Deep learning-based compressed SENSE improved diffusion-weighted image quality and liver cancer detection: A prospective study.

PURPOSE: To assess whether diffusion-weighted imaging (DWI) with Compressed SENSE (CS) and deep learning (DL-CS-DWI) can improve image quality and lesion detection in patients at risk for hepatocellular carcinoma (HCC). METHODS: This single-center prospective study enrolled consecutive at-risk participants who underwent 3.0 T gadoxetate disodium-enhanced MRI. Conventional DWI was acquired using parallel imaging (PI) with SENSE (PI-DWI). In CS-DWI and DL-CS-DWI, CS but not PI with SENSE was used to accelerate the scan with 2.5 as the acceleration factor. Qualitative and quantitative image quality were independently assessed by two masked reviewers, and were compared using the Wilcoxon signed-rank test. The detection rates of clinically-relevant (LR-4/5/M based on the Liver Imaging Reporting and Data System v2018) liver lesions for each DWI sequence were independently evaluated by another two masked reviewers against their consensus assessments based on all available non-DWI sequences, and were compared by the McNemar test. RESULTS: 67 participants (median age, 58.0 years; 56 males) with 197 clinically-relevant liver lesions were enrolled. Among the three DWI sequences, DL-CS-DWI showed the best qualitative and quantitative image qualities (p range, <0.001-0.039). For clinically-relevant liver lesions, the detection rates (91.4%-93.4%) of DL-CS-DWI showed no difference with CS-DWI (87.3%-89.8%, p = 0.230-0.231) but were superior to PI-DWI (82.7%-85.8%, p = 0.015-0.025). For lesions located in the hepatic dome, DL-CS-DWI demonstrated the highest detection rates (94.8%-97.4% vs 76.9%-79.5% vs 64.1%-69.2%, p = 0.002-0.045) among the three DWI sequences. CONCLUSION: In patients at high-risk for HCC, DL-CS-DWI improved image quality and detection for clinically-relevant liver lesions, especially for the hepatic dome.

Enhancing gadoxetic acid-enhanced liver MRI: a synergistic approach with deep learning CAIPIRINHA-VIBE and optimized fat suppression techniques.

OBJECTIVE: To investigate whether a deep learning (DL) controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-volumetric interpolated breath-hold examination (VIBE) technique can improve image quality, lesion conspicuity, and lesion detection compared to a standard CAIPIRINHA-VIBE technique in gadoxetic acid-enhanced liver MRI. METHODS: This retrospective single-center study included 168 patients who underwent gadoxetic acid-enhanced liver MRI at 3 T using both standard CAIPIRINHA-VIBE and DL CAIPIRINHA-VIBE techniques on pre-contrast and hepatobiliary phase (HBP) images. Additionally, high-resolution (HR) DL CAIPIRINHA-VIBE was obtained with 1-mm slice thickness on the HBP. Three abdominal radiologists independently assessed the image quality and lesion conspicuity of pre-contrast and HBP images. Statistical analyses involved the Wilcoxon signed-rank test for image quality assessment and the generalized estimation equation for lesion conspicuity and detection evaluation. RESULTS: DL and HR-DL CAIPIRINHA-VIBE demonstrated significantly improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE (p < 0.001), with a shorter acquisition time (DL vs standard, 11 s vs 17 s). However, the former presented a more synthetic appearance (both p < 0.05). HR-DL CAIPIRINHA-VIBE showed superior lesion conspicuity to standard and DL CAIPIRINHA-VIBE on HBP images (p < 0.001). Moreover, HR-DL CAIPIRINHA-VIBE exhibited a significantly higher detection rate of small (< 2 cm) solid focal liver lesions (FLLs) on HBP images compared to standard CAIPIRINHA-VIBE (92.5% vs 87.4%; odds ratio = 1.83; p = 0.036). CONCLUSION: DL and HR-DL CAIPIRINHA-VIBE achieved superior image quality compared to standard CAIPIRINHA-VIBE. Additionally, HR-DL CAIPIRINHA-VIBE improved the lesion conspicuity and detection of small solid FLLs. DL and HR-DL CAIPIRINHA-VIBE hold the potential clinical utility for gadoxetic acid-enhanced liver MRI. CLINICAL RELEVANCE STATEMENT: DL and HR-DL CAIPIRINHA-VIBE hold promise as potential alternatives to standard CAIPIRINHA-VIBE in routine clinical liver MRI, improving the image quality and lesion conspicuity, enhancing the detection of small (< 2 cm) solid focal liver lesions, and reducing the acquisition time. KEY POINTS: • DL and HR-DL CAIPIRINHA-VIBE demonstrated improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE, in addition to a shorter acquisition time. • DL and HR-DL CAIPIRINHA-VIBE yielded a more synthetic appearance than standard CAIPIRINHA-VIBE. • HR-DL CAIPIRINHA-VIBE showed improved lesion conspicuity than standard CAIPIRINHA-VIBE on HBP images, with a higher detection of small (< 2 cm) solid focal liver lesions.

