Enhanced Crystal Nucleation in Glass-Forming Liquids by Tensile Fracture in the Glassy State

Crystal nucleation in a supercooled liquid typically attains its maximal rate near the glass transition temperature Tg and slows down with further cooling, becoming exceedingly slow in the glassy state. We report that cooling a liquid well below its Tg can actually increase the rate of nucleation because of tensile fracture. Cooling liquid griseofulvin (an antifungal drug) approximately 80 K below its Tg induces extensive network fracture due to tensile stress from a thermally less expansive container, and reheating the sample above Tg leads to crystallization that otherwise would not occur. An extensive statistical study revealed a direct connection between fracture and crystal nucleation. This phenomenon explains puzzling results in the literature concerning anomalous nucleation in deeply supercooled liquids and is relevant for selecting storage conditions to ensure the physical stability of amorphous drugs

Crack- and Bubble-Induced Fast Crystal Growth of Amorphous Griseofulvin

Physical stability is one of the major concerns in the development of amorphous materials. Herein, we report the fast crystal growth of amorphous griseofulvin initiated by the air bubbles or cracks in the bulk samples. The study of crystallization kinetics revealed that the enhanced crystallizations induced by bubbles or cracks in the bulk could be attributed to the interface-facilitated processes. In addition, the formation of air–liquid or air–solid interfaces in the interior of bulk materials can favor heterogeneous nucleation, thus resulting in a ripple effect on crystallizations. These findings are relevant for understanding of the crystallization behavior of amorphous materials in supercooled liquids and glasses

Crack- and Bubble-Induced Fast Crystal Growth of Amorphous Griseofulvin

Physical stability is one of the major concerns in the development of amorphous materials. Herein, we report the fast crystal growth of amorphous griseofulvin initiated by the air bubbles or cracks in the bulk samples. The study of crystallization kinetics revealed that the enhanced crystallizations induced by bubbles or cracks in the bulk could be attributed to the interface-facilitated processes. In addition, the formation of air–liquid or air–solid interfaces in the interior of bulk materials can favor heterogeneous nucleation, thus resulting in a ripple effect on crystallizations. These findings are relevant for understanding of the crystallization behavior of amorphous materials in supercooled liquids and glasses

Data_Sheet_1_Multi-Omics Analysis After Vaginal Administration of Bacteroides fragilis in Chickens.ZIP

The reproductive tract of chickens is an important organ for egg formation. The vagina is in close contact with the external environment, which may lead to the invasion of a variety of pathogenic bacteria, affect the internal and external quality of eggs, and even increase mortality and cause economic loss. In recent years, probiotics as a substitute for antibiotics have brought economic benefits in livestock and poultry production. In the present study, we investigated the effects of vaginal administration of Bacteroides fragilis on the cloacal microbiota, vaginal transcriptome and metabolomics of chickens and evaluated the beneficial potential of B. fragilis. The results showed that B. fragilis treatment could affect the microbial composition of the cloaca. Transcriptome analysis found that the immune-related genes CCN3, HAS2, and RICTOR were upregulated, that the inflammatory genes EDNRB, TOX, and NKX2-3 were downregulated, and that DEGs were also enriched in the regulation of the inflammatory response, cellular metabolism, and synaptic response pathways. In addition, the differential metabolites were mainly related to steroid hormone biosynthesis, unsaturated fatty acid biosynthesis, and arachidonic acid metabolism, and we identified associations between specific differential metabolites and genes. Overall, this study provides a theoretical basis for the application of B. fragilis as a potential probiotic in livestock and poultry production.</p

DataSheet_1_Synthesis and Evaluation of Technetium-99m-Labeled pH (Low) Insertion Peptide Variant 7 for Early Diagnosis of MDA-MB-231 Triple-Negative Breast Cancer by Targeting the Tumor Microenvironment.pdf

ObjectiveTo prepare technetium-99m (99mTc)-labeled pH (low) insertion peptide variant 7 [pHLIP (Var7)] and carry out small-animal single-photon-emission computed tomography (SPECT)/computed tomography (CT) imaging of tumor-bearing nude mice in vivo to study its value in the early diagnosis of triple-negative breast cancer (TNBC).MethodsThe pHLIP (Var7) sequence was synthesized via solid-phase peptide synthesis. Four amino acids, Gly-(D)-Ala-Gly-Gly, were attached to the N-terminus of pHLIP (Var7) to form a strong chelating group containing an N4 structure. The peptide was labeled with 99mTc using a direct labeling method. We determined the in vitro binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells. Serial biodistribution studies and small-animal SPECT/CT imaging in MDA-MB-231 TNBC-bearing mice were performed using 99mTc-pHLIP (Var7).ResultsThe radiochemical yield and purity of 99mTc-pHLIP (Var7) were 99.49 ± 0.17% and 99.63 ± 0.44%, respectively. The radiochemical purity was still more than 96% after 24 h in serum. The binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells continuously increased in an acidic environment and was significantly higher than the cell-binding fraction (P 99mTc-kVar7 at different pH values (pH = 6.0, 6.5, 7.0 and 7.4) at each time point (P 99mTc-pHLIP (Var7) in tumors at each time point was significantly greater than that of 99mTc-kVar7 (P 99mTc-pHLIP (Var7) but could not be imaged after injection of 99mTc-kVar7.Conclusion99mTc-pHLIP (Var7) showed a high radiochemical yield and stability and was highly concentrated in tumor tissues. Although there was strong radioactive background in the abdomen of tumor-bearing nude mice, it did not hinder early diagnosis of TNBC.</p

