Patterns of cervical lymph node involvement in mono-focal papillary thyroid carcinoma patients with different capsular status: A multi-center analysis.

OBJECTIVE: The characteristics of cervical lymph node involvement in papillary thyroid carcinoma (PTC) patients with different degree of capsular invasion remains unclear, especially for those with mono-focal lesion who have traditionally been considered as low neck metastasis risk subgroup. STUDY DESIGN: Retrospective cohort study. SETTING: Three academic teaching hospital. METHODS: A total of 1276 mono-focal PTC patients were retrospectively analyzed. RESULTS: Mono-focal PTC patients with extrathyroidal extension (ETE) showed significantly higher central lymph node metastasis (CLNM) rate than those without. For patients with no gross ETE (gETE), those with minimal ETE (mETE) also showed more commonly CLNM than those with encapsulated lesions. However, the lateral lymph node metastasis (LLNM) rates of patients with mETE and encapsulated tumors were comparable, both lower than that of patients with gETE. Age ≥40, male, and MTD ≥0.5 cm were identified as independent risk factors of CLNM for those with encapsulated tumors and were enrolled for creating a prediction model. In terms of LLNM, only MTD ≥1.0 cm was confirmed as independent risk factors of LLNM for patients with positive gETE. CONCLUSIONS: The presence and degree of ETE may have different effects on the risk of central and lateral lymph node metastasis. gETE demonstrates a strong correlation with both CLNM and LLNM while mETE is only associated with CLNM in mono-focal PTC patients. A comprehensive model is established in the aim of predicting neck involvement according to the capsular status and the corresponding stratified risk factors, which may aid clinical decision-making for the management of neck regions.

Silencing expression of PHF14 in glioblastoma promotes apoptosis, mitigates proliferation and invasiveness via Wnt signal pathway.

BACKGROUND: The plant homeodomain (PHD) finger protein 14 (PHF14) is a vital member of PHD finger protein families. Abnormal expression of PHF14 has been identified in various cancers and is known to be implicated in the pathogenesis of tumors. This study investigates the role and the underlying mechanisms of PHF14 in GBM (glioblastoma multiforme). METHODS: Tissue microarrays and public databases interrogation were used to explore the relationship between the expression of PHF14 and GBM. Three stable PHF14-silenced cell lines (U251, U87MG and A172) were constructed to assess the biological functions changes of GBM cells in vitro. In addition, tumorigenicity in vivo was also performed using U87MG cell line. To understand the mechanism of action of PHF14, RNA-Seq, qRT-PCR, Western blot, IC50 assay and subsequent pathway analysis were performed. RESULTS: Our results showed that the expression of PHF14 was upregulated in glioma, especially in GBM. Overexpression of PHF14 translated to poor prognosis in glioma patients. In vitro assays revealed that silencing expression of PHF14 in glioma cells inhibited migration, invasiveness and proliferation and promoted cell apoptosis. Animal assay further confirmed that over-expression of PHF14 was a dismal prognostic factor. Analysis based on RNA-Seq suggested a PHF14-dependent regulation of Wnt signaling networks, which was further validated by qRT-PCR, Western blot and IC50 analysis. In addition, the mRNA expression of several key markers of EMT (epithelial-mesenchymal transition) and angiogenesis was found to change upon PHF14 silencing. CONCLUSIONS: Our data provide a new insight into the biological significance of PHF14 in glioma and its potential application in therapy and diagnosis.

Formation and reactions of the 1, 8-naphthyridine (napy) ligated geminally dimetallated phenyl complexes [(napy)Cu2(Ph)]+, [(napy)Ag2(Ph)]+ and [(napy)CuAg(Ph)].

