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Abstract 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.

Background: Patients with acute tubular necrosis (ATN) not only have severe renal failure, but also have many comorbidities, which can be life-threatening and require timely treatment. Identifying the influencing factors of ATN and taking appropriate interventions can effectively shorten the duration of the disease to reduce mortality and improve patient prognosis.Methods: Mortality prediction models were constructed by using the random survival forest (RSF) algorithm and the Cox regression. Next, the performance of both models was assessed by the out-of-bag (OOB) error rate, the integrated brier score, the prediction error curve, and area under the curve (AUC) at 30, 60 and 90 days. Finally, the optimal prediction model was selected and the decision curve analysis and nomogram were established.Results: RSF model was constructed under the optimal combination of parameters (mtry = 10, nodesize = 88). Vasopressors, international normalized ratio (INR)_min, chloride_max, base excess_min, bicarbonate_max, anion gap_min, and metastatic solid tumor were identified as risk factors that had strong influence on mortality in ATN patients. Uni-variate and multivariate regression analyses were used to establish the Cox regression model. Nor-epinephrine, vasopressors, INR_min, severe liver disease, and metastatic solid tumor were identified as important risk factors. The discrimination and calibration ability of both predictive models were demonstrated by the OOB error rate and the integrated brier score. However, the prediction error curve of Cox regression model was consistently lower than that of RSF model, indicating that Cox regression model was more stable and reliable. Then, Cox regression model was also more accurate in predicting mortality of ATN patients based on the AUC at different time points (30, 60 and 90 days). The analysis of decision curve analysis shows that the net benefit range of Cox regression model at different time points is large, indicating that the model has good clinical effectiveness. Finally, a nomogram predicting the risk of death was created based on Cox model.Conclusion: The Cox regression model is superior to the RSF algorithm model in predicting mortality of patients with ATN. Moreover, the model has certain clinical utility, which can provide clinicians with some reference basis in the treatment of ATN and contribute to improve patient prognosis.

This trial was performed to determine the effects of dietary supplementation of dry dandelion (Taraxacum mongolicum Hand. -Mazz.) on carcase traits, breast meat quality, muscle fatty and amino acid composition and antioxidant capacity of broiler chickens. A total of 120 Arbour Acres broiler chickens were randomly allotted to three groups and fed basal diet (CON), basal diet supplemented with 0.5 g/kg (LD) or 1.0 g/kg (HD) of dandelion. The results showed that compared with LD group, the eviscerated percentage of HD group tended to be higher (p = 0.090), while the abdominal fat yield tended to be lower (p = 0.078). In addition, dandelion quadratically increased redness, water loss rate, the proportion of C20:2, C20:4n-6, C22:6n-3 and the sum of n-3 PUFA and decreased cooking loss of Pectoralis major (PA) muscle (p

The flower buds and fruits of Sophora japonica are known as Flos sophorae immaturus (Chinese Huaimi, FSI), Flos sophorae (Chinese Huaihua, FLS) and Fructus sophorae (Chinese Huaijiao, FRS) due to their different physiological forms. FSI and FLS are precious resources of homology of medicine and food, while FRS is a valuable Chinese herb, and all of which have been used for thousands of years. There are great differences in the active ingredients, functions and toxicological properties of FSI, FLS and FRS. However, they are often confused and assumed to have fairly similar validity, which is detrimental to their precision development of resources of homology of medicine and food. This review summarized the active constituents, analytical techniques and pharmacological properties of FSI, FLS and FRS, then systematically compared their differences. The article will help people better understand and distinguish the differences and characteristics of FSI, FLS and FRS in bioactive constituents, content of functional components and pharmacological properties, which can contribute to their highly efficient targeted applications in the future food and medical fields.

Abstract 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

Abstract 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

Abstract 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.

The eastern extension of the Tibetan Plateau (EETP) has complex terrain, unique climate characteristics, and significant regional differences. Based on the hourly precipitation data from 444 stations over the EETP, the characteristics of the extreme precipitation event (EPE) diurnal cycle over the EETP and their regional differences during the warm season (May–September) have been indicated and revealed in this study. The mean duration of EPEs at most stations over the EETP is over 6 h, except for some stations in the eastern part of the Tibetan Plateau and Yunnan province. In addition to the Qinba Mountain area, EPEs developed rapidly in most stations. EPEs with long (short) durations usually start at night (afternoon). But in the southwestern part of the Sichuan Basin (eastern part of the Tibetan Plateau), long-duration EPEs and short-duration EPEs often start at night (afternoon to early night). Meanwhile, the long-duration EPEs lead to the nocturnal diurnal peaks and eastward propagating features of extreme precipitation amount (EPA) over the EETP. In the Sichuan Basin (the eastern part of the Tibetan Plateau), the onset and peak moments of total EPEs show a single diurnal peak and appear at midnight (late afternoon to early night). The onset and peak moments of EPEs in the Yunnan–Guizhou Plateau and the Qinba Mountain area exhibit two diurnal peaks, one at midnight and the other from afternoon to early night. Over the EETP, for the long-duration EPEs, the peak moments are often delayed by 2–3 h compared to the start moment, while for the short-duration EPEs, the peak moment and the start moment almost coincide.

