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Regulatory dendritic cell (DCregs)-based immunotherapy is a potential therapeutic tool for transplant rejection. We generated DCregs from murine induced pluripotent stem cells (iPSCs), which could remain in a “stable immature stage” even under strong stimulation. Harnessing this characteristic, we hypothesized that iPS-DCregs worked as a negative vaccine to generate regulatory T cells (Tregs), and induced donor-specific allograft acceptance. We immunized naive CBA (H-2Kk) mice with B6 (H-2Kb) iPS-DCregs and found that Tregs (CD4+CD25+FOXP3+) significantly increased in CBA splenocytes. Moreover, immunized CBA recipients permanently accepted B6 cardiac grafts in a donor-specific pattern. We demonstrated mechanistically that donor-type iPS-DCregs triggered transforming growth factor β1 secretion, under which the donor-antigen peptides directed naive CD4+ T cells to differentiate into donor-specific FOXP3+ Tregs instead of into effector T cells in vivo. These findings highlight the potential of iPS-DCregs as a key cell therapy resource in clinical transplantation.

The combined use of chemical and organic fertilizers is considered a good method to sustain high crop yield and enhance soil organic carbon (SOC), but it is still unclear when and to what extent chemical fertilizers could be replaced by organic fertilizers. We selected a long-term soil fertility experiment in Gongzhuling, Northeast China Plain to examine the temporal dynamics of crop yield and SOC in response to chemical nitrogen, phosphorus, and potassium (NPK) fertilizers and manure, applied both individually and in combination, over the course of three decades (1980–2010). We aimed to test 1) which fertilizer application is the best for increasing both maize yield and SOC in this region, and 2) whether chemical fertilizers can be replaced by manure to maintain high maize yield and enhance SOC, and if so, when this replacement should be implemented. We observed that NPK fertilizers induced a considerable increase in maize yield in the first 12 years after the initiation of the experiment, but manure addition did not. In the following years, the addition of both NPK fertilizers and manure led to an increase in maize yield. SOC increased considerably in treatments with manure but remained the same or even declined with NPK treatments. The increase in maize yield induced by NPK fertilizers alone declined greatly with increasing SOC, whereas the combination of NPK and manure resulted in high maize yield and a remarkable improvement in SOC stock. Based on these results we suggested that NPK fertilizers could be at least partially replaced by manure to sustain high maize yield after SOC stock has reached 41.96 Mg C ha−1 in the Northeast China Plain and highly recommend the combined application of chemical fertilizers and manure (i.e., 60 Mg ha−1).

Primary biliary cholangitis is an autoimmune liver disease. Here, the authors show that variants in interleukin genes which potentially deregulate their expression are associated with this condition, and suggest that the IL21 signalling pathway may have a role in disease aetiology.

Abstract At present, all cell strains derived from acute lymphoblastic leukemia (ALL) patients with the long arm of chromosome 11 aberration are accompanied with mixed lineage leukemia (MLL) gene rearrangement. In this study, we established a permanent ALL cell strain CHH-1 with the long arm of chromosome 11 aberration and without MLL rearrangement, hoping that it could be used for the research of ALL with such genetic abnormality. CHH-1 cell strain was certified through morphology, immunophenotype, genetics and immunoglobulin (Ig) gene rearrangement analysis. Cell characteristics including tumorigenic ability, semisolid colony forming ability, telomerase activity, autocrine and invasion were further detected. Cells were with an add(11)(q23) structural abnormality without MLL rearrangement, and were consistent with the genetic abnormality of the patient. In addition, these cells had features of tumor-forming ability, high colony forming capacity, unique cytokine autocrine mode, high telomerase activity, and high invasion ability. CHH-1 may prove to be a useful cell model for the research of human leukemia with genetic aberration in chromosome 11, and help explore the role of such genetic abnormality in the pathogenesis, progression and prognosis of ALL, and in developing new target drugs.

The embryonic process of forming a complex structure such as the heart remains poorly understood. Here, we show that Six2 marks a dynamic subset of second heart field progenitors. Six2-positive (Six2+) progenitors are rapidly recruited and assigned, and their descendants are allocated successively to regions of the heart from the right ventricle (RV) to the pulmonary trunk. Global ablation of Six2+ progenitors resulted in RV hypoplasia and pulmonary atresia. An early stage-specific ablation of a small subset of Six2+ progenitors did not cause any apparent structural defect at birth but rather resulted in adult-onset cardiac hypertrophy and dysfunction. Furthermore, Six2 expression depends in part on Shh signaling, and Shh deletion resulted in severe deficiency of Six2+ progenitors. Collectively, these findings unveil the chronological features of cardiogenesis, in which the mammalian heart is built sequentially by temporally distinct populations of cardiac progenitors, and provide insights into late-onset congenital heart disease.

Carvedilol, a third generation beta blocker, is in clinical use for heart failure patients. However, besides adrenergic receptor blockade, the pharmacological effects of carvedilol on cardiomyocytes remain unknown. AMP-activated protein kinase (AMPK) is an emerging target recognized for heart failure treatment. The mechanical properties and intracellular Ca2+ properties were measured in isolated cardiomyocyte contractile functions in response to ischemic stress. Treatment of cardiomyocytes with carvedilol augmented phosphorylation of AMPK and downstream acetyl CoA carboxylase (ACC), and ameliorated hypoxia-induced impairment in maximal velocity of shortening (+dL/dt) and relengthening (-dL/dt), and the impaired peak height and peak shortening (PS) amplitude caused by hypoxia. Carvedilol treatment improved calcium homeostasis with rescuing the peak Ca2+ signal, the maximum rate of Ca2+ change during contraction (+dF/dt) and the maximum rate of Ca2+ change during relaxation (-dF/dt) under hypoxia conditions. In mouse hearts perfused ex vivo with carvedilol, the function of post-ischemia left ventricle was improved and an augmentation in myocardial glucose uptake and glucose oxidation, and inhibition of fatty acid oxidation during ischemia and reperfusion. The protective effect of carvedilol was further supported in an in vivo regional ischemia model by ligation of left anterior descending coronary artery (LAD), mice treated with carvedilol followed by LAD occlusion and reperfusion showed significant size reduction in infarcted myocardium and improved cardiac functions. Therefore, Carvedilol as a clinical drug can modulate cardiac AMPK signaling pathway to reduce ischemic insults by ischemia and reperfusion.

Ginsenoside Re (GS-Re), which is a major monomeric member of the ginseng trialcohol saponin family, is one of the main active components of ginseng and plays an important role in protecting the cardiovascular system. Here, we report a novel function by which GS-Re regulates the eNOS/NO/cGMP pathway, which affects the platelet-derived growth factor-BB (PDGF-BB)-induced proliferation of vascular smooth muscle cells (VSMCs). GS-Re inhibited PDGF-BB-induced VSMC proliferation in a concentration-dependent manner without cytotoxicity, and the endothelial nitric oxide synthase (eNOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) antagonized the antiproliferative effect of GS-Re. The flow cytometry analysis suggested that GS-Re regulates VSMC proliferation by influencing the cell cycle transition from G0/G1 to S phase and decreasing the expression of G0/G1-specific regulatory proteins, including proliferating cell nuclear antigen (PCNA), cyclin D1, and CDK4, in PDGF-BB-treated VSMCs, consequently upregulating the protein expression of p21. After GS-Re treatment, the levels of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) and the phos-eNOS Ser1177/eNOS protein ratio were obviously increased. In addition, treatment with L-NAME blocked the eNOS/NO/cGMP signaling pathway, and the protein levels of PCNA, cyclin D1, and CDK4 were markedly increased in GS-Re-treated VSMCs, while p21 expression was decreased in PDGF-BB-induced VSMCs. Overall, these findings reveal that GS-Re can inhibit the proliferation of VSMCs through G0/G1 cell cycle arrest, which is closely related to eNOS/NO/cGMP pathway activation. The present results provide basic pharmacological evidence of the potential prevention and treatment of cardiovascular diseases by GS-Re.

