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In the current study, we assessed the relationship between mutations and the blood cell counts and early progression of patients with diffuse large-B cell lymphoma (DLBCL). A total of 109 patients with newly diagnosed DLBCL were included in this study.

This paper explored training methods to improve the Theory of Mind levels of Chinese college students with hearing loss and investigated the transfer effect of training. Ninety Chinese college students with hearing loss were randomly divided into two groups: the ToM training group and the physical-conversation training group. The ToM training group received ToM training, and the physical-conversation training group as the control group received physical-conversation training. All the participants attended four separate 60-min lectures. The ToM Story Task and the False Belief Task were used to assess the training’s effect, and the ToM animation task was adopted to investigate the transfer effect. Before training, the level of ToM of the two participant groups was similar. After training, the ToM level of Chinese college students with hearing loss who participated in ToM training was significantly higher than the students who underwent physical-conversation training. Moreover, the findings revealed that ToM training has long-term transfer effects. This study thus showed that ToM training can effectively improve the ToM level of Chinese college students with hearing loss.

A methodology is proposed to study the interplay between tooth wear and contact fatigue under elastohydrodynamic lubrication condition. The modeling methodology includes the influence of contact fatigue on wear and the influence of wear on contact fatigue. First, the changes in film pressure and film thickness of oil at each meshing point caused by contact fatigue are introduced according to the surface wear model, and the change of wear model is analyzed to study the effect of contact fatigue on wear. Then, according to the elastohydrodynamic lubrication theory, the change in film pressure affected by tooth surface wear is analyzed to study the effect of wear on contact fatigue. Finally, the influence of lubrication conditions on the interplay between tooth surface wear and contact fatigue is analyzed. In addition, an experimental fatigue study is performed and introduced into the model predictions to improve the accuracy of the proposed methodology.

AVI file - 24K, BMMCs from fes+/+ and fes-/- mice were loaded with CellTracker green or CellTracker orange, respectively, prior to mixing and addition to fibronectin-coated coverslips with an SCF-embedded agarose drop. Time lapse microscopy was then performed for 8-18 hours

KIT receptor is required for mast cell development, survival, and migration toward its ligand stem cell factor (SCF). Many solid tumors express SCF and this leads to mast cell recruitment to tumors and release of mediators linked to tumor angiogenesis, growth, and metastasis. Here, we investigate whether FES protein-tyrosine kinase, a downstream effector of KIT signaling in mast cells, is required for migration of mast cells toward SCF-expressing mammary tumors. Using a novel agarose drop assay for chemotaxis of bone marrow–derived mast cells (BMMC) toward SCF, we found that defects in chemotaxis of fes-null BMMCs correlated with disorganized microtubule networks in polarized cells. FES displayed partial colocalization with microtubules in polarized BMMCs and has at least two direct microtubule binding sites within its N-terminal F-BAR and SH2 domains. An oligomerization-disrupting mutation within the Fer/CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain had no effect on microtubule binding, whereas microtubule binding to the SH2 domain was dependent on the phosphotyrosine-binding pocket. FES involvement in mast cell recruitment to tumors was tested using the AC2M2 mouse mammary carcinoma model. These tumor cells expressed SCF and promoted BMMC recruitment in a KIT- and FES-dependent manner. Engraftment of AC2M2 orthotopic and subcutaneous tumors in control or fes-null mice, revealed a key role for FES in recruitment of mast cells to the tumor periphery. This may contribute to the reduced tumor growth and metastases observed in fes-null mice compared with control mice. Taken together, FES is a potential therapeutic target to limit the progression of tumors with stromal mast cell involvement. Mol Cancer Res; 10(7); 881–91. ©2012 AACR.

Anaerobic ammonium oxidation (Anammox) was an innovative process for nitrogen removal. In this study, the influence of sulfate in different concentrations (100, 200, 300, and 400 mg L

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.

