While microbial bioremediation is a promising strategy for antibiotic removal, the potential of fungi in mitigating antibiotic contamination and its associated ecological impacts in aquaculture systems remains largely unexplored. This study evaluated the bioremediation efficacy of the fungus Cladosporium cladosporioides 11 (CC11) in a simulated aquaculture ecosystem. The introduction of CC11 significantly accelerated enrofloxacin (ENR) removal in the aquaculture system and mitigated ENR bioaccumulation in crucian carp. Meanwhile, CC11 application notably lowered the accumulation of total nitrogen and ammonium nitrogen in the water column. Metagenomic analysis revealed that CC11 helped maintain a more active nitrogen-cycling microbial community, sustaining higher abundances of key genes involved in nitrogen fixation (nifB/K/T/Z) and assimilatory nitrate reduction (nasA/C/E/B/D) under ENR stress. Furthermore, CC11 restored specific bacterial taxa correlated with these functional genes, including methylotrophs associated with nif genes and Comamonadaceae members linked to nas genes, thereby reinforcing the functional network for nitrogen transformation. These findings demonstrate that CC11 acts as a multifunctional bioremediation agent, capable of simultaneously enhancing antibiotic removal and regulating nitrogen dynamics, offering a sustainable strategy for managing ENR pollution in aquaculture environments.
This study aimed to explore the construction and application of a nomogram model for early-stage cervical central lymph node metastasis (CLNM) in papillary thyroid cancer (PTC) combined with Hashimoto's thyroiditis (HT). The study included 360 patients with pathologically diagnosed PTC. Of these, 100 patients had PTC with concurrent HT. Univariate and multivariate analyses were conducted to identify risk factors for CLNM in patients with PTC and HT. A nomogram was designed to guide clinical decision-making. Age, gender, thyroid peroxidase antibody status, tumor diameter, tumor location, multifocal lesions, capsular invasion, calcification, aspect ratio ≥1, irregular morphology, and tumor diameter ≥1 cm strongly correlated with CLNM in patients with PTC combined with HT. Notably, capsular invasion, aspect ratio ≥1, calcification, and irregular morphology were risk factors for CLNM in patients with PTC combined with HT. A nomogram was constructed to visualize and graphically calculate the probability of CLNM development in these patients. Our findings indicated that the independent risk factors for CLNM development in patients with PTC combined with HT are capsular invasion, aspect ratio ≥1, calcification, and irregular morphology. The nomogram model developed in this study has great potential for clinical applications.
The efficacy of diversion ileostomy followed by radical surgery for locally advanced upper-half rectal cancer remains uncertain. This study seeks to compare the effectiveness of treatment with and without diversion ileostomy in preventing anastomotic leakage (AL) and to identify a subset who may benefit from diversion ileostomy after AL occurs in Chinese patients with stage II and III upper-half rectal cancer. A retrospective study enrolled a total of 809 patients with locally advanced upper-half rectal cancer between 2017 and 2021, with 27.6% (n = 223) treated with diversion ileostomy and 72.4% (n = 586) treated without diversion ileostomy. The Diversion(+) group (n = 172) and Diversion(-) group (n = 172) were compared for perioperative outcomes through 1:1 propensity score matching (PSM). The selection of variables for multivariable logistic regression was determined through bivariate logistic regression analysis. Additionally, optimal cutoff values for risk factors were identified using ROC curve analysis. Within the entire cohort, patients in the Diversion(+) group exhibited a lower distance from the anal verge (DAV) and higher rates of chemoradiotherapy (CRT), diabetes, cN2 stage, mrCRM positivity, EMVI positivity, and CEA elevation compared to those in the Diversion(-) group. Following