Effect of composition and architecture on the thermodynamic behavior of AuCu nanoparticles.

The chemical and physical properties of nanomaterials ultimately rely on their crystal structures, chemical compositions and distributions. In this paper, a series of AuCu bimetallic nanoparticles with well-defined architectures and variable compositions has been addressed to explore their thermal stability and thermally driven behavior by molecular dynamics simulations. By combination of energy and Lindemann criteria, the solid-liquid transition and its critical temperature were accurately identified. Meanwhile, atomic diffusion, bond order, and particle morphology were examined to shed light on thermodynamic evolution of the particles. Our results reveal that composition-dependent melting point of AuCu nanoparticles significantly departs from the Vegard's law prediction. Especially, chemically disordered (ordered) alloy nanoparticles exhibited markedly low (high) melting points in comparison with their unary counterparts, which should be attributed to enhancing (decreasing) atomic diffusivity in alloys. Furthermore, core-shell structures and heterostructures demonstrated a mode transition between the ordinary melting and the two-stage melting with varying Au content. AuCu alloyed nanoparticles presented the evolution tendency of chemical ordering from disorder to order before melting and then to disorder during melting. Additionally, as the temperature increases, the shape transformation was observed in AuCu nanoparticles with heterostructure or L10 structure owing to the difference in thermal expansion coefficients of elements and/or of crystalline orientations. Our findings advance the fundamental understanding on thermodynamic behavior and stability of metallic nanoparticles, offering theoretical insights for design and application of nanosized particles with tunable properties.

Hepatic Arterial Infusion Chemotherapy vs Transcatheter Arterial Chemoembolization as Adjuvant Therapy Following Surgery for MVI-Positive Hepatocellular Carcinoma: A Multicenter Propensity Score Matching Analysis.

Background: Microvascular invasion (MVI) is a significant pathological feature in hepatocellular carcinoma (HCC), adjuvant hepatic arterial infusion chemotherapy (a-HAIC) and adjuvant transcatheter arterial chemoembolization (a-TACE), are commonly used for HCC patients with MVI. This study aims to evaluate the efficacies of two adjuvant therapies after surgical treatment for HCC, compare them, and identify the significant factors. Methods: Clinical data from two randomized controlled trials involving HCC patients with MVI after surgical treatment were retrospectively reviewed. Propensity score matching (PSM) analysis was performed to balance baseline differences between patients who received a-HAIC or a-TACE, and control groups who underwent hepatectomy alone. Disease-free survival (DFS) and overall survival (OS) rates were compared. Results: In total of 549 patients were collected from two randomized controlled trials. Using the PSM and Kaplan-Meier method, the median DFS of the a-HAIC, a-TACE, and control groups was 63.2, 21.7, and 11.2 months (P<0.05). The a-HAIC group show significantly better 1-, 3-, and 5-year OS rates compared to the a-TACE and control groups (96.3%, 80.0%, 72.8% vs 84.4%, 57.0%, 29.8% vs 84.5%, 62.8%, 53.4%, P<0.05). But the OS rates of a-TACE and control groups showed no significant difference (P=0.279). Multivariate analysis identified a-HAIC (HR=0.449, P=0.000) and a-TACE (HR=0.633, P=0.007) as independent protective factors. For OS, a-HAIC (HR=0.388, P=0.003) was identified as an independent protective factor, too. Conclusion: Compared to a-TACE and the control group, a-HAIC demonstrated greater benefits in preventing tumor recurrence and improving survival in HCC patients with MVI.

Boosting the oxygen reduction reaction activity of dual-atom catalysts on N-doped graphene by regulating the N coordination environment.

