Integrating network pharmacology with pharmacological research to elucidate the mechanism of modified Gegen Qinlian Decoction in treating porcine epidemic diarrhea.

Porcine Epidemic Diarrhea Virus (PEDV) poses a significant threat to neonatal piglets, particularly due to the limited efficacy of existing vaccines and the scarcity of efficacious therapeutic drugs. Gegen Qinlian Decoction (GQD) has been employed for over two millennia in treating infectious diarrhea. Nonetheless, further scrutiny is required to improve the drug's efficacy and elucidate its underlying mechanisms of action. In this study, a modified GQD (MGQD) was developed and demonstrated its capacity to inhibit the replication of PEDV. Animal trials indicated that MGQD effectively alleviated pathological damage in immune tissues and modulated T-lymphocyte subsets. The integration of network analysis with UHPLC-MS/MS facilitated the identification of active ingredients within MGQD and elucidated the molecular mechanisms underlying its therapeutic effects against PEDV infections. In vitro studies revealed that MGQD significantly impeded PEDV proliferation in IPEC-J2 cells, promoting cellular growth via virucidal activity, inhibition of viral attachment, and disruption of viral biosynthesis. Furthermore, MGQD treatment led to increased expression levels of IFN-α, IFN-ß, and IFN-λ3, while concurrently decreasing the expression of TNF-α, thereby enhancing resistance to PEDV infection in IPEC-J2 cells. In conclusion, our findings suggest that MGQD holds promise as a novel antiviral agent for the treatment of PEDV infections.

Adsorption mechanism of cefradine on three microplastics: A combined molecular dynamics simulation and density functional theory calculation study.

Microplastics and antibiotics are receiving increasing attention as two emerging pollutants in the aquatic ecosystem. The absorption of antibiotics by microplastics can potentially intensify their impact on marine organisms and human health. However, the detailed mechanisms underlying this interaction remain to be elucidated. Through molecular dynamics (MD) simulations and density functional theory (DFT) calculations, this study investigated the adsorption of cefradine (CED) onto three typical microplastics (MPs)-polyethylene (PE), polypropylene (PP), and polyamide (PA). The results of the molecular dynamics simulations showed that the interaction energy between CED and microplastics followed the order of PA-CED > PP-CED > PE-CED, indicating that PA microplastics had the highest adsorption capacity for CED antibiotics. The total energy contribution of the microplastics-cefradine (MPs-CED) systems suggested that the van der Waals and electrostatic interactions were the two primary mechanisms for the adsorption of CED by these three microplastics. In DFT calculations, the adsorption of CED on PA was found to be significantly influenced by both electrostatic and van der Waals effects, while the main driving force in the adsorption of PE and PP is van der Waals effect. In addition, IGMH analysis and AIM topological analysis confirmed that the adsorption of CED on PA relied heavily on the synergistic effect of hydrogen bonding and the van der Waals effect. The findings of this study validate the results obtained from molecular dynamics simulations, laying a foundation for a comprehensive exploration of the interaction mechanisms between microplastics and organic pollutants by integrating MD simulations and DFT calculations.

Mitigating aging and doxorubicin induced bone loss in mature mice via mechanobiology based treatments.