Clinicopathological and molecular genetic alterations in monomorphic-epitheliotropic intestinal T-cell lymphoma of the small intestine.

BACKGROUND: Small intestinal monomorphic-epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma originating in the gastrointestinal tract. This study aimed to investigate the clinicopathological features, immunophenotypes, and molecular genetic changes of MEITL. METHODS: The clinicopathological data for three patients with surgically resected MEITL of the small intestine were collected. Next, immunohistochemical labeling, Epstein-Barr virus (EBV) in situ hybridization, assessment of clonal rearrangement of T-cell receptor (TCR) genes, and next-generation sequencing (NGS) were performed. RESULTS: Of the three patients, two were male and one was female, with ages of 61, 67, and 73 years, respectively. Clinical manifestations were predominantly abdominal pain and distension. Histopathology revealed infiltrative growth of small-to-medium-sized lymphocytes with a consistent morphology between the intestinal walls, accompanied by an obvious pro-epithelial phenomenon. The expression of CD3, CD8, CD43, CD56, TIA-1, CD103, H3K36me3, and Bcl-2 was detected, and the Ki-67 proliferation index ranged from 50% to 80%. All three patients tested negative for EBER. However, monoclonal rearrangement of the TCR gene was detected in them. NGS testing showed a JAK3 mutation in all three cases. Further, STAT5B, SETD2, and TP53 mutations were each observed in two cases, and a BCOR mutation was found in one case. All patients were treated with chemotherapy after surgery. Two patients died 7 and 15 month post-operation, and one patient survived for 5 months of follow-up. CONCLUSIONS: Our findings demonstrate that mutations in JAK3 and STAT5B of the JAK/STAT pathway and inactivation of the oncogene SETD2 markedly contribute to the lymphomagenesis of MEITL.

Protective effects of Huang-Qi-Ge-Gen decoction against diabetic liver injury through regulating PI3K/AKT/Nrf2 pathway and metabolic profiling.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Qi-Ge-Gen decoction (HGD) is a traditional Chinese medicine prescription that has been used for centuries to treat "Xiaoke" (the name of diabetes mellitus in ancient China). However, the ameliorating effects of HGD on diabetic liver injury (DLI) and its mechanisms are not yet fully understood. AIM OF THE STUDY: To elucidate the ameliorative effect of HGD on DLI and explore its material basis and potential hepatoprotective mechanism. MATERIALS AND METHODS: A diabetic mice model was induced by feeding a high-fat diet and injecting intraperitoneally with streptozotocin (40 mg kg-1) for five days. After the animals were in confirmed diabetic condition, they were given HGD (3 or 12 g kg-1, i. g.) for 14 weeks. The effectiveness of HGD in treating DLI mice was evaluated by monitoring blood glucose and blood lipid levels, liver function, and pathological conditions. Furthermore, UPLC-MS/MS was used to identify the chemical component profile in HGD and absorption components in HGD-treated plasma. Network pharmacology and molecular docking were performed to predict the potential pathway of HGD intervention in DLI. Then, the results of network pharmacology were validated by examining biochemical parameters and using western blotting. Lastly, urine metabolites were analyzed by metabolomics strategy to explore the effect of HGD on the metabolic profile of DLI mice. RESULTS: HGD exerted therapeutic potential against the disorders of glucose metabolism and lipid metabolism, liver dysfunction, liver steatosis, and fibrosis in a DLI model mice induced by HFD/STZ. A total of 108 chemical components in HGD and 18 absorption components in HGD-treated plasma were preliminarily identified. Network pharmacology and molecular docking results of the absorbed components in plasma indicated PI3K/AKT as a potential pathway for HGD to intervene in DLI mice. Further experiments verified that HGD markedly reduced liver oxidative stress in DLI mice by modulating the PI3K/AKT/Nrf2 signaling pathway. Moreover, 19 differential metabolites between normal and DLI mice were detected in urine, and seven metabolites could be significantly modulated back by HGD. CONCLUSIONS: HGD could ameliorate diabetic liver injury by modulating the PI3K/AKT/Nrf2 signaling pathway and urinary metabolic profile.

Noninvasive prediction of insufficient biochemical response after ursodeoxycholic acid treatment in patients with primary biliary cholangitis based on pretreatment nonenhanced MRI.

OBJECTIVES: To explore the feasibility of pretreatment nonenhanced magnetic resonance imaging (MRI) in predicting insufficient biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC). METHODS: From January 2009 to April 2022, consecutive PBC patients who were treated with UDCA and underwent nonenhanced MRI within 30 days before treatment were retrospectively enrolled. All MR images were independently evaluated by two blinded radiologists. Uni- and multivariable logistic regression analyses were performed to develop a predictive model for 12-month insufficient biochemical response. Model performances were evaluated by computing the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: A total of 74 patients (50.6 ± 11.9 years; 62 females) were included. Three pretreatment MRI features, including hepatomegaly (odds ratio [OR]: 4.580; p = 0.011), periportal hyperintensity on T2-weighted imaging (T2WI) (OR: 4.795, p = 0.008), and narrowing of the bile ducts (OR: 3.491; p = 0.027) were associated with 12-month insufficient biochemical response in the multivariable analysis. A predictive model based on the above indicators had an AUC of 0.781, sensitivity of 85.4%, and specificity of 61.5% for predicting insufficient biochemical response. CONCLUSIONS: A noninvasive model based on three pretreatment MRI features could accurately predict 12-month insufficient biochemical response to UDCA in patients with PBC. Early identification of PBC patients at increased risk for insufficient response can facilitate the timely initiation of additional treatment. CLINICAL RELEVANCE STATEMENT: A noninvasive predictive model constructed by incorporating three pretreatment MRI features may help identify patients with primary biliary cholangitis at high risk of insufficient biochemical response to ursodeoxycholic acid and facilitate the timely initiation of additional treatment. KEY POINTS: • Noninvasive imaging features based on nonenhanced pretreatment MRI may predict an insufficient biochemical response to UDCA in PBC patients. • A combined model based on three MRI features (hepatomegaly, periportal hyperintensity on T2-weighted imaging, and narrowing of the bile ducts) further improved the predictive efficacy for an insufficient biochemical response to UDCA in PBC patients, with high sensitivity and specificity. • The nomogram of the combined model showed good calibration and predictive efficacy for an insufficient biochemical response to UDCA in PBC patients. In particular, the calibration curve visualised the clinical applicability of the prediction model.

Endovascular thrombectomy for acute ischemic stroke in elderly patients with large ischemic cores.

BACKGROUND: Understanding the benefits and risks of endovascular therapy (EVT) is crucial for elderly patients with large ischemic cores, as the combination of advanced age and extensive brain infarction may negatively impact clinical outcomes. METHODS: The study retrospectively analyzed clinical outcomes for elderly stroke patients (age ≥ 70) with large ischemic cores (Alberta Stroke Program Early CT Score [ASPECTS] < 6 or ischemic cores ≥ 70 ml) in the anterior circulation using data from our prospective database between June 2018 and January 2022. The effectiveness and risks of EVT in those patients were investigated, with the primary outcome being fair outcome (modified Rankin Scale, mRS ≤ 3). RESULTS: Among 182 elderly patients with large ischemic core volume (120 in the EVT group and 62 in the non-EVT group), 20.9% (38/182, 22.5% in the EVT group vs. 17.7% in the non-EVT group) achieved a fair outcome. Meanwhile, 49.5% (90/182, 45.8% in the EVT group vs. 56.5% in the non-EVT group) of them died at 3 months. The benefits of EVT numerically exceeded non-EVT treatment for those aged ≤ ~ 85 years or with a mismatch volume ≥ ~ 50 ml. However, after adjustment, EVT was associated with an increased risk of symptomatic intracranial hemorrhage (aOR 4.24, 95%CI 1.262-14.247). CONCLUSIONS: This study highlights the clinical challenges faced by elderly patients with large infarctions, resulting in poor outcomes at 3 months. EVT may still provide some benefits in this population, but it also carries an increased risk of intracranial hemorrhage.

Preoperative prediction of cholangiocyte phenotype hepatocellular carcinoma on contrast-enhanced MRI and the prognostic implication after hepatectomy.

BACKGROUND: Hepatocellular carcinoma (HCC) expressing cytokeratin (CK) 7 or CK19 has a cholangiocyte phenotype that stimulates HCC proliferation, metastasis, and sorafenib therapy resistance This study aims to noninvasively predict cholangiocyte phenotype-positive HCC and assess its prognosis after hepatectomy. METHODS: Between January 2010 and May 2022, preoperative contrast-enhanced MRI was performed on consecutive patients who underwent hepatectomy and had pathologically confirmed solitary HCC. Two abdominal radiologists separately assessed the MRI features. A predictive model for cholangiocyte phenotype HCC was created using logistic regression analysis and five-fold cross-validation. A receiver operating characteristic curve was used to calculate the model performance. Kaplan-Meier and log-rank methods were used to evaluate survival outcomes. RESULTS: In total, 334 patients were included in this retrospective study. Four contrast-enhanced MRI features, including "rim arterial phase hyperenhancement" (OR = 5.9, 95% confidence interval [CI]: 2.9-12.0, 10 points), "nodule in nodule architecture" (OR = 3.5, 95% CI: 2.1-5.9, 7 points), "non-smooth tumor margin" (OR = 1.6, 95% CI: 0.8-2.9, 3 points), and "non-peripheral washout" (OR = 0.6, 95% CI: 0.3-1.0, - 3 points), were assigned to the cholangiocyte phenotype HCC prediction model. The area under the curves for the training and independent validation set were 0.76 and 0.73, respectively. Patients with model-predicted cholangiocyte phenotype HCC demonstrated lower rates of recurrence-free survival (RFS) and overall survival (OS) after hepatectomy, with an estimated median RFS and OS of 926 vs. 1565 days (p < 0.001) and 1504 vs. 2960 days (p < 0.001), respectively. CONCLUSIONS: Contrast-enhanced MRI features can be used to predict cholangiocyte phenotype-positive HCC. Patients with pathologically confirmed or MRI model-predicted cholangiocyte phenotype HCC have a worse prognosis after hepatectomy. CRITICAL RELEVANCE STATEMENT: Four contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC and a worse prognosis following hepatectomy; these features may assist in predicting prognosis after surgery and improve personalized treatment decision-making. KEY POINTS: • Four contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC. • A noninvasive cholangiocyte phenotype HCC predictive model was established based on MRI features. • Patients with cholangiocyte phenotype HCC demonstrated a worse prognosis following hepatic resection.

Influence of Job Burnout on Decision-Making and Coping With Stress Among Nurses.

Job burnout is highly prevalent among health care workers. This study determined the effect of job burnout on decision-making and coping with stress among nurses. Two hundred seventy-seven nurses in Xijing Hospital were investigated using the Job Burnout Scale, Decision Scale, and Simple Stress Coping Style Scale. The total score of job burnout was 107.8 ± 16.479 (severe burnout) and clinical decision-making consciousness was 123.75 ± 16.094 (moderate decision-making consciousness). No statistical differences existed in different gender samples (P > .05). Burnout and clinical decision-making awareness of clinical nurses were stronger than nursing interns and regular trainee nurses, but the occupational pressure of nursing interns was the highest (P < .05). Marital status also showed significant differences in job burnout; unmarried nurses were more prone to burnout (P < .05). In conclusions, burnout is a serious issue among nurses, which is closely related with clinical decision-making awareness, negative coping, and occupational stress. Nurse identity and marital status had significant effects on burnout.

Moshen granule ameliorates membranous nephropathy by regulating NF-ƙB/Nrf2 pathways via aryl hydrocarbon receptor signalling.

Considerable achievements were realized in illuminating underlying pathological mechanisms of patients with idiopathic membranous nephropathy (IMN). Although IMN patients are well diagnosed before they reach renal failure, no currently available drug intervention is effective in halting IMN progression. In this study, we assess Moshen granule (MSG) effect on IMN patients and cationic bovine serum albumin (CBSA)-induced rats. Increasing studies has indicated that activation of aryl hydrocarbon receptor (AHR) was related to oxidative stress and inflammation. We further determine MSG effect on AHR, nuclear factor ƙB (NF-ƙB) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the CBSA-induced rats. MSG markedly reduces proteinuria and improves kidney function in both IMN patients and rats induced by CBSA. MSG markedly inhibits increased mRNA expressions of intrarenal AHR and its four downstream target genes including CYP1A1, CYP1A2, CYP1B1 and COX-2 compared with untreated CBSA-induced rats. This is accompanied by markedly downregulated protein expressions of p-IƙBα and NF-ƙB p65 and its downstream gene products including MCP-1, COX-2, 12-LOX, iNOS, p47phox and p67phox, while markedly preserves protein expressions of Nrf2 and its downstream gene products including catalase, HO-1, GCLM, GCLC, MnSOD and NQO1 in the kidney tissues. These data suggests MSG blunts podocyte damage through inhibiting activation of NF-ƙB/Nrf2 pathway via AHR signaling. This finding may provide a promising therapy for treatment of IMN through oxidative stress and inflammation.

A cytodiagnosis of adenoid cystic carcinoma of the tracheobronchial tree through a systematic clinical case comparison and analysis.

BACKGROUND: Primary adenoid cystic carcinoma (AdCC) of the tracheobronchial tree is very rare with a high risk for recurrence and metastasis. The diagnosis of AdCC by histologic and immunohistochemical means has been well studied clinically. However, the identification of AdCC by cytologic features remains elusive due to the atypical features the cancer presents. This study aimed to describe the cytologic features of AdCC by using bronchial brushing, which could aid in distinguishing AdCC from other pulmonary carcinomas. METHODS: The cytopathological features of bronchial brushing smears collected from seven cases were histologically diagnosed as AdCC. The defined cytologic features, which could potentially be diagnostic, were systemically analyzed. RESULTS: Four out of the seven cytologic cases were inconcordance with the histologic diagnosis and cytologically classified as positive for malignant cells, small cell carcinoma, or atypical cells. Three cases showed a characteristic adenoid structure and magenta stroma forming globule, which was distinguished from the four cases. Cytologically, the above mentioned three cases were uniform with relatively small bland nuclei and little cytoplasm. In this study, only one case showed atypical polygonal medium-sized cells with conspicuous nucleoli. CONCLUSIONS: Unlike fine-needle aspiration cytology, magenta stroma globules might offer an alternate clue for cytodiagnosis of AdCC clinically. Bronchial brushings cytology was more present in bland uniform cells with high nuclear to cytoplasmic ratios and background mucoid substance. More cases should be collected and confirmed using histopathology with careful film reading to reduce the rate of misdiagnosis.

Expression of Ferroptosis-Related Proteins Glutathione Peroxidase 4, Nuclear Factor Erythroid 2-Related Factor 2, and Solute Carrier Family 7 Member 11 in Gastric Cancer Patients.

BACKGROUND/AIMS: The aim of this study was to investigate the expression of ferroptosis-related targets glutathione peroxidase 4, nuclear factor erythroid 2-related factor 2, and solute carrier family 7 member 11 in gastric cancer and the correlation between their expression and the clinicopathological characteristics and prognosis of gastric cancer patients. MATERIALS AND METHODS: Forty-two gastric cancer samples and paracancerous samples were included, and all cases were detected with glutathione peroxidase 4, nuclear factor erythroid 2-related factor 2, and solute carrier family 7 member 11 by immunohistochemistry. Six gastric cancer cell lines and 1 normal gastric epithelial cell were stably cultured, and the expression of target genes of different cell lines was detected using western blot and polymerase chain reaction. Public data were downloaded from the database, and analyses were performed by software including Statistical Package for the Social Sciences and Prism. RESULTS: A high glutathione peroxidase 4 expression level was found in 7 (16.67%) cancer tissues and 0 (0.00%) paracancerous tissues (P = .012). Nuclear factor erythroid 2-related factor 2 was upregulated in 23 (54.76%) cancer tissues and 2 (4.76%) paracancerous tissues (P < .001). Solute carrier family 7 member 11 showed increased expression in 4 (9.52%) cancer tissues and 1 (2.38%) paracancerous tissue (P = .356). No significant association existed between their expression and the clinicopathological characteristics and prognosis of gastric cancer patients. Glutathione peroxidase 4 and nuclear factor erythroid 2-related factor 2 expressions were higher in all 6 gastric cancer cell lines compared to normal gastric epithelial cells. CONCLUSION: Glutathione peroxidase 4 and nuclear factor erythroid 2-related factor 2 expressions were significantly higher in gastric cancer, which may be potential biomarkers of gastric cancer.

Effect of fermented dandelion on productive performance, meat quality, immune function, and intestinal microbiota of broiler chickens.

BACKGROUND: Dandelion has a great potential to be used as feed additive. Using microbial fermentation technology to degrade cell walls is conducive to enable better release of bioactive compounds of dandelion. This study intended to explore the effect of fermented dandelion (FD) on production performance, meat quality, immune function, and intestinal microbiota of broiler chickens. One-hundred and twenty 1-day-old male Arbor Acres broiler chickens were randomly allotted into three treatments: CON (basal diet, control), LFD and HFD (basal diet with 500 and 1000 mg/kg FD, respectively), with five replicates of eight birds each. The experiment lasted for 42 days. RESULTS: The results showed that birds in HFD group had increased ADG during 1-21 days (P < 0.05). On day 21, the bursa of Fabricius index of birds in LFD group was higher (P < 0.05), while the serum contents of IFN-γ and TNF-ɑ were lower in HFD group (P < 0.05). FD supplementation decreased the observed_species, shannon, chao1 and ace indexes (P < 0.05) as well as the abundance of Bacteroidota, Bacteroides, and Alistipes (P < 0.05). Birds in HFD group had higher abundance of Firmicutes and lower abundance of Verrucomicrobiota (P < 0.05). LFD group had lower abundance of unidentified_bacteria (P < 0.05). On day 42, the abdominal fat yield of HFD group was decreased (P < 0.05). Birds in LFD group had lower L* and b* values of breast muscle (P < 0.05), while higher spleen index. The CAT activities of breast muscle of FD groups were higher (P < 0.05). CONCLUSION: In summary, dietary FD supplementation at 1000 mg/kg improved production performance and immune function and modulated microbiota composition in ileum of broiler chickens. FD can be supplemented in the diet to enhance performance and health of broiler chickens, of which 1000 mg/kg FD is more effective.

Identification of in vivo metabolites of Citri Sarcodactylis Fructus by UHPLC-Q/Orbitrap HRMS.

INTRODUCTION: Citri Sarcodactylis Fructus has the effects of relieving cough, removing phlegm, and reducing asthma, but little is known about the metabolic and distribution of its chemical constituents in vivo. Therefore, it is necessary to study the metabolism of Citri Sarcodactylis Fructus in vivo. OBJECTIVE: We aimed to (1) analyze the distribution of prototype compounds and metabolites of the chemical constituents of Citri Sarcodactylis Fructus in rat and (2) infer the metabolites and metabolic pathways of the chemical constituents. MATERIALS AND METHODS: A C18 column (3 × 100 mm, 2.6 µm) was used. The mobile phase was water containing 0.1% formic acid (eluent A) and acetonitrile containing 0.1% formic acid (eluent B) at a discharge rate of 0.3 mL/min. Mass spectra of biological samples were collected in electrospray ionization (ESI) positive ion mode in the m/z 100-1500 scan range. The obtained biological samples were then subjected to chemical analysis, including plasma, urine, feces, and heart, liver, spleen, lungs, kidneys, stomach, and small intestine tissues. Prototype compounds and metabolites were identified. RESULTS: In all, 40 prototype compounds and 78 metabolites, including 26 phase I metabolites and 52 phase II metabolites, were identified using UHPLC-Q/Orbitrap HRMS. Eight possible metabolic pathways (reduction, hydrolysis, dehydration, methylation, hydroxylation, sulfation, glucuronidation, and demethylation) were proposed. The prototype compounds were predominantly distributed in lung tissues. The metabolites were mainly distributed in plasma and kidney tissues. CONCLUSION: We systematically investigated the metabolites of Citri Sarcodactylis Fructus in vivo. We suggest metabolic pathways that might be relevant for further metabolic studies and screening of active ingredients of Citrus Sarcodactylis Fructus in vivo.

Cytotoxicity of 4 Wild Mushrooms in a Case of Yunnan Sudden Unexplained Death.

OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS: The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

Characteristics of dissolved organic matter composition in biochar: Effects of feedstocks and pyrolysis temperatures.

Biochar has widely used in soil pollution remediation due to its advantages of high efficiency and environmental sustainability. Dissolved organic matter (DOM) released by biochar plays a non-negligible role in the migration and transformation of pollutants in environment, and its composition was regarded as main impact factor. In this study, 28 biochar were investigated to detect the effect of pyrolysis temperature and feedstock on DOM content and components. Results showed that the content of DOM released from biochar at low pyrolysis temperatures (300-400 ℃) was higher than that from high pyrolysis temperatures (500-600 ℃). In addition, the specific UV-Visible absorbance at 254 nm (SUVA254) results expressed that DOM from peanut shell biochar (PSBC), rice husk biochar (RHBC) and bamboo biochar (BBC) had higher humification at high temperatures. Moreover, one fulvic acid-like (C2) and two humic acid-like (C1, C3) substances were main fluorescent components of biochar-derived DOM identified by parallel factor analysis based on excitation emission matrices fluorescence spectroscopies (EEM-PARAFAC). With the increase of pyrolysis temperature, humic acid substances content gradually decreased. The correlation analysis results revealed that pyrolysis temperatures and O/C, H/C, DOM content, the biological index (BIX), humification index (HIX), C1% and C3% was negatively correlated (p < 0.001). Thus, the pyrolysis temperatures take important roles in composition of DOM released from biochar, and this research would provide a reference for the application of biochar in the environment.

RNF8 depletion attenuates hepatocellular carcinoma progression by inhibiting epithelial-mesenchymal transition and enhancing drug sensitivity.