Development of low-cost and high-efficiency oxygen reduction reaction (ORR) catalysts is of significance for fuel cells and metal-air batteries. Here, by regulating the N environment, a series of dual-atom embedded N5-coordinated graphene catalysts, namely M1M2N5 (M1, M2 = Fe, Co, and Ni), were constructed and systematically investigated by DFT calculations. The results reveal that all M1M2N5 configurations are structurally and thermodynamically stable. The strong adsorption of *OH hinders the proceeding of ORR on the surface of M1M2N5, but M1M2N5(OH2) complexes are formed to improve their catalytic activity. In particular, FeNiN5(OH2) and CoNiN5(OH2) with the overpotentials of 0.33 and 0.41 V, respectively, possess superior ORR catalytic activity. This superiority should be attributed to the reduced occupation of d-orbitals of Fe and Co atoms in the Fermi level and the apparent shift of dyz and dz2 orbitals of Ni atoms towards the Fermi level after adsorbing *OH, thus regulating the active sites and exhibiting appropriate adsorption strength for reaction intermediates. This work provides significant insight into the ORR mechanism and theoretical guidance for the discovery and design of low-cost and high-efficiency graphene-based dual-atom ORR catalysts.

Structural Determination and Hierarchical Evolution of Transition Metal Clusters Based on an Improved Self-Adaptive Differential Evolution with Neighborhood Search Algorithm.

Determining the optimal structures and clarifying the corresponding hierarchical evolution of transition metal clusters are of fundamental importance for their applications. The global optimization of clusters containing a large number of atoms, however, is a vastly challenging task encountered in many fields of physics and chemistry. In this work, a high-efficiency self-adaptive differential evolution with neighborhood search (SaNSDE) algorithm, which introduced an optimized cross-operation and an improved Basin Hopping module, was employed to search the lowest-energy structures of CoN, PtN, and FeN (N = 3-200) clusters. The performance of the SaNSDE algorithm was first evaluated by comparing our results with the parallel results collected in the Cambridge Cluster Database (CCD). Subsequently, different analytical methods were introduced to investigate the structural and energetic properties of these clusters systematically, and special attention was paid to elucidating the structural evolution with cluster size by exploring their overall shape, atomic arrangement, structural similarity, and growth pattern. By comparison with those results listed in the CCD, 13 lower-energy structures of FeN clusters were discovered. Moreover, our results reveal that the clusters of three metals had different magic numbers with superior stable structures, most of which possessed high symmetry. The structural evolution of Co, Pt, and Fe clusters could be, respectively, considered as predominantly closed-shell icosahedral, Marks decahedral, and disordered icosahedral-ring growth. Further, the formation of shell structures was discovered, and the clusters with hcp-, fcc-, and bcc-like configurations were ascertained. Nevertheless, the growth of the clusters was not simply atom-to-atom piling up on a given cluster despite gradual saturation of the coordination number toward its bulk limit. Our work identifies the general growth trends for such a wide region of cluster sizes, which would be unbearably expensive in first-principles calculations, and advances the development of global optimization algorithms for the structural prediction of clusters.

NiPd co-doped nitrogen-coordinated graphene as a high-efficiency electrocatalyst for oxygen reduction reactions: a first-principles determination.

High-energy-density fuel cells and metal-air batteries are difficult to commercialize on a large scale mainly because of the sluggish oxygen reduction reaction (ORR) at the cathode. Hence, the development of high-efficiency and low-cost electrocatalysts as Pt substitutes for the ORR is of significance for the mass applications of these devices. In this work, we thoroughly investigated the structural and catalytic properties of NiPd co-doped N-coordinated graphene (denoted as NiPdN6-G) as an ORR electrocatalyst by using density-functional theory (DFT) calculations. Our results show that NiPdN6-G is structurally and thermodynamically stable. Furthermore, we explored all the possible paths and intermediates of the ORR, and identified the preferable active sites and the most stable adsorption configurations of the intermediates and transition states. In general, there are 15 possible reaction paths, of which 8 paths have lower energy barriers than pure Pt, and the maximum energy barrier and overpotential of the ORR for the optimal path are only 0.14 eV and 0.37 V, respectively. This work demonstrates that NiPdN6-G should be a promising candidate for substituting Pt and Pt-based catalysts for the ORR in energy conversion and storage devices.

Risk factors associated with indoor transmission during home quarantine of COVID-19 patients.