PSM, a satisfactory balance of baseline variables was achieved between the two groups. There were no statistically significant differences in AL rates (7.0% vs. 5.8%, p = 0.659) or AL grade distribution (Grade A: 0.6% vs. 0%, Grade B: 5.2% vs. 4.1%, Grade C: 1.2% vs. 1.7%, p = 0.691) between the two groups. However, the Diversion(+) group demonstrated a higher incidence of postoperative complications (30.8% vs. 17.4%, p = 0.004), Clavien-Dindo III-IV complications (2.9% vs. 2.3%, p = 0.013), particularly wound infections (8.1% vs. 1.2%, p = 0.002), and early postoperative inflammatory small bowel obstruction (EPISBO) (8.7% vs. 1.2%, p = 0.001) compared to the Diversion(-) group. Results from multivariate logistic regression analysis revealed that male gender (OR = 2.354, p = 0.014) was the only independent risk factor associated with AL, while the presence of diversion ileostomy (with vs. without, OR = 1.144, p = 0.686) did not show significant associations. In patients with AL, the onset of the AL was observed to occur later in the Diversion(+) group compared to the Diversion(-) group (7.0 +/- 3.3 vs. 3.4 +/- 1.4 days, p < 0.001), while the recovery time was significantly shorter (11.3 +/- 4.7 vs. 20.3 +/- 7.2 days, p < 0.001). Similarly, in Grade C AL patients, the occurence time was delayed in the Diversion(+) group compared to the Diversion(-) group (8.7 +/- 4.7 vs. 3.2 +/- 1.5 days, p = 0.008), with a shorter recovery time (19.3 +/- 2.1 vs. 25.7 +/- 6.7 days, p = 0.031). A trend was observed indicating a longer interval before ileostomy restoration in the AL patients compared to the non-AL patients (7.6 +/- 4.9 months vs. 5.5 +/- 2.9 months, p = 0.079). In addition, DAV (OR = 0.078, p = 0.002) was identified as the only independent factor associated with potential-diversion-benefit in patients with AL, with an optimal cutoff point of 8.6 cm. The utilization of diversion ileostomy as a preventative measure for AL in cases of locally advanced upper-half rectal cancer is not universally endorsed due to potential complications such as small bowel obstruction and wound infection. Nevertheless, in the occurrence of AL, diversion ileostomy may prove advantageous for patient recuperation. Particularly, male patients with a DAV ranging from 7 to 8.6 cm may experience benefits from undergoing diversion ileostomy subsequent to AL in cases of locally advanced upper-half rectal cancer.
Killer cell lectin-like receptor G1 (KLRG1) has traditionally been regarded as an inhibitory receptor of T cell exhaustion in chronic infection and inflammation. However, its exact role in hepatitis B virus (HBV) infection remains elusive. CD8+ T cells from 190 patients with chronic hepatitis B were analyzed ex vivo for checkpoint and apoptosis markers, transcription factors, cytokines and subtypes in 190 patients with chronic hepatitis B. KLRG1+ and KLRG1- CD8+ T cells were sorted for transcriptome analysis. The impact of the KLRG1-E-cadherin pathway on the suppression of HBV replication mediated by virus-specific T cells was validated in vitro. As expected, HBV-specific CD8+ T cells expressed higher levels of KLRG1 and showed an exhausted molecular phenotype and function. However, despite being enriched for the inhibitory molecules, thymocyte selection-associated high mobility group box protein (TOX), eomesodermin (EOMES), and Helios, CD8+ T cells expressing KLRG1 produced significant levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, perforin, and granzyme B, demonstrating not exhausted but active function. Consistent with the in vitro phenotypic assay results, RNA sequencing (RNA-seq) data showed that signature effector T cell and exhausted T cell genes were enriched in KLRG1+ CD8+ T cells. Furthermore, in vitro testing confirmed that KLRG1-E-cadherin binding inhibits the antiviral efficacy of HBV-specific CD8+ T cells. Based on these findings, we concluded that KLRG1+ CD8+ T cells are not only a terminally exhausted subgroup but also exhibit functional diversity, despite inhibitory signs in HBV infection.
