NbC Nanoparticles Decorated Carbon Nanofibers as Highly Active and Robust Heterostructural Electrocatalysts for Ammonia Synthesis.

Transition-metal carbides with metallic properties have been extensively used as electrocatalysts due to their excellent conductivity and unique electronic structures. Herein, NbC nanoparticles decorated carbon nanofibers (NbC@CNFs) are proposed as an efficient and robust catalyst for electrochemical synthesis of ammonia from nitrate/nitrite reduction, which achieves a high Faradaic efficiency (FE) of 94.4 % and a large ammonia yield of 30.9 mg h-1 mg-1 cat.. In situ electrochemical tests reveal the nitrite reduction at the catalyst surface follows the *NO pathway and theoretical calculations reveal the formation of NbC@CNFs heterostructure significantly broadens density of states nearby the Fermi energy. Finite element simulations unveil that the current and electric field converge on the NbC nanoparticles along the fiber, suggesting the dispersed carbides are highly active for nitrite reduction.

Crystalline modulation of zirconia for efficient nitrate reduction to ammonia under ambient conditions.

Zirconia as a polycrystalline catalyst can be effectively tuned by doping low-valence elements and meanwhile form abundant oxygen vacancies. Herein, the crystalline structures of zirconia are modulated by scandium doping and proposed as a robust catalyst for nitrate reduction to ammonia. The tetragonal zirconia achieves a maximum ammonia yield of 16.03 mg h-1 mgcat.-1, superior to the other crystal forms. DEMS tests unveil the reaction pathway and theoretical calculations reveal the low free energy of -0.22 eV for nitrate adsorption at the tetragonal zirconia.

Peer Victimization and Subjective Well-Being Among Chinese Adolescents: Moderated Mediation by Forgiveness and Self-Esteem.

Considerable developmental research has shown an association between peer victimization and subjective well-being among adolescents. However, the mediating processes and protective factors that constrain this association are less understood. To fill these gaps, we investigated whether self-esteem mediates the association between peer victimization and subjective well-being and whether forgiveness moderates the direct and indirect associations of peer victimization with adolescents' subjective well-being via self-esteem. A large sample of 2,758 adolescents (Mage = 13.53 years, SD = 1.06) from 10 middle schools in China participated in this study. Participants provided data on demographic variables, peer victimization, self-esteem, forgiveness, and subjective well-being by answering anonymous questionnaires. After controlling for demographic covariates, we found that self-esteem mediated the relationship between peer victimization and subjective well-being. Furthermore, as a protective factor, forgiveness moderated the relationship between peer victimization and self-esteem. Consistent with the protective-reactive model, when adolescents experienced more peer victimization, those with higher forgiveness levels exhibited a greater decline in self-esteem, and low self-esteem was then associated with decreased subjective well-being. These findings demonstrate the utility of examining both mediating and moderating factors in this relationship and highlight the negative impact of peer victimization on adolescent self-worth and the limited role of forgiveness as a protective factor.

Cleavage of non-polar C(sp2)‒C(sp2) bonds in cycloparaphenylenes via electric field-catalyzed electrophilic aromatic substitution.

Electrophilic aromatic substitution (EAS) is one of the most fundamental reactions in organic chemistry. Using an oriented external electric field (OEEF) instead of traditional reagents to tune the EAS reactivity can offer an environmentally friendly method to synthesize aromatic compounds and hold the promise of broadening its scope. Despite these advantages, OEEF catalysis of EAS is difficult to realize, due to the challenge of microscopically orienting OEEF along the direction of electron reorganizations. In this work, we demonstrate OEEF-catalyzed EAS reactions in a series of cycloparaphenylenes (CPPs) using the scanning tunneling microscope break junction (STM-BJ) technique. Crucially, the unique radial π-conjugation of CPPs enables a desired alignment for the OEEF to catalyze the EAS with Au STM tip (or substrate) acting as an electrophile. Under mild conditions, the OEEF-catalyzed EAS reactions can cleave the inherently inert C(sp2)-C(sp2) bond, leading to high-yield (~97%) formation of linear oligophenylenes terminated with covalent Au-C bonds. These results not only demonstrate the feasibility of OEEF catalysis of EAS, but also offer a way of exploring new mechanistic principles of classic organic reactions aided by OEEF.

