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Rationale and Objectives: Computer‐aided detection (CAD) of pulmonary nodules reduces the impact of observer variability, improving the reliability and reproducibility of nodule assessments in clinical practice. Therefore, this study aimed to assess the impact of CAD on inter‐observer agreement in the follow‐up management of subsolid nodules. Materials and Methods: A dataset comprising 60 subsolid nodule cases was constructed based on the National Cancer Center lung cancer screening data. Five observers independently assessed all low‐dose computed tomography scans and assigned follow‐up management strategies to each case according to the National Comprehensive Cancer Network (NCCN) guidelines, using both manual measurements and CAD assistance. The linearly weighted Cohen's kappa test was used to measure agreement between paired observers. Agreement among multiple observers was evaluated using the Fleiss kappa statistic. Results: The agreement of the five observers for NCCN follow‐up management categorization was moderate when measured manually, with a Fleiss kappa score of 0.437. Utilizing CAD led to a notable enhancement in agreement, achieving a substantial consensus with a Fleiss kappa value of 0.623. After using CAD, the proportion of major and substantial management discrepancies decreased from 27.5% to 15.8% and 4.8% to 1.5%, respectively (p < 0.01). In 23 lung cancer cases presenting as part‐solid nodules, CAD significantly elevates the average sensitivity in detecting lung cancer cases presenting as part‐solid nodules (overall sensitivity, 82.6% vs. 92.2%; p < 0.05). Conclusion: The application of CAD significantly improves inter‐observer agreement in the follow‐up management strategy for subsolid nodules. It also demonstrates the potential to reduce substantial management discrepancies and increase detection sensitivity in lung cancer cases presenting as part‐solid nodules. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles (Fe2O3 NPs) is the main component of air pollution particles in urban rail transit environment. People are more exposed to Fe2O3 NPs, however, the studies on relationship between Fe2O3 NPs and respiratory health are limited. In the present study, acute airway inflammation caused by Fe2O3 NPs and its possible mechanism were investigated. BALB/c mice were intratracheally challenged with different concentrations of Fe2O3 NPs. Fe2O3 NPs induced bronchial epithelial barrier function damage, infiltration of neutrophils and lymphocytes into the airway submucosa, secretion of mucus in the airway epithelium and elevated expression of eosinophil major basic protein (EMBP) in lungs. Compared with the control group, Fe2O3 NPs increased eosinophils by 20 times in bronchoalveolar lavage fluid (BALF), and markedly increased eosinophils related cytokines and chemokines, including interleukin (IL) ‐5, IL‐33, thymic stromal lymphopoietin (TSLP), monocyte chemotactic protein (MCP)‐3, eotaxin, tumor necrosis factor (TNF)‐α, keratinocyte chemoattractant (KC). Furthermore, Fe2O3 NPs up‐regulated levels of IL‐5, MCP‐3, eotaxin, and KC in serum. In vitro studies showed that Fe2O3 NPs increased the genes and proteins expression of Toll‐like receptors (TLR)‐2, TLR4, TNF receptor associated factor 6 (TRAF6), myeloid differentiation factor 88 (MyD88), nuclear factor (NF)‐κB, and TNF‐α in RAW267.4 cells. The downstream inflammatory cytokine protein expression and release such as TNF‐α was significantly decreased after using TLR2/TLR4 inhibitor OxPAPC, but not MyD88 inhibitor ST2825. These results suggest that TLR2 and TLR4 played important role in Fe2O3 NPs inducing acute eosinophilic airway inflammation in the murine lung. [ABSTRACT FROM AUTHOR]

Emulating key synaptic functions in electronic devices is quite significant in bioinspired applications. Artificial synaptic thin film transistors (TFT) offer a promising solution for efficient synapse simulation. Herein, artificial synapses based on indium-gallium-zinc oxide (IGZO) TFT are fabricated and the photoelectric plasticity is investigated. Versatile synaptic functions including paired-pulse facilitation, paired-pulse depression, and short-term memory to long-term memory transition are emulated. More importantly, these synaptic functions can be mediated by modulating the composition ratio of IGZO film. These achievements represent a major advance toward implementation of full synaptic functionality in neuromorphic hardware and the strategy that combines the photonics and the electrics has great prospects in optoelectronic applications. [ABSTRACT FROM AUTHOR]

To optimise the performance of photo-field-effect transistor, a back-gate hybrid structure was developed. In this hybrid phototransistor, lead sulphide (PbS) thin film was prepared using physical vapour deposition as a photosensitive layer. Discontinuous and uniform PbS film was obtained by controlling the deposition rate and time of PbS powders. Amorphous indium gallium zinc oxide (IGZO) with high mobility was used as an active layer. In this work, The hybrid structure phototransistor shows an excellent performance: device mobility (μ) reach 8.7 cm2V-1s-1, and responsivity achieve 2.7 ×104 A/W in visible spectrum and 5.7 A/W in near-infrared spectrum, respectively. Furthermore, the transistor exhibits detectivity up to 2.79 ×1013 cmHz1/2W-1. The device also exhibits characteristics of the ideal diode: the saturation current of the diode is as small as 0.422 nA, and the responsivity of diode is ~0.74 A/W. Simplified manufacturing processes effectively reduce the cost of fabricated device and provide better device stability. [ABSTRACT FROM AUTHOR]