Previous studies on successful anastomosis after intersphincteric resection (ISR) for low rectal cancer (LRC) primarily focused on anastomotic complications rather than functional outcomes. Here, we improved the anastomotic success criteria by considering surgical, oncological, and functional outcomes and proposed a new composite outcome, “textbook anastomotic success” (TASS). This retrospective single-center study included patients with LRC treated with ISR from January 2014 to April 2020. TASS was defined as (1) no anastomotic complications occurring after ISR; (2) ileostomy was closed and there was no severe intestinal dysfunction 2 years after ISR; and (3) no local recurrence within 2 years of surgery. TASS was achieved upon meeting all indicators. We analyzed 259 patients with LRC, with 125 (48.3
Our objective was to explore the factors associated with the prognosis of allergic asthmatic children with poor compliance with subcutaneous immunotherapy (SCIT). A telephonic follow-up was conducted in 616 asthmatic children who received SCIT treatment from June 2005 to October 2010. The status of asthmatic controlled was based on their level of asthma symptom control when they were followed-up. Seven factors, including sex, age, family history of allergic disease, severity of mite allergy, times of SCIT, whether inhaled corticosteroids regularly, and with rhinitis or not, were analyzed. In total, 322 asthmatic children discontinued the 3-year course of SCIT. Of the 127 children included in the final analysis, 85 (66.9%) were asthmatic controlled patients and 42 (33.1%) were asthmatic uncontrolled patients. The median (interquartile range) age of the 127 asthmatic children was 7.1 +/- 4.8 years. The proportion of male and female was 87/40. In the seven factors, family history of allergic diseases ( p = 0.035), whether inhaling corticosteroids regularly ( p = 0.007), were significantly related to the level of asthma symptom control, whereas the age of these asthmatic children, severity of mite allergy, times of SCIT, and asthma with rhinitis or not had no relation to the level of asthma symptom control. Our findings revealed that the family history of allergic diseases was an important factor affecting the prognosis of childhood asthma, and inhaling corticosteroids regularly after discontinuing SCIT could significantly improve their prognosis. These results could provide value in clinical asthma treatment.
Hepatitis B virus (HBV) clearance depends on an effective adaptive immune response, especially HBV-specific T cell-mediated cellular immunity; however, it is difficult to produce enough HBV-specific T cells effectively. In this work, we investigated the proportions of stimulated cells, serum, and culture media as the three primary factors to determine the most effective procedure and applied it to HLA-A2 (+) people. In parallel, we also examined the correlation between clinical parameters and HBV-specific immunity. Concerning amplification efficiency, 4 × 105 cells stimulation was superior to 2 × 106 cells stimulation, AIM-V medium outperformed 1640 medium, and fetal bovine serum (FBS) exceeded human AB serum under comparable conditions. As expected, this procedure is also suitable for developing HBV-specific CD8 + T cells in HLA-A2(+) individuals. Expanded HBV-specific T cell responses decreased with treatment time and were negatively correlated with HBV DNA and HBsAg. Furthermore, the number of HBV-specific IFN-γ + SFCs was strongly correlated with the ALT level and negatively correlated with the absolute lymphocyte count and the ALB concentration. We confirm that stimulating 4 × 105 PBMCs in AIM-V medium supplemented with 10
Objective:To observe the role of Huaiqihuang Granules (HQ) in the long-term management of bronchial asthma in young children, and the effective effect on concomitant rhinitis.Methods:A prospective real-world multicenter study was conducted in children aged 2-5 years with asthma diagnosed in the outpatient department (from April 2016 to March 2019)who received either inhaled corticosteroid (ICS)/leukotriene receptor antagonist (LTRA)(control group); inhaled ICS/LTRA plus HQ(combination group), or HQ alone(HQ group). All patients were followed up at week 4, 8, 12 after treatment. The number of days with asthma symptoms, the frequency of severe asthma attacks, the level of asthma control, and the days with rhinitis symptoms in the last 4 weeks were recorded. Differences before and after treatment, and those among groups after treatment were compared using Kruskal- Wallis H test or Wilcoxon rank-sum test. Results:A total of 2 234 eligible patients were recruited, and 2 147 cases completed followed-up visits, including 477, 1 374 and 296 cases in the control group, combination group, and HQ group, respectively. After the treatment, all 3 groups showed significant declines in the days with asthma symptoms, frequency of severe asthma attack and the days with rhinitis symptoms (all P<0.01), and the rate of well-controlled asthma increased significantly ( P<0.01). It lasted until the end of follow-up. Among groups, patients in the combination group showed significantly less days of asthma symptoms than those of the other 2 group at week 8 and 12[0(0, 0.9) d vs.0(0, 0.3) d, P<0.05; 0(0, 0.1) d vs. 0(0, 1.0) d, P<0.01]. Patients in the combination group and HQ group showed a significantly lower rate of severe asthma attacks than that of the control group at week 12 [0(0, 1), 0(0, 1), 0(0, 2), all P<0.05]. The well-controlled rate of asthma in the combination group was significantly higher than that of the control group and HQ group at week 8 and 12 (89.6% vs. 85.9% vs.82.1%, H=15.28; 90.9% vs. 84.1% vs. 81.8%, χ2=29.32, all P<0.01). Conclusions:HQ can significantly alleviate symptoms of asthma and rhinitis, severe attack of asthma, and increase the control rate of asthma when used as an additional treatment or used alone.
