Pairwise machine learning-based automatic diagnostic platform utilizing CT images and clinical information for predicting radiotherapy locoregional recurrence in elderly esophageal cancer patients.

OBJECTIVE: To investigate the feasibility and accuracy of predicting locoregional recurrence (LR) in elderly patients with esophageal squamous cell cancer (ESCC) who underwent radical radiotherapy using a pairwise machine learning algorithm. METHODS: The 130 datasets enrolled were randomly divided into a training set and a testing set in a 7:3 ratio. Clinical factors were included and radiomics features were extracted from pretreatment CT scans using pyradiomics-based software, and a pairwise naive Bayes (NB) model was developed. The performance of the model was evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). To facilitate practical application, we attempted to construct an automated esophageal cancer diagnosis system based on trained models. RESULTS: To the follow-up date, 64 patients (49.23%) had experienced LR. Ten radiomics features and two clinical factors were selected for modeling. The model demonstrated good prediction performance, with area under the ROC curve of 0.903 (0.829-0.958) for the training cohort and 0.944 (0.849-1.000) for the testing cohort. The corresponding accuracies were 0.852 and 0.914, respectively. Calibration curves showed good agreement, and DCA curve confirmed the clinical validity of the model. The model accurately predicted LR in elderly patients, with a positive predictive value of 85.71% for the testing cohort. CONCLUSIONS: The pairwise NB model, based on pre-treatment enhanced chest CT-based radiomics and clinical factors, can accurately predict LR in elderly patients with ESCC. The esophageal cancer automated diagnostic system embedded with the pairwise NB model holds significant potential for application in clinical practice.

Bone-metastatic lung adenocarcinoma cells bearing CD74-ROS1 fusion interact with macrophages to promote their dissemination.

Approximately 40% of patients with lung adenocarcinoma (LUAD) often develop bone metastases during the course of their disease. However, scarcely any in vivo model of LUAD bone metastasis has been established, leading to a poor understanding of the mechanisms underlying LUAD bone metastasis. Here, we established a multiorgan metastasis model via the left ventricular injection of luciferase-labeled LUAD cells into nude mice and then screened out lung metastasis (LuM) and bone metastasis (BoM) cell subpopulations. BoM cells exhibited greater stemness and epithelial-mesenchymal transition (EMT) plasticity than LuM cells and initially colonized the bone and subsequently disseminated to distant organs after being reinjected into mice. Moreover, a CD74-ROS1 fusion mutation (C6; R34) was detected in BoM cells but not in LuM cells. Mechanistically, BoM cells bearing the CD74-ROS1 fusion highly secrete the C-C motif chemokine ligand 5 (CCL5) protein by activating STAT3 signaling, recruiting macrophages in tumor microenvironment and strongly inducing M2 polarization of macrophages. BoM cell-activated macrophages produce a high level of TGF-ß1, thereby facilitating EMT and invasion of LUAD cells via TGF-ß/SMAD2/3 signaling. Targeting the CD74-ROS1/CCL5 axis with Crizotinib (a ROS1 inhibitor) and Maraviroc (a CCL5 receptor inhibitor) in vivo strongly impeded bone metastasis and secondary metastasis of BoM cells. Our findings reveal the critical role of the CD74-ROS1/STAT3/CCL5 axis in the interaction between LUAD bone metastasis cells and macrophages for controlling LUAD cell dissemination, highlighting the significance of the bone microenvironment in LUAD bone metastasis and multiorgan secondary metastasis, and suggesting that targeting CD74-ROS1 and CCL5 is a promising therapeutic strategy for LUAD bone metastasis.

P4HA2 activates mTOR via hydroxylation and targeting P4HA2-mTOR inhibits lung adenocarcinoma cell growth.

