Quantum chemical calculations in combination with unbiased global searches reveal a unique binary B7Mg4+ cluster, in which a vertically oriented Mg2 dimer is incorporated into a ringent (or Pac-Man ...shaped) B7 disk, forming a hybrid Mg2B7 molecular wheel with pseudo-seven-fold in-plane coordination. The hybrid wheel assumes a plier shape. The remaining Mg2 dimer floats on the hybrid wheel via electrostatic interaction, with relatively minor covalent Mg–B bonding. The B7Mg4+ cluster can be described as a charge transfer Mg22+Mg2B7− complex. Chemical bonding analysis indicates double 6π/6σ aromaticity in B7Mg4+ cluster. The unique plier shape of the cluster is elucidated using the concept of electronic transmutation, in which the vertical Mg2 dimer closely mimics the chemistry of an atomic B− or C site.
Polypropylene (PP) is notch sensitive and brittle under severe conditions of deformation, limiting wider range of its usage as a structural load-bearing polymer. Hence, in this work the magnesium ...borate whisker (MBw), with similar mechanical properties to carbon fiber but much less expensive than polycrystalline silicon carbide, was modified by boric acid ester (BAE) and then used to fabricate PP composites. The mechanical properties, morphology, and non-isothermal crystallization property of virgin PP, PP/MBw, and PP/BAE-MBw composites were studied through mechanical testing, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC), respectively. The non-isothermal crystallization data was analyzed via Mo, Kissinger, and Dobreva methods. The results reveal that the incorporation of BAE-MBw into PP matrix results in higher tensile strength and impact strength than those of virgin PP and PP/MBw composite. The activation energies based on Kissinger were 190.20 kJ/mol for virgin PP, 206.59 kJ/mol for PP/MBw, and 218.98 kJ/mol for PP/BAE-MBw. The nucleation activities of whiskers determined by the Dobreva model were 0.86 for PP/MBw and 0.75 for PP/BAE-MBw. As a result, the whiskers, especially the modified whiskers, act as active substrates to facilitate heterogeneous nucleation, which leads to an increase in crystallization rate.
Safety and efficacy of allogeneic anti-CD19 chimeric antigen receptor T cells (CAR-T cells) in persons with CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) relapsing after an allotransplant ...remain unclear. Forty-three subjects with B-ALL relapsing post allotransplant received CAR-T cells were analyzed. 34 (79%; 95% confidence interval CI: 66, 92%) achieved complete histological remission (CR). Cytokine release syndrome (CRS) occurred in 38 (88%; 78, 98%) and was greater than or equal tograde-3 in 7. Two subjects died from multiorgan failure and CRS. Nine subjects (21%; 8, 34%) developed less than or equal tograde-2 immune effector cell-associated neurotoxicity syndrome (ICANS). Two subjects developed less than or equal tograde-2 acute graft-versus-host disease (GvHD). 1-year event-free survival (EFS) and survival was 43% (25, 62%). In 32 subjects with a complete histological remission without a second transplant, 1-year cumulative incidence of relapse was 41% (25, 62%) and 1-year EFS and survival, 59% (37, 81%). Therapy of B-ALL subjects relapsing post transplant with donor-derived CAR-T cells is safe and effective but associated with a high rate of CRS. Outcomes seem comparable to those achieved with alternative therapies but data from a randomized trial are lacking.
