Synthesis of Oxazolidines and Dihydroxazines via Cyclization of α‑Aminated Ketones

A new approach to oxazolidines and dihydroxazines was developed by regioselective cyclization of α-aminated ketones under transition metal-free conditions. Oxazolidine derivatives were generated in the presence of chloro benziodoxole and TFA, while dihydroxazines were formed without a hypervalent iodine reagent. The reaction was performed under room temperature and gave the products in good to excellent yields

Terrace-Rich Ultrathin PtCu Surface on Earth-Abundant Metal for Oxygen Reduction Reaction

The activity and stability of the platinum electrode toward the oxygen reduction reaction are size-dependent. Although small nanoparticles have high Pt utilization, the undercoordinated Pt sites on their surface are assumed to have too strong oxygen binding strength, thus often leading to compromised activity and surface instability. Herein, we report an extended nanostructured PtCu ultrathin surface to reduce the number of low-coordination sites without sacrificing the electrochemical active surface area (ECSA). The surface shows (111)-oriented characteristics, as proven by electrochemical probe reactions and spectroscopies. The PtCu surface brings over an order of magnitude increase in specific activity relative to commercial Pt/C and nearly 4-fold enhancement in ECSA compared to traditional thin films. Moreover, due to the weak absorption of air impurities (e.g., SO2, NO, CO) on highly coordinated sites, the catalyst displays enhanced contaminant tolerance compared with nanoparticulate Pt/C. This work promises a broad screening of extended nanostructured surface catalysts for electrochemical conversions

Complexation Behaviors of a Tridentate Phenanthroline Carboxamide Ligand with Trivalent f‑Block Elements in Different Anion Systems: A Thermodynamic and Crystallographic Perspective

The counteranion has a strong influence on the complexation behavior of tridentate phenanthroline carboxamide ligands with actinides and lanthanides, but the thermodynamic and underlying interaction mechanism at the molecular level is still not clear. In this work, a tridentate ligand, N-ethyl-N-tolyl-2-amide-1,10-phenanthroline (Et-Tol-PTA), was synthesized, and the effects of different anions (Cl–, NO3–, and ClO4–) on the complexation behavior of Et-Tol-PTA with typical lanthanides were thoroughly studied by using 1H nuclear magnetic resonance (NMR) spectroscopy, ultraviolet–visible (UV–vis) spectrophotometry, and single-crystal X-ray diffraction. The NMR spectroscopic titration of Lu­(III) showed that there were three species (1:1, 2:1, and 3:1 ligand–metal complexes) formed in Cl– solution systems while two species (2:1 and 1:1) were formed in NO3– and ClO4– solution systems. When Et-Tol-PTA was titrated with La­(III), two species (2:1 and 1:1) were formed in NO3– systems and only one species (1:1) was formed in Cl– and ClO4– systems. In addition, the stability constant was determined via UV–vis spectroscopic titration, which showed that the complexation strength between Et-Tol-PTA and Eu­(III) decreased in the following order: ClO4– > NO3– > Cl–. This indicated that Et-Tol-PTA had the strongest complexation ability with Eu­(III) in the ClO4– system. The structures of Et-Tol-PTA complexed with EuCl3, Eu­(NO3)3, and Eu­(ClO4)3 were further elucidated by single-crystal X-ray diffraction and agreed well with the results of UV–vis titration experiments. The results of this work revealed that the mechanisms of complexation of lanthanides with the asymmetric ligand Et-Tol-PTA were strongly affected by different anionic environments in solution and in the solid state. These findings may lead to the improvement of the separation of trivalent actinides and lanthanides in nuclear waste

Table_1_Integrated analysis of multi-omics data reveals T cell exhaustion in sepsis.xlsx