Aging leads to a reduced anabolic response to mechanical stimuli and a loss of bone mass and structural integrity. Chemotherapy agents such as doxorubicin exacerbate the degeneration of aging skeleton and further subject older cancer patients to a higher fracture risk. To alleviate this clinical problem, we proposed and tested a novel mechanobiology-based therapy. Building upon prior findings that i) Yoda1, the Piezo1 agonist, promoted bone growth in young adult mice and suppressed bone resorption markers in aged mice, and ii) moderate tibial loading protected bone from breast cancer-induced osteolysis, we hypothesized that combined Yoda1 and moderate loading would improve the structural integrity of adult and aged skeletons in vivo and protect bones from deterioration after chemotherapy. We first examined the effects of 4-week Yoda1 (dose 5 mg/kg, 5 times/week) and moderate tibial loading (4.5 N peak load, 4 Hz, 300 cycles for 5 days/week), individually and combined, on mature mice (∼50 weeks of age). Combined Yoda1 and loading was found to mitigate age-associated cortical and trabecular bone loss better than individual interventions. As expected, the non-treated controls experienced an average drop of cortical polar moment of inertia (Ct.pMOI) by -4.3 % over four weeks and the bone deterioration occurred in the majority (64 %) of the samples. Relative to no treatment, loading alone, Yoda1 alone, and combined Yoda1 and loading increased Ct.pMOI by +7.3 %, +9.5 %, +12.0 % and increased the % of samples with positive Ct.pMOI changes by +32 %, +26 %, and +43 %, respectively, suggesting an additive protection of aging-related bone loss for the combined therapy. We further tested if the treatment efficacy was preserved in mature mice following two weeks (six injections) of doxorubicin at the dose of 2.5 or 5 mg/kg. As expected, doxorubicin increased osteocyte apoptosis, altered bone remodeling, and impaired bone structure. However, the effects induced by DOX were too severe to be rescued by Yoda1 and loading, alone or combined, although loading and Yoda1 individually, or combined, increased the number of mice showing positive responsiveness by 0 %, +15 %, and +29 % relative to no intervention after doxorubicin exposure. Overall, this study supported the potentials and challenges of the Yoda1-based strategy in mitigating the detrimental skeletal effects caused by aging and doxorubicin.

Long-term outcomes and associated factors of Crohn's disease patients achieving transmural healing based on magnetic resonance enterography: a Chinese retrospective cohort study.

Background: Transmural healing (TH) has emerged as a potential treatment goal for Crohn's disease (CD). However, further research is needed to confirm its benefits and risk factors associated with TH remain unclear. Objectives: We aimed to assess the value of TH based on magnetic resonance enterography (MRE) in Chinese CD patients regarding the long-term outcomes and its associated factors. Design: Retrospective, observational cohort study. Methods: Patients with CD diagnosed by colonoscopy and MRE examination between 2015 and 2022 were included. All patients were evaluated with endoscopy together with MRE within 6-12 months after baseline and followed up for at least 6 months after evaluation. The primary endpoint was the occurrence of major outcomes during the follow-up, including drug escalation, hospitalization, and surgery. The cumulative probabilities of major outcomes were calculated using Kaplan-Meier survival curves. Logistic regression analyses were used to predict TH within 6-12 months after baseline. Results: A total of 175 patients were included in the study. Of these, 69 (39.4%) patients achieved mucosal healing (MH), but only 34 (19.4%) of them achieved TH. The median follow-up duration was 17.4 months (interquartile range, 11.6-25.5), and major outcomes occurred in 58.3% of patients. A lower occurrence rate of major outcomes was noted in patients who achieved TH than in those who achieved MH only (p = 0.012). The baseline lymphocyte/C-reactive protein ratio (LCR) [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.02-2.50; p = 0.039] and bowel wall thickness (BWT) (OR, 0.72; 95% CI, 0.59-0.90; p = 0.003) were independent predictors associated with TH. According to multivariate Cox regression analysis, low LCR [hazard ratio (HR), 2.34; 95% CI, 1.51-3.64; p < 0.001], and no healing (HR, 5.45; 95% CI, 2.28-13.00; p < 0.001) were associated with an increased risk of major outcomes. Conclusion: Patients with CD who achieved TH showed improved prognosis compared to those who achieved MH only. Baseline LCR and BWT might predict TH.

Multi-omic characterization of allele-specific regulatory variation in hybrid pigs.

Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

Genome-wide detection of multiple variants associated with teat number in French Yorkshire pigs.