Photochromic metal–organic complexes (PMOCs) have received huge attention of chemists, thanks to their diverse structural characteristic and various available photo-modulate physicochemical ...functionalities. The organic ligand plays a crucial role in the quest of PMOCs with specific photo-responsive functionalities. The multiple coordination modes of polydentate ligands also provide possibilities for forming isomeric MOCs, which may open a new perspective on the research of PMOCs. The exploration of suitable PMOC systems is significant for the yield of isomeric PMOCs. Taking into account extant PMOCs based on polypyridines and carboxylate as electron acceptors (EAs) and donors (EDs), the covalent fusion of suitable pyridyl and carboxyl species may produce single functionalized ligands bearing ED and EA moieties for the building of novel PMOCs. In this study, the coordination assembly of bipyridinedicarboxylate (2,2′-bipyridine-4,4′-dicarboxylic acid, H2bpdc) and Pb2+ ions generate two isomeric MOCs, Pb(bpdc)·H2O (1 and 2), which have the same chemical compositions with main discrepancies in the coordination mode of bpdc2– ligands. As expected, supramolecular isomers 1 and 2 exhibited different photochromic performance, thanks to the distinct microscopic functional structural units. A schematic encryption and anti-counterfeiting device based on complexes 1 and 2 has also been studied. Compared with the extensively studied PMOCs supported by photoactive ligands like pyridinium and naphthalimide-derivatives and PMOCs derived from mixed electron-accepting polydentate N-ligands and electron-donating ligands, our work provides a new idea for building PMOCs based on pyridinecarboxylic acid ligands.
Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the ...brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understood.
Here, we used morris water maze, elisa and gas chromatography-time of flight/mass spectrometry to observe the changes in cognition, neuropathology and metabolomics in the hippocampus of APP/PS1 mice and wild-type (C57) mice caused by chronic unpredictable mild stress (CUMS), we also further explored the correlation between cognition and metabolomics.
We found that 4 weeks of CUMS aggravated cognitive impairment and increased amyloid-β deposition in APP/PS1 mice, but did not affect C57 mice. Under non-stress conditions, compared with C57 mice, there were 8 different metabolites in APP/PS1 mice. However, following CUMS, 3 different metabolites were changed compared with untreated C57 mice. Compared to APP/PS1 mice, there were 7 different metabolites in APP/PS1+CUMS mice. Among these alterations, 3-hydroxybutyric acid, valine, serine, beta-alanine and o-phosphorylethanolamine, which are involved in sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.
The results indicate that APP/PS1 mice are more vulnerable to stress than C57 mice, and the metabolic mechanisms of stress-related cognitive impairment in APP/PS1 mice are related to multiple pathways and networks, including sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.
Doping alkali metals into boron clusters can effectively compensate for the intrinsic electron deficiency of boron and lead to interesting boron-based binary clusters, owing to the small ...electronegativity of the former elements. We report on the computational design of a three-layered sandwich cluster, Na5B7, on the basis of global-minimum (GM) searches and electronic structure calculations. It is shown that the Na5B7 cluster can be described as a charge-transfer complex: Na42+B73−Na+. In this sandwich cluster, the B73− core assumes a molecular wheel in shape and features in-plane hexagonal coordination. The magic 6π/6σ double aromaticity underlies the stability of the B73− molecular wheel, following the (4n + 2) Hückel rule. The tetrahedral Na4 ligand in the sandwich has a Na42+ charge-state, which is the simplest example of three-dimensional aromaticity, spherical aromaticity, or superatom. Its 2σ electron counting renders σ aromaticity for the ligand. Overall, the sandwich cluster has three-fold 6π/6σ/2σ aromaticity. Molecular dynamics simulation shows that the sandwich cluster is dynamically fluxional even at room temperature, with a negligible energy barrier for intramolecular twisting between the B7 wheel and the Na4 ligand. The Na5B7 cluster offers a new example for dynamic structural fluxionality in molecular systems.
Background： Atopic dermatitis （AD） is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic ...diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczemaJAD and to propose Chinese diagnostic criteria for adult/adolescent AD. Methods： A hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients （12 years and over） with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and-investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software. Results： A total of 2662 valid questionnaires were collected （1369 male and 1293 female）. Of all 2662 patients, 2062 （77.5%） patients had the disease after 12 years old, while only 600 （22.5%） patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine （80.4%） patients had the disease for more than 6 months. One thousand one hundred and forty-four （43.0%） patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight （58.2%） patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients. Conclusion： Late-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.
