Response signatures of intestinal microbiota and gene transcription of yellow catfish (Pelteobagrus fulvidraco) to Aeromonas hydrophila infection.

Bacterial intestinal inflammation is a common disease of yellow catfish (Pelteobagrus fulvidraco) in high-density aquaculture. Understanding the interactions between host and intestinal bacteria is helpful to intestinal inflammatory disease control. Here, we constructed a model of intestinal inflammation after Aeromonas hydrophila infection in yellow catfish, and characterized variations in gene expression and microbiome in the gut through high-throughput sequencing. Furthermore, host gene-microbiome interactions were identified. Histology observation showed disordered distribution of columnar epithelial cells and decrease of goblet cells in intestine. A total of 4741 genes showed differentially expression, mostly in comparisons between 12 hpi group with each other groups respectively, including control, 24 hpi and 48 hpi groups. These genes were enriched in immune-related pathways including the IL-17 signaling pathway, triggering strong inflammatory response at the invading stage within 12 h. Subsequently, the host strengthened energy consumption by activating carbohydrate and lipid metabolism pathways to repair the intestinal mucosal immune defense line. In addition, fish with A. hydrophila infection show decreased richness of gut microbial, reduced relative abundance of probiotics including Akkermansia, and elevated pathogenic bacteria such as Plesimonas. An integrative analysis identified A. hydrophila-related genes, such as il22 and stat3, for which expression level is close associated with the shift of A. hydrophila-related bacteria relative abundance, such as Akkermansia and Cetobacterium. Aside from picturing the variations of intestine gene expression and mucosal microbiome of yellow catfish coping with A. hydrophila infection, our study probed the underlying host-microbe interactions in A. hydrophila infection induced intestinal inflammatory, providing new insights for disease control in aquaculture.

Effects of Aeromonas infection on the immune system, physical barriers and microflora structure in the intestine of juvenile grass carp (Ctenopharyngodon idella).

Grass carp (Ctenopharyngodon idella) is an intensively cultured and economically important herbivorous fish species in China, but its culture is often impacted by Aeromonas pathogens such as Aeromonas hydrophila and Aeromonas veronii. In this study, healthy grass carp were separately infected with A. hydrophila or A. veronii for 12, 24, 48 or 72 h. The results showed that the mRNA expression levels of intestinal inflammatory factors (tnf-α, il-1ß and il-8), complement factors (c3 and c4), antimicrobial peptides (hepcidin, nk-lysin and ß-defensin-1), immunoglobulins (igm and igt), and immune pathway-related signaling molecules (tlr1, tlr2, tlr4, myd88, irak4, irak1, traf6, nf-κb p65 and ap-1) were differentially upregulated in response to A. hydrophila and A. veronii challenge. Additionally, the expression levels of the intestinal pro-apoptotic genes tnfr1, tnfr2, tradd, caspase-8, caspase-3 and bax were significantly increased, whereas the expression of the inhibitory factor bcl-2 was significantly downregulated, indicating that Aeromonas infection significantly induced apoptosis in the intestine of grass carp. Moreover, the expression of intestinal tight junction proteins (occludin, zo-1, claudin b and claudin c) was significantly decreased after infection with Aeromonas. Histopathological analysis indicated the Aeromonas challenge caused severe damage to the intestinal villi with adhesions and detachment of intestinal villi accompanied by severe inflammatory cell infiltration at 12 h and 72 h. The 16S rRNA sequencing results showed that Aeromonas infection significantly altered the structure of the intestinal microflora of the grass carp at the phylum (Proteobacteria, Fusobacteria, Bacteroidetes and Firmicutes) and genus (Proteus, Cetobacterium, Bacteroides, and Aeromonas) levels. Take together, the findings of this study revealed that Aeromonas infection induces an intestinal immune response, triggers cell apoptosis, destroys physical barriers and alters microflora structure in the intestine of juvenile grass carp; the results will help to reveal the pathogenesis of intestinal bacterial diseases in grass carp.