Valorization of chitin biomass into N-containing chemical 3-acetamido-5-acetylfuran catalyzed by simple Lewis acid.

3-Acetamido-5-acetylfuran(3A5AF) is a nitrogen-containing fine chemical and has broad application prospects and high research value. Herein, we report a mild and efficient method for the synthesis of 3A5AF from N-acetyl-d-glucosamine (NAG). The influence of solvent, temperature and additive on the catalytic performance was also studied. The Lewis acids with high catalytic efficiency have been smoothly screened. The highest yield (41.57%) of 3A5AF was obtained in the presence of B2O3 and MgCl2·6H2O at 180 °C for 60 min under normal atmospheric conditions. The reaction pathway was explored by LC-MS, 1H NMR, 13C NMR and FT-IR spectra. Compared with the microwave method and hydrothermal method, the optimized reaction condition was relatively mild. Moreover, the catalyst MgCl2·6H2O is low-cost and environmentally friendly.

Laparoscopic versus open repair of congenital duodenal obstruction: a systematic review and meta-analysis.

PURPOSE: To assess the safety and efficacy of laparoscopic versus open repair of congenital duodenal obstruction (CDO), we conducted a systematic review and meta-analysis (CDO). METHODS: A literature search was conducted to identify studies that compared laparoscopic surgery (LS) and open surgery (OS) for neonates with CDO. Meta-analysis was used to pool and compare variables such as operative time, time to feeding, length of hospital stay, anastomotic leak or stricture, postoperative ileus, wound infection, and overall postoperative complications. RESULTS: Among the 1348 neonatal participants with CDO in the ten studies, 304 received LS and 1044 received OS. When compared to the OS approach, the LS approach resulted in shorter hospital stays, faster time to initial and full feeding, longer operative time, and less wound infection. However, no significant difference in secondary outcomes such as anastomotic leak or stricture, postoperative ileus, and overall postoperative complications was found between LS and OS. CONCLUSIONS: LS is a safe, feasible and effective surgical procedure for neonatal CDO when compared to OS. Compared with OS, LS has a faster time to feeding, a shorter hospital stay, and less wound infection. Furthermore, in terms of anastomotic leak or stricture, postoperative ileus, and overall postoperative complications, LS is equivalent to OS. We conclude that LS should be considered an acceptable option for CDO.

Laparoscopic versus Open Reduction of Intussusception in Infants and Children: A Systematic Review and Meta-analysis.

We conducted a systematic review and meta-analysis to compare the efficacy and safety between laparoscopic reduction (LR) and open reduction (OR) of intussusception in infants and children. Literature searches were conducted to identify studies having compared LR and OR for children with intussusception failed to enema reduction. Parameters such as operative time, time to oral intake, length of hospital stay, overall postoperative complications, and recurrence were pooled and compared by meta-analysis. Among the 502 pediatric participants included in the 11 studies, 275 had received LR and 227 received OR. There were shorter length of hospital stays and time to oral intake with the LR approach compared with OR. However, no significant difference was found between LR and OR in the secondary outcome, such as the overall postoperative complications and recurrence. LR is a feasible, safe, and effective surgical procedure alternative to OR for pediatric intussusception. Compared with OR, LR has the advantage of shorter hospital stay and faster time to oral intake. Besides, the overall postoperative complications may be slightly lower in LR. We conclude that LR should be considered an acceptable option for children.

Single cycloparaphenylene molecule devices: Achieving large conductance modulation via tuning radial π-conjugation.

Conjugated macrocycles cycloparaphenylenes (CPPs) have unusual size-dependent electronic properties because of their unique radially π-conjugated structures. Contrary to linearly π-conjugated molecules, their highest occupied molecular orbital (HOMO)­lowest unoccupied molecular orbital (LUMO) gap shrinks as the molecular size reduces, and this feature can, in principle, be leveraged to achieve unexpected size-dependent transport properties. Here, we examine charge transport characteristics of [n]CPPs (n = 5 to 12) at the single molecule level using the scanning tunneling microscope­break junction technique. We find that the [n]CPPs have a much higher conductance than their linear oligoparaphenylene counterparts at small ring size and at the same time show a large tunneling attenuation coefficient comparable to saturated alkane series. These results show that the radially π-conjugated molecular systems can offer much larger conductance modulation range than standard linear molecules and can be a new platform for building molecular devices with highly tunable transport behaviors.