BackgroundSepsis is a heterogeneous disease, therefore the single-gene-based biomarker is not sufficient to fully understand the disease. Higher-level biomarkers need to be explored to identify important pathways related to sepsis and evaluate their clinical significance.MethodsGene Set Enrichment Analysis (GSEA) was used to analyze the sepsis transcriptome to obtain the pathway-level expression. Limma was used to identify differentially expressed pathways. Tumor IMmune Estimation Resource (TIMER) was applied to estimate immune cell abundance. The Spearman correlation coefficient was used to find the relationships between pathways and immune cell abundance. Methylation and single-cell transcriptome data were also employed to identify important pathway genes. Log-rank test was performed to test the prognostic significance of pathways for patient survival probability. DSigDB was used to mine candidate drugs based on pathways. PyMol was used for 3-D structure visualization. LigPlot was used to plot the 2-D pose view for receptor-ligand interaction.ResultsEighty-four KEGG pathways were differentially expressed in sepsis patients compared to healthy controls. Of those, 10 pathways were associated with 28-day survival. Some pathways were significantly correlated with immune cell abundance and five pathways could be used to distinguish between systemic inflammatory response syndrome (SIRS), bacterial sepsis, and viral sepsis with Area Under the Curve (AUC) above 0.80. Seven related drugs were screened using survival-related pathways.ConclusionSepsis-related pathways can be utilized for disease subtyping, diagnosis, prognosis, and drug screening.</p

DataSheet_1_Integrated analysis of multi-omics data reveals T cell exhaustion in sepsis.pdf

BackgroundSepsis is a heterogeneous disease, therefore the single-gene-based biomarker is not sufficient to fully understand the disease. Higher-level biomarkers need to be explored to identify important pathways related to sepsis and evaluate their clinical significance.MethodsGene Set Enrichment Analysis (GSEA) was used to analyze the sepsis transcriptome to obtain the pathway-level expression. Limma was used to identify differentially expressed pathways. Tumor IMmune Estimation Resource (TIMER) was applied to estimate immune cell abundance. The Spearman correlation coefficient was used to find the relationships between pathways and immune cell abundance. Methylation and single-cell transcriptome data were also employed to identify important pathway genes. Log-rank test was performed to test the prognostic significance of pathways for patient survival probability. DSigDB was used to mine candidate drugs based on pathways. PyMol was used for 3-D structure visualization. LigPlot was used to plot the 2-D pose view for receptor-ligand interaction.ResultsEighty-four KEGG pathways were differentially expressed in sepsis patients compared to healthy controls. Of those, 10 pathways were associated with 28-day survival. Some pathways were significantly correlated with immune cell abundance and five pathways could be used to distinguish between systemic inflammatory response syndrome (SIRS), bacterial sepsis, and viral sepsis with Area Under the Curve (AUC) above 0.80. Seven related drugs were screened using survival-related pathways.ConclusionSepsis-related pathways can be utilized for disease subtyping, diagnosis, prognosis, and drug screening.</p

Importance of Robust and Reliable Nanochannel Sealing for Enhancing Drug Delivery Efficacy of Hollow Mesoporous Nanocontainer

Hollow mesoporous silica nanoparticles (HMSNPs) have been widely explored in the biomedical field as drug delivery nanocarriers by virtue of their large hollow cavity. However, the connectivity between the internal cavity and the outside environment by numerous nanochannels on the mesoporous shell allows for possible drug leakage, leading to nonsufficient drug loading due to unreliable capping of the nanopores. In addition, the issue of ensuring effective utilization of the hollow cavity for achieving high drug loading capacity of HMSNPs is seldom addressed. Thus, in this work, HMSNPs with the diameter of about 400 nm were prepared and completely encapsulated by growing an ultrathin nanolayer of aluminum oxide (Al2O3) of about 20 nm on the surface of the mesoporous shell with template-assisted sol–gel chemistry. The robust sealing layer of Al2O3 can ensure “zero release” of the delivery system under neutral conditions, which is crucial for achieving high drug loading capacity by physical encapsulation of cargo molecules within the hollow cavity. The Al2O3-coated HMSNP (denoted as HMSNP Al2O3 can improve the drug loading capacity up to about 35 wt %, realizing loading efficiency as high as ten times the maximum value without Al2O3 under the same conditions. Besides, the encapsulation nanolayer of Al2O3 would be degraded under the acidic condition to realize pH-responsive controlled release of the cargo molecules. We further carried out in vitro drug delivery experiments by using human epithelial cervix adenocarcinoma (HeLa) cells as the model and revealed much higher drug delivery efficacy within cancer cells compared to free doxorubicin (Dox) and Dox loaded HMSNP without sealing (HMSNP@Dox). The current work not only clarifies the importance of the surface encapsulation of the nanochannels when using HMSNPs as nanocarriers, but also provides a strategy to prepare fully encapsulated core–shell structures, which holds great potential for physically encapsulating various theranostic reagents in the biomedical field

