Search

Abstract Background Colorectal cancer (CRC) is a complex malignancy characterized by diverse molecular profiles, clinical outcomes, and limited precision in prognostic markers. Addressing these challenges, this study utilized multi-omics data to define consensus molecular subtypes in CRC and elucidate their association with clinical outcomes and underlying biological processes. Methods Consensus molecular subtypes were obtained by applying ten integrated multi-omics clustering algorithms to analyze TCGA-CRC multi-omics data, including mRNA, lncRNA, miRNA, DNA methylation CpG sites, and somatic mutation data. The association of subtypes with prognoses, enrichment functions, immune status, and genomic alterations were further analyzed. Next, we conducted univariate Cox and Lasso regression analyses to investigate the potential prognostic application of biomarkers associated with multi-omics subtypes derived from weighted gene co-expression network analysis (WGCNA). The function of one of the biomarkers MID2 was validated in CRC cell lines. Results Two CRC subtypes linked to distinct clinical outcomes were identified in TCGA-CRC cohort and validated with three external datasets. The CS1 subtype exhibited a poor prognosis and was characterized by higher tumor-related Hallmark pathway activity and lower metabolism pathway activity. In addition, the CS1 was predicted to have less immunotherapy responder and exhibited more genomic alteration compared to CS2. Then a prognostic model comprising five genes was established, with patients in the high-risk group showing substantial concordance with the CS1 subtype, and those in the low-risk group with the CS2 subtype. The gene MID2, included in the prognostic model, was found to be correlated with epithelial–mesenchymal transition (EMT) pathway and distinct DNA methylation patterns. Knockdown of MID2 in CRC cells resulted in reduced colony formation, migration, and invasion capacities. Conclusion The integrative multi-omics subtypes proposed potential biomarkers for CRC and provided valuable knowledge for precision oncology.

Abstract Radiotherapy benefits patients with advanced esophageal squamous cell carcinoma (ESCC) in terms of symptom relief and long-term survival. In contrast, a substantial proportion of ESCC patients have not benefited from radiotherapy. This study aimed to establish and validate an artificial neural network-based radiomics model for the pretreatment prediction of the radiotherapy response of advanced ESCC by using integrated data combined with feasible baseline characteristics of computed tomography. A total of 248 patients with advanced ESCC who underwent baseline CT and received radiotherapy were enrolled in this study and were analyzed by two types of radiomics models, machine learning and deep learning. As a result, the Att. Resnet50 pretrained network model indicated superior performance, with AUCs of 0.876, 0.802 and 0.732 in the training, internal validation, and external validation cohorts, respectively. Similarly, our Att. Resnet50 pretrained network model showed excellent calibration and significant clinical benefit according to the C index and decision curve analysis. Herein, a novel pretreatment radiomics model was established based on deep learning methods and could be used for radiotherapy response prediction in advanced ESCC patients, thus providing reliable evidence for therapeutic decision-making.

Mining gene expression data is valuable for discovering novel biomarkers and therapeutic targets in hepatocellular carcinoma (HCC). Although emerging data mining tools are available for pan-cancer–related gene data analysis, few tools are dedicated to HCC. Moreover, tools specifically designed for HCC have restrictions such as small data scale and limited functionality. Therefore, we developed IHGA, a new interactive web server for discovering genes of interest in HCC on a large-scale and comprehensive basis. Integrative HCC Gene Analysis (IHGA) contains over 100 independent HCC patient-derived datasets (with over 10,000 tissue samples) and more than 90 cell models. IHGA allows users to conduct a series of large-scale and comprehensive analyses and data visualizations based on gene mRNA levels, including expression comparison, correlation analysis, clinical characteristics analysis, survival analysis, immune system interaction analysis, and drug sensitivity analysis. This method notably enhanced the richness of clinical data in IHGA. Additionally, IHGA integrates artificial intelligence (AI)–assisted gene screening based on natural language models. IHGA is free, user-friendly, and can effectively reduce time spent during data collection, organization, and analysis. In conclusion, IHGA is competitive in terms of data scale, data diversity, and functionality. It effectively alleviates the obstacles caused by HCC heterogeneity to data mining work and helps advance research on the molecular mechanisms of HCC.

An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation, tumor progression and metastasis. This makes iron metabolism an attractive therapeutic target. Unfortunately, current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities. We report here a dual-therapeutic prodrug, DOXjade, that allows for iron chelation chemo-photothermal cancer therapy. This prodrug takes advantage of the clinically approved iron chelator deferasirox (ExJade®) and the topoisomerase 2 inhibitor, doxorubicin (DOX). Loading DOXjade onto ultrathin 2D Ti3C2 MXene nanosheets produces a construct, Ti3C2-PVP@DOXjade, that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites, while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%. Antitumor mechanistic investigations reveal that upon activation, Ti3C2-PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor (TfR). A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo. The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.

