Application of advanced diffusion models from diffusion weighted imaging in a large cohort study of breast lesions.

BACKGROUND: To evaluate multiple parameters in multiple b-value diffusion-weighted imaging (DWI) in characterizing breast lesions and predicting prognostic factors and molecular subtypes. METHODS: In total, 504 patients who underwent 3-T magnetic resonance imaging (MRI) with T1-weighted dynamic contrast-enhanced (DCE) sequences, T2-weighted sequences and multiple b-value (7 values, from 0 to 3000 s/mm2) DWI were recruited. The average values of 13 parameters in 6 models were calculated and recorded. The pathological diagnosis of breast lesions was based on the latest World Health Organization (WHO) classification. RESULTS: Twelve parameters exhibited statistical significance in differentiating benign and malignant lesions. alpha demonstrated the highest sensitivity (89.5%), while sigma demonstrated the highest specificity (77.7%). The stretched-exponential model (SEM) demonstrated the highest sensitivity (90.8%), while the biexponential model demonstrated the highest specificity (80.8%). The highest AUC (0.882, 95% CI, 0.852-0.912) was achieved when all 13 parameters were combined. Prognostic factors were correlated with different parameters, but the correlation was relatively weak. Among the 6 parameters with significant differences among molecular subtypes of breast cancer, the Luminal A group and Luminal B (HER2 negative) group had relatively low values, and the HER2-enriched group and TNBC group had relatively high values. CONCLUSIONS: All 13 parameters, independent or combined, provide valuable information in distinguishing malignant from benign breast lesions. These new parameters have limited meaning for predicting prognostic factors and molecular subtypes of malignant breast tumors.

Incorporating multiple magnetic resonance diffusion models to differentiate low- and high-grade adult gliomas: a machine learning approach.

Background: Accurate grading of gliomas is a challenge in imaging diagnosis. This study aimed to evaluate the performance of a machine learning (ML) approach based on multiparametric diffusion-weighted imaging (DWI) in differentiating low- and high-grade adult gliomas. Methods: A model was developed from an initial cohort containing 74 patients with pathology-confirmed gliomas, who underwent 3 tesla (3T) diffusion magnetic resonance imaging (MRI) with 21 b values. In all, 112 histogram features were extracted from 16 parameters derived from seven diffusion models [monoexponential, intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), fractional order calculus (FROC), continuous-time random walk (CTRW), stretched-exponential, and statistical]. Feature selection and model training were performed using five randomly permuted five-fold cross-validations. An internal test set (15 cases of the primary dataset) and an external cohort (n=55) imaged on a different scanner were used to validate the model. The diagnostic performance of the model was compared with that of a single DWI model and DWI radiomics using accuracy, sensitivity, specificity, and the area under the curve (AUC). Results: Seven significant multiparametric DWI features (two from the stretched-exponential and FROC models, and three from the CTRW model) were selected to construct the model. The multiparametric DWI model achieved the highest AUC (0.84, versus 0.71 for the single DWI model, P<0.05), an accuracy of 0.80 in the internal test, and both AUC and accuracy of 0.76 in the external test. Conclusions: Our multiparametric DWI model differentiated low- (LGG) from high-grade glioma (HGG) with better generalization performance than the established single DWI model. This result suggests that the application of an ML approach with multiple DWI models is feasible for the preoperative grading of gliomas.

ArsR Family Regulator MSMEG_6762 Mediates the Programmed Cell Death by Regulating the Expression of HNH Nuclease in Mycobacteria.

Programmed cell death (PCD) is the result of an intracellular program and is accomplished by a regulated process in both prokaryotic and eukaryotic organisms. Here, we report a programed cell death process in Mycobacterium smegmatis, an Actinobacteria species which involves a transcription factor and a DNase of the HNH family. We found that over-expression of an ArsR family member of the transcription factor, MSMEG_6762, leads to cell death. Transcriptome analysis revealed an increase in the genes' transcripts involved in DNA repair and homologous recombination, and in three members of HNH family DNases. Knockout of one of the DNase genes, MSMEG_1275, alleviated cell death and its over-expression of programmed cell death. Purified MSMEG_1275 cleaved the M. smegmatis DNA at multiple sites. Overall, our results indicate that the MSMEG_6762 affects cell death and is mediated, at least partially, by activation of the HNH nuclease expression under a stress condition.