BACKGROUND: Teat number is a vital reproductive trait in sows, crucial for providing immunity and nutrition to piglets during lactation. However, "missing heritability" in Single Nucleotide Polymorphism (SNP)-based Genome-Wide Association Studies (GWAS) has led to an increasing focus on structural variations in the genetic analysis of complex biological traits. RESULTS: In this study, we generated a comprehensive CNV map in a population of French Yorkshire pigs (n = 644) and identified 429 CNVRs. Notably, 44% (189 CNVRs) of these were detected for the first time. Subsequently, we conducted GWAS for teat number in the French Yorkshire pig population using both 80K chip and its imputed data, as well as a GWAS analysis based on CNV regions (CNVR). Interestingly, 80K chip GWAS identified two SNPs located on Sus scrofa chromosome 5 (SSC5) that were simultaneously associated with Total Teat Number (TTN), Left Teat Number (LTN), and Right Teat Number (RTN). The leading SNP (WU_10.2_5_76130558) explained 3.33%, 2.69%, and 2.67% of the phenotypic variance for TTN, LTN, and RTN, respectively. Moreover, through imputed GWAS, we successfully identified 30 genetic variants associated with TTN located within the 73.22 -73.30 Mb region on SSC5. The two SNPs identified in the 80K chip GWAS were also located in this region. In addition, CNVR-based GWAS revealed three significant CNVRs associated with TTN. Finally, through gene annotation, we pinpointed two candidate genes, TRIM66 and PRICKLE1, which are related to diverse processes such as breast cancer and abnormal vertebral development. CONCLUSIONS: Our research provides an in-depth analysis of the complex genetic structure underlying teat number, contributing to the genetic enhancement of sows with improved reproductive performance and, ultimately, bolstering the economic benefits of swine production enterprises.

Polyprenylated acylphloroglucinols from Hypericum sampsonii with cytotoxicity against pancreatic carcinomas.

Chemical investigation on the 80% EtOH extract of the air dried aerial parts of Hypericum sampsonii resulted in the isolation of two new polycyclic polyprenylated derivatives, hypersampines A and B (1 and 2). The structures of the new compounds were elucidated by spectroscopic data (NMR, IR, and UV) and high resolution mass analysis. The two isolated polyprenylated acylphloroglucinols were tested in vitro for cytotoxic activities against 6 pancreatic cell lines. As a result, compounds 1 and 2 possessed modest cytotoxic activities against all the tested tumor cell lines with IC50 values less than 40 µM.

MRI radiomics enhances radiologists' ability for characterizing intestinal fibrosis in patients with Crohn's disease.

OBJECTIVES: We aimed to develop MRI-based radiomic models (RMs) to improve the diagnostic accuracy of radiologists in characterizing intestinal fibrosis in patients with Crohn's disease (CD). METHODS: This retrospective study included patients with refractory CD who underwent MR before surgery from November 2013 to September 2021. Resected bowel segments were histologically classified as none-mild or moderate-severe fibrosis. RMs based on different MR sequence combinations (RM1: T2WI and enhanced-T1WI; RM2: T2WI, enhanced-T1WI, diffusion-weighted imaging [DWI], and apparent diffusion coefficient [ADC]); RM3: T2WI, enhanced-T1WI, DWI, ADC, and magnetization transfer MRI [MTI]), were developed and validated in an independent test cohort. The RMs' diagnostic performance was compared to that of visual interpretation using identical sequences and a clinical model. RESULTS: The final population included 123 patients (81 men, 42 women; mean age: 30.26 ± 7.98 years; training cohort, n = 93; test cohort, n = 30). The area under the receiver operating characteristic curve (AUC) of RM1, RM2, and RM3 was 0.86 (p = 0.001), 0.88 (p = 0.001), and 0.93 (p = 0.02), respectively. The decision curve analysis confirmed a progressive improvement in the diagnostic performance of three RMs with the addition of more specific sequences. All RMs performance surpassed the visual interpretation based on the same MR sequences (visual model 1, AUC = 0.65, p = 0.56; visual model 2, AUC = 0.63, p = 0.04; visual model 3, AUC = 0.77, p = 0.002), as well as the clinical model composed of C-reactive protein and erythrocyte sedimentation rate (AUC = 0.60, p = 0.13). CONCLUSIONS: The RMs, utilizing various combinations of conventional, DWI and MTI sequences, significantly enhance radiologists' ability to accurately characterize intestinal fibrosis in patients with CD. CRITICAL RELEVANCE STATEMENT: The utilization of MRI-based RMs significantly enhances the diagnostic accuracy of radiologists in characterizing intestinal fibrosis. KEY POINTS: MRI-based RMs can characterize CD intestinal fibrosis using conventional, diffusion, and MTI sequences. The RMs achieved AUCs of 0.86-0.93 for assessing fibrosis grade. MRI-radiomics outperformed visual interpretation for grading CD intestinal fibrosis.