Introduction: Evidence demonstrates that N6-methyladenosine (m6A) modification plays an increasingly important role in the development of tumors. The aim of this study is to explore the expression of m6A-related regulators in lung adenocarcinoma, identify the effect of altered key factors modified by m6A on the prognosis of patients with lung adenocarcinoma. Methods: A comprehensive analysis of m6A-related gene expressions in patients with lung adenocarcinoma based on The Cancer Genome Atlas database (TCGA) and the CBioPortal database. A prognostic risk score was established based on a linear combination of 4 key gene expression levels using the regression coefficients of the multivariate Cox regression models. Immunohistochemical staining analysis was performed to validate the relationship between the protein expression level of m6A regulators and the prognosis of patients retrospectively. The possible mechanism and prospective therapeutic targets of these key m6A molecules were explored by the M6A2Target database and the CMAP database. Results: Mutation pattern analysis revealed that 32% of 656 patients had genetic alterations. Four genes (writer: methyltransferase like 3 [METTL3] and three readers: insulin like growth factor 2 mRNA binding protein 2 [IGF2BP2], heterogeneous nuclear ribonucleoprotein C [HNRNPC], and heterogeneous nuclear ribonucleoprotein A2/B1 [HNRNPA2B1]) were selected to construct a survival risk prediction model and the results of immunohistochemical staining showed that the expression of these four m6A genes was significantly different between lung adenocarcinoma tissues and normal lung tissues ( p

Flexible polymer-based composites exhibiting high dielectric constant as well as low dielectric loss have been intensively investigated for their potential utilization in electronics and electricity industry and energy storage. Resulting from the polar -CN on the side chain, polyarylene ether nitrile (PEN) shows relatively high dielectric constant which has been extensively investigated as one of the hot spots as dielectric materials. However, the dielectric constant of PEN is still much lower than the ceramic dielectrics such as BaTiO3, TiO2, and Al2O3. In this review, recent and in-progress advancements in the designing and preparing strategies to obtain high-k PEN-based nanocomposites are summarized. According to the types of the added fillers, the effects of organic fillers, dielectric ceramic fillers, and conductive fillers on electric properties of PEN-based composites are investigated. In addition, other factors including the structures and sizes of the additive, the compatibility between the additive agent and the PEN, and the interface which affects the dielectric properties of the obtained composite materials are investigated. Finally, challenges facing in the design of more effective strategies for the high-k PEN-based dielectric materials are discussed.

Metallopolymeric superstructures (MPS) are hybrid functional materials that find wide applications in environmental, energy, catalytic and biomedical-related scenarios, while their fabrication usually suffers from the complicated polymerization between monomeric ligands and metal ions. In this work, we have developed a facile one-step protocol to fabricate metallopolymeric superstructures with different morphology including nanospheres, nanocubes, nanorods, and nanostars for environmental remediation application. Specifically, we have firstly synthesized the amphiphilic block copolymers (BCP) bearing hydrophobic aromatic backbone and hydrophilic pendent carboxylic/sulfonic groups, which have been subsequently transformed into MPS via the metal ions mediated self-assembly in mixed solution of dimethylformamide (DMF) and H2O. Based on SEM, FTIR, XRD and XPS characterization, we have revealed that the fine morphology and condensed structures of MPS can be modulated via the metal ions and BCP concentration, and the obtained MPS can be employed as efficient adsorbents for the removal of methylene blue with maximum adsorption capacity approaching 936.13 mg/g.

The 2009 swine-origin influenza virus (S-OIV) H1N1 pandemic has caused more than 18,000 deaths worldwide. Vaccines against the 2009 A/H1N1 influenza virus are useful for preventing infection and controlling the pandemic. The kinetics of the immune response following vaccination with the 2009 A/H1N1 influenza vaccine need further investigation.58 volunteers were vaccinated with a 2009 A/H1N1 pandemic influenza monovalent split-virus vaccine (15 µg, single-dose). The sera were collected before Day 0 (pre-vaccination) and on Days 3, 5, 10, 14, 21, 30, 45 and 60 post vaccination. Specific antibody responses induced by the vaccination were analyzed using hemagglutination inhibition (HI) assay and enzyme-linked immunosorbent assay (ELISA). After administration of the 2009 A/H1N1 influenza vaccine, specific and protective antibody response with a major subtype of IgG was sufficiently developed as early as Day 10 (seroprotection rate: 93%). This specific antibody response could maintain for at least 60 days without significant reduction. Antibody response induced by the 2009 A/H1N1 influenza vaccine could not render protection against seasonal H1N1 influenza (seroconversion rate: 3% on Day 21). However, volunteers with higher pre-existing seasonal influenza antibody levels (pre-vaccination HI titer ≥1∶40, Group 1) more easily developed a strong antibody protection effect against the 2009 A/H1N1 influenza vaccine as compared with those showing lower pre-existing seasonal influenza antibody levels (pre-vaccination HI titer