Mammalian target of rapamycin (mTOR) kinase functions as a central regulator of cell growth and metabolism, and its complexes mTORC1 and mTORC2 phosphorylate distinct substrates. Dysregulation of mTOR signaling is commonly implicated in human diseases, including cancer. Despite three decades of active research in mTOR, much remains to be determined. Here, we demonstrate that prolyl 4-hydroxylase alpha-2 (P4HA2) binds directly to mTOR and hydroxylates one highly conserved proline 2341 (P2341) within a kinase domain of mTOR, thereby activating mTOR kinase and downstream effector proteins (e.g. S6K and AKT). Moreover, the hydroxylation of P2341 strengthens mTOR stability and allows mTOR to accurately recognize its substrates such as S6K and AKT. The growth of lung adenocarcinoma cells overexpressing mTORP2341A is significantly reduced when compared with that of cells overexpressing mTORWT. Interestingly, in vivo cell growth assays show that targeting P4HA2-mTOR significantly suppresses lung adenocarcinoma cell growth. In summary, our study reveals an undiscovered hydroxylation-regulatory mechanism by which P4HA2 directly activates mTOR kinase, providing insights for therapeutically targeting mTOR kinase-driven cancers.

Effect of prehabilitation on postoperative outcomes in the frail older people: A systematic review and meta-analysis.

OBJECTIVE: The study investigates the impact of preoperative rehabilitation on the surgical prognosis of frail older patients. METHOD: The effect sizes of all studies retrieved and included by the nine databases were analyzed and expressed as RR and WMD. RESULTS: 8 studies with 902 participants met the criteria for inclusion. A significant reduction in total complications (RR = 0.84, 95 % CI = 0.73 to 0.97, P = 0.021) and the 6MWT after surgery (WMD = 74.76, 95 % CI = 44.75 to 104.77, P = 0.000) was observed in the prehabilitation group. But it had no differences in mortality(RR = 1.89, 95 % CI = 0.75 to 4.72, P = 0.176), readmission rates(RR = 1.04, 95 % CI = 0.56 to 1.91, P = 0.906) and LOS(WMD = -0.24, 95 % CI = -1.00 to 0.52, P = 0.540). CONCLUSIONS: Prehabilitation had positive effect on postoperative complications and functional recovery in frail older patients.

Predicting Breast Cancer Subtypes Using Magnetic Resonance Imaging Based Radiomics With Automatic Segmentation.

OBJECTIVE: The aim of the study is to demonstrate whether radiomics based on an automatic segmentation method is feasible for predicting molecular subtypes. METHODS: This retrospective study included 516 patients with confirmed breast cancer. An automatic segmentation-3-dimensional UNet-based Convolutional Neural Networks, trained on our in-house data set-was applied to segment the regions of interest. A set of 1316 radiomics features per region of interest was extracted. Eighteen cross-combination radiomics methods-with 6 feature selection methods and 3 classifiers-were used for model selection. Model classification performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: The average dice similarity coefficient value of the automatic segmentation was 0.89. The radiomics models were predictive of 4 molecular subtypes with the best average: AUC = 0.8623, accuracy = 0.6596, sensitivity = 0.6383, and specificity = 0.8775. For luminal versus nonluminal subtypes, AUC = 0.8788 (95% confidence interval [CI], 0.8505-0.9071), accuracy = 0.7756, sensitivity = 0.7973, and specificity = 0.7466. For human epidermal growth factor receptor 2 (HER2)-enriched versus non-HER2-enriched subtypes, AUC = 0.8676 (95% CI, 0.8370-0.8982), accuracy = 0.7737, sensitivity = 0.8859, and specificity = 0.7283. For triple-negative breast cancer versus non-triple-negative breast cancer subtypes, AUC = 0.9335 (95% CI, 0.9027-0.9643), accuracy = 0.9110, sensitivity = 0.4444, and specificity = 0.9865. CONCLUSIONS: Radiomics based on automatic segmentation of magnetic resonance imaging can predict breast cancer of 4 molecular subtypes noninvasively and is potentially applicable in large samples.