Pathways linking workplace violence and suicidal ideation/non-suicidal self-injury among nurse staff: the mediating role of loneliness and depressive symptoms.

BACKGROUND: Nurses face disproportionately high rates of suicidal ideation and non-suicidal self-injury (NSSI). The role of workplace violence, loneliness, and depressive symptoms in exacerbating these issues is poorly understood. This study aims to explore these relationships to inform interventions for improving nurses' mental health. METHODS: A cross-sectional study involving 1,774 Chinese nurse staff selected through convenient sampling methods was conducted. Workplace violence, depressive symptoms, and loneliness were assessed using the Chinese versions of the Workplace Violence Scale (WVS), the 9-item Patient Health Questionnaire (PHQ-9), and a three-item loneliness scale, respectively. Participants completed self-report questionnaires anonymously to ensure adherence to ethical standards. Statistical analysis utilized structural equation modeling (SEM) to examine the intricate relationships among variables, thereby elucidating the impact of workplace violence, loneliness, and depressive symptoms on nurses' suicidal ideation/NSSI outcomes. RESULTS: Nurse staff 165 (7.8%) were reported different level of suicidal ideation and 139 (7.8%) participants were reported different level of NSSI. And the final model of workplace violence on suicidal ideation shown a good model fit index (CMIN/DF = 3.482 NFI = 0.969 CFI = 0.977 TLI = 0.955 RFI = 0.938, RMSEA = 0.037 SRMR = 0.035). The pathway of workplace violence to loneliness (ß = 0.163, P < 0.001), the indirect effect of workplace violence on suicidal ideation via loneliness and depressive symptoms were 0.100 (95%CI = 0.085, 0.121), the indirect effect of loneliness on suicidal ideation via depressive symptoms were 0.128 (95%CI = 0.100, 0.158). Similarly, the final model of workplace violence on NSSI shown a good model fit index (CMIN/DF = 3.482 NFI = 0.967 CFI = 0.976 TLI = 0.953 RFI = 0.935, RMSEA = 0.037 SRMR = 0.034), the pathways of workplace violence to NSSI (ß = 0.115, P < 0.001), the indirect effect of workplace violence on NSSI via loneliness and depressive symptoms were 0.075 (95%CI = 0.055, 0.096), the indirect effect of loneliness on NSSI via depressive symptoms were 0.102 (95%CI = 0.076, 0.130). CONCLUSION: Our study unveils the role of workplace violence in nurses' suicidal ideation and NSSI, mediated by loneliness and depressive symptoms. Interventions targeting workplace violence are crucial for nurses' well-being, potentially reducing loneliness and depressive symptoms and lowering the risk of suicidal ideation and NSSI. However, further research is needed to explore additional mediators and pathways, employing longitudinal designs to establish causality and develop tailored interventions for nurses affected by workplace violence.

Psychosocial characteristics pattern correlated with suicidal ideation and non-suicidal self-injury among nurse staff: a latent profile analysis.