Purpose: The study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves. Methods: A retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined. Results: A total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger (p = 0.019), more commonly unvaccinated (p = 0.048) or exposed to infections (p < 0.001), and had higher rates of symptoms (p = 0.003) or shared living room (p < 0.001). Risk factors analysis showed that the 2019-nCov antigen positive (OR = 1.86, 95%CI 1.40-2.48, p < 0.001), symptoms development (OR = 1.86, 95%CI 1.34-2.58, p < 0.001), direct contact exposure (OR = 1.47, 95%CI 1.09-1.96, p = 0.010) were independent risk factors for the cohabitant transmission of COVID-19, and a separate room with a separate toilet could reduce the risk of family transmission (OR = 0.62, 95%CI 0.41-0.92, p = 0.018). Conclusion: Patients showing negative 2019-nCov antigen tests, being asymptomatic, living in a separate room with a separate toilet, or actively avoiding direct contact with cohabitants were at low risk of family transmission, and the study recommended that avoiding direct contact and residential disinfection could reduce the risk of all cohabitants within the same house being infected with COVID-19.

Asymmetric redox benzylation of enals enabled by NHC/Ru cooperative catalysis.

The development of general methods for asymmetric benzylation of prochiral carbon nucleophiles remains a challenge in organic synthesis. The merging of ruthenium catalysis and N-heterocyclic carbene (NHC) catalysis for asymmetric redox benzylation of enals has been achieved, which opens up strategic opportunities for the asymmetric benzylation reactions. A wide range of 3,3'-disubstituted oxindoles with a stereogenic quaternary carbon center widely existing in natural products and biologically interesting molecules is successfully obtained with excellent enantioselectivities [up to 99% enantiomeric excess (ee)]. The generality of this catalytic strategy was further highlighted by its successful application in the late-stage functionalization of oxindole skeletons. Furthermore, the linear correlation between ee values of NHC precatalyst and the product elucidated the independent catalytic cycle of either the NHC catalyst or the ruthenium complex.

Computational determination of a graphene-like TiB4 monolayer for metal-ion batteries and a nitrogen reduction electrocatalyst.

As an emerging two-dimensional (2D) material, the TiB4 monolayer possesses intrinsic advantages in electrochemical applications owing to its graphene-like structure and metallic characteristics. In this work, we performed density functional calculations to investigate the electrochemical properties of the TiB4 monolayer as an anode material for Li/Na/K ion batteries and as an electrocatalyst for the nitrogen reduction reaction (NRR). Our investigation reveals that Li/Na/K ions could be steadily adsorbed on the TiB4 monolayer with moderate adsorption energies, and tended to diffuse along two adjacent C-sites with lower energy barriers (0.231/0.094/0.067 eV for Li/Na/K ions) compared to the currently reported transition-metal boride monolayers. Furthermore, a N2 molecule can be spontaneously captured by the TiB4 monolayer with a negative Gibbs free energy (-0.925 eV and -0.326 eV for end-on and side-on adsorptions, respectively), hence provoking a conversion into NH3 along the most efficient reaction pathway (i.e., N2* → N2H* → HNNH* → H2NNH* → H3NNH* → NH* → NH2* → NH3*). In the hydrogenation process, the TiB4 monolayer exhibits much higher catalytic activity for the NRR as compared with other electrocatalysts, which should be attributed to the spontaneous achievement (ΔG < 0) at all hydrogenation reaction steps except the potential-determining step. Moreover, the TiB4 monolayer exhibits higher selectivity toward the NRR than the hydrogen evolution reaction. Our work advances the mechanistic understanding on the electrochemical properties of the TiB4 monolayer as an anode material for metal-ion batteries and as a NRR electrocatalyst, and provides significant guidance for developing high-performance multifunctional 2D materials.

Diastereodivergent Desymmetric Annulation to Access Spirooxindoles: Chemical Probes for Mitosis.