We study the effects of centralized health management based on hot spring resorts on the physical examination index and sleep quality of people at high risk of chronic diseases. We recruited 114 volunteers at high risk of chronic diseases. We then divided them into 57 in the intervention group and 57 in the control group. The intervention group collectively received 4 weeks (28 days) of comprehensive health management interventions at Tongjing Hotspring Resort, including regular schedules, balanced diet, appropriate exercise, targeted health education, etc. The main outcomes are physical examination indicators (height, weight, waist circumference, blood pressure, lipids, and glucose) and sleep quality. Both groups underwent a questionnaire and physical examination at baseline, 2 weeks and 4 weeks. Intragroup comparisons grouped by exposure criteria showed decreases in BMI, waist circumference, triglycerides, total cholesterol, and blood glucose in the intervention group at both 2 and 4 weeks (all P < 0.05); however, in the control group, only triglycerides decreased at 4 weeks (P < 0.05). Intergroup comparisons showed BMI and waist circumference were significantly lower in the intervention group than in the control group at 4 weeks (all P < 0.05). Intragroup comparisons of insomnia severity index (ISI) scores showed a significant decrease in the intervention group at both 2 and 4 weeks (all P < 0.001) with no significant change in the control group (P > 0.05). Intergroup comparisons showed that the insomnia severity index (ISI) scores were significantly higher in the intervention group than in the control group at baseline (P = 0.006) but became significantly lower than the control group at 2 and 4 weeks (all P < 0.001). Thus, this pattern significantly improved BMI, waist circumference, triglycerides, and sleep in the intervention group.Trial registration numberChinese Clinical Trials Registry: ChiCTR2100053201, registered 14 Nov 2021. (Retroactive Registration)
Pyroptosis is a form of programmed cell death mediated by gasdermins, particularly gasdermin D (GSDMD), which is widely expressed in tissues throughout the body. GSDMD belongs to the gasdermin family, which is expressed in a variety of cell types including epithelial cells and immune cells. It is involved in the regulation of anti-inflammatory responses, leading to its differential expression in a wide range of diseases. In this review, we provide an overview of the current understanding of the major activation mechanisms and effector pathways of GSDMD. Subsequently, we examine the importance and role of GSDMD in different diseases, highlighting its potential as a pan-biomarker. We specifically focus on the biological characteristics of GSDMD in several diseases and its promising role in diagnosis, early detection, and differential diagnosis. Furthermore, we discuss the application of GSDMD in predicting prognosis and monitoring treatment efficacy in cancer. This review proposes a new strategy to guide therapeutic decision-making and suggests potential directions for further research into GSDMD.
This systematic review and meta-analysis aimed to investigate the efficacy and acceptability of systemic therapy in treatment of children and adolescents with depression. Six databases were used to identify randomized controlled trials (RCTs) applying systemic therapy (ST). Random-effects meta-analyses were conducted to estimate efficacy and acceptability of intervention. The primary outcome of efficacy was defined as changes of depressive symptoms. Secondary outcomes of efficacy included response rate and function improvement. Nine RCTs (n = 640) were included. For the immediate efficacy of depressive symptoms, ST was superior to waiting-list (WL) (n = 117, SMD -1.75, 95% CI -2.96 to -0.54), similar to treat as usual (TAU) (n = 146, SMD -0.45, 95% CI -1.14 to 0.24) or supportive psychotherapy (n = 263, SMD -0.04, 95%CI -0.28 to 0.20), superior to psychodynamic psychotherapy (n = 72, SMD -0.66, 95%CI -1.13 to -0.18) and inferior to cognitive behavior therapy (CBT) (n = 72, SMD 0.58, 95%CI 0.11 to 1.05). About response rate, ST (47.7%) was superior to WL, similar to TAU and supportive therapy and dynamic psychotherapy, and inferior to CBT. ST was comparable to CBT, supportive therapy and dynamic therapy on function improvement (SMD 0.18, 95% CI -0.12 to 0.49). As for acceptability, no significant difference was found between ST (11.9%) and controls (OR 0.97, 95%CI 0.61 to 1.56). In treating youths with depression, ST was superior to WL, similar to supportive psychotherapy and TAU, inferior to CBT, similar or superior to dynamic psychotherapy on symptoms relief. ST demonstrated comparable acceptability to TAU and guideline-recommended psychotherapies. Considering small sample size, the conclusion should be treated cautiously.