BACKGROUND: Nurses frequently endure elevated levels of psychosocial stress, which often correlates with an increased suicide risk. This study aimed to investigate the impact of latent psychosocial characteristic patterns on suicidal ideation and non-suicidal self-injury among nursing staff. METHOD: Participants were recruited from the Dehong districts of Yunnan province, China, between July 11th and July 26th, 2022. Subgroups were identified using variables linked to suicidal ideation and non-suicidal self-injury, including perceived cognitive deficits, anxiety symptoms, depressive symptoms, resilience, social support, childhood trauma, loneliness, and sleep quality. Measurement tools included the Perceived Deficit Questionnaire-5-item (PDQ-5), Generalized Anxiety Disorder-7 items (GAD-7), Patient Health Questionnaire (PHQ-9), Connor-Davidson Resilience Scale-10 items (CD-RISC10), Multidimensional Scale of Perceived Social Support (MSPSS), Childhood Trauma Questionnaire-Short Form (CTQ-SF), Three-Item Loneliness Scale, and a single-item sleep quality scale. RESULTS: Latent profile analysis (LPA) revealed four distinct psychosocial characteristic patterns: "class 1," "class 2," "class 3," and "class 4." Compared to class 2, individuals in class 1 had a sixfold increased risk of suicidal ideation (OR = 6.59, 95%CI = 4.42-9.81) and a fivefold increased risk of non-suicidal self-injury (OR = 5.13, 95%CI = 3.38-7.78). Similarly, class 4 individuals had twice the risk of suicidal ideation (OR = 2.13, 95%CI = 1.25-3.62) and non-suicidal self-injury (OR = 2.13, 95%CI = 1.25-3.65) compared to class 2. Conversely, class 3 individuals had a lower risk of suicidal ideation (OR = 0.21, 95%CI = 0.11-0.42) and non-suicidal self-injury (OR = 0.15, 95%CI = 0.07-0.36) than class 2. Additionally, divorced/other marital status individuals had a higher risk of suicidal ideation (OR = 2.34, 95%CI = 1.02-5.35) and non-suicidal self-injury (OR = 2.58, 95%CI = 1.01-6.65) compared to married individuals, while unmarried individuals had a lower risk of suicidal ideation (OR = 0.58, 95%CI = 0.37-0.91). CONCLUSIONS: The study identified eight important psychosocial factors divided into four latent pattern classes. Individuals in "class 1" and "class 4" were more likely to have a higher risk of suicidal ideation and non-suicidal self-injury, while those in "class 3" were more likely to have a lower risk of both outcomes. It is suggested that further research should focus on "class 1" and "class 4" for targeted intervention.

Coupled hydraulics and carbon economy underlie age-related growth decline and revitalisation of sand-fixing shrubs after crown removal.

Crown removal revitalises sand-fixing shrubs that show declining vigour with age in drought-prone environments; however, the underlying mechanisms are poorly understood. Here, we addressed this knowledge gap by comparing the growth performance, xylem hydraulics and plant carbon economy across different plant ages (10, 21 and 33 years) and treatments (control and crown removal) using a representative sand-fixing shrub (Caragana microphylla Lam.) in northern China. We found that growth decline with plant age was accompanied by simultaneous decreases in soil moisture, plant hydraulic efficiency and photosynthetic capacity, suggesting that these interconnected changes in plant water relations and carbon economy were responsible for this decline. Following crown removal, quick resprouting, involving remobilisation of root nonstructural carbohydrate reserves, contributed to the reconstruction of an efficient hydraulic system and improved plant carbon status, but this became less effective in older shrubs. These age-dependent effects of carbon economy and hydraulics on plant growth vigour provide a mechanistic explanation for the age-related decline and revitalisation of sand-fixing shrubs. This understanding is crucial for the development of suitable management strategies for shrub plantations constructed with species having the resprouting ability and contributes to the sustainability of ecological restoration projects in water-limited sandy lands.

Comparative analysis of [18F]F-FAPI PET/CT, [18F]F-FDG PET/CT and magnetization transfer MR imaging to detect intestinal fibrosis in Crohn's disease: A prospective animal model and human cohort study.