Tyrosine autophosphorylation plays a crucial regulatory role in the kinase activities of fibroblast growth factor receptors (FGFRs), and in the recruitment and activation of downstream intracellular signaling pathways. Biophysical and biochemical investigations of FGFR kinase domains in membrane environments offer key insights into phosphorylation mechanisms. Hence, we constructed nickel chelating nanodiscs based on a 22-residue peptide. The spontaneous anchoring of N-terminal His6-tagged FGFR1c kinase domain (FGFR1K) onto peptide nanodiscs grants FGFR1K orientations occurring on native plasma membranes. Following membrane incorporation, the autophosphorylation of FGFR1K, as exemplified by Y653 and Y654 in the A-loop and the total tyrosine phosphorylation, increase significantly. This in vitro reconstitution system may be applicable to studies of other membrane associated phenomena.

Summary: Reprogramming somatic cells to pluripotency by Oct4, Sox2, Klf4, and Myc represent a paradigm for cell fate determination. Here, we report a combination of Jdp2, Jhdm1b, Mkk6, Glis1, Nanog, Essrb, and Sall4 (7F) that reprogram mouse embryonic fibroblasts or MEFs to chimera competent induced pluripotent stem cells (iPSCs) efficiently. RNA sequencing (RNA-seq) and ATAC-seq reveal distinct mechanisms for 7F induction of pluripotency. Dropout experiments further reveal a highly cooperative process among 7F to dynamically close and open chromatin loci that encode a network of transcription factors to mediate reprogramming. These results establish an alternative paradigm for reprogramming that may be useful for analyzing cell fate control. : Wang et al. report a 7F reprogramming system for iPSC generation and the underlying mechanism for inducing pluripotency through a TF network, opening an alternative path for reprogramming cell fate.

Sepsis is a systemic inflammatory response syndrome caused by infection. With high morbidity and mortality of this disease, there is a need to find early effective diagnosis and assessment methods to improve the prognosis of patients. Heparin-binding protein (HBP) is a granular protein derived from polynuclear neutrophils. The biosynthetic HBP in neutrophils is rapidly released under the stimulation of bacteria, resulting in increased vascular permeability and edema. It is reasonable to speculate that the HBP in plasma may serve as a novel diagnostic marker for sepsis, bacterial skin infection, acute bacterial meningitis, leptospirosis, protozoan parasites, and even some noncommunicable diseases. It implies that in the detection and diagnosis of sepsis, it will be possible to make relevant diagnosis through this new indicator in the future. In this review, we summarize the typical biological function of HBP and its latest research progress to provide theoretical basis for clinical prediction and diagnosis of sepsis.

Objective. To determine the subcellular localization of epithelial cell adhesion molecule (EpCAM) in labial salivary gland (LSG) and evaluate the diagnostic use of the extracellular domain of EpCAM (EpEX) and intracellular domain (EpICD) for primary Sjögren’s syndrome (pSS). Methods. Immunohistochemical (IHC) analysis was conducted using EpEX and EpICD domain-specific antibodies on labial salivary gland biopsy (LSGB) from participants. Chi-square or Fisher’s exact analysis, Mann–Whitney U-test, and Kruskal-Wallis test compared differences among groups. Independent risk factors of pSS were determined by multiple logistic regression analysis. Receiver-operator characteristic curves (ROC) were carried out to estimate the diagnostic value. Results. Compared to non-SS controls, loss of membranous EpEX and EpICD expression was observed in LSGB of pSS patients, which occurred in parallel with increased accumulation of cytoplastic and nuclear EpICD. The subcellular EpEX/EpICD expressions were associated with various features of pSS patients, especially histopathological grade of LSGB. Furthermore, high IHC scores of membranous EpEX were independent risk factors for pSS, even for the pSS patients at early stage. The IHC scores of subcellular EpEX/EpICD were of great diagnostic value for pSS with high sensitivity (70-80%) and specificity (85-95%). Conclusion. This study first found the aberrant expression pattern of EpCAM in LSG of pSS patients. The IHC scores of subcellular EpEX/EpICD were demonstrated to have the potential to act as diagnostic biomarkers for pSS.

Objective. Familial dysalbuminemic hyperthyroxinemia (FDH) has now become an established cause for spurious asymptomatic hyperthyroxinemia. Several different codon mutations on albumin gene had been identified. We here provided an established but rarely reported heterozygous mutation based on gene sequencing results from a Chinese family. Methods. The proband is a 14-year-old girl with light goiter and asymptomatic clinical presentations, whose thyroid function test by a one-step immunoassay showed increased free thyroxine (FT4) and free triiodothyronine (FT3) but nonsuppressed thyrotropin (TSH). All thyroid auto-antibodies were in the normal range. Blood samples were collected from her and most of her immediate family members for target gene sequencing and verification. Results. Hyperthyroxinemia was also confirmed in the proband’s mother and one of her uncles and his son. In the proband and these three pedigrees, the high-throughput gene screening sequencing and the following Sanger sequencing disclosed a heterozygous mutation in the albumin gene, which located in its exon 7 (c.725G > A), and correspondingly leads to an arginine replacement with a histidine (R242H) in its protein. This is an established mutation named as R218H if present without signal peptide sequence. Conclusions. For patients with asymptomatic hyperthyroxinemia, FDH should be clinically excluded before embarking on further investigations for other specific causes.

Worldwide morbidity and mortality from acute myocardial infarction (AMI) and related heart failure remain high. While effective early reperfusion of the criminal coronary artery after a confirmed AMI is the typical treatment at present, collateral myocardial ischemia-reperfusion injury (MIRI) and pertinent cardioprotection are still challenging to address and have inadequately understood mechanisms. Therefore, unveiling the related novel molecular targets and networks participating in triggering and resisting the pathobiology of MIRI is a promising and valuable frontier. The present study specifically focuses on the recent MIRI advances that are supported by sophisticated bio-methodology in order to bring the poorly understood interrelationship among pro- and anti-MIRI participant molecules up to date, as well as to identify findings that may facilitate the further investigation of novel targets.