Abstract Background and aims Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. The aim of the present study was to characterize the clinical features and therapeutic response of patients with IgG4-RD and identify risk factors for disease relapse. Methods We collected baseline data of eligible patients with IgG4-RD and analyzed clinical features by interview and review of medical records. The patients who received glucocorticoids (GC) therapy with at least 3 months follow-up were used to characterize the therapeutic response and identify risk factors for relapse. Result Totally 127 IgG4-RD patients, including 92 males and 35 females, were enrolled in the present study. The median age of onset was 63.0 years, ranging from 23 to 86. The pancreas, bile duct and lymph nodes were the most frequently involved organs. The serum IgG4 level was elevated in 94.5% of the patients and was correlated with the number of organs involved. Patients classified as head and neck limited group were more likely to be female. Compared to Mikulicz syndrome and systemic involvement group, pancreato-hepatobiliary group had higher aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin and lower IgG4 level. Mikulicz syndrome and systemic involvement group had the highest IgG4-RD RI score, IgG level. Among 92 patients who received medical therapy with at least 3 months follow-up, 76 received GC alone or in combination with immunomodulator (IM) and 16 patients did not take GC. 74 out of the 76 patients (97.3%) achieved remission, with 59 of them remained in remission and 15 of them relapsed. Whereas 16 patients did not take GC, among them, 6 patients achieved remission with one relapsed. On multivariate analysis, higher initial score of ACR/EULAR IgG4-RD Classification Criteria and GC withdrawal were independent predictors for relapse. Conclusion Four phenotypes of IgG4-RD showed different demographic and serological features. GC + IM therapy was safe and effective and might protect patients from relapse. The independent risk factors of relapse were GC withdrawal and higher score of ACR/EULAR IgG4-RD Classification Criteria.

Curcumenol, an effective ingredient of Wenyujin, has been reported that exerted its antitumor potential in a few cancer types. However, the effect and molecular mechanism of curcumenol in lung cancer are largely unknown. Here, we found that curcumenol induced cell death and suppressed cell proliferation in lung cancer cells. Next, we demonstrated that ferroptosis was the predominant method that contributed to curcumenol-induced cell death of lung cancer in vitro and vivo for the first time. Subsequently, using RNA sequencing, we found that the long non-coding RNA H19 (lncRNA H19) was significantly downregulated in lung cancer cells treated with curcumenol, when compared to untreated controls. Overexpression of lncRNA H19 eliminated the anticancer effect of curcumenol, while lncRNA H19 knockdown promoted ferroptosis induced by curcumenol treatment. Mechanistically, we showed that lncRNA H19 functioned as a competing endogenous RNA to bind to miR-19b-3p, thereby enhanced the transcription activity of its endogenous target, ferritin heavy chain 1 (FTH1), a marker of ferroptosis. In conclusion, our data show that the natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis, and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death. Therefore, our findings will hopefully provide a valuable drug for treating lung cancer patients.

Abstract Background RNF8 is an E3 ligase identified as a critical DNA damage-responsive protein. Recently, multiple reports have shown that RNF8 could be used as an important therapeutic target for cancer chemo/radiotherapy. However, the understanding of RNF8 remains limited due to the lack of its interactome reference map and comprehensive analysis of RNF8 in diverse cancers, which underscores the need to map the interactome of RNF8 via high-throughput methods. Results A two-way identification method based on LC–MS was designed for the identification of the RNF8 interactome with high-specificity. By in silico analysis and in vitro validation, we identified a new reference map of the RNF8 interactome network containing many new targets, such as YBX1, DNMT1, and HDCA1, new biological functions and the gene-disease associations of RNF8. Our results revealed a close relationship between RNF8 and neurodegenerative diseases or tumor-infiltrating immune cells using bulk RNA-seq and scRNA-seq datasets. As a proof of concept of our interactome map, we validated the direct binding between RNF8 and YBX1 and showed that RNF8 catalyzed the ubiquitination of YBX1. These results demonstrated that RNF8 might be a crucial regulator of YBX1. Conclusions Our work provides a unique framework for researchers and clinicians who seek to better explore or understand RNF8-regulated biological functions in cancers. This study will hopefully facilitate the rational design and further development of anti-RNF8 therapy in cancers. Graphical abstract

Abstract Background Dandelion is becoming an exploitable alternative to the widely prohibited antibiotics in the poultry production. This research aimed to investigate the effects of dandelion on the growth performance and intestinal barrier function of broiler chickens maintained under standard condition of management. One-hundred and sixty 1-day-old Arbor Acres (AA) male broiler chickens were randomly divided into four groups, with five replicates of eight birds each. The birds were fed a basal diet supplemented without (control group, [CON]) or with 500 (low dose [LD]) or 1000 (high dose [HD]) mg/kg dandelion or with 250 mg/kg chlortetracycline 20% premix (CTC) for 42 days, including the starter phase (d 1 to 21) and the grower phase (d 22 to 42). Body weight (BW) of each bird and feed consumption of each replicate were measured at d 21 and d 42. The ileal tissues were collected on day 21 and 42 to determine expression of genes coding for tight junction protein and mucin as well as ELISA analysis for immune factor. The ileal digesta was collected for microbiota and short chain fatty acids analysis. Results Compared with CON group, during day 1–21, the average daily feed intake (ADFI) and feed/gain ratio (F/G) of LD group were lower (P < 0.05); during day 22–42, the F/G of LD and CTC group tended to be lower (P = 0.07); during the overall phase, the ADFI of HD and CTC groups were decreased (P

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types; however, the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown. In the study, we investigated the effect of baicalin on bladder cancer cells 5637 and KU-19-19. As a result, we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells. Subsequently, we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo, accompanied by reactive oxygen species (ROS) accumulation and intracellular chelate iron enrichment. The ferroptosis inhibitor deferoxamine but not necrostatin-1, chloroquine (CQ), N-acetyl-l-cysteine, l-glutathione reduced, or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK) rescued baicalin-induced cell death, indicating ferroptosis contributed to baicalin-induced cell death. Mechanistically, we show that ferritin heavy chain 1 (FTH1) was a key determinant for baicalin-induced ferroptosis. Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells. Taken together, our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis, which will hopefully provide a prospective compound for bladder cancer treatment.

Accumulating evidence suggests that chronic inflammation may play a critical role in various malignancies, including bladder cancer. This hypothesis stems in part from inflammatory cells observed in the urethral microenvironment. Chronic inflammation may drive neoplastic transformation and the progression of bladder cancer by activating a series of inflammatory molecules and signals. Recently, it has been shown that the microbiome also plays an important role in the development and progression of bladder cancer, which can be mediated through the stimulation of chronic inflammation. In effect, the urinary microbiome can play a role in establishing the inflammatory urethral microenvironment that may facilitate the development and progression of bladder cancer. In other words, chronic inflammation caused by the urinary microbiome may promote the initiation and progression of bladder cancer. Here, we provide a detailed and comprehensive account of the link between chronic inflammation, the microbiome and bladder cancer. Finally, we highlight that targeting the urinary microbiome might enable the development of strategies for bladder cancer prevention and personalized treatment.