High-Strength Magnetic Hydrogels with Photoweldability Made by Stepwise Assembly of Magnetic-Nanoparticle-Integrated Aramid Nanofiber Composites

Hydrogels capable of transforming in response to a magnetic field hold great promise for applications in soft actuators and biomedical robots. However, achieving high mechanical strength and good manufacturability in magnetic hydrogels remains challenging. Here, inspired by natural load-bearing soft tissues, a class of composite magnetic hydrogels is developed with tissue-mimetic mechanical properties and photothermal welding/healing capability. In these hydrogels, a hybrid network involving aramid nanofibers, Fe3O4 nanoparticles, and poly(vinyl alcohol) is accomplished by a stepwise assembly of the functional components. The engineered interactions between nanoscale constituents enable facile materials processing and confer a combination of excellent mechanical properties, magnetism, water content, and porosity. Furthermore, the photothermal property of Fe3O4 nanoparticles organized around the nanofiber network allows near-infrared welding of the hydrogels, providing a versatile means to fabricate heterogeneous structures with custom designs. Complex modes of magnetic actuation are made possible with the manufactured heterogeneous hydrogel structures, suggesting opportunities for further applications in implantable soft robots, drug delivery systems, human–machine interactions, and other technologies

High-Strength Magnetic Hydrogels with Photoweldability Made by Stepwise Assembly of Magnetic-Nanoparticle-Integrated Aramid Nanofiber Composites

Hydrogels capable of transforming in response to a magnetic field hold great promise for applications in soft actuators and biomedical robots. However, achieving high mechanical strength and good manufacturability in magnetic hydrogels remains challenging. Here, inspired by natural load-bearing soft tissues, a class of composite magnetic hydrogels is developed with tissue-mimetic mechanical properties and photothermal welding/healing capability. In these hydrogels, a hybrid network involving aramid nanofibers, Fe3O4 nanoparticles, and poly(vinyl alcohol) is accomplished by a stepwise assembly of the functional components. The engineered interactions between nanoscale constituents enable facile materials processing and confer a combination of excellent mechanical properties, magnetism, water content, and porosity. Furthermore, the photothermal property of Fe3O4 nanoparticles organized around the nanofiber network allows near-infrared welding of the hydrogels, providing a versatile means to fabricate heterogeneous structures with custom designs. Complex modes of magnetic actuation are made possible with the manufactured heterogeneous hydrogel structures, suggesting opportunities for further applications in implantable soft robots, drug delivery systems, human–machine interactions, and other technologies

High-Strength Magnetic Hydrogels with Photoweldability Made by Stepwise Assembly of Magnetic-Nanoparticle-Integrated Aramid Nanofiber Composites

Hydrogels capable of transforming in response to a magnetic field hold great promise for applications in soft actuators and biomedical robots. However, achieving high mechanical strength and good manufacturability in magnetic hydrogels remains challenging. Here, inspired by natural load-bearing soft tissues, a class of composite magnetic hydrogels is developed with tissue-mimetic mechanical properties and photothermal welding/healing capability. In these hydrogels, a hybrid network involving aramid nanofibers, Fe3O4 nanoparticles, and poly(vinyl alcohol) is accomplished by a stepwise assembly of the functional components. The engineered interactions between nanoscale constituents enable facile materials processing and confer a combination of excellent mechanical properties, magnetism, water content, and porosity. Furthermore, the photothermal property of Fe3O4 nanoparticles organized around the nanofiber network allows near-infrared welding of the hydrogels, providing a versatile means to fabricate heterogeneous structures with custom designs. Complex modes of magnetic actuation are made possible with the manufactured heterogeneous hydrogel structures, suggesting opportunities for further applications in implantable soft robots, drug delivery systems, human–machine interactions, and other technologies

Comparison of Al-CPI with other monomeric type-2 cystatins^a).

a)<p>The Cα of conserved amino acid residues were chosen for all the distance measurements.</p