The depression incidence is much higher in patients with diabetes mellitus (DM), and the majority of these cases remain under-diagnosed. Type 1 diabetes mellitus (T1D) is now widely thought to be an organ-specific autoimmune disease. As a chronic autoimmune condition, T1D is characterized by T cell-mediated selective loss of insulin-producing β-cells. The age of onset of T1D is earlier than T2D, and T1D patients have an increased vulnerability to depression due to its diagnosis and treatment burden occurring in a period when the individuals are young. The literature has suggested that inflammatory cytokines play a wide role in both diseases. In this review, the mechanisms behind the initiation and propagation of the autoimmune response in T1D and depression are analyzed, and the contribution of cytokines to both conditions is discussed. This review outlines the immunological mechanism of T1D and depression, with a particular emphasis on the role of tumor necrosis factor-α (TNF-α), IL-1β, and interferon-γ (IFN-γ) cytokines and their signaling pathways. The purpose of this review is to highlight the possible pathways of the cytokines shared by these two diseases via deciphering their cytokine cascades. They may provide a basic groundwork for future study of the possible mechanism that links these two diseases and to develop new compounds that target the same pathway but can conquer two diseases.

Clinical studies treating pediatric and adult solid tumors, such as glioblastoma (GBM), with a triple-drug regimen of temozolomide (TMZ), bevacizumab (BEV), and irinotecan (IRI) [TBI] have demonstrated various efficacies, but with no unexpected toxicities. The TBI regimen has never been studied in recurrent GBM (rGBM) patients. In this retrospective study, we investigated the outcomes and side effects of rGBM patients who had received the TBI regimen. We identified 48 adult rGBM patients with a median age of 56 years (range: 26–76), who received Tumor Treating Fields (TTFields) treatment for 30 days or longer, and concurrent salvage chemotherapies. The patients were classified into two groups based on chemotherapies received: TBI with TTFields (TBI+T, N = 18) vs. bevacizumab (BEV)-based chemotherapies with TTFields (BBC+T, N = 30). BBC regimens were either BEV monotherapy, BEV+IRI or BEV+CCNU. Patients in TBI+T group received on average 19 cycles of TMZ, 26 and 21 times infusions with BEV and IRI, respectively. Median overall survival (OS) and progression-free survival (PFS) for rGBM (OS-R and PFS-R) patients who received TBI+T were 18.9 and 10.7 months, respectively. In comparison, patients who received BBC+T treatment had OS-R and PFS-R of 11.8 (P > 0.05) and 4.7 (P < 0.05) months, respectively. Although the median PFS results were significantly different by 1.5 months (6.6 vs. 5.1) between TBI+T and BBC+T groups, the median OS difference of 14.7 months (32.5 vs. 17.8) was more pronounced, P < 0.05. Patients tolerated TBI+T or BBC+T treatments well and there were no unexpected toxicities. The most common side effects from TBI+T treatment included grade III hypertension (38.9%) and leukopenia (22.2%). In conclusion, the TBI regimen might play a role in the improvement of PFS-R and OS-R among rGBM patients. Prospective studies with a larger sample size are warranted to study the efficacy and toxicity of TBI+T regimen for rGBM.

A de novo missense variant in Rag GTPase protein C (RagCS75Y) was recently identified in a syndromic dilated cardiomyopathy (DCM) patient. However, its pathogenicity and the related therapeutic strategy remain unclear. We generated a zebrafish RragcS56Y (corresponding to human RagCS75Y) knock-in (KI) line via TALEN technology. The KI fish manifested cardiomyopathy-like phenotypes and poor survival. Overexpression of RagCS75Y via adenovirus infection also led to increased cell size and fetal gene reprogramming in neonatal rat ventricle cardiomyocytes (NRVCMs), indicating a conserved mechanism. Further characterization identified aberrant mammalian target of rapamycin complex 1 (mTORC1) and transcription factor EB (TFEB) signaling, as well as metabolic abnormalities including dysregulated autophagy. However, mTOR inhibition failed to ameliorate cardiac phenotypes in the RagCS75Y cardiomyopathy models, concomitant with a failure to promote TFEB nuclear translocation. This observation was at least partially explained by increased and mTOR-independent physical interaction between RagCS75Y and TFEB in the cytosol. Importantly, TFEB overexpression resulted in more nuclear TFEB and rescued cardiomyopathy phenotypes. These findings suggest that S75Y is a pathogenic gain-of-function mutation in RagC that leads to cardiomyopathy. A primary pathological step of RagCS75Y cardiomyopathy is defective mTOR–TFEB signaling, which can be corrected by TFEB overexpression, but not mTOR inhibition.

Erythropoietin (EPO) plays an important role in erythropoiesis by its action in blocking apoptosis of progenitor cells and protects both photoreceptors and retinal ganglion cells from induced or inherited degeneration. A modified form of EPO, EPO-R76E has attenuated erythropoietic activity but is effective in inhibiting apoptosis, oxidative stress, and inflammation in several models of retinal degeneration. In this study, we used recombinant Adeno Associated Virus (AAV) to provide long-term sustained delivery of EPO-R76E and demonstrated its effects in a mouse model of dry-AMD in which retinal degeneration is induced by oxidative stress in the retinal pigment epithelial (RPE) cells. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE/choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific EPO expression. Retinal function was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress, which is implicated as a potential cause of Age-Related Macular Degeneration.

A transparent polyamide, poly(4,4′-aminocyclohexyl methylene dodecanedicarboxylamide) (PAPACM12), was studied and characterized by in situ wide-angle X-ray diffraction (WAXD) to establish the relationship between its crystallization behavior, crystalline form transition under external fields, and macroscopic properties. During the heating process, cold crystallization occurred and increased, and there was no form transition below the melting point. During the isothermal process, PAPACM12 exhibited the same crystalline structure as that during the heating process. The crystalline structure of PAPACM12 was attributed to α-form crystal, which is the stable form, according to the WAXD diffraction peaks of the conventional AABB-type polyamides. During stretching deformation, the crystal transition from α-form to γ-form and strain-induced crystallization were observed to contribute to the PAPACM12 with higher breaking strength and elongation. This study firstly determine the crystalline structure of transparent polyamides, and then the controlled strain-induced crystallization and transformation are demonstrated to be effective preparation methods for polyamides with high properties.

The surface porous ultrahigh molecular weight polyethylene (UHMWPE) composites were successfully fabricated with NaCl and graphene oxide (GO) in the hot-pressing procedure. The GO sheets were evenly dispersed in UHMWPE with the sedimentation method of GO in saturated NaCl. The morphologies, chemical compositions, mechanical, and tribological properties of GO and surface porous GO/NaCl/UHMWPE were investigated. The results show that GO sheet and NaCl could be evenly dispersed in UHMWPE. The regular pores are present on the surface of UHMWPE after NaCl dissolution in distilled water. The wear resistance properties are improved significantly, and the friction properties increased slightly with the addition of GO and NaCl.

The corepressor NCoR is required for tamoxifen-mediated ERα-dependent transcriptional repression. Here, the authors show that COPS5 confers tamoxifen-resistance through the degradation of NCOR, the recruitment of the co-activator PCAF to ERα binding sites and the subsequent ERα transcriptional activity.