Tuft cells are solitary chemosensory epithelial cells with microvilli at the top, which are found in hollow organs such as the gastrointestinal tract, pancreas, and lungs. Recently, an increasing number of studies have revealed the chemotactic abilities and immune function of the tuft cells, and numerous efforts have been devoted to uncovering the role of tuft cells in tumors. Notably, accumulating evidence has shown that the specific genes (POU2F3, DCLK1) expressed in tuft cells are involved in vital processes related with carcinogenesis and cancer development. However, the interaction between the tuft cells and cancer remains to be further elucidated. Here, based on an introduction of biological functions and specific markers of the tuft cells, we have summarized the functional roles and potential therapeutic implications of tuft cells in cancers, including pancreatic cancer, lung cancer, gastric cancer, colon cancer, and liver cancer, which is in the hope of inspiring the future research in validating tuft cells as novel strategies for cancer therapies.

Background: Recent studies demonstrate that N6-methyladenosine (m6A) methylation plays a crucial role in colorectal cancer (CRC). Therefore, we conducted a comprehensive analysis to assess the m6A modification patterns and identify m6A-modified genes in patients with CRC recurrence.Methods: The m6A modification patterns were comprehensively evaluated by the NMF algorithm based on the levels of 27 m6A regulators, and tumor microenvironment (TME) cell-infiltrating characteristics of these modification patterns were systematically assessed by ssGSEA and CIBERSORT algorithms. The principal component analysis algorithm based on the m6A scoring scheme was used to explore the m6A modification patterns of individual tumors with immune responses. The weighted correlation network analysis and univariable and multivariable Cox regression analyses were applied to identify m6A-modified gene signatures. The single-cell expression dataset of CRC samples was used to explore the tumor microenvironment affected by these signatures.Results: Three distinct m6A modification patterns with significant recurrence-free survival (RFS) were identified in 804 CRC patients. The TME characterization revealed that the m6A modification pattern with longer RFS exhibited robust immune responses. CRC patients were divided into high- and low-score subgroups according to the m6A score individually, which was obtained from the m6A-related signature genes. The patients with low m6A scores had both longer RFS and overall survival (OS) with altered immune cell infiltration. Notably, m6A-modified genes showed significant differences related to the prognosis of CRC patients in the meta-GEO cohort and TCGA cohort. Single-cell expression indicated that ALVRL1 was centrally distributed in endothelial tip cells and stromal cells.Conclusion: The m6A modification plays an indispensable role in the formation of TME diversity and complexity. Importantly, the signatures (TOP2A, LRRC58, HAUS6, SMC4, ACVRL1, and KPNB1) were identified as m6A-modified genes associated with CRC recurrence, thereby serving as a promising predictive biomarker or therapeutic target for patients with CRC recurrence.

PurposeAs a coreceptor in Wnt and HGF signaling, glypican-3 (GPC-3) promotes the progression of tumor and is associated with a poor prognosis in hepatocellular carcinoma (HCC). GPC-3 has evolved as a target molecule in various immunotherapies, including chimeric antigen receptor T cell. However, its evaluation still relies on invasive histopathologic examination. Therefore, we aimed to develop an easy-to-use and noninvasive risk score integrating preoperative gadoxetic acid–enhanced magnetic resonance imaging (EOB-MRI) and clinical indicators to predict positive GPC-3 expression in HCC.Methods and materialsConsecutive patients with surgically-confirmed solitary HCC who underwent preoperative EOB-MRI between January 2016 and November 2021 were retrospectively included. EOB-MRI features were independently evaluated by two masked abdominal radiologists and the expression of GPC-3 was determined by two liver pathologists. On the training dataset, a predictive scoring system for GPC-3 was developed against pathology via logistical regression analysis. Model performances were characterized by computing areas under the receiver operating characteristic curve (AUCs).ResultsA total of 278 patients (training set, n=156; internal validation set, n=39; external validation set, n=83) with solitary HCC (208 [75%] with positive GPC-3 expression) were included. Serum alpha-fetoprotein >10 ng/ml (AFP, odds ratio [OR]=2.3, four points) and five EOB-MR imaging features, including tumor size >3.0cm (OR=0.5, -3 points), nonperipheral “washout” (OR=3.0, five points), infiltrative appearance (OR=9.3, 10 points), marked diffusion restriction (OR=3.3, five points), and iron sparing in solid mass (OR=0.2, -7 points) were significantly associated with positive GPC-3 expression. The optimal threshold of scoring system for predicting GPC-3 positive expression was 5.5 points, with AUC 0.726 and 0.681 on the internal and external validation sets, respectively.ConclusionBased on serum AFP and five EOB-MRI features, we developed an easy-to-use and noninvasive risk score which could accurately predict positive GPC-3 HCC, which may help identify potential responders for GPC-3-targeted immunotherapy.

The moistening impact of El Niño on the tropical lower stratosphere has been extensively studied, yet a long-standing challenge is its potential nonlinearities regarding the strength of El Niño. Extreme El Niño’s hydration in 2015/2016 was unprecedented in the satellite era, providing a great opportunity to distinguish the differential response of water vapor to extreme and moderate El Niño. Using ERA5 and MERRA-2 reanalysis data from 1979–2019, we compare the composite tropical lower stratospheric water vapor anomalies throughout all extreme and moderate El Niño episodes since the satellite era. We validate the variations in the lower stratospheric water vapor during the two distinct El Niño episodes using a three-dimensional chemistry transport model simulating the same period. The model reproduces the observed pattern in lower stratospheric water vapor. Both demonstrate that robust moistening during extreme El Niño events occurs throughout the tropical lower stratosphere. However, moderate El Niño events seem to have a weak effect on lower stratospheric water vapor. In comparison to moderate El Niño, the strong convective activities induced by extreme El Niño release large amounts of latent heat, causing extensive and intense warming in the tropical upper troposphere and lower stratosphere, thus greatly increasing the water vapor content in the tropical lower stratosphere. Additionally, moderate El Niño events have strong seasonality in their hydration effect in the tropics, whereas the intense moistening effect of extreme El Niño events prevails in all seasons during their episodes.

