Probing

The isomer depletion of ^{93m}Mo was recently reported [Chiara et al., Nature (London) 554, 216 (2018)NATUAS0028-083610.1038/nature25483] as the first direct observation of nuclear excitation by electron capture (NEEC). However, the measured excitation probability of 1.0(3)% is far beyond the theoretical expectation. In order to understand the inconsistency between theory and experiment, we produce the ^{93m}Mo nuclei using the ^{12}C(^{86}Kr,5n) reaction at a beam energy of 559 MeV and transport the reaction residues to a detection station far away from the target area employing a secondary beam line. The isomer depletion is expected to occur during the slowdown process of the ions in the stopping material. In such a low γ-ray background environment, the signature of isomer depletion is not observed, and an upper limit of 2×10^{-5} is estimated for the excitation probability. This is consistent with the theoretical expectation. Our findings shed doubt on the previously reported NEEC phenomenon and highlight the necessity and feasibility of further experimental investigations for reexamining the isomer depletion under low γ-ray background.

Large Isospin Asymmetry in

ß-delayed one-proton emissions of ^{22}Si, the lightest nucleus with an isospin projection T_{z}=-3, are studied with a silicon array surrounded by high-purity germanium detectors. Properties of ß-decay branches and the reduced transition probabilities for the transitions to the low-lying states of ^{22}Al are determined. Compared to the mirror ß decay of ^{22}O, the largest value of mirror asymmetry in low-lying states by far, with δ=209(96), is found in the transition to the first 1^{+} excited state. Shell-model calculation with isospin-nonconserving forces, including the T=1, J=2, 3 interaction related to the s_{1/2} orbit that introduces explicitly the isospin-symmetry breaking force and describes the loosely bound nature of the wave functions of the s_{1/2} orbit, can reproduce the observed data well and consistently explain the observation that a large δ value occurs for the first but not for the second 1^{+} excited state of ^{22}Al. Our results, while supporting the proton-halo structure in ^{22}Al, might provide another means to identify halo nuclei.

[Construction and analysis of competitive endogenous RNA regulatory network related to gastric cancer].

Objective: To construct the competitive endogenous RNA (ceRNA) network related to gastric cancer and explore the molecular mechanism. Methods: The expression profiles of lncRNA, miRNA and mRNA in gastric cancer and paracancer tissues were analyzed by biochip technology, edgeR package in R software was used to filtrate differential expression genes (multiple change of >1.5 times, P<0.05) and volcano map was drawn. Based on the online miRNA-lncRNA prediction tool lncBase database and the miRNA Target gene prediction database (miRTarBase, target-scan, miRDB, starBase), the relationship between miRNA, lncRNA and mRNA was predicted. Cytoscape software was used to construct lncRNA-miRNA-mRNA ceRNA network and key genes (hub genes) were identified based on cytohubba calculation of degree score of each node. Then Hub genes related to the prognosis of gastric cancer were verified in the TCGA database. The GO and KEGG enrichment analysis of differentially expressed mRNA was performed using the online biological information annotation database DAVID, P<0.05 and false discovery rate (FDR)<0.05 were used as cut-off criteria. R software was used to download the RNA sequencing data and mirna-seq data of gastric cancer and adjacent tissues in TCGA database, edgeR package was used to screen out differentially expressed mRNA, miRNA and lncRNA, and some differentially expressed genes in our data were verified. In OncoLnc database, STAD project of TCGA data was selected and hub gene was input. Patients were divided into two groups based on the median value for hub genes and Kaplan-meier analysis was performed. Results: The differentially expressed 766 mRNA, 110 lncRNA and 10 miRNA were screened out, among them 90 mRNA, 4 lncRNA and 6 miRNA were used to construct the ceRNA network, and 2 of the 20 hub genes were related to the prognosis of patients. MLK7-AS1, SPP1, SULF1, hsa-miR-1307-3p were upregulated in gastric cancer tissues from our biochip, while MT2A, MT1X were downregulated, which were consistent with the results of TCGA gastric cancer database. The differentially expressed mRNAs were significantly enriched in the biological process (BP) and the mineral absorption pathway. CHST1 was negatively correlated while miR-183-5p was positively corelated with the survival of patients. Conclusion: The establishment of ceRNA network for gastric cancer is conducive to further understanding of the molecular biological mechanism. CHST1 and miR-183-5p can be used as prognostic factors of gastric cancer.

[Trend in proportion and clinicopathological characteristics of young women with stage â a2 to â ¡a2 cervical cancer].

Objective: To analyze the 13 years trend in proportion, risks factors and clinicopathological characteristics of young women with stage Ⅰa2 to Ⅱa2 cervical cancer by using multi-center data of cervical cancer in China. Methods: The clinicopathological data of 46 313 patients with cervical cancer treated from 37 hospitals in China were obtained from January 2004 to December 2016. Using clinical and pathologic data, each patient's stage was reclassified by the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system. A total of 19 041 patients were selected according to the following criteria: FIGO stage Ⅰa2 to Ⅱa2, underwent type B or C radical hysterectomy and pelvic lymphadenectomy. All the patients were divided into two groups: the study group of 1 888 patients aged 35 years or younger and the control group of 17 153 patients aged over 35 years. The 13 years trend in proportion of young women with stage Ⅰa2 to Ⅱa2 cervical cancer, risks factors and clinicopathological characteristics of two groups were retrospectively analyzed. Results: (1) The total number of hospitalized patients with stage Ⅰa2 to Ⅱa2 cervical cancer increased annually. However, a downward trend of patients aged 35 years or younger was observed (P<0.01) . The constituent ratio of patients aged 35 years or younger was significantly greater during 2004-2010 than that during 2011-2016 [12.6% (820/6 484) and 8.5% (1 068/12 557) , respectively; χ(2)=82.101, P<0.01]. (2) Compared with patients aged over 35 years, patients aged 35 years or younger had an earlier age at menarche, a later age at marriage, lesser gravida and parity (all P<0.01). The positive rate of high-risk HPV infection was not statistically different between two groups (all P>0.05). (3) The proportions of stage Ⅰ, exophytic type and non-squamous histological type in patients aged 35 years or younger were clearly higher than those in patients aged over 35 years (83.4% vs 68.5%, P<0.01; 63.2% vs 56.2%, P<0.01; 13.9% vs 12.0%, P<0.05, respectively). Whereas the poor differentiation ratios of the two groups had no statistical significance (P>0.05). (4) As for the postoperative pathological risk factors, the rate of surgical margin involvement in patients aged 35 years or younger was lower than that aged over 35 years (1.1% vs 1.8%, P<0.05), and the rate of depth of stromal invasion >1/2 in patients aged 35 years or younger was lower than that in patients aged over 35 years (40.1% vs 50.9%, P<0.01). In addition, there were no significant difference in parametrial margin involvement, tumor size and lymph vascular space invasion between two groups (all P>0.05). Conclusions: The trend in proportion among hospitalized patients for stage Ⅰa2 to Ⅱa2 cervical cancer in young women is decreasing yearly. Compared with cervical cancer in middle-aged and elderly women, cervical cancer in young women have an earlier age at menarche, a higher proportion of stage Ⅰ patients and non-squamous histological type. In terms of the postoperative pathological risk factors, the rate of surgical margin involvement and depth of stromal invasion >1/2 in young women with cervical cancer are lower than in middle-aged and elderly women.

Involvement of M1 Macrophage Polarization in Endosomal Toll-Like Receptors Activated Psoriatic Inflammation.

Psoriasis is a chronic inflammatory skin disorder that affects ~2%-3% of the worldwide population. Inappropriate and excessive activation of endosomal Toll-like receptors 7, 8, and 9 (TLRs 7-9) at the psoriatic site has been shown to play a pathogenic role in the onset of psoriasis. Macrophage is a major inflammatory cell type that can be differentiated into phenotypes M1 and M2. M1 macrophages produce proinflammatory cytokines, and M2 macrophages produce anti-inflammatory cytokines. The balance between these two types of macrophages determines the progression of various inflammatory diseases; however, whether macrophage polarization plays a role in psoriatic inflammation activated by endosomal TLRs has not been investigated. In this study, we investigated the function and mechanism of macrophages related to the pathogenic role of TLRs 7-9 in the progression of psoriasis. Analysis of clinical data in database revealed significantly increased expression of macrophage markers and inflammatory cytokines in psoriatic tissues over those in normal tissues. In animal studies, depletion of macrophages in mice ameliorated imiquimod, a TLR 7 agonist-induced psoriatic response. Imiquimod induced expression of genes and cytokines that are signature of M1 macrophage in the psoriatic lesions. In addition, treatment with this TLR 7 agonist shifted macrophages in the psoriatic lesions to a higher M1/M2 ratio. Both of the exogenous and endogenous TLR 7-9 ligands activated M1 macrophage polarization. M1 macrophages expressed higher levels of proinflammatory cytokines and TLRs 7-9 than M2 macrophages. These results suggest that by rendering macrophages into a more inflammatory status and capable of response to their ligands in the psoriatic sites, TLR 7-9 activation drives them to participate in endosomal TLR-activated psoriatic inflammation, resulting in an amplified inflammatory response. Our results also suggest that blocking M1 macrophage polarization could be a strategy which enables inhibition of psoriatic inflammation activated by these TLRs.

[The influence of Thymidine Phosphorylase genetic variation on clinical outcomes and safety of colorectal cancer patients received adjuvant chemotherapy after R0 resection].

Objective: To study the association between Thymidine Phosphorylase (TYMP) genetic variation and clinical outcomes and safety of postoperative colorectal cancer (CRC) patients. Methods: A total of 235 patients with colorectal cancer underwent surgical treatment were included in this retrospective analysis. Peripheral blood and the postoperative tissue specimen of the CRC patients were collected for the genotyping of polymorphism and TYMP mRNA expression, respectively. The correlation between polymorphism and clinical outcomes and safety of postoperative CRC patients were analysed. Results: Located in the upstream, 5633C>T was of clinical significance. The prevalence of 5633C>T in TYMP among the CRC patients were as follows: CC genotype 149 cases (63.40%), CT genotype 73 cases (31.06%), TT genotype 13 cases (5.54%), minor allele frequency of 5633C>T is 0.21. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.313). CT genotype and TT genotype patients were merged in the comparison of prognosis. The survival analysis of patients with different genotypes found that the median Overall Survival (OS) of CT/TT genotype and CC genotype were 5.8 and 4.5 year, which was statistically significant (P=0.009). Adjusted in multivariate Cox regression analysis, CT/TT genotype was an independent favorable factor for OS (HR=0.67, P=0.015). Additionally, of the 87 postoperative tissue specimens, the results showed that the expression of TYMP in cancer tissues of the patients with CT or TT genotypes were significantly higher than those of the wild type CC genotype patients (P=0.019). And the safety analysis showed that the incidence of grade 3 hand-foot syndrome among CT/TT genotype patients were higher than that of CC genotype patients (33.72% vs 20.13%, OR=1.68, P=0.021). Conclusion: The polymorphism 5633C>T of TYMP may impact the prognosis of CRC patients received adjuvant chemotherapy by influencing the mRNA expression of TYMP.

Observation of enhanced monopole strength and clustering in (12)Be.

In a recent breakup-reaction experiment using a Be12 beam at 29 MeV/nucleon, the 0+ band head of the expected He4+He8 molecular rotation was clearly identified at about 10.3 MeV, from which a large monopole matrix element of 7.0±1.0 fm2 and a large cluster-decay width were determined for the first time. These findings support the picture of strong clustering in Be12, which has been a subject of intense investigations over the past decade. The results were obtained thanks to a specially arranged detection system around zero degrees, which is essential in determining the newly emphasized monopole strengths to signal the cluster formation in a nucleus.

The relationship and diagnostic efficacy of N-terminal propeptide type III collagen in pathological changes associated with non-alcoholic steatohepatitis.

OBJECTIVE: This study delves into the role of N-terminal propeptide type III collagen (PIIINP) in the diagnosis and management of liver pathological changes associated with non-alcoholic steatohepatitis (NASH). PATIENTS AND METHODS: We collected baseline information, pathological data, and serum PIIINP levels of 168 patients diagnosed with non-alcoholic fatty liver disease (NAFLD) via ultrasound imaging in our hospital. Based on the non-alcoholic fatty liver disease activity score (NAS), patients with different NAFLD patterns were divided into a Definite NASH group and a Not/borderline group. Differences in PIIINP levels and pathological features between the two groups were compared and analyzed. The diagnostic value of PIIINP for NASH was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: Patients with NASH exhibited significantly higher values of homeostatic model assessment for insulin resistance (HOMA-IR), fibrosis biomarker fibrosis-4 (FIB-4), aminotransferase-to-platelet ratio index (APRI), and serum PIIINP levels than those classified as Not/borderline. A marked increase in the serum concentrations of PIIINP was observed with the severity of fatty degeneration, lobular inflammation, and hepatocellular ballooning. The AUC of PIIINP for diagnosing definite NASH was 0.766 (95% CI: 0.694, 0.839), APRI was 0.634 (95% CI: 0.549, 0.718), and FIB-4 was 0.621 (95% CI: 0.534, 0.708). The AUC of PIIINP for diagnosing definite NASH was significantly higher than that of APRI and FIB-4 (all p<0.05). Utilizing the predetermined threshold values for diagnostic parameters, the PIIINP measure demonstrated a sensitivity of 71.6% and a specificity of 73.6% in diagnosing definitive NASH when its value exceeded 7.72 ng/dL. This yielded a Youden index of 0.45. Similarly, when the APRI measure exceeded 0.21, it exhibited a sensitivity of 60.5% and a specificity of 63.2%, resulting in a Youden index of 0.24. Moreover, when the FIB-4 index surpassed 0.26, it showed a sensitivity of 46.9% and a specificity of 79.3%, culminating in a Youden index of 0.26. CONCLUSIONS: NASH patients in this study exhibited significantly elevated PIIINP serum levels, which were closely associated with hepatocyte pathological changes. PIIINP demonstrated superior competence in diagnosing NASH than APRI and FIB-4 and thus offers a viable alternative for the clinical diagnosis of NASH.

Virulence Characterization of International Collections of the Wheat Stripe Rust Pathogen, Puccinia striiformis f. sp. tritici.

Wheat stripe rust (yellow rust [Yr]), caused by Puccinia striiformis f. sp. tritici, is an economically important disease of wheat worldwide. Virulence information on P. striiformis f. sp. tritici populations is important to implement effective disease control with resistant cultivars. In total, 235 P. striiformis f. sp. tritici isolates from Algeria, Australia, Canada, Chile, China, Hungary, Kenya, Nepal, Pakistan, Russia, Spain, Turkey, and Uzbekistan were tested on 20 single Yr-gene lines and the 20 wheat genotypes that are used to differentiate P. striiformis f. sp. tritici races in the United States. The 235 isolates were identified as 129 virulence patterns on the single-gene lines and 169 virulence patterns on the U.S. differentials. Virulences to YrA, Yr2, Yr6, Yr7, Yr8, Yr9, Yr17, Yr25, YrUkn, Yr28, Yr31, YrExp2, Lemhi (Yr21), Paha (YrPa1, YrPa2, YrPa3), Druchamp (Yr3a, YrD, YrDru), Produra (YrPr1, YrPr2), Stephens (Yr3a, YrS, YrSte), Lee (Yr7, Yr22, Yr23), Fielder (Yr6, Yr20), Tyee (YrTye), Tres (YrTr1, YrTr2), Express (YrExp1, YrExp2), Clement (Yr9, YrCