A spatially resolved single-cell genomic atlas of the adult human breast.

The adult human breast is comprised of an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue1-3. Although most previous studies have focused on the breast epithelial system4-6, many of the non-epithelial cell types remain understudied. Here we constructed the comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics study profiled 714,331 cells from 126 women, and 117,346 nuclei from 20 women, identifying 12 major cell types and 58 biological cell states. These data reveal abundant perivascular, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. Spatial mapping using four different technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells, as well as distinct molecular differences between ductal and lobular regions. Collectively, these data provide a reference of the adult normal breast tissue for studying mammary biology and diseases such as breast cancer.

Research on the efficient EM modeling method from multilayered anisotropic medium-metal composite targets.

The paper presents a high-frequency modeling approach tailored for the electromagnetic (EM) scattering characteristics from electrically large radar targets coated with multi-layered anisotropic mediums (MLAMs). The approach begins by deriving the plane-wave spectrum expression for the incident EM field within MLAMs. It then employs spectral domain full-wave analysis method (SDFWAM) to obtain an analytical representation of the scattering field, further leveraging saddle point evaluation (SPE) to derive asymptotic solutions in the spatial domain. By integrating principles of physical optics (PO) and the tangent plane approximation, the far-field scattering characteristics of target enveloped in the specified medium are efficiently delineated. Validations against standard structure and the Misty satellite model reveal the method's pronounced alignment with the method of moments - finite element method (MoM-FEM) hybrid numerical algorithm, underscoring its notable computational efficiency. Furthermore, in conjunction with scattering sources decomposition technique, the approach is applied to optimize the radar cross-section (RCS) of the Su-57 aircraft, achieving precise and intelligent RCS control at minimal material cost. In conclusion, this research offers pivotal technological and theoretical foundations for EM scattering prediction, stealth design, and performance assessment in radar target domains.

A Lightweight Convolutional Neural Network Based on Dynamic Level-Set Loss Function for Spine MR Image Segmentation.

BACKGROUND: Spine MR image segmentation is important foundation for computer-aided diagnostic (CAD) algorithms of spine disorders. Convolutional neural networks segment effectively, but require high computational costs. PURPOSE: To design a lightweight model based on dynamic level-set loss function for high segmentation performance. STUDY TYPE: Retrospective. POPULATION: Four hundred forty-eight subjects (3163 images) from two separate datasets. Dataset-1: 276 subjects/994 images (53.26% female, mean age 49.02 ± 14.09), all for disc degeneration screening, 188 had disc degeneration, 67 had herniated disc. Dataset-2: public dataset with 172 subjects/2169 images, 142 patients with vertebral degeneration, 163 patients with disc degeneration. FIELD STRENGTH/SEQUENCE: T2 weighted turbo spin echo sequences at 3T. ASSESSMENT: Dynamic Level-set Net (DLS-Net) was compared with four mainstream (including U-net++) and four lightweight models, and manual label made by five radiologists (vertebrae, discs, spinal fluid) used as segmentation evaluation standard. Five-fold cross-validation are used for all experiments. Based on segmentation, a CAD algorithm of lumbar disc was designed for assessing DLS-Net's practicality, and the text annotation (normal, bulging, or herniated) from medical history data were used as evaluation standard. STATISTICAL TESTS: All segmentation models were evaluated with DSC, accuracy, precision, and AUC. The pixel numbers of segmented results were compared with manual label using paired t-tests, with P < 0.05 indicating significance. The CAD algorithm was evaluated with accuracy of lumbar disc diagnosis. RESULTS: With only 1.48% parameters of U-net++, DLS-Net achieved similar accuracy in both datasets (Dataset-1: DSC 0.88 vs. 0.89, AUC 0.94 vs. 0.94; Dataset-2: DSC 0.86 vs. 0.86, AUC 0.93 vs. 0.93). The segmentation results of DLS-Net showed no significant differences with manual labels in pixel numbers for discs (Dataset-1: 1603.30 vs. 1588.77, P = 0.22; Dataset-2: 863.61 vs. 886.4, P = 0.14) and vertebrae (Dataset-1: 3984.28 vs. 3961.94, P = 0.38; Dataset-2: 4806.91 vs. 4732.85, P = 0.21). Based on DLS-Net's segmentation results, the CAD algorithm achieved higher accuracy than using non-cropped MR images (87.47% vs. 61.82%). DATA CONCLUSION: The proposed DLS-Net has fewer parameters but achieves similar accuracy to U-net++, helps CAD algorithm achieve higher accuracy, which facilitates wider application. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Cascade Synthesis of Fe-N2-Fe Dual-Atom Catalysts for Superior Oxygen Catalysis.