Long-term exposure to ambient fine particulate matter constituents and mortality from total and site-specific gastrointestinal cancer.

BACKGROUND: Ambient fine particulate matter (PM2.5) exposure has been associated with an increased risk of gastrointestinal cancer mortality, but the attributable constituents remain unclear. OBJECTIVES: To investigate the association of long-term exposure to PM2.5 constituents with total and site-specific gastrointestinal cancer mortality using a difference-in-differences approach in Jiangsu province, China during 2015-2020. METHODS: We split Jiangsu into 53 spatial units and computed their yearly death number of total gastrointestinal, esophagus, stomach, colorectum, liver, and pancreas cancer. Utilizing a high-quality grid dataset on PM2.5 constituents, we estimated 10-year population-weighted exposure to black carbon (BC), organic carbon (OC), sulfate, nitrate, ammonium, and chloride in each spatial unit. The effect of constituents on gastrointestinal cancer mortality was assessed by controlling time trends, spatial differences, gross domestic product (GDP), and seasonal temperatures. RESULTS: Overall, 524,019 gastrointestinal cancer deaths were ascertained in 84.77 million population. Each interquartile range increment of BC (0.46 µg/m3), OC (4.56 µg/m3), and nitrate (1.41 µg/m3) was significantly associated with a 27%, 26%, and 34% increased risk of total gastrointestinal cancer mortality, respectively, and these associations remained significant in PM2.5-adjusted models and constituent-residual models. We also identified robust associations of BC, OC, and nitrate exposures with site-specific gastrointestinal cancer mortality. The mortality risk generally displayed increased trends across the total exposure range and rose steeper at higher levels. We did not identify robust associations for sulfate, ammonium, or chlorine exposure. Higher mortality risk ascribed to constituent exposures was identified in total gastrointestinal and liver cancer among women, stomach cancer among men, and total gastrointestinal and stomach cancer among low-GDP regions. CONCLUSIONS: This study offers consistent evidence that long-term exposure to PM2.5-bound BC, OC, and nitrate is associated with total and site-specific gastrointestinal cancer mortality, indicating that these constituents need to be controlled to mitigate the adverse effect of PM2.5 on gastrointestinal cancer mortality.

The impact of digital infrastructure on provincial green innovation efficiency-empirical evidence from China.

In the epoch of the digital economy, technological innovation and energy conservation are significantly facilitated by digital infrastructure, leading to substantial improvements in green innovation efficiency at the provincial level. This study employed the feasible generalized least square (FGLS) method to examine the effects of digital infrastructure on the green innovation efficiency across 30 provinces in the Chinese mainland, utilizing panel data from 2011 to 2020. Additionally, this investigation delves into the intervening role of industrial structure upgrading and the amplifying effects of environmental regulation and human capital on the process. Findings indicate that, to begin with, digital infrastructure contributes to the meaningful enhancement of green innovation efficiency within provinces. Subsequently, the industrial structure upgrading partially mediates the impact of digital infrastructure on the efficiency of provincial green innovation. Lastly, both human capital and environmental regulations amplify the beneficial influence of digital infrastructure on the effectiveness of green innovation at the provincial level. This study provides valuable insights into the mechanisms through which digital infrastructure boosts green innovation efficiency, aiding policymakers in formulating appropriate policies to augment digital infrastructure, thereby promoting provincial green innovation efficiency.

Real-world safety of Levetiracetam: Mining and analysis of its adverse drug reactions based on FAERS database.

