CircPVT1 promotes ER-positive breast tumorigenesis and drug resistance by targeting ESR1 and MAVS.

The molecular mechanisms underlying estrogen receptor (ER)-positive breast carcinogenesis and endocrine therapy resistance remain incompletely understood. Here, we report that circPVT1, a circular RNA generated from the lncRNA PVT1, is highly expressed in ERα-positive breast cancer cell lines and tumor samples and is functionally important in promoting ERα-positive breast tumorigenesis and endocrine therapy resistance. CircPVT1 acts as a competing endogenous RNA (ceRNA) to sponge miR-181a-2-3p, promoting the expression of ESR1 and downstream ERα-target genes and breast cancer cell growth. Furthermore, circPVT1 directly interacts with MAVS protein to disrupt the RIGI-MAVS complex formation, inhibiting type I interferon (IFN) signaling pathway and anti-tumor immunity. Anti-sense oligonucleotide (ASO)-targeting circPVT1 inhibits ERα-positive breast cancer cell and tumor growth, re-sensitizing tamoxifen-resistant ERα-positive breast cancer cells to tamoxifen treatment. Taken together, our data demonstrated that circPVT1 can work through both ceRNA and protein scaffolding mechanisms to promote cancer. Thus, circPVT1 may serve as a diagnostic biomarker and therapeutic target for ERα-positive breast cancer in the clinic.

Dual electronic effects achieving a high-performance Ni(II) pincer catalyst for CO2 photoreduction in a noble-metal-free system.

A carbazolide-bis(NHC) NiII catalyst (1; NHC, N-heterocyclic carbene) for selective CO2 photoreduction was designed herein by a one-stone-two-birds strategy. The extended π-conjugation and the strong σ/π electron-donation characteristics (two birds) of the carbazolide fragment (one stone) lead to significantly enhanced activity for photoreduction of CO2 to CO. The turnover number (TON) and turnover frequency (TOF) of 1 were ninefold and eightfold higher than those of the reported pyridinol-bis(NHC) NiII complex at the same catalyst concentration using an identical Ir photosensitizer, respectively, with a selectivity of ∼100%. More importantly, an organic dye was applied to displace the Ir photosensitizer to develop a noble-metal-free photocatalytic system, which maintained excellent performance and obtained an outstanding quantum yield of 11.2%. Detailed investigations combining experimental and computational studies revealed the catalytic mechanism, which highlights the potential of the one-stone-two-birds effect.

Electronic Effect Promoted Visible-Light-Driven CO2-to-CO Conversion in a Water-Containing System.

The design of unsaturated nonprecious metal complexes with high catalytic performance for photochemical CO2 reduction is still an important challenge. In this paper, four coordinatively unsaturated Co-salen complexes 1-4 were explored in situ using o-phenylenediamine derivatives and 5-methylsalicylaldehyde as precursors of the ligands in 1-4. It was found that complex 4, bearing a nitro substituent (-NO2) on the aromatic ring of the salen ligand, exhibits the highest photochemical performance for visible-light-driven CO2-to-CO conversion in a water-containing system, with TONCO and CO selectivity values of 5300 and 96%, respectively. DFT calculations and experimental results revealed that the promoted photocatalytic activity of 4 is ascribed to the electron-withdrawing effect of the nitro group in 4 compared to 1-3 (with -CH3, -F, and -H groups, respectively), resulting in a lower reduction potential of active metal centers CoII and lower barriers for CO2 coordination and C-O cleavage steps for 4 than those for catalysts 1-3.

Distribution of type VI secretion system (T6SS) in clinical Klebsiella pneumoniae strains from a Chinese hospital and its potential relationship with virulence and drug resistance.

