been shown to be capable of repairing oxidative damage, while it has not been demonstrated that it can prevent oxidative stress or how it develops. In this work, we investigated the prevention of oxidative stress and its mechanism in SBE based on the H2O2-induced oxidative damage model in Caco-2 cells; the results indicate that SBE can reduce the contents of ROS and MDA and increase the activities of SOD and CAT in preventing oxidative stress. Then, at the mRNA and protein level, SBE can up-regulate and down-regulate the expression of related genes (NFE2L2, KEAP1, HMOX1, NQO1, SOD1, CAT, and GPX1) and proteins involved in the Nrf2-Keap1-ARE signaling pathway. In conclusion, SBE plays a preventive role in oxidative stress through the Nrf2-Keap1-ARE signaling pathway.

Benefits of Combining Sonchus brachyotus DC. Extracts and Synbiotics in Alleviating Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease, commonly abbreviated to NAFLD, is a pervasive ailment within the digestive system, exhibiting a rising prevalence, and impacting individuals at increasingly younger ages. Those afflicted by NAFLD face a heightened vulnerability to the onset of profound liver fibrosis, cardiovascular complications, and malignancies. Currently, NAFLD poses a significant threat to human health, and there is no approved therapeutic treatment for it. Recent studies have shown that synbiotics, which regulate intestinal microecology, can positively impact glucolipid metabolism, and improve NAFLD-related indicators. Sonchus brachyotus DC., a Chinese herb, exhibits hepatoprotective and potent antioxidant properties, suggesting its potential therapeutic use in NAFLD. Our preclinical animal model investigation suggests that the synergy between Sonchus brachyotus DC. extracts and synbiotics is significantly more effective in preventing and treating NAFLD, compared to the isolated use of either component. As a result, this combination holds the potential to introduce a fresh and encouraging therapeutic approach to addressing NAFLD.

Early acquired resistance to EGFR-TKIs in lung adenocarcinomas before radiographic advanced identified by CT radiomic delta model based on two central studies.

Early acquired resistance (EAR) to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinomas before radiographic advance cannot be perceived by the naked eye. This study aimed to discover and validate a CT radiomic model to precisely identify the EAR. Training cohort (n = 67) and internal test cohort (n = 29) were from the First Affiliated Hospital of Fujian Medical University, and external test cohort (n = 29) was from the Second Affiliated Hospital of Xiamen Medical College. Follow-up CT images at three different times of each patient were collected: (1) baseline images before EGFR-TKIs therapy; (2) first follow-up images after EGFR-TKIs therapy (FFT); (3) EAR images, which were the last follow-up images before radiographic advance. The features extracted from FFT and EAR were used to construct the classic radiomic model. The delta features which were calculated by subtracting the baseline from either FFT or EAR were used to construct the delta radiomic model. The classic radiomic model achieved AUC 0.682 and 0.641 in training and internal test cohorts, respectively. The delta radiomic model achieved AUC 0.730 and 0.704 in training and internal test cohorts, respectively. Over the external test cohort, the delta radiomic model achieved AUC 0.661. The decision curve analysis showed that when threshold of the probability of the EAR to the EGFR-TKIs was between 0.3 and 0.82, the proposed model was more benefit than treating all patients. Based on two central studies, the delta radiomic model derived from the follow-up non-enhanced CT images can help clinicians to identify the EAR to EGFR-TKIs in lung adenocarcinomas before radiographic advance and optimize clinical outcomes.

Application value of CT radiomic nomogram in predicting T790M mutation of lung adenocarcinoma.

BACKGROUND: The purpose of this study was to develop a radiomic nomogram to predict T790M mutation of lung adenocarcinoma base on non-enhanced CT lung images. METHODS: This retrospective study reviewed demographic data and lung CT images of 215 lung adenocarcinoma patients with T790M gene test results. 215 patients (including 52 positive) were divided into a training set (n = 150, 36 positive) and an independent test set (n = 65, 16 positive). Multivariate logistic regression was used to select demographic data and CT semantic features to build clinical model. We extracted quantitative features from the volume of interest (VOI) of the lesion, and developed the radiomic model with different feature selection algorithms and classifiers. The models were trained by a 5-fold cross validation strategy on the training set and assessed on the test set. ROC was used to estimate the performance of the clinical model, radiomic model, and merged nomogram. RESULTS: Three demographic features (gender, smoking, emphysema) and ten radiomic features (Kruskal-Wallis as selection algorithm, LASSO Logistic Regression as classifier) were determined to build the models. The AUC of the clinical model, radiomic model, and nomogram in the test set were 0.742(95%CI, 0.619-0.843), 0.810(95%CI, 0.696-0.907), 0.841(95%CI, 0.743-0.938), respectively. The predictive efficacy of the nomogram was better than the clinical model (p = 0.042). The nomogram predicted T790M mutation with cutoff value was 0.69 and the score was above 130. CONCLUSION: The nomogram developed in this study is a non-invasive, convenient, and economical method for predicting T790M mutation of lung adenocarcinoma, which has a good prospect for clinical application.