Screening of a Prognostic Gene Signature for Relapsed/Refractory Acute Myeloid Leukemia Based on Altered Circulating CircRNA Profiles.

Background: Relapsed/refractory acute myeloid leukemia (R/R-AML) has dismal prognosis due to chemotherapy resistance. Circular RNAs (circRNAs) have shown emerging roles in chemotherapy resistance in various cancers including hematologic malignancies. However, the potential roles of circRNAs in AML progression and drug resistance remain largely undetermined. Methods: In this study, circulating circRNAs expression profiles were analyzed among R/R-AML, de novo AML and healthy controls (HC) using a human circRNA Array. Bioinformatic analysis was carried out to explore the differentially expressed circRNAs (DE-circRNAs). GO, KEGG pathway analysis, along with circRNA-miRNA-mRNA network analysis, were conducted to identify the potential biological pathways involved in R/R-AML. Finally, the UALCAN database was used to assess the prognosis of different target DE-circRNAs-related mRNAs. Results: Forty-eight DE-circRNAs were upregulated, whereas twenty-seven DE-circRNAs were downregulated in R/R-AML samples. Up-regulated DE-circRNAs in R/R-AML samples were mainly enrichment in the biological processes and pathways of cell migration, microRNAs in cancers, Rap1 and Ras signaling pathways. Six DE-circRNAs were randomly selected to further explore their relationships with R/R-AML. GO and KEGG pathway analyses of the six candidate DE-circRNAs-related target mRNAs were mainly involved in the regulation of signal transduction and Ras signaling pathway. By overlapping our RNA-sequencing results of differentially expressed genes (DEGs) in R/R-AML samples with the candidate DE-circRNAs-predicted target mRNAs, we identified sixty-eight overlapping targeted mRNAs. Using UALCAN database analysis, we identified that AML patients with six upregulated DE-circRNA-related genes (ECE1, PI4K2A, SLC9A6, CCND3, PPP1R16B, and TRIM32) and one downregulated gene DE-circRNA-related genes (ARHGAP10) might have a poor prognosis. Conclusion: This study revealed the overall alterations of circRNAs in R/R-AML. DE-circRNAs and their related genes might be used as potential early, sensitive and stable biomarkers for AML diagnosis, R/R-AML monitoring, and even as novel treatment targets for R/R-AML.

Lactic acid induced defense responses in tobacco against Phytophthora nicotianae.

Induced resistance is considered an eco-friendly disease control strategy, which can enhance plant disease resistance by inducing the plant's immune system to activate the defense response. In recent years, studies have shown that lactic acid can play a role in plant defense against biological stress; however, whether lactic acid can improve tobacco resistance to Phytophthora nicotianae, and its molecular mechanism remains unclear. In our study, the mycelial growth and sporangium production of P. nicotianae were inhibited by lactic acid in vitro in a dose-dependent manner. Application of lactic acid could reduce the disease index, and the contents of total phenol, salicylic acid (SA), jasmonic acid (JA), lignin and H2O2, catalase (CAT) and phenylalanine ammonia-lyase (PAL) activities were significantly increased. To explore this lactic acid-induced protective mechanism for tobacco disease resistance, RNA-Seq analysis was used. Lactic acid enhances tobacco disease resistance by activating Ca2+, reactive oxygen species (ROS) signal transduction, regulating antioxidant enzymes, SA, JA, abscisic acid (ABA) and indole-3-acetic acid (IAA) signaling pathways, and up-regulating flavonoid biosynthesis-related genes. This study demonstrated that lactic acid might play a role in inducing resistance to tobacco black shank disease; the mechanism by which lactic acid induces disease resistance includes direct antifungal activity and inducing the host to produce direct and primed defenses. In conclusion, this study provided a theoretical basis for lactic acid-induced resistance and a new perspective for preventing and treating tobacco black shank disease.