OBJECTIVES: The type VI secretion system (T6SS) in Klebsiella pneumoniae strains isolated from the bloodstream, intestinal, the pyogenic liver abscess has been reported. Here we aimed to characterize T6SS in 248 Klebsiella pneumoniae isolates with all kinds of specimens from a Chinese hospital and to investigate the potential association of T6SS with virulence and drug resistance. METHODS: T6SS genes, capsular serotyping genes, drug resistance genes, and virulence genes were identified by polymerase chain reaction (PCR). Antibiotic susceptibilities were examined by the disk diffusion method. To assess biofilm formation of these clinical Klebsiella pneumoniae isolates, 96-well microtiter plate assays were performed. MLST was used to analyze the genotypes of these Klebsiella pneumoniae isolates. RESULTS: The frequency of T6SS genes among the clinical Klebsiella pneumoniae isolates was 72.2%. The T6SS-positive isolates displayed higher resistance to piperacillin-tazobactam, ciprofloxacin, levofloxacin, meropenem than the T6SS-negative isolates (P < 0.05). The T6SS-positive isolates formed significantly more biofilm mass than the T6SS-negative isolates (mean ± standard deviation [SD], 0.3 ± 0.09 vs.0.16 ± 0.06; P < 0.01). Compared to the T6SS-negative isolates, the T6SS-positive isolates had a higher frequency of virulence genes (rmpA, fimH, entB, kfu, ybtS) and the pLVPK-like plasmid (P < 0.05). CONCLUSION: In conclusion, the prevalence of the type VI secretion system is high in clinical Klebsiella pneumoniae isolates in a Chinese teaching hospital. T6SS-positive strains show higher biofilm-forming activity with high drug resistance and exhibit higher virulence potential.

Highly Efficient Visible-Light-Driven CO2-to-CO Conversion by Coordinatively Unsaturated Co-Salen Complexes in a Water-Containing System.

The development of cost-effective catalysts for CO2 reduction is highly desired but remains a significant challenge. The unsaturated coordination metal center in a catalyst is favorable for the process of catalytic CO2 reduction. In this paper, two asymmetric salen ligands were used to synthesize two coordinatively unsaturated Co-salen complexes. The two Co-salen complexes exhibit an unsaturated coordination pattern and display high activity and CO selectivity for visible-light-driven CO2 reduction in a water-containing system. The photocatalytic performance of 2 is higher than that of 1 because the reduction potential of the catalytic CoII center and the energy barrier of the catalytic transition states of 2 are lower than those of 1, with turnover numbers (TONCO), turnover frequencies (TOF), and CO selectivity values of 8640, 0.24 s-1, and 97% for 2, respectively. The photocatalytic reduction of CO2 to CO for 2 is well supported by control experiments and density functional theory (DFT) calculations.

Perineural Invasion is a Better Prognostic Indicator than Lymphovascular Invasion and a Potential Adjuvant Therapy Indicator for pN0M0 Esophageal Squamous Cell Carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) at pN0M0 can be more locally aggressive and disseminated than those with lymph node and distant metastasis. Perineural invasion (PNI) is reported as a poor prognostic factor in cancer and is thought to be related to regional tumor spread and metastasis. However, its clinicopathological role and meaning for treatment in pN0M0 ESCC are unknown. PATIENTS AND METHODS: We applied scoring methods of PNI and lymphatic and vascular invasion (LI, VI) based on immunohistochemistry staining on tumor tissues of pN0M0 ESCC patients. ROC analyses, Kaplan-Meier analyses, Cox regression, and χ2 test were performed for survival analysis, comparison of PNI with LI and VI, and exploration of the relevance between PNI and other clinicopathological features. RESULTS: Presence of PNI was significantly associated with poor survival in pN0M0 patients, whereas LI and VI were not predictive of outcome (P > 0.05). Neural invasion index (NII), defined as the ratio of the number of tumor-invaded nerves to the total number of nerves per tumor microsection, was the most consistent measure of PNI (P = 0.006, HR = 6.892, 1.731-27.428). Postoperative radiotherapy significantly improved survival in high-NII patients (P = 0.035, HR = 0.390, 0.163-0.936). CONCLUSIONS: PNI is an important risk factor for the outcome of pN0M0 ESCC patients. NII can be used for risk assessment and to tailor adjuvant radiotherapy in this population.

Encapsulation of Single Iron Sites in a Metal-Porphyrin Framework for High-Performance Photocatalytic CO2 Reduction.

