A novel protein FNDC3B-267aa encoded by circ0003692 inhibits gastric cancer metastasis via promoting proteasomal degradation of c-Myc.

BACKGROUND: Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive. METHODS: We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc. RESULTS: We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis. CONCLUSIONS: Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC.

Rhodium-Catalyzed Tandem Asymmetric Allylic Decarboxylative Addition and Cyclization of Vinylethylene Carbonates with N-Nosylimines.

A enantioselective tandem transformation, concerning asymmetric allylic decarboxylative addition and cyclization of N-nosylimines with vinylethylene carbonates (VECs), in the presence of [Rh(C2H4)2Cl]2, chiral sulfoxide-N-olefin tridentate ligand has been developed. The reaction of VECs with various substituted N-nosylimines proceeded smoothly under mild conditions, providing highly functionalized oxazolidine frameworks in good to high yields with good to excellent enantioselectivity.

Leaf senescence attributes: the novel and emerging role of sugars as signaling molecules and the overlap of sugars and hormones signaling nodes.

Sugars are the primary products of photosynthesis and play multiple roles in plants. Although sugars are usually considered to be the building blocks of energy storage and carbon transport molecules, they have also gradually come to be acknowledged as signaling molecules that can initiate senescence. Senescence is an active and essential process that occurs at the last developmental stage and corresponds to programmed degradation of: cells, tissues, organs, and entire organisms. It is a complex process involving: numerous biochemical changes, transporters, genes, and transcription factors. The process is controlled by multiple developmental signals, among which sugar signals are considered to play a vital role; however, the regulatory pathways involved are not fully understood. The dynamic mechanistic framework of sugar accumulation has an inconsistent effect on senescence through the sugar signaling pathway. Key metabolizing enzymes produce different sugar signals in response to the onset of senescence. Diverse sugar signal transduction pathways and a variety of sugar sensors are involved in controlling leaf senescence. This review highlights the processes underlying initiation of sugar signaling and crosstalk between sugars and hormones signal transduction pathways affecting leaf senescence. This summary of the state of current knowledge across different plants aids in filling knowledge gaps and raises key questions that remain to be answered with respect to regulation of leaf senescence by sugar signaling pathways.

Unexpected Cascade Sequence Forming the C(sp3)-N/C(sp2)-C(sp2) Bond: Direct Access to γ-Lactam-Fused Pyridones with Anticancer Activity.

An unexpected Ugi cascade reaction was developed for the facile construction of γ-lactam-fused pyridone derivatives with high tolerance of substrates. A C(sp3)-N bond and a C(sp2)-C(sp2) bond were formed together, accompanied by a chromone ring-opening in Ugi adducts, under the basic conditions without any metal catalyst for the whole process. Screening data of several difficult-to-inhibit cancer cell lines demonstrated that 7l displayed a high cytotoxicity against HCT116 cells (IC50 = 5.59 ± 0.78 µM). Taken together, our findings revealed new insights into the molecular mechanisms underlying compound 7l and provided potential usage of this scaffold for cancer therapeutics.

Darinaparsin (ZIO-101) enhances the sensitivity of small-cell lung cancer to PARP inhibitors.

Small-cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine carcinoma of the lung associated with early metastasis and an exceptionally poor prognosis. Little progress has been made in developing efficacious targeted therapy for this recalcitrant disease. Herein, we showed that H3.3, encoded by two genes (H3F3A and H3F3B), was prominently overexpressed in SCLC. Darinaparsin (ZIO-101), a derivative of arsenic trioxide, dose- and time-dependently inhibited the viability of SCLC cells in an H3.3-dependent manner. More importantly, ZIO-101 treatment resulted in substantial accumulation of H3.3 and PARP1 besides induction of G2/M cell cycle arrest and apoptosis in SCLC cells. Through integrative analysis of the RNA-seq data from Cancer Cell Line Encyclopedia dataset, JNCI and Genomics of Drug Sensitivity in Cancer 2 datasets, we found that H3F3A expression was negatively correlated with the IC50 values of PARP inhibitors (PARPi). Furthermore, co-targeting H3.3 and PARP1 by ZIO-101 and BMN673/olaparib achieved synergistic growth inhibition against SCLC in vitro and in vivo. In conclusion, it is feasible to target H3.3 by ZIO-101 to potentiate the response rate of PARPi in SCLC patients.

