Heterobimetallic NiFe Complex for Photocatalytic CO2 Reduction: United Efforts of NiFe Dual Sites.

Catalytic CO2 reduction poses a significant challenge for the conversion of CO2 into chemicals and fuels. Ni-Fe carbon monoxide dehydrogenase ([NiFe]-CODH) effectively mediates the reversible conversion of CO2 and CO at a nearly thermodynamic equilibrium potential, highlighting the heterobimetallic cooperation for the design of CO2 reduction catalysts. However, numerous NiFe biomimetic model complexes have realized little success in CO2 reduction catalysis, which underscores the crucial role of precise bimetallic configuration and functionality. Herein, we presented a heterobimetallic NiFe complex for the photocatalytic reduction of CO2 to CO, demonstrating significantly enhanced catalytic performance compared to the homonuclear NiNi catalyst. Photocatalytic and mechanistic investigations revealed that with the assistance of a redox-active phenanthroline ligand, NiFe achieves dual-site activation of CO2 through a pivotal intermediate, NiII(µ-CO22--κC:κO)FeII, where the Lewis acidity of the FeII site plays an important role, as corroborated in the homonuclear FeFe system. This study introduces the first heteronuclear NiFe molecular catalyst capable of efficiently catalyzing the reduction of CO2 to CO, deepening insights into heterobimetallic cooperation and offering a novel strategy for designing highly active and selective CO2 reduction catalysts.

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.

Prediction of postoperative mortality in older surgical patients by clinical frailty scale: A systematic review and meta-analysis.

AIMS: To systematically evaluate the predictive efficacy of clinical frailty scale (CFS) for postoperative mortality older surgical patients, and to evaluate the prevalence of frailty in the included studies. DESIGN: A systematic review and meta-analysis of observational studies was conducted, utilizing the MOOSE guidelines for the evaluation of both. Quality assessment of the articles was also performed. DATA SOURCES: The protocol was registered (CRD42023423552). Relevant English and Chinese language studies published until October 20th, 2023 were retrieved from PubMed, Web of Science, Embase, Medline, CINAHL,Cochrane, WAN FANG DATA, VIP Information, CNKI, and SinoMed databases. REVIEW METHODS: Study were included in which frailty was measured by the CFS and postoperative mortality was reported for older surgery patients. A meta-analysis to predict postoperative mortality and frailty prevalence was performed using STATA 17.0 software. RESULTS: Sixteen cohort studies were included (5,864 participants) from 1,513 records. All studies' Newcastle-Ottawa Scale (NOS) scores were above 6 points. It was found that the prevalence of surgical frailty in the older was 0.36(CI 0.20-0.52). Patients assessed as frail by the CFS were associated with higher all-cause mortality (OR:4.01; CI 2.59-6.23). Subgroup analysis shows that frailty was associated with1-month mortality (OR:3.85; CI 1.11-13.45) and 1-year mortality (OR:4.43; CI 2.18-8.99). CONCLUSIONS: The prevalence of frailty is high in older surgical patients, and CFS can effectively predict the mortality of older surgical patients with frailty.

Pivotal Role of Geometry Regulation on O-O Bond Formation Mechanism of Bimetallic Water Oxidation Catalysts.

In this study, we highlight the impact of catalyst geometry on the formation of O-O bonds in Cu2 and Fe2 catalysts. A series of Cu2 complexes with diverse linkers are designed as electrocatalysts for water oxidation. Interestingly, the catalytic performance of these Cu2 complexes is enhanced as their molecular skeletons become more rigid, which contrasts with the behavior observed in our previous investigation with Fe2 analogs. Moreover, mechanistic studies reveal that the reactivity of the bridging O atom results in distinct pathways for O-O bond formation in Cu2 and Fe2 catalysts. In Cu2 systems, the coupling takes place between a terminal CuIII -OH and a bridging µ-O⋅ radical. Whereas in Fe2 systems, it involves the coupling of two terminal Fe-oxo entities. Furthermore, an in-depth structure-activity analysis uncovers the spatial geometric prerequisites for the coupling of the terminal OH with the bridging µ-O⋅ radical, ultimately leading to the O-O bond formation. Overall, this study emphasizes the critical role of precisely adjusting the spatial geometry of catalysts to align with the O-O bonding pathway.

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.

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.

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.

New two-stage pH combined with dissolved oxygen control strategy for cyclic ß-1,2 glucans synthesis.