Application of immersion B-scan ultrasonography in diagnosis of complex retinal detachment, persistent hyperplastic primary vitreous and intraocular tumors.

AIM: To evaluate the diagnostic value of panoramic immersion B-scan ultrasonography (Pano-immersion B-scan, PIB) in complex retinal detachment (RD), persistent hyperplastic primary vitreous (PHPV) and intraocular tumors. METHODS: The clinical data of 44 patients collected from May 2012 to December 2019 in Chinese PLA General Hospital was retrospectively studied. All of these patients underwent PIB of the eye, because it was difficult to diagnose by routine ocular fundus examination, conventional ultrasound or/and ultrasonic biomicroscope (UBM) due to opacity of refractive media, pupillary occlusion, large involvement or special location of the lesion. The imaging features of difficult cases in PIB were analyzed. The diagnosis accuracy rating of PIB were evaluated and contrasted with conventional ultrasound or UBM by the standard of intraoperative diagnosis or/and pathological results. RESULTS: According to intraoperative diagnosis or pathological results as gold standard, among the 44 cases, there were 19 cases missed diagnosis, misdiagnosed or difficult-to-diagnose by conventional ultrasound or UBM, including 4 cases of long-standing RD difficult to diagnose, 4 cases misdiagnosed, and 11 cases incompletely observed or miss diagnosed. The diagnostic accuracy rate of PIB and conventional ultrasound or UBM were 100% (44/44) and 56.82% (25/44), and the sensitivity of them were 100% and 56.82%. All the patients underwent PIB and were diagnosed as RD (15 cases), retinal and choroidal detachment (4 cases), subchoroidal hematocele (1 case), vitreous opacity and/or organic membrane formation (4 cases), PHPV (12 cases), iris and/or ciliary body tumors (3 cases), and choroidal tumors (6 cases). According to the intraoperative diagnosis or pathological results, the diagnostic coincidence rate of PIB was 100%, which was significantly higher than conventional ultrasound and UBM. CONCLUSION: PIB can help to accurately diagnose complex RD, PHPV, and intraocular masses with special location or/and excessive size. It has important diagnostic value for patients with equivocal findings at conventional ultrasound examination.

TIF1γ inhibits lung adenocarcinoma EMT and metastasis by interacting with the TAF15/TBP complex.

The molecular underpinnings of lung adenocarcinoma (LUAD) metastasis remain poorly defined. Here, using human LUAD cell lines, we find that transcriptional intermediary factor 1 γ (TIF1γ) binds to TATA box binding protein (TBP) in competition with TBP-associated factor 15 (TAF15) and impedes TAF15/TBP-mediated interleukin 6 (IL-6) transactivation. TIF1γ modifies TAF15 through multi-mono-ubiquitylation and drives nuclear export of TAF15. Functionally, TAF15 accelerates epithelial-mesenchymal transition (EMT) and metastasis of LUAD cells, acting in just the opposite way as TIF1γ. Low TIF1γ or high TAF15 expression levels are shown in metastatic LUAD specimens and correlate with poor survival of individuals with LUAD. Our findings suggest that the TAF15/TBP complex is required for IL-6 activation-induced EMT and invasion, which are inhibited by TIF1γ. This study highlights the crucial interaction between TIF1γ and the TAF15/TBP complex for regulating EMT and metastasis in LUAD.

RGS6 suppresses TGF-ß-induced epithelial-mesenchymal transition in non-small cell lung cancers via a novel mechanism dependent on its interaction with SMAD4.