With the increasing incorporation of plant-based ingredients into the grouper diet, the issue of aflatoxin B1 (AFB1) contamination in the diet has become a significant concern. In this study, the negative effects of AFB1 on the growth and liver health of hybrid groupers (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂) were investigated in the context of growth, liver histology, serum biochemical indices, and integrated transcriptomic and metabolomic data. A total of 540 healthy hybrid groupers, initially weighing 11.59 ± 0.03 g, were randomly divided into six groups (three replicates of 30 fish each): the control group was fed a basal diet, and the experimental groups were supplemented with 7 (AF7), 30 (AF30), 111 (AF111), 445 (AF445) and 2230 μg/kg AFB1 (AF2230) in the basal diet respectively, for 56 days. Groups control, AF445, and AF2230 were selected for subsequent histological, muscle fatty acid, and transcriptomic and metabolomic analyses based on the results of hybrid grouper growth and serum biochemical indices. Compared to the control group, both whole-body crude lipid and muscle crude lipid contents showed significant decreases in the AF2230 group (P

The aim of study was to explore the beneficial effects of adding inositol to high-lipid diets on intestinal digestive enzymes, tissue morphology, and intestinal microbiota in juvenile hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ Epinephelus lanceolatu). Six isonitrogenous (CP 51 %) and isolipidic (CL 16 %) diets were formulated, each containing different levels of inositol: 0 % (J1, as the control group), 0.04 % (J2), 0.08 % (J3), 0.16 % (J4), 0.32 % (J5) and 0.64 % (J6) inositol. Grouper (initial body weight of 6.76 ± 0.34 g) were fed experimental diets continuously for 8 weeks. Results showed that inositol significantly increased the specific growth rate of J3, J4, J5, J6 groups compared to the control group (P > 0.05). Amylase, lipase, and trypsin activities generally increased with higher inositol levels. Amylase activities were significantly higher in J4, J5, and J6 groups compared to the control group (P < 0.05), while lipase and trypsin activities were significantly higher in all inositol-treated groups (P < 0.05). Inositol did not significantly affect intestinal plica height (P > 0.05), but increased plica width, muscularis thickness, and goblet cell number (P < 0.05). Analysis of intestinal microbiota revealed a higher number of OTUs in the J3 group compared to J1 and J6 groups (P < 0.05), with no significant differences in Ace and Chao1 indices (P > 0.05). The Simpson index was significantly higher in the J3 group compared to J1 group (P < 0.05), with no significant differences between J6 and J1, J3 groups (P > 0.05). The dominant intestinal phylum mainly consists of Proteobacteria and Cyanobacteria, while the dominant family mainly consists of Vibrionaceae and Burkholderiaceae. In summary, supplementing high-lipid diets with appropriate inositol can enhance digestive ability, improve the morphology of hybrid grouper intestines, increase the abundance of beneficial bacterial microbiota, maintain intestinal health, and promote growth.

Improvement of cultivated cotton adaptability to extreme climate events under climate change promotes sustainable cotton production. Extreme rainfall leads to a significant decrease in cotton yield, which may be related to changes in soil water consumption (SWC) and the vertical distribution of yield, but relevant research is still scarce. Here, a two-year cotton sowing date experiment was conducted in which geostatistics, sensor technology, the spatial grid method, and principal component analysis were combined to analyze cotton utilization of soil water during extreme rainfall (2021) and normal (2022) years. The reasons for cotton yield reduction under extreme rainfall and strategies to improve cotton production adaptability to extreme rainfall were discussed. Under extreme rainfall, the morphogenesis and reproductive organ development of cotton were inhibited. The accumulation of SWC and its relationship with the biomass accumulation of cotton on different sowing dates under extreme rainfall exhibited nearly opposite characteristics to those in a normal year. Simultaneously, the two-year yield showed the opposite trend with the change in sowing date. There existed a trade-off strategy for the vertical distribution (i.e., on the upper, middle and lower fruiting branches) of cotton yield. Extreme rainfall reduced the yield at lower fruiting branches and increased the boll-forming rate of the upper fruiting branches, which was closely related to seed cotton yield, lint yield and water productivity (WP). Optimizing the cotton sowing date (early sowing should be appropriate in this study) may improve the adaptability of cotton production under extreme rainfall, but further long-term studies are needed. This study highlights the critical practice of climate-smart agriculture and has reference value for the sustainable development of cotton production.