To preliminarily explore a nondrug intervention method and evaluate its effects (sleep quality, physical examination indicators, and general physical symptoms) on people with sleep disorders. The intervention was based on regular balneotherapy, coupled with targeted health education, appropriate exercise, diet management, and other sleep-promoting measures. It was the combined effects that we evaluated. We recruited 31 volunteers with sleep disorders to receive a 7-day sleep-promoting experience in Tianxing International Hot Spring City, Nanchuan District, Chongqing. The intervention adopted a plan that combined balneotherapy with various sleep-promoting measures. Persisting baths in hot springs 1-2 times per day targeted health lectures about 1 h every morning, appropriate exercise every day (sleep-aid yoga, forest hiking, morning exercises, etc.), and diet management (the principle is to control oil, salt, and sugar, diversify food, keep meat and vegetable balanced, and control total calories. The dinner is light and easy to digest). During the intervention period, all participants followed the above intervention plan, and they lived in the spa resort to accept unified arrangement. This study adopted a self-contrast method by comparing the changes in sleep quality, physical examination indicators, and general physical symptoms before and after the intervention through physical examinations and questionnaire surveys. After the intervention, the subjects' total score of Insomnia Severity Index (ISI) decreased significantly (P = 0.006), and all seven dimensions showed a decrease, four of which included early morning awakening, sleep dissatisfaction, noticeability of sleep problems by others, and distress caused by sleep problems decreased significantly (all P < 0.05). The subjects' body mass index, waist circumference, fasting blood glucose, and triglycerides decreased significantly (all P < 0.05), and systolic blood pressure increased significantly (P = 0.006). Total cholesterol, high-density lipoprotein, low-density lipoprotein, and diastolic blood pressure did not change significantly (all P > 0.05). To some extent, all general health problems were improved than before the intervention (the improvement rate was up to 70% or more). The non-pharmacological intervention of balneotherapy combined with various sleep-promoting measures showed positive effects on sleep quality, general physical symptoms, and some physical examination indicators of sleep disorders. This comprehensive intervention may be an effective way to improve people's health with sleep disorders.
Objectives: In this study, we propose a deep learning-based approach to predict Intensity-modulated radiation therapy (IMRT) quality assurance (QA) gamma passing rates using delivery fluence informed by log files. Methods: A total of 112 IMRT plans for chest cancers were planned and measured by portal dosimetry equipped on TrueBeam linac. The convolutional neural network (CNN) based learning model was trained using delivery fluence as inputs and gamma passing rates (GPRs) of 4 different criteria (3%/3 mm, 2%/3 mm, 3%/2 mm, and 2%/2 mm) as outputs. Model performance for both validation and test sets was assessed using mean absolute error (MAE), mean squared error (MSE), root MSE (RMSE), Spearman rank correlation coefficients (Sr), and Determination coefficient (R-2) between the measured and predicted GPR values. Results: In the test set, the MAE of the prediction model were 0.402, 0.511, 1.724, and 2.530, the MSE were 0.640, 0.986, 6.654, and 9.508, the RMSE were 0.800, 0.993, 2.580, and 3.083, the Sr were 0.643, 0.684, 0.821, and 0.824 (P < .001) and the R-2 were 0.4110, 0.4666, 0.6677, and 0.6769 for 3%/3 mm, 3%/2 mm, 2%/3 mm, and 2%/2 mm, respectively. The MAE and RMSE of the prediction model decreased with stricter gamma criteria while the Sr and R-2 between measured and predicted GPR values increased. Conclusions: The CNN prediction model based on delivery fluence informed by log files could accurately predict IMRT QA passing rates for different gamma criteria. It could reduce QA workload and improve efficiency in pretreatment QA. Our results suggest that the CNN prediction model based on delivery fluence informed by log files may be a promising tool for the gamma evaluation of IMRT QA.