Purpose
Anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) therapy has shown promise in tumor immunotherapy. Our objectives were to measure pre-treatment serum-soluble PD-L1 ...(sPD-L1) levels and to assess the relationships between sPD-L1 levels and clinical characteristics, prognosis, and tumor tissue PD-L1 expression in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
Methods
Pre-treatment serum sPD-L1 levels were measured with an enzyme-linked immunosorbent assay (ELISA) in 81 patients with HBV-related HCC and compared to those in 49 healthy controls. The association between serum sPD-L1 levels and prognosis was assessed using survival analysis. The correlation between paired serum sPD-L1 levels and tumor PD-L1 expression (in resected tissue homogenates) was assessed in a separate group of 20 patients with HBV-related HCC.
Results
Median sPD-L1 concentration in patients with HBV-related HCC was 5.129 (range 0.140–12.391) ng/mL and in healthy controls was 0.836 (range 0.105–2.168) ng/mL (
p
< 0.001). On multivariate analysis, sPD-L1 levels were significant independent predictors of disease-free survival (hazard ratio HR 3.503; 95% confidence interval CI, 1.559–7.871;
p
= 0.002) and overall survival (HR 3.399; 95% CI 1.308–8.831;
p
= 0.012). Positive correlation (r = 0.527,
p
= 0.017) between serum sPD-L1 and tumor PD-L1 expression was observed. Tumor expression of PD-L1 was significantly higher in those with serum sPD-L1 concentrations above vs. below the median level of 5.471 ng/ml (
p
= 0.012).
Conclusions
In patients with HBV-related HCC, serum sPD-L1 concentrations were elevated, and positively correlated with tumor PD-L1 expression. Lower pre-treatment serum sPD-L1 levels were predictors of more favorable disease-free and overall survival. Serum sPD-L1 testing has a potential role in HBV-related HCC disease assessment, systemic therapy choices and survival prediction.
Elemental boron clusters feature double chain structures and hypercoordinate molecular wheels, owing to their electron-deficiency. We report on the structural, electronic, and bonding properties of a ...series of binary Be2B5q (q = +1, 0, −1) clusters using quantum chemical calculations. The cationic cluster assumes an inverse sandwich geometry, being composed of a pentagonal B5 ring and two capping Be atoms. It can be formally described as a charge-transfer Be2+B53−Be2+ complex, with a minor covalent component between the B5 ring and two Be atoms. The B53− unit is shown to be chemically robust with double 6π/2σ aromaticity, suggesting the potential to be developed as a new inorganic ligand. Its 6π framework mimics that of the cyclopentadienyl anion (C5H5−), although a π sextet is not possible in bare boron clusters of similar sizes. The neutral inverse sandwich is similar to the cation, except for a distortion to lower symmetry. The anionic cluster has a molecular wheel structure, governed by double 2π/6σ aromaticity. Thus, sequential reduction in the series leads to a structural transformation from inverse sandwich to molecular wheel, further demonstrating the robustness of the B53− unit with exactly 18 electrons. Although the cationic inverse sandwich and anionic molecular wheel (with 20 electrons) differ by two electrons, they are the same in terms of total number of delocalized π/σ electrons: 6π/2σ versus 2π/6σ. The bicapping Be atoms in an inverse sandwich interact with boron rings in peculiar ways, thus effectively stabilizing the delocalized π framework with respect to the σ one. Double π/σ aromaticity appears to be a crucial bonding concept in boron-based alloy clusters.
After the discovery of fullerene-C60, it took almost two decades for the possibility of boron-based fullerene structures to be considered. So far, there has been no experimental evidence for these ...nanostructures, in spite of the progress made in theoretical investigations of their structure and bonding. Here we report the observation, by photoelectron spectroscopy, of an all-boron fullerene-like cage cluster at B40(-) with an extremely low electron-binding energy. Theoretical calculations show that this arises from a cage structure with a large energy gap, but that a quasi-planar isomer of B40(-) with two adjacent hexagonal holes is slightly more stable than the fullerene structure. In contrast, for neutral B40 the fullerene-like cage is calculated to be the most stable structure. The surface of the all-boron fullerene, bonded uniformly via delocalized σ and π bonds, is not perfectly smooth and exhibits unusual heptagonal faces, in contrast to C60 fullerene.
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