This research examined the impacts of varying silybin dosages in high-lipid diets on the growth, hepatic histology, immunity, and immune-related gene expression of juvenile hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂). The grouper (with an initial body weight of 8.27 ± 0.08 g) were fed diets containing silybin at levels of 0 g/kg (S1, control group), 0.05 g/kg (S2), 0.10 g/kg (S3), 0.15 g/kg (S4), 0.20 g/kg (S5), 0.25 g/kg (S6), and 0.50 g/kg (S7) for 8 weeks. The study results suggest that the silybin-treated groups displayed an initial increase followed by a decrease in final body weight and specific growth rate, with the highest value observed in the group S5. In serum samples, silybin supplementation of high-lipid diets resulted in increased activities of alkaline phosphatase (AKP), superoxide dismutase (SOD) and catalase (CAT) enzymes, decreased activities of aspartate transaminase (AST) and alanine transaminase (ALT) enzymes and increased total antioxidant capacity (T-AOC) content. In liver, the addition of silybin to high-lipid diets increased SOD, CAT, and lysozyme (LYZ) enzyme activities, increased T-AOC and immunoglobulin M (IgM) contents, and decreased reactive oxygen species (ROS) and malondialdehyde (MDA) contents. Contrasted with the control group, the addition of silybin at 0.05–0.50 g/kg enhanced the hepatic histomorphology, for example, ameliorating the indistinctness of cell outlines and diminishing the hepatocyte vacuolation. Silybin treatment significantly upregulated the expression of liver sod, cat, gpx, nrf2, keap1, hsp70, hsp90, tlr22, myd88, il-1β, tnf-α and il-6(P < 0.05). Silybin treatment significantly upregulated the expression of tlr22, myd88, il-1β, tnf-α, and il-6 of head kidney (P < 0.05). After vibrio harveyi challenge, groups S5-S6 showed higher survival than the control. Incorporating silybin into high-lipid diets boosts grouper's growth, antioxidant, and immune abilities. Regression analysis implies adding 0.23 g/kg silybin to the diets of juvenile hybrid grouper.

The aim of this experiment was to investigate the effects of dietary lycopene (LCP) on growth performance, antioxidant, and immunity of hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂) fed with high-lipid diets (HLD, CL16 %). Hybrid groupers (20.56±0.17 g) were selected and fed four diets containing 0, 100, 200 and 400 mg/kg of LCP, named L0, L1, L2 and L3. The results showed that: FBW and SGR were significantly higher in all dietary LCP group compared to the L0 group (P< 0.05). In serum, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) content were significantly higher in group L2 than in group L0, and alkaline phosphatase (AKP) content in L3 group was significantly lower (P< 0.05). In the liver, malondialdehyde (MDA) content were significantly lower in all LCP groups than in the L0 group (P< 0.05); catalase (CAT), AKP, and acid phosphatase (ACP) activities were significantly higher in all LCP group than in the L0 group (P< 0.05); SOD, Aspartate aminotransferase (GOT) and glutamate-pyruvate transaminase (GPT) activities in the liver were significantly higher in the L2 group than in the L0 group (P< 0.05). Dietary supplementation of 200–400 mg/kg LCP significantly up-regulated mRNA levels of hepatic sod, gsh-px, cat, nuclear factor erythroid 2-related factor 2 (nrf2), heat stimulating protein 90 (hsp90) and transforming growth factor-β (tgfβ), and significantly down-regulated mRNA levels of hepatic kelch-like ECH-associated protein 1 (keap1) and interleukin-1β (il1β) (P< 0.05). The optimal levels of LCP were 282.22 mg/kg, 246.83 mg/kg and 248.5 mg/kg for FBW, serum GSH-Px activity and hepatic immunoglobulin M (IgM) content, respectively. In conclusion, the addition of 200–300 mg/kg LCP could promote the growth performance of hybrid grouper, improve the antioxidant capacity, and alleviate the oxidative damage of liver caused by HLD.

This 60-day experiment investigated the influences of growth, fat metabolism and hepatic health of largemouth bass (Micropterus salmoides) fed varying fat diets. 225 fish (34 ± 0.04 g) were divided into three groups and fed diets with fat levels of 10 % (Low-fat diet, LFD), 14 % (Medium-fat diet, MFD) and 18 % (High-fat diet, HFD), respectively. The results revealed that fish fed HFD exhibited significantly better protein efficiency ratio (PER) and lower feed conversion ratio (FCR) than LFD group (P0.05). Dietary fat levels significantly decreased hepatosomatic index (HSI) of fish (P0.05). The contents of fat and ash in whole-body, and hepatic fat contents were increased with dietary fat levels (P0.05). Serum biochemical indexes and serum alanine aminotransferase (ALT) activity, liver glutathione peroxidase (GSH-Px) and catalase (CAT) activities were increased significantly with rising dietary fat levels (P0.05). The expression of srebp-1 and acc in liver were down-regulated, but atgl, aco and bax were up-regulated with rising dietary fat contents (P0.05). The histology of liver indicated the size and quantity of fat droplets increased with increment of dietary fat intake. Conclusion: the dietary fat levels of 14 %-18 % could be conducive to better growth of largemouth bass in this study.