Background: Whether wedge resection of a tumor before lobectomy (Wed + Lob) can improve the prognosis of non-small cell lung cancer (NSCLC) has yet to be determined comprehensively. This study aimed to compare the effects of Wed + Lob with those of direct lobectomy (Lob) on survival and tumor cell dissemination in patients with T1N0M0 NSCLC. Methods: A cohort of 813 patients with T1N0M0 NSCLC who underwent lobectomy at a single center in China was investigated. After propensity score matching, the overall survival (OS) and disease-free survival (DFS) of patients were estimated using Kaplan-Meier plots. Associations between surgical strategies and patient survival were computed as hazard ratios and 95% confidence intervals using Cox proportional hazards regression models. Changes in folate receptor-positive circulating tumor cells (FR+ CTCs) after lobectomy were analyzed in another cohort from our hospital. Results: A total of 401 Wed + Lob cases were matched with 255 Lob cases according to their propensity scores. Although no significant differences were found in OS, multivariate analysis showed that patients with T1N0M0 NSCLC in the Wed + Lob group had significantly improved DFS (HR =0.583; P=0.012) compared to those in the Lob group. After surgery, a decrease in FR+ CTCs was observed in 21 of 23 patients (91.3%) in the Wed + Lob group and in 16 of 23 patients (69.6%) in the Lob group [mean changes: 6.10 (+/- 7.80) FU per 3 mL vs. 1.31 (+/- 4.39) FU per 3 mL; P=0.014]. Conclusions: Wed + Lob may improve DFS and reduce tumor cell dissemination in patients with T1N0M0 NSCLC.
Purpose: Wound healing of the corneal epithelium mainly involves two types of cells: limbal stem/progenitor cells (LSCs) and differentiated central corneal epithelial cells (CECs). The healing ability of CECs is still debatable, and its correlated transcriptomic alterations during wound healing are yet to be elucidated. This study aimed to determine the healing ability and mechanisms underlying the actions of CECs using rabbit ocular surface injury models. Methods: A central corneal ring-like residual epithelium model was used to investigate the healing ability of CECs. Uninjured and injury-stimulated LSCs and CECs were collected for transcriptomic analysis. The analysis results were verified by quantitative reverse transcriptase polymerase chain reaction, immunofluorescence staining, and two types of rabbit corneal injury models. Results: During wound healing, the upregulated genes in LSCs were mostly enriched in the mitotic cell cycle–related processes, but those in CECs were mostly enriched in cell adhesion and migration. CECs could repair the epithelial defects successfully at one-time injuries. However, after repetitive injuries, the CECs repaired notably slower and failed to completely heal the defect, but the LSCs repaired even faster than the one-time injury. Conclusions: Our results indicated rabbit CECs repair the epithelial defect mainly depending on migration and its proliferative ability is limited, and LSCs are the main source of regenerative epithelial cells. Translational Relevance: This study provides information on gene expression in the corneal epithelium during wound healing, indicating that regulation of the cell cycle, cell adhesion, and migration may be the basis for future treatment strategies for corneal wound healing.
Cyclic GMP-AMP synthase (cGAS) is a crucial DNA sensor and plays an important role in host antiviral innate immune responses. During hepatitis B virus (HBV) infection, the cGAS signaling pathway can suppress HBV replication. As an important regulatory protein of HBV, hepatitis B virus X protein (HBx) may serve as an antagonistic character to the cGAS/STING signaling pathway. In this study, we aim to investigate the functional role of HBx in the cGAS/STING signaling pathway. The effects of HBx on IFN-β promoter activity were measured by Dual-luciferase reporter assays. Ubiquitination and autophagy were analyzed by Western-blot and Co-immunoprecipitation assays. Our results show that HBx down-regulates IFN-I production by directly promoting ubiquitination and autophagy degradation of cGAS. HBV can antagonize host cGAS DNA sensing to promote HBV replication and provide novel insights to develop novel approaches against HBV infection.