Regulator of G-protein signaling 6 (RGS6) is a newly discovered tumor suppressor that has been shown to be protective in development of various cancers such as breast cancer and bladder cancer. But the mechanisms underlying these tumor-suppressing functions of RGS6 are not fully understood. Here, we discover a novel function of RGS6 in suppressing TGF-ß-induced epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) cells and in vivo NSCLC metastasis. Using both bioinformatics and experimental tools, we showed that RGS6 was downregulated in lung cancer tissues compared to noncancerous counterparts, and low expression of RGS6 was associated with poor survival of lung cancer patients. Overexpression of RGS6 suppressed TGF-ß-induced EMT in vitro and TGF-ß-promoted metastasis in vivo, by impairing gene expression of downstream effectors induced by the canonical TGF-ß-SMAD signaling. The ability of RGS6 to suppress TGF-ß-SMAD-mediated gene expression relied on its binding to SMAD4 to prevent complex formation between SMAD4 and SMAD2/3, but independent of its regulation of the G-protein signaling. Interaction between RGS6 and SMAD4 caused less nuclear entry of p-SMAD3 and SMAD4, resulting in inefficient SMAD3-mediated gene expression. Taken together, our findings reveal a novel and noncanonical role of RGS6 in regulation of TGF-ß-induced EMT and metastasis of NSCLC and identify RGS6 as a prognostic marker and a potential novel target for NSCLC therapy.

Accuracy of segmented measurement of axial length in ultra-high myopia filled with silicone oil using immersion B-scan ultrasonography.

AIM: To evaluate the accuracy of segmented measurement of axial length (AL) in high myopia filled with silicone oil by immersion B-scan ultrasonography (immersion B-scan). METHODS: From June 2016 to June 2020, a total of 67 ultra-high myopia inpatients (67 eyes) who underwent silicone oil removal combined with cataract extraction and intraocular lens (IOL) implantation were retrospectively enrolled. The preoperative axial length (AL) of 31 patients with severe cataract were segmented measured using immersion B-scan (B-scan group) and another 36 patients with mild or moderate cataract were measured using IOLMaster 500 (IOLMaster group). The post-operative ALs in two groups were both measured using IOLMaster 500. The IOL power was calculated with Haigis formula. The differences in ALs between pre- and post-surgery, as well as the postoperative refractive spherical equivalent, absolute refractive error, the prediction deviation of postoperative refraction and best corrected visual acuity (BCVA) were compared. RESULTS: The pre- and post-operative ALs were 30.46±1.63 mm (range 28.09-33.51 mm) and 30.42±1.70 mm (range 28.03-33.90 mm) in B-scan group (t=0.644, P=0.542) and 30.51±1.21 mm (range 28.03-33.90 mm) and 30.43±1.27mm (range 28.54-33.50 mm) in IOLMaster group (t=1.843, P=0.074), respectively. Three months after surgery, BCVA were 0.45±0.13 (range 0.3-0.9) and 0.44±0.20 (range 0.2-1.0) in B-scan and IOLMaster group respectively (t=0.086, P=0.932). There was no significant difference of the postoperative spherical equivalent (-3.11±0.65 D vs -3.21±0.51 D, t=0.671, P=0.505) and the absolute refractive error (0.589±0.340 vs 0.470±0.245 D, t=1.615, P=0.112) between two groups. In B-scan group, absolute refractive error within ±0.50 D was found in 18 eyes (58.1%), within ±1.00 D in 26 eyes (83.9%), and within ±1.50 D in 31 eyes (100%). In IOLMaster group, absolute refractive error within ±0.50 D was found in 23 eyes (63.9%), within ±1.00 D in 34 eyes (94.4%), and within ±1.50 D in 36 eyes (Z=0.757, P=0.449). CONCLUSION: The segmented measurement of ALs by immersion B-scan shows comparable measurement accuracy with that of IOLMaster 500 in ultra-high myopia patients with severe cataract secondary to silicone oil filling and can obtain an ideal postoperative refractive state.

RNA demethylase ALKBH5 inhibits TGF-ß-induced EMT by regulating TGF-ß/SMAD signaling in non-small cell lung cancer.