Our previous study on plant oil substitution for fish oil found that corn oil induced inflammatory responses in grouper, while olive oil was effective in anti-inflammatory and immune enhancing. As a vital active ingredient in olive oil, squalene has been widely studied for its antioxidant and anti-inflammatory properties. Therefore, the present study was designed to use corn oil as the main lipid source to create a model of inflammation or low immunity and investigate the regulatory effect of squalene on the immunity of grouper, and to perform hepatic transcriptomic and metabolomic assays of grouper using omics technology, with the aim of providing basic data for the study of the mechanism of squalene. The results showed: squalene ingestion did not affect the growth performance of grouper (P > 0.05) but significantly improved immunity and the resistance of grouper to Vibrio harveyi (P

Abstract Objective To assess the efficacy of ibutilide administration during radiofrequency catheter ablation of persistent atrial fibrillation (AF), to explore the success rate of conversion and related influential factors, and to analyze the effects of ibutilide on postoperative recurrence. Methods A total of 192 patients with persistent AF who underwent catheter ablation from January 1, 2019, to December 31, 2021. These patients failed in conversion of AF to normal sinus rhythm by intraoperative catheter ablation. Patients were categorized into effective group (115 cases) and ineffective group (77 cases) based on whether sinus rhythm was restored after application of ibutilide. Results The overall success rate of conversion using ibutilide administration was 59.9%. The success rate was associated with weight ((68.12 ± 11.72 vs. 72.83 ± 12.08) kg, P = 0.008), the duration of AF ((34.67 ± 55.68 vs. 66.52 ± 95.21) months, p = 0.008), diameter of left atrium (LAD) ((44.39 ± 5.80 vs. 47.36 ± 6.10) mm,P = 0.002), and N-terminal pro-brain natriuretic peptide (NT-proBNP) level ((854.85 ± 770.84 vs. 662.88 ± 659.18) pg/ml,P = 0.030). The results showed the duration of AF was associated with early recurrence, while early recurrence was not a risk factor for late recurrence. And duration of AF was associated with postoperative maintenance time of normal sinus rhythm, whereas successful conversion into normal sinus rhythm using ibutilide administration had no influence on postoperative maintenance time of normal sinus rhythm. Conclusion Ibutilide showed to be effective in catheter ablation of AF, the success rate of conversion was correlated with the duration of AF, LA diameter, and NT-proBNP level. Besides, the duration of AF was found as a risk factor for early postoperative recurrence, while ibutilide administration for successful conversion had no influence on predicting postoperative recurrence and had no influence on postoperative maintenance time of sinus rhythm.

The study was designed to evaluate the effect of available phosphorus on growth performance, antioxidant capacity and non-specific immunity in hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatus) fed with high-lipid diets. Juvenile fish (8.06 ± 0.02 g) were subjected to six different dietary treatments over a period of eight weeks. These treatments consisted of diets (16% lipid level and 45% protein level) containing 0.3%, 0.58%, 0.67%, 0.76%, 0.85% and 0.94% available phosphorus (MCP), designated P1 (control), P2, P3, P4, P5 and P6, respectively. The results showed that (1) P1 group had suppressed final weight, weight gain and specific growth rate, while the other phosphorus experimental groups had significantly higher growth performance than the P1 group (P

Abstract Background Microbial communities are of critical importance in the human host. The lung and gut microbial communities represent the most essential microbiota within the human body, collectively referred to as the gut-lung axis. However, the differentiation between these communities and their influence on clinical outcomes in critically ill patients remains uncertain. Methods An observational cohort study was obtained in the intensive care unit (ICU) of an affiliated university hospital. Sequential samples were procured from two distinct anatomical sites, namely the respiratory and intestinal tracts, at two precisely defined time intervals: within 48 h and on day 7 following intubation. Subsequently, these samples underwent a comprehensive analysis to characterize microbial communities using 16S ribosomal RNA (rRNA) gene sequencing and to quantify concentrations of fecal short-chain fatty acids (SCFAs). The primary predictors in this investigation included lung and gut microbial diversity, along with indicator species. The primary outcome of interest was the survival status at 28 days following mechanical ventilation. Results Sixty-two mechanically ventilated critically ill patients were included in this study. Compared to the survivors, the diversity of microorganisms was significantly lower in the deceased, with a significant contribution from the gut-originated fraction of lung microorganisms. Lower concentrations of fecal SCFAs were detected in the deceased. Multivariate Cox regression analysis revealed that not only lung microbial diversity but also the abundance of Enterococcaceae from the gut were correlated with day 28 mortality. Conclusion Critically ill patients exhibited lung and gut microbial dysbiosis after mechanical ventilation, as evidenced by a significant decrease in lung microbial diversity and the proliferation of Enterococcaceae in the gut. Levels of fecal SCFAs in the deceased served as a marker of imbalance between commensal and pathogenic flora in the gut. These findings emphasize the clinical significance of microbial profiling in predicting the prognosis of ICU patients.