Chrysosplenol D protects mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via TLR4-MAPKs/NF-κB signaling pathways.

This study investigated the effect and mechanism of chrysosplenol D (CD) on LPS-induced acute lung injury in mice. Histological changes in the lungs were measured by hematoxylin-eosin staining. The levels of IL-6, IL-1ß, and TNF-α in the bronchoalveolar lavage fluid were detected by ELISA. The levels of oxidative stress were detected by the cuvette assay. Immune cells in peripheral blood, the levels of reactive oxygen species, and apoptosis of primary lung cells were detected by flow cytometry. The mRNA levels of TLR4, MyD88, IL-1ß, and NLRP3 were measured by quantitative real-time polymerase chain reaction. The levels of proteins in apoptosis and the TLR4-MAPKs/NF-κB signaling pathways were detected by Western blot. Hematoxylin-eosin staining showed that CD could improve lung injury; decrease the levels of inflammatory factors, oxidative stress, reactive oxygen species, and cell apoptosis; and regulate the immune system. Moreover, CD could down-regulate the mRNA levels of TLR4, MyD88, NLRP3, and IL-1ß in lung, and the protein levels of Keap-1, Cleaved-Caspase-3/Caspase-3, Cleaved-Caspase-9/Caspase-9, TLR4, MyD88, p-ERK/ERK, p-JNK/JNK, p-p38/p38, p-p65/p65, NLRP3, and IL-1ß, and up-regulated the levels of Bcl-2/Bax, p-Nrf2/Nrf2, and HO-1. The results suggested that CD could protect mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via the TLR4-MAPKs/NF-κB signaling pathways.

Hedyotis diffusa plus Scutellaria barbata Suppress the Growth of Non-Small-Cell Lung Cancer via NLRP3/NF-κB/MAPK Signaling Pathways.

Hedyotis diffusa (HD) plus Scutellaria barbata (SB) have been widely used in antitumor clinical prescribes as one of herb pairs in China. We investigated the effect of aqueous extract from Hedyotis diffusa plus Scutellaria barbata at the equal weight ratio (HDSB11) in inhibiting the growth of murine non-small-cell lung cancer cell (NSCLC) line LLC in vivo and in vitro in this study. Compared with other aqueous extracts, HDSB11 showed the lowest IC50 in inhibiting cell proliferation at 0.43 mg/ml. Besides, HDSB11 effectively suppressed colony formation and induced cell apoptosis. The further assessment of HDSB11 on the murine Lewis-lung-carcinoma-bearing mouse model showed it significantly inhibited tumors' bioluminescence at the dose of 30 g crude drug/kg. Mechanistically, HDSB11 attenuated the expressions of NLRP3, procaspase-1, caspase-1, PRAP, Bcl-2, and cyclin D1 and downregulated the phosphorylation levels of NF-κB, ERK, JNK, and p38 MAPK. In conclusion, HDSB11 could alleviate cell proliferation and colony formation and induce apoptosis in vitro and tumor growth in vivo, partly via NF-κB and MAPK signaling pathways to suppress NLRP3 expression.

Ethyl Acetate Fraction from Hedyotis diffusa plus Scutellaria barbata Exerts Anti-Breast Cancer Effect via miR-200c-PDE7B/PD-L1-AKT/MAPK Axis.