Efficient CO2 reduction with earth-abundant photocatalysts is a highly attractive but very challenging process for chemists. Herein, we synthesized an indium-porphyrin framework, In(H2TCPP)(1-n)[Fe(TCPP)(H2O)](1-n)[DEA](1-n) (In-FenTCPP-MOF; H2TCPP = tetrakis(4-benzoic acid)porphyrine; DEA = diethylamine), with a porphyrin ring supporting the single-site iron for the high-performance visible-light-driven conversion of CO2 to CO. A high CO yield of 3469 µmol g-1 can be achieved by a 24 h photocatalytic reaction with a high CO selectivity (ca. 99.5%). This activity was much higher than that of its cobalt analogues or the Fe-free indium-based metal-organic framework (MOF). Systematic experimental and theoretical studies indicate that the porphyrin-supported iron centers in the MOF matrix serve as efficient active sites, which can accept electrons from the photoexcited MOFs in order to mediate CO2 reduction.

SHOX CNE9/10 Knockout in U2OS Osteosarcoma Cells and Its Effects on Cell Growth and Apoptosis.

BACKGROUND Osteosarcoma is a common malignant tumor of musculoskeletal stromal cells. Osteosarcoma clinical behavior depends mostly on the histologic grade, the site of primary tumor, the response to chemotherapy, and the presence of pulmonary metastases. The aim of this study was to knockout SHOX CNE9/10 in U2OS osteosarcoma cells and to analyze the effects on cell growth and apoptosis. MATERIAL AND METHODS U2OS cells with CNE9 knockout and U2OS cells with CNE10 knockout were established via the CRISPR/Cas9 system. Sanger sequencing was used to detect the success of the knockdown experiment. Western blotting and quantitative polymerase chain reaction were used to detect the expression levels of short stature homeobox-containing gene (SHOX) protein and messenger RNA (mRNA) after knockdown of CNE9 and CNE10. The cell viability and apoptotic rate were detected by the Cell Counting Kit-8 method and by flow cytometry. RESULTS The Sanger sequencing results showed that the knockdown experiment was successful. The levels of SHOX mRNA and protein were significantly reduced after knocking down CNE9 and CNE10. Knockdown of CNE9 and CNE10 significantly increased the growth and inhibited the apoptosis of U2OS osteosarcoma cells. CNE9/CNE10 knockdown U2OS cells were successfully constructed. CONCLUSIONS Knockdown of CNE9 and CNE10 promoted U2OS cell growth and inhibited apoptosis by decreasing SHOX expression. This CNE9/CNE10 knockout U2OS cell model could provide a bridge for the research on SHOX and CNEs in osteosarcoma.

A Molecular Cobalt Hydrogen Evolution Catalyst Showing High Activity and Outstanding Tolerance to CO and O2.

There is a demand to develop molecular catalysts promoting the hydrogen evolution reaction (HER) with a high catalytic rate and a high tolerance to various inhibitors, such as CO and O2 . Herein we report a cobalt catalyst with a penta-dentate macrocyclic ligand (1-Co), which exhibits a fast catalytic rate (TOF=2210 s-1 ) in aqueous pH 7.0 phosphate buffer solution, in which proton transfer from a dihydrogen phosphate anion (H2 PO4 - ) plays a key role in catalytic enhancement. The electrocatalyst exhibits a high tolerance to inhibitors, displaying over 90 % retention of its activity under either CO or air atmosphere. Its high tolerance to CO is concluded to arise from the kinetically labile character of undesirable CO-bound species due to the geometrical frustration posed by the ligand, which prevents an ideal trigonal bipyramid being established.

A Copper(II) Molecular Catalyst for Efficient and Selective Photochemical Reduction of CO2 to CO in a Water-Containing System.

A catalyst developed from a CuII complex of (Et4 N)[Cu(pyN2Me2 )(HCO2 )]⋅0.5 CH3 OH⋅H2 O (1⋅0.5 CH3 OH⋅H2 O; pyN2Me2 =bis(2,6-dimethylphenyl)-2,6-pyridinedicarboxamidate(2-)) shows a high activity to catalyze the reduction reaction of CO2 to CO driven by visible light in 4:1 acetonitrile/water (v:v) using [Ru(phen)3 ](PF6 )2 as photosensitizer and TEOA as sacrificial reductant, with a high TON of 9900 and a high CO selectivity of 98 %. The results of isotope labeling experiment, durability tests and energy dispersive spectroscopy reveal that 1 is robust during the photocatalytic process.

Dinuclear Metal Synergistic Catalysis Boosts Photochemical CO2 -to-CO Conversion.

The solar-driven CO2 reduction is a challenge in the field of "artificial photosynthesis", as most catalysts display low activity and selectivity for CO2 reduction in water-containing reaction systems as a result of competitive proton reduction. Herein, we report a dinuclear heterometallic complex, [CoZn(OH)L1 ](ClO4 )3 (CoZn), which shows extremely high photocatalytic activity and selectivity for CO2 reduction in water/acetonitrile solution. It achieves a selectivity of 98 % for CO2 -to-CO conversion, with TON and TOF values of 65000 and 1.8 s-1 , respectively, 4, 19, and 45-fold higher than the values of corresponding dinuclear homometallic [CoCo(OH)L1 ](ClO4 )3 (CoCo), [ZnZn(OH)L1 ](ClO4 )3 (ZnZn), and mononuclear [CoL2 (CH3 CN)](ClO4 )2 (Co), respectively, under the same conditions. The increased photocatalytic performance of CoZn is due to the enhanced dinuclear metal synergistic catalysis (DMSC) effect between ZnII and CoII , which dramatically lowers the activation barriers of both transition states of CO2 reduction.

A Dinuclear Cobalt Cryptate as a Homogeneous Photocatalyst for Highly Selective and Efficient Visible-Light Driven CO2 Reduction to CO in CH3 CN/H2 O Solution.

A dinuclear cobalt complex [Co2 (OH)L1 ](ClO4 )3 (1, L1 =N[(CH2 )2 NHCH2 (m-C6 H4 )CH2 NH(CH2 )2 ]3 N) displays high selectivity and efficiency for the photocatalytic reduction of CO2 to CO in CH3 CN/H2 O (v/v=4:1) under a 450 nm LED light irradiation, with a light intensity of 100 mW cm-2 . The selectivity reaches as high as 98 %, and the turnover numbers (TON) and turnover frequencies (TOF) reach as high as 16896 and 0.47 s-1 , respectively, with the calculated quantum yield of 0.04 %. Such high activity can be attributed to the synergistic catalysis effect between two CoII ions within 1, which is strongly supported by the results of control experiments and DFT calculations.

Management of deep sacral and ischial pressure injuries with free-style local perforator flaps: A D+P+DPD model.

BACKGROUND: Previous reports on the treatment of sacral and ischial pressure injuries have not provided clear algorithms for surgical therapies. The objective of this study was to establish a reconstruction algorithm to guide the selection of an ideal free-style perforator flap that can be tailored to the defect in question. METHODS: We used 23 perforator flaps to reconstruct 14 sacral and 8 ischial defects in 22 patients over 5 years. A reconstruction algorithm system was developed based on the anatomical features of the perforator vessels (diameter, D; pulsatility [++∼+++], P) and their position in the skin island (DPD) (ie, D+P+DPD). A perforator-based propeller flap was applied as the first-line choice; if this plan was not feasible, we applied an altered V-Y advancement model or another second-choice technique. RESULTS: All flaps survived, and only 1 patient experienced partial wound dehiscence, which healed by secondary intention. After an average follow-up period of 11.2 months, no patient experienced recurrence or infection. CONCLUSIONS: Free-style perforator flap selection is determined by pressure injury and the desired advantage of a specific approach. The use of free-style perforator-based propeller flaps allows a surgeon to transfer healthy tissue into the defect, shifts the suture line away from the bony prominence, and preserves additional future donor sites. In cases where unexpected variations are encountered, the V-Y advancement model or another technique can be used. The simplified surgical algorithm (D+P+DPD) can provide versatility and reliability, achieve a durable, natural esthetic outcome, and minimize injuries to future donor sites.

Unveiling the Activity and Mechanism Alterations by Pyrene Decoration on a Co(II) Macrocyclic Catalyst for CO2 Reduction.

Mechanistic studies involving characterization of crucial intermediates are desirable for rational optimization of molecular catalysts toward CO2 reduction, while fundamental challenges are associated with such studies. Herein we present the systematic mechanistic investigations on a pyrene-appended CoII macrocyclic catalyst in comparison with its pyrene-free prototype. The comparative results also verify the reasons of the higher catalytic activity of the pyrene-tethered catalyst in noble-metal-free CO2 photoreduction with various photosensitizers, where a remarkable apparent quantum yield of 36±3 % at 425 nm can be obtained for selective CO production. Electrochemical and spectroelectrochemical studies in conjunction with DFT calculations between the two catalysts have characterized the key CO-bound intermediates and revealed their different CO-binding behavior, demonstrating that the pyrene group endows the corresponding CoII catalyst a lower catalytic potential, a higher stability, and a greater ease in CO release, all of which contribute to its better performance.

Discovery and validation of combined biomarkers for the diagnosis of esophageal intraepithelial neoplasia and esophageal squamous cell carcinoma.

Early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) can improve the prognosis. The purpose of this study was to identify biomarkers for ESCC and esophageal precancerous lesions (intraepithelial neoplasia, IEN). Based on the proteomic and genomic data of esophageal tissue including previously reported data, up-regulated proteins with copy number amplification in esophageal cancer were screened as candidate biomarkers. Five proteins, including KDM2A, RAD9A, ECT2, CYHR1 and TONSL, were confirmed by immunohistochemistry on ESCC and normal esophagus (NE). Then, we investigated the expression of 5 proteins in 236 participants (60 NEs, 93 IENs and 83 ESCCs) which were randomly divided into training set and test set. When distinguishing ESCC from NE, the area under curve (AUC) of the multiprotein model was 0.940 in the training set, while the lowest AUC of a protein was 0.735. In the test set, the results were similar. When distinguishing ESCC from IEN or distinguishing IEN from NE, the diagnostic efficiency of the multi-protein models were also improved compared with that of single protein. Our findings suggest that combined detection of KDM2A, RAD9A, ECT2, CYHR1 and TONSL can be used as potential biomarkers for the early diagnosis of ESCC and precancerous lesion development prediction. SIGNIFICANCE: Candidate biomarkers including KDM2A, RAD9A, ECT2, CYHR1 and TONSL screened by integrating genomic and proteomic data from the esophagus can be used as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma and precancerous lesion development prediction.

SIRT5 desuccinylates and activates SOD1 to eliminate ROS.

Cu/Zn superoxide dismutase (SOD1) is a key antioxidant enzyme. Deficiency of SOD1 is associated with various human diseases, including cancer. Here, we report that SOD1 is succinylated and that succinylation decreases its activity. SIRT5 binds to, desuccinylates and activates SOD1. SOD1-mediated ROS reduction is increased when SIRT5 is co-expressed. Furthermore, mutation of the SOD1 succinylation site inhibits the growth of lung tumor cells. These results reveal a novel post-translational regulation of SOD1 by means of succinylation and SIRT5-dependent desuccinylation, which is important for the growth of lung tumor cells.

The expression of cytoglobin as a prognostic factor in gliomas: a retrospective analysis of 88 patients.

BACKGROUND: Evidence suggests that cytoglobin (Cygb) may function as a tumor suppressor gene. METHODS: We immunohistochemically evaluated the expression of Cygb, phosphatidylinositol-3 kinase (PI-3K), phosphorylated (p)-Akt, Interleukin-6 (IL-6), tumor necrosis factor-α (TNFα) and vascular endothelial growth factor (VEGF) in 88 patients with 41 high-grade gliomas and 47 low-grade gliomas. Intratumoral microvessel density (IMD) was also determined and associated with clinicopathological factors. RESULTS: Low expression of Cygb was significantly associated with the higher histological grading and tumor recurrence. A significant negative correlation emerged between Cygb expression and PI3K, p-Akt, IL-6, TNFα or VEGF expression. Cygb expression was negatively correlated with IMD. There was a positive correlation between PI3K, p-Akt, IL-6, TNFα and VEGF expression with IMD.High histologic grade, tumor recurrence, decreased Cygb expression, increased PI3K expression, increased p-Akt expression and increased VEGF expression correlated with patients' overall survival in univariate analysis. However, only histological grading and Cygb expression exhibited a relationship with survival of patients as independent prognostic factors of glioma by multivariate analysis. CONCLUSIONS: Cygb loss may contribute to tumor recurrence and a worse prognosis in gliomas. Cygb may serve as an independent predictive factor for prognosis of glioma patients.