Abstract Considering that the benefits of hydropower stations from regulating and consuming new energy are restricted during the dry season due to the inadequate regulation capacity, this paper focuses on the accommodation capacity evaluation of hydropower for wind‐ photovoltaic (PV, for short) power generation in different supply‐grid‐load conditions. First, the factors that influence hydropower stations' accommodation capacity were initially examined in this study, in terms of power supply, power grid, and load. Then, two new indices, namely the regulatory factor of installed capacity and the regulatory factor of electric quantity, were put forward to evaluate the capacity of hydropower for accommodating wind‐PV. To reduce the peak regulation burden on the power grid and encourage the consumption of clean energy, a two‐objective optimization model with maximum source‐load matching and clean energy consumption was devised. And a two‐tier binary algorithm and progressive optimization coupled strategy was proposed to solve the model. Finally, the cascade hydropower stations in the north Panxi section of the Yalong River and the surrounding wind farm and PV power stations were taken as examples to examine the sensitivity of the factors. The results show that with each 5% increase in the regulatory electric quantity, the regulatable installed wind‐PV capacity and consumable wind‐PV electric quantity were increased by 7.57% and 8.21%, respectively, rank only second to transmission capacity. Considering the large investment required for transmission channel expansion, this result reveals that the most effective and economical way to promote wind‐PV consumption is to increase the regulated electric quantity of hydropower stations in the river basin.

Abstract Background Nuclear acetyl-CoA pools govern histone acetylation that controls synaptic plasticity and contributes to cognitive deterioration in patients with Alzheimer’s disease (AD). Nuclear acetyl-CoA pools are generated partially from local acetate that is metabolized by acetyl-CoA synthetase 2 (ACSS2). However, the underlying mechanism of histone acetylation dysregulation in AD remains poorly understood. Methods We detected ACSS2 expression and histone acetylation levels in the brains of AD patients and 5 × FAD mice. When we altered ACSS2 expression by injecting adeno-associated virus into the dorsal hippocampus of 5 × FAD mice and replenished ACSS2 substrate (acetate), we observed changes in cognitive function by Morris water maze. We next performed RNA-seq, ChIP-qPCR, and electrophysiology to study molecular mechanism underlying ACSS2-mediated spatial learning and memory in 5 × FAD mice. Results We reported that ACSS2 expression and histone acetylation (H3K9, H4K12) were reduced in the hippocampus and prefrontal cortex of 5 × FAD mice. Reduced ACSS2 levels were also observed in the temporal cortex of AD patients. 5 × FAD mice exhibited a low enrichment of acetylated histones on the promoters of NMDARs and AMPARs, together with impaired basal and activity-dependent synaptic plasticity, all of which were rescued by ACSS2 upregulation. Moreover, acetate replenishment enhanced ac-H3K9 and ac-H4K12 in 5 × FAD mice, leading to an increase of NMDARs and AMPARs and a restoration of synaptic plasticity and cognitive function in an ACSS2-dependent manner. Conclusion ACSS2 is a key molecular switch of cognitive impairment and that targeting ACSS2 or acetate administration may serve as a novel therapeutic strategy for the treatment of intermediate or advanced AD. Graphical Abstract Nuclear acetyl-CoA pools are generated partly from local acetate that is metabolized by acetyl-CoA synthetase 2 (ACSS2). Model depicts that ACSS2 expression is downregulated in the brains of 5×FAD model mice and AD patients. Of note, ACSS2 downregulation mediates a reduction in ionotropic glutamate receptor expression through histone acetylation, which exacerbates synaptic plasticity impairment in AD. These deficits can be rescued by ACSS2 upregulation or acetate supplementation (GTA, an FDA-approved food additive), which may serve as a promising therapeutic strategy for AD treatment.

ObjectivesTo investigate the etiology, clinical manifestations, imaging features, and treatment of patients with infratentorial superficial siderosis (iSS), enhance clinicians' comprehension of this rare disease, and conduct oral deferiprone intervention and subsequent monitoring.MethodsSix patients diagnosed with iSS based on magnetic resonance imaging (MRI) and susceptibility weighted imaging (SWI) were enrolled from 2021 to 2023 at the First Affiliated Hospital of Fujian Medical University. Their clinical datas were summarized, and the etiology and imaging characteristics were analyzed. Follow-up was conducted through telephone or outpatient visits.ResultsAmong the 6 patients, there were 3 males and 3 females. The onset age ranged from 35 to 71 years, with an average onset age of 53 years. The clinical symptoms mainly included acoustic disturbances (6/6), gait imbalance (6/6), dysolfactory (6/6), cognitive impairment (2/6), epilepsy (2/6), and pyramidal tract sign (2/6). Evidence of superficial siderosis was observed on MRI across the cortex, brainstem, cerebellum, and spinal cord in all patients. T2-space sequence MRI revealed two instances of dural tear. During the follow-up period ranging from 1 month to 3 years, three patients who received oral deferiprone treatment showed improvement, whereas the remaining three patients who declined deferiprone treatment demonstrated progression.ConclusionThe primary clinical manifestations of iSS include bilateral sensorineural hearing disturbances, progressive cerebellar ataxia, and spinal cord lesions. The key diagnostic criteria involve the presence of linear hypointensity on T2-WI in the surface region of the nervous system. Dural tear caused by various factors is considered to be the most common cause of iSS, and its treatment mainly involves surgical intervention for hemorrhagic primary diseases as well as pharmacotherapy with deferiprone.

