Fabrication of Self-Wrinkling Polymer Films with Tunable Patterns through an Interfacial-Fuming-Induced Surface Instability Process.

Inspired by the superglue fuming method for fingerprint collection, this study developed a novel interfacial-fuming-induced surface instability process to generate wrinkled patterns on polymeric substrates. High-electronegativity groups are introduced on the substrate surface to initiate the polymerization of monomer vapors, such as ethyl cyanoacrylate, which results in the formation of a stiff poly(ethyl cyanoacrylate) capping layer. Moreover, interfacial polymerization resulted in the covalent bonding of the substrate, which led to the volumetric shrinkage of the composite and the accumulation of compressive strain. This process ultimately resulted in the development and stabilization of wrinkled surface morphologies. The authors systematically examined parameters such as the modulus of the epoxy substrate, prestrain, the flow rate of fuming, and operating temperature. The aforementioned technique can be easily applied to architectures with complex outer morphologies and inner surfaces, thereby enabling the construction of surface patterns under ambient conditions without vacuum limitations or precise process control. This study is the first to combine fuming-induced interfacial polymerization with surface instability to create robust wrinkles. The proposed method enables the fabrication of intricate microwrinkled patterns and has considerable potential for use in various practical applications, including microfluidics, optical components, bioinspired adhesive devices, and interfacial engineering.

Shear banding in monodisperse polymer melt.

We performed a series of molecular dynamics simulations on monodisperse polymer melts to investigate the formation of shear banding. Under high shear rates, shear banding occurs, which is intimately accompanied by the entanglement heterogeneity. Interestingly, the same linear relationship between the end-to-end distance Ree and entanglement density Z is observed at homogeneous flow before the onset of shear banding and at the shear banding state, where Ree ∼ ln(Wi0.87)-ξ0Z is proposed as the criterion to describe the dynamic force balance of the molecular chain in flow with a high rate. Deviating from this relation leads to a force imbalance and results in the emergence of shear banding. We establish a scaling relation between the disentanglement rate Vd and the Weissenberg number Wi as Vd∼Wi0.87 for stable flow in homogeneous shear and shear banding states. The formation of shear banding prevents chains from further stretching and disentanglement. The transition from homogeneous shear to shear banding partially dissipates the increased free energy from shear and reduces the free energy of the system.

Bond Orientation-Determined Enthalpic Stress in Polymer Glasses upon Deformation.

The mechanical properties of polymer glass are determined by both intermolecular local packing structures and aligned intrachain configurations. These configurations involve multiple space scales, and the underlying mechanism is not well understood yet. By applying mechanical stimulation to cold-drawn polymer glasses, the present simulation work shows a one-to-one correspondence between arising retractive stress and the segment orientation parameter on the length scale of the intrachain connecting bond. Such retractive stress is a newly produced enthalpic stress when segment orientation on the length scale of bonds and particle mobility coexist. This reveals a potential mechanism of how the intrachain orientation on the length scale of bonds influences the mechanical behaviors of polymer glasses.

Screening of a high-yield strain of avermectin B1a by colony analysis in situ / Selección in situ de una cepa de alto rendimiento de avermectina B1a mediante análisis de colonias

Avermectin, an agricultural antibiotic, is widely used as an agricultural insecticide and an important lead compound of antibiotics. It is manufactured by Streptomyces avermitilis through fermentation. Manufacturers pay special attention to screening for strains with high fermentation capacity based on morphological properties of the colony and by the result of shake flask fermentation. These traditional screening methods are time-consuming and labor-intensive and require specialized equipment. Moreover, evaluation of colony appearance is highly subjective. To improve and accelerate the screening process, we developed a rapid in situ screening method. Forty-four strains isolated naturally from the spores of industrial high-yielding strains were studied. The data show that the colony fermentation titer is highly correlated with the yield from the shake flask fermentation of avermectin, and the Pearson’s R is 0.990. The total titer of avermectins by shake flask fermentation is also highly correlated with the B1a titer (Pearson’s R is 0.994). This result also shows that strains can be quickly screened by analyzing the colony titer. Pigment rings of the colonies that appeared after growing and maturing on the new medium plate were analyzed. The chosen colonies were directly marked and punched and then extracted with methanol. The fermentation ability can be evaluated by measuring the absorbance at 245 nm. This methodology can be applied in both natural breeding and mutation breeding conditions. By continuously breeding from 2008 to 2020, the flask titer of avermectin B1a increased from 4582 ± 483 to 9197 ± 1134 μg/mL.(AU)