Precise design of highly isoform-selective p21-activated kinase 4 inhibitors: computational insights into the selectivity mechanism through molecular dynamics simulation and binding free energy calculation

Understanding the selectivity mechanisms of inhibitors towards highly similar protein kinases is the first step in discovering new selective candidate for satisfactory safety profile. P21-activated kinases (PAKs) are pertain to a family of serine/threonine (Ser/Thr) protein kinases, which are the first Rho family GTPase-regulated kinases identified and served as important downstream mediators of Ras-Rac and Cdc42 function. Among PAKs, PAK4 is emerging as a promising target for cancer treatment. Since the PAK2 inhibition correlates with increased acute cardiovascular toxicity, which may be enhanced by PAK1 inhibitor, selective inhibition of PAK4 over PAK1 is crucial in discovering safe anticancer candidates with optimal therapeutic efficacy. While the conserved ATP-binding pockets of both PAK1/4 make it challenging to discriminating selective inhibitors between PAK1 and PAK4, thus the selectivity mechanism of PAK1/4 inhibitors will be explored in this present study through, computational strategies which combine molecular docking, structural comparison, molecular dynamics simulation and molecular mechanics/generalized Born surface area calculation. The research would provide valuable insight into the selectivity mechanism of PAK4 inhibitors over PAK1 and thus be helpful for designing selective PAK4 inhibitors. Communicated by Ramaswamy H. Sarma</p

In Situ Generated HypoIodite Activator for the C2 Sulfonylation of Heteroaromatic <i>N</i>‑oxides

A mild approach for direct C2 sulfonylation of heteroaromatic <i>N</i>-oxides with sulfonyl hydrazides affording 2-sulfonyl quinolines/pyridines has been developed. A variety of heteroaromatic <i>N</i>-oxides and sulfonyl hydrazides participate effectively in this transformation which uses hypoiodites (generated in situ from NaI and TBHP) as a means of substrate activators. In this reaction, the <i>N</i>-oxide plays a dual role, acting as a traceless directing group as well as a source of oxygen atom

Data_Sheet_1_Global Patterns and Drivers of Litter Decomposition Under Nitrogen Enrichment: A Meta-Analysis.docx

Nitrogen (N) enrichment has substantially altered patterns of terrestrial litter decomposition, with positive, neutral, and negative effects. However, the general response patterns and drivers of litter decomposition to N enrichment rates are poorly understood, and how litter decomposition has changed under the N enrichment rate, especially in different ecosystems, still requires further study. We reviewed 118 published papers dealing with litter mass remaining after N enrichment to assess the influences of various environmental and experimental factors on the relationships between N enrichment and litter decomposition in grasslands, forests, and wetland ecosystems. The results indicated that N enrichment had an insignificant effect on litter decomposition globally. However, the effects varied greatly among ecosystem types, with an increase in litter decomposition of 3.91% in grasslands and 1.82% in wetlands and a decrease of 1.23% in forests. When forests were subdivided into plantations, primary, and secondary forests, the results showed that N enrichment significantly slowed litter decomposition rate by 2.96% in plantations but had no significant influence in primary and secondary forests. However, litter decomposition was significantly influenced by the level of N addition in plantations and secondary forests, with an increase in litter mass loss at low N addition (50 kg N ha–1 year–1) and a decrease in litter mass loss at high N addition (>50 kg N ha–1 year–1). The magnitude and direction of the N effect are affected by experimental and environmental factors. Specifically, mixed N enrichment (for example, urea and glycine) exerted a stronger effect on litter decomposition compared with an N fertilizer alone. Our findings indicated the different effects of N on litter decomposition in forests and grasslands and knowledge which will greatly advance our ability to accurately evaluate and predict global C cycling under increased N deposition, which should improve future models of global biogeochemical cycling.</p

Additional file 1 of Experimental periodontitis induced hypoadiponectinemia by IRE1α-mediated endoplasmic reticulum stress in adipocytes

Supplementary Material