INTRODUCTION: Levetiracetam is a relatively new and widely utilized anti-seizure medication; however, limited information is available regarding its adverse effects. This study aims to thoroughly investigate, evaluate, and present evidence on the safety profile of Levetiracetam, relying on data from the FDA Adverse Event Reporting System (FAERS) database to facilitate informed clinical decision-making. METHODS: We employed various statistical measures, including Reporting Odds Ratio (ROR), Proportionate Reporting Ratio (PRR), and analysis by the Medicines and Healthcare Products Regulatory Agency (MHRA), to identify signals of adverse reactions associated with Levetiracetam. Positive signals consistent with Designated Medical Event (DME) were singled out for focused comparison and discussion. RESULTS: The analysis of 26,182 adverse events linked to Levetiracetam as the primary suspected drug revealed 692 positive signals spanning 22 System Organ Classes (SOCs). Nervous system disorders were the most frequently reported, followed by psychiatric disorders, and general disorders and administration site conditions. 11 positive signals consistent with Preferred Terms (PTs) in DME were identified, predominantly concentrated in 6 SOCs. Among these, rhabdomyolysis, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) exhibited relatively large values of A, ROR, and Chi-squared. Additionally, PTs related to spontaneous abortion, drug interaction, urethral atresia, ventricular septal defect, and atrial septal defect showed significant strength. CONCLUSIONS: The study indicates that Levetiracetam carries a potential risk of causing rhabdomyolysis, SJS, TEN, DRESS as well as spontaneous abortion. Signals related to drug interaction, urethral atresia, ventricular septal defect, and atrial septal defect warrant heightened attention in clinical use.

Gradient-based optimization for quantum architecture search.

Quantum Architecture Search (QAS) has shown significant promise in designing quantum circuits for Variational Quantum Algorithms (VQAs). However, existing QAS algorithms primarily explore circuit architectures within a discrete space, which is inherently inefficient. In this paper, we propose a Gradient-based Optimization for Quantum Architecture Search (GQAS), which leverages a circuit encoder, decoder, and predictor. Initially, the encoder embeds circuit architectures into a continuous latent representation. Subsequently, a predictor utilizes this continuous latent representation as input and outputs an estimated performance for the given architecture. The latent representation is then optimized through gradient descent within the continuous latent space based on the predicted performance. The optimized latent representation is finally mapped back to a discrete architecture via the decoder. To enhance the quality of the latent representation, we pre-train the encoder on a substantial dataset of circuit architectures using Self-Supervised Learning (SSL). Our simulation results on the Variational Quantum Eigensolver (VQE) indicate that our method outperforms the current Differentiable Quantum Architecture Search (DQAS).

Predicting the Prognosis of HIFU Ablation of Uterine Fibroids Using a Deep Learning-Based 3D Super-Resolution DWI Radiomics Model: A Multicenter Study.

RATIONALE AND OBJECTIVES: To assess the feasibility and efficacy of a deep learning-based three-dimensional (3D) super-resolution diffusion-weighted imaging (DWI) radiomics model in predicting the prognosis of high-intensity focused ultrasound (HIFU) ablation of uterine fibroids. METHODS: This retrospective study included 360 patients with uterine fibroids who received HIFU treatment, including Center A (training set: N = 240; internal testing set: N = 60) and Center B (external testing set: N = 60) and were classified as having a favorable or unfavorable prognosis based on the postoperative non-perfusion volume ratio. A deep transfer learning approach was used to construct super-resolution DWI (SR-DWI) based on conventional high-resolution DWI (HR-DWI), and 1198 radiomics features were extracted from manually segmented regions of interest in both image types. Following data preprocessing and feature selection, radiomics models were constructed for HR-DWI and SR-DWI using Support Vector Machine (SVM), Random Forest (RF), and Light Gradient Boosting Machine (LightGBM) algorithms, with performance evaluated using area under the curve (AUC) and decision curves. RESULT: All DWI radiomics models demonstrated superior AUC in predicting HIFU ablated uterine fibroids prognosis compared to expert radiologists (AUC: 0.706, 95% CI: 0.647-0.748). When utilizing different machine learning algorithms, the HR-DWI model achieved AUC values of 0.805 (95% CI: 0.679-0.931) with SVM, 0.797 (95% CI: 0.672-0.921) with RF, and 0.770 (95% CI: 0.631-0.908) with LightGBM. Meanwhile, the SR-DWI model outperformed the HR-DWI model (P < 0.05) across all algorithms, with AUC values of 0.868 (95% CI: 0.775-0.960) with SVM, 0.824 (95% CI: 0.715-0.934) with RF, and 0.821 (95% CI: 0.709-0.933) with LightGBM. And decision curve analysis further confirmed the good clinical value of the models. CONCLUSION: Deep learning-based 3D SR-DWI radiomics model demonstrated favorable feasibility and effectiveness in predicting the prognosis of HIFU ablated uterine fibroids, which was superior to HR-DWI model and assessment by expert radiologists.