Screening of a high-yield strain of avermectin B1a by colony analysis in situ.

Avermectin, an agricultural antibiotic, is widely used as an agricultural insecticide and an important lead compound of antibiotics. It is manufactured by Streptomyces avermitilis through fermentation. Manufacturers pay special attention to screening for strains with high fermentation capacity based on morphological properties of the colony and by the result of shake flask fermentation. These traditional screening methods are time-consuming and labor-intensive and require specialized equipment. Moreover, evaluation of colony appearance is highly subjective. To improve and accelerate the screening process, we developed a rapid in situ screening method. Forty-four strains isolated naturally from the spores of industrial high-yielding strains were studied. The data show that the colony fermentation titer is highly correlated with the yield from the shake flask fermentation of avermectin, and the Pearson's R is 0.990. The total titer of avermectins by shake flask fermentation is also highly correlated with the B1a titer (Pearson's R is 0.994). This result also shows that strains can be quickly screened by analyzing the colony titer. Pigment rings of the colonies that appeared after growing and maturing on the new medium plate were analyzed. The chosen colonies were directly marked and punched and then extracted with methanol. The fermentation ability can be evaluated by measuring the absorbance at 245 nm. This methodology can be applied in both natural breeding and mutation breeding conditions. By continuously breeding from 2008 to 2020, the flask titer of avermectin B1a increased from 4582 ± 483 to 9197 ± 1134 µg/mL.

Activation of the human chemokine receptor CX3CR1 regulated by cholesterol.

As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand CX3CL1, which shows notable potential as a therapeutic target in atherosclerosis, cancer, and neuropathy. However, the drug development of CX3CR1 is hampered partially by the lack of structural information. Here, we present two cryo-electron microscopy structures of CX3CR1-Gi1 complexes in ligand-free and CX3CL1-bound states at 2.8- and 3.4-Å resolution, respectively. Together with functional data, the structures reveal the key factors that govern the recognition of CX3CL1 by both CX3CR1 and US28. A much smaller conformational change of helix VI upon activation than previously solved class A GPCR-Gi complex structures is observed in CX3CR1, which may correlate with three cholesterol molecules that play essential roles in conformation stabilization and signaling transduction. Thus, our data deepen the understanding of cholesterol modulation in GPCR (G protein-coupled receptor) signaling and provide insights into the diversity of G protein coupling.

Comparative Transcriptome Profiling Reveals Defense-Related Genes Against Ralstonia solanacearum Infection in Tobacco.

Bacterial wilt (BW) caused by Ralstonia solanacearum (R. solanacearum), is a vascular disease affecting diverse solanaceous crops and causing tremendous damage to crop production. However, our knowledge of the mechanism underlying its resistance or susceptibility is very limited. In this study, we characterized the physiological differences and compared the defense-related transcriptomes of two tobacco varieties, 4411-3 (highly resistant, HR) and K326 (moderately resistant, MR), after R. solanacearum infection at 0, 10, and 17 days after inoculation (dpi). A total of 3967 differentially expressed genes (DEGs) were identified between the HR and MR genotypes under mock condition at three time points, including1395 up-regulated genes in the HR genotype and 2640 up-regulated genes in the MR genotype. Also, 6,233 and 21,541 DEGs were induced in the HR and MR genotypes after R. solanacearum infection, respectively. Furthermore, GO and KEGG analyses revealed that DEGs in the HR genotype were related to the cell wall, starch and sucrose metabolism, glutathione metabolism, ABC transporters, endocytosis, glycerolipid metabolism, and glycerophospholipid metabolism. The defense-related genes generally showed genotype-specific regulation and expression differences after R. solanacearum infection. In addition, genes related to auxin and ABA were dramatically up-regulated in the HR genotype. The contents of auxin and ABA in the MR genotype were significantly higher than those in the HR genotype after R. solanacearum infection, providing insight into the defense mechanisms of tobacco. Altogether, these results clarify the physiological and transcriptional regulation of R. solanacearum resistance infection in tobacco, and improve our understanding of the molecular mechanism underlying the plant-pathogen interaction.