Dual-atom catalysts (DACs) have been proposed to break the limitation of single-atom catalysts (SACs) in the synergistic activation of multiple molecules and intermediates, offering an additional degree of freedom for catalytic regulation. However, it remains a challenge to synthesize DACs with high uniformity, atomic accuracy, and satisfactory loadings. Herein, we report a facile cascade synthetic strategy for DAC via precise electrostatic interaction control and neighboring vacancy construction. We synthesized well-defined, uniformly dispersed dual Fe sites which were connected by two nitrogen bonds (denoted as Fe-N2-Fe). The as-synthesized DAC exhibited superior catalytic performances towards oxygen reduction reaction, including good half-wave potential (0.91 V), high kinetic current density (21.66 mA cm-2), and perfect durability. Theoretical calculation revealed that the DAC structure effectively tunes the oxygen adsorption configuration and decreases the cleavage barrier, thereby improving the catalytic kinetics. The DAC-based zinc-air batteries exhibited impressive power densities of 169.8 and 52.18 mW cm-2 at 25 oC and -40 oC, which is 1.7 and 2.0 times higher than those based on Pt/C+Ir/C, respectively. We also demonstrated the universality of our strategy in synthesizing other M-N2-M DACs (M= Co, Cu, Ru, Pd, Pt, and Au), facilitating the construction of a DAC library for different catalytic applications.

iPSC-based model of Vogt-Koyanagi-Harada disease for phenotype recapitulation and drug screening.

Vogt-Koyanagi-Harada (VKH) disease, a major blinding eye disease, is characterized by an autoimmune response against melanocytes in multiple organs throughout the body. Currently, the aetiology and pathogenesis of VKH disease are unclear, and the treatment strategy needs to be further optimized. The retinal pigment epithelium (RPE), a monolayer of pigmented cells of the fundus, is essential for maintaining normal visual function and is involved in both the acute and chronic stages of VKH disease. Therefore, the functions of the RPE may play a critical role in the aetiology and treatment of VKH disease. Herein, we established a human induced pluripotent stem cell (hiPSC) RPE model of VKH disease by reprogramming peripheral blood mononuclear cells (PBMCs) into iPSCs and then differentiating them into RPE cells. Patient-derived RPE cells exhibited barrier disruption, impaired phagocytosis, and depigmentation compared with those from normal controls, which was consistent with the features of VKH disease. Furthermore, a small molecular compound targeting EGR2 was found to rescue the barrier and phagocytic functions of the hiPSC-RPE cells through high-throughput virtual screening and functional studies, suggesting a promising strategy for the treatment of VKH disease.

sRNA21, a novel small RNA, protects Mycobacterium abscessus against oxidative stress.