Anisotropic Scattering Caused by Apical Oxygen Vacancies in Thin Films of Overdoped High-Temperature Cuprate Superconductors.

There is a hot debate on the anomalous behavior of superfluid density ρ_{s} in overdoped La_{2-x}Sr_{x}CuO_{4} films in recent years. The linear drop of ρ_{s} at low temperatures implies the superconductors are clean, but the linear scaling between ρ_{s} (in the zero temperature limit) and the transition temperature T_{c} is a hallmark of the dirty limit in the Bardeen-Cooper-Schrieffer (BCS) framework [I. Bozovic et al., Nature (London) 536, 309 (2016)NATUAS0028-083610.1038/nature19061]. This dichotomy motivated exotic theories beyond the standard BCS theory. We show, however, that such a dichotomy can be reconciled naturally by the role of increasing anisotropic scattering caused by the apical oxygen vacancies. Furthermore, the anisotropic scattering also explains the "missing" Drude weight upon doping in the optical conductivity, as reported in the THz experiment [F. Mahmood et al., Phys. Rev. Lett. 122, 027003 (2019)PRLTAO0031-900710.1103/PhysRevLett.122.027003]. Therefore, the overdoped cuprates can actually be described consistently by the d-wave BCS theory with the unique anisotropic scattering.

ALA_PDT Promotes Ferroptosis-Like Death of Mycobacterium abscessus and Antibiotic Sterilization via Oxidative Stress.

Mycobacterium abscessus is one of the common clinical non-tuberculous mycobacteria (NTM) that can cause severe skin infection. 5-Aminolevulinic acid photodynamic therapy (ALA_PDT) is an emerging effective antimicrobial treatment. To explore whether ALA_PDT can be used to treat M. abscessus infections, we conducted a series of experiments in vitro. We found that ALA_PDT can kill M. abscesses. Mechanistically, we found that ALA_PDT promoted ferroptosis-like death of M. abscesses, and the ROS scavenger N-Acetyl-L-cysteine (NAC) and ferroptosis inhibitor Ferrostatin-1 (Fer-1) can mitigate the ALA_PDT-mediated sterilization. Furthermore, ALA_PDT significantly up-regulated the transcription of heme oxygenase MAB_4773, increased the intracellular Fe2+ concentration and altered the transcription of M. abscessus iron metabolism genes. ALA_PDT disrupted the integrity of the cell membrane and enhanced the permeability of the cell membrane, as evidenced by the boosted sterilization effect of antibiotics. In summary, ALA_PDT can kill M. abscesses via promoting the ferroptosis-like death and antibiotic sterilization through oxidative stress by changing iron metabolism. The study provided new mechanistic insights into the clinical efficacy of ALA_PDT against M. abscessus.

Mycobacterium tuberculosis Rv0580c Impedes the Intracellular Survival of Recombinant Mycobacteria, Manipulates the Cytokines, and Induces ER Stress and Apoptosis in Host Macrophages via NF-κB and p38/JNK Signaling.