Gas-phase ion trap mass spectrometry experiments and density functional theory calculations have been used to examine the routes to the formation of the 1,8-naphthyridine (napy) ligated geminally dimetallated phenyl complexes [(napy)Cu2(Ph)]+, [(napy)Ag2(Ph)]+ and [(napy)CuAg(Ph)]+ via extrusion of CO2 or SO2 under collision-induced dissociation conditions from their corresponding precursor complexes [(napy)Cu2(O2CPh)]+, [(napy)Ag2(O2CPh)]+, [(napy)CuAg(O2CPh)]+ and [(napy)Cu2(O2SPh)]+, [(napy)Ag2(O2SPh)]+, [(napy)CuAg(O2SPh)]+. Desulfination was found to be more facile than decarboxylation. Density functional theory calculations reveal that extrusion proceeds via two transition states: TS1 enables isomerization of the O, O-bridged benzoate to its O-bound form; TS2 involves extrusion of CO2 or SO2 with the concomitant formation of the organometallic cation and has the highest barrier. Of all the organometallic cations, only [(napy)Cu2(Ph)]+ reacts with water via hydrolysis to give [(napy)Cu2(OH)]+, consistent with density functional theory calculations which show that hydrolysis proceeds via the initial formation of the adduct [(napy)Cu2(Ph)(H2O)]+ which then proceeds via TS3 in which the coordinated H2O is deprotonated by the coordinated phenyl anion to give the product complex [(napy)Cu2(OH)(C6H6)]+, which then loses benzene.

Substituent effects in the decarboxylation reactions of coordinated arylcarboxylates in dinuclear copper complexes, [(napy)Cu2(O2CC6H4X)]+ †.

A combination of gas-phase ion trap mass spectrometry experiments and density functional theory (DFT) calculations have been used to examine the role of substituents on the decarboxylation of 25 different coordinated aromatic carboxylates in binuclear complexes, [(napy)Cu2(O2CC6H4X)]+, where napy is the ligand 1,8-naphthyridine (molecular formula, C8H6N2) and X = H and the ortho ( o), meta ( m) and para ( p) isomers of F, Br, CN, NO2, CF3, OAc, Me and MeO. Two competing unimolecular reaction pathways were found: decarboxylation to give the organometallic cation [(napy)Cu2(C6H4X)]+ or loss of the neutral copper benzoate to yield [(napy)Cu]+. The substituents on the aryl group influence the branching ratios of these product channels, but decarboxylation is always the dominant pathway. Density functional theory calculations reveal that decarboxylation proceeds via two transition states. The first enables a change in the coordination mode of the coordinated benzoate in [(napy)Cu2(O2CC6H4X)]+ from the thermodynamically favoured O, O-bridged form to the O-bound form, which is the reactive conformation for the second transition state which involves extrusion of CO2 with concomitant formation of the CO2 coordinated organometallic cation, [(napy)Cu2(C6H4X)(CO2)]+, which then loses CO2 in the final step to yield [(napy)Cu2(C6H4X)]+. In all cases the barrier is highest for the second transition state. The o-substituted benzoates show a lower activation energy than the m-substituted ones, while the p-substituted ones have the highest energy, which is consistent with the experimentally determined normalised collision energy required to induce fragmentation of [(napy)Cu2(O2CC6H4X)]+.

Relationship between health literacy and COVID-19 knowledge: A cross-sectional study.

Background: Health literacy (HL) is a protective factor for some chronic diseases. However, its role in the Coronavirus Disease 2019 (COVID-19) pandemic has not been clarified. This study aims to explore the association between HL and COVID-19 knowledge among residents in Ningbo. Methods: A total of 6,336 residents aged 15-69 years in Ningbo were selected by multi-stage stratified random sampling method. The "Health Literacy Questionnaire of Chinese Citizens (2020)" was used to evaluate the relationship between COVID-19 knowledge and HL. Chi-square test, Mann-Whitney U test and logistic regression were used to analyze the data. Results: The HL and COVID-19 knowledge levels of Ningbo residents were 24.8% and 15.7%, respectively. After adjusting for confounding factors, people with adequate HL were the more likely to have adequate COVID-19 knowledge compared with those with limited HL (OR = 3.473, 95% CI = 2.974-4.057, P <0.001). Compared with the limited HL group, the adequate HL group had a higher rate of COVID-19 knowledge, a more positive attitude, and a more active behavior. Conclusion: COVID-19 knowledge is significantly associated with HL. Improving HL may influence people's knowledge about COVID-19, thereby changing people's behaviors, and finally combating the pandemic.

Unveiling Structural Diversity of Uranyl Compounds of Aprotic 4,4'-Bipyridine N,N'-Dioxide Bearing O-Donors.