Comparison between an SGLT2 inhibitor and insulin in tumor-to-tissue contrasts in 18F-FDG PET imaging of diabetic mice.

18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has been widely utilized for tumor diagnosis. Hyperglycemia affects the 18F-FDG uptake and reduces tumor-to-tissue contrasts, however, ideal hypoglycemic drugs are lacking. This study compared the role of insulin with the novel widely used hypoglycemic drug, sodium-glucose cotransporter 2 (SGLT2) inhibitor, on 18F-FDG PET imaging in diabetic conditions. The streptozotocin (STZ)-induced diabetic C57BL/6N mice were inoculated with B16 (mouse melanoma) cells to establish the xenograft tumor model. After the mice had been administrated with dapagliflozin (30 mg/kg, IG) or insulin (0.75 U/kg, IP) for one hour, 9.25 MBq/10 g 18F-FDG was injected. Biodistributions were detected by gamma counting and microPET imaging. The results showed dapagliflozin did not significantly affect the 18F-FDG uptake in tumors but reduced uptake in reference tissues, resulting in a significant increase in the tumor-to-skeletal muscle ratio. Conversely, insulin increased 18F-FDG uptake in tumors without significant reduction in uptake in reference tissues; Although there was an observable improvement in tumor imaging, it did not reach significantly statistical differences. This study suggests that insulin and SGLT2 inhibitor yield comparable effects on the quality of 18F-FDG PET imaging in diabetic patients. Nevertheless, SGLT2 inhibitors would be more suitable when skeletal muscle is used as reference tissue.

Overexpressing GmCGS2 Improves Total Amino Acid and Protein Content in Soybean Seed.

Soybean (Glycine max (L.) Merr.) is an important source of plant protein, the nutritional quality of which is considerably affected by the content of the sulfur-containing amino acid, methionine (Met). To improve the quality of soybean protein and increase the Met content in seeds, soybean cystathionine γ-synthase 2 (GmCGS2), the first unique enzyme in Met biosynthesis, was overexpressed in the soybean cultivar "Jack", producing three transgenic lines (OE3, OE4, and OE10). We detected a considerable increase in the content of free Met and other free amino acids in the developing seeds of the three transgenic lines at the 15th and 75th days after flowering (15D and 75D). In addition, transcriptome analysis showed that the expression of genes related to Met biosynthesis from the aspartate-family pathway and S-methyl Met cycle was promoted in developing green seeds of OE10. Ultimately, the accumulation of total amino acids and soluble proteins in transgenic mature seeds was promoted. Altogether, these results indicated that GmCGS2 plays an important role in Met biosynthesis, by providing a basis for improving the nutritional quality of soybean seeds.

Global, regional, and national burden of chronic respiratory diseases and associated risk factors, 1990-2019: Results from the Global Burden of Disease Study 2019.

Background: The burden of chronic respiratory diseases has changed over the three decades. This study aims to describe the spatiotemporal trends of prevalence, mortality, and disability-adjusted life years (DALY) due to chronic respiratory diseases (CRDs) worldwide during 1990-2019 using data from the Global Burden of Disease Study 2019 (GBD 2019). Methods: The prevalence, mortality, and DALY attributable to CRDs and risk factors from 1990 to 2019 were estimated. We also assessed the driving factors and potentiality for improvement with decomposition and frontier analyses, respectively. Results: In 2019, 454.56 [95% uncertainty interval (UI): 417.35-499.14] million individuals worldwide had a CRD, showing a 39·8% increase compared with 1990. Deaths due to CRDs were 3.97 (95%UI: 3.58-4.30) million, and DALY in 2019 was 103.53 (95%UI: 94.79-112.27) million. Declines by average annual percent change (AAPC) were observed in age-standardized prevalence rates (ASPR) (0.64% decrease), age-standardized mortality rates (ASMR) (1.92%), and age-standardized DALY rates (ASDR) (1.72%) globally and in 5 socio-demographic index (SDI) regions. Decomposition analyses represented that the increase in overall CRDs DALY was driven by aging and population growth. However, chronic obstructive pulmonary disease (COPD) was the leading driver of increased DALY worldwide. Frontier analyses witnessed significant improvement opportunities at all levels of the development spectrum. Smoking remained a leading risk factor (RF) for mortality and DALY, although it showed a downward trend. Air pollution, a growing factor especially in relatively low SDI regions, deserves our attention. Conclusion: Our study clarified that CRDs remain the leading causes of prevalence, mortality, and DALY worldwide, with growth in absolute numbers but declines in several age-standardized estimators since 1990. The estimated contribution of risk factors to mortality and DALY demands the need for urgent measures to improve them. Systematic review registration: http://ghdx.healthdata.org/gbd-results-tool.