On the basis of a novel two-stage pH combined with dissolved oxygen (DO) control strategy in fed-batch fermentation, this research addresses the influence of pH on cyclic ß-1,2-glucans (CßGs) biosynthesis and melanin accumulation during the production of CßGs by Rhizobium radiobacter ATCC 13,333. Under these optimal fermentation conditions, the maximum cell concentration and CßGs concentration in a 7-L stirred-tank fermenter were 7.94 g L-1 and 3.12 g L-1, which were the maximum production reported for R. radiobacter. The melanin concentration of the fermentation broth was maintained at a low level, which was beneficial to the subsequent separation and purification of the CßGs. In addition, a neutral extracellular oligosaccharide (COGs-1) purified by the two-stage pH combined with DO control strategy fermentation medium was structurally characterized. Structural analyses indicated that COGs-1 was a family of unbranched cyclic oligosaccharides composed of only ß-1,2-linked D-glucopyranose residues with degree of polymerization between 17 and 23, namely CßGs. This research provides a reliable source of CßGs and structural basis for further studies of biological activity and function. KEY POINTS: • A two-stage pH combined with DO control strategy was proposed for CßGs production and melanin biosynthesis by Rhizobium radiobacter. • The final extracellular CßGs production reached 3.12 g L-1, which was the highest achieved by Rhizobium radiobacter. • The existence of CßGs could be detected by TLC quickly and accurately.

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.

Selective Four-Electron Reduction of Oxygen by a Nonheme Heterobimetallic CuFe Complex.

We report herein the first nonheme CuFe oxygen reduction catalyst ([CuII (bpbp)(µ-OAc)2 FeIII ]2+ , CuFe-OAc), which serves as a functional model of cytochrome c oxidase and can catalyze oxygen reduction to water with a turnover frequency of 2.4×103  s-1 and selectivity of 96.0 % in the presence of Et3 NH+ . This performance significantly outcompetes its homobimetallic analogues (2.7 s-1 of CuCu-OAc with %H2 O2 selectivity of 98.9 %, and inactive of FeFe-OAc) under the same conditions. Structure-activity relationship studies, in combination with density functional theory calculation, show that the CuFe center efficiently mediates O-O bond cleavage via a CuII (µ-η1 : η2 -O2 )FeIII peroxo intermediate in which the peroxo ligand possesses distinctive coordinating and electronic character. Our work sheds light on the nature of Cu/Fe heterobimetallic cooperation in oxygen reduction catalysis and demonstrates the potential of this synergistic effect in the design of nonheme oxygen reduction catalysts.

Heterobimetallic NiFe Cooperative Molecular Water Oxidation Catalyst.

We reported herein the development of heterobimetallic NiFe molecular platform to understand NiFe synergistic effect in water oxidation catalysis. Compared to homonuclear bimetallic compounds (NiNi and FeFe), NiFe complex possesses more remarkable catalytic water oxidation performance. Mechanistic studies suggest that this remarkable difference is attributed to the fact that NiFe synergy can effectively promote O-O bond formation. The generated NiIII (µ-O)FeIV =O is the key intermediate and O-O bond was formed via intramolecular oxyl-oxo coupling between bridged O radical and terminal FeIV =O moiety.

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.

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.

Effectiveness of Contrast-enhanced MR Angiography for Visualization of the Prostatic Artery prior to Prostatic Arterial Embolization.

Background A major technical challenge of prostatic arterial embolization (PAE) is the identification and catheterization of the prostatic arteries (PAs). Recently, MR angiography has been shown to help visualize PAs, but the clinical utility of MR angiography for this purpose is not known. Purpose To determine the efficacy of contrast material-enhanced MR angiography in identifying the PA and to evaluate its role in PAE for benign prostatic hyperplasia (BPH). Materials and Methods In this prospective study, 100 consecutive men who were scheduled to undergo PAE for BPH from January 2015 to May 2017 were assigned by using a randomized block design to either group A (n = 50; mean age, 71.7 years ± 11.9 [standard deviation]) without MR angiography or group B (n = 50; mean age, 72.3 years ± 12.2) with MR angiography prior to PAE. MR angiography findings of the PA anatomy were compared with those of digital subtraction angiography (DSA). The Student t test and Wilcoxon rank-sum test were used to compare the differences between the parameters indicating the performance of PAE. Results The mean age of the 100 men in the study was 72.0 years ± 11.8 (range, 51-88 years). Compared with DSA as the reference standard, MR angiography identified PAs with a sensitivity of 91.5% (97 of 106) and a positive predictive value of 100% (97 of 97). With the knowledge of tube obliquity and anatomy, group B had lower procedure times than group A (82.3 minutes ± 5.4 vs 123.9 minutes ± 12.4, P < .001) and shorter fluoroscopy times (13.8 minutes ± 2.7 vs 28.5 minutes ± 8.0, P < .001). Additionally, radiation dose was reduced for group A versus group B, from a median of 920 to 339 mGy (P = .004). Conclusion Contrast-enhanced MR angiography can accurately show anatomy for the prostate arteries, leading to shorter prostatic artery embolization times and lower radiation dose than when preprocedural prostate MR angiography is not performed. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Prince in this issue.