PURPOSE: Accurately and early detection of intestinal fibrosis in Crohn's disease (CD) is crucial for clinical management yet remains an unmet need. Fibroblast activation protein inhibitor (FAPI) PET/CT has emerged as a promising tool to assess fibrosis. We aimed to investigate the diagnostic capability of [18F]F-FAPI PET/CT in detecting intestinal fibrosis and compared it with[18F]F-FDG PET/CT and magnetization transfer MR imaging (MTI). METHODS: Twenty-two rats underwent TNBS treatment to simulate fibrosis development, followed by three quantitative imaging sessions within one week. Mean and maximum standardized uptake values (SUVmean and SUVmax) were calculated on[18F]F-FAPI and [18F]F-FDG PET/CT, along with normalized magnetization transfer ratio on MTI. Intestinal fibrosis was assessed pathologically, with MTI serving as imaging standard for fibrosis. The diagnostic efficacy of imaging parameters in fibrosis was compared using pathological and imaging standards. Ten patients with 34 bowel strictures were prospectively recruited to validate their diagnostic performance, using the identical imaging protocol. RESULTS: In CD patients, the accuracy of FAPI uptake (both AUCs = 0.87, both P ≤ 0.01) in distinguishing non-to-mild from moderate-to-severe fibrosis was higher than FDG uptake (both AUCs = 0.82, P ≤ 0.01) and comparable to MTI (AUCs = 0.90, P ≤ 0.001). In rats, FAPI uptake responded earlier to fibrosis development than FDG and MTI; consistently, during early phase, FAPI uptake showed a stronger correlation (SUVmean: R = 0.69) with pathological fibrosis than FDG (SUVmean: R = 0.17) and MTI (R = 0.52). CONCLUSION: The diagnostic efficacy of [18F]F-FAPI PET/CT in detecting CD fibrosis is superior to [18F]F-FDG PET/CT and comparable to MTI, exhibiting great potential for early detection of intestinal fibrosis.

CT-based radiomics signature of visceral adipose tissue and bowel lesions for identifying patients with Crohn's disease resistant to infliximab.

PURPOSE: To develop a CT-based radiomics model combining with VAT and bowel features to improve the predictive efficacy of IFX therapy on the basis of bowel model. METHODS: This retrospective study included 231 CD patients (training cohort, n = 112; internal validation cohort, n = 48; external validation cohort, n = 71) from two tertiary centers. Machine-learning VAT model and bowel model were developed separately to identify CD patients with primary nonresponse to IFX. A comprehensive model incorporating VAT and bowel radiomics features was further established to verify whether CT features extracted from VAT would improve the predictive efficacy of bowel model. Area under the curve (AUC) and decision curve analysis were used to compare the prediction performance. Clinical utility was assessed by integrated differentiation improvement (IDI). RESULTS: VAT model and bowel model exhibited comparable performance for identifying patients with primary nonresponse in both internal (AUC: VAT model vs bowel model, 0.737 (95% CI, 0.590-0.854) vs. 0.832 (95% CI, 0.750-0.896)) and external validation cohort [AUC: VAT model vs. bowel model, 0.714 (95% CI, 0.595-0.815) vs. 0.799 (95% CI, 0.687-0.885)), exhibiting a relatively good net benefit. The comprehensive model incorporating VAT into bowel model yielded a satisfactory predictive efficacy in both internal (AUC, 0.840 (95% CI, 0.706-0.930)) and external validation cohort (AUC, 0.833 (95% CI, 0.726-0.911)), significantly better than bowel alone (IDI = 4.2% and 3.7% in internal and external validation cohorts, both p < 0.05). CONCLUSION: VAT has an effect on IFX treatment response. It improves the performance for identification of CD patients at high risk of primary nonresponse to IFX therapy with selected features from RM. CRITICAL RELEVANCE STATEMENT: Our radiomics model (RM) for VAT-bowel analysis captured the pathophysiological changes occurring in VAT and whole bowel lesion, which could help to identify CD patients who would not response to infliximab at the beginning of therapy. KEY POINTS: • Radiomics signatures with VAT and bowel alone or in combination predicting infliximab efficacy. • VAT features contribute to the prediction of IFX treatment efficacy. • Comprehensive model improved the performance compared with the bowel model alone.