As an aprotic O-donor ligand, 4,4'-bipyridine N,N'-dioxide (DPO) shows good potential for the preparation of uranyl coordination compounds. In this work, by regulating reactant compositions and synthesis conditions, diverse coordination assembly between uranyl and DPO under different reaction conditions was achieved in the presence of other coexisting O-donors. A total of ten uranyl-DPO compounds, U-DPO-1 to U-DPO-10, have been synthesized by evaporation or hydro/solvothermal treatment, and the possible competition and cooperation of DPO with other O-donors for the formation of these uranyl-DPO compounds are discussed. Starting with an aqueous solution of uranyl nitrate, it is found that an anionic nitrate or hydroxyl group is involved in the coordination sphere of uranyl in U-DPO-1 ((UO2)(NO3)2(H2O)2·(DPO)), U-DPO-2 ((UO2)(NO3)2(DPO)), and U-DPO-3 ((UO2)(DPO)(µ2-OH)2), where DPO takes three different kinds of coordination modes, i.e. uncoordinated, monodentate, and biconnected. The utilization of UO2(CF3SO3)2 in acetonitrile, instead of an aqueous solution of uranyl nitrate, precludes the participation of nitrate and hydroxyl, and ensures the engagement of DPO ligands (4-5 DPO ligands for each uranyl) in a uranyl coordination sphere of U-DPO-4 ([(UO2)(CF3SO3)(DPO)2](CF3SO3)), U-DPO-5 ([UO2(H2O)(DPO)2](CF3SO3)2) and U-DPO-6 ([(UO2)(DPO)2.5](CF3SO3)2). Moreover, when combined with anionic carboxylate ligands, terephthalic acid (H2TPA), isophthalic acid (H2IPA), and succinic acid (H2SA), DPO works well with them to produce four mixed-ligand uranyl compounds with similar structures of two-dimensional (2D) networks or three-dimensional (3D) frameworks, U-DPO-7 ((UO2)(TPA)(DPO)), U-DPO-8 ((UO2)2(DPO)(IPA)2·0.5H2O), U-DPO-9 ((UO2)(SA)(DPO)·H2O), and U-DPO-10 ((UO2)2(µ2-OH)(SA)1.5(DPO)). Density functional theory (DFT) calculations conducted to probe the bonding features between uranyl ions and different O-donor ligands show that the bonding ability of DPO is better than that of anionic CF3SO3 -, nitrate, and a neutral H2O molecule and comparable to that of an anionic carboxylate group. Characterization of physicochemical properties of U-DPO-7 and U-DPO-10 with high phase purity including infrared (IR) spectroscopy, thermogravimetric analysis (TGA), and luminescence properties is also provided.

Axial Oxygen Ligands Regulating Electronic and Geometric Structure of Zn-N-C Sites to Boost Oxygen Reduction Reaction.

Zn-N-C possesses the intrinsic inertia for Fenton-like reaction and can retain robust durability in harsh circumstance, but it is often neglected in oxygen reduction reaction (ORR) because of its poor catalytic activity. Zn is of fully filled 3d10 4s2 configuration and is prone to evaporation, making it difficult to regulate the electronic and geometric structure of Zn center. Here, guided by theoretical calculations, five-fold coordinated single-atom Zn sites with four in-plane N ligands is constructed and one axial O ligand (Zn-N4 -O) by ionic liquid-assisted molten salt template method. Additional axial O not only triggers a geometry transformation from the planar structure of Zn-N4 to the non-planar structure of Zn-N4 -O, but also induces the electron transfer from Zn center to neighboring atoms and lower the d-band center of Zn atom, which weakens the adsorption strength of *OH and decreases the energy barrier of rate determining step of ORR. Consequently, the Zn-N4 -O sites exhibit improved ORR activity and excellent methanol tolerance with long-term durability. The Zn-air battery assembled by Zn-N4 -O presents a maximum power density of 182 mW cm-2 and can operate continuously for over 160 h. This work provides new insights into the design of Zn-based single atom catalysts through axial coordination engineering.

Colossal negative thermal expansion in a cucurbit[8]uril-enabled uranyl-organic polythreading framework via thermally induced relaxation.