Analysis of oil synthesis pathway in Cyperus esculentus tubers and identification of oleosin and caleosin genes.

The tubers of the widely distributed Cyperus esculentus are rich in oil, and therefore, the plant is considered to have a high utilization value in the vegetable oil industry. Oleosins and caleosins are lipid-associated proteins found in oil bodies of seeds; however oleosins and caleosins genes have not been identified in C. esculentus. In this study, we performed transcriptome sequencing and lipid metabolome analysis of C. esculentus tubers at four developmental stages to obtain the information on their genetic profile, expression trends, and metabolites in oil accumulation pathways. Overall, 120,881 non-redundant unigenes and 255 lipids were detected; 18 genes belonged to the acetyl-CoA carboxylase (ACC), malonyl-CoA:ACP transacylase (MCAT), ß-ketoacyl-ACP synthase (KAS), and fatty acyl-ACP thioesterase (FAT) gene families involved in fatty acid biosynthesis, and 16 genes belonged to the glycerol-3-phosphate acyltransferase (GPAT), diacylglycerol acyltransferase 3 (DGAT3), phospholipid:diacylglycerol acyltransferase (PDAT), FAD2, and lysophosphatidic acid acyltransferase (LPAAT) gene families playing important roles in triacylglycerol synthesis. We also identified 9 oleosin- and 21 caleosin-encoding genes in C. esculentus tubers. These results provide detailed information on the C. esculentus transcriptional and metabolic profiles, which can be used as reference for the development of strategies to increase oil content in C. esculentus tubers.

Oxyberberrubine, a novel liver microsomes-mediated secondary metabolite of berberine, alleviates hyperuricemic nephropathy in mice.

BACKGROUND: Berberrubine (BRB), one of the major metabolites of berberine (BBR), exerts an anti-hyperuricemic effect even superior to BBR. Liver is an important location for drug transformation. Nevertheless, there are few studies on the bioactivities and metabolites of BRB. PURPOSE: We investigated whether oxyberberrubine (OBR), a liver metabolite of BRB, exerted urate-lowering and reno-protective effects in hyperuricemic mice. METHODS: Liver microsomes were used to incubate BRB for studying its biotransformation. We isolated and identified its new metabolite OBR, and investigated its anti-hyperuricemic and reno-protective effects. In this work, the hyperuricemic mice model was established by receiving potassium oxonate (PO) and hypoxanthine (HX) for 7 consecutive days. 1 h after modeling, different dosages of OBR (5, 10 and 20 mg/kg), BRB (20 mg/kg) or febuxostat (Fex, 5 mg/kg) were given mice by gavage. RESULTS: Results showed that OBR possessed potent anti-hyperuricemic and reno-protective effects in hyperuricemic mice. Serum uric acid (UA) level was lowered, and the activities of xanthine oxidase (XOD) as well as adenosine deaminase (ADA) in the liver were suppressed after treatment with OBR. Hepatic expressions of XOD were remarkably decreased at mRNA and protein levels by OBR treatment. In addition, OBR prominently alleviated renal injury, embodied in markedly reduced serum creatinine and blood urea nitrogen (BUN) levels, decreased inflammatory mediators (TNF-α, IL-1ß, IL-6 and IL-18) levels, mRNA expression of CYP27B1 and repairment of renal tissues damage. Besides, OBR down-regulated renal expression of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 at mRNA and protein levels. CONCLUSIONS: In short, our study indicated that OBR possessed superior anti-hyperuricemic and reno-protective effects, at least in part, through the inhibition of XOD, URAT1, GLUT9 and NLRP3 inflammasome signaling pathway in the kidney.