Spirooxindoles have emerged as promising architectures for engineering biologically active compounds. The diastereodivergent construction of unique scaffolds of this type with full control of continuous chiral centers including an all-carbon quaternary stereogenic center is yet to be developed. Here, we report an unprecedented diastereodivergent desymmetric [3 + 3] annulation of oxabicyclic alkenes with enals enabled by N-heterocyclic carbene (NHC)/Rh cooperative catalysis, leading to a series of enantiomerically enriched spirooxindole lactones with excellent enantioselectivities (up to >99% ee) and diastereoselectivities (up to >95:5 dr). The combined catalyst system comprises a rhodium complex that controls the configuration at the electrophilic carbon and an NHC catalyst that controls the configuration at the nucleophilic oxindole-containing carbon; thus, four stereoisomers of the spirooxindole products can be readily obtained simply by switching the configurations of the two chiral catalysts. Transformations of the chiral spirooxindoles delivered synthetically useful compounds. Importantly, those chiral spirooxindoles arrested mammalian cells in mitosis and exhibited potent antiproliferative activities against HeLa cells. Significantly, both absolute and relative configurations exert prominent effects on the bioactivities, underscoring great importance of catalytic asymmetric diastereodivergent synthesis beyond creating useful tools for the exploration of structure-activity relationships.

Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study.

PURPOSE: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

Thermally Activated Microstructural Evolution of PtIrCu Alloyed Nanorings: Insights from Molecular Dynamics Simulations.

Nanoalloys have attracted extensive interest from the research and industrial community due to their unique properties. In this work, the thermally activated microstructural evolution and resultant collapse of PtIrCu nanorings were investigated using molecular dynamics simulations. Three PtIrCu nanorings with a fixed outer radius and varied inner radii were addressed to investigate the size effects on their thermal and shape stabilities. The shape factor was introduced to monitor their shape changes, and a common neighbor analysis was employed to characterize the local structures of atoms. The results reveal that both the thermal and shape stabilities of these nanorings can be remarkably improved by decreasing the inner radius. Furthermore, they all experienced the evolutionary process from ring to pie and spherelike morphologies, finally resulting in structural collapse. The stacking faults were observed in these rings during the heating process. Our work sheds light on the fundamental understanding of alloyed nanorings subjected to heating, hence offering a theoretical foundation for their syntheses and applications.

Effectiveness of a 4-Day Mindfulness-Based Intervention in a 2-Month Follow-Up for Chinese Incarcerated People.

Mindfulness-based interventions, an evidence-based stress reduction approach, may help incarcerated people cope with stress-related problems in the challenging environment of prison. However, due to their unique living environment, the duration and instructor guidance required by standard mindfulness-based interventions would be infeasible in most prisons. Therefore, the aims of the current study were to test the effects of two different 4-day interventions (i.e., instructor-guided and audio-based) with content similar to Mindfulness-Based Cognitive Therapy for newly incarcerated males, and to compare the effectiveness of the two interventions relative to a no-intervention control group. Using daily assessments, we explored changes in perceived stress, insomnia, and negative affect in the 56 days following the instructor-guided (N = 25), audio-based (N = 21), and control (N = 44) intervention; length of mindfulness practice during the follow-up was also compared between the two intervention groups. Hierarchical linear model results showed significantly greater linear decreases in perceived stress after both mindfulness interventions during the 56-day follow-up (γ11 = -0.011, p < .001, 95% CI [-0.017, -0.004] for instructor-guided intervention; γ12 = -0.013, p < .001, 95% CI [-0.018, -0.006] for audio-based intervention), as compared to the control group. Compared to the control group, the instructor-guided group reported a significantly greater decrease in insomnia (γ11 = -0.007, p < .001, 95% CI [-0.014, -0.002]), but the audio-based group did not (γ12 = -0.002, p = .160, 95% CI [-.007, .004]). Neither mindfulness-based intervention group reported a significantly greater decrease in negative affect compared to the control group (γ11 = -0.002, p = .170, 95% CI [-0.005, 0.001] for instructor-guided intervention; γ12 = -0.002, p = .150, 95% CI [-0.006, 0.002] for audio-based intervention). No significant difference between the two intervention groups was found in the change of outcomes (γ11 = 0.002, -0.005 and 0.000, p = .350, .130 and .390, 95% CI [-0.008, 0.011], 95% CI [-0.014, 0.004] and 95% CI [-0.004, 0.006] subsequently for perceived stress, insomnia and negative affect). Daily mindfulness practice was significantly longer for the audio-based group on the first day of follow-up (γ02 = -0.758, p < .05, 95% CI [-1.333, -0.129]), but it gradually decreased to the same amount as the instructor-guided group (t (32) = 0.051, p = .959). Short-term mindfulness interventions, either instructor-guided or audio-based, appear to be beneficial for Chinese prisoners in reducing stress. Live instruction may have potential benefit in reducing insomnia and sustaining daily practice.