The Mycobacterium tuberculosis (M. tb) genome encodes a large number of hypothetical proteins, which need to investigate their role in physiology, virulence, pathogenesis, and host interaction. To explore the role of hypothetical protein Rv0580c, we constructed the recombinant Mycobacterium smegmatis (M. smegmatis) strain, which expressed the Rv0580c protein heterologously. We observed that Rv0580c expressing M. smegmatis strain (Ms_Rv0580c) altered the colony morphology and increased the cell wall permeability, leading to this recombinant strain becoming susceptible to acidic stress, oxidative stress, cell wall-perturbing stress, and multiple antibiotics. The intracellular survival of Ms_Rv0580c was reduced in THP-1 macrophages. Ms_Rv0580c up-regulated the IFN-γ expression via NF-κB and JNK signaling, and down-regulated IL-10 expression via NF-κB signaling in THP-1 macrophages as compared to control. Moreover, Ms_Rv0580c up-regulated the expression of HIF-1α and ER stress marker genes via the NF-κB/JNK axis and JNK/p38 axis, respectively, and boosted the mitochondria-independent apoptosis in macrophages, which might be lead to eliminate the intracellular bacilli. This study explores the crucial role of Rv0580c protein in the physiology and novel host-pathogen interactions of mycobacteria.

Mycobacterium smegmatis msmeg_3314 is involved in pyrazinamide and fluoroquinolones susceptibility via NAD+/NADH dysregulation.

Aim: To identify and characterize new mycobacterium pyrazinamide (PZA) resistance genes in addition to pncA, rpsA and panD. Materials & methods: To screen a Tn7 M. smegmatis mc2155 transposon library using 50 µM PZA and a PZA hypersensitive mutant (M492) was obtained. MIC was further used to confirm the hypersensitivity of M492 mutant by culturing the mutant in Middlebrook 7H9 liquid medium at 37°C. Results:msmeg_3314 is the gene underlying the hypersensitive phenotype of mutant M492. The observed resistance to PZA and fluoroquinolones involved the alteration of Mycobacterium cell wall permeability and the dissipation of the proton motive force. NAD+/NADH dysregulation and attenuated glyoxylate shunt might underlie the declined scavenging capacity of reactive oxygen species in the msmeg_3314-deficient mutants. Conclusion:msmeg_ 3314 is a novel gene involved in pyrazinamide resistance and might be a new candidate for drugs target.

Mycobacterium tuberculosis PE31 (Rv3477) Attenuates Host Cell Apoptosis and Promotes Recombinant M. smegmatis Intracellular Survival via Up-regulating GTPase Guanylate Binding Protein-1.

The Mycobacterium (M.) tuberculosis comprising proline-glutamic acid (PE) subfamily proteins associate with virulence, pathogenesis, and host-immune modulations. While the functions of most of this family members are not yet explored. Here, we explore the functions of "PE only" subfamily member PE31 (Rv3477) in virulence and host-pathogen interactions. We have expressed the M. tuberculosis PE31 in non-pathogenic Mycobacterium smegmatis strain (Ms_PE31) and demonstrated that PE31 significantly altered the cell facet features including colony morphology and biofilm formation. PE31 expressing M. smegmatis showed more resistant to the low pH, diamide, H2O2 and surface stress. Moreover, Ms_PE31 showed higher intracellular survival in macrophage THP-1 cells. Ms_PE31 significantly down-regulated the production of IL-12p40 and IL-6, while up-regulates the production of IL-10 in macrophages. Ms_PE31 also induced the expression of guanylate-binding protein-1 (GBP-1) in macrophages. Further analysis demonstrates that Ms_PE31 inhibits the caspase-3 activation and reduces the macrophages apoptosis. Besides, the NF-κB signaling pathway involves the interplay between Ms_PE31 and macrophages. Collectively, our finding identified that PE31 act as a functionally relevant virulence factor of M. tuberculosis.

Ultrafine antimony (Sb) nanoparticles encapsulated into a carbon microfiber framework as an excellent LIB anode with a superlong life of more than 5000 cycles.

