Blocking CD40 Alleviates Th1 and Th17 Cell Responses in Elastin Peptide-Induced Murine Emphysema.

Purpose: To investigate the role of the CD40-CD40 ligand (CD40L) pathway in the regulation of Th1, Th17, and regulatory T (Treg)-cell responses in an elastin peptide (EP)-induced autoimmune emphysema mouse model. Methods: BALB/c mice were transnasally treated with EP on day 0, injected intravenously with anti-CD40 antibody via the tail vein on day 33, and sacrificed on day 40. The severity of emphysema was evaluated by determining the mean linear intercept (MLI) and destructive index (DI) from lung sections. The proportions of myeloid dendritic cells (mDCs) and Th1, Th17, and Treg cells in the blood, spleen, and lungs were determined via flow cytometry. The levels of the cytokines interleukin (IL)-6, IL-17, interferon (IFN)-γ, and transforming growth factor (TGF)-ß were detected via enzyme-linked immunosorbent assay. Ifnγ, IL17a, Rorγt and Foxp3 transcription levels were detected via polymerase chain reaction. Results: CD40+ mDCs accumulated in the lungs of EP-stimulated mice. Blocking the CD40-CD40L pathway with an anti-CD40 antibody alleviated Th1 and Th17 responses; increased the proportion of Treg cells; decreased MLI and DI; reduced the levels of cytokines IL-6, IL-17, and IFN-γ as well as the transcription levels of Ifnγ, IL17a, and Rorγt; and upregulated the expression of TGF-ß and Foxp3. Conclusion: The CD40-CD40L pathway could play a critical role in Th1, Th17 and Treg cell dysregulation in EP-mediated emphysema and could be a potential therapeutic target.

Whole genome sequencing of multidrug-resistant Proteus mirabilis strain PM1162 recovered from a urinary tract infection in China.

OBJECTIVES: Proteus mirabilis is an important opportunistic Gram-negative pathogen. This study reports the whole genome sequence of multidrug-resistant (MDR) P. mirabilis PM1162 and explores its antibiotic resistance genes (ARGs) and their genetic environments. METHODS: P. mirabilis PM1162 was isolated from a urinary tract infection in China. Antimicrobial susceptibility was determined, and whole genome sequencing (WGS) was performed. ARGs, insertion sequence (IS) elements, and prophages were identified using ResFinder, ISfinder, and PHASTER software, respectively. Sequence comparisons and map generation were performed using BLAST and Easyfig, respectively. RESULTS: On its chromosome, P. mirabilis PM1162 harboured 15 ARGs, including cat, tet(J), blaCTX-M-14 (three copies), aph(3')-Ia, qnrB4, blaDHA-1, qacE, sul1, armA, msr(E), mph(E), aadA1, and dfrA1. We focused our analysis on the four related MDR regions: (1) genetic contexts associated with blaCTX-M-14; (2) the prophage containing blaDHA-1, qnrB4, and aph(3')-Ia; (3) genetic environments associated with mph(E), msr(E), armA, sul, and qacE; and (4) the class II integron harbouring dfrA1, sat2, and aadA1. CONCLUSION: This study reported the whole genome sequence of MDR P. mirabilis PM1162 and the genetic context of its ARGs. This comprehensive genomic analysis of MDR P. mirabilis PM1162 provides a deeper understanding of its MDR mechanism and elucidates the horizontal spread of its ARGs, thus providing a basis for the containment and treatment of the bacteria.

Identification of the Unique Clinical and Genetic Features of Chinese Lung Cancer Patients With EGFR Germline Mutations in a Large-Scale Retrospective Study.