Effects of Chemotherapy on Serum Lipids in Chinese Postoperative Breast Cancer Patients.

PURPOSE: Chemotherapy is a comprehensive therapy for breast cancer; nevertheless, its associated adverse effects are drawing increasing attention with the continuous improvement of the efficacy. The changes in serum lipids of breast cancer patients caused by chemotherapy have been reported by previous studies, whereby the former increase the incidence rate of cardiovascular disorders. However, the variations in the changes of serum lipids with different chemotherapy regimens have seldom been reported. METHODS: From January 2011 to December 2017, 1740 breast cancer patients treated with chemotherapy were recruited at the First Affiliated Hospital of Nanjing Medical University. The chemotherapy regimens included anthracycline-based, taxane-based, and anthracycline-plus-taxane-based regimens, dose-dense and standard-interval regimens. Lipid profiles that contained TG (triglyceride), TC (total cholesterol), HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol) and Lpa (lipoprotein a) levels were collected prior to the first, second and last cycles of chemotherapy. The changes of serum lipids with the same or different chemotherapy regimens were analyzed and compared. RESULTS: It was observed that the levels of TG, TC, LDL-C and Lpa increased significantly while that of HDL-C decreased after adjuvant chemotherapy in breast cancer patients (P<0.05). Besides, dose-dense regimens had more influence in TG and HDL-C and less influence in TC and LDL-C than standard-interval regimens. HDL-C was more sensitive to anthracycline-based regimens than taxane-based regimens. The level of TG with anthracycline-plus-taxane-based regimens was higher than that with only anthracycline-based or taxane-based regimens, and the level of HDL-C with anthracycline-plus-taxane-based regimen showed lower than that with taxane-based regimen. CONCLUSION: In summary, this study proposed that dyslipidemia was strongly associated with chemotherapy in Chinese breast cancer patients after operative treatment. Furthermore, the changes in levels of serum lipids varied among patients with different chemotherapy regimens and taxane had less effect on dyslipidemia than anthracycline.

The analysis of differential diagnosis of benign and malignant thyroid nodules based on ultrasound reports.

BACKGROUND: Thyroid cancer is a common endocrine tumor, the incidence of which is increasing each year. Early diagnosis and treatment can effectively prevent thyroid cancer. This article uses Chinese's ultrasound reports to determine the value of early diagnosis. METHODS: The clinical data center of the First Affiliated Hospital of Nanjing Medical University was screened for patients diagnosed with a thyroid nodule, who had undergone a thyroid function test, ultrasound records and pathological assessment. A total of 811 patients with a total of 1,290 pathologically confirmed nodules (506 benign and 784 malignant) were enrolled. Logistic regression was used to analyze the variables that significantly affected malignant nodules. The sensitivity and specificity of ultrasound thyroid imaging-reporting and data system (TI-RADS) classification results for benign and malignant tumors were calculated. RESULTS: The age of the patients had a very significant difference in the classification of benign and malignant nodules (P<0.001), and the marital status was significantly different (P<0.05). Gender and medical insurance had no significant effect (P>0.05). Thyroglobulin (TG), free thyroxine (FT4), and free triiodothyronine (FT3) had significant effects (P=0.003) on the incidence of malignant nodules in patients, while thyroid-stimulating hormone (TSH) had no significant effect (P>0.05). Ultrasound analysis showed a Youden's index of 78.97%, a positive predictive value of 93.20%, and a negative predicted value of 84.10% at the most excellent classification effect. The sensitivity was 89.0%, the specificity was 89.9%; much greater than the classification model based on the thyroid function test (sensitivity =80.6%, specificity =55.8%). CONCLUSIONS: The present study verifies the effectiveness of using TI-RADS classification for diagnosis of benign and malignant thyroid nodules, and explores the use of new analysis methods for clinical data. To reduce dependence on the doctors, ultrasound image data and clinical phenotypic data can be further used to assist clinical decision making.