[Comparison of fluorescence spectroscopy and plasma-mass spectrometry results of the Meso/Cenozoic basic rocks in SE China and its geo-implication].

With comparison of the fluorescence spectroscopy and plasma-mass spectroscopy analysis results of the Meso/Cenozoic basic rocks of SE China, the authors found that the average SiO2 content of the Mesozoic basic rocks in this area is about 50%, while that of the Cenozoic basic rocks is about 43%. The former belongs to the basic group and the later to the ultrabasic group in igneous rock classification. Cenozoic basalts, accompanied with high magnesium content and low silica-alumina component, are obviously basic or ultrabasic rocks. Distinctive difference in the content of trace elements and of REE is also presented between the Mesozoic and the Cenozoic basic rocks. Distribution models of both trace elements and REE of the Mesozoic basic rocks are similar to those of the upper crust, and the models of the Cenozoic basic rocks are like those of OIB, indicating that basic rocks of the Cenozoic and OIB should originate from the mantle while that of the Mesozoic is from the bottom part of the upper crust with relationship to the evolution of the Mesozoic crustal magma layer of this area.

[Discussion on diagenesis of Xilingang pluton-constrained by X-ray Fluorescence spectroscopy, plasma mass spectrometry and Raman spectroscopy].

The results on Xilingang pluton, mainly consisting of red beds, granites containing numerous debris of red beds and granites, obtained by X-ray fluorescence spectroscopy, plasma mass spectrometry and Raman spectroscopy show: (1) Xilingang pluton from red beds, granites containing numerous debris of red beds to granites has obvious characteristics of decreasing silicon and alkali content, and rising ignition loss, dark mineral content and oxidation index; (2) Chondrite-normalized REE distribution curves and primitive mantle-normalized spider diagram for trace elements of redbed, granites containing numerous debris of red beds and granites have a good consistency, the distribution characteristics of elements are similar to Nanling transformation-type granite; (3) The value of Raman spectrogram characteristic peak of quartz crystal in Xilingang granite decreased from the center of quartz crystal, and FWHM is steady. According to the above, the authors believe that Xilingang granite formed was related to in-situ melting of red beds and underlying strata and magma consolidation. Volatile components were discharged continuously, and oxidation index decreased gradually in the melting process. In the process of diagenesis, the top of pluton tend to be an ongoing silicon and alkali increase, while TFeO and MgO continue to migrate to bottom, and crystallization environment is a relatively closed and steady system.

A modified perforator-based stepladder V-Y advancement flap in the Achilles tendon area for coverage of larger posterior heel defects.

BACKGROUND: Posterior heel defect coverage is challenging because of the paucity of suitable flaps. The traditional local stepladder V-Y advancement flap is recommended only for small defects because of the lack of an axial pedicle. This study reports our experience of using the perforator-based stepladder V-Y advancement flaps in a larger posterior heel defect repair. METHODS: Twenty-two patients with posterior heel defects were treated with modified perforator-based stepladder V-Y advancement flaps in the Achilles tendon area for 11 years. Sixteen males and six females aged 3-74 years underwent surgery. The defect size, perforator characteristics, flap size, flap movement, sural nerve, lesser saphenous vein, deep fascia, flap survival, and outcome quality were analyzed. RESULTS: The perforators were found to predominate within two 2-cm intervals: 0-2 cm and 4-6 cm proximal to the tip of the lateral malleolus. Twenty-one perforator-based flaps healed uneventfully, and only one developed tip necrosis on the lower edge, which healed by secondary intention. The maximum distance of distal movement was 5.0 cm for the modified flap in contrast to 2.5 cm for the traditional flap. All flaps allowed adequate and durable reconstruction to be achieved, with excellent contouring after 2-28 months of follow-up. CONCLUSIONS: The perforator-based stepladder V-Y advancement flap resulted in good outcomes for larger posterior heel defects compared with conventional transfer methods. The flap is a reliable, well-vascularized, sensate, and pliable local flap option that uses similar tissue from adjacent skin for defect repair and creates an internal gliding surface for the Achilles tendon.