Lys05 induces lysosomal membrane permeabilization and increases radiosensitivity in glioblastoma.

Glioblastoma (GBM) is one of the most malignant primary brain tumors and its prognosis is very poor. Lysosome-dependent cell death is mainly caused by lysosomal membrane permeabilization (LMP), a process in which the lysosome loses its membrane integrity and lysosomal contents are released into the cytosol. Lysosomotropic agent, a kind of compound that selectively accumulates in the lysosomes, is one of the most important inducers of LMP. As a newly-synthetic lysosomotropic agent, Lys05 showed efficient autophagy inhibiting and antitumor effect. But its mechanisms are not well illustrated. Here, we studied whether Lys05 has antiglioma activity. We found that Lys05 decreased cell viability and reduced cell growth of glioma U251 and LN229 cells. After Lys05 treatment, autophagic flux is inhibited and lysosome function is impaired. We also found that Lys05 caused LMP and mitochondrial depolarization. Finally, Lys05 increased radiosensitivity in an LMP-dependent manner. For the first time, our findings indicate that LMP contributes to radiosensitivity in GBM cells. Therefore, LMP inducer, Lys05 might be a promising compound in the treatment of GBM cells.

The effects of long-term application of fomesafen on weed seedbank and resistance levels of Amaranthus retroflexus L.

Amaranthus retroflexus L. is one of the invasive malignant weeds in soybean fields. Diphenyl ether herbicides are commonly used to control weeds in soybean fields currently, among which fomesafen is the most widely used. With the long-term use of fomesafen, the weed species in soybean fields in multiple areas declined, and the control effect of fomesafen against Amaranthus retroflexus decreased significantly. This study aims to confirm the effects of long-term use of fomesafen on weed community richness and the current resistance level of Amaranthus retroflexus. In this paper, the result of seed germination indicated that the weed community richness decreased significantly due to the long-term application of fomesafen, and the primary dominant weed was Amaranthus retroflexus. The result of the whole-plant bioassay showed that Amaranthus retroflexus has developed resistance to fomesafen, and the resistance index was 50~59 g a.i. ha-1. The resistance level and mechanism of Amaranthus retroflexus were clarified by target gene detection, enzyme activity determination, and gene expression analysis. The results showed that there were both target resistance with Arg128Gly mutation in the PPX2 gene and non-target resistance (NTSR), with increased activity of metabolic enzymes (cytochromes P450 (P450s) and glutathione S-transferase (GSTs)) and protective enzymes (peroxidase (POD) and catalase (CAT)) in Amaranthus retroflexus.

Risk factors for post-traumatic stress disorder in nurses from the regional medical alliance during the COVID-19 epidemic: A prospective cross-sectional study.

Mental health issues among nursing professionals have been increasingly reported during the coronavirus disease (COVID-19) pandemic. However, there is a paucity of research on post-traumatic stress disorder (PTSD) among nurses working in Medical Alliances. In this study, we aimed to investigate the risk factors associated with PTSD in the Regional Medical Alliance (MA) in Shantou (China) during the COVID-19 pandemic. A total of 1286 nurses from four MA hospitals participated in the study from February to March 2020. Our findings revealed that the incidences of PTSD, depression, anxiety, and sleep disorders among nurses from MA were 15.6%, 35.5%, 18.3%, and 36.4%, respectively. Moreover, PTSD was positively correlated with depression, anxiety, and sleep disorders. In addition, the results of logistic regression analysis showed that working in a tertiary hospital, older age, more severe depression, more severe anxiety, and prevalent sleep disorders were independent risk factors for PTSD among nurses. Therefore, mental health interventions targeting high-risk nurses in MA with an incidence of PTSD are urgently needed.

Transcriptomic analysis of Amaranthus retroflex resistant to PPO-inhibitory herbicides.

Amaranthus retroflexus L. is one of the malignant weeds which can cause a reduction in the soybean yield. We found a population of A. retroflexus (R-Q) resistant to fomesafen through the initial screening of whole-plant dose response bioassay in the research. The resistance index of the population (R-Q) was 183 times of the sensitive population (S-N). The resistant and sensitive populations were used as experimental materials in the paper. Strand-specific RNA-Seq analyses of R‒Q and S‒N populations obtained from herbicide-treated and mock-treated leaf samples after treatment were conducted to generate a full-length transcriptome database. We analyzed differentially expressed genes (DEGs) among the R-Q and S‒N A. retroflexus populations treated with recommended dose and mock-treated on the 1st (24 h) and 3rd (72 h) days to identify genes involved in fomesafen resistance. All 82,287 unigenes were annotated by Blastx search with E-value < 0.00001 from 7 databases. A total of 94,815 DEGs among the three group comparisons were identified. Two nuclear genes encoding PPO (PPX1 and PPX2) and five unigenes belonging to the AP2-EREBP, GRAS, NAC, bHLH and bZIP families exhibited different expression patterns between individuals of S‒N and R-Q populations. The A. retroflexus transcriptome and specific transcription factor families which can respond to fomesafen in resistant and susceptible genotypes were reported in this paper. The PPX1 and PPX2 genes of the target enzyme were identified. The study establishes the foundation for future research and provides opportunities to manage resistant weeds better.