Antimony (Sb) anode has attracted increasing attention given its high theoretical capacity and suitable working potential. Nonetheless, its practical application is largely hindered by huge volume changes during the cyclic process, resulting in unsatisfactory long-term cycled stabilities at high current density. In this work, large-scale ultrafine Sb nanoparticles are functionally designed to encapsulate into a 3D carbon microfiber framework (CMF) via a scalable electrospinning approach followed by a thermal treatment process. This fabrication strategy effectively avoids the change in the volume of the Sb anode and provides a fast conductive network to serve as an efficient 3D e/Li+ transport pathway. Benefiting from this novel structural design, an ultrafine Sb nanoparticles@carbon microfiber framework (U-Sb-NPs@CMF) composite anode used for lithium-ion batteries (LIBs) delivers a high reversible capacity of 622 mAh g-1 after 200 cycles at 0.5 A g-1 and 507 mAh g-1 after 2000 cycles at 2 Ag-1 and a high-capacity retention of 350 mAh g-1 even after 5000 long-term cycles. These outstanding charge-discharge performances suggest that the U-Sb-NPs@CMF composite is a promising candidate for an anode material in the application of LIBs.

Enhanced Synergetic Catalytic Effect of Mo2C/NCNTs@Co Heterostructures in Dye-Sensitized Solar Cells: Fine-Tuned Energy Level Alignment and Efficient Charge Transfer Behavior.

A highly efficient and stable electrocatalyst with the novel heterostructure of Co-embedded and N-doped carbon nanotubes supported Mo2C nanoparticles (Mo2C/NCNTs@Co) is creatively constructed by adopting the one-step metal catalyzed carbonization-nitridation strategy. Systematic characterizations and density functional theory (DFT) calculations reveal the advanced structural and electronic properties of Mo2C/NCNTs@Co heterostructure, in which the Co-embedded and N-doped CNTs with tunable diameters present electron-donating effect and the work function is correspondingly regulated from 4.91 to 4.52 eV, and the size-controlled Mo2C nanoparticles exhibit Pt-like 4d electronic structure and the well matched work function (4.85 eV) with I-/I3- redox couples (4.90 eV). As a result, the conductive NCNTs@Co substrate with fine-tuned energy level alignment accelerates the electron transportation and the electron migration from NCNTs@Co to Mo2C, and the active Mo2C shows high affinity for I3- adsorption and high charge transfer ability for I3- reduction, which reach a decent synergetic catalytic effect in Mo2C/NCNTs@Co heterostructure. The DSSC with Mo2C/NCNTs@Co CE achieves a high photoelectric conversion efficiency of 8.82% and exceptional electrochemical stability with a residual efficiency of 7.95% after continuous illumination of 200 h, better than Pt-based cell. Moreover, the synergistic catalytic mechanism toward I3- reduction is comprehensively studied on the basis of structure-activity correlation and DFT calculations. The advanced heterostructure engineering and electronic modulation provide a new design principle to develop the efficient, stable, and economic hybrid catalysts in relevant electrocatalytic fields.

Comparison of Microbiomes and Resistomes in Two Karst Groundwater Sites in Chongqing, China.

Karst groundwater is an important water resource, as it accounts for about 15% of the total landscape of the earth and supplies 20% of potable water worldwide. The antibiotics resistance is an emerging global concern, and antibiotics residual and increase of antibiotic resistance genes represent serious global concerns and emerging pollutants. There is no report on the antibiotic resistance genes in groundwater. To survey resistome and microbiome in karst groundwater, two karst water samples were chosen for metagenome and metatranscriptome study, namely the 37th spring (C) and Dongcao spring (R) in Beibei, Chongqing, China. The two sites differ significantly in sulfur content, geochemical parameters, community structure, antibiotic resistance genes, and mechanisms, and these results may be influenced by anthropogenic activities. Combining with the Antibiotic Resistance Genes Database, three types of resistance genes baca, sul2, sul1 are present in R and C, and ant3ia, ermc, tetpa are also present in R. The number of all resistance genes in R was more than C, and Proteobacteria, Bacteroidetes, Nitrospirae are the main sources of antibiotic resistance genes. In addition, a large number of genes related to antibiotic gene transmission and drug resistance were found in both samples. Karst groundwater is an important source of drinking water and a possible venue for the transmission of microbial antibiotic resistance genes. However, few studies addressed this issue in karst groundwater, despite its widespread and great importance to global ecosystem. Karst groundwater is a reservoir for antibiotic resistant genes, and measures to control these resistant genes are urgently needed.