Numerical calculation of free-energy barriers for entangled polymer nucleation.

The crystallization of entangled polymers from their melt is investigated using computer simulation with a coarse-grained model. Using hybrid Monte Carlo simulations enables us to probe the behavior of long polymer chains. We identify solid-like beads with a centrosymmetry local order parameter and compute the nucleation free-energy barrier at relatively high supercooling with adaptive-bias windowed umbrella sampling. Our results demonstrate that the critical nucleus sizes and the heights of free-energy barriers do not significantly depend on the molecular weight of the polymer; however, the nucleation rate decreases with the increase in molecular weight. Moreover, an analysis of the composition of the critical nucleus suggests that intra-molecular growth of the nucleated cluster does not contribute significantly to crystallization for this system.

Detecting pioglitazone use and risk of cardiovascular events using electronic health record data in a large cohort of Chinese patients with type 2 diabetes.

BACKGROUND: Pioglitazone may have a protective effect against cardiovascular disease risk among type 2 diabetes (T2D) patients, but evidence from China is lacking. This study investigated the association using electronic health records (EHR) data from a Chinese cohort of T2D patients. METHODS: All T2D patients from the First Affiliated Hospital of Nanjing Medical University who were prescribed at least one oral antidiabetic drug and were aged ≥18 years between 1 July 2005 and 30 June 2017 were eligible for inclusion (n = 71 783). Pioglitazone use was determined in 6-month study intervals, with outcome events of myocardial infarction (MI), ischemic stroke, and heart failure. Poisson regression was used to estimate adjusted rate ratios (RRs) with 95% confidence intervals (CIs). RESULTS: In multivariable analysis adjusted for potential confounders, pioglitazone use, compared with no use, was associated with a significant 39% decreased risk of MI (RR = 0.61; 95% CI = 0.42-0.90; P = 0.012). Pioglitazone use was also associated with a non-significant reduction in risk of heart failure or stroke. When MI, heart failure, and stroke were combined as a composite outcome, pioglitazone use was associated with a 30% decrease in risk (RR = 0.70; 95% CI = 0.56-0.88; P = 0.002). CONCLUSIONS: This study demonstrates that applying informatics tools to a large EHR database could be a good way to efficiently conduct clinical observational research. In addition, the findings validated the favorable effect of pioglitazone on the risk of MI among T2D patients in China, with the use of pioglitazone decreasing the risk of MI among those with T2D.

Concordance assessment of Watson for Oncology in breast cancer chemotherapy: first China experience.

BACKGROUND: IBM Watson for Oncology (WFO) is an artificial intelligence cognitive computing system that provides confidence-ranked, evidence-based treatment recommendations for cancer. We examine the level of agreement for breast cancer chemotherapy between WFO recommended and clinical use in a large population of breast cancer cases. METHODS: A total of 1,301 breast cancer patients were reviewed in The First Affiliated Hospital with Nanjing Medical University, China from June 2013 to December 2017. Patients' data were entered manually into WFO by the trained senior oncology fellows. Chemotherapy recommendations were provided in 3 categories, "Recommended", "For Consideration", and "Not Recommended". Concordance was achieved when oncologists' treatment suggestions were in the "Recommended" or "For Consideration" categories. RESULTS: The chemotherapy regimen concordance was 69.4% among all breast cancer cases, 65.0% among the cases in adjuvant chemotherapy (AC) group and 96.7% among the cases in neoadjuvant chemotherapy (NAC) group. The concordance varied greatly in subset analysis with respect to TNM stage and molecular subtype. AC recommendations were concordant in 92.3% of stage III breast cancer and 50.8% of stage I. However, the concordance varied by molecular subtype, which was higher for triple negative breast cancer (89.3%) than others. The chemotherapy regimen concordance declined significantly with increasing age, except for the age group 41-50 years. CONCLUSIONS: Chemotherapy regimens provided by WFO did not exhibit a high degree of agreement with those suggested by oncologists in clinical practice in the hospital in China. The current effort is underway to enhance WFO's capabilities as a cognitive decision support tool by incorporating regional guidelines, enabling oncologists and patients to benefit from WFO worldwide.