Comparison of Platelet-Rich Fibrin and Iodoform Gauze in the Treatment of Localized Alveolitis.

PURPOSE: Iodoform gauze is commonly used to treat patients with localized alveolitis; however, saliva can easily dilute the iodoform concentration. This study aimed to compare the efficacies of platelet-rich fibrin (PRF) and iodoform gauze in treating localized alveolitis. METHODS: This prospective randomized controlled trial enrolled patients with localized alveolitis who received treatment at our hospital from January 2018 to July 2021. They were randomly assigned to the control (treated with iodoform gauze) or experimental (treated with PRF) groups. Treatment method was the predictor variable. The primary outcome variable was clinical efficacy, defined as symptom resolution 1 week after treatment. Secondary outcome variables included granulation tissue (GT) quantitative score, analgesic drug dosage, and pain score determined using a visual analog scale (VAS). Patient demographics were used as covariates. Data analysis was performed by carrying out the χ2 and Mann-Whitney rank sum tests; P values <.05 indicated statistical significance. RESULTS: This study included 60 patients, equally and randomly divided into the control and PRF groups (n = 30 each). There were no significant differences in demographic characteristics of patients between the 2 groups. One week after treatment, the PRF group showed a higher healing rate (93.3% vs 60.0%) and better GT quantitative score (3.13 ± 0.63 vs 1.70 ± 0.75) than the control group (P < .05). Moreover, the number of analgesic tablets consumed within 1 week postoperatively was lesser in the PRF group than in the control group (3.93 ± 1.53 vs 9.67 ± 3.16, P < .05). The PRF group exhibited significantly lower VAS pain scores than those of the control group on the 3rd day (1.10 ± 1.03 vs 4.17 ± 1.49) and 7th day (0.30 ± 0.60 vs 1.73 ± 1.44, P < .05) postoperatively. CONCLUSIONS: Compared with iodoform gauze, PRF is associated with higher healing rate, faster promotion of GT growth in the extraction socket, better relief of alveolar pain, and lower intake of analgesic drugs when treating localized alveolitis.

[Effect of Zhenwu Decoction on electrical remodeling of cardiomyocytes in heart failure via I_(to)/Kv channels].

This study aimed to investigate the underlying mechanism of Zhenwu Decoction in the treatment of heart failure by regulating electrical remodeling through the transient outward potassium current(I_(to))/voltage-gated potassium(Kv) channels. Five normal SD rats were intragastrically administered with Zhenwu Decoction granules to prepare drug-containing serum, and another seven normal SD rats received an equal amount of distilled water to prepare blank serum. H9c2 cardiomyocytes underwent conventional passage and were treated with angiotensin Ⅱ(AngⅡ) for 24 h. Subsequently, 2%, 4%, and 8% drug-containing serum, simvastatin(SIM), and BaCl_2 were used to interfere in H9c2 cardiomyocytes for 24 h. The cells were divided into a control group [N, 10% blank serum + 90% high-glucose DMEM(DMEM-H)], a model group(M, AngⅡ + 10% blank serum + 90% DMEM-H), a low-dose Zhenwu Decoction-containing serum group(Z1, AngⅡ + 2% drug-containing serum of Zhenwu Decoction + 8% blank serum + 90% DMEM-H), a medium-dose Zhenwu Decoction-containing serum group(Z2, AngⅡ + 4% drug-containing serum of Zhenwu Decoc-tion + 6% blank serum + 90% DMEM-H), a high-dose Zhenwu Decoction-containing serum group(Z3, AngⅡ + 8% drug-containing serum of Zhenwu Decoction + 2% blank serum + 90% DMEM-H), an inducer group(YD, AngⅡ + SIM + 10% blank serum + 90% DMEM-H), and an inhibitor group(YZ, AngⅡ + BaCl_2 + 10% blank serum + 90% DMEM-H). The content of ANP in cell extracts of each group was detected by ELISA. The relative mRNA expression levels of ANP, Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 were detected by real-time quantitative PCR. The protein expression of Kv1.4, Kv4.2, Kv4.3, DPP6, and KChIP2 was detected by Western blot. I_(to) was detected by the whole cell patch-clamp technique. The results showed that Zhenwu Decoction at low, medium, and high doses could effectively reduce the surface area of cardiomyocytes. Compared with the M group, the Z1, Z2, Z3, and YD groups showed decreased ANP content and mRNA level, increased protein and mRNA expression of Kv4.2, Kv4.3, DPP6, and KChIP2, and decreased protein and mRNA expression of Kv1.4, and the aforementioned changes were the most notable in the Z3 group. Compared with the N group, the Z1, Z2, and Z3 groups showed significantly increased peak current and current density of I_(to). The results indicate that Zhenwu Decoction can regulate myocardial remodeling and electrical remodeling by improving the expression trend of Kv1.4, Kv4.2, Kv4.3, KChIP2, and DPP6 proteins and inducing I_(to) to regulate Kv channels, which may be one of the mechanisms of Zhenwu Decoction in treating heart failure and related arrhythmias.