Ascites is one of the most common complications of cirrhosis, and there is a dearth of knowledge about ascites-related pathologic metabolism. In this study, 122 alcoholic liver disease (ALD) patients, including 49 cases without ascites, 18 cases with mild-ascites, and 55 cases with large-ascites (1) were established according to the International Ascites Club (2), and untargeted metabolomics coupled with pattern recognition approaches were performed to profile and extract metabolite signatures. A total of 553 metabolites were uniquely discovered in patients with ascites, of which 136 metabolites had been annotated in the human metabolome database. Principal component analysis (PCA) analysis was used to further identify 21 ascites-related fingerprints. The eigenmetabolite calculated by reducing the dimensions of the 21 metabolites could be used to effectively identify those ALD patients with or without ascites. The eigenmetabolite showed a decreasing trend during ascites production and accumulation and was negatively related to the disease progress. These metabolic fingerprints mainly belong to the metabolites in lipid metabolism and the amino acid pathway. The results imply that lipid and amino acid metabolism disturbance may play a critical role in the development of ascites in ALD patients and could be a potent prognosis marker.
Objective Unexplained infertility (UIF) or recurrent pregnancy loss (RPL) affects 10%–15% of couples in their reproductive years and is multifactorial and not completely elucidated. In this study, we attempt to determine the endometrial expression pattern of non-coding RNA activated by DNA damage (NORAD) in women with UIF and RPL, as well as its clinical significance. Methods The microarray dataset GSE165004 was used to identify differentially expressed RNAs in the endometrial samples between women with RPL and fertile women and between women with UIF and fertile women. A total of 142 women were included in this retrospective analysis, including 32 women with UIF, 48 women with RPL, and 62 fertile women. The relative expression level of NORAD in the endometrial tissues was quantified by qRT-PCR. Results NORAD stood out as an only overlapped lncRNA among differentially expressed RNAs in the endometrial samples between RPL and fertile women and between UIF and fertile women. It was showed that the endometrial tissues of UIF and RPL both were demonstrated with lower relative expression levels of NORAD (UIF: 2.09 ± 0.68; RPL: 1.98 ± 0.65) than the endometrial tissues of normal fertility (4.32 ± 1.04) (P < 0.001). Pearson correlation analysis demonstrated that the serum level of E2 was negatively correlated with the relative expression level of NORAD in the endometrial tissues of UIF (r = −0.630) and RPL (r = −0.696). Results of ROC curves showed that the endometrial expression of NORAD could be used to differentiate RPL and UIF with an AUC of 0.977 (95% CI: 0.956–0.999) and 0.970 (95% CI: 0.941–0.998), sensitivity of 0.873 and 0.955, and specificity of 0.845 and 0.948, respectively. Conclusion The findings obtained from the study showed that the low endometrial expression of NORAD was linked to fertility-related problems, such as UIF and RPL.
As a stem variety of lettuce, the fleshy stem is the main product organ of stem lettuce. The molecular mechanism of fleshy stem expansion in stem lettuce is a complex biological process. In the study, the material accumulation, gene expression, and morphogenesis during fleshy stem expansion process were analyzed by the comparative analysis of metabolome, transcriptome and the anatomical studies. The anatomical studies showed that the occurrence and activity of vascular cambium mainly led to the development of fleshy stems; and the volume of pith cells gradually increased and arranged tightly during the expansion process. A total of 822 differential metabolites and 9,383 differentially expressed genes (DEGs) were identified by the metabolomics and transcriptomics analyses, respectively. These changes significantly enriched in sugar synthesis, glycolysis, and plant hormone anabolism. The expression profiles of genes in the sugar metabolic pathway gradually increased in fleshy stem expansion process. But the sucrose content was the highest in the early stage of fleshy stem expansion, other sugars such as fructose and glucose content increased during fleshy stem expansion process. Plant hormones, including IAA, GA, CTK, and JA, depicted important roles at different stem expansion stages. A total of 1,805 DEGs were identified as transcription factors, such as MYB, bHLH, and bZIP, indicating that these transcription factor families might regulate the fleshy stems expansion in lettuce. In addition, the expression patterns identified by qRT-PCR were consistent with the expression abundance identified by the transcriptome data. The important genes and metabolites identified in the lettuce fleshy stem expansion process will provide important information for the further molecular mechanism study of lettuce fleshy stem growth and development.