The distribution and ecological risks of 11 phenolic compounds were studied in Weihe River, Northwest China. The concentrations of phenolic compounds were determined by ultra-high performance liquid chromatography (UPLC). The total concentration of 11 phenolic compounds (∑PC11) ranged from 0.06 to 14.12 μg/L with an average of 5.22 μg/L in water, from 0.92 to 34,885 μg/g with an average of 4,446 μg/g in suspended particulate matter (SPM), and from 3.54 to 34.09 μg/g with an average of 11.09 μg/g in sediment. For individual phenolic compound, the mean concentration of pentachlorophenol was the highest in water (2.65 μg/L) and in SPM (3,865 μg/g), while in sediment the mean concentration of 2,4,6-trichlorophenol was the highest (3.05 μg/g). The total concentration of 5 chlorophenols (∑CP5) was significantly higher than that of 6 non-chlorophenols (∑NCP6) in all three studied compartments. The phenolic compounds in Weihe River were at moderate levels in water and at high levels in sediment. The ecological risk assessment results indicated that phenolic compounds exhibited a high ecological risk in Weihe River water. In most sites, the distribution coefficient (Kd) (SPM) was much higher than Kd (sediment), which probably suggested fresh phenolic compounds input in Weihe River. HIGHLIGHTS This is the first systematic study of phenolic compounds in rivers in northwest China.; The results of ecological risk assessment indicated that phenolic compounds exhibited a high ecological risk in Weihe River water.; The total concentration of 5 chlorophenols (∑CP5) was significantly higher than that of 6 non-chlorophenols (∑NCP6) both in water and sediment.;

BackgroundColorectal cancer (CRC) is one of the most common malignancies and its incidence and mortality are increasing yearly. 5-Fluorouracil (5-FU) has long been used as a standard first-line treatment for CRC patients. Although 5-FU-based chemotherapy is effective for advanced CRC, the consequent resistance remains a key problem and causes the poor prognosis of CRC patients. Thus, there is an urgent need to identify new biomarkers to predict the response to 5-FU-based chemotherapy.MethodsCRC samples were retrieved from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). The immune-related genes were retrieved from the ImmPort database. Single-cell sequencing results from colorectal cancer were obtained by the ArrayExpress database. 5-FU resistance-related genes were filtered and validated by R packages. ESTIMATE algorithms were used to assess the tumor microenvironment (TME). KEGG and GO analysis were performed to explore the biological signaling pathway for resistant-response patients and sensitive-response patients in the tumor microenvironment. pRRophetic algorithms were used to predict 5-FU sensitivity. GSEA and GSVA analysis was performed to excavate the biological signaling pathway of the RBP7 gene.ResultsNine immune-related genes were identified to be associated with 5-FU resistance and poor disease-free survival (DFS) of CRC patients and the signature of these genes was developed in a DFS-prognostic model. Four immune-related genes were determined to be associated with 5-FU resistance and overall survival (OS) of CRC patients. The signature of these genes was developed an OS-prognostic model. ESTIMATE scores showed a significant difference between 5-FU resistant and 5-FU sensitive CRC patients. Resistant-response patients and sensitive-response patients to 5-FU based chemotherapy showed different GO and KEGG enrichment on the tumor microenvironment. RBP7, as a tumor immune microenvironment (TIME) related gene, was found to have the potential of predicting chemotherapy resistance and poor prognosis of CRC patients. GSEA analysis showed multiple signaling differences between the high and low expression of RBP7 in CRC patients. Hypoxia and TNFα signaling via NFκB gene sets were significantly different between chemotherapy resistant (RBP7High) and chemotherapy sensitive (RBP7Low) patients. Single-cell RNA-seq suggested RBP7 was centrally distributed in endothelial stalk cells, endothelial tip cells, and myeloid cells.ConclusionsImmune-related genes will hopefully be potential prognostic biomarkers to predict chemotherapy resistance for CRC. RBP7 may function as a tumor microenvironment regulator to induce 5-FU resistance, thereby affecting the prognosis of CRC patients.

Erianin is a major bisbenzyl compound extracted from Dendrobium chrysotoxum Lindl., an important traditional Chinese herb. In recent years, a growing body of evidence has proved the potential therapeutic effects of erianin on various cancers, including hepatoma, melanoma, non-small-cell lung carcinoma, myelogenous leukemia, breast cancer, and osteosarcoma. Especially, the pharmacological activities of erianin, such as antioxidant and anticancer activity, have been frequently demonstrated by plenty of studies. In this study, we firstly conducted a systematic review on reported anticancer activity of erianin. All updated valuable information regarding the underlying action mechanisms of erianin in specific cancer was recorded and summarized in this paper. Most importantly, based on the molecular structure of erianin, its potential molecular targets were analyzed and predicted by means of the SwissTargetPrediction online server (http://www.swisstargetprediction.ch). In the meantime, the potential therapeutic targets of 10 types of cancers in which erianin has been proved to have anticancer effects were also predicted via the Online Mendelian Inheritance in Man (OMIM) database (http://www.ncbi.nlm.nih.gov/omim). The overlapping targets may serve as valuable target candidates through which erianin exerts its anticancer activity. The clinical value of those targets was subsequently evaluated by analyzing their prognostic role in specific cancer using Kaplan-Meier plotter (http://Kmplot.com/analysis/) and Gene Expression Profiling Interactive Analysis (GEPIA) (http://gepia.cancer-pku.cn/). To better assess and verify the binding ability of erianin with its potential targets, molecular flexible docking was performed using Discovery Studio (DS). The valuable targets obtained from the above analysis and verification were further mapped to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway using the Database for Annotation, Visualization and Integrated Discovery (DAVID) (http://david.abcc.ncifcrf.gov/) to explore the possible signaling pathways disturbed/regulated by erianin. Furthermore, the in silico prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of erianin was also performed and provided in this paper. Overall, in this study, we aimed at 1) collecting all experiment-based important information regarding the anticancer effect and pharmacological mechanism of erianin, 2) providing the predicted therapeutic targets and signaling pathways that erianin might act on in cancers, and 3) especially providing in silico ADMET properties of erianin.

Objective: In this study, we aimed to develop an amino-terminal fragment (ATF) peptide-targeted liposome carrying β-elemene (ATF24-PEG-Lipo-β-E) for targeted delivery into urokinase plasminogen activator receptor-overexpressing bladder cancer cells combined with cisplatin (DDP) for bladder cancer treatment. Methods: The liposomes were prepared by ethanol injection and high-pressure microjet homogenization. The liposomes were characterized, and the drug content, entrapment efficiency, and in vitro release were studied. The targeting efficiency was investigated using confocal microscopy, ultra-fast liquid chromatography, and an orthotopic bladder cancer model. The effects of ATF24-PEG-Lipo-β-E combined with DDP on cell viability and proliferation were evaluated by a Cell Counting Kit-8 (CCK-8) assay, a colony formation assay, and cell apoptosis and cell cycle analyses. The anticancer effects were evaluated in a KU-19-19 bladder cancer xenograft model. Results: ATF24-PEG-Lipo-β-E had small and uniform sizes (˜79 nm), high drug loading capacity (˜5.24 mg/mL), high entrapment efficiency (98.37 ± 0.95%), and exhibited sustained drug release behavior. ATF24-PEG-Lipo-β-E had better targeting efficiency and higher cytotoxicity than polyethylene glycol (PEG)ylated β-elemene liposomes (PEG-Lipo-β-E). DDP, combined with ATF24-PEG-Lipo-β-E, exerted a synergistic effect on cellular apoptosis and cell arrest at the G2/M phase, and these effects were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 pathways. Furthermore, the in vivo antitumor activity showed that the targeted liposomes effectively inhibited the growth of tumors, using the combined strategy. Conclusions: The present study provided an effective strategy for the targeted delivery of β-elemene (β-E) to bladder cancer, and a combined strategy for bladder cancer treatment.

Objective: This study aimed to develop a new polyethylene glycol (PEG)ylated β-elemene liposome (PEG-Lipo-β-E) and evaluate its characterization, pharmacokinetics, antitumor effects and safety in vitro and in vivo. Methods: The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization. Characterization of the liposomes was conducted, and drug content, entrapment efficiency (EE), in vitro release and stability were studied by ultra-fast liquid chromatography (UFLC) and a liquid surface method. Blood was drawn from rats to establish the pharmacokinetic parameters. The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model. Histological analyses were performed to evaluate safety. Results: The PEG-Lipo-β-E showed good stability and was characterized as 83.31 ± 0.181 nm in size, 0.279 ± 0.004 in polydispersity index (PDI), −21.4 ± 1.06 mV in zeta potential, 6.65 ± 0.02 in pH, 5.024 ± 0.107 mg/mL in β-elemene (β-E) content, and 95.53 ± 1.712% in average EE. The Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) indicated the formation of PEG-Lipo-β-E. Compared to elemene injection, PEG-Lipo-β-E demonstrated a 1.75-fold decrease in clearance, a 1.62-fold increase in half-life, and a 1.76-fold increase in area under the concentration-time curves (AUCs) from 0 hour to 1.5 hours (P < 0.05). PEG-Lipo-β-E also showed an enhanced anticancer effect in vivo. Histological analyses showed that there was no evidence of toxicity to the heart, kidney, liver, lung or spleen. Conclusions: The present study demonstrates PEG-Lipo-β-E as a new formulation with ease of preparation, high EE, good stability, improved bioavailability and antitumor effects.

With the rapid growth of application demands and the real-time change of environmental situations, the defects of the UAV task network in adaptability, flexibility, and resilience are becoming more and more prominent. The current network architecture that the junction of points and lines is fixed cannot dynamically provide capacity requirements in real-time due to the failure nodes encountered in the Unmanned Aerial Vehicle (UAV) task scheduling process. To address this challenging issue, this paper proposes a flexible network architecture supporting dynamic fault-tolerant task scheduling model (DSM-FNA) for the UAV cluster. To be specific this paper resorts to super network theory, combining the management theory of flexible network and resilience network to carry out the organizational calculation on the model, and also draw upon linear transformation function to weight and stratify the capability value according to the ability requirement required by the task. Then, a flexible network architecture dynamic scheduling algorithm (FDSA) is proposed, and the substitution strategy is designed for the failure point, to realize the capability and dynamically adapt to the task. Finally, compared with the classical Max-Min algorithm and other algorithms, it is verified that the FDSA algorithm performs better dynamic adjustment for quick response in case of UAV cluster emergencies.

Abstract Background The Liver Imaging Reporting and Data System (LI-RADS) and European Association for the Study of the Liver (EASL) criteria are widely used for diagnosing hepatocellular carcinoma (HCC). Radiomics allows further quantitative tumor heterogeneity profiling. This study aimed to compare the diagnostic accuracies of the version 2018 (v2018) EASL, LI-RADS criteria and radiomics models for HCC in high-risk patients. Methods Ethical approval by the institutional review board and informed consent were obtained for this study. From July 2015 to September 2018, consecutive high-risk patients were enrolled in our tertiary care hospital and underwent gadoxetic acid-enhanced magnetic resonance (MR) imaging and subsequent hepatic surgery. We constructed a multi-sequence-based three-dimensional whole-tumor radiomics signature by least absolute shrinkage and selection operator model and multivariate logistic regression analysis. The diagnostic accuracies of the radiomics signature was validated in an independent cohort and compared with the EASL and LI-RADS criteria reviewed by two independent radiologists. Results Two hundred twenty-nine pathologically confirmed nodules (173 HCCs, mean size: 5.74 ± 3.17 cm) in 211 patients were included. Among them, 201 patients (95%) were infected with hepatitis B virus (HBV). The sensitivity and specificity were 73 and 71% for the radiomics signature, 91 and 71% for the EASL criteria, and 86 and 82% for the LI-RADS criteria, respectively. The areas under the receiver operating characteristic curves (AUCs) of the radiomics signature (0.810), LI-RADS (0.841) and EASL criteria (0.811) were comparable. Conclusions In HBV-predominant high-risk patients, the multi-sequence-based MR radiomics signature, v2018 EASL and LI-RADS criteria demonstrated comparable overall accuracies for HCC.