BACKGROUND: Hedyotis diffusa (HD) Willd. and Scutellaria barbata (SB) D. Don in different ratios have been frequently used to treat various cancers in clinical Traditional Chinese Medicine prescriptions. However, the optimal ratio, active fraction, and molecular mechanisms associated with the anti-breast cancer role of this herbal couplet have not been elaborated. METHODS: To screen out the optimal ratio of this herbal couplet, we compare aqueous extracts of HD, SB, or HD plus SB in different weight ratios (HS11, HS12, HS21) for their anticancer effects on murine breast cancer 4T1 cells in vitro and in vivo. EA11, the ethyl acetate fraction from HS11 (the aqueous extract of the couplet at an equal weight ratio), is further assessed for its antiproliferative effect as well as the antitumorigenic impact with the aid of immunocompetent mice. Colony formation, flow cytometry, western blot, ELISA, and qRT-PCR are used to elucidate mechanisms underlying EA11-led effects. RESULTS: HS11 presents the most potential suppression of 4T1 cell proliferation and tumor growth among these aqueous extracts. The comparison results show that EA11 is more effective than HS11 in vitro and in vivo. EA11 inhibits colony formation and induces apoptosis in a concentration-dependent manner. EA11 reduces the protein expressions of PDE7B, PD-L1, ß-catenin, and cyclin D1 while elevating the concentration of cellular cAMP and miR-200c expression in 4T1 cells. Additionally, EA11 exerts its anticancer effect partially via the inactivation of MAPK and AKT signaling pathways. CONCLUSIONS: This study implicates that EA11 prevents breast tumor development by interfering with the miR-200c-PDE7B/PD-L1-AKT/MAPK axis. EA11 may represent a potential therapeutic candidate for breast cancer.

Ethyl Acetate Fraction from Hedyotis diffusa plus Scutellaria barbata Suppresses Migration of Bone-Metastatic Breast Cancer Cells via OPN-FAK/ERK/NF-κB Axis.

Hedyotis diffusa plus Scutellaria barbata is a couplet of medicinal that has been commonly used to treat inflammation-related diseases and various types of tumors. However, the effect of this couplet on tumor cell migration has not been elucidated. With the aid of MCF-7-BOM, a bone-metastatic subline of ER + breast cancer MCF-7, we showed that ethyl acetate fraction extracted at an equal weight ratio of Hedyotis diffusa plus Scutellaria barbata (EA11) inhibited cell migration of MCF-7-BOM in a concentration-dependent manner. To define the underlying molecular mechanism, we revealed that EA11 reduced the expression of osteopontin (OPN) and interfered with the FAK/ERK/NF-κB signaling pathways, which are both critical for breast cancer bone metastasis. This study strongly suggested EA11 may represent a potential therapeutic agent against bone metastasis of breast cancer.

TGFß inhibition enhances the generation of hematopoietic progenitors from human ES cell-derived hemogenic endothelial cells using a stepwise strategy.

Embryonic hematopoiesis is a complex process. Elucidating the mechanism regulating hematopoietic differentiation from pluripotent stem cells would allow us to establish a strategy to efficiently generate hematopoietic cells. However, the mechanism governing the generation of hematopoietic progenitors from human embryonic stem cells (hESCs) remains unknown. Here, on the basis of the emergence of CD43(+) hematopoietic cells from hemogenic endothelial (HE) cells, we demonstrated that VEGF was essential and sufficient, and that bFGF was synergistic with VEGF to specify the HE cells and the subsequent transition into CD43(+) hematopoietic cells. Significantly, we identified TGFß as a novel signal to regulate hematopoietic development, as the TGFß inhibitor SB 431542 significantly promoted the transition from HE cells into CD43(+) hematopoietic progenitor cells (HPCs) during hESC differentiation. By defining these critical signaling factors during hematopoietic differentiation, we can efficiently generate HPCs from hESCs. Our strategy could offer an in vitro model to study early human hematopoietic development.

Retinoic acid enhances the generation of hematopoietic progenitors from human embryonic stem cell-derived hemato-vascular precursors.

Current induction schemes directing hematopoietic differentiation of human embryonic stem cells (hESCs) are not well defined to mimic the sequential stages of hematopoietic development in vivo. Here, we report a 3-stage method to direct differentiation of hESCs toward hematopoietic progenitors in chemically defined mediums. In the first 2 stages, we efficiently generated T-positive primitive streak/mesendoderm cells and kinase domain receptor-positive (KDR(+)) platelet-derived growth factor receptor α-negative (PDGFRα(-)) hemato-vascular precursors sequentially. In the third stage, we found that cells in a spontaneous differentiation condition mainly formed erythroid colonies. Addition of all-trans retinoic acid (RA) greatly enhanced generation of hematopoietic progenitors in this stage while suppressing erythroid development. The RA-treated cells highly expressed definitive hematopoietic genes, formed large numbers of multilineage and myeloid colonies, and gave rise to greater than 45% CD45(+) hematopoietic cells. When hematopoietic progenitors were selected with CD34 and C-Kit, greater than 95% CD45(+) hematopoietic cells could be generated. In addition, we found that endogenous RA signaling at the second stage was required for vascular endothelial growth factor/basic fibroblast growth factor-induced hemato-vascular specification, whereas exogenously applied RA efficiently induced KDR(-)PDGFRα(+) paraxial mesoderm cells. Our study suggests that RA signaling plays diverse roles in human mesoderm and hematopoietic development.