A long-term (18 years) effect of different fertilization and tillage management practices- fallowing treatment (no fertilizer, no cultivation); CK (no fertilizer, cultivation); N (nitrogen fertilizer); NP (nitrogen and phosphorus fertilizer); NK (nitrogen and potassium fertilizer); PK (phosphorus and potassium fertilizer); NPK (nitrogen, phosphorus, and potassium fertilizer); M1NPK (chemical fertilizer plus manure); 1.5M1NPK (1.5 times M1NPK); NPKS (mineral fertilizer plus straw); Rot (3-year crop rotation of maize-maize-soybean with M1NPK), and M2NPK (2 times manure plus mineral fertilizer) - on the content of total nitrogen and organic forms of nitrogen and the nitrogen content in different particle-size fractions were studied in topsoil (0-20 cm) in Black Soil of NE China by using the methods of Bremner. The results showed that the combined application of organic and mineral fertilizers could significantly increase the contents and proportions of total nitrogen and organic nitrogen forms in soil. Comparing to CK treatment, the content of total nitrogen and hydrolyzable nitrogen increased in the fallow and organic materials treatments. Compared with M1NPK treatment, rotation was more beneficial to increasing organic nitrogen content, especially remarkably increasing amino acid nitrogen. The nitrogen response of sand, silt, and clay was most sensitive on manure; the effects of fallow and manure treatments on sand were notable, the nitrogen content in sand with NPKS increased by 40.86% compared with CK treatment. Our results imply that fallow/rotation managements, and manure/straw application can improve soil fertility.

The yeast (Saccharomyces cerevisiae) strain 2137 involved in lychee wine production was used to investigate acetate metabolism at different temperatures during lychee wine fermentation. Fermentation tests were conducted using lychee juice supplemented with acetic acid. The ability of yeast cells to metabolize acetic acid was stronger at 20 °C than at 25 °C or 30 °C. The addition of acetic acid suppressed the yeast cell growth at the tested temperatures. The viability was higher and the reactive oxygen species concentration was lower at 20 °C than at 30 °C; this result indicated that acid stress adaptation protects S. cerevisiae from acetic-acid-mediated programmed cell death. The acetic acid enhanced the thermal death of yeast at high temperatures. The fermentation temperature modified the metabolism of the yeasts and the activity of related enzymes during deacidification, because less acetaldehyde, less glycerol, more ethanol, more succinic acid and more malic acid were produced, with higher level of acetyl–CoA synthetase and isocitrate lyase activity, at 20 °C.

This paper reviews the evolution of planetary boundary layer (PBL) parameterization schemes that have been used in the operational version of the Hurricane Weather Research and Forecasting (HWRF) model since 2011. Idealized simulations are then used to evaluate the effects of different PBL schemes on hurricane structure and intensity. The original Global Forecast System (GFS) PBL scheme in the 2011 version of HWRF produces the weakest storm, while a modified GFS scheme using a wind-speed dependent parameterization of vertical eddy diffusivity (Km) produces the strongest storm. The subsequent version of the hybrid eddy diffusivity and mass flux scheme (EDMF) used in HWRF also produces a strong storm, similar to the version using the wind-speed dependent Km. Both the intensity change rate and maximum intensity of the simulated storms vary with different PBL schemes, mainly due to differences in the parameterization of Km. The smaller the Km in the PBL scheme, the faster a storm tends to intensify. Differences in hurricane PBL height, convergence, inflow angle, warm-core structure, distribution of deep convection, and agradient force in these simulations are also examined. Compared to dropsonde and Doppler radar composites, improvements in the kinematic structure are found in simulations using the wind-speed dependent Km and modified EDMF schemes relative to those with earlier versions of the PBL schemes in HWRF. However, the upper boundary layer in all simulations is much cooler and drier than that in dropsonde observations. This model deficiency needs to be considered and corrected in future model physics upgrades.

This paper discusses how Liu Cixin’s 2000 novella “The Wandering Earth” was adapted into a family melodrama that ultimately reinforces the authority of the Father and the nation-state. It analyzes the complex mechanisms, such as mise en abyme and scapegoating, that serve to condone the patriarch’s power, as well as the intertextuality tying the film to the socialist culture. This paper analyses the social context that foregrounds the conversion from symbolic patricide (breaking the established system) to symbolic patrilineality (integration into the social order) in the film and also discusses the inherent tension between the radical apocalyptic vision offered in the original science fiction story and the cultural industry serving the interests of the established order.

Recently, extensive studies have focused on exploring a variety of silicon (Si) nanostructures among which Si quantum dots (Si QDs) may be applied in all Si tandem solar cells (TSCs) for the time to come. By virtue of its size tunability, the optical bandgap of Si QDs is capable of matching solar spectra in a broad range and thus improving spectral response. In the present work, size-controllable Si QDs are successfully obtained through the formation of Si QDs/SiC multilayers (MLs). According to the optical absorption measurement, the bandgap of Si QDs/SiC MLs shows a red shift to the region of long wavelength when the size of dots increases, well conforming to quantum confinement effect (QCE). Additionally, heterojunction solar cells (HSCs) based on Si QDs/SiC MLs of various sizes are presented and studied, which demonstrates the strong dependence of photovoltaic performance on the size of Si QDs. The measurement of external quantum efficiency (EQE) reveals the contribution of Si QDs to the response and absorption in the ultraviolet–visible (UV-Vis) light range. Furthermore, Si QDs/SiC MLs-based solar cell shows the best power conversion efficiency (PCE) of 10.15% by using nano-patterned Si light trapping substrates.

In the present study, plasma spray welding was used to prepare an in-situ niobium carbide (NbC) reinforced Ni-based composite coating on the low carbon steel, and the phase composition and the microstructure of the composite coatings were studied. The wear resistance and the wear mechanism of the composite coatings were also researched by the wear tests. The results showed that the main phases of the composite coating were NbC, γ-Ni, Cr23C6, Ni3Si, CrB, Cr5B3, Cr7C3 and FeNi3. A number of fine in-situ NbC particles and numerous chromium carbide particles were distributed in the γ-Ni matrix. The increase in the mass fraction of Nb and NiCr-Cr3C2 could lead to the increase in NbC particles in the composite coatings. Due to the high hardness of NbC and chromium carbides, the micro-hardness and the wear resistance of the composite coatings were advanced. The composite coating with the powder mixtures of 20% (Nb + NiCr-Cr3C2) and 80% NiCrBSi had the highest micro-hardness and the best wear resistance in this study. The average micro-hardness reached the maximum value 1025HV0.5. The volume loss was 39.2 mm3, which was merely 37% of that of the NiCrBSi coating and 6% of that of the substrate under the identical conditions.

With the development of fine surgery and desire for low-injury methods, the frictional properties of surgical sutures are one of the crucial factors that can cause damage to tissue, especially for some fragile and sensitive human tissues such as the eyeball. In this study, dopamine hydrochloride and graphene oxide were used as external application agents to prepare a biological coating for the surface of multifilament surgical sutures. The effects of this biocoating on the surface morphology, chemical properties, mechanical properties, and tribological properties of surgical sutures were studied. The friction force and the coefficient of friction of surgical sutures penetrating through a skin substitute were evaluated using a penetration friction apparatus and a linear elastic model. The tribological mechanism of the coating on the multifilament surgical sutures was investigated according to the results of the tribological test. The results showed that there were uniform dopamine and graphene oxide films on the surface of the surgical sutures, and that the fracture strength and yield stress of the coated sutures both increased. The surface wettability of the surgical sutures was improved after the coating treatment. The friction force and the coefficient of friction of the multifilament surgical sutures with the dopamine hydrochloride and graphene oxide coating changed little compared to those of the untreated multifilament surgical sutures.