Erianin, a natural product derived from Dendrobium chrysotoxum Lindl, has been proved to play antitumor activity in various cancers. However, the effects and molecular mechanisms of erianin in bladder cancer cells remain unexplored. In this study, we found that erianin triggered cell death and cell cycle arrest in bladder cancer cells. Then we demonstrated that erianin could promote the accumulation of lethal lipid-based reactive oxygen species (ROS) and the depletion of glutathione (GSH), suggesting the induction of ferroptosis. In the further study, the ferroptosis inhibitor deferoxamine (DFO), N-Acetylcysteine (NAC) and GSH but not necrostatin-1, CQ or Z-VAD-FMK rescued erianin-caused cell death, showing ferroptosis played a major role in erianin-caused cell death. In vivo, we also showed that erianin suppressed the tumor growth by inducing ferroptosis. Mechanistically, we demonstrated that nuclear factor E2-related factor 2 (NRF2) inactivation was a key determinant of ferroptosis caused by erianin. In bladder cancer cells, the compound tert-butylhydro-quinone (TBHQ), an activator of NRF2, suppressed erianin-induced ferroptosis. Whereas, NRF2 inhibition used shRNA augmented the ferroptosis response induced by erianin treatment. In conclusion, our data provide the first evidence that erianin can initiate ferroptosis-like cell death and lipid peroxidation in bladder cancer, which will hopefully become a promising anticancer compound for the treatment of bladder cancer.

With the rapid development of intelligent unmanned technology, unmanned combat swarms are faced with a highly aggressive, highly uncertain, and highly dynamic battlefield environment, and the operation mode of unmanned combat has gradually shifted from single-platform operations to swarm networking collaboration combat development. Aiming at the typical characteristics of the unmanned swarm combat system, this paper proposes a role assignment model for organizational reconfiguration at the swarm layer and builds an unmanned swarm organization reconfiguration role-assignment mechanism model (SORAM) based on the fourth-order directed motif. The method starts from the organizational domain of the swarm system and takes the task as the the dependent variable of the role assignment of the swarm organization, quantifies the importance of the motif from a statistical point of view, and establishes a multi-objective model considering the similarity of the structure. The swarm reconfiguration role optimization method of SR-NSGA-2 provides a reference for the online adaptation of the swarm links. Finally, combined with a simulated combat simulation case, the usability and effectiveness of the method are tested.

BackgroundMicrosatellite instability (MSI) is one of the important factors that determine the effectiveness of immunotherapy in colorectal cancer (CRC) and serves as a prognostic biomarker for its clinical outcomes.PurposeTo investigate whether the metabolic parameters derived from18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) can predict MSI status in patients with CRC.Materials and MethodsA retrospective analysis was performed on CRC patients who underwent 18F-FDG PET/CT examination before surgery between January 2015 and April 2021. The metabolic 18F-FDG PET/CT parameters of the primary CRC lesion were calculated and recorded with different thresholds, including the maximum, peak, and mean standardized uptake value (SUVmax, SUVpeak, and SUVmean), as well as the metabolic tumor volume (MTV) and the total lesion glycolysis (TLG). The status of MSI was determined by immunohistochemical assessment. The difference of quantitative parameters between MSI and microsatellite stability (MSS) groups was assessed, and the receiver operating characteristic (ROC) analyses with area under ROC curves (AUC) was used to evaluate the predictive performance of metabolic parameters.ResultsA total of 44 patients (24 men and 20 women; mean ± standard deviation age: 71.1 ± 14.2 years) were included. There were 14 patients in the MSI group while there were 30 in the MSS group. MTV30%, MTV40%, MTV50%, and MTV60%, as well as TLG50% and TLG60% showed significant difference between two groups (all p-values

Biochar (BC) is considered to be a great potential adsorbent to remove various contaminants, but the sorption capacity for chromium (Cr) is predominantly limited for the net negative charge. In this study, BC from rice husk was impregnated with Mn(NO3)2 solution to synthesize MnOx-modified BC (MnOBCs) for enhancing Cr(VI) removal in an aqueous solution. MnOBCs were characterized, and MnOx (manganese ore) was found to be the dominant crystal in MnOBCs. Batch sorption and kinetic experiments combined with spectral analysis were carried out to elucidate the sorption capacity and mechanisms of Cr(VI) sorption onto BC and MnOBCs. Results showed that the sorption kinetic process fitted to the Elovich model, and the modification enhanced the sorption capacity of Cr(VI) on BC. Compared to ion strength, pH is the main control factor for Cr(VI) fixed on BC and MnOBCs, and the sorption amount decreased with the pH value increasing. Moreover, X-ray photoelectron spectroscopy results showed that the proportion of Mn(II) decreased from 33.59% to 8.33%, and that of Mn(VI) increased from 30.58% to 52.72% after Cr(VI) sorption on MnOBCs. Meanwhile, the reduction reaction of Cr(VI) occurred during the sorption process on the BC and MnOBCs surface, and the reduction reaction was more obvious on the MnOBCs surface. MnOx loaded in BC can enhance the electrostatic attraction and redox capacity, which can improve the removal of Cr(VI) in an aqueous solution. This study provides information on the sorption and redox of Cr(VI) on BC, and allows us to better understand the mechanism of Cr(VI) removal in solutions by MnOBCs.