Recombinant human endostatin injection (Endostar) combined with PF chemotherapy and sequential intensity-modulated radiotherapy is tolerable and improves prognosis of locally advanced nasopharyngeal carcinoma: a randomized, open, multicenter phase II clinical study.

Nasopharyngeal carcinoma (NPC) is not only a common malignant disease of the head and neck, but also presented as locoregionally advanced NPC at diagnosis with poor prognosis. The efficacy of current chemoradiotherapy is unsatisfactory; therefore, in this study, we evaluated the safety and efficacy of treating locally advanced NPC using recombinant human endostatin injection (Endostar), combined with a cisplatin plus 5-fluorouracil (PF) regimen and sequential intensity-modulated radiotherapy (IMRT), and compared it with PF plus IMRT regimen. This phase II study included 83 eligible patients with stages III-IVa NPC (8th AJCC/UICC) who were randomized 1:1 into control (n = 42) and experimental (n = 41) groups. The control group received PF chemotherapy and IMRT for locally advanced NPC; One cycle of induction chemotherapy (IC) was administered before IMRT, and three cycles of adjuvant chemotherapy (AC) were administered four weeks post-radiotherapy. The experimental group received additional Endostar therapy. All patients were followed up for at least 5 years. The primary endpoints were progression-free survival (PFS) and the objective response rate. The secondary endpoints included overall survival and treatment-related toxicities. The short-term efficacy was evaluated at the end of the fourth chemotherapy cycle. Our results showed that the complete response rate of nasopharyngeal lesions was not significantly different between the experimental and control groups (80.5 vs. 71.4%, P = 0.335); however, there were significant differences in the complete response rates of cervical metastatic lymph nodes (75.6 vs. 40.5%, P = 0.001), especially for cervical N3 lymph nodes in the experimental group (55.6 vs. 9.5%, P = 0.004). The overall median follow-up time was 69.7 months. Patients in the experimental group showed significantly prolonged PFS by about four months (hazard ratio [HR] = 0.64, 95% CI: 0.41-0.99, P = 0.045). There was no significant difference in the median overall survival (P = 0.374). Furthermore, subgroup analysis indicated that the risk of death in patients with cervical N3 lymph nodes in the experimental group was reduced by 52% (HR = 0.48, 95% CI: 0.23-0.99, P = 0.046). Moreover, the incidence of radiation-induced grades 3-4 oral mucositis was significantly lower in the experimental group (29.3% vs. 54.8%, P = 0.019), while no significant differences in other severe adverse reactions were observed between the two groups (P>0.05). Taken together, our study indicated that, in patients with locally advanced NPC, Endostar in combination with PF chemotherapy and sequential IMRT significantly improved PFS, had tolerable treatment-related toxicities, improved the prognoses of patients with cervical N3 lymph nodes, and reduced the incidence of radiation-related oral mucositis.

DINs: Deep Interactive Networks for Neurofibroma Segmentation in Neurofibromatosis Type 1 on Whole-Body MRI.