Exploring the Potential of Mesoporous Silica as a Carrier for Puerarin: Characterization, Physical Stability, and In Vivo Pharmacokinetics.

The aim of this study was to evaluate the use of a novel porous silica carrier, AEROPERL® 300 Pharma (AP), to improve the in vitro release and oral bioavailability of puerarin (PUE) in solid dispersions (SDs). PUE-AP SD formulations with different ratios of drug to silica (RDS) were prepared by the solvent method. The scanning electron microscopy (SEM) results indicated that the dispersion of PUE improved as the concentration of AP was increased. The differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results revealed that PUE mostly existed in an amorphous state in the SDs. The rate of drug dissolution from the SDs was significantly higher than that from the PUE powder (p < 0.05). The in vitro drug release percentage from the PUE-AP SDs increased as the RDS was reduced. The oral bioavailability of PUE from the SDs improved when using AP, as indicated by AUC(0-∞), which was 2.05 and 2.01 times greater than that of the PUE (API) and PVP K30 SDs, respectively (p < 0.05). The drug content, in vitro release profiles, and the amorphous state of PUE in the PUE-AP SDs showed no significant changes after being stored at room temperature for 6 months or under accelerated conditions (40 ± 2°C, 75 ± 5% relative humidity) for 3 months. AP has a high pore volume, large specific surface area, excellent flowability, and hydrophilic properties, making it capable of improving the dissolution and bioavailability of poorly water-soluble drugs.

Circular RNA hsa_circ_0008305 (circPTK2) inhibits TGF-ß-induced epithelial-mesenchymal transition and metastasis by controlling TIF1γ in non-small cell lung cancer.

BACKGROUND: TGF-ß promotes tumor invasion and metastasis through inducing epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) are recognized as functional non-coding RNAs involved in human cancers. However, whether and how circRNAs contribute to TGF-ß-induced EMT and metastasis in NSCLC remain vague. Here, we investigated the regulation and function of Circular RNA hsa_circ_0008305 (circPTK2) in TGF-ß-induced EMT and tumor metastasis, as well as a link between circPTK2 and transcriptional intermediary factor 1 γ (TIF1γ) in NSCLC. METHODS: Circular RNAs were determined by human circRNA Array analysis, real-time quantitative reverse transcriptase PCR and northern blot. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were employed to test the interaction between circPTK2 and miR-429/miR-200b-3p. Ectopic overexpression and siRNA-mediated knockdown of circPTK2, TGF-ß-induced EMT, Transwell migration and invasion in vitro, and in vivo experiment of metastasis were used to evaluate the function of circPTK2. Transcription and prognosis analyses were done in public databases. RESULTS: CircPTK2 and TIF1γ were significantly down-regulated in NSCLC cells undergoing EMT induced by TGF-ß. CircPTK2 overexpression augmented TIF1γ expression, inhibited TGF-ß-induced EMT and NSCLC cell invasion, whereas circPTK2 knockdown had the opposite effects. CircPTK2 functions as a sponge of miR-429/miR-200b-3p, and miR-429/miR-200b-3p promote TGF-ß-induced EMT and NSCLC cell invasion by targeting TIF1γ. CircPTK2 overexpression inhibited the invasion-promoting phenotype of endogenous miR-429/miR-200b-3p in NSCLC cells in response to TGF-ß. CircPTK2 overexpression significantly decreased the expression of Snail, an important downstream transcriptional activator of TGF-ß/Smad signaling. In an in vivo experiment of metastasis, circPTK2 overexpression suppressed NSCLC cell metastasis. Moreover, circPTK2 expression was dramatically down-regulated and positively correlated with TIF1γ expression in human NSCLC tissues. Especially, circPTK2 was significantly lower in metastatic NSCLC tissues than non-metastatic counterparts. CONCLUSION: Our findings show that circPTK2 (hsa_circ_0008305) inhibits TGF-ß-induced EMT and metastasis by controlling TIF1γ in NSCLC, revealing a novel mechanism by which circRNA regulates TGF-ß-induced EMT and tumor metastasis, and suggesting that circPTK2 overexpression could provide a therapeutic strategy for advanced NSCLC.

Association between Allergic Diseases and Irritable Bowel Syndrome: A Retrospective Study.