This study investigated the effects of varying doses of dietary aflatoxin B1 (AFB1) on the growth, intestinal health, and muscle quality of hybrid grouper. Four diets with varying AFB1 concentrations (0, 30, 445, and 2,230 μg kg−1) were used. Elevating AFB1 concentrations led to a decline in growth indexes, specifically the weight gain rate and the specific growth rate, although the survival rate remained unchanged. Morphological indicators showed a dose-dependent decline with AFB1 exposure. Intestinal MDA content and hindgut reactive oxygen species (ROS) levels increased, while antioxidant indexes and digestive enzymes decreased with higher AFB1 levels. AFB1 negatively influenced hindgut tight junction protein and antioxidant-related gene expression while promoting inflammation-related gene expression. The presence of AFB1 in the experiment led to a decrease in beneficial intestinal bacteria, such as Prevotella, and an increase in harmful intestinal bacteria, such as Prevotellaceae_NK3B31_group. Muscle lipid and unsaturated fatty acid content significantly decreased, while muscle protein and liver AFB1 content increased dramatically with higher AFB1 concentrations. AFB1 caused myofibrillar cleavage and myofilament damage, leading to increased spaces between muscle fibers. In conclusion, diets with AFB1 levels exceeding 30 μg kg−1 inhibited hybrid grouper growth, while levels surpassing 445 μg kg−1 resulted in hindgut ROS accumulation, inflammation, elevated intestinal permeability, reduced digestive enzyme activity, and compromised muscle quality.

BackgroundThe characteristics of aortic annulus changes in aortic regurgitation (AR) patients are poorly understood, and predictive factors among aortic valve disease are yet to be established.ObjectiveThis study seeks to elucidate the pattern of annular size fluctuations across different cardiac phases in AR patients and to identify predictors for annular enlargement during either systole or diastole in aortic valve diseases.MethodsA retrospective analysis was conducted on 55 patients with severe aortic valve diseases, including 26 patients with aortic stenosis (AS) and 29 with AR, to discern the two groups' contrasting and analogous patterns of annular changes. The patient sample was expanded to 107 to investigate the factors influencing the size of the annulus during different cardiac phases. Based on our findings, patients were then divided into two groups: those with an annulus that is larger during systole (83 patients) and those where the annulus is larger during diastole (24 patients).ResultsTypically, AR patients exhibit a dynamic annulus, with both perimeter and area being largest during mid-systole. These dimensions diminish progressively and then increase again in early diastole, a pattern consistent with observations in AS patients. Among 107 patients, 21% had diastolic enlargement. Systolic measurements would lead to prosthesis undersizing in 17% of these. Male gender and lower systolic annulus minimum relative to body surface area (AnMin index) were predictors of diastolic enlargement, with ROC curve areas of 0.70 and 0.87 for AR and AS, respectively.ConclusionsSystolic measurements are recommended for AR patients. Gender and the AnMin index are significant predictors, particularly potent in AS patients.

Background: The etiology of aortic stenosis (AS) significantly impacts transcatheter heart valve (THV) implantation, with rheumatic etiology posing challenges. The concept of valve anchoring during transcatheter aortic valve replacement (TAVR) for patients with aortic regurgitation (AR) remains unclear. Objective: This study aims to investigate the clinical and CT anatomical characteristics of various aortic valve diseases. Methods: A retrospective analysis was conducted on consecutive patients who underwent CT for severe aortic diseases between April 2019 and February 2023. CT analysis was performed in eight anatomical landmarks: left ventricular outflow tract (LVOT), aortic annulus, sinus of Valsalva (SOV), sinotubular junction (STJ), ascending aorta (AAO), coronary height, aortic angle, and aortic valve calcification volume. Results: 121 patients with severe aortic valve disease were included, divided into AS (71 cases, 59%) and AR (50 cases, 41%) groups. In patients with AR, the absolute diameters of the annulus, LVOT, SOV, STJ, and AAO, as well as the heights of SOV and STJ and the cardiac angle, are larger than those in patients with AS (all P