Engineering the Core-Shell-Structured NCNTs-Ni2Si@Porous Si Composite with Robust Ni-Si Interfacial Bonding for High-Performance Li-Ion Batteries.

A new strategy has been innovatively proposed for wrapping the Ni-incorporated and N-doped carbon nanotube arrays (Ni-NCNTs) on porous Si with robust Ni-Si interfacial bonding to form the core-shell-structured NCNTs-Ni2Si@Si. The hierarchical porous silicon core was first fabricated via a novel self-templating synthesis route based on two crucial strategies: in situ thermal evaporation of crystal water from the perlite for producing porous SiO2 and subsequent magnesiothermic reduction of porous SiO2 into porous Si. Ni-NCNTs were subsequently constructed based on the Ni-catalyzed tip-growth mechanism and were further engineered to fully wrap the porous Si microparticles by forming the Ni2Si alloy at the heterojunction interface. When the prepared NCNTs-Ni2Si@Si was evaluated as the anode material for Li-ion batteries, the hierarchical porous system in the Si core and the rich void spaces in carbon nanotube arrays contributed to the remarkable accommodation of volume expansion of Si as well as the significant increase of Li+ diffusion and Si utilization. Moreover, the Ni2Si alloy, which chemically linked the Ni-NCNTs and porous Si, not only provided good electronic contact between the Si core and carbon shell but also effectively prevented the CNTs' detachment from the Si core during cycling. The multifunctional structural design rendered the whole electrode highly stable and active in Li storage, and the electrochemically active NCNTs-Ni2Si@Si electrode delivered a high reversible capacity of 1547 mAh g-1 and excellent cycling stability (85% capacity retention after 600 discharge-charge cycles) at a current density of 358 mA g-1 (0.1 C) as well as good rate performance (778 mAh g-1 at 2 C), showing great potential as an efficient and stable anode for high energy density Li-ion batteries.

Carbon framework microbelt supporting SnOx as a high performance electrode for lithium ion batteries.

Facile preparation of rational SnOx-based electrode materials with excellent electrochemical performance is highly desired for lithium ion batteries (LIBs). In this work, carbon framework microbelt supporting SnOx nanoparticles (CFM-SnOx) were prepared via a facile electrospinning technology and annealing treatment process. The as-synthesized CFM-SnOx electrode exhibits high reversible capacity of 768 mAh g-1 at 0.2 A g-1 after 200 cycles, high rate capacity of 535 mAh g-1 at high current density of 3.2 A g-1. The facile synthesis and superior performance indicate that the as-synthesized CFM-SnOx is a competitive anode material for LIBs.

The Synergistic Effect of Exogenous Glutamine and Rifampicin Against Mycobacterium Persisters.

Persisters, stochastic dormant variants of normal bacteria cell, represent a significant portion of the survivors upon exposure to antibiotics and other environmental stresses, which contributes substantially to high level antibiotics tolerance. Glutamine is a crucial component of the Mycobacteria nitrogen pool that is indispensable for survival upon stresses. To study whether a synergistic effect exists between glutamine and antibiotics against Mycobacterial persisters, the efficacy of rifampicin alone or together with exogenous glutamine upon Mycobacterium smegmatis mc2 155 persisters was monitored. The result showed that glutamine decreases M. smegmatis tolerance to rifampicin upon starvation. The reactive oxygen species level of the strains treated with rifampicin and glutamine increased. The synergism of glutamine and rifampicin to kill persisters might derive from altering the oxidative phosphorylation and TCA cycle, as both evidenced by both ATP level increase and transcriptome change. Glutamine might represent a synergistic agent of rifampicin to kill Mycobacteria persisters.

Electrical property of macroscopic graphene composite fibers prepared by chemical vapor deposition.

Graphene fibers are promising candidates in portable and wearable electronics due to their tiny volume, flexibility and wearability. Here, we successfully synthesized macroscopic graphene composite fibers via a two-step process, i.e. first electrospinning and then chemical vapor deposition (CVD). Briefly, the well-dispersed PAN nanofibers were sprayed onto the copper surface in an electrified thin liquid jet by electrospinning. Subsequently, CVD growth process induced the formation of graphene films using a PAN-solid source of carbon and a copper catalyst. Finally, crumpled and macroscopic graphene composite fibers were obtained from carbon nanofiber/graphene composite webs by self-assembly process in the deionized water. Temperature-dependent conduct behavior reveals that electron transport of the graphene composite fibers belongs to hopping mechanism and the typical electrical conductivity reaches 4.59 × 103 S m-1. These results demonstrated that the graphene composite fibers are promising for the next-generation flexible and wearable electronics.

Controllable Carrier Type in Boron Phosphide Nanowires Toward Homostructural Optoelectronic Devices.

The p-n junction is one important and fundamental building block of the optoelectronic age. However, electrons and holes will be severely scattered in heterostructures led by the grain boundary at the alloy interface between two dissimilar semiconductors. In this work, we present boron phosphide (BP) nanowires with artificially controllable carrier type for the fabrication of homojunctions via adjusting borane/phosphine ratio during the deposition process, both prove high crystallization with fewer impurities. The homojunctions that consist of  n-type and p-type BP nanowires show apparent photovoltaic effect [external quantum efficiency ≈ 10% under a ∼0.4 pW light @ 600 nm] and the quenched photoluminescence within the junction area, which indicates the effective separation and transfer of photogenerated charge carriers at the interface. The achievement of controllable carrier type implemented in the same material ushers in a frontier for the design of nanoscale homojunctions toward advanced optoelectronic devices.

Directed growth of graphene nanomesh in purified argon via chemical vapor deposition.

Graphene nanomeshes (GNMs), new graphene nanostructures with tunable bandgaps, are potential building blocks for future electronic or photonic devices, and energy storage and conversion materials. In previous works, GNMs have been successfully prepared on Cu foils by the H2 etching effect. In this paper, we investigated the effect of Ar on the preparation of GNMs, and how the mean density and shape of them vary with growth time. In addition, scanning electron microscopy (SEM) and high resolution transmission electron microscopy (TEM) revealed the typical hexagonal structure of GNM. Atomic force microscopy (AFM) and x-ray photoelectron spectroscopy (XPS) indicated that large copper oxide nanoparticles produced by oxidization in purified Ar can play an essential catalytic role in preparing GNMs. Then, we exhibited the key reaction details for each growth process and proposed a growth mechanism of GNMs in purified Ar.

Coupling efficiency model for spectral beam combining of high-power fiber lasers calculated from spectrum.

We utilize the spectral broadening of Yb-doped fiber lasers in the spectral beam combining scheme to develop an analytical model of the coupling efficiency, which forms a critical factor in evaluating the practicality of the beam combination system. The simulation results predict a trend similar to the measured ones. Via increasing the number of simulating lasers, the model can be extended to calculate the combining efficiency of the resulting multiple-beam-combination system and estimate the optimal output power and combining efficiency. Moreover, the analytical model is suitable to investigate key parameters of Yb-doped lasers and filters, which is beneficial in enhancing the combining efficiency.

Large-area, high-quality monolayer graphene from polystyrene at atmospheric pressure.

Graphene films have been attracting great interest owing to their unique physical properties. In this paper, we develop an efficient method to prepare large-area monolayer graphene (97.5% coverage) by atmospheric pressure chemical vapor deposition on Cu foils using polystyrene in a short time (3 min). Raman spectroscopy, transmission electron microscopy and scanning electron microscopy are employed to confirm the thickness and uniformity of the graphene films. Graphene films on glass substrates show high optical transmittance and electrical conductivity. Magnetic transport studies demonstrate that the as-grown monolayer graphene exhibits a high carrier mobility of 3395 cm2 V-1 s-1 at 25 K. On the basis of the analysis, it is concluded that our method is a simple, safe and versatile approach for the synthesis of monolayer graphene.