AlkB homolog 5 (ALKBH5) has been revealed as a key RNA N6 -methyladenosine (m6 A) demethylase that is implicated in development and diseases. However, the function of ALKBH5 in TGF-ß-induced epithelial-mesenchymal transition (EMT) and tumor metastasis of non-small-cell lung cancer (NSCLC) remains unknown. Here, we firstly show that ALKBH5 expression is significantly reduced in metastatic NSCLC. ALKBH5 overexpression inhibits TGF-ß-induced EMT and invasion of NSCLC cells, whereas ALKBH5 knockdown promotes the corresponding phenotypes. ALKBH5 overexpression suppresses TGF-ß-stimulated NSCLC cell metastasis in vivo. ALKBH5 overexpression decreases the expression and mRNA stability of TGFßR2 and SMAD3 but increases those of SMAD6, while ALKBH5 knockdown causes the opposite results. Importantly, ALKBH5 overexpression or knockdown leads respectively to an attenuated or augmented phosphorylation of SMAD3, an indispensable downstream effector that activates TGF-ß/SMAD signaling. Moreover, m6 A-binding proteins YTHDF1/3 promotes TGFßR2 and SMAD3 expression, and YTHDF2 inhibits SMAD6 expression. YTHDF1/2/3 facilitates TGF-ß-stimulated EMT and invasion of NSCLC cells. Mechanistically, ALKBH5 affects TGFßR2, SMAD3 and SMAD6 expression and mRNA stability by erasing m6 A modification in NSCLC cells. ALKBH5 weakens YTHDF1/3-mediated TGFßR2 and SMAD3 mRNA stabilization, and abolishes YTHDF2-mediated SMAD6 mRNA degradation, supporting the notion that ALKBH5 inhibits TGF-ß-induced EMT and invasion of NSCLC cells via YTHD1/2/3-mediated mechanism. Taken together, our findings highlight an important role of ALKBH5 in regulating TGF-ß/SMAD signaling, and establish a mechanistic interaction of ALKBH5 with TGFßR2/SMAD3/SMAD6 for controlling TGF-ß-induced EMT in NSCLCs.

RNA-binding proteins and cancer metastasis.

RNA-binding proteins (RBPs) can regulate gene expression through post-transcriptionally influencing all manner of RNA biology, including alternative splicing (AS), polyadenylation, stability, and translation of mRNAs, as well as microRNAs (miRNAs) and circular RNAs (circRNAs) processing. There is accumulating evidence reinforcing the perception that dysregulation or dysfunction of RBPs can lead to various human diseases, including cancers. RBPs influence diverse cancer-associated cellular phenotypes, such as proliferation, apoptosis, senescence, migration, invasion, and angiogenesis, contributing to the initiation and development of tumors, as well as clinical prognosis. Metastasis is the leading cause of cancer-related recurrence and death. Therefore, it is necessary to elucidate the molecular mechanisms behind tumor metastasis. In fact, a growing body of published research has proved that RBPs play pivotal roles in cancer metastasis. In this review, we will summarize the recent advances for helping us understand the role of RBPs in tumor metastasis, and discuss dysfunctions and dysregulations of RBPs affecting metastasis-associated processes including epithelial-mesenchymal transition (EMT), migration, and invasion of cancer cells. Furthermore, we will discuss emerging RBP-based strategy for the treatment of cancer metastasis.

Enhanced solubility of curcumin by complexation with fermented cyclic ß-1,2-glucans.

Curcumin (CUR) is a low-solubility polyphenolic compound with many physiological functions. Cyclic ß-1,2-glucans (cyclosophoraoses [Cys]), which contain rings of different sizes with degrees of polymerization ranging from 17 to 23, were obtained from Rhizobium radiobacter ATCC 1333, a soil microorganism. The complexation ability and solubility enhancement of cyclic ß-1,2-glucans with insoluble curcumin were investigated. Phase-solubility analysis revealed that the stoichiometric ratio of the inclusion complexes was 1:1. The stability constant of Cys was 930 M-1, which was 7.68 times that of α-cyclodextrin (α-CD) and 2.09 times that of ß-cyclodextrin (ß-CD). The characteristics of the curcumin/Cys inclusion complexes were successfully determined by using Fourier transform infrared (FTIR) spectrometry, differential scanning calorimetry (DSC), nuclear magnetic resonance (1H NMR) spectroscopy, and scanning electron microscopy (SEM). Moreover, a 1:1 molecular model of the curcumin/Cys inclusion complexes was established through molecular docking analysis. These findings indicated that cyclic ß-1,2-glucans successfully formed complexes with curcumin, which suggested that they could be used as solubility-increasing agents. To the best of our knowledge, this is the first report in which curcumin has been embedded into cyclic ß-1,2-glucans resulting in an increase in its aqueous solubility.