BACKGROUND: During infection, Mycobacterium abscessus encounters numerous environmental changes and adapts to them using a variety of complex mechanisms. Non-coding small RNAs (sRNAs) have been shown in other bacteria to be involved in post-transcriptional regulatory pathways, including environmental stress adaptation. However, the potential role of sRNAs in the resistance to oxidative stress in M. abscessus was not clearly described. METHODS: In the present study, we analyzed putative sRNAs identified by RNA-sequencing (RNA-seq) experiments in M. abscessus ATCC_19977 under oxidative stress, and the transcription profiles of sRNAs with differential expression were verified by quantitative reverse transcription-PCR (qRT-PCR). Six sRNA overexpression strains were constructed, and the differences in growth curves between these strains and the control strain were verified. An upregulated sRNA under oxidative stress was selected and named sRNA21. The survival ability of the sRNA21 overexpression strain was assessed, and computer-based approaches were used to predict the targets and pathways regulated by sRNA21. The total ATP production and NAD+ /NADH ratio of the sRNA21 overexpression strain were measured. The expression level of antioxidase-related genes and the activity of antioxidase were tested to confirm the interaction of sRNA21 with the predicted target genes in silico. RESULTS: In total, 14 putative sRNAs were identified under oxidative stress, and the qRT-PCR analysis of six sRNAs showed comparable results to RNA-seq assays. Overexpression of sRNA21 in M. abscessus increased cell growth rate and intracellular ATP level before and after peroxide exposure. The expression of genes encoding alkyl hydroperoxidase and superoxide dismutase was significantly increased, and superoxide dismutase activity was enhanced in the sRNA21 overexpression strain. Meanwhile, after sRNA21 overexpression, the intracellular NAD+ /NADH ratio decreased, indicating changes in redox homeostasis. CONCLUSIONS: Our findings show that sRNA21 is an oxidative stress-induced sRNA that increases M. abscessus survival and promotes the expression of antioxidant enzymes under oxidative stress. These findings may provide new insights into the adaptive transcriptional response of M. abscessus to oxidative stress.

Research on the computational method of creeping waves diffraction of arbitrary complex target based on the planar mesh model.

For a long time, due to the difficulty of obtaining accurate propagation trajectories, the research on creeping waves is limited to canonical geometries or simple targets, which leads to the situation that it is relatively mature in theoretical research on creeping waves, while the practical application scope of creeping waves for complex targets is narrow. In this paper, a thorough electromagnetic computation method for creeping waves on complex planar mesh model is systematically proposed. This approach broadens the field of creeping waves applications due to the generality of planar mesh models in electromagnetic engineering. The contents consist of the tracing of creeping waves, the calculation of the diffraction field, and the coupling effect with other scattering mechanisms. Aiming at the trajectory of creeping waves, we propose a set of tracing algorithms that enable rapid, real-time tracing based on analytical geometry and related computer graphics algorithms. Utilizing information such as vertices, triangles, and topological relations in the mesh model, one can recover the mathematical properties of the surfaces of the model and then, the corresponding parameters can be obtained. Therefore, the uniform geometrical theory of diffraction (UTD) can be used to accurately calculate the diffraction field. Moreover, for complex targets, the multiple coupling effect caused by creeping waves is the main source of radar echoes in many cases, which is not unimportant. Hence based on the electromagnetic accurate modeling, the coupling mechanism of creeping waves and various scattering mechanisms are studied. The research content is expected to have high application values in target recognition and characteristics.

LSW-Net: Lightweight Deep Neural Network Based on Small-World properties for Spine MR Image Segmentation.

BACKGROUND: Segmenting spinal tissues from MR images is important for automatic image analysis. Deep neural network-based segmentation methods are efficient, yet have high computational costs. PURPOSE: To design a lightweight model based on small-world properties (LSW-Net) to segment spinal MR images, suitable for low-computing-power embedded devices. STUDY TYPE: Retrospective. POPULATION: A total of 386 subjects (2948 images) from two independent sources. Dataset I: 214 subjects/779 images, all for disk degeneration screening, 147 had disk degeneration, 52 had herniated disc. Dataset II: 172 subjects/2169 images, 142 patients with vertebral degeneration, 163 patients with disc degeneration. 70% images in each dataset for training, 20% for validation, and 10% for testing. FIELD STRENGTH/SEQUENCE: T1- and T2-weighted turbo spin echo sequences at 3 T. ASSESSMENT: Segmentation performance of LSW-Net was compared with four mainstream (including U-net and U-net++) and five lightweight models using five radiologists' manual segmentations (vertebrae, disks, spinal fluid) as reference standard. LSW-Net was also deployed on NVIDIA Jetson nano to compare the pixels number in segmented vertebrae and disks. STATISTICAL TESTS: All models were evaluated with accuracy, precision, Dice similarity coefficient (DSC), and area under the receiver operating characteristic (AUC). Pixel numbers segmented by LSW-Net on the embedded device were compared with manual segmentation using paired t-tests, with P < 0.05 indicating significance. RESULTS: LSW-Net had 98.5% fewer parameters than U-net but achieved similar accuracy in both datasets (dataset I: DSC 0.84 vs. 0.87, AUC 0.92 vs. 0.94; dataset II: DSC 0.82 vs. 0.82, AUC 0.88 vs. 0.88). LSW-Net showed no significant differences in pixel numbers for vertebrae (dataset I: 5893.49 vs. 5752.61, P = 0.21; dataset II: 5073.42 vs. 5137.12, P = 0.56) and disks (dataset I: 1513.07 vs. 1535.69, P = 0.42; dataset II: 1049.74 vs. 1087.88, P = 0.24) segmentation on an embedded device compared to manual segmentation. DATA CONCLUSION: Proposed LSW-Net achieves high accuracy with fewer parameters than U-net and can be deployed on embedded device, facilitating wider application. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: 1.