Novel Ag3PO4/ZnWO4-modified graphite felt electrode for photoelectrocatalytic removal of harmful algae: Performance and mechanism.

A novel Ag3PO4/ZnWO4-modified graphite felt electrode (AZW@GF) was prepared by drop coating method and applied to photoelectrocatalytic removal of harmful algae. Results showed that approximately 99.21% of chlorophyll a and 91.57% of Microcystin-LR (MCLR) were degraded by the AZW@GF-Pt photoelectrocatalytic system under the optimal operating conditions with a rate constant of 0.02617 min-1 and 0.01416 min-1, respectively. The calculated synergistic coefficient of photoelectrocatalytic algal removal and MC-LR degradation by the AZW@GF-Pt system was both larger than 1.9. In addition, the experiments of quenching experiments and electron spin resonance (ESR) revealed that the photoelectrocatalytic reaction mainly generated •OH and •O2- for algal removal and MC-LR degradation. Furthermore, the potential pathway for photoelectrocatalytic degradation of MC-LR was proposed. Finally, the photoelectrocatalytic cycle algae removal experiments were carried out on AZW@GF electrode, which was found to maintain the algae removal efficiency at about 91% after three cycles of use, indicating that the photoelectrocatalysis of AZW@GF electrode is an effective emergency algae removal technology.

A biguanide chitosan-based hydrogel adhesive accelerates the healing of bacterial-infected wounds.

The development of tissue adhesives with good biocompatibility and potent antimicrobial properties is crucial for addressing the high incidence of surgical site infections in emergency and clinical settings. Herein, an injectable hydrogel adhesive composed of chitosan biguanidine (CSG), oxidized dextran (ODex) and tannin (TA) was synthesized primarily through Schiff-base reactions, hydrogen bonding, and electrostatic interactions. TA was introduced into the CSG/ODex hydrogel to prepare a physicochemically double cross-linked hydrogel. The hydrogel formulation incorporating 2 wt% TA (CSG/ODex-TA2) exhibited rapid gelation, moderate mechanical properties, good tissue adhesion, and sustained release behavior of TA. Both in vitro and in vivo studies demonstrated that CSG/ODex-TA2 showed significantly enhanced adhesion and antibacterial effectiveness compared to the CSG/ODex hydrogel and commercial fibrin glue. Leveraging the positive charge of CSG, the CSG/ODex-TA2 hydrogel demonstrated a strong contact antibacterial effect, while the sustained release of TA provided diffusion antibacterial capabilities. By integrating contact and diffusion antibacterial mechanisms into the hydrogel, a promising approach was developed to boost antibacterial efficiency and accelerate the healing of wounds infected with methicillin-resistant Staphylococcus aureus (MRSA). The CSG/ODex-TA2 hydrogel has excellent biocompatibility, hemostatic properties, and antibacterial capabilities, making it a promising candidate for improving in vivo wound care and combating bacterial infections.

The TGFß2-Snail1-miRNATGFß2 Circuitry is Critical for the Development of Aggressive Functions in Breast Cancer.