A new two-dimensional folding sheet-like coordination polymer assembled from cadmium(II) and (S)-2-(benzylamino)succinic acid: synthesis, structure and properties.

A new two-dimensional (2D) coordination polymer, namely, poly[[diaqua[µ3-(S)-2-(benzylamino)succinato-κ4N,O1:O1':O4]cadmium(II)] monohydrate], {[Cd(C11H11NO4)(H2O)2]·H2O}n, has been synthesized by the solvothermal reaction of Cd(CH3COO)2·2H2O with the synthesized ligand (S)-2-(benzylamino)succinic acid (H2L). The title compound has been structurally characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction analysis. In the crystal structure, each CdII cation binds to three carboxylate groups from three symmetry-related L2- dianions. The tetradentate L2- ligand links three symmetry-related CdII cations into a 2D folding sheet, which can be simplified as a uninodal (3,3)-connected hcb net with the point symbol (63). In the lattice, all the folding sheets are arranged in an interdigitated fashion and aggregate into zipper-like arrays through interlayer π-π interactions. The large and nonpolar side chain may play an important role in the formation and aggregation of the 2D sheet. The thermal stability and photoluminescence properties of the title compound were investigated, and it exhibits a blue emission with a quantum yield of 8%.

A new three-dimensional twofold interpenetrated cadmium(II) metal-organic framework: synthesis, structure and photoluminescence properties. Corrigendum.

In the article by Zhang & Wang [Acta Cryst. (2021), C77, 691-697], the topology of the title compound is corrected.

A new three-dimensional twofold interpenetrated cadmium(II) metal-organic framework: synthesis, structure and photoluminescence properties.

The design and synthesis of metal-organic frameworks (MOFs) have attracted much interest due to the aesthetics of their crystalline architectures and their potential applications as new functional materials. A new twofold interpenetrated three-dimensional (3D) MOF, namely, poly[[triaqua(µ4-(2R,2'R)-2,2'-{[1,4-phenylenebis(carbonyl)]bis(azanediyl)}dipropionato-κ7O1:O1,O1':O4:O4,O4',O4'')(µ3-(2R,2'R)-2,2'-{[1,4-phenylenebis(carbonyl)]bis(azanediyl)}dipropionato-κ3O1:O4:O4)dicadmium(II)] dihydrate], {[Cd2(C14H14N2O6)2(H2O)3]·2H2O}n, (I), has been synthesized by the reaction of Cd(CH3COO)2·2H2O with the synthesized ligand (2R,2'R)-2,2'-{[1,4-phenylenebis(carbonyl)]bis(azanediyl)}dipropionic acid (H2L). Single-crystal X-ray diffraction analysis reveals that the carboxylate groups from two crystallographically independent L2- dianions link the cadmium cations into a one-dimensional helical secondary building unit (SBU). The resulting SBUs are extended into a 3D metal-organic framework via the terephthalamide moiety of the ligand as a spacer. In the crystal, two independent MOFs interpenetrate each other, thus producing a twofold interpenetrated 3D architecture, which shows an unprecedented 2-nodal (7,9)-connected net with the point (Schläfli) symbol (37·46·58)(38·411·516·6). MOF (I) was further characterized by elemental analysis, IR spectroscopy, powder X-ray diffraction and thermogravimetric analysis. The photoluminescence properties and UV-Vis absorption spectrum of (I) have also been investigated. The MOF exhibits enhanced fluorescence emission with a high photoluminescence quantum yield of 31.55% and a longer lifetime compared with free H2L.