Near-infrared (NIR) imaging with indocyanine green (ICG) may assist in intraoperative decision making and improving surgical margin in bone and soft tissue tumor surgery.

BACKGROUND AND OBJECTIVES: Negative surgical margins are significant in improving patient outcomes. However, surgeons can only rely on visual and tactile information to identify tumor margins intraoperatively. We hypothesized that intraoperative fluorescence imaging with indocyanine green (ICG) could serve as an assistive technology to evaluate surgical margins and guide surgery in bone and soft tissue tumor surgery. METHODS: Seventy patients with bone and soft tissue tumors were enrolled in this prospective, non-randomized, single-arm feasibility study. All patients received intravenous indocyanine green (0.5 mg/kg) before surgery. Near-infrared (NIR) imaging was performed on in situ tumors, wounds, and ex vivo specimens. RESULTS: 60/70 tumors were fluorescent at NIR imaging. The final surgical margins were positive in 2/55 cases, including 1/40 of the sarcomas. Surgical decisions were changed in 19 cases by NIR imaging, and in 7/19 cases final pathology demonstrated margins were improved. Fluorescence analysis showed that the tumor-to-background ratio (TBR) of primary malignant tumors was higher than that of benign, borderline, metastatic, and tumors ≥5 cm in size had higher TBR than those <5 cm. CONCLUSIONS: ICG fluorescence imaging may be a beneficial technique to assist in surgical decision making and improving surgical margins in bone and soft tissue tumor surgery.

A Novel Anderson-Type POMs-Based Hybrids Flame Retardant for Reducing Smoke Release and Toxicity of Epoxy Resins.

Smoke emission and smoke toxicity have drawn more attention to improving the fire safety of polymers. In this work, a polyoxometalates (POMs)-based hybrids flame retardant (P-AlMo6 ) epoxy resin (EP) is prepared with toxicity-reduction and smoke-suppression properties via a peptide coupling reaction between POMs and organic molecules with double DOPO (bisDOPA). It combines the good compatibility of the organic molecule and the superior catalytic performance of POMs. Compared to pure EP, the glass transition temperature and flexural modulus of EP composite with 5 wt.% P-AlMo6 (EP/P-AlMo6 -5) are raised by 12.3 °C and 57.75%, respectively. Notably, at low flame-retardant addition, the average CO to CO2 ratio (Av-COY/Av-CO2 Y) is reduced by 33.75%. Total heat release (THR) and total smoke production (TSP) are lowered by 44.4% and 53.7%, respectively. The Limited Oxygen Index (LOI) value achieved 31.7% and obtained UL-94 V-0 rating. SEM, Raman, X-ray photoelectron spectroscopy, and TG-FTIR are applied to analyze the flame-retardant mechanism in condensed and gas phase. Outstanding flame retardant, low smoke toxicity properties are attained due to the catalytic carbonization ability of metal oxides Al2 O3 and MoO3 produced from the breakdown of POMs. This work advances the development of POMs-based hybrids flame retardants with low smoke toxicity properties.

Using Nitroxides to Enhance Carbon Fiber Interfacial Adhesion and as an Anchor for "Graft to" Surface Modification Strategies.