Baicalin, as a natural active ingredient extracted and isolated from the traditional Chinese medicine Scutellaria baicalensis Georgi., has been potentially used in various areas for its antioxidative, antitumor, anti-inflammatory, and anti-proliferative activities. Although several studies have reported the antitumor effects of baicalin against various cancer types, its beneficial effects on lung cancer have not yet been elucidated. Therefore, the therapeutic effects and molecular mechanisms of baicalin on lung cancer cell lines H1299 and H1650 were investigated. Here, the results of its antitumor activity were shown. We found that Akt/mTOR pathway inhibition was the essential determinant in baicalin-induced cell cycle arrest. Furthermore, when the Akt Agonist SC79 or Akt plasmid transfection was performed, the antitumor effect of baicalin was significantly abrogated in both H1299 and H1650 cells. In conclusion, we found that baicalin exerted its antitumor activity mainly by inducing Akt-dependent cell cycle arrest and promoting apoptosis, which show great potential for developing a new drug for lung cancer treatment.

Driverless vision is one of the important applications of robot perception. With the development of driverless vehicles, the perception and understanding of the surrounding environment are becoming more and more important. When the types of surrounding objects are too complex, the ability of the computer to recognise the environment is poor. To improve the recognition accuracy of the computer and enhance the ability of segmentation, in this study, depth estimation is used to predict depth information to assist semantic segmentation, and then edge features of objects are introduced to enhance the contour of objects. A neural network-based semantic segmentation model is proposed. Finally, the intrinsic mechanism of attention is used to increase the correlation between channels. The experimental results on the CamVid data set show that this model can obtain better evaluation results and improve the segmentation accuracy of images compared with other models.

Purpose: To assess the performance of T1 mapping and residual liver volume (RLV) on Gd-EOBDTPA-enhanced MRI in pretreatment estimation of liver function in patients with liver tumors. Indocyanine green retention rate at 15 min (ICG R-15) was used as a reference standard.Methods: Ethical approval from the institutional review board and informed consent were obtained for this prospective study. We enrolled 155 patients with liver tumors who underwent pretreatment Gd-EOB-DTPA-enhanced MRI. T1 relaxation time before (T1-pre), 20 min after (T1-post) Gd-EOB-DTPA injection and RLV were measured. The absolute reduction (ΔT1) and reduction rate (ΔT1%) of T1 relaxation time, volume-assisted ΔT1 (ΔT1*RLV) and volume-assisted ΔT1% (ΔT1%*RLV) were calculated accordingly. The correlation of MR parameters with ICG R-15 was determined using Spearman's rank correlation analysis. Patients were classified into the normal liver function (NLF) group if their ICG R-15 levels were

ObjectiveColorectal cancer is a malignant tumor of the digestive system with high morbidity and mortality. 5-fluorouracil remains a widely used chemotherapeutic drug in the treatment of advanced colorectal cancer, but chemotherapy drugs are prone to develop drug resistance, p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to 5-fluorouracil. β-elemene has been proved to have the potential of reverse chemotherapy drug resistance, but the mechanism is unknown. This study aimed to investigate the effect of β-elemene to 5-fluorouracil in drug-resistant p53-deficient colorectal cancer cells HCT116p53–/–, and determine the possible molecular mechanism of β-elemene to reverse 5-fluorouracil resistance.MethodsThe effect of β-elemene on HCT116p53–/– cell activity was detected by Cell counting Kit-8. Cell proliferation was detected by monoclonal plate. The apoptosis was detected by flow cytometry and western blot. The autophagy was detected by western blot, immunofluorescence and transmission electron microscope. Determine the role of Cyclin-related protein Cyclin D3 in β-elemene reversing the resistance of HCT116p53–/– to 5-fluorouracil was detected by overexpression of Cyclin D3. The effect of β-elemene on the tumorigenic ability of p53-deficient colorectal cancer cells was detected establishing HCT116p53–/– all line xenograft model.ResultsFor p53 wildtype colorectal cancer cells, β-elemene could augment the sensitivity of 5-fluorouracil, for p53-deficient colorectal cancer cells, β-elemene significantly inhibited cell proliferation in a concentration-dependent manner, and reversed the resistance of HCT116p53–/– to 5-fluorouracil by inducing pro-death autophagy and Cyclin D3-dependent cycle arrest.Conclusionβ-elemene enhances the sensitivity of p53 wild-type cells to 5-fluorouracil, β-elemene can reverse the resistance of HCT116p53–/– to 5-fluorouracil by inducing pro-death autophagy and Cyclin D3-dependent cycle arrest in p53-deficient colorectal cancer, which will provide a new method for the treatment of p53 deletion colorectal cancer patients.

Abstract Background Collaborative projects such as The Cancer Genome Atlas (TCGA) have generated various -omics and clinical data on cancer. Many computational tools have been developed to facilitate the study of the molecular characterization of tumors using data from the TCGA. Alternative splicing of a gene produces splicing variants, and accumulating evidence has revealed its essential role in cancer-related processes, implying the urgent need to discover tumor-specific isoforms and uncover their potential functions in tumorigenesis. Result We developed TSVdb, a web-based tool, to explore alternative splicing based on TCGA samples with 30 clinical variables from 33 tumors. TSVdb has an integrated and well-proportioned interface for visualization of the clinical data, gene expression, usage of exons/junctions and splicing patterns. Researchers can interpret the isoform expression variations between or across clinical subgroups and estimate the relationships between isoforms and patient prognosis. TSVdb is available at http://www.tsvdb.com, and the source code is available at https://github.com/wenjie1991/TSVdb. Conclusion TSVdb will inspire oncologists and accelerate isoform-level advances in cancer research.