Heterogeneity and prognosis of programmed cell death-ligand 1 expression in the circulating tumor cells of non-small cell lung cancer.

Due to tumor heterogeneity, the consistency of programmed cell death-ligand 1 (PD-L1) expression between circulating tumor cells (CTCs) and tissue is controversial. This study aimed to establish a method for detecting CTC PD-L1 expression and exploring the impact of the same on the prognosis of lung cancer. In 32 patients with non-small cell lung cancer, lung cancer cells in the blood were enriched using CD326 immunomagnetic beads. Goat anti-mouse polyclonal CD326 antibody stained the epithelial lung cancer cells and anti-PD-L1 antibody was used to detect the expression of CTC PD-L1. The DAKO Link 48 automatic staining device detected the expression in lung cancer tissue. The consistency of PD-L1 expression was analyzed in lung cancer tissue and CTCs. The effect of plasma interferon gamma, tumor necrosis factor alpha, and interleukin-2 on PD-L1 expression and prognosis was analyzed. The number of CTCs detected in patients was 1-36, with a median of 2. There was no significant difference in PD-L1 expression fractions between CTCs and paired tumor tissue (p>0.05). The correlation coefficient was 0.20. Regardless of lung cancer tissue or CTCs, there was no statistically significant difference in the blood cytokine levels between the two groups with positive or negative PD-L1 expression (p>0.05). There was no correlation between CTCs and PD-L1 in 23 untreated patients. The expression of PD-L1 in CTCs and lung cancer tissue is heterogeneous and unaffected by the peripheral cytokines' levels. PD-L1 expression has no correlation between CTCs and tissues and is not related to prognosis.

Iron-Catalyzed Water Oxidation: O-O Bond Formation via Intramolecular Oxo-Oxo Interaction.

Herein, we report the importance of structure regulation on the O-O bond formation process in binuclear iron catalysts. Three complexes, [Fe2 (µ-O)(OH2 )2 (TPA)2 ]4+ (1), [Fe2 (µ-O)(OH2 )2 (6-HPA)]4+ (2) and [Fe2 (µ-O)(OH2 )2 (BPMAN)]4+ (3), have been designed as electrocatalysts for water oxidation in 0.1 M NaHCO3 solution (pH 8.4). We found that 1 and 2 are molecular catalysts and that O-O bond formation proceeds via oxo-oxo coupling rather than by the water nucleophilic attack (WNA) pathway. In contrast, complex 3 displays negligible catalytic activity. DFT calculations suggested that the anti to syn isomerization of the two high-valent Fe=O moieties in these catalysts takes place via the axial rotation of one Fe=O unit around the Fe-O-Fe center. This is followed by the O-O bond formation via an oxo-oxo coupling pathway at the FeIV FeIV state or via oxo-oxyl coupling pathway at the FeIV FeV state. Importantly, the rigid BPMAN ligand in complex 3 limits the anti to syn isomerization and axial rotation of the Fe=O moiety, which accounts for the negligible catalytic activity.

Quaking 5 suppresses TGF-ß-induced EMT and cell invasion in lung adenocarcinoma.