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that involves the central and peripheral nervous systems. Accurate detection and segmentation of neurofibromas are essential for assessing tumor burden and longitudinal tumor size changes. Automatic convolutional neural networks (CNNs) are sensitive and vulnerable as tumors' variable anatomical location and heterogeneous appearance on MRI. In this study, wepropose deep interactive networks (DINs) to address the above limitations. User interactions guide the model to recognize complicated tumors and quickly adapt to heterogeneous tumors. We introduce a simple but effective Exponential Distance Transform (ExpDT) that converts user interactions into guide maps regarded as the spatial and appearance prior. Comparing with popular Euclidean and geodesic distances, ExpDT is more robust to various image sizes, which reserves the distribution of interactive inputs. Furthermore, to enhance the tumor-related features, we design a deep interactive module to propagate the guides into deeper layers. We train and evaluate DINs on three MRI data sets from NF1 patients. The experiment results yield significant improvements of 44% and 14% in DSC comparing with automated and other interactive methods, respectively. We also experimentally demonstrate the efficiency of DINs in reducing user burden when comparing with conventional interactive methods.

Risk Factors for the Development of Hemophagocytic Lymphohistiocytosis in Children With Severe Adenovirus Pneumonia: A Single-Center Retrospective Study.

Objective: To investigate and analyze the relevant risk factors for hemophagocytic lymphohistiocytosis (HLH) in children with severe adenovirus pneumonia (SAP). Methods: A retrospective study of children with SAP was performed in 30 cases developing HLH and 94 cases not developing HLH from December 2018 to August 2019. The binary logistic regression analysis was used to identify risk factors that were significantly associated with the development of HLH after the univariate analysis, and the receiver operating characteristic (ROC) curve was performed to find out the cut-off value for the significant relevant factors. Results: Two factors were associated with the development of HLH, which were the length of fever (OR = 1.331, 95%CI: 1.002-1.769) and triglycerides (TG) (OR = 17.345, 95%CI: 1.358-221.538). The cut-off value of the length of fever was 12.5 days, and the cut-off value of TG was 3.02 mmol/L. Conclusion: Children with SAP who had a duration of fever over 12.5 days and the TG level over 3.02 mmol/L are more likely to develop HLH.

Screening and identification of salt-tolerance genes in Sophora alopecuroides and functional verification of SaAQP.

MAIN CONCLUSION: Overexpression of SaAQP can improve the salt tolerance of transgenic soybean hairy roots and A. thaliana. Salt stress severely affects crop yield and food security. There is a need to improve the salt tolerance of crops, but the discovery and utilization of salt-tolerance genes remains limited. Owing to its strong stress tolerance, Sophora alopecuroides is ideal for the identification of salt-tolerance genes. Therefore, we aimed to screen and identify the salt-tolerance genes in S. alopecuroides. With a yeast expression library of seedlings, salt-tolerant genes were screened using a salt-containing medium to simulate salt stress. By combining salt-treatment screening and transcriptome sequencing, 11 candidate genes related to salt tolerance were identified, including genes for peroxidase, inositol methyltransferase, aquaporin, cysteine synthase, pectinesterase, and WRKY. The expression dynamics of candidate genes were analyzed after salt treatment of S. alopecuroides, and salt tolerance was verified in yeast BY4743. The candidate genes participated in the salt-stress response in S. alopecuroides, and their overexpression significantly improved the salt tolerance of yeast. Salt tolerance mediated by SaAQP was further verified in soybean hairy roots and Arabidopsis thaliana, and it was found that SaAQP might enhance the salt tolerance of A. thaliana by participating in a reactive oxygen species scavenging mechanism. This result provides new genetic resources in plant breeding for salt resistance.

Quantitative proteomic and lipidomics analyses of high oil content GmDGAT1-2 transgenic soybean illustrate the regulatory mechanism of lipoxygenase and oleosin.