Cross-sectional imaging: current status and future potential in adult celiac disease.

Celiac disease (CD), triggered by exposure to gluten in genetically susceptible individuals, is an immune-mediated small bowel disease affecting about 1% of the population worldwide. But the prevalence of CD varies with age, sex, and location. A strict gluten-free diet remains the primary treatment for CD, currently. Most of patients with CD respond well to gluten-free diet with good prognosis, while some patients fail to get symptomatic relief or histological remission (e.g., nonresponsive or refractory CD). Because of heterogeneous clinical appearance, the diagnosis of CD is difficult. Moreover, malignant complications and poor outcomes accompanied with refractory CD present great challenges in disease management. Over the past three decades, cross-sectional imaging techniques (computed tomography [CT] and magnetic resonance imaging [MRI]) play an important role in small bowel inflammatory and neoplastic diseases. Compared with endoscopic techniques, cross-sectional imaging permits clearly presentation of both intraluminal and extraluminal abnormalities. It provides vascular and functional information, thus improving the possibility as diagnostic and follow-up tool. The value of cross-sectional imaging for patients with suspected or confirmed CD has been gradually demonstrated. Studies revealed that certain features suggested by cross-sectional imaging could help to establish the early diagnosis of CD. Besides, the potential contributions of cross-sectional imaging may lie in the evaluation of disease activity and severity, which helps guiding management strategies. The purpose of this review is to provide current overviews and future directions of cross-sectional imaging in adult CD, thus facilitating the understanding and application in clinical practice. CLINICAL RELEVANCE STATEMENT: In this review, we systematically summarized the existing knowledge of cross-sectional imaging in adult CD and analyzed their possible roles in clinical practice, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. KEY POINTS: • Regarding a condition described as "celiac iceberg", celiac disease remains underdiagnosed and undertreated. • Cross-sectional imaging is helpful in clinical management of celiac disease, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. • Cross-sectional imaging should be considered as the valuable examination in patients suspected from celiac disease.

Validation of disease severity index for predicting complicated disease in Crohn's disease: A comparison study with Lémann index.

BACKGROUND: Disease Severity Index (DSI) provides comprehensive assessment of bowel damage (BD). AIMS: To evaluate DSI in patients with Crohn's disease (CD) at high risk of disease progression, compared to Lémann Index (LI). METHODS: Patients with CD in our center were reviewed consecutively between 2017 and 2019. DSI, LI, and complicated CD course were analyzed. RESULTS: The median LI and DSI of included 300 patients were 1.63 (IQR 1.25-3.13) and 42 (IQR 32-51), respectively. 152 patients (50.7%) experienced a complicated disease course (median 5.1 months; IQR 1.1-20.2). DSI (AUC 0.66; 95% CI 0.60-0.72) better predicted a complicated course of CD over LI (AUC 0.56; 95% CI 0.50-0.63; P = 0.007). The cumulative probability of complicated CD course in severe patients was higher than those with 'mild CD' (P < 0.001). The Cox analysis identified DSI>43 (HR 2.18; 95% CI 1.54-3.09; P < 0.001), B2/3 vs. B1 (HR 2.80; 95% CI 1.99-3.94; P < 0.001), and a higher level of CRP (HR 1.01; 95% CI 1.00-1.02; P = 0.005) as independent prognostic factors for complicated CD. However, LI was not associated with complicated CD (P = 0.164). CONCLUSIONS: Higher DSI was associated with complicated disease outcomes. DSI might play a better role than LI in identifying patients at high risks of disease progression.

Occurrence and Health Risks of Organic Micropollutants in Tap Water in Dalian.