Quaking (QKI) proteins belong to the signal transduction and activation of RNA (STAR) family of RNA-binding proteins that have multiple functions in RNA biology. Here, we show that QKI-5 is dramatically decreased in metastatic lung adenocarcinoma (LUAD). QKI-5 overexpression inhibits TGF-ß-induced epithelial-mesenchymal transition (EMT) and invasion, whereas QKI-5 knockdown has the opposite effect. QKI-5 overexpression and silencing suppresses and promotes TGF-ß-stimulated metastasis in vivo, respectively. QKI-5 inhibits TGF-ß-induced EMT and invasion in a TGFßR1-dependent manner. KLF6 knockdown increases TGFßR1 expression and promotes TGF-ß-induced EMT, which is partly abrogated by QKI-5 overexpression. Mechanistically, QKI-5 directly interacts with the TGFßR1 3' UTR and causes post-transcriptional degradation of TGFßR1 mRNA, thereby inhibiting TGF-ß-induced SMAD3 phosphorylation and TGF-ß/SMAD signaling. QKI-5 is positively regulated by KLF6 at the transcriptional level. In LUAD tissues, KLF6 is lowly expressed and positively correlated with QKI-5 expression, while TGFßR1 expression is up-regulated and inversely correlated with QKI-5 expression. We reveal a novel mechanism by which KLF6 transcriptionally regulates QKI-5 and suggest that targeting the KLF6/QKI-5/TGFßR1 axis is a promising targeting strategy for metastatic LUAD.

[Corrigendum] Ski prevents TGF­ß­induced EMT and cell invasion by repressing SMAD­dependent signaling in non­small cell lung cancer.

Following the publication of the above paper, an interested reader drew to our attention apparent anomalies associated with Figs. 2, 3 and 4; essentially, these three figures contained panels exhibiting overlapping data, such that data purportedly relating to different experiments were apparently drawn from the same original sources. [Specifically, the Ski, +TGF­ß1 data panel in Fig. 2B, the Mock, +TGF­ß1 data panel in Fig. 3A, and the +TGF­ß1, +SIS3 data panel in Fig. 4B in the original figures were chosen incorrectly.] Upon investigating this matter with the authors, the authors have realized that they made errors in the compilation of the affected figures. The errors were made inadvertently, and the authors have been able to identify the correct data for each of the figures concerned. The corrected versions of these figures are shown opposite and on the next page. Note that these errors did not affect the overall conclusions reported in the study. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum; furthermore, the authors apologize for any inconvenience caused to the readership of the Journal. [the original article was published in Oncology Reports 34: 87-94, 2015; DOI: 10.3892/or.2015.3961].

Prostatic Artery Embolization for Benign Prostatic Hyperplasia: Bleomycin-Eluting versus Bland Microspheres in a Canine Model.

PURPOSE: To prospectively assess safety and efficacy of prostatic artery embolization (PAE) with bleomycin-eluting microspheres for benign prostatic hyperplasia (BPH) in a canine model. MATERIALS AND METHODS: Twelve adult male beagles (mean age, 1.6 y ± 0.2; range, 1.2-2.0 y) were randomly assigned to group A (n = 6; PAE with bleomycin-eluting 30-60-µm HepaSphere microspheres) and group B (n = 6; PAE with bland 30-60-µm HepaSphere microspheres) between April 2017 and November 2018. Plasma bleomycin concentration in group A was measured within 7 days. Prostate volume (PV) and ischemic volume after PAE were measured by magnetic resonance imaging. Prostates and adjacent organs were harvested after the last magnetic resonance study and histopathologically examined. RESULTS: Plasma bleomycin concentration peaked at 10 minutes at 2,055.0 ng/mL ± 606.1 and lasted for 1,440 min at low levels after PAE. PV reduction percentage was greater in group A than in group B at 1 month (74.1% ± 4.3 vs 63.7% ± 3.5; P = .006) and 3 months (61.5% ± 6.7 vs 46.1% ± 3.8; P = .001) after PAE. Proportion of prostate ischemic volume was greater in group A than in group B (75.3% ± 3.0 vs 62.0% ± 7.1; P = .006) at 1 month after PAE. Proportion of prostate ischemic volume at 1 month positively correlated with PV percentage reduction at 3 months in group A (r = 0.840, P = .036) and group B (r = 0.844, P = .035). There were no complications or nontarget embolization to surrounding organs after the procedures. CONCLUSIONS: In a canine model, PAE with bleomycin-eluting microspheres was feasible and well tolerated and caused ischemic necrosis and reduction in PV.