KEY MESSAGE: Proteomic and lipidomics analyses of WT and GmDGAT1-2 transgenic soybeans showed that GmDGAT1-2 over-expression induced lipoxygenase down-regulatation and oleoin up-regulatation, which significantly changed the compositions and total fatty acid. The main goal of soybean breeding is to increase the oil content. Diacylglycerol acyltransferase (DGAT) is a key rate-limiting enzyme in fatty acid metabolism and may regulate oil content. Herein, 10 GmDGAT genes were isolated from soybean and transferred into wild-type (WT) Arabidopsis. The total fatty acid was 1.2 times higher in T3 GmDGAT1-2 transgenic Arabidopsis seeds than in WT. Therefore, GmDGAT1-2 was transferred into WT soybean (JACK), and four T3 transgenic soybean lines were obtained. The results of high-performance gas chromatography and Soxhlet extractor showed that, compared with those of JACK, oleic acid (18:1), and total fatty acid levels in transgenic soybean plants were much higher, but linoleic acid (18:2) was lower than WT. Palmitic acid (16:0), stearic acid (18:0), and linolenic acid (18:3) were not significantly different. For mechanistic studies, 436 differentially expressed proteins (DEPs) and 180 differentially expressed metabolites (DEMs) were identified between WT (JACK) and transgenic soybean pods using proteomic and lipidomics analyses. Four lipoxygenase proteins were down-regulated in linoleic acid metabolism while four oleosin proteins were up-regulated in the final oil formation. The results showed an increase in the total fatty acid and 18:1 composition, and a decrease in the 18:2 composition of fatty acid. Our study brings new insights into soybean genetic transformation and the deep study of molecular mechanism that changes the total fatty acid, 18:1, and 18:2 compositions in GmDGAT1-2 transgenic soybean.

CUL4high Lung Adenocarcinomas Are Dependent on the CUL4-p21 Ubiquitin Signaling for Proliferation and Survival.

Cullin (CUL) 4A and 4B ubiquitin ligases are often highly accumulated in human malignant neoplasms and are believed to possess oncogenic properties. However, the underlying mechanisms by which CUL4A and CUL4B promote pulmonary tumorigenesis remain largely elusive. This study reports that CUL4A and CUL4B are highly expressed in patients with non-small cell lung cancer (NSCLC), and their high expression is associated with disease progression, chemotherapy resistance, and poor survival in adenocarcinomas. Depletion of CUL4A (CUL4Ak/d) or CUL4B (CUL4Bk/d) leads to cell cycle arrest at G1 and loss of proliferation and viability of NSCLC cells in culture and in a lung cancer xenograft model, suggesting that CUL4A and 4B are oncoproteins required for tumor maintenance of certain NSCLCs. Mechanistically, increased accumulation of the cell cycle-dependent kinase inhibitor p21/Cip1/WAF1 was observed in lung cancer cells on CUL4 silencing. Knockdown of p21 rescued the G1 arrest of CUL4Ak/d or CUL4Bk/d NSCLC cells, and allowed proliferation to resume. These findings reveal that p21 is the primary downstream effector of lung adenocarcinoma dependence on CUL4, highlight the notion that not all substrates respond equally to abrogation of the CUL4 ubiquitin ligase in NSCLCs, and imply that CUL4Ahigh/CUL4Bhigh may serve as a prognostic marker and therapeutic target for patients with NSCLC.

ECMO-assisted resection of left main bronchial malignant tumor and left pneumonectomy with comprehensive nursing support: a case report.

BACKGROUND: Patients with Extracorporeal Membrane Oxygenation (ECMO) undergoing primary bronchial malignancy resection and left pneumonectomy via bilateral thoracic approach are rare for there exist few reports available to date. And the nursing experience about this disease is rare reported. CASE PRESENTATION: This study reported a 50-year-old man with adenoid cystic carcinoma in left main bronchus by computed tomography (CT), fiberoptic bronchoscopy, and puncture biopsy. The case is the first report about operation method and the comprehensive nursing care, including conventional nursing, airway management, fluid management, nutritional support, and psychosocial support for patients undergoing primary bronchial malignancy resection and left pneumonectomy. After multidisciplinary treatment and comprehensive care, the patient was cured and discharged on the 17th day after surgery. CONCLUSION: This study reported a rare case with bronchial malignancy resection and left pneumonectomy and discussed its nursing care. A skilled management of ECMO, intraoperative position transformation, and prevention, as well as control of pulmonary complications are fundamental in caring patients with bronchial tumors. Monitoring of pulmonary function and blood pressure, adequate nutrition, and psychological support could be contributing factors for successful treatment during the postoperative stage.