It is an ongoing goal to achieve the effective regulation of the thermal expansion properties of materials. In this work, we propose a method for incorporating host-guest complexation into a framework structure and construct a flexible cucurbit[8]uril uranyl-organic polythreading framework, U3(bcbpy)3(CB8). U3(bcbpy)3(CB8) can undergo huge negative thermal expansion (NTE) and has a large volumetric coefficient of -962.9 × 10-6 K-1 within the temperature range of 260 K to 300 K. Crystallographic snapshots of the polythreading framework at various temperatures reveal that, different from the intrinsic transverse vibrations of the subunits of metal-organic frameworks (MOFs) that experience NTE via a well-known hinging model, the remarkable NTE effect observed here is the result of a newly-proposed thermally induced relaxation process. During this process, an extreme spring-like contraction of the flexible CB8-based pseudorotaxane units, with an onset temperature of ∼260 K, follows a period of cumulative expansion. More interestingly, compared with MOFs that commonly have relatively strong coordination bonds, due to the difference in the structural flexibility and adaptivity of the weakly bonded U3(bcbpy)3(CB8) polythreading framework, U3(bcbpy)3(CB8) shows unique time-dependent structural dynamics related to the relaxation process, the first time this has been reported in NTE materials. This work provides a feasible pathway for exploring new NTE mechanisms by using tailored supramolecular host-guest complexes with high structural flexibility and has promise for the design of new kinds of functional metal-organic materials with controllable thermal responsive behaviour.

Elevated ETV6 Expression in Glioma Promotes an Aggressive In Vitro Phenotype Associated with Shorter Patient Survival.

Background: GBM astrocytes may adopt fetal astrocyte transcriptomic signatures involved in brain development and migration programs to facilitate diffuse tumor infiltration. Our previous data show that ETS variant 6 (ETV6) is highly expressed in human GBM and fetal astrocytes compared to normal mature astrocytes. We hypothesized that ETV6 played a role in GBM tumor progression. Methods: Expression of ETV6 was first examined in two American and three Chinese tissue microarrays. The correlation between ETV6 staining intensity and patient survival was calculated, followed by validation using public databases-TCGA and REMBRANDT. The effect of ETV6 knockdown on glioma cell proliferation (EdU), viability (AnnexinV labeling), clonogenic growth (colony formation), and migration/invasion (transwell assays) in GBM cells was tested. RNA sequencing and Western blot were performed to elucidate the underlying molecular mechanisms. Results: ETV6 was highly expressed in GBM and associated with an unfavorable prognosis. ETV6 silencing in glioma cells led to increased apoptosis or decreased proliferation, clonogenicity, migration, and invasion. RNA-Seq-based gene expression and pathway analyses revealed that ETV6 knockdown in U251 cells led to the upregulation of genes involved in extracellular matrix organization, NF-κB signaling, TNF-mediated signaling, and the downregulation of genes in the regulation of cell motility, cell proliferation, PI3K-AKT signaling, and the Ras pathway. The downregulation of the PI3K-AKT and Ras-MAPK pathways were further validated by immunoblotting. Conclusion: Our findings suggested that ETV6 was highly expressed in GBM and its high expression correlated with poor survival. ETV6 silencing decreased an aggressive in vitro phenotype probably via the PI3K-AKT and Ras-MAPK pathways. The study encourages further investigation of ETV6 as a potential therapeutic target of GBM.

Deficiency of Intellectual Disability-Related Gene Brpf1 Attenuated Hippocampal Excitatory Synaptic Transmission and Impaired Spatial Learning and Memory Ability.

Patients with monoallelic bromodomain and PHD finger-containing protein 1 (BRPF1) mutations showed intellectual disability. The hippocampus has essential roles in learning and memory. Our previous work indicated that Brpf1 was specifically and strongly expressed in the hippocampus from the perinatal period to adulthood. We hypothesized that mouse Brpf1 plays critical roles in the morphology and function of hippocampal neurons, and its deficiency leads to learning and memory deficits. To test this, we performed immunofluorescence, whole-cell patch clamp, and mRNA-Seq on shBrpf1-infected primary cultured hippocampal neurons to study the effect of Brpf1 knockdown on neuronal morphology, electrophysiological characteristics, and gene regulation. In addition, we performed stereotactic injection into adult mouse hippocampus to knock down Brpf1 in vivo and examined the learning and memory ability by Morris water maze. We found that mild knockdown of Brpf1 reduced mEPSC frequency of cultured hippocampal neurons, before any significant changes of dendritic morphology showed. We also found that Brpf1 mild knockdown in the hippocampus showed a decreasing trend on the spatial learning and memory ability of mice. Finally, mRNA-Seq analyses showed that genes related to learning, memory, and synaptic transmission (such as C1ql1, Gpr17, Htr1d, Glra1, Cxcl10, and Grin2a) were dysregulated upon Brpf1 knockdown. Our results showed that Brpf1 mild knockdown attenuated hippocampal excitatory synaptic transmission and reduced spatial learning and memory ability, which helps explain the symptoms of patients with BRPF1 mutations.

Activating Titanium Dioxide as a New Efficient Electrocatalyst: From Theory to Experiment.

Though transition-metal-based materials have emerged as the most promising alternatives to Pt-based electrocatalysts in hydrogen evolution reaction (HER), only a few of them (Fe-, Co-, Ni-, W-, and Mo-based materials) are used as efficient HER electrocatalysts, while others are generally considered as HER-inactive materials with poor activities. Here, a theory-guided experiment is carried out to activate titanium dioxide as a new efficient HER electrocatalyst. First-principles simulations indicate that the hydrogen adsorption free energy could be optimized through tuning the structural and electronic properties of TiO2. Then Cu-doped amorphous TiO2 is successfully prepared based on the theoretical results. The activated TiO2 expectedly shows excellent HER performance with a low overpotential of 92 mV at 10 mA cm-2 in alkaline media, which is far superior to that of the crystalline TiO2 (over 400 mV). The origin of HER activity is further investigated in detail. The corrugation of the amorphous surface helps stabilize the adsorbed water molecule, crucial for the water dissociation of the Volmer step. The Cu doping can strengthen the orbital hybridization of H1s and O2p favoring the hydrogen adsorption/desorption and improve the electrical conductivity. Our work highlights the great potential of traditionally inactive materials in HER electrocatalysis and helps deepen our understanding of the catalytic mechanism.

Design Superior Alkaline Hydrogen Evolution Electrocatalyst by Engineering Dual Active Sites for Water Dissociation and Hydrogen Desorption.

In alkaline media, the water-dissociation-related Volmer process always suppresses the hydrogen formation/desorption process, which makes it challenging to develop non-noble-metal alkaline electrocatalysts with excellent catalytic activity. Here, we proposed a two-pronged strategy to simultaneously promote the kinetic process of both water dissociation and hydrogen desorption with the Co-doped WO2/amorphous CoxW hybrid electrocatalyst. Impressively, the optimized hybrid exhibits an outstanding hydrogen evolution reaction (HER) activity with the quite small Tafel slope of 19.77 mV dec-1 and ultralow overpotential of just 25 mV to reach a current density of 10 mA cm-2 in alkaline media. Both experiments and density functional theory calculations reveal that the top-level HER performance can be attributed to the cooperation of two different active components, in which the water molecule can easily be activated on the amorphous CoxW with low energy barrier (ΔGw = 0.46 eV), while hydrogen atoms can rapidly desorb from the Co-doped WO2 with an optimal Gibbs free energy of hydrogen adsorption (ΔGH* = -0.06 eV). Also, the density functional theory calculation further confirms that the H* tends to combine with another H* via Tafel step rather than Heyrovsky step. The findings provide unique insights for the development of the state-of-the-art non-noble-metal HER electrocatalyst with a Pt-like kinetic behavior in alkaline media.

Plasma-Assisted Synthesis of Self-Supporting Porous CoNPs@C Nanosheet as Efficient and Stable Bifunctional Electrocatalysts for Overall Water Splitting.

The utilization of a highly active and robust bifunctional catalyst for simultaneously producing H2 and O2 is still a major challenging issue, which is vital for improving the efficiency of overall water splitting. Herein, we employ a novel plasma-assisted strategy to rapidly and conveniently synthesize the three-dimensional (3D) porous composite nanosheets assembled on monodispersed Co nanoparticles encapsulated in a carbon framework (CoNPs@C) on a carbon cloth. Such a novel 3D hierarchical porous nanosheet improves the exposure and accessibility of active sites as well as ensures high electroconductibility. Moreover, the coating of a few graphene layers on the surface of catalysts favors improvement of the catalytic activity. Benefited from these multiple merits, the CoNPs@C composite nanosheets enable a low overpotential of 153 mV at -10 mA cm-2 for hydrogen evolution reaction. Furthermore, they are also capable of catalyzing the oxygen evolution reaction with high efficiency to achieve current density of 10 mA cm-2 at the overpotential of 270 mV. Remarkably, when assembled as an alkaline water electrolyzer, the bifunctional CoNPs@C composite nanosheets can afford a water-splitting current density of 10 mA cm-2 at a cell voltage of 1.65 V.