Acute kidney injury (AKI) is a common complication of hospitalization with high mortality. Approximately 30% of patients receiving cisplatin, the first-line chemotherapy treatment, develop AKI. NSC228155 is a novel compound with potential anti-cancer and anti-bacterial effects. Its therapeutic efficacy in other diseases is unclear. In the present study, we investigated the effect of NSC228155 on cisplatin-induced AKI. The mice were consecutively treated with 2.5 mg/kg of NSC228155 for five days and injected with cisplatin (22 mg/kg) via intraperitoneal injection on day three. NSC228155 strikingly improved the renal function by decreasing the serum creatinine by 52.6% in the cisplatin-induced AKI mice model. Pathologically, NSC228155 profoundly alleviated the tubular damage in Periodic Acid-Schiff staining, and significantly reduced the expression of tubular injury markers and apoptosis in the cisplatin-injured mice kidneys. NSC228155 effectively restored the mitochondrial homeostasis by decreasing damaged mitochondria, activating signals for mitochondrial dynamics and recycling, and corrected mitochondrial dysfunction in ATP production and oxidative stress in the cisplatin model. Transcriptomics and metabolomics analysis on the mice renal cortex suggested that NSC228155 profoundly corrected energy metabolism, especially citrate cycle-related pathways, oxidative stress, and endoplasmic reticulum (ER) stress in the cisplatin-induced AKI kidneys. NSC228155 effectively inhibited ER stress induced by cisplatin or tunicamycin in mice kidneys and HK-2 cells. Co-treatment of NSC228155 with 4-phenylbutyrate or MnTBAP showed a similar therapeutic effect in AKI as the inhibitors or NSC228155 alone did, and corrected the mitochondrial dysfunction and ER stress, respectively, indicating the crosstalk between ER and mitochondria played essential roles in the therapeutic effect of NSC228155 in AKI. Together, these results consistently demonstrated that NSC228155 alleviated cisplatin-induced AKI by restoring the homeostasis in mitochondria and ER, suggesting a therapeutic potential and perhaps a novel strategy for drug discovery.

Pathogenic bacterial infections in freshwater-farmed fish have high morbidity and mortality. As an effective broad spectrum antibacterial agent, silver nanoparticles (AgNPs) have great application potential in the field of aquaculture. However, due to the easy aggregation and oxidation properties of AgNPs, their practical applications are rather limited. Herein, nanocomposites of AgNPs and carbon nanodots (AgNPs@C-dots) were synthesized by using carbon nanodots as a reductant and a stabilizer. Their antibacterial activity and biosafety were systematically investigated. AgNPs@C-dots exhibit superior aggregation stability, excellent biocompatibility, and enhanced antibacterial activity compared to common AgNPs (reduced by sodium citrate).

Supplementary materials and methods

Purpose: Emerging studies demonstrate that long noncoding RNAs (lncRNA) participate in the regulation of various cancers. In the current study, a novel lncRNA-TTN-AS1 has been identified and explored in esophageal squamous cell carcinoma (ESCC).Experimental Design: To discover a new regulatory circuitry in which RNAs crosstalk with each other, the transcriptome of lncRNA-miRNA-mRNA from ESCC and adjacent nonmalignant specimens were analyzed using multiple microarrays and diverse bioinformatics platforms. The functional role and mechanism of a novel lncRNA-TTN-AS1 were further investigated by gain-of-function and loss-of-function assays in vivo and in vitro. An ESCC biomarker panel, consisting of lncRNA-TTN-AS1, miR-133b, and FSCN1, was validated by qRT-PCR and in situ hybridization using samples from 148 patients.Results: lncRNA-TTN-AS1 as an oncogene is highly expressed in ESCC tissues and cell lines, and promotes ESCC cell proliferation and metastasis. Mechanistically, lncRNA-TTN-AS1 promotes expression of transcription factor Snail1 by competitively binding miR-133b, resulting in the epithelial–mesenchymal transition (EMT) cascade. Moreover, lncRNA-TTN-AS1 also induces FSCN1 expression by sponging miR-133b and upregulation of mRNA-stabilizing protein HuR, which further promotes ESCC invasion cascades. We also discovered and validated a clinically applicable ESCC biomarker panel, consisting of lncRNA-TTN-AS1, miR-133b, and FSCN1, that is significantly associated with overall survival and provides additional prognostic evidence for ESCC patients.Conclusions: As a novel regulator, lncRNA-TTN-AS1 plays an important role in ESCC cell proliferation and metastasis. The lncRNA-TTN-AS1/miR133b/FSCN1 regulatory axis provides bona fide targets for anti-ESCC therapies. Clin Cancer Res; 24(2); 486–98. ©2017 AACR.

Negative correlation between lncRNA-TTN-AS1 and miR-133b in ESCC tissues and cell lines.