Flow-induced density fluctuation assisted nucleation in polyethylene.

The nucleation processes of polyethylene under quiescent and shear flow conditions are comparatively studied with all-atom molecular dynamics simulations. Under both conditions, nucleation is demonstrated to be a two-step process, which, however, proceeds via different intermediate orders. Quiescent nucleation is assisted by local order structures, while flow-induced nucleation is promoted by density fluctuation, which is a coupling effect of conformational and orientational orderings. Flow drives the transformation from flexible chains to conformational ordered segments and circumvents the entropic penalty, which is the most peculiar and rate-limited step in polymer crystallization. This work suggests that the acceleration of the nucleation rate in orders of magnitude by flow is mainly attributed to the different kinetics pathway via conformational/orientational ordering-density fluctuation-nucleation.

Extraction of BI-RADS findings from breast ultrasound reports in Chinese using deep learning approaches.

BACKGROUND: The wide adoption of electronic health record systems (EHRs) in hospitals in China has made large amounts of data available for clinical research including breast cancer. Unfortunately, much of detailed clinical information is embedded in clinical narratives e.g., breast radiology reports. The American College of Radiology (ACR) has developed a Breast Imaging Reporting and Data System (BI-RADS) to standardize the clinical findings from breast radiology reports. OBJECTIVES: This study aims to develop natural language processing (NLP) methods to extract BI-RADS findings from breast ultrasound reports in Chinese, thus to support clinical operation and breast cancer research in China. METHODS: We developed and compared three different types of NLP approaches, including a rule-based method, a traditional machine learning-based method using the Conditional Random Fields (CRF) algorithm, and deep learning-based approaches, to extract all BI-RADS finding categories from breast ultrasound reports in Chinese. RESULTS: Using a manually annotated dataset containing 540 reports, our evaluation shows that the deep learning-based method achieved the best F1-score of 0.904, when compared with rule-based and CRF-based approaches (0.848 and 0.881 respectively). CONCLUSIONS: This is the first study that applies deep learning technologies to BI-RADS findings extraction in Chinese breast ultrasound reports, demonstrating its potential on enabling international collaborations on breast cancer research.

Coupling between intra- and inter-chain orderings in flow-induced crystallization of polyethylene: A non-equilibrium molecular dynamics simulation study.

Non-equilibrium molecular dynamics simulations have been performed to study the molecular mechanism of flow-induced crystallization (FIC) of polyethylene (PE). The end-to-end distance of chain Rete and the content of trans conformation Ctrans are extracted out to represent intra-chain conformation ordering at whole chain and segment levels, respectively, while orientation correlation function P, density ρ, and bond orientational order parameter Q4 are taken to depict inter-chain orders. Imposing the extension induces the intra-chain conformational ordering to occur first, which further couples with the inter-chain order and results in the formation of hexagonal packing. Further increasing strain leads to the appearance of orthorhombic order. The results demonstrate that the FIC of PE proceeds via a multi-stage ordering process, during which coupling occurs among stress, intra-chain conformation, and inter-chain orientation and density orderings. Analyzing the flow-induced energy evolution unveils that not only entropy but also energy plays an important role in the FIC.