BACKGROUND: The relationship between allergic disease and irritable bowel syndrome (IBS) is poorly understood. We aimed to investigate the potential association as well as the underlying immunological mechanisms. METHODS: A retrospective case-control study of 108 atopic patients from among outpatients in an allergy clinic (allergic rhinitis [AR], n = 49; chronic urticaria [CU], n = 59) and 74 controls from among ward companions was conducted from November 2016 to March 2017. The detection rates and related gastrointestinal (GI) symptoms of IBS, as well as immunological indices, were calculated. RESULTS: CU patients had a trend of increase in the detection of IBS compared to controls (OR = 4.846; 95% CI 0.967-24.279, p = 0.077). Loose stools (OR = 2.406; 95% CI 1.075-5.386, p < 0.05) and viscous stools (OR = 2.665; 95% CI 1.250-5.682, p < 0.05) were more common in CU patients. Atopic patients positive for serum total immunoglobulin E (IgE) (OR = 3.379; 95% CI 1.088-10.498, p < 0.05) or house dust mite (HDM)-specific IgE (OR = 3.640; 95% CI 1.228-10.790, p < 0.05) were more likely to have abdominal bloating. Besides, a positive association between levels of total IgE and severity of abdominal bloating was observed (p < 0.05). An HDM-specific IgE-positive reaction was independently associated with abdominal bloating in atopic patients (p < 0.05). CONCLUSIONS: Allergic disease has a clear clinical association with IBS with more frequent and severe symptoms of IBS. CU patients have a tendency to suffer from IBS, usually with diarrhea. Serum total IgE and HDM-specific IgE are positively correlated with GI symptoms in atopic patients.

Predicting Neoadjuvant Chemotherapy in Nonconcentric Shrinkage Pattern of Breast Cancer Using 1H-Magnetic Resonance Spectroscopic Imaging.

OBJECTIVE: The aim of this study was to explore the response to neoadjuvant chemotherapy (NAC) in nonconcentric shrinkage pattern of breast cancer (BC) patients using H-magnetic resonance spectroscopy. METHODS: Twenty-five BC patients were the study cohort. All patients received AT-based regimen as first-line treatment. Tumor response to chemotherapy was evaluated after the second and fourth cycles using magnetic resonance imaging and magnetic resonance spectroscopy. Final histopathology following surgery after 4 to 8 cycles of NAC served as a reference. Changes in total choline integral* (tCho) and tumor size in response versus nonresponse groups were compared using the 2-way Mann-Whitney nonparametric test. Receiver operating characteristic (ROC) analyses were undertaken, and the area under the ROC curve compared among them. RESULTS: H-magnetic resonance spectroscopy revealed a negative tCho integral* in 6 cases at the first follow-up and 14 cases at the second follow-up. Based on pathology (Miller-Payne system), there were 16 cases of response, and 9 cases of nonresponse. The tCho integral* was significantly different between the response and nonresponse groups at the second follow-up (P = 0.027). The tumor size changes were not significantly different in the response and nonresponse groups at the second follow-up study (P > 0.05). The comparison of ROC curves among the change in tCho integral* and tumor size at baseline and both follow-ups revealed the maximum area under the ROC curve of the change in tCho integral* to be 0.747 at the second follow-up, sensitivity to be 93.75%, and positive predictive value to be 78.9%. CONCLUSIONS: In nonconcentric shrinkage pattern after NAC of BC, when tumor size is difficult to reflect the response, tCho integral* reduction may be a predictive marker.

Changes in Hemodynamic Response Patterns in Motor Cortices Measured by Task-Based Functional Magnetic Resonance Imaging in Patients With Moyamoya Disease.

OBJECTIVE: We aimed to study the value of blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) in assessing cerebral hemodynamic changes for moyamoya disease (MMD). METHODS: We recruited 15 healthy volunteers, 15 patients with MMD without dyskinesia, and 30 patients with MMD who experienced paroxysmal limb dyskinesia. The BOLD-fMRI scans were obtained during grasping motions of the left or right hand. Hemodynamic response curves in the primary motor cortices were generated. Six response parameters including negative response time (Tnr), maximum signal intensity of negative response, time to peak, maximum peak arrival time, maximum signal intensity of positive response, and positive response time were measured. RESULTS: The hemodynamic response curve in the primary motor cortices of MMD patients showed extended Tnr, prolonged positive response time, and delayed time to peak than those of the controls. The response curve showed longer Tnr and maximum peak arrival time in the primary motor cortices on the affected side of the dyskinesia group. CONCLUSIONS: Blood oxygen level-dependent fMRI is an effective technique to assess hemodynamic changes in patients with MMD.