Supplementary figure legends

Supplementary Figure Legends 1-6 from Fes Tyrosine Kinase Expression in the Tumor Niche Correlates with Enhanced Tumor Growth, Angiogenesis, Circulating Tumor Cells, Metastasis, and Infiltrating Macrophages

Supplementary Figure 6 from Fes Tyrosine Kinase Expression in the Tumor Niche Correlates with Enhanced Tumor Growth, Angiogenesis, Circulating Tumor Cells, Metastasis, and Infiltrating Macrophages

Supplementary Figure 2 from Fes Tyrosine Kinase Expression in the Tumor Niche Correlates with Enhanced Tumor Growth, Angiogenesis, Circulating Tumor Cells, Metastasis, and Infiltrating Macrophages

Supplementary Figure 4 from Fes Tyrosine Kinase Expression in the Tumor Niche Correlates with Enhanced Tumor Growth, Angiogenesis, Circulating Tumor Cells, Metastasis, and Infiltrating Macrophages

Supplementary Figure 3 from Fes Tyrosine Kinase Expression in the Tumor Niche Correlates with Enhanced Tumor Growth, Angiogenesis, Circulating Tumor Cells, Metastasis, and Infiltrating Macrophages

Supplementary Figure 1 from Fes Tyrosine Kinase Expression in the Tumor Niche Correlates with Enhanced Tumor Growth, Angiogenesis, Circulating Tumor Cells, Metastasis, and Infiltrating Macrophages

Supplementary Figure 5 from Fes Tyrosine Kinase Expression in the Tumor Niche Correlates with Enhanced Tumor Growth, Angiogenesis, Circulating Tumor Cells, Metastasis, and Infiltrating Macrophages

Late embryogenesis abundant (LEA) proteins are important developmental proteins in the response of plants to abiotic stress. In our previous study, BcLEA73 was differentially expressed under low-temperature stress. Herein, we combined bioinformatics analysis, subcellular localization, expression assays, and stress experiments (including salt, drought, and osmotic stress) to identify and analyze the BcLEA gene family. Gene cloning and functional analysis of BcLEA73 were performed in tobacco and Arabidopsis. Based on the sequence homology and the available conservative motif, 82 BrLEA gene family members were identified and were divided into eight subfamilies in the genome-wide database of Chinese cabbage. The analysis showed that the BrLEA73 gene was located on chromosome A09 and belonged to the LEA_6 subfamily. Quantitative real-time PCR analysis indicated that the BcLEA genes were differentially expressed to varying degrees in the roots, stems, leaves, and petioles of Wucai. The overexpressed BcLEA73 transgenic plants exhibited no significant differences in root length and seed germination rates compared to the wild-type (WT) plants under control conditions. Under salt and osmotic stress treatment, the root length and seed germination rates of the BcLEA73-OE strain were significantly greater than those of WT plants. Under salt stress, the total antioxidant capacity (T-AOC) of the BcLEA73-OE lines increased significantly, and the relative conductivity, (REL), hydrogen peroxide (H2O2) content, and superoxide anion (O2−) production rate decreased significantly. Under drought treatment, the survival rate of the BcLEA73-OE lines was significantly higher than that of WT plants. These results showed that the BcLEA73 gene of Wucai functions in enhancing the tolerance of plants to salt, drought, and osmotic stress. This study provides a theoretical basis to explore the relevant functions of the BcLEA gene family members of Wucai.

Faithful chromosome segregation of 8 duplicated haploid genomes into 8 daughter male gametes is essential for male gametogenesis and mosquito transmission ofPlasmodium. Plasmodiumevolves the endomitosis for this multinucleated cell division. However, the mechanism underlying the spindle-kinetochore attachment remains elusive. End-binding proteins (EBs) are the conserved microtubule (MT) plus-end binding proteins and play an important role in regulating MT plus-end dynamics. Here we report thatPlasmodiumEB1 is a unique orthologue distinct from the canonical eukaryotic EB1. Bothin vitroandin vivoassays revealed thatPlasmodiumEB1 lost MT plus-end tracking but gained MT-lattice affinity. This MT-binding feature of EB1 is contributed by both the CH domain and the linker region. EB1-deficient parasites produce male gametocytes that develop to the anucleated male gametes, leading to defective mosquito transmission of parasite. EB1 is localized at the nucleoplasm of male gametocytes. Upon gametogenesis, EB1 decorates the full-length of spindle MTs and regulates spindle structure. The kinetochores attach to spindle MTs laterally throughout three rounds of endomitosis and this attachment is EB1-dependent. Consequently, impaired spindle-kinetochore attachment was observed in EB1-deficient parasites. These results indicate that a parasite-specific EB1 with MT-lattice affinity has evolved to fulfill the spindle-kinetochore lateral attachment in male gametogenesis.

Vancomycin is recommended for the treatment of skin and soft tissue infections (SSTI) and bone and joint infections (BJI). However, a detailed investigation of the pharmacokinetic profile and optimal dosing regimens of vancomycin in pediatric patients with SSTI and BJI is lacking. We successfully developed a new PopPK model of vancomycin in this population by using scavenged blood samples with the typical values for clearance (CL) of 0.14 L/h/kg and volume of distribution (V) of 0.5 L/kg. Body weight was confirmed as the significant covariate on CL and V. The optimal dosing regimens of 75 mg/kg/day and 80 mg/kg/day were recommended for this specific population.