Cell Division Cycle 2 Protects Neonatal Rats Against Hyperoxia-Induced Bronchopulmonary Dysplasia.

PURPOSE: Hyperoxia-induced bronchopulmonary dysplasia (BPD) is a lung disease in preterm infants. We aimed to explore the role of cell division cycle 2 (CDC2) on histopathologic changes of lung tissues, as well as the viability, apoptosis, and inflammation of lung cells in rats with hyperoxia-induced BPD. MATERIALS AND METHODS: Hyperoxia-induced BPD in neonatal rats and hyperoxia-induced A549 cells were constructed. The mRNA expression of CDC2 was detected by qRT-PCR. The fibrosis score of lung tissues was evaluated by hematoxylin-eosin staining. The viability and apoptosis of A549 cells were detected by cell counting kit-8 assay and flow cytometry. The protein expressions of bcl-2, bax, and caspase-3 were measured by western blot. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß in A549 cells were detected by enzyme-linked immunosorbent assay. The pcDNA3.1-CDC2 was injected into rats to determine the role of CDC2 in hyperoxia-induced BPD in vivo. RESULTS: The expression of CDC2 was decreased in lung tissues of neonatal rats with hyperoxia-induced BPD and hyperoxia-induced A549 cells. The fibrosis score was increased in the lung tissues of neonatal rats with hyperoxia-induced BPD. Overexpression of CDC2 increased the viability and protein expression of bcl-2; and inhibited the apoptosis, inflammation, and protein expression of bax and caspase-3 in hyperoxia-induced A549 cells. Up-regulation of CDC2 alleviated the histopathologic changes in lung tissues of neonatal rats with hyperoxia-induced BPD. CONCLUSION: Overexpression of CDC2 promoted the viability and inhibited the apoptosis and inflammation of hyperoxia-induced cells, and alleviated the histopathologic changes of lung tissues in neonatal rats with hyperoxia-induced BPD.

CRL4 Ubiquitin Pathway and DNA Damage Response.

DNA damage occurs in a human cell at an average frequency of 10,000 incidences per day by means of external and internal culprits, damage that triggers sequential cellular responses and stalls the cell cycle while activating specific DNA repair pathways. Failure to remove DNA lesions would compromise genomic integrity, leading to human diseases such as cancer and premature aging. If DNA damage is extensive and cannot be repaired, cells undergo apoptosis. DNA damage response (DDR) often entails posttranslational modifications of key DNA repair and DNA damage checkpoint proteins, including phosphorylation and ubiquitination. Cullin-RING ligase 4 (CRL4) enzyme has been found to target multiple DDR proteins for ubiquitination. In this chapter, we will discuss key repair and checkpoint proteins that are subject to ubiquitin-dependent regulation by members of the CRL4 family during ultraviolet light (UV)-induced DNA damage.

Functional activation of a novel R2R3-MYB protein gene, GmMYB68, confers salt-alkali resistance in soybean (Glycine max L.).

Soil salinity significantly reduces soybean (Glycine max L.) production worldwide. Plants resistance to stress conditions is a complex characteristic regulated by multiple signaling pathways. The v-Myb avian myeloblastosis viral oncogene homolog (MYB) transcription factor (TF) plays a crucial role in plant development, secondary metabolism, and abiotic stress responses. GmMYB68-overexpression and RNA interference (RNAi) lines were established for examining the function of G. max GmMYB68 in plant responses to abiotic stresses. The predicted amino acid sequence of GmMYB68 was similar to that of R2R3-MYB proteins. Quantitative real-time PCR analysis revealed that GmMYB68 expression varied in response to abiotic stresses. GmMYB68-overexpression lines showed enhanced resistance to salt and alkali stresses and their osmotic adjustment and photosynthetic rates were also stronger than that of GmMYB68-RNAi and wild type plants. Although wild type and transgenic plants showed no significant differences in agronomic traits under normal conditions, the overexpression of GmMYB68 increased grain number and 100-grain weights under salt stress. Our study identified a valuable TF associated with stress response in soybean, as its overexpression might help improve salt and alkali tolerance in soybean and other crops.