Novel treatment for refractory rheumatoid arthritis with total glucosides of paeony and nobiletin codelivered in a self-nanoemulsifying drug delivery system.

Patients with refractory rheumatoid arthritis (RA) remain a substantial clinical problem, while the overexpression of P-glycoprotein (P-gp) on their lymphocytes may contribute to resistance to anti-rheumatic drugs. This study aims to develop a novel treatment for refractory RA consisting of the combination of total glucosides of paeony (TGPs) and the P-gp inhibitor nobiletin (N), which are codelivered in a self-nanoemulsifying drug delivery system (SNEDDS). Based on the solubility, compatibility, and pseudoternary phase diagram tests, a nano-SNEDDS formulation composed of capryol 90-cremophor EL35-tcranscutol HP (CET) to codeliver TGP and N was developed, and this formulation increased the bioavailability of TGP by 435.04% (indicated with paeoniflorin). A modified adjuvant-induced arthritis (AIA) rat model was verified for the overexpression of P-gp in lymphocytes and resistance to methotrexate (MTX) treatment at the reported anti-inflammatory dosage. CET formulation not only increased the solubility and permeability of TGP but also inhibited the function and expression of P-gp, leading to enhanced bioavailability and intracellular concentration in the lymphocytes of AIA rats and consequently boosting the anti-arthritic effects of TGP. Moreover, TGP and N coloaded CET reduced the expression of P-gp in AIA rats partly by inhibiting the phosphorylated AKT and HIF-1α pathways. In summary, TGP-N coloaded SNEDDS is a novel and effective treatment for refractory RA.

Nonunion of humeral medial condyle fracture caused by excessive functional exercise: a case report and review of the literature.

BACKGROUND: Medial epicondyle fractures are one of the more common humerus fractures, but humeral medial condyle fracture (HMCF) is rare. Nonunion of medial humeral condyle fractures due to functional exercise is less common. CASE PRESENTATION: We report a 5-year-old patient with a nonunion HMCF due to excessive functional exercise, who bruised the elbow 1 year ago and had no positive findings on all imaging studies. On this physical examination, there was a snapping and palpable lump in the elbow joint during movement, but the patient did not feel any discomfort and the range of motion of the joint was normal. X rays and computed tomography (CT) showed that the left HMCF was discontinuous, the broken ends were dislocated, and the joint alignment was poor. Open reduction (OR) and screw fixation was used during the operation, and the patient recovered well at 3-month follow-up. CONCLUSIONS: The rarity and low radiographic appearance of displaced HMCF are easily overlooked and can eventually lead to nonunion HMCF, especially when radiographically difficult to visualize before age 5 years. Therefore, regardless of whether there are signs or imaging abnormalities in the growth process of adolescents, they should be vigilant, shorten the time interval for re-examination, and early detection and timely treatment can avoid some complications caused by this.

Different roles of E proteins in t(8;21) leukemia: E2-2 compromises the function of AETFC and negatively regulates leukemogenesis.