Human coronavirus 229E (HCoV-229E) and NL63 (HCoV-NL63) are endemic causes of upper respiratory infections such as the “common cold” but may occasionally cause severe lower respiratory tract disease in the elderly and immunocompromised patients. There are no approved antiviral drugs or vaccines for these common cold coronaviruses (CCCoV). The recent emergence of COVID-19 and the possible cross-reactive antibody and T cell responses between these CCCoV and SARS-CoV-2 emphasize the need to develop experimental animal models for CCCoV. Mice are an ideal experimental animal model for such studies, but are resistant to HCoV-229E and HCoV-NL63 infections. Here, we generated 229E and NL63 mouse models by exogenous delivery of their receptors, human hAPN and hACE2 using replication-deficient adenoviruses (Ad5-hAPN and Ad5-hACE2), respectively. Ad5-hAPN- and Ad5-hACE2-sensitized IFNAR −/− and STAT1 −/− mice developed pneumonia characterized by inflammatory cell infiltration with virus clearance occurring 7 d post infection. Ad5-hAPN- and Ad5-hACE2-sensitized mice generated virus-specific T cells and neutralizing antibodies after 229E or NL63 infection, respectively. Remdesivir and a vaccine candidate targeting spike protein of 229E and NL63 accelerated viral clearance of virus in these mice. 229E- and NL63-infected mice were partially protected from SARS-CoV-2 infection, likely mediated by cross-reactive T cell responses. Ad5-hAPN- and Ad5-hACE2-transduced mice are useful for studying pathogenesis and immune responses induced by HCoV-229E and HCoV-NL63 infections and for validation of broadly protective vaccines, antibodies, and therapeutics against human respiratory coronaviruses including SARS-CoV-2.

To rapidly analyze the dynamic characteristics of a compliant stroke amplification mechanism (CSAM) with completely distributed compliance, an analytical model based on the dynamic stiffness matrix with consideration of the damping effect is proposed. The natural frequency of the CSAM is optimized without attenuation of the amplification ratio based on this model. The optimized CSAM exhibits an approximately 112% higher natural frequency than the original mechanism along the main motion direction. The optimization result is verified through finite element simulation, with less than a 7% difference being observed. Moreover, the effects of frequency on the amplification ratio and input stiffness of the optimized CSAM are also discussed. The structural resonance is defined as the failure criterion of the optimized CSAM, and the sensitivity of the failure probability to manufacturing errors at different positions is analyzed. The findings show that the failure probability of the CSAM is more sensitive to parameters associated with the coordinates of the output stage and vertex.

Contact fatigue of carbon steel gear tooth surface under different lubrication conditions were investigated and the model of the effect of lubrication conditions on contact fatigue is established. Electrochemical corrosion will form nonferrous oxide on the tooth surface, and the crack corrosion between the nonferrous oxide and the Fe matrix may become the initiation position of contact fatigue. A high temperature generated by frictional heat can accelerate the plastic deformation. Micro damage less than Hertzian contact is easier to expand into macro pitting. The pressure around the micro damage increases when the micro damage partially coincides with the contact width, so the tooth surface around the pit is more likely to produce new pit, and then form the superposition and aggregation. The larger the lubricating oil supply, the larger the contact width, and the larger the width of the micro damage can be activated, the improvement of lubrication can promote the propagation of micro damage.

Bi2Sr2Ca2Cu3O10+δ (Bi-2223) precursors for the fabrication of high temperature superconducting tapes were prepared by spray pyrolysis technique followed by a calcination process. The influences of precursor powder phase composition on the phase evolution dynamics and final current capacity of Bi-2223 superconducting tapes were systematically studied. It was interesting to notice that slight increase of Cu content in chemical composition could cause obvious variations of both the phase composition and the morphology of CuO particles in precursors. Therefore, the Bi-2223 phase formation process during the sintering process of tapes could be affected, and the current capacity changed accordingly. On the other hand, during the calcination temperature optimization process, the Bi-2223 phase content in precursors changed accordingly, thus the Bi-2223 phase formation dynamics were also studied. More Bi-2223 nuclei were formed due to the pre-existed Bi-2223 grains, which worked as inhomogeneous nuclei centers. Thus, although the final Bi-2223 phase contents were similar in all the tapes, the particle size and texture structure of Bi-2223 varied greatly, which caused a dramatic decrease of critical current in Bi-2223 tapes with the formation of Bi-2223 in precursors. Therefore, it could be concluded that both the morphology of CuO particles and the Bi-2223 phase content in precursors were the factors controlling the phase evolution dynamics during Bi-2223 tape sintering process.