To improve the water solubility of phosphoramidate siloxane and decrease the amount of flame-retardant additives used in the functional coating for cotton fabrics, a water-soluble phosphoramidate siloxane polymer (PDTSP) was synthesized by sol-gel technology and flame-retardant cotton fabrics were prepared with a multistep coating process. A vertical flammability test, limited oxygen index (LOI), thermogravimetric analysis, and cone calorimetry were performed to investigate the thermal behavior and flame retardancy of PDTSP-coated fabrics. The coated cotton fabrics and their char residues after combustion were studied by attenuated total reflection infrared spectroscopy (FTIR-ATR), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). All results presented that PDTSP-coated cotton fabrics had good flame retardancy and char-forming properties. PDTSP coating was demonstrated to posess gas-phase flame-retardant mechanism as well as a condensed phase flame-retardant mechanism, which can be confirmed by thermogravimetric analysis-Fourier transform infrared spectroscopy (TG-IR) and cone calorimetry test. Also, the preparation process had little effect on the tensile strength of cotton fabrics, although the air permeability and whiteness had a slight decrease. After different washing cycles, the coated samples still maintained good char-forming properties.

Over the past couple of decades, extensive research has been conducted on silicon (Si) based solar cells, whose power conversion efficiency (PCE) still has limitations because of a mismatched solar spectrum. Recently, a down-shifting effect has provided a new way to improve cell performances by converting ultraviolet (UV) photons to visible light. In this work, caesium lead bromide perovskite quantum dots (CsPbBr3 QDs) are synthesized with a uniform size of 10 nm. Exhibiting strong absorption of near UV light and intense photoluminescence (PL) peak at 515 nm, CsPbBr3 QDs show a potential application of the down-shifting effect. CsPbBr3 QDs/multicrystalline silicon (mc-Si) hybrid structured solar cells are fabricated and systematically studied. Compared with mc-Si solar cells, CsPbBr3 QDs/mc-Si solar cells have obvious improvement in external quantum efficiency (EQE) within the wavelength ranges of both 300 to 500 nm and 700 to 1100 nm, which can be attributed to the down-shifting effect and the anti-reflection property of CsPbBr3 QDs through the formation of CsPbBr3 QDs/mc-Si structures. Furthermore, a detailed discussion of contact resistance and interface defects is provided. As a result, the coated CsPbBr3 QDs are optimized to be two layers and the solar cell exhibits a highest PCE of 14.52%.

This study analyses Global Positioning System dropsondes to document the axisymmetric tropical cyclone (TC) boundary-layer structure, based on storm intensity. A total of 2608 dropsondes from 42 named TCs in the Atlantic basin from 1998 to 2017 are used in the composite analyses. The results show that the axisymmetric inflow layer depth, the height of maximum tangential wind speed, and the thermodynamic mixed layer depth are all shallower in more intense TCs. The results also show that more intense TCs tend to have a deep layer of the near-saturated air inside the radius of maximum wind speed (RMW). The magnitude of the radial gradient of equivalent potential temperature (θe) near the RMW correlates positively with storm intensity. Above the inflow layer, composite structures of TCs with different intensities all possess a ring of anomalously cool temperatures surrounding the warm-core, with the magnitude of the warm-core anomaly proportional to TC intensity. The boundary layer composites presented here provide a climatology of how axisymmetric TC boundary layer structure changes with intensity.

Rod and cone phosphodiesterase 6 (PDE6) are key effector enzymes of the vertebrate phototransduction pathway. Rod PDE6 consists of two catalytic subunits PDE6α and PDE6β and two identical inhibitory PDE6γ subunits, while cone PDE6 is composed of two identical PDE6α’ catalytic subunits and two identical cone-specific PDE6γ’ inhibitory subunits. Despite their prominent function in regulating cGMP levels and therefore rod and cone light response properties, it is not known how each subunit contributes to the functional differences between rods and cones. In this study, we generated an rd10/cpfl1 mouse model lacking rod PDE6β and cone PDE6α’ subunits. Both rod and cone photoreceptor cells are degenerated with age and all PDE6 subunits degrade in rd10/cpfl1 mice. We expressed cone PDE6α’ in both rods and cones of rd10/cpfl1 mice by adeno-associated virus (AAV)-mediated delivery driven by the ubiquitous, constitutive small chicken β-actin promoter. We show that expression of PDE6α’ rescues rod function in rd10/cpfl1 mice, and the restoration of rod light sensitivity is attained through restoration of endogenous rod PDE6γ and formation of a functional PDE6α’γ complex. However, improved photopic cone responses were achieved only after supplementation of both cone PDE6α’ and PDE6γ’ subunits but not by PDE6α’ treatment alone. We observed a two fold increase of PDE6α’ levels in the eyes injected with both PDE6α’ plus PDE6γ’ relative to eyes receiving PDE6α’ alone. Despite the presence of both PDE6γ’ and PDE6γ, the majority of PDE6α’ formed functional complexes with PDE6γ’, suggesting that PDE6α’ has a higher association affinity for PDE6γ’ than for PDE6γ. These results suggest that the presence of PDE6γ’ augments cone PDE6 assembly and enhances its stability. Our finding has important implication for gene therapy of PDE6α’-associated achromatopsia.

CD8+CD28− T suppressor cells (Ts) have been recently documented to play an important role in alloimmunity. Therefore, understanding and optimizing the conditions under which these cells are generated and/or expanded would greatly facilitate further research and potential clinical use. In this study, we describe rapid expansion of human allospecific CD8+CD28− Ts cells through coculture of CD8+ T cells with human leukocyte antigen-mismatched donor antigen-presenting cells plus IL-15 in a relative short period of time in vitro. Interestingly, IL-15 promotes the expansion of CD8+CD28− Ts cells through several parallel mechanisms. The expanded CD8+CD28− Ts cells upregulate expression of CD132, CD25, and programmed cell death protein 1 (PD-1), but downregulate expression of CD122, GZM-B, and perforin, while exhibiting no cytotoxicity. Most importantly, the expanded CD8+CD28− Ts cells vigorously inhibit CD4+ T cells proliferation in a contact-dependent and donor-specific manner both in vitro and in vivo. Interestingly, the co-inhibitory molecules PD-1 and programmed death-ligand 1 play an obligatory role in the mechanisms of CD8+CD28− Ts cells suppression. Taken together, our study report novel methodology for IL-15-induced expansion of human CD8+CD28− Ts cells and possible mechanisms. These findings may facilitate understanding of transplant rejection and promote clinical application of CD8+CD28− Ts cell-based strategies for inducing and monitoring transplant tolerance in the future.