Organic micropollutants (OMPs) in tap water may pose risks to human health. Previous studies on the potential health risks of OMPs in tap water may have underestimated the potential health risks of OMPs due to their limited coverage in target pollutants and incomplete toxicity data. In this study, tap water samples were collected in 37 sampling sites in Dalian, China. More than 1,200 target pollutants were screened by combining screening analysis and target analysis. A total of 93 OMPs were detected, with concentration summation ranging from 157 to 1.7 × 104 ng/L among different sampling sites. A total of 17 OMPs (12 agrochemicals, 3 pharmaceuticals and personal care products, and 2 other compounds) were detected in over 80% of the sampling sites. Especially, imidacloprid, tebuconazole, and atrazine-desethyl were found in all the sampling sites. Computational toxicology models were adopted to predict the missing toxicity threshold values of the identified chemicals. Noncarcinogenic risks were estimated to be negligible among all the sampling sites, while carcinogenic risks at six sites were above 10-6 but below 10-4, indicating non-negligible risks. Griseofulvin contributed the most to the carcinogenic risk. This study offers valuable insights that can guide future initiatives to safeguard tap water safety.

Genome-Wide Association Study Identifies the Crucial Candidate Genes for Teat Number in Crossbred Commercial Pigs.

The number of teats is a crucial reproductive trait with significant economic implications on maternal capacity and litter size. Consequently, improving this trait is essential to facilitate genetic selection for increased litter size. In this study, we performed a genome-wide association study (GWAS) of the number of teats in a three-way crossbred commercial Duroc × (Landrace × Yorkshire) (DLY) pig population comprising 1518 animals genotyped with the 50K BeadChip. Our analysis identified crucial quantitative trait loci (QTL) for the number of teats, containing the ABCD4 and VRTN genes on porcine chromosome 7. Our results establish SNP variants of ABCD4 and VRTN as new molecular markers for improving the number of teats in DLY pigs. Furthermore, the most significant noteworthy single nucleotide polymorphism (SNP) (7_97568284) was identified within the ABCD4 gene, exhibiting a significant association with the total teat number traits. This SNP accounted for a substantial proportion of the genetic variance, explaining 6.64% of the observed variation. These findings reveal a novel gene on SSC7 for the number of teats and provide a deeper understanding of the genetic mechanisms underlying reproductive traits.

Low-dose LPS alleviates early brain injury after SAH by modulating microglial M1/M2 polarization via USP19/FOXO1/IL-10/IL-10R1 signaling.

BACKGROUND: Low-dose lipopolysaccharide (LPS) protects against early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanism underlying the neuroprotective roles of low-dose LPS remain largely undefined. METHODS: A SAH mice model was established and the pathological changes of brain were evaluated by wet-dry weight method, HE and Nissl staining, and blood-brain barrier (BBB) permeability assay. Cell apoptosis and inflammation were monitored by TUNEL, flow cytometry and ELISA assays. qRT-PCR, immunofluorescence and Western blot were used to detect the expression of microglial polarization-related or oxidative stress-associated markers. Bioinformatics analysis, luciferase and ChIP assays were employed to detect the direct association between FOXO1 and IL-10 promoter. The ubiquitination of FOXO1 in the in vitro SAH model was detected by co-IP. RESULTS: Low-dose LPS alleviated SAH-induced neurological dysfunction, brain edema, BBB disruption, damage in the hippocampus, neuronal apoptosis and inflammation via modulating microglial M1/M2 polarization by IL-10/IL-10R1 signaling. Mechanistic studies showed that FOXO1 acted as a transcriptional activator of IL-10. USP19 mediated the deubiquitination of FOXO1 to activate IL-10/IL-10R1 signaling, thereby regulating microglial M1/M2 polarization. Functional experiments revealed that low-dose LPS upregulated USP19 to modulate microglial M1/M2 polarization via FOXO1/IL-10/IL-10R1 signaling in SAH mice. CONCLUSION: Low-dose LPS protected against EBI after SAH by modulating microglial M1/M2 polarization via USP19/FOXO1/IL-10/IL-10R1 signaling.