BACKGROUND: Epidemiological surveys have suggested that lung cancer has inherited susceptibility and shows familial aggregation. However, the distribution and prevalence of epidermal growth factor receptor (EGFR) germline variants and their roles in lung cancer genetic predisposition in Chinese population remain to be elucidated. METHODS: In this study, EGFR germline and somatic variants were retrospectively reviewed from the next-generation sequencing results of 31,906 patients with lung cancer. Clinical information was also collected for patients with confirmed EGFR germline mutations. RESULTS: A total of 22 germline EGFR variants were identified in 64 patients with lung cancer, accounting for 0.2% of the total cases studied. Five patients were diagnosed as multiple primary carcinomas. Family history was documented in 31.3% (20/64) of patients, 55% of which were diagnosed as lung cancer. G863D was the most frequent EGFR germline mutation, followed by P848L, D1014N, and K757R. Somatic EGFR-sensitive mutations were identified in 51.6% of patients with germline EGFR mutations. The proportion of L858R mutation, exon 19 deletion, and rare sensitive mutation was 50%, 17.6%, and 32.4%, respectively. D1014N and T790M mutations were common in young patients. The family members of patients with P848L, R776H, V769M, and V774M mutations were more commonly diagnosed with cancers. A total of 19 patients were confirmed to have received EGFR tyrosine kinase inhibitors (TKIs), but the response to EGFR-TKIs differed among patients with different EGFR mutations. CONCLUSION: Chinese patients with lung cancer harbored unique and dispersive EGFR germline mutations and showed unique clinical and genetic characteristics, with varied response patterns to EGFR-TKI treatment.

High Temperature Deformation Behavior and Microstructure Evolution of Low-Density Steel Fe30Mn11Al1C Micro-Alloyed with Nb and V.

The thermal processing parameters is very important to the hot rolling and forging process for producing grain refinement in lightweight high-manganese and aluminum steels. In this work, the high temperature deformation behaviors of a low-density steel of Fe30Mn11Al1C alloyed with 0.1Nb and 0.1V were studied by isothermal hot compression tests at temperatures of 850-1150 °C and strain rates between 0.01 s-1 and 10 s-1. It was found that the flow stress constitutive model could be effectively established by the Arrhenius based hyperbolic sine equation with an activation energy of about 389.1 kJ/mol. The thermal processing maps were developed based on the dynamic material model at different strains. It's shown that the safe region for high temperatures in a very broad range of both deformation temperature and deformation strain and only a small unstable high deformation region, located at low temperatures lower than 950 °C. The deformation microstructures were found to be fully recrystallized microstructure in the safe deformation region and the grain size decreases along with decreasing temperature and increasing strain rate. Whereas the deformation microstructures is composed by grain refinement-recrystallized grains and a small fraction of non-recrystallized microstructure in the unstable deformation region, indicating that the deformation behaviors controlled by continuous dynamic recrystallization. The Hall Petch relationship between microhardness and the grain size of the high temperature deformed materials indicates that high strength low-density steel could be developed by a relative low temperature deformation and high strain rate.

Clinical Utility of Circulating Tumor Cells in the Early Detection of Lung Cancer in Patients with a Solitary Pulmonary Nodule.

Objective: Lung cancer is the most common cancer and can appear as a solitary pulmonary nodule. Early detection of lung cancer in this patient population would be beneficial for the disease management. In this study, the potential application of circulating tumor cells (CTCs) on early detection of lung cancer in this population was investigated. Methods: The number of CTCs in bronchoalveolar lavage fluid and serum levels of tumor-related markers, cancer antigen 125 (CA125), carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) were measured in patients with a solitary pulmonary nodule. The association between CTCs and lung cancer was examined. The diagnosis performances of CTCs and selected tumor-related markers were compared. Results: The CTC positivity was significantly associated with lung cancer (P = .009). The sensitivity of CTCs and CA125, CEA, NSE, and CA125/CEA/NSE was 75%, 5.6%, 0%, 25%, and 33%, respectively. The sensitivity of CTCs was improved from 75% to 83% by the combination with CA125 or NSE. Conclusion: CTCs may be helpful for the early detection of lung cancer in patients with a solitary pulmonary nodule.

Steam Selective Etching: A Strategy to Effectively Enhance the Flexibility and Suppress the Volume Change of Carbonized Paper-Supported Electrodes.