Summary: Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis. : Seiler et al. report that 119 splicing factor genes carry putative driver mutations over 33 tumor types in TCGA. The most common mutations appear to be mutually exclusive and are associated with lineage-independent altered splicing. Samples with these mutations show deregulation of cell-autonomous pathways and immune infiltration. Keywords: splicing, SF3B1, U2AF1, SRSF2, RBM10, FUBP1, cancer, mutation

OBJECTIVE:Pain management is a huge challenge in the treatment of rheumatoid arthritis (RA), and central sensitization is reportedly involved in the development of pain. The current study was undertaken to explore the possible role of N-methyl-D-aspartate receptors (NMDARs) in the spinal mechanism of central sensitization in RA using a collagen-induced arthritis (CIA) model. METHODS:Mechanical hypersensitivity was assessed in C57BL/6 mice, before and after the induction of CIA via administration of chick type II collagen. Analgesic drugs, receptor antagonist, and kinase inhibitor were administrated intrathecally in the spinal cord. Protein expression and phosphorylation changes were detected via immunoblotting. RESULTS:CIA mice developed significant mechanical hypersensitivity, and spinal administration of the NMDAR antagonist D-2-amino-5-phosphonovaleric acid (D-APV) effectively attenuated peripheral pain hypersensitivity. There was specific enhancement of synaptic NR2B-containing NMDAR (NR2BR) expression in the spinal dorsal horns of the mice. Both the increased total protein expression of NR2B subunit and the enhanced total phosphorylation level of NR2B subunit at 1472 tyrosine promoted the synaptic expression of NMDAR in the mice. Intrathecal injection of tramadol suppressed synaptic NMDAR expression mainly by changing the synaptic phosphorylation state of NR2B subunit at Tyr1472. Extracellular signal-regulated protein kinases 2 (ERK2) activity synchronized with the synaptic expression of NR2BR, which was downregulated by the action of tramadol. CONCLUSION:Specific enhancement of NR2BR in the spinal dorsal horn may be vital for central sensitization in the CIA model of RA. The NR2BR/ERK2 pathway may be a promising target for pain management in RA patients.

BACKGROUND AND OBJECTIVE:Markov micro-simulation models are being increasingly used in health economic evaluations. An important feature of the Markov micro-simulation model is its ability to consider transition probabilities of heterogeneous subgroups with different risk profiles. A survival analysis is generally performed to accurately estimate the transition probabilities associated with the risk profiles. This study aimed to apply a flexible parametric survival model (FPSM) to estimate individual transition probabilities. MATERIALS AND METHODS:The data were obtained from a cohort study investigating ischemic stroke outcomes in Western China. In total, 585 subjects were included in the analysis. To explore the goodness of fit of the FPSM, we compared the estimated hazard ratios and baseline cumulative hazards, both of which are necessary to the calculate individual transition probabilities, and the Markov micro-simulation models constructed using the FPSM and Cox model to determine the validity of the two Markov micro-simulation models and cost-effectiveness results. RESULTS:The flexible parametric proportional hazards model produced hazard ratio and baseline cumulative hazard estimates that were similar to those obtained using the Cox proportional hazards model. The simulated cumulative incidence of recurrent ischemic stroke and 5-years cost-effectiveness of Incremental cost-effectiveness Ratios (ICERs) were also similar using the two approaches. A discrepancy in the results was evident between the 5-years cost-effectiveness and the 10-years cost-effectiveness of ICERs, which were approximately 0.9 million (China Yuan) and 0.5 million (China Yuan), respectively. CONCLUSIONS:The flexible parametric survival model represents a good approach for estimating individual transition probabilities for a Markov micro-simulation model.

Safety issues associated with transcription factors or viruses may be avoided with the use of chemically induced pluripotent stem cells (CiPSCs), thus promoting their clinical application. Previously, we had successfully developed and standardized an induction method using small-molecule compound, with simple operation, uniform induction conditions, and clear constituents. In order to verify that the CiPSCs were indeed reprogrammed from mouse embryonic fibroblasts (MEFs), and further explore the underlying mechanisms, FSP-tdTomato mice were used to construct a fluorescent protein-tracking system of MEFs, for revealing the process of CiPSC reprogramming. CiPSCs were identified by morphological analysis, mRNA, and protein expression of pluripotency genes, as well as teratoma formation experiments. Results showed that after 40-day treatment of tdTomato-MEFs with small-molecule compounds, the cells were presented with prominent nucleoli, high core-to-cytoplasmic ratio, round shape, group and mass arrangement, and high expression of pluripotency gene. These cells could differentiate into three germ layer tissues in vivo. As indicated by the above results, tdTomato-MEFs could be reprogrammed into CiPSCs, a lineage that possesses pluripotency similar to mouse embryonic stem cells (mESCs), with the use of small-molecule compounds. The establishment of CiPSC lineage, tracked by fluorescent protein, would benefit further studies exploring its underlying mechanisms. With continuous expression of fluorescent proteins during cellular differentiation, this cell lineage could be used for tracking CiPSC transplantation and differentiation into functional cells.

The Wnt/β-catenin pathway is implicated in left-right (LR) axis determination; however, the underlying mechanism remains elusive. Prompted by our recent discovery that Wnt signaling regulates ciliogenesis in the zebrafish Kupffer's vesicle (KV) via Foxj1a, a ciliogenic transcription factor, we decided to elucidate functions of Foxj1a in Wnt-regulated LR pattern formation. We showed that targeted injection of wnt8a mRNA into a single cell at the 128-cell stage is sufficient to induce ectopic foxj1a expression and ectopic cilia. By interrogating the transcription circuit of foxj1a regulation, we found that both Lef1 and Tcf7 bind to a consensus element in the foxj1a promoter region. Depletion of Lef1 and Tcf7 inhibits foxj1a transcription in the dorsal forerunner cells, downregulates cilia length and number in KV, and randomizes LR asymmetry. Targeted overexpression of a constitutively active form of Lef1 also induced an ectopic protrusion that contains ectopic transcripts for sox17, foxj1a, and charon, and ectopic monocilia. Further genetic studies using this ectopic expression platform revealed two distinct functions of Foxj1a; mediating Wnt-governed monocilia length elongation as well as charon transcription. The novel Foxj1a-charon regulation is conserved in KV, and importantly, it is independent of the canonical role of Foxj1a in the biosynthesis of motile cilia. Together with the known function of motile cilia movement in generating asymmetric expression of charon, our data put forward a hypothesis that Foxj1a confers both ciliary and non-ciliary functions of Wnt signaling, which converge on charon to regulate LR pattern formation.

Recurrent mutations in the spliceosome are observed in several human cancers, but their functional and therapeutic significance remains elusive. SF3B1, the most frequently mutated component of the spliceosome in cancer, is involved in the recognition of the branch point sequence (BPS) during selection of the 3′ splice site (ss) in RNA splicing. Here, we report that common and tumor-specific splicing aberrations are induced by SF3B1 mutations and establish aberrant 3′ ss selection as the most frequent splicing defect. Strikingly, mutant SF3B1 utilizes a BPS that differs from that used by wild-type SF3B1 and requires the canonical 3′ ss to enable aberrant splicing during the second step. Approximately 50% of the aberrantly spliced mRNAs are subjected to nonsense-mediated decay resulting in downregulation of gene and protein expression. These findings ascribe functional significance to the consequences of SF3B1 mutations in cancer.