NleC is one of the virulence factors that is injected into infected host cells by enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC) via a needle-like protein complex called the type III secretion system (T3SS). The cytosolic NleC specifically cleaves the p65 subunit of NF-κB in the p65-p50 heterodimeric complex just after the Cys38 site in its N-terminal domain. The degradation of the remainder of the p65 C-terminal domain by the proteasome disrupts the NF-κB signalling pathway, thus dampening the host inflammatory response. Here, the crystal structure of NleC is reported at 1.55 Å resolution. In conjunction with biochemical analyses, the structure reveals that NleC is a member of the zincin zinc protease family and that the configuration of the NleC active site resembles that of the metzincin clan of metallopeptidases but without the canonical Met turn of astacin. The extended zinc-binding motif of NleC (HEXXHXXTXXXD) includes three metal ligands. The fifth zinc ligand, a conserved tyrosine (a bound water molecule is the fourth ligand), lies 45 residues downstream of the zincin motif. Furthermore, the electrostatic potential complementarity between NleC and p65 also contributes to the cleavage activity of the protease. These results not only provide important insights into the mechanism of how NleC recognizes its substrates, but also shed light on the design of new antibiotics for the food-borne diseases arising from EPEC and EHEC. [ABSTRACT FROM AUTHOR]

The crystal structure of triclinic hen egg-white lysozyme (HEWL) has been refined against diffraction data extending to 0.65 Å resolution measured at 100 K using synchrotron radiation. Refinement with anisotropic displacement parameters and with the removal of stereochemical restraints for the well ordered parts of the structure converged with a conventional R factor of 8.39% and an Rfree of 9.52%. The use of full-matrix refinement provided an estimate of the variances in the derived parameters. In addition to the 129-residue protein, a total of 170 water molecules, nine nitrate ions, one acetate ion and three ethylene glycol molecules were located in the electron-density map. Eight sections of the main chain and many side chains were modeled with alternate conformations. The occupancies of the water sites were refined and this step is meaningful when assessed by use of the free R factor. A detailed description and comparison of the structure are made with reference to the previously reported triclinic HEWL structures refined at 0.925 Å (at the low temperature of 120 K) and at 0.95 Å resolution (at room temperature). [ABSTRACT FROM AUTHOR]

Proper solution of a macromolecular crystal structure based on anomalous scattering and/or isomorphous differences requires that the anomalous differences in reflection amplitudes be measured properly and that the correct enantiomer of the substructure be selected. If this information is wrong then the resulting electron-density maps will not show the correct structural features, but the reflection phases and map features will be related to the correct ones in a specific way. This text aims to explain how misinterpretation of the Bijvoet differences or of the substructure affects the resulting phases and electron-density maps. [ABSTRACT FROM AUTHOR]

X-ray single-wavelength anomalous diffraction (SAD) data from a crystal of proteinase K were collected using synchrotron radiation of 0.98 Å wavelength at SER-CAT 22-­ID beamline, Advanced Photon Source, Argonne National Laboratory. At this wavelength, the expected Bijvoet ratio resulting from the presence of one calcium, one chloride and ten S atoms in the 279-residue protein is extremely small at ∼0.46%. The direct-methods program SHELXD located 11 anomalous sites using data truncated to 2 Å resolution. SHELXE was used to produce an easily interpretable electron-density map. This study shows that an accurate beamline and a good-quality crystal provide the possibility of successfully using a very weak anomalous signal of sulfur measured at a short wavelength for phasing a protein structure, even if a small degree of radiation damage is present. [ABSTRACT FROM AUTHOR]

Background: The healing period of bone-implant osseointegration usually varies from 3 to 6 months or even longer. Failure may occur during this time. This study aimed to investigate whether osseointegration of dental implants can be enhanced by the combination of growth factors. Methods: Sixty-four implants were coated with polylactic acid and divided into four groups. Group 1 was applied with 1.0 mg recombinant human bone morphogenetic protein-2 (rhBMP-2) and 200 µg recombinant human basic fibroblast growth factor (rhbFGF), group II with 1.0 mg rhBMP-2 and 250 µg recombinant human insulin-like growth factor-I (rhIGF-I), group III with 1.0 mg rhBMP-2, and group IV without growth factors as control. In total, 16 rabbits were used, and two osteotomies were drilled on each side of the femur, in which four different groups were randomly placed. Four weeks after implanting, 20 mg calcein green/kg body weight was administered intravenously, and 8 weeks after implanting, 20 mg alizarin/kg body weight was administered intravenously. Twelve weeks after implanting, the animals were sacrificed. The block of bone with implants was embedded in methylmethacrylate and sectioned, and the percentage of new bone surrounding the implant was analyzed by confocal laser scanning microscopy. Results: There was a statistical difference in bone formation between rhBMP-2-applied groups and the non applied group at 4 or 8 weeks, and no significant difference between groups I and II (although bone formation in group II was greater than that in group I at 4 weeks). The bone formation in group II was greater than that in group III at 4 or 8 weeks. The formed bone in group I was also greater than the one in group III at 8 weeks, but there was no difference at 4 weeks. Conclusions: rhBMP-2 could increase new bone formation, and it acted synergistically with rhbFGF and rhIGF-I to improve bone-implant osseointegration. The combination of rhBMP-2 and rhbFGF (group 1) showed faster growth of new bone than other groups at 8 months. [ABSTRACT FROM AUTHOR]