There have been contradictory reports on the biological role of transforming growth factor-ßs (TGFßs) in breast cancer (BC), especially with regard to their ability to promote epithelial-mesenchymal transition (EMT). Here, we show that TGFß2 is preferentially expressed in mesenchymal-like BCs and maintains the EMT phenotype, correlating with cancer stem cell-like characteristics, growth, metastasis and chemo-resistance and predicting worse clinical outcomes. However, this is only true in ERα- BC. In ERα+ luminal-type BC, estrogen receptor interacts with p-Smads to block TGFß signalling. Furthermore, we also identify a microRNAs (miRNAs) signature (miRNAsTGFß2 ) that is weakened in TGFß2-overexpressing BC cells. We discover that TGFß2-Snail1 recruits enhancer of zeste homolog-2 to convert miRNAsTGFß2 promoters from an active to repressive chromatin configuration and then repress miRNAsTGFß2 transcription, forming a negative feedback loop. On the other hand, miRNAsTGFß2 overexpression reverses the mesenchymal-like traits in agreement with the inhibition of TGFß2-Snail1 signalling in BC cells. These findings clarify the roles of TGFß2 in BC and suggest novel therapeutic strategies based on the TGFß2-Snail1-miRNAsTGFß2 loop for a subset type of human BCs.

A new raspberry ketone synthesis gene RinPKS4 identified in Rubus idaeus L. by transcriptome analysis.

Raspberry ketone accounts for the characteristic aroma of the raspberry fruit. In order to explore the genes involved in raspberry ketone synthesis, the transcriptome in fruit tissues of two red raspberry varieties "Polka" and "Orange legend", were sequenced and 24213 single genes were obtained. As the red raspberry fruit ripening, genes involved in flavonoid and anthocyanin synthesis were up-regulated, while those associated with lignin synthesis were down-regulated. A gene (RinPKS4) highly related to raspberry ketone synthesis was identified by transcriptome analysis, and RinPKS4 gene was over-expressed in raspberry in order to further understand the function of RinPKS4 gene in raspberry ketone synthesis. The results showed that the gene expression level of RinPKS4 in the leaf tissues of a transgenic lines increased by about 4-fold and the content of raspberry ketone increased by 42.64% compared with the wide type. This study lays a theoretical foundation for further study on the synthesis and regulation of raspberry ketone in red raspberry.

Insights into Dietary Different Co-Forms of Lysine and Glutamate on Growth Performance, Muscle Development, Antioxidation and Related Gene Expressions in Juvenile Grass Carp (Ctenopharyngodon idellus).

The study aimed to compare the effects of crystalline L-lysine and L-glutamate (CAA), Lys-Glu dipeptide (KE) on the growth and muscle development of grass carp (Ctenopharyngodon idellus), and related molecular mechanisms. Five experimental diets (CR, 0.5% CAA, 1.5% CAA, 0.5% KE, 1.5% KE) containing Lys and Glu as free (Lys and Glu, CAA) dipeptide (Lys-Glu, KE) forms were prepared, respectively. A total of 450 juvenile grass carp with an initial weight of 10.69 ± 0.07 g were randomly assigned to 15 cages, and 5 treatments with 3 replicates of 30 fish each for 61 days of feeding. The results showed that the group of 0.5% KE exhibited the best growth performances according to the indicator's weight gain rate (WGR) and specific growth rate (SGR), although no statistically significant occurred among all groups; diet supplemented with 0.5% CAA significantly elevated the condition factor (CF) and viscerasomatic index (VSI) of juvenile grass carp. Diet supplemented with different Lys and Glu co-forms at different levels promoted the muscle amino acid content compared with those of CR group. Comparing with the CR group and other groups, the hardness of 0.5% CAA group significantly increased, and the springiness of 0.5% KE group excelled. Both the muscle fiber diameter and density of 0.5% KE group showed significant difference with those of the CR group, and a negative correlation between them was also observed. To uncover the related molecular mechanism of the differences caused by the different co-forms of Lys and Glu, the effect of different diets on the expressions of protein absorption, muscle quality, and antioxidation-related genes was analyzed. The results suggested that comparing with those of CR group, the dipeptide KE inhibited the expressions of genes associated with protein metabolism, such as AKT, S6K1, and FoxO1a but promoted PCNA expression, while the free style of CAA would improve the FoxO1a expression. Additionally, the muscle development-related genes (MyoD, MyOG, and Myf5) were significantly boosted in CAA co-form groups, and the expressions of fMYHCs were blocked but fMYHCs30 significantly promoted in 0.5% KE group. Finally, the effect of different co-forms of Lys and Glu on muscle antioxidant was examined. The 0.5% CAA diet was verified to increase GPX1a but obstruct Keap1 and GSTP1 expressions, resulting in enhanced SOD activity and reduced MDA levels in plasma. Collectively, the different co-forms of Lys and Glu influenced the growth of juvenile grass carp, and also the muscle development and quality through their different regulation on the protein metabolism, muscle development- and antioxidative-related genes.