Quinomycin G (1), a new analogue of echinomycin, together with a new cyclic dipeptide, cyclo-(l-Pro-4-OH-l-Leu) (2), as well as three known antibiotic compounds tirandamycin A (3), tirandamycin B (4) and staurosporine (5), were isolated from Streptomyces sp. LS298 obtained from a marine sponge Gelliodes carnosa. The planar and absolute configurations of compounds 1 and 2 were established by MS, NMR spectral data analysis and Marfey’s method. Furthermore, the differences in NMR data of keto-enol tautomers in tirandamycins were discussed for the first time. Antibacterial and anti-tumor activities of compound 1 were measured against 15 drug-sensitive/resistant strains and 12 tumor cell lines. Compound 1 exhibited moderate antibacterial activities against Staphylococcuse pidermidis, S. aureus, Enterococcus faecium, and E. faecalis with the minimum inhibitory concentration (MIC) values ranged from 16 to 64 μg/mL. Moreover, it displayed remarkable anti-tumor activities; the highest activity was observed against the Jurkat cell line (human T-cell leukemia) with an IC50 value of 0.414 μM.

Background/Aims: MicroRNAs (miRNAs) play an essential role in the tumorigenesis of gastric carcinoma (GC). MiR-429 has been recently reported to inhibit GC growth, but the underlying mechanisms are not clear. Methods: Here, we studied the levels of miR-429 and anti-apoptotic protein Bcl-2 in GC specimens. We performed bioinformatics analyses and used luciferase-reporter assay to analyze the relationship between miR-429 and Bcl-2 in GC cells. Cell survival upon Fluorouracil treatment was analyzed in a CCK assay. Cell apoptosis was measured by flow cytometry based FITC Annexin V apoptosis detection assay. Results: MiR-429 levels were significantly decreased and Bcl-2 levels were significantly increased in GC specimens, compared to the paired adjacent non-tumor gastric tissue. Moreover, the levels of miR-429 and Bcl-2 inversely correlated in GC specimens. MiR-429-low subjects had an overall inferior survival, compared to miR-429-high subjects. Bioinformatics analyses showed that miR-429 targeted the 3'-UTR of Bcl-2 mRNA to inhibit its translation, which was confirmed by luciferase-reporter assay. Overexpression of miR-429 inhibited Bcl-2-mediated cell survival against apoptosis induced by Fluorouracil, while depletion of miR-429 augmented it. Conclusion: Our data suggest that miR-429 suppression in GC promotes Bcl-2-mediated cancer cell survival against chemotherapy-induced cell death. Re-expression of miR-429 levels in GC cells may enhance cancer apoptosis during chemotherapy.

A 22-year field experiment was conducted in Gongzhuling, Jilin province, China to investigate corn yield response to fertilization practice. Compared to an unfertilized control (CK), all fertilization treatments, including inorganic nitrogen fertilizer only (N), balanced inorganic fertilizers (NPK), NPK plus corn straw (SNPK), and NPK plus farmyard manure (MNPK), resulted in significant increases in corn yield. However, only organic matter amendments sustained increasing yield trends, with annual rates of 0.137 and 0.194 t ha− 1 for the SPNK and MNPK treatments, respectively (P < 0.05). During the 22 years, the daily mean, maximum and minimum temperatures increased by 0.50, 0.53, and 0.46 °C per decade, whereas precipitation displayed no significant change but showed large seasonal variation. According to a regression analysis, increased air temperature exerted positive effects on corn yields under the SNPK and the MNPK treatments. Under both treatments, soil organic carbon contents and soil nutrient availabilities increased significantly compared to their initial levels in 1990, whereas soil bulk density and total porosity changed slightly under the two treatments, which showed higher soil water storage than other treatments. In contrast, significant increases in soil bulk density and decreases in soil total porosity and soil nutrient availability were observed under the CK, N and NPK treatments. The contributions of soil fertility to corn yield were 28.4%, 37.9%, 38.4%, 39.0%, and 42.9% under CK, N, NPK, SNPK, and MNPK treatments, respectively, whereas climate changes accounted for 27.0%, 14.6%, 12.4%, 11.8%, and 10.8%. These results indicate that, in Northeast China, organic matter amendments can mitigate negative and exploit positive effects of climate change on crop production by enhancing soil quality.

Background: Nonsteroidal anti-inflammatory drugs are the first-line option for treating ankylosing spondylitis (AS) in China. However, no large-scale controlled trials have been conducted in this ethnic population. Objective: To evaluate the efficacy and safety of 6 weeks’ treatment with celecoxib in patients with AS in China. Methods: This Phase 3, double-blind, parallel-group study randomized patients with AS aged ≥18 to 65 years 1:1 to receive celecoxib 200 mg once daily or diclofenac sustained release 75 mg once daily. After 6 weeks, patients could use celecoxib 400 mg once daily or maintain blinded therapy. The primary efficacy end point was mean change from baseline at Week 6 for Patient’s Global Assessment of Pain Intensity score (100-mm visual analog scale). Noninferiority was established if the upper bound of the CI was

AIM:To study the effect of β-blockers combined with carbonic anhydrase inhibitors on postoperative intraocular pressure(IOP)control of neovascular glaucoma. METHODS:Seventy-four patients(80 eyes)with neovascular glaucoma received surgical treatment in our hospital from May 2012 to October 2014 were randomly divided into observation group and control group. Observation group received β-blockers combined with carbonic anhydrase inhibitors treatment. Control group received monotherapy of β-blocker. Then IOP, cytokine levels, curative effect were compared between the two groups. RESULTS:Curative effect:the efficacy rate of observation group(93%)was significantly higher than that of control group(74%, χ2=4.931, Pt=13.422, 11.555, 8.129, Pt=11.762, 7.608, 5.275, 3.780, 7.450, 2.625, PCONCLUSION: The therapy of β-blockers combined with carbonic anhydrase inhibitors can help to reduce the level of postoperative IOP in neovascular glaucoma patients, regulate the synthesis of cytokines, and then improve therapy effect.

Immune evasion is a well-recognized hallmark of cancer and recent studies with immunotherapy agents have suggested that tumors with increased numbers of neoantigens elicit greater immune responses. We hypothesized that the immune system presents a common selective pressure on high mutation burden tumors and therefore immune evasion mutations would be enriched in high mutation burden tumors. The JAK family of kinases is required for the signaling of a host of immune modulators in tumor, stromal, and immune cells. Therefore, we analyzed alterations in this family for the hypothesized signature of an immune evasion mutation. Here, we searched a database of 61,704 unique solid tumors for alterations in the JAK family kinases (JAK1/2/3, TYK2). We used The Cancer Genome Atlas and Cancer Cell Line Encyclopedia data to confirm and extend our findings by analyzing gene expression patterns. Recurrent frameshift mutations in JAK1 were associated with high mutation burden and microsatellite instability. These mutations occurred in multiple tumor types including endometrial, colorectal, stomach, and prostate carcinomas. Analyzing gene expression signatures in endometrial and stomach adenocarcinomas revealed that tumors with a JAK1 frameshift exhibited reduced expression of interferon response signatures and multiple anti-tumor immune signatures. Importantly, endometrial cancer cell lines exhibited similar gene expression changes that were expected to be tumor cell intrinsic (e.g. interferon response) but not those expected to be tumor cell extrinsic (e.g. NK cells). From these data, we derive two primary conclusions: 1) JAK1 frameshifts are loss of function alterations that represent a potential pan-cancer adaptation to immune responses against tumors with microsatellite instability; 2) The mechanism by which JAK1 loss of function contributes to tumor immune evasion is likely associated with loss of the JAK1-mediated interferon response.