Paper-supported electrodes with high flexibility have attracted much attention in flexible Li-ion batteries. However, they are restricted by the heavy inactive paper substrate and large volume change during the lithiation-delithiation process, which will lead to low capacity and poor rate capability and cyclability. Converting the paper substrate to carbon fiber by carbonization can substantially eliminate the "dead mass", but it becomes very brittle. This study reports a water-steam selective etching strategy that successfully addresses these problems. With the help of steam etching, pores are created, and transition-metal oxides are embedded into the fiber. These effectively accommodate the volume change and enhances the kinetics of ion and electron transport. The pores release the mechanical stress from bending, ensuring the sufficient bendability of carbonized paper. Benefiting from these merits, the steam-etched samples show high flexibility and possess outstanding electrochemical performance, including ultra-high capacity and superior cycling stability with capacity retention over 100% after 1500 cycles at 2 A g-1. Furthermore, a flexible Li-ion full battery using the steam-etched Fe2O3@CNF anode and LiFePO4/steam-etched CNF cathode delivers a high capacity of 623 mAh g-1 at 100 mA g-1 and stable electrochemical performances under the bent state, holding great promise for next-generation wearable devices.

Flexible C-Mo2C fiber film with self-fused junctions as a long cyclability anode material for sodium-ion battery.

Electrospun carbon fiber films have high contact resistance at the fiber junctions, which causes poor cycling stability and limits their further improvement in energy storage performances. To eliminate the contact resistance of the film, we provide a new strategy to fuse the fiber junctions by introducing MoO2 in the fibers, which replaces the C-C interface by a more active C-MoO2-C interface at the fiber junction to promote mass transfer. MoO2 reacts with C matrix to generate Mo2C and form self-fused junctions during the carbonization process. Due to much lower charge transfer and sodium diffusion resistance, the C-Mo2C fiber film with self-fused junctions shows much better cyclability with capacity retention of 90% after 2000 cycles at a constant current density of 1 A g-1. Moreover, the Mo2C particles provide many electrochemically active sites, leading to additional improvement in sodium storage. The C-Mo2C fiber film has a capacity of 134 mA h g-1 at 1 A g-1 and a high capacity of 99 mA h g-1 even at 5 A g-1.

Dynamic reverse phase transformation induced high-strain-rate superplasticity in low carbon low alloy steels with commercial potential.

Superplastic materials are capable of exhibiting large tensile elongation at elevated temperature, which is of great industrial significance because it forms the basis of a fabrication method to produce complex shapes. Superplasticity with elongation larger than 500% has been widely realized in many metals and alloys, but seldomly been succeeded in low carbon low alloy steel, even though it is commercially applied in the largest quantity. Here we report ultrahigh superplastic elongation of 900-1200% in the FeMnAl low carbon steels at high strain rate of 10-2-10-3 s-1. Such high-strain-rate superplasticity was attributed to dynamic austenite reverse phase transformation from a heavily cold rolled ferrite to fine-grained ferrite/austenite duplex microstructure and subsequent limited dynamic grain coarsening, under which a large fraction of high angle boundaries can be resulted for superplastic deformation. It is believed that this finding of the low carbon low alloy steel with ultrahigh superplasticity and relative low cost would remarkably promote the application of superplastic forming technique in automobile, aeronautical, astronautical and other fields.

Ultrahigh Charpy impact toughness (~450J) achieved in high strength ferrite/martensite laminated steels.

Strength and toughness are a couple of paradox as similar as strength-ductility trade-off in homogenous materials, body-centered-cubic steels in particular. Here we report a simple way to get ultrahigh toughness without sacrificing strength. By simple alloying design and hot rolling the 5Mn3Al steels in ferrite/austenite dual phase temperature region, we obtain a series of ferrite/martensite laminated steels that show up-to 400-450J Charpy V-notch impact energy combined with a tensile strength as high as 1.0-1.2 GPa at room temperature, which is nearly 3-5 times higher than that of conventional low alloy steels at similar strength level. This remarkably enhanced toughness is mainly attributed to the delamination between ferrite and martensite lamellae. The current finding gives us a promising way to produce high strength steel with ultrahigh impact toughness by simple alloying design and hot rolling in industry.