FIN56, a novel ferroptosis inducer, triggers lysosomal membrane permeabilization in a TFEB-dependent manner in glioblastoma.

Objective: To explore the anti-tumor effect of FIN56, a novel ferroptosis inducer, on glioblastoma and its underlying mechanisms. Methods: Two human glioblastoma cell lines, LN229 and U118 were applied in this study. Anti-tumor effect was measured by CCK-8 assay, EdU assay and cell cycle analysis. Fluorescent probes, immunofluorescence, plasmid transfection, shRNA knocking out, reverse transcription PCR, western blot analysis, and transmission electron microscopy were used to study the underlying mechanisms. At last, a subcutaneous nude mice model was used to study the anti-tumor effect of FIN56 in vivo. The GraphPad Prism software program was applied for statistical analysis. Results: FIN56 decreased cell viability, inhibited cell proliferation and caused cell cycle arrest on LN229 and U118 cells. Further study showed that FIN56 induced ferroptosis and induced lysosomal membrane permeabilization in a ferroptosis and transfactor EB dependent manner. Animal study demonstrated that FIN56 inhibited glioma growth and caused ferroptosis in vivo. Conclusion: FIN56 is a promising anti-tumor compound.

Effect of pH on the Catalytic Degradation of Rhodamine B by Synthesized CDs/g-C3N4/Cu x O Composites.

The narrow pH range of Fenton oxidation restricts its applicability in water pollution treatment. In this work, a CDs/g-C3N4/Cu x O composite was synthesized via a stepwise thermal polymerization method using melamine, citric acid, and Cu2O. Adding H2O2 to form a heterogeneous Fenton system can degrade Rhodamine B (Rh B) under dark conditions. The synthesized composite was characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and N2 adsorption/desorption isotherms. The results showed that CDs, Cu2O, and CuO were successfully loaded on the surface of g-C3N4. By evaluating the catalytic activity on Rh B degradation in the presence of H2O2, the optimal contents of citric acid and Cu2O were 3 and 2.8%, respectively. In contrast to a typical Fenton reaction, which is favored in acidic conditions, the catalytic degradation of Rh B showed a strong pH-dependent relation when the pH is raised from 3 to 11, with the removal from 45 to 96%. Moreover, the recyclability of the composite was evaluated by the removal ratio of Rhodamine B (Rh B) after each cycle. Interestingly, recyclability is also favored in alkaline conditions and shows the best performance at pH 10, with the removal ratio of Rh B kept at 95% even after eight cycles. Through free radical trapping experiments and electron spin resonance (ESR) analysis, the hydroxyl radical (•OH) and the superoxide radical (•O2 -) were identified as the main reactive species. Overall, a mechanism is proposed, explaining that the higher catalytic performance in the basic solution is due to the dominating surface reaction and favored in alkaline conditions.

Identification of an exosomal long non-coding RNAs panel for predicting recurrence risk in patients with colorectal cancer.

Recurrence is a major cause of cancer-related deaths in colorectal cancer (CRC) patients, but the current strategies are limited to predict this clinical behavior. Our aim is to develop a recurrence prediction model based on long non-coding RNAs (lncRNAs) in exosomes of serum to improve the prediction accuracy. In discovery phase, 11 lncRNAs were found to be associated with CRC recurrence in tissues using high-throughput lncRNAs microarray and reverse transcription quantitative real-time PCR. And, 9 of them were correlated with their expression levels of serum exosomes. In training phase, a model based on 5-exosomal lncRNAs (exolncRNAs) panel was constructed, and showed high distinguish capability for recurrent CRC patients. ROC showed the panel was superior to serum CEA and CA19-9 in prediction of CRC recurrence. In both training and test sets, high-risk patients defined by the 5-exolncRNAs panel had poor recurrence free and overall survival. And, COX model showed it was an independent factor for CRC prognosis. Moreover, there was a significant relationship in detection of 5-exolncRNAs between plasma samples and paired serum samples. In summary, the 5-exolncRNAs panel robustly stratifies CRC patients' risk of recurrence, enabling more accurate prediction of prognosis.