The phosphorus activation coefficient (PAC, the ratio of available P to total P) is an important indicator of soil P availability and the transformation of P fractions. Understanding the details of the PAC is useful to estimate soil available P status and to provide P management guidance. In this research, soils from five long-term (23 years) fertilization treatments in three croplands were selected to examine the relationships between the PAC and P fractions and to analyse the influencing factors. PAC was affected by both soil types and fertilization treatments. Compared to the unfertilized control (CK) treatment, long-term P application significantly increased the PAC, all of the inorganic P (Pi) fractions and most of the organic P (Po) fractions in all the three soils, particularly in chemical fertilizer combined with manure treatment (NPKM). The PAC was significantly correlated to all of the Pi fractions proportions (P

Aim. In this study, we aimed to investigate the effects of febuxostat, a novel inhibitor of xanthine oxidase (XO), on renal damage in streptozotocin- (STZ-) induced diabetic rats. Methods. Diabetes was induced by the intraperitoneal injection of STZ in male Sprague-Dawley rats. Sham-injected rats served as controls. The control and diabetic rats were treated with and without febuxostat for 8 weeks, respectively. Fasting blood and 24-h urine samples were collected every 4 weeks. Rat livers were extracted for detecting gene expression, content, and bioactivity of XO. Results. Diabetic rats showed significantly increased serum uric acid (SUA), serum creatinine (SCr), and urea nitrogen (BUN) levels. Daily urinary albumin (UAE), uric acid (UUA), and creatinine (UCr) excretion were also significantly increased in these rats. In diabetic rats, at week 8, febuxostat decreased SUA by 18.9%, while UAA was increased by 52.0%. However, UCr and urinary urea nitrogen (UUN) levels remained unchanged, while SCr and BUN levels decreased by >30% in these rats. Although hepatic gene expression, content, and activity of XO increased significantly in diabetic rats, febuxostat only slightly decreased its content. Conclusions. Febuxostat significantly attenuated renal damage in STZ-induced diabetic rats in addition to exerting hypouricemic effect.

Increasing basic farmland soil productivity has significance in reducing fertilizer application and maintaining high yield of crops. In this study, we defined that the basic soil productivity (BSP) is the production capacity of a farmland soil with its own physical and chemical properties for a specific crop season under local environment and field management. Based on 22-yr (1990–2011) long-term experimental data on black soil (Typic hapludoll) in Gongzhuling, Jilin Province, Northeast China, the decision support system for an agro-technology transfer (DSSAT)-CERES-Maize model was applied to simulate the yield by BSP of spring maize (Zea mays L.) to examine the effects of long-term fertilization on changes of BSP and explore the mechanisms of BSP increasing. Five treatments were examined: (1) no-fertilization control (control); (2) chemical nitrogen, phosphorus, and potassium (NPK); (3) NPK plus farmyard manure (NPKM); (4) 1.5 time of NPKM (1.5NPKM) and (5) NPK plus straw (NPKS). Results showed that after 22-yr fertilization, the yield by BSP of spring maize significantly increased 78.0, 101.2, and 69.4% under the NPKM, 1.5NPKM and NPKS, respectively, compared to the initial value (in 1992), but not significant under NPK (26.9% increase) and the control (8.9% decrease). The contribution percentage of BSP showed a significant rising trend (PNPKM>NPK≈NPKS, indicating that organic manure combined with chemical fertilizers (1.5NPKM and NPKM) could more effectively increase BSP compared with the inorganic fertilizer application alone (NPK) in the black soil. This study showed that soil organic matter (SOM) was the key factor among various fertility factors that could affect BSP in the black soil, and total N, total P and/or available P also played important role in BSP increasing. Compared with the chemical fertilization, a balanced chemical plus manure or straw fertilization (NPKM or NPKS) not only increased the concentrations of soil nutrient, but also improved the soil physical properties, and structure and diversity of soil microbial population, resulting in an iincrease of BSP. We recommend that a balanced chemical plus manure or straw fertilization (NPKM or NPKS) should be the fertilization practices to enhance spring maize yield and improve BSP in the black soil of Northeast China.

Near-field electrospray was used to deposit zinc acetate precursor particles over comb electrodes. These particles were heated and oxidized to form a zinc oxide (ZnO) semiconductor at 500 °C. The resulting ZnO thin film on the comb electrode was incorporated into a gas sensor, which was examined using a custom built measurement system. The current that was measured through the electrodes was used to calculate the resistance of the ZnO between the fingers of the comb electrode. The resistance decreased as the sensor was exposed to the target gas of ethanol, while the sensing response (R0/Rg) increased at higher concentrations of target gas. The ZnO sensor displayed high sensitivity because of the small diameters and high specific surface area of the electrospray particles. The ZnO sensors show great promise for use as micro/nano gas sensors as they exhibit high sensitivity, repeatability and stability.

A novel linear α, ω-di (chloro phosphoramide)-terminated polydimethylsiloxane (CPN-PDMS) was successfully synthesized and utilized as a formaldehyde-free water-repellent and flame-retardant for cotton fabrics. The flame retardancy of treated cotton fabrics was estimated by limiting oxygen index (LOI) test, vertical flammability test, and cone calorimetry test. The cotton fabrics treated with 350 g/L CPN-PDMS obtained excellent flame retardancy with an LOI value of 30.6% and the char length was only 4.3 cm. Combustion residues were studied using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) analysis. Results show that CPN-PDMS can effectively enhance water repellency and fire resistance of cotton fabrics. Furthermore, the breaking strength test and the whiteness test strongly prove that the tensile strength and whiteness of the treated cotton fabrics were slightly lower than that of the pure cotton fabrics. The wash stability test showed that after 30 laundering cycles, the treated cotton fabrics still had an LOI value of 28.5% and a water-repellent effect of grade 80, indicating that CPN-PDMS was an excellent washing durability additive. In summary, these property enhancements of treated cotton fabrics were attributed to the synergistic effect of silicon-phosphorus-nitrogen elements in CPN-PDMS.

The dispensing resolution of high-viscosity liquid is essential for adhesive micro-bonding. In comparison with the injection technique, the transfer printing method appears to be promising. Herein, an analytical model was developed to describe the dynamic mechanism of squeezing-and-deforming a viscous droplet between plates in a transfer printing process: as the distance between plates decreases, the main constituents of contact force between the droplet and substrate can be divided into three stages: surface tension force, surface tension force and viscous force, and viscous force. According to the above analysis, the transfer printing method was built up to dispense high-viscosity adhesives, which replaced the geometric parameters, utilized the critical contact force to monitor the adhesive droplet status, and served as the criterion to trigger the liquid-bridge stretching stage. With a home-made device and a simple needle-stamp, the minimum dispensed amount of 0.05 nL (93.93 Pa·s) was achieved. Moreover, both the volume and the contact area of adhesive droplet on the substrate were approximately linear to the critical contact force. The revealed mechanism and proposed method have great potential in micro-assembly and other applications of viscous microfluidics.