The objective of this study was to examine how the respiratory metabolism of the snakehead Channa argus changed when it shifted from breathing water to breathing air, and how increased metabolic demands caused by temperature, feeding, and exhaustive exercise affect its survival in air. The results demonstrated that the oxygen consumption rate (MO2) of the snakehead was lower for aerial respiration than aquatic respiration by 12.1, 24.5 and 20.4% at 20, 25, and 30°C, respectively. Survival time was significantly shortened with increasing temperature and was negatively correlated with the resting MO2 in air (MO2Air). No obvious feeding metabolic response was observed in the snakeheads fed at 1% and 3% body mass levels while breathing air. The maximum MO2Air of the snakehead after exhaustive exercise was significantly higher than the resting MO2Air of the control group. The results suggest that the snakehead could survive out of water by breathing air for varying lengths of time, depending on ambient temperature and metabolic demand. Additionally, some degree of metabolic depression occurs in the snakehead when breathing air. The metabolic demand associated with exercise in the snakehead, but not that associated with feeding, can be supported by its capacity for breathing air to some extent.

β-Elemene is a sesquiterpene compound extracted from the herb Curcuma Rhizoma and is used in traditional Chinese medicine (TCM) to treat several types of cancer, with no reported severe adverse effects. Recent studies, using in vitro and in vivo studies combined with molecular methods, have shown that β-elemene can inhibit cell proliferation, arrest the cell cycle, and induce cell apoptosis. Recent studies have identified the molecular targets of β-elemene that may have a role in cancer therapy. This review aims to discuss the anticancer potential of β-elemene through its actions on several molecular targets including kinase enzymes, transcription factors, growth factors and their receptors, and proteins. β-Elemene also regulates the expression of several key molecules that are involved in tumor angiogenesis and metastasis including vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), E-cadherin, N-cadherin, and vimentin. Also, β-elemene has been shown to have regulatory effects on the immune response and increases the sensitivity of cancer cells to chemoradiotherapy and has shown effects on multidrug resistance (MDR) in malignancy. Recent studies have shown that β-elemene can induce autophagy, which prevents cancer cells from undergoing apoptosis. Therefore, the molecular mechanisms for the treatment effects on cancer of the herbal extract, β-elemene, which has been used for centuries in traditional Chinese medicine, are now being studied and identified.

Ferroptosis is an iron-dependent, oxidative cell death, and is characterized by iron-dependent accumulation of reactive oxygen species (ROS) within the cell. It has been implicated in various human diseases, including cancer. Recently, ferroptosis, as a non-apoptotic form of cell death, is emerging in specific cancer types; however, its relevance in colorectal cancer (CRC) is unexplored and remains unclear. Here, we showed that ferroptosis inducer RSL3 initiated cell death and ROS accumulation in HCT116, LoVo, and HT29 CRC cells over a 24 h time course. Furthermore, we found that ROS levels and transferrin expression were elevated in CRC cells treated with RSL3 accompanied by a decrease in the expression of glutathione peroxidase 4 (GPX4), indicating an iron-dependent cell death, ferroptosis. Overexpression GPX4 resulted in decreased cell death after RSL3 treatment. Therefore, RSL3 was able to induce ferroptosis on three different CRC cell lines in vitro in a dose- and time-dependent manner, which was due to increased ROS and an increase in the cellular labile iron pool. Moreover, this effect was able to be reversed by overexpression of GPX4. Taken together, our results suggest that the induction of ferroptosis contributed to RSL3-induced cell death in CRC cells and ferroptosis may be a pervasive and dynamic form of cell death for cancer treatment.

This study aimed to test the hypothesis that the aerial survival of the northern snakehead is involved not only with suprabranchial chamber respiration but also with physiological regulations. The aerial survival time and oxygen consumption rate (VO2) were determined in snakeheads with either normal or injured suprabranchial organs. Some hematological and biochemical parameters were assessed during aerial exposure. The results showed that resting VO2 decreased when switching from water to air in both the control and the suprabranchial organ-injured fish, with decreases of 22.4% and 23.5%, respectively. Resting VO2 in air was not different between the control and the suprabranchial organ-injured fish. The red blood cell (RBC) count and hemoglobin concentration showed no marked changes, while RBC size increased when exposed to air. The liver lactate concentration remained unchanged, and the white muscle lactate concentration decreased when switching from water to air. The blood ammonia concentration tended to increase during aerial respiration. These results suggest that the aerial survival of the snakehead is positively associated with a combination of factors, including respiration of suprabranchial organs and other accessory organs, depressed metabolic demands and increased oxygen transport, and negatively associated with the accumulation of blood ammonia but not anaerobic metabolism.

(-)-Epigallocatechin-3-gallate (EGCG) is the most extensive studied tea polyphenol for its anti-cancer function. In this study, we report a novel mechanism of action for EGCG-mediated cell death by identifying the critical role of lysosomal membrane permeabilization (LMP). First, EGCG-induced cell death in human cancer cells (both HepG2 and HeLa) was found to be caspase-independent and accompanied by evident cytosolic vacuolization, only observable when cells were treated in serum-free medium. The cytosolic vacuolization observed in EGCG-treated cells was most probably caused by lysosomal dilation. Interestingly, EGCG was able to disrupt autophagic flux at the degradation stage by impairment of lysosomal function, and EGCG-induced cell death was independent of Atg5 or autophagy. The key finding of this study is that EGCG is able to trigger LMP, as evidenced by Lyso-Tracker Red staining, cathepsin D cytosolic translocation and cytosolic acidification. Consistently, a lysosomotropic agent, chloroquine, effectively rescues the cell death via suppressing LMP-caused cytosolic acidification. Lastly, we found that EGCG promotes production of intracellular ROS upstream of LMP and cell death, as evidenced by increased level of ROS in cells treated with EGCG and the protective effects of antioxidant N-acetylcysteine (NAC) against EGCG-mediated LMP and cell death. Taken together, data from our study reveal a novel mechanism underlying EGCG-induced cell death involving ROS and LMP. Therefore, understanding this lysosome-associated cell death pathway shed new lights on the anti-cancer effects of EGCG.

Objective 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. Conclusion 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.