1,2‐Bisphosphines have been identified as one class of important and powerful chiral ligands in asymmetric catalysis with transition metals. Herein, a copper(I)‐catalyzed asymmetric ...hydrophosphination of α,β‐unsaturated phosphine sulfides was developed with the assistance of “soft–soft” interaction between copper(I)‐catalyst and the phosphine sulfide moiety, which afforded 1,2‐bisphosphine derivatives with diversified electronic nature and steric hindrance in high to excellent yields with high to excellent enantioselectivity. Moreover, the challenging catalytic asymmetric hydrophosphination/protonation reaction was achieved with excellent enantioselectivity. Strikingly, the dynamic kinetic resolution of racemic diarylphosphines was also successfully carried out with high to excellent diastereo‐ and enantioselectivities. Interestingly, the nucleophilic copper(I)‐diphenylphosphide species was characterized by 31P NMR spectrum and mass spectrum. At last, three products were transformed to chiral 1,2‐bisphosphines, which were employed as ligands in Rh‐catalyzed asymmetric hydrogenation of α‐amino‐α,β‐unsaturated ester. The α‐amino acid derivative was produced in high enantioselectivity, which demonstrated the utility of the present methodology.
A catalytic asymmetric conjugate hydrophosphination of α,β‐unsaturated phosphine sulfides with diarylphosphines allows rapid construction of chiral 1,2‐bisphosphine derivatives with diversified electronic nature and steric hindrance. This reaction is facilitated by the “soft–soft” interaction between copper(I) catalysts and phosphine sulfides.
Novel 3D Ni1−xCoxSe2 mesoporous nanosheet networks with tunable stoichiometry are successfully synthesized on Ni foam (Ni1−xCoxSe2 MNSN/NF with x ranging from 0 to 0.35). The collective effects of ...special morphological design and electronic structure engineering enable the integrated electrocatalyst to have very high activity for hydrogen evolution reaction (HER) and excellent stability in a wide pH range. Ni0.89Co0.11Se2 MNSN/NF is revealed to exhibit an overpotential (η10) of 85 mV at −10 mA cm−2 in alkaline medium (pH 14) and η10 of 52 mV in acidic solution (pH 0), which are the best among all selenide‐based electrocatalysts reported thus far. In particular, it is shown for the first time that the catalyst can work efficiently in neutral solution (pH 7) with a record η10 of 82 mV for all noble metal‐free electrocatalysts ever reported. Based on theoretical calculations, it is further verified that the advanced all‐pH HER activity of Ni0.89Co0.11Se2 is originated from the enhanced adsorption of both H+ and H2O induced by the substitutional doping of cobalt at an optimal level. It is believed that the present work provides a valuable route for the design and synthesis of inexpensive and efficient all‐pH HER electrocatalysts.
An integrated electrocatalyst comprising 3D mesoporous Ni0.89Co0.11Se2 nanosheet networks on Ni foam is synthesized, and it demonstrates very high activities and excellent stabilities for hydrogen evolution reaction (HER) in all‐pH conditions. Theoretical calculations verify that electronic structure engineering by optimal Co doping enhances the adsorption of H+ and H2O, leading to the advanced all‐pH HER activity of the catalyst.
As one kind of Burgers-type equation, the extended coupled (2+1)-dimensional Burgers system is used to describe certain wave process in oceanography, acoustics or hydrodynamics. With the Riccati ...projective equation method and symbolic computation, the variable separation solution is derived. Due to the arbitrary functions in the variable separation solutions, the fractal and chaotic structures are studied based on the gradient function (say,
U
in the text). Some excitation properties of the solutions are analyzed and figures are plotted to show the shape and the structure.