Correction: Inhibition of HIF-1α by PX-478 enhances the anti-tumor effect of gemcitabine by inducing immunogenic cell death in pancreatic ductal adenocarcinoma.

[This corrects the article DOI: 10.18632/oncotarget.2948.].

Memory stem T cells generated by Wnt signaling from blood of human renal clear cell carcinoma patients.

OBJECTIVE: Memory stem T cells (Tscm) have attracted attention because of their enhanced self-renewal, multipotent capacity, and anti-tumor capacities. However, little is known about Tscm in patients with renal clear cell carcinoma (RCC) and the role of Wnt signaling in these cells. We evaluated Tscm from RCC patients concerning their activation of Wnt signaling in vitro and explored the mechanism of preferential survival. METHODS: Flow cytometry identified surface markers and cytokines produced from accumulated Tscm in the presence of the glycogen synthase kinase beta inhibitor TWS119. Apoptosis was evaluated after induction using tumor necrosis factor-alpha. Immunofluorescence and Western blot analyses were used to investigate the activation of the nuclear factor-kappa B (NF-КB) pathway. RESULTS: RCC patients had a similar percentage of CD4+ and CD8+ Tscm as healthy donors. Activation of Wnt signaling by TWS119 resulted in the accumulation of Tscm in activated T cells, but reversal of differentiated T cells to Tscm was not achieved. Preferential survival of Tscm was associated with increased anti-apoptotic ability mediated downstream of the NF-КB activation pathway. CONCLUSIONS: The finding that Tscm can accumulate by Wnt signaling in vitro in blood from RCC patients will help in devising new cancer therapy strategies of Tscm-based adoptive immunotherapy, such as dendritic cell-stimulated Tscm, and T cell receptor or chimeric antigen receptor-engineered Tscm.

Expedite recovery from esophagectomy and reconstruction for esophageal squamous cell carcinoma after perioperative management protocol reinvention.

BACKGROUND: Surgery for esophageal cancer is invasive and challenging, and always to be followed with arduous post-operative care and recovery. This study, maybe one of the first in Asian populations, is to determine whether a reinvented protocol for perioperative management for esophageal cancer surgery which is being implemented in our department, will lead to a faster convalescence and also significantly decrease financial burdens garnered by patients during hospitalization. METHODS: Operated on by the same surgeon and team in the same hospital, consecutive patients who had received esophagectomy and reconstruction for esophageal squamous cell carcinoma were retrospectively reviewed. On the basis of two different treatment periods, patients were divided into two groups: A and B. Group A was patients who had received the new reinvented protocol between 2012 and 2016, while group B patients were those having received the previous protocol between 2008 and 2011. Their demographics, post-operative outcome, and hospital charges were collected and compared. RESULTS: There were 64 patients in group A, and 69 in group B. Ventilator days (P<0.001), ICU stay (P<0.001), and post-operative stay (P<0.001) were significantly shorter in group A patients. Complication rates were similar between the two groups. No hospital mortality was noted in either group. Hospital charges in group A were found to be perceptively lower, although not statistically significant (P value =0.078). CONCLUSIONS: The current protocol of perioperative care effectively ameliorated convalescence after esophagectomy and reconstruction for esophageal squamous cell carcinoma without increasing complication rate or mortality. It is also potentially more practical in future health care policies during this era of financial shortage.