Thermally activated microstructural evolution of metallic heterophase nanoparticles: insights from molecular dynamics simulations.

A crystal phase is a key factor to determine the physical and chemical properties of crystalline materials. As a new class of nanoscale structures, heterophase nanoparticles, which assemble conventional and unconventional phases, exhibit exceptional properties in comparison with their single-phase counterparts. In this work, we explored the thermodynamic stability of Au, Co, and AuCo heterophase nanoparticles with fcc and hcp phases by using molecular dynamics simulations. These heterostructured nanoparticles were continuously heated to examine their thermally activated structural evolutions. Au and Co single-phase nanoparticles were also considered for comparison. The results show that the phase transition between fcc and hcp is absent in these heterophase nanoparticles despite the existence of an unconventional phase. Although the melting of Au and Co heterophase nanoparticles is homogeneous, AuCo heterophase nanoparticles show heterogeneous melting, i.e., the Au fcc domain firstly melts, followed by the melting of the Co hcp domain, exhibiting a typical two-stage melting characteristic and resulting in the existence of a solid-core/liquid-shell structure within a considerable temperature region. Furthermore, the mutual diffusion of atoms between fcc and hcp domains is observed in the Au and Co heterophase nanoparticles. However, the unidirectional diffusion from the Au domain to the Co domain is found in the AuCo heterophase nanoparticles prior to their overall melting. This study deepens the fundamental understanding of the thermodynamic evolution of metallic heterogeneous nanoparticles and provides mechanistic and quantitative guidance for the rational design and applications of nanoscale multiphase heterostructures.

An Improved Self-Adaptive Differential Evolution with the Neighborhood Search Algorithm for Global Optimization of Bimetallic Clusters.

Global optimization of multicomponent cluster structures is considerably time-consuming due to the existence of a vast number of isomers. In this work, we proposed an improved self-adaptive differential evolution with the neighborhood search (SaNSDE) algorithm and applied it to the global optimization of bimetallic cluster structures. The cross operation was optimized, and an improved basin hopping module was introduced to enhance the searching efficiency of SaNSDE optimization. Taking (PtNi)N (N = 38 or 55) bimetallic clusters as examples, their structures were predicted by using this algorithm. The traditional SaNSDE algorithm was carried out for comparison with the improved SaNSDE algorithm. For all the optimized clusters, the excess energy and the second difference of the energy were calculated to examine their relative stabilities. Meanwhile, the bond order parameters were adopted to quantitatively characterize the cluster structures. The results reveal that the improved SaNSDE algorithm possessed significantly higher searching capability and faster convergence speed than the traditional SaNSDE algorithm. Furthermore, the lowest-energy configurations of (PtNi)38 clusters could be classified as the truncated octahedral and disordered structures. In contrast, all the optimal (PtNi)55 clusters were approximately icosahedral. Our work fully demonstrates the high efficiency of the improved algorithm and advances the development of global optimization algorithms and the structural prediction of multicomponent clusters.

Development and Validation of a Novel Nomogram for Predicting Vessels that Encapsulate Tumor Cluster in Hepatocellular Carcinoma.