The AML1-ETO fusion protein, generated by the t(8;21) chromosomal translocation, is causally involved in nearly 20% of acute myeloid leukemia (AML) cases. In leukemic cells, AML1-ETO resides in and functions through a stable protein complex, AML1-ETO-containing transcription factor complex (AETFC), that contains multiple transcription (co)factors. Among these AETFC components, HEB and E2A, two members of the ubiquitously expressed E proteins, directly interact with AML1-ETO, confer new DNA-binding capacity to AETFC, and are essential for leukemogenesis. However, the third E protein, E2-2, is specifically silenced in AML1-ETO-expressing leukemic cells, suggesting E2-2 as a negative factor of leukemogenesis. Indeed, ectopic expression of E2-2 selectively inhibits the growth of AML1-ETO-expressing leukemic cells, and this inhibition requires the bHLH DNA-binding domain. RNA-seq and ChIP-seq analyses reveal that, despite some overlap, the three E proteins differentially regulate many target genes. In particular, studies show that E2-2 both redistributes AETFC to, and activates, some genes associated with dendritic cell differentiation and represses MYC target genes. In AML patients, the expression of E2-2 is relatively lower in the t(8;21) subtype, and an E2-2 target gene, THPO, is identified as a potential predictor of relapse. In a mouse model of human t(8;21) leukemia, E2-2 suppression accelerates leukemogenesis. Taken together, these results reveal that, in contrast to HEB and E2A, which facilitate AML1-ETO-mediated leukemogenesis, E2-2 compromises the function of AETFC and negatively regulates leukemogenesis. The three E proteins thus define a heterogeneity of AETFC, which improves our understanding of the precise mechanism of leukemogenesis and assists development of diagnostic/therapeutic strategies.

Ir-Catalyzed Chemo-, Regio-, and Enantioselective Allylic Enolization of 6,6-Dimethyl-3-((trimethylsilyl)oxy)cyclohex-2-en-1-one Involving Keto-Enol Isomerization.

The utilization of 6,6-dimethyl-3-((trimethylsilyl)oxy)cyclohex-2-en-1-one made from an unsymmetrical 4,4-dimethylcyclohexane-1,3-dione in iridium-catalyzed allylic enolization involving keto-enol isomerization is accomplished under mild conditions. The chemoselectivity, regioselectivity, and enantioselectivity are facilitated by the quaternary carbon and adjusting the reaction conditions. This method provides the substituted 2-(but-3-en-2-yl)-3-hydroxy-6,6-dimethylcyclohex-2-en-1-ones in good to high yields with high level of chemo-, regio-, and enantioselectivities. The chiral carbon-fluorine bond formation is induced by an adjacent chiral carbon center of the allylated 3-hydroxy-6,6-dimethylcyclohex-2-en-1-one, as well.

Exopolysaccharide from Lactobacillus rhamnosus ZFM231 alleviates DSS-induced colitis in mice by regulating gut microbiota.

BACKGROUND: The exopolysaccharides (EPS) produced by Lactobacillus and other probiotics are associated with many benefits, such as immune regulation, antioxidant properties, antitumor effect, and regulation of intestinal microbe homeostasis. In the present study, the modulatory effect of EPS produced by Lactobacillus rhamnosus ZFM231 on the intestinal flora of mice with inflammatory bowel disease induced by dextran sulfate solution was investigated. RESULTS: Results indicated that weight loss, colonic length, the disease activity index score and colonic tissue damage in mice were significantly improved by EPS treatment. Compared with the model group, in the EPS-treated group, the diversity of and the composition of gut microbiota at both phylum and genus levels were found to recover to the levels of normal group, indicating the effective modulation on gut microbiota by EPS; short-chain fatty acids, including acetic acid, propionic acid and butyric acid produced by intestinal microbial metabolism, increased significantly; the level of anti-inflammatory factor transforning growth factor-ß significantly increased and the level of pro-inflammatory factor tumor necrosis factor-α significantly decreased in the colonic cells of EPS-treated mice. CONCLUSION: It is clear that EPS produced by L. rhamnosus ZFM231 could find application in functional foods with the property of anti-ulcerative colitis. The experimental results provide new insights into the probiotic effect of EPS. © 2022 Society of Chemical Industry.

Therapeutic Effect of an Anti-Human Programmed Death-Ligand 1 (PD-L1) Nanobody on Polymicrobial Sepsis in Humanized Mice.