TRIM33 plays a critical role in regulating dendritic cell differentiation and homeostasis by modulating Irf8 and Bcl2l11 transcription.

The development of distinct dendritic cell (DC) subsets, namely, plasmacytoid DCs (pDCs) and conventional DC subsets (cDC1s and cDC2s), is controlled by specific transcription factors. IRF8 is essential for the fate specification of cDC1s. However, how the expression of Irf8 is regulated is not fully understood. In this study, we identified TRIM33 as a critical regulator of DC differentiation and maintenance. TRIM33 deletion in Trim33fl/fl Cre-ERT2 mice significantly impaired DC differentiation from hematopoietic progenitors at different developmental stages. TRIM33 deficiency downregulated the expression of multiple genes associated with DC differentiation in these progenitors. TRIM33 promoted the transcription of Irf8 to facilitate the differentiation of cDC1s by maintaining adequate CDK9 and Ser2 phosphorylated RNA polymerase II (S2 Pol II) levels at Irf8 gene sites. Moreover, TRIM33 prevented the apoptosis of DCs and progenitors by directly suppressing the PU.1-mediated transcription of Bcl2l11, thereby maintaining DC homeostasis. Taken together, our findings identified TRIM33 as a novel and crucial regulator of DC differentiation and maintenance through the modulation of Irf8 and Bcl2l11 expression. The finding that TRIM33 functions as a critical regulator of both DC differentiation and survival provides potential benefits for devising DC-based immune interventions and therapies.

Risk factors for surgical site infection of pilon fractures

OBJECTIVES: Pilon fracture is a complex injury that is often associated with severe soft tissue damage and high rates of surgical site infection. The goal of this study was to analyze and identify independent risk factors for surgical site infection among patients undergoing surgical fixation of a pilon fracture. METHODS: The medical records of all pilon fracture patients who underwent surgical fixation from January 2010 to October 2012 were reviewed to identify those who developed a surgical site infection. Then, we constructed univariate and multivariate logistic regressions to evaluate the independent associations of potential risk factors with surgical site infection in patients undergoing surgical fixation of a pilon fracture. RESULTS: A total of 519 patients were enrolled in the study from January 2010 to October 2012. A total of 12 of the 519 patients developed a surgical site infection, for an incidence of 2.3%. These patients were followed for 12 to 29 months, with an average follow-up period of 19.1 months. In the final regression model, open fracture, elevated postoperative glucose levels (≥125 mg/dL), and a surgery duration of more than 150 minutes were significant risk factors for surgical site infection following surgical fixation of a pilon fracture. CONCLUSIONS: Open fractures, elevated postoperative glucose levels (≥125 mg/dL), and a surgery duration of more than 150 minutes were related to an increased risk for surgical site infection following surgical fixation of a pilon fracture. Patients exhibiting the risk factors identified in this study should be counseled regarding the possible surgical site infection that may develop after surgical fixation. .