We previously found that squalene may influence immunity of grouper by affecting the Wnt/β-Catenin signaling pathway, but the exact mechanism is uncertain. We thus propose to interfere with the Wnt/β-Catenin signaling pathway and downstream pathways by intraperitoneal injection of PBS buffer (PBS), squalene (Sq), squalene + TWS119 (Wnt/β-Catenin signaling pathway activator, Sq + TWS119), and squalene + IWR-1 (Wnt/β-Catenin signaling pathway inhibitor, Sq + IWR-1) to initially elucidate the mechanism of squalene in hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatu). The results showed: The injection test did not damage the liver structure of grouper, but Sq and Sq+TWS119 groups significantly increased the survival of Vibrio harveyi challenged and antioxidant capacity of grouper, and Sq+IWR-1 significantly decreased the survival of Vibrio harveyi challenged in grouper. The Sq and Sq+TWS119 groups activated the PI3K-Akt and Wnt/β-Catenin signaling pathway and upregulated the expression of anti-inflammatory factors in the NF-κB pathway, whereas Sq+IWR-1 inhibited the PI3K-Akt and Wnt/β-Catenin signaling pathway and upregulated the expression of pro-inflammatory factors in the NF-κB pathway. Conclusively, squalene can activate the PI3K-Akt-regulated Wnt/β-Catenin signaling pathway by binding to the interleukin 21 receptor, and the activation of Wnt/β-Catenin signaling pathway can inhibit NF-κB-mediated inflammatory response, consequently improving the immunity and disease resistance of grouper. It is expected that the regulation of NF-κB signaling pathway by Wnt/β-Catenin signaling pathway would contribute to the treatment the inflammation and inflammation-related diseases, and of course provide potential for the prevention of inflammation in aquaculture animals.

With the increasing consumption of plant-based ingredients in aquafeeds, aflatoxin B1 (AFB1) contamination has become an issue of concern. This experiment aimed to investigate the effect of dietary AFB1 levels on the growth and liver function of hybrid grouper and the mechanisms involved. Six diets with different AFB1 levels were formulated at concentrations of 0 μgkg−1 (AFB0), seven μgkg−1 (AFB7), 30 μgkg−1 (AFB30), 111 μgkg−1 (AFB111), 445 μgkg−1 (AFB445) and 2230 μgkg−1 (AFB2230). A total of 540 healthy hybrid grouper with an initial weight of 11.59 ± 0.03 g were selected and randomly divided into six groups of three replicates of 30 fish each for a trial period of eight weeks. The results showed that with increasing dietary AFB1 levels, growth performance decreased, feed conversion ratio increased, and serum liver damage indicators increased. Liver section results also showed a significant hepatic inflammatory response and increased liver ROS levels in the high AFB1 dietary dose group. In addition, combined with the expression of critical genes in the liver, it was shown that high dietary AFB1 levels disrupted normal liver lipid and protein metabolism, reduced liver antioxidant capacity, and upregulated liver inflammation-related gene expression.

Due to its randomness, intermittence, and volatility, the high-proportional integration of wind and solar power poses challenges to the safe and stable operation of power systems. Cascade hydropower stations have a high response speed, high adjustability, and stable output. This study proposed a hydro-wind-solar hybrid system and investigated its short-term optimal coordinated operation based on deep learning and a double-layer nesting algorithm. A stochastic complementary scheduling model was constructed to maximize the cascade energy storage. The particle swarm optimization algorithm-dynamic programming (PSO-DP) coupled with the inner and outer nesting optimization algorithm reduces the problem-solving complexity. The hybrid system was applied to a national comprehensive development base of renewable energy with integrated wind, solar, and hydropower in China. Studies have shown the following: The hydro-wind-solar hybrid system has a certain degree of scalability. The utilization of deep learning methods can fully consider the uncertainty of wind and solar. The internal and external nested optimization algorithm, which realizes the reasonable and efficient distribution of water and electricity, and improves the future power generation capacity of cascade hydropower stations, was used to solve the problem. This study provided a valuable reference for the large-scale utilization of other renewable energy sources worldwide.

This study aimed to assess the impact of α-lipoic acid on the growth performance, antioxidant capacity and immunity in hybrid groupers (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatus) fed with a high-lipid diet. Groupers (8.97 ± 0.01 g) were fed six different diets, with α-lipoic acid content in diets being 0, 400, 800, 1200, 1600, and 2000 mg/kg, named S1, S2, S3, S4, S5, and S6, respectively. The results show that the addition of 2000 mg/kg α-lipoic acid in the diet inhibited the growth, weight gain rate (WGR), and specific growth rate (SGR), which were significantly lower than other groups. In serum, catalase (CAT) and superoxide dismutase (SOD) were significantly higher in the S5 group than in the S1 group. In the liver, CAT, SOD and total antioxidative capacity (T-AOC) levels were significantly increased in α-lipoic acid supplemented groups. α-lipoic acid significantly upregulated liver antioxidant genes sod and cat, anti-inflammatory factor interleukin 10 (il10) and transforming growth factor β (tgfβ) mRNA levels. Conclusion: the addition of 2000 mg/kg of α-lipoic acid inhibits the growth of hybrid groupers. In addition, 400–800 mg/kg α-lipoic acid contents improve the antioxidant capacity of groupers and have a protective effect against high-lipid-diet-induced liver oxidative damage.