BACKGROUND Immunosuppression is regarded as the main cause of death induced by sepsis. Anti-programmed death-ligand 1 (PD-L1) therapy is promising in reversing sepsis-induced immunosuppression but no evidence is available on use of commercially available anti-PD-L1 medications for this indication. The present preclinical study was performed to investigate the therapeutic effect of an anti-PD-L1 nanobody (KN035) in sepsis. MATERIAL AND METHODS The level of expression of PD-L1 in PD-L1 humanized mice was confirmed with flow cytometry. Plasma concentrations of KN035 at different dosages at different time points were detected using an enzyme-linked immunosorbent assay. PD-L1 humanized mice were allocated into 4 groups: sham, cecal ligation and puncture (CLP), isotype (isotype+CLP), and PD-L1 (KN035+CLP). The 7-day survival rate was observed to investigate outcomes in CLP mice. Disease severity was assessed with histopathological scoring of mice lungs and livers. Immune status was assessed based on cell apoptosis in the spleen and bacterial clearance. RESULTS PD-L1 levels were significantly elevated in peripheral lymphocytes, monocytes, and neutrophils after CLP surgery. Blood concentrations of KN035 showed that 2.5 mg/kg had potential to be an ideal dosage for KN035 therapy. Survival analysis demonstrated that KN035 was associated with significantly reduced mortality on Day 7 after surgery (P=0.0083). The histopathological tests showed that KN035 alleviated sepsis-induced injury in the lungs and liver. KN035 reduced the number of apoptotic cells in the spleen and almost eliminated bacterial colonies in the peritoneal lavage fluid from the CLP mice. CONCLUSIONS KN035, an anti-PD-L1 antibody, can improve the rate of survival in CLP mice and alleviate sepsis-induced apoptosis in the spleen.

Strain tuning of closed topological nodal lines and opposite pockets in quasi-two-dimensional α-phase FeSi2.

Following topological nodal point semimetals, topological nodal line semimetals with one dimensional (1D) topological elements have recently aroused great interest worldwide in the fields of quantum chemistry and condensed matter physics. In this study, by means of first-principles, we predict that quasi-two-dimensional (2D) α-FeSi2 with a P4/mmm space group is a topological nodal line semimetal with two nodal lines close to the Fermi level, in the kz = 0 and kz = π planes. Usually, topological nodal line semimetals can be classified into type I, type II, and hybrid-type categories, each type with different physical properties. Importantly, for the first time, we find that type I, type II, and hybrid-type nodal lines can be realized in a realistic material, i.e., quasi-2D α-FeSi2, by strain switching. The realization of tunable nodal line types occurs because quasi-2D α-FeSi2 has special opposite-pocket-behaving bands around the Fermi level. The results presented herein reflect that α-FeSi2 is a valuable candidate for spintronics application by utilization of type I, type II, and hybrid-type topological nodal line semimetals in a single material tuned by mechanical strain.

Development and Investigation of a NASICON-Type High-Voltage Cathode Material for High-Power Sodium-Ion Batteries.

Herein, we introduce a 4.0 V class high-voltage cathode material with a newly recognized sodium superionic conductor (NASICON)-type structure with cubic symmetry (space group P21 3), Na3 V(PO3 )3 N. We synthesize an N-doped graphene oxide-wrapped Na3 V(PO3 )3 N composite with a uniform carbon coating layer, which shows excellent rate performance and outstanding cycling stability. Its air/water stability and all-climate performance were carefully investigated. A near-zero volume change (ca. 0.40 %) was observed for the first time based on in situ synchrotron X-ray diffraction, and the in situ X-ray absorption spectra revealed the V3.2+ /V4.2+ redox reaction with high reversibility. Its 3D sodium diffusion pathways were demonstrated with distinctive low energy barriers. Our results indicate that this high-voltage NASICON-type Na3 V(PO3 )3 N composite is a competitive cathode material for sodium-ion batteries and will receive more attention and studies in the future.

Efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy: a systematic appraisal and meta-analysis.

BACKGROUND: The clinical significance of stem cell therapy in the treatment of dilated cardiomyopathy remains unclear. This systemic appraisal and meta-analysis aimed to assess the efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy. After searching the PubMed, Embase, and Cochrane library databases until November 2017, we conducted a meta-analysis to evaluate the efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy. METHODS: The weighted mean difference (WMD), standard mean difference (SMD), relative risk (RR), and 95% confidence interval (CI) were summarized in this meta-analysis. Both fixed effects and random effects models were used to combine the data. Sensitivity analyses were conducted to evaluate the impact of an individual dataset on the pooled results. RESULTS: A total of eight randomized controlled trials, which involved 531 participants, met the inclusion criteria in this systematic appraisal and meta-analysis. Our meta-analysis showed that stem cell therapy improves left ventricular ejection fraction (SMD = 1.09, 95% CI 0.29 to 1.90, I2 = 92%) and reduces left ventricular end-systolic volume (SMD = - 0.36, 95% CI - 0.61 to - 0.10, I2 = 20.5%) and left ventricular end-diastolic chamber size (SMD = - 0.48, 95% CI - 0.89 to - 0.07, I2 = 64.8%) in patients with dilated cardiomyopathy. However, stem cell therapy has no effect on mortality (RR = 0.72, 95% CI 0.50 to 1.02, I2 = 30.2%) and 6-min-walk test (WMD = 51.52, 95% CI - 24.52 to 127.55, I2 = 94.8%). CONCLUSIONS: This meta-analysis suggests that stem cell therapy improves left ventricular ejection fraction and reduces left ventricular end-systolic volume and left ventricular end-diastolic chamber size in patients with dilated cardiomyopathy. However, future well-designed large studies might be necessary to clarify the effect of stem cell therapy in patients with dilated cardiomyopathy.

MRI-based nomogram estimates the risk of recurrence of primary nonmetastatic pancreatic neuroendocrine tumors after curative resection.

BACKGROUND: Accurate estimation of the recurrence of pancreatic neuroendocrine tumors help with prognosis, guide follow-up, and avoid futile treatments. PURPOSE: To investigate whether MRI features could preoperatively estimate the recurrence of pancreatic neuroendocrine tumors (PNETs) and to refine a novel prognostic model through developing a nomogram incorporating various MRI features. STUDY TYPE: Retrospective. POPULATION: In all, 81 patients with clinicopathologically confirmed nonmetastatic PNETs. FIELD STRENGTH/SEQUENCES: 1.5 T MR, including T1 -weighted, T2 -weighted, and diffusion-weighted imaging sequences. ASSESSMENT: Qualitative and quantitative MRI features of PNET were assessed by three experienced radiologists. STATISTICAL TESTS: Uni- and multivariable analyses for recurrence-free survival (RFS) were evaluated using a Cox proportional hazards model. The MRI-based nomogram was then designed based on multivariable logistic analysis in our study and the performance of the nomogram was validated according to C-index, calibration, and decision curve analyses. RESULTS: MRI features, including tumor size (hazard ratio [HR]: 14.131; P = 0.034), enhancement pattern (HR: 21.821, P = 0.032), and the apparent diffusion coefficient (ADC) values (HR: 0.055, P = 0.038) were significant independent predictors of RFS at multivariable analysis. The performance of the nomogram incorporating various MRI features (with a C-index of 0.910) was improved compared with that based on tumor size, enhancement pattern, and ADC alone (with C-index values of 0.672, 0.851, and 0.809, respectively). The calibration curve of the nomogram exhibited perfect consistency between estimation and observation at 0.5, 1, and 2 years after surgery. The decision curve showed that a nomogram incorporating three features had more favorable clinical predictive usefulness than any single feature. DATA CONCLUSION: MRI features can be considered effective recurrence predictors for PNETs after surgery. The preliminary nomogram incorporating various MRI features could assess the risk of recurrence in PNETs and may be used to optimize individual treatment strategies. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:397-409.

Pararhodobacter oceanensis sp. nov., isolated from marine intertidal sediment and emended description of the genus Pararhodobacter.