Background Chronic spontaneous urticaria (CSU) is defined by itchy hives, angioedema, or both for at least 6 weeks. Omalizumab, an anti-IgE antibody that affects mast cell and basophil function, is a ...promising new treatment option. As of now, however, the efficacy and safety of different doses of omalizumab used in clinical trials for CSU have not been systematically analyzed and summarized. Objective We sought to assess the efficacy and safety of different doses of omalizumab for the treatment of CSU in a meta-analysis of clinical trial results. Methods Suitable trials were identified by searching PubMed, Medline, Embase, and Web of Science databases and with the help of omalizumab's manufacturers. Only double-blind, randomized, placebo-controlled studies with omalizumab-treated versus placebo-treated patients with CSU were included in this analysis. Results We identified 7 randomized, placebo-controlled studies with 1312 patients with CSU. Patients treated with omalizumab (75-600 mg every 4 weeks) had significantly reduced weekly itch and weekly wheal scores compared with the placebo group. Omalizumab's effects were dose dependent, with the strongest reduction in weekly itch and weekly wheal scores observed with 300 mg. Rates of complete response were significantly higher in the omalizumab group (relative risk, 4.55; P < .00001) and dose dependent, with the highest rates in the 300-mg group. Rates of patients with adverse events were similar in the omalizumab and placebo groups. Conclusion This meta-analysis provides high-quality evidence for the efficacy and safety of omalizumab in patients with CSU and for treating these patients with 300 mg of omalizumab every 4 weeks.
This study scrutinizes the impact of globalization, non-renewable energy consumption, and economic growth on CO2 emission for selected South Asian economies during 1985–2018 under the EKC framework. ...For this purpose, we apply a fully modified ordinary least square (FMOLS) technique. The empirical findings of this study identify that globalization is positively associated with CO2 emission. The results also indicate that non-renewable energy consumption increasing environmental pollution. Moreover, the results confirm the EKC hypothesis in the South Asian region; this means that at the early stages of development, when economic growth increases, environmental pollution also increases, but environmental degradation starts to decrease with the increases in economic growth after the threshold point. The empirical outcomes suggest that the government should subsidize and promote renewable energy sources to tackle the problem of environmental degradation.
•The impact of energy consumption and globalization on CO2 emission is studied.•A group of South Asian countries is covered.•The results supported the EKC hypothesis in South Asian countries.•Energy consumption is a significant source of CO2 emission.•Globalization is positively associated with CO2 emission.
•A new approach is proposed to search for the interaction solutions, which can decrease the complexity of the associated nonlinear algebraic equations via reducing the number of the variables.•The ...fast calculation approach provides the condition for the predictability of the interaction solution.•Interaction phenomena between lump wave and a stipe, and lump wave and soliton solution are discussed and numerically simulated.
The cylindrical Kadomtsev-Petviashvili (cKP) equation related to cylindrical geometry, as one type of the variable-coefficient KP equation, is widely used to describe nonlinear phenomena in fluid, plasma and other fields. With symbolic computation, we have derived the multi-soliton solutions, rational solutions, lump solutions and interaction solutions to the cKP equation based on its bilinear representation. The interaction solutions include two types: The interaction between lump and stripe, and the interaction between lump and soliton. Moreover, we have proposed a new approach to search for the interaction solutions, which can decrease the complexity of the associated nonlinear algebraic equations via reducing the number of the variables. The fast calculation approach provides the condition for the predictability of the interaction solution.
The development of highly thermally conductive composites with excellent electrical insulation has attracted extensive attention, which is of great significance to solve the increasingly severe heat ...concentration issue of electronic equipment. Herein, we report a new strategy to prepare boron nitride nanosheets (BNNSs) via an ion-assisted liquid-phase exfoliation method. Then, silver nanoparticle (AgNP) modified BNNS (BNNS@Ag) was obtained by in situ reduction properties. The exfoliation yield of BNNS was approximately 50% via the ion-assisted liquid-phase exfoliation method. Subsequently, aramid nanofiber (ANF)/BNNS@Ag composites were prepared by vacuum filtration. Owing to the "brick-and-mortar" structure formed inside the composite and the adhesion of AgNP, the interfacial thermal resistance was effectively reduced. Therefore, the in-plane thermal conductivity of ANF/BNNS@Ag composites was as high as 11.51 W m
K
, which was 233.27% higher than that of pure ANF (3.45 W m
K
). The addition of BNNS@Ag maintained tensile properties (tensile strength of 129.14 MPa). Moreover, the ANF/BNNS@Ag films also had good dielectric properties and the dielectric constant was below 2.5 (10
Hz). Hence, the ANF/BNNS@Ag composite shows excellent thermal management performance, and the electrical insulation and mechanical properties of the matrix are retained, indicating its potential application prospects in high pressure and high temperature application environments.
Immune checkpoint inhibitors had a great effect in triple-negative breast cancer (TNBC); however, they benefited only a subset of patients, underscoring the need to co-target alternative pathways and ...select optimal patients. Herein, we investigated patient subpopulations more likely to benefit from immunotherapy and inform more effective combination regimens for TNBC patients.