Nitroxide groups covalently grafted to carbon fibers are used as anchoring sites for TEMPO-terminated polymers (poly-n-butylacrylate and polystyrene) in a "graft to" surface modification strategy. All surface-modified fibers are evaluated for their physical properties, showing that several treatments have enhanced the tensile strength and Young's modulus compared to the control fibers. Up to an 18% increase in tensile strength and 12% in Young's modulus are observed. Similarly, the evaluation of interfacial shear strength in an epoxy polymer shows improvements of up to 144% relative to the control sample. Interestingly, the polymer-grafted surfaces show smaller increases in interfacial shear strength compared to surfaces modified with a small molecule only. This counterintuitive result is attributed to the incompatibility, both chemical and physical, of the grafted polymers to the surrounding epoxy matrix. Molecular dynamics simulations of the interface suggest that the diminished increase in mechanical shear strength observed for the polymer grafted surfaces may be due to the lack of exposed chain ends, whereas the small molecule grafted interface exclusively presents chain ends to the resin interface, resulting in good improvements in mechanical properties.

In vitro susceptibility testing of tetracycline-class antibiotics against slowly growing non-tuberculous mycobacteria.

Non-tuberculous mycobacterial infections are gradually increasing worldwide, with slow-growing mycobacteria such as Mycobacterium avium, Mycobacterium intracellulare and Mycobacterium kansasii accounting for the majority of cases. The use of tetracyclines has received renewed attention in recent years, and this study was designed to investigate the antibacterial activity of omadacycline, eravacycline, tigecycline, sarecycline, minocycline and doxycycline against M. avium, M. intracellulare and M. kansasii. Susceptibility testing of six tetracyclines was conducted against M. avium, M. intracellulare and M. kansasii isolates, and all the clinical isolates were collected from January 2012 to December 2018. All six agents exhibited poor antibacterial activity against slowly growing mycobacteria (SGM) isolates of three subspecies with MIC50 and MIC90 ≥8 µg/mL. M. intracellulare and M. kansasii had lower resistance rates to omadacycline than the other five drugs. The severe resistance of SGM to tetracycline suggests that developing tetracycline-class antibiotics needs to overcome existing resistance mechanisms.

Neutrophil-Derived IL-6 Potentially Drives Ferroptosis Resistance in B Cells in Lupus Kidney.

Ferroptosis resistance is vital for B cell development, especially in inflammatory diseases, yet the underlying mechanism is still unclear. In this study, based on the scRNA-seq technique and flow cytometry, we discovered a proportion of neutrophils exhibited upregulated expression of the IL-6 and correlated with the expression of IL-6 receptor and SLC7A11 from B cells in lupus kidney. Moreover, we identified that in lupus kidney, neutrophils could provide IL-6 to facilitate ferroptosis resistance in B cells via SLC7A11, and inhibition of SLC7A11 could significantly enhance ferroptosis in B cells and could decrease B cell proliferation. This study helps understand the crosstalk between neutrophils and B cells in the kidney in the development of lupus.

Effect of Internal Mechanical Environment of Porous Scaffolds on Mechano-driven Bone Ingrowth: A Numerical Study.

Porous cages with lower global stiffness induce more bone ingrowth and enhance bone-implant anchorage. However, it's dangerous for spinal fusion cages, which usually act as stabilizers, to sacrifice global stiffness for bone ingrowth. Intentional design on internal mechanical environment might be a promising approach to promote osseointegration without undermining global stiffness excessively. In this study, three porous cages with different architectures were designed to provide distinct internal mechanical environments for bone remodeling during spinal fusion process. A design space optimization-topology optimization based algorithm was utilized to numerically reproduce the mechano-driven bone ingrowth process under three daily load cases, and the fusion outcomes were analyzed in terms of bone morphological parameters and bone-cage stability. Simulation results show that the uniform cage with higher compliance induces deeper bone ingrowth than the optimized graded cage. Whereas, the optimized graded cage with the lowest compliance exhibits the lowest stress at the bone-cage interface and better mechanical stability. Combining the advantages of both, the strain-enhanced cage with locally weakened struts offers extra mechanical stimulus while keeping relatively low compliance, leading to more bone formation and the best mechanical stability. Thus, the internal mechanical environment can be well-designed via tailoring architectures to promote bone ingrowth and achieve a long-term bone-scaffold stability.

Around the world in electrochemistry: a review of the electrochemistry curriculum in high schools.

Electrochemistry education of future researchers and citizens is crucial if we are to decarbonise economies and reach targets for net zero. In this paper, we take an overview of electrochemistry within school education. We used curriculum documents obtained from national and state education department websites and from local teachers, examples of assessments and insights from the chemistry education literature to evaluate the extent of electrochemistry education around the world. We found that there is a great deal of electrochemistry included in the intended curriculum for high schools although there is variability depending on how early students are able to specialise in a smaller number of subjects. A range of contexts are used to illustrate the key ideas including galvanic and electrolytic cells, electrolysis and analysis. There is generally constructive alignment between assessment items and the intended curriculum although in some cases assessment was more simplistic than the intended curriculum would suggest. The effectiveness of the taught curriculum is undermined by low teacher confidence in teaching electrochemistry especially more advanced concepts. Additionally, there are a number of misconceptions generated when students learn electrochemistry with some of these potentially arising from published resources such as textbooks. Supplementary Information: The online version contains supplementary material available at 10.1007/s10008-023-05548-0.

Towards Building a Trustworthy Deep Learning Framework for Medical Image Analysis.

Computer vision and deep learning have the potential to improve medical artificial intelligence (AI) by assisting in diagnosis, prediction, and prognosis. However, the application of deep learning to medical image analysis is challenging due to limited data availability and imbalanced data. While model performance is undoubtedly essential for medical image analysis, model trust is equally important. To address these challenges, we propose TRUDLMIA, a trustworthy deep learning framework for medical image analysis, which leverages image features learned through self-supervised learning and utilizes a novel surrogate loss function to build trustworthy models with optimal performance. The framework is validated on three benchmark data sets for detecting pneumonia, COVID-19, and melanoma, and the created models prove to be highly competitive, even outperforming those designed specifically for the tasks. Furthermore, we conduct ablation studies, cross-validation, and result visualization and demonstrate the contribution of proposed modules to both model performance (up to 21%) and model trust (up to 5%). We expect that the proposed framework will support researchers and clinicians in advancing the use of deep learning for dealing with public health crises, improving patient outcomes, increasing diagnostic accuracy, and enhancing the overall quality of healthcare delivery.

A Novel Leucyl-tRNA Synthetase Inhibitor, MRX-6038, Expresses Anti-Mycobacterium abscessus Activity In Vitro and In Vivo.

Therapeutic options for Mycobacterium abscessus infections are extremely limited, and new drugs are needed. The anti-M. abscessus activity of MRX-6038, a new leucyl-tRNA synthetase inhibitor, was evaluated in vitro and in vivo. Antimicrobial susceptibility testing was performed on 12 nontuberculosis mycobacteria (NTM) reference strains and 227 clinical NTM isolates. A minimum bactericidal concentration assay was conducted to distinguish the bactericidal versus bacteriostatic activity of MRX-6038. The synergy between MRX-6038 and 12 clinically important antibiotics was determined using a checkerboard assay. The activity of MRX-6038 against M. abscessus residing inside macrophages was also evaluated. Finally, the potency of MRX-6038 in vivo was determined in a neutropenic mouse model that mimicked a pulmonary M. abscessus infection. MRX-6038 exhibited high anti-M. abscessus activity against extracellular M. abscessus in culture, with a MIC50 of 0.063 mg/L and a MIC90 of 0.125 mg/L. Fifty percent of the activity was bactericidal, and fifty percent was bacteriostatic. A synergy between MRX-6038 and clarithromycin or azithromycin was found in 25% of strains. No antagonism was evident between MRX-6038 and 12 antibiotics commonly used to treat NTM infections. MRX-6038 also exhibited activity against intracellular NTM, which caused a significant reduction in the bacterial load in the lungs of M. abscessus-infected neutropenic mice. In conclusion, MRX-6038 was active against M. abscessus in vitro and in vivo, and it represents a potential candidate for incorporation into strategies by which M. abscessus infections are treated.

In silico and in vivo studies of the effect of surface curvature on the osteoconduction of porous scaffolds.

Recent evidence shows that the curvature of porous scaffold plays a significant role in guiding tissue regeneration. However, the underlying mechanism remains controversial to date. In this study, we developed an in silico model to simulate the effect of surface curvature on the osteoconduction of scaffold implants, which comprises the primary aspects of bone regeneration. Selective laser melting was used to manufacture a titanium scaffold with channels representative of different strut curvatures for in vivo assessment. The titanium scaffold was implanted in the femur condyles of rabbits to validate the mathematical model. Simulation results suggest that the curvature affected the distribution of growth factors and subsequently induced the migration of osteoblast lineage cells and bone deposition to the locations with higher curvature. The predictions of the mathematical model are in good agreement with the in vivo assessment results, in which newly formed bone first appeared adjacent to the vertices of the major axes in elliptical channels. The mechanism of curvature-guided osteoconduction may provide a guide for the design optimization of scaffold implants to achieve enhanced bone ingrowth.

Synthesis and characterization of a novel magnetic resin (m-MAR resin) and its removal performance for alkaline amino acids.

Alkaline amino acids as dissolved organic nitrogen (DON) have raised much concern in drinking water treatment due to poor removal in conventional treatment process and high potential for nitrogenous disinfection by-products (N-DBPs). This work was intended to devise a new magnetic adsorption resin (noted as m-MAR resin) for the efficient reduction of alkaline amino acids and explore the application potential of combined MIEX and m-MAR resins. The distribution and composition of DON and amino acids was clarified for different water sources in Lake Taihu basin, in which alkaline amino acids accounted for a higher proportion. The removal of different nitrogenous organics by MIEX resin was also examined, where the resin was effective in removing phycocyanin (65.6%) and glutamic acid (74.2%), reducing the generation of disinfection by-products (DBPs). The m-MAR resin was manufactured and characterized to cope with alkaline amino acids, and batch experiments were undertaken to investigate its adsorption behaviors on histidine and arginine under different operating conditions. The maximal adsorption capacities of arginine and histidine onto m-MAR resin were 2.84 mg/g and 1.62 mg/g, respectively, which was better than MIEX resin. The removal mechanism of the two basic amino acids by m-MAR resin was mainly due to the hydrogen bonding and the acid-base reaction. Moreover, the reusability of the m-MAR resin was elucidated after six successive adsorption-desorption cycles. Finally, the effectiveness of combined MIEX and m-MAR resin in treating DON derived from Microcystis aeruginosa reached 35.2% and the DON concentration in Lake Taihu could be reduced from 0.56 to 0.16 mg/L, which simultaneously decreased the generation potential of N-DBPs. The enhancement of coagulation by the combined process of m-MIER and m-MAR as pretreatment was estimated.

In vitro activity of rifabutin against Mycobacterium abscessus, clinical isolates.

The antibiotic options available for Mycobacterium abscessus (M. abscessus) infection are limited and no definitive therapeutic strategies have been formulated. The recent discovery that rifabutin is active against M. abscessus has raised interest in using rifabutin to treat this intractable disease. In this study, we evaluated the in vitro activity of rifabutin against 194 M. abscessus clinical isolates collected during 2012 January to 2017 December. As expected, rifabutin demonstrated considerably lower MICs against M. abscessus, with an MIC50 of 2 µg/mL and MIC90 of 4 µg/mL, respectively. Notably, the anti-M.abscessus activity was even stronger among clarithromycin-insusceptible strains. In addition, M. abscessus isolates with a rough morphotype were more sensitive to rifabutin compared with those forming smooth colonies when considered as a whole or in separate subspecies. Results from synergistic experiments revealed that the in vitro activity of rifabutin was significantly enhanced by the addition of amikacin, suggesting a promising strategy for M. abscessus infection combination treatment. Finally, five and three mutation patterns in rpoB and arr, respectively, were identified among the 194 strains through whole genome sequencing. However, none of them conferred rifabutin resistance. Our study is among the first to report the susceptibility of M. abscessus to rifabutin in vitro with a large amount of clinical isolates, suggesting that rifabutin is active, both alone and in combination, against M. abscessus and is worth considering as part of a combination treatment regimen for M. abscessus infections.