BACKGROUND: Vessels that encapsulate tumor cluster (VETC) is associated with poor prognosis in hepatocellular carcinoma (HCC). Vessels that encapsulate tumor cluster estimation before initial treatment is helpful for clinical doctors. We aimed to construct a novel predictive model for VETC, using preoperatively accessible clinical parameters and imagine features. METHODS: Totally, 365 HCC patients who received curative hepatectomy in the Sun Yat-Sen University Cancer Center from 2013 to 2014 were enrolled in this study. Vessels that encapsulate tumor cluster pattern was confirmed by immunochemistry staining. 243 were randomly assigned to the training cohort while the rest was assigned to the validation cohort. Independent predictive factors for VETC estimation were determined by univariate and multivariate logistic analysis. We further constructed a predictive nomogram for VETC in HCC. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curve, and calibration curve. Besides, the decision curve was plotted to evaluate the clinical usefulness. Ultimately, Kaplan-Meier survival curves were utilized to confirm the association between the nomogram and survival. RESULTS: Immunochemistry staining revealed VETC in 87 patients (23.8%). lymphocyte to monocyte ratio (>7.75, OR = 4.06), neutrophil (>7, OR = 4.48), AST to ALT ratio (AAR > .86, OR = 2.16), ALT to lymphocyte ratio index (BLRI > 21.73, OR = 2.57), alpha-fetoprotein (OR = 1.1), and tumor diameter (OR = 2.65) were independent predictive factors. The nomogram incorporating these predictive factors performed well with an area under the curve (AUC) of .746 and .707 in training and validation cohorts, respectively. Calibration curves indicated the predicted probabilities closely corresponded with the actual VETC status. Moreover, the decision curve proved our nomogram could provide clinical benefits with patients. Finally, low probability of VETC group had significantly longer recurrence free survival (RFS) and overall survival (OS) than the high probability of the VETC group (all P < .001). CONCLUSION: A novel predictive nomogram integrating clinical indicators and image characteristics shows strong predictive VETC performance and might provide standardized net clinical benefits.

Stereodivergent propargylic alkylation of enals via cooperative NHC and copper catalysis.

Despite that asymmetric stereodivergent synthesis has experienced great success to provide unusual processes for the creation of chirality complexity, concepts appliable to asymmetric stereodivergent catalysis are still limited. The dependence on the unusual capacity of each catalyst to precisely control the reactive site planar in the region poses unparalleled constraints on this field. Here, we first demonstrate that the chiral Cu-allenylidene species can participate in the stereodivergent propargylic alkylation of enals, in concert with chiral N-heterocyclic carbenes (NHCs). Thus, all four stereoisomers were obtained with excellent enantioselectivity and diastereoselectivity (up to >99% e.e. and >95:5 d.r.) from the same starting materials by simply altering chiral Cu-Pybox complex and NHC combinations. The rich chemistry workable in the products enables the structurally diverse synthesis of chiral functional molecules and holds great potential in alkaloid synthesis, as showcased by the preparation of the key building block to access (-)-perophoramidine.

Postnatal deletion of ß-catenin in preosteoblasts regulates global energy metabolism through increasing bone resorption and adipose tissue fibrosis.

Many studies revealed bone can regulate global energy metabolism and our previous study also showed that Wnt/ß-catenin pathway is involved in this process. To better understand the participation of canonical Wnt pathway in energy metabolism, we examined the ß-catenin knock-out (ß-cat KO) mice by crossing the osterix-cre transgenic mice with ß-cateninflox/flox mice. First, we identified that postnatal deletion of ß-catenin in preosteoblasts led to decreased fat mass and increased energy expenditure in mice. Osteoprotegerin administration largely rescued the decreased fat mass and partly normalized the energy expenditure accompanied by the inhibition of bone resorption. Anti-resorption with alendronate or RANKL-antibody could also partly rescued the decreased bone mass, decreased fat mass and increased energy expenditure in ß-cat KO mice. We further found that the adipose cells in the inguinal fat tissue were smaller and the extracellular matrix components around adipocytes accumulated more in ß-cat KO mice than their controls by histomorphology. Gene analysis by RT-PCR showed that the expression of collagen VI is 4.8 folds in adipose tissue of the ß-cat KO mice compared with the control mice. We further detected the expression of cytokines which were related to fibrosis and the data showed that the level of TGF-beta1 was elevated in both of bone marrow serum and adipose tissue derived from the ß-cat KO mice. After administration of TGF-beta1 neutralizing antibody, the impaired energy metabolism was partly rescued in ß-cat KO mice. Besides, anti-resorption treatment and TGF-beta1 antibody could partly suppress the increased expression of genes related to fat tissue fibrosis. These results indicate that the abnormal global energy metabolism in ß-cat KO mice may be attributed to increasing bone resorption and adipose tissue fibrosis.

Long noncoding RNA TINCR facilitates hepatocellular carcinoma progression and dampens chemosensitivity to oxaliplatin by regulating the miR-195-3p/ST6GAL1/NF-κB pathway.

BACKGROUND: Long non-coding RNAs (lncRNA) have an essential role in progression and chemoresistance of hepatocellular carcinoma (HCC). In-depth study of specific regulatory mechanisms is of great value in providing potential therapeutic targets. The present study aimed to explore the regulatory functions and mechanisms of lncRNA TINCR in HCC progression and oxaliplatin response. METHODS: The expression of TINCR in HCC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR). Cell proliferation, migration, invasion, and chemosensitivity were evaluated by cell counting kit 8 (CCK8), colony formation, transwell, and apoptosis assays. Luciferase reporter assays and RNA pulldown were used to identify the interaction between TINCR and ST6 beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) via miR-195-3p. The corresponding functions were verified in the complementation test and in vivo animal experiment. RESULTS: TINCR was upregulated in HCC and associated with poor patient prognosis. Silencing TINCR inhibited HCC proliferation, migration, invasion, and oxaliplatin resistance while overexpressing TINCR showed opposite above-mentioned functions. Mechanistically, TINCR acted as a competing endogenous (ceRNA) to sponge miR-195-3p, relieving its repression on ST6GAL1, and activated nuclear factor kappa B (NF-κB) signaling. The mouse xenograft experiment further verified that knockdown TINCR attenuated tumor progression and oxaliplatin resistance in vivo. CONCLUSIONS: Our finding indicated that there existed a TINCR/miR-195-3p/ST6GAL1/NF-κB signaling regulatory axis that regulated tumor progression and oxaliplatin resistance, which might be exploited for anticancer therapy in HCC.

Computational screening of MBene monolayers with high electrocatalytic activity for the nitrogen reduction reaction.

As an emerging family of two-dimensional (2D) materials, transition metal borides (MBenes) have attracted increasing interest due to their potential applications in electrochemistry, especially electrocatalysis. In this work, we addressed six MB (M = Sc, Ti, V, Cr, Mo and W) monolayers as catalysts to explore their electrocatalytic activity for the nitrogen reduction reaction (NRR) using first-principles calculations. Our results demonstrated that N2 molecules could be strongly adsorbed on these MB monolayers to provoke the NRR process. Furthermore, we examined five possible catalytic reaction pathways of the NRR, i.e., the alternating, distal, and three mixed pathways, on the MB monolayers with N2 adsorption (both side-on and end-on) configurations, and screened out three highly efficient NRR catalysts: VB, CrB, and MoB monolayers with the onset potential of -0.396, -0.277, and -0.403 V, respectively. By comparison of the limiting potentials, the most effective reaction pathways of the NRR were ascertained to be the alternating pathway on the VB monolayer with the end-on configuration and the mixed I pathway on the CrB monolayer with the end-on configuration and on the MoB monolayer with the side-on configuration. Our work sheds light on the electrocatalytic mechanisms of the NRR on 2D MBenes, and provides a theoretical foundation for developing highly efficient MBene electrocatalysts for the NRR.

Oxygen adsorption on high-index faceted Pt nanoparticles.

High-index faceted Pt nanoparticles with excellent electrocatalytic performances are promising to efficiently accelerate the oxygen reduction reactions in fuel cells. By adopting the hybrid grand canonical Monte Carlo reactive molecular dynamics (GCMC/RMD) simulations, we examined the oxygen adsorption on three 24-facet nanoparticles respectively enclosed by {310}, {311}, and {331} high-index facets. The site-dependent adsorption energies on each open-structure surface are calculated. Meanwhile, the adsorption ratios under various pressures and temperatures are presented. It is revealed that the adsorption capacity of these high-index faceted nanoparticles is considerably higher than that of the ones terminated by low-index facets. Moreover, oxygen adsorption exerts a significant impact on their thermodynamic behaviors.