We conducted exploratory analyses in the FUSCC cohort to characterize a novel patient selection method and actionable targets for TNBC immunotherapy. We investigated this in vivo and launched a phase 2 trial to assess the clinical value of such criteria and combination regimen. Furthermore, we collected clinicopathological and next-generation sequencing data to illustrate biomarkers for patient outcomes.
CD8-positivity could identify an immunomodulatory subpopulation of TNBCs with higher possibilities to benefit from immunotherapy, and angiogenesis was an actionable target to facilitate checkpoint blockade. We conducted the phase II FUTURE-C-Plus trial to assess the feasibility of combining famitinib (an angiogenesis inhibitor), camrelizumab (a PD-1 monoclonal antibody) and chemotherapy in advanced immunomodulatory TNBC patients. Within 48 enrolled patients, the objective response rate was 81.3% (95% CI, 70.2-92.3), and the median progression-free survival was 13.6 months (95% CI, 8.4-18.8). No treatment-related deaths were reported. Patients with CD8- and/or PD-L1- positive tumors benefit more from this regimen. PKD1 somatic mutation indicates worse progression-free and overall survival.
This study confirms the efficacy and safety of the triplet regimen in immunomodulatory TNBC and reveals the potential of combining CD8, PD-L1 and somatic mutations to guide clinical decision-making and treatments.
ClinicalTrials.gov: NCT04129996 . Registered 11 October 2019.
Insulin/IGF-1 Signaling (IIS) is known to constrain longevity by inhibiting the transcription factor FOXO. How phosphorylation mediated by IIS kinases regulates lifespan beyond FOXO remains unclear. ...Here, we profile IIS-dependent phosphorylation changes in a large-scale quantitative phosphoproteomic analysis of wild-type and three IIS mutant Caenorhabditis elegans strains. We quantify more than 15,000 phosphosites and find that 476 of these are differentially phosphorylated in the long-lived daf-2/insulin receptor mutant. We develop a machine learning-based method to prioritize 25 potential lifespan-related phosphosites. We perform validations to show that AKT-1 pT492 inhibits DAF-16/FOXO and compensates the loss of daf-2 function, that EIF-2α pS49 potently inhibits protein synthesis and daf-2 longevity, and that reduced phosphorylation of multiple germline proteins apparently transmits reduced DAF-2 signaling to the soma. In addition, an analysis of kinases with enriched substrates detects that casein kinase 2 (CK2) subunits negatively regulate lifespan. Our study reveals detailed functional insights into longevity.
Gastric cancer(GC),which is mainly induced by Helicobacter pylori(H.pylori)infection,is one of the leading causes of cancer-related death in the developing world.Active inflammation initiated by ...H.pylori infection and maintained by inherent immune disorders promotes carcinogenesis and postoperative recurrence.However,the presence with H.pylori in tumors has been linked to a better prognosis,possibly due to the induction of antitumor immunity.Tumor infiltrations of tumorassociated macrophages,myeloid-derived suppressor cells,neutrophils,Foxp3+regulatory T cells are correlated with poor prognosis.Tumor infiltrating CD8+cytotoxic T lymphocytes,dendritic cells,and CD45RO T cells are generally associated with good prognosis of GC,although some subsets of these immune cells have inverse prognosis prediction values.High ratios of Foxp3+/CD4+and Foxp3+/CD8+in tumors are associated with a poor prognosis;whereas high Th1/Th2ratio in tumors predicts a good prognosis.High levels of interleukin(IL)-6,IL-10,IL-32,and chemokine C-C motif ligands(CCL)7 and CCL21 in circulation,high expression of CXC chemokine receptor 4,chemokine C-C motif receptor(CCR)3,CCR4,CCR5,CCR7,hypoxiainducible factor-1α,signal transducer activator of transcription-3,cyclooxygenase-2,and orphan nuclear receptor 4A2 in tumors are associated with an unfavorable prognosis.Increased serum levels of matrix metalloproteinases(MMP)-3,MMP-7,and MMP-11 and increased levels of MMP-9,MMP-12,and MMP-21 in tumors are consistently associated with poor survival of GC.Further emphasis should be put on the integration of these biomarkers and validation in large cohorts for personalized prediction of GC postoperative prognosis.
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