A Gram-stain-negative, rod-shaped, non-motile and facultatively anaerobic bacterium, designated AM505T, was isolated from Shuangdao Bay in Weihai, China. Cells of strain AM505T were 0.4-0.8 µm wide, 1.3-3.3 µm long, catalase-positive and oxidase-positive. Strain AM505T was tolerant to moderate salt conditions. Growth occurred at 4-40 °C (optimum, 28-33 °C), pH 6.5-9.5 (pH 7.5-8.0) and with 0.5-9.0 % NaCl (w/v; 2.0-4.0 %). A phylogenetic analysis of the 16S rRNA gene indicated that strain AM505T was a member of the genus Pararhodobacter within the family Rhodobacteraceae. The most closely related neighbour was Pararhodobacter aggregans DSM 18938T (97.6 %). The average nucleotide identity value between AM505T and P. aggregans DSM 18938T was 75.3 %. The major respiratory quinone of strain AM505T was ubiquinone-10 and the predominant cellular fatty acids (>10 %) were summed feature 8 (consisting of C18 : 1ω7c and/or C18 : 1ω6c), 11-methyl C18 : 1ω7c and C18 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and an unidentified aminolipid. The genomic DNA G+C content was 63.0 mol%. Based on our polyphasic taxonomic study, strain AM505T should be a novel species in the genus Pararhodobacter, for which the name Pararhodobacteroceanensis sp. nov. is proposed. The type strain is AM505T (=KCTC 62407T=MCCC 1H00289T).

Inhibition of Notch signaling pathway enhanced the radiosensitivity of breast cancer cells.

This study aimed to investigate the effect of inhibiting the Notch signaling pathway on the radiosensitivity of breast cancer cells. Human breast cancer cell lines (MCF-7 and T47D) were selected and treated with radiation of different doses. Cells were treated with Gamma secretase inhibitor (GSI) to analyze the effects of GSI on the Notch signaling, which were detected by Immunofluorescence assay, RT-qPCR, and Western blot analysis. Besides, Transwell assay, Scratch test, colony formation assay, MTT assay, and flow cytometry were conducted to show the effects of GSI on the invasion and migration, survival fraction, cell viability, and apoptosis of MCF-7 and T47D cells after radiation therapy. Moreover, cell transfection with a dominant negative mutant of RBPJ, the key transcription factor of Notch signaling pathway, were also applied to show the inhibition of Notch signaling pathway. Initially, we found that the 4 Gy radiation activated Notch signaling pathway, and enhanced the invasion and migration of MCF-7 and T47D cells. However, GSI inhibited the Notch signaling pathway, and reversed the enhancement of radiation on the migration and invasion, promoted the enhancement of apoptosis and inhibition of proliferation of MCF-7 and T47D cells induced by radiation. Except that, we also determined that GSI and dnRBPJ suppressed the upregulation of Notch signaling after radiation therapy. Our study demonstrated that inhibition of the Notch signaling pathway enhanced the radiosensitivity of breast cancer cells, which may provide evident for a beneficial adjuvant therapy in the breast cancer treatment.

Anti-inflammatory activities of hepatocyte growth factor in post-ischemic heart failure.

Hepatocyte growth factor (HGF) alleviates acute and chronic inflammation in experimental inflammatory bowel disease, glomerulonephritis, and airway inflammation. However, the anti-inflammatory effects of HGF on myocardial infarction are not defined. The current study assessed the anti-inflammatory effects of HGF in post-ischemic heart failure. The left anterior descending coronary artery was ligated in rats, and adenovirus containing human HGF (Ad-HGF) or control virus (Ad-GFP) was administered intramyocardially. The quantity of proinflammatory cytokines secreted by cardiomyocytes, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß, was evaluated. Cardiac function and LV remodeling were assessed using echocardiography and collagen deposition, respectively. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) four weeks after injection were significantly increased in Ad-HGF-treated animals compared to the Ad-GFP group. HGF gene therapy improved ventricular geometry with a significantly decreased left ventricular end-diastolic diameter (LVEDD) and markedly reduced myocardial collagen deposition. Treatment with Ad-HGF significantly decreased the mRNA levels of TNF-α, IL-6, and IL-1ß in the non-infarcted region four weeks after injection. Changes of the TNF-α, IL-6, and IL-1ß levels in the non-infarcted region positively correlated with the LVEDD 4 weeks after infarction. Treatment of acute myocardial infarction (AMI) with Ad-HGF in the early stage of MI reduced the pro-inflammatory cytokine levels and preserved cardiac function. These findings indicated that Ad-HGF gene therapy alleviated ventricular remodeling after infarction by reducing inflammation.