Despite substantial advances that have been made in understanding the etiology of hepatocellular carcinoma (HCC), the early-stage diagnosis and treatment of advanced-stage HCC remain a major challenge. RNF8, an E3 ligase important for the DNA damage response, has been proven to facilitate the progression of breast and lung cancer, but its role in HCC remains unclear. In this study, we find that the expression of RNF8 is up-regulated in HCC tissues and positively correlated with poor prognosis of HCC. Furthermore, silencing RNF8 by siRNAs attenuates the migration of HCC cells and inhibits epithelial-mesenchymal transition (EMT) by regulating the expressions of proteins including N-cadherin, ß-catenin, snail, and ZO-1. Moreover, Kaplan‒Meier survival analysis shows that high RNF8 expression predicts poor survival benefits from sorafenib. Finally, cell viability assay demonstrates that RNF8 depletion enhances the sensitivity of HCC cells to sorafenib and lenvatinib treatment. We hypothesize that the inhibitory role of RNF8 in EMT and its enhancing effects on anti-cancer drugs orchestrate the protective effects of RNF8 deficiency in HCC, which indicates its potential in clinical application.

EPOR activation attenuates colitis via enhancing LC3B-dependent apoptotic cell clearance.

Systemic immune activation and excessive inflammatory response, induced by intestinal barrier damage, are the major characteristics of inflammatory bowel disease (IBD). Excessive apoptotic cell accumulation leads to the production of a large number of inflammatory factors, further aggravating IBD development. Gene set enrichment analysis data showed that the homodimeric erythropoietin receptor (EPOR) was highly expressed in the whole blood of patients with IBD. EPOR is specifically expressed in intestinal macrophages. However, the role of EPOR in IBD development is unclear. In this study, we found that EPOR activation significantly alleviated colitis in mice. Furthermore, in vitro, EPOR activation in bone marrow-derived macrophage (BMDMs) promoted microtubule-associated protein 1 light chain 3B (LC3B) activation and mediated the clearance of apoptotic cells. Moreover, our data showed that EPOR activation facilitated the expression of phagocytosis- and tissue-repair-related factors. Our findings suggest that EPOR activation in macrophages promotes apoptotic cell clearance, probably via LC3B-associated phagocytosis (LAP), providing a new mechanism for understanding pathological progression and a novel potential therapeutic target for colitis.

ULK1 Depletion Protects Mice from Diethylnitrosamine-Induced Hepatocarcinogenesis by Promoting Apoptosis and Inhibiting Autophagy.

Purpose: The uncoordinated-51 like kinase 1 (ULK1) is an important serine/threonine protein kinase involved in autophagy, especially for the initiation stage. Previous studies have shown that ULK1 could be used as a prognostic marker in predicting poor progression-free survival and a therapeutic target for hepatocellular carcinoma (HCC) when treated with sorafenib; however, its role during hepatocarcinogenesis remains to be elucidated. Methods: CCK8 and colony formation assay were used to detect cell growth ability. Western blotting was performed to determine expression level of protein. Data from public database were downloaded to analyze expression of ULK1 at mRNA level and predict survival time. RNA-seq was conducted to reveal disturbed gene profile orchestrated by ULK1 depletion. A diethylnitrosamine (DEN)-induced HCC mice model was used to uncover the role of ULK1 in hepatocarcinogenesis. Results: ULK1 was up-regulated in liver cancer tissues and cell lines, and knockdown of ULK1 promoted apoptosis and suppressed proliferation of liver cancer cells. In in vivo experiments, Ulk1 depletion attenuated starvation-induced autophagy in mice liver, reduced diethylnitrosamine (DEN)-induced hepatic tumor number and size, and prevented tumor progression. Further, RNA-seq analysis revealed a close relationship between Ulk1 and immunity with significant changes in gene sets enriched in the interleukin and interferon pathways. Conclusion: ULK1 deficiency prevented hepatocarcinogenesis and inhibited hepatic tumor growth, and might be a molecular target for the prevention and treatment of HCC.