Mouse lysocardiolipin acyltransferase controls the development of hematopoietic and endothelial lineages during in vitro embryonic stem-cell differentiation.

The blast colony-forming cell (BL-CFC) was identified as an equivalent to the hemangioblast during in vitro embryonic stem (ES) cell differentiation. However, the molecular mechanisms underlying the generation of the BL-CFC remain largely unknown. Here we report the isolation of mouse lysocardiolipin acyltransferase (Lycat) based on homology to zebrafish lycat, a candidate gene for the cloche locus. Mouse Lycat is expressed in hematopoietic organs and is enriched in the Lin(-)C-Kit(+)Sca-1(+) hematopoietic stem cells in bone marrow and in the Flk1(+)/hCD4(+)(Scl(+)) hemangioblast population in embryoid bodies. The forced Lycat transgene leads to increased messenger RNA expression of hematopoietic and endothelial genes as well as increased blast colonies and their progenies, endothelial and hematopoietic lineages. The Lycat small interfering RNA transgene leads to a decrease expression of hematopoietic and endothelial genes. An unbiased genomewide microarray analysis further substantiates that the forced Lycat transgene specifically up-regulates a set of genes related to hemangioblasts and hematopoietic and endothelial lineages. Therefore, mouse Lycat plays an important role in the early specification of hematopoietic and endothelial cells, probably acting at the level of the hemangioblast.

HBsAg and HBx knocked into the p21 locus causes hepatocellular carcinoma in mice.

Hepatocellular carcinoma (HCC) affects males in a significantly higher proportion than females and is one of the human cancers etiologically related to viral factors. Many studies provide strong evidence of the direct role that hepatitis B virus (HBV) plays in hepatic carcinogenesis, but the functions of HBV surface antigen (HBsAg) and X protein (HBx) in hepatocarcinogenesis through direct or indirect mechanisms are still being debated. We generated two HBV gene knock-in transgenic mouse lines by homologous recombination. HBsAg and HBx genes were integrated into the mouse p21 locus. Both male and female p21-HBx transgenic mice developed HCC after the age of 18 months; however, male p21-HBsAg transgenic mice began to develop HCC 3 months earlier. The expression of a number of genes related to metabolism and genomic instability largely resembled the molecular changes during the development of HCC in humans. ER-beta (estrogen receptor-beta) was extremely up-regulated only in tumor tissues of male p21-HBsAg mice, providing genetic evidence that HBsAg might be the major risk factor affecting the gender difference in the causes of HCC. In conclusion, these mice might serve as good models for studying the different roles of HBsAg and HBx in early events of HBV-related hepatocarcinogenesis.

Mutation analysis of the Smad3 gene in human osteoarthritis.

Osteoarthritis (OA) is the most common joint disease worldwide. Recent studies have shown that targeted disruption of Smad3 in mouse results in OA. To reveal the possible association between the Smad3 gene mutation and human OA, we employed polymerase chain reaction-single strand conformation polymorphism and sequencing to screen mutations in all nine exons of the Smad3 gene in 32 patients with knee OA and 50 patients with only bone fracture. A missense mutation of the Smad3 gene was found in one patient. The single base mutation located in the linker region of the SMAD3 protein was A --> T change in the position 2 of codon 197 and resulted in an asparagine to isoleucine amino-acid substitution. The expressions of matrix metalloproteinase 2 (MMP-2) and MMP-9 in sera of the patient carrying the mutation were higher than other OA patients and controls. This is the first report showing that the Smad3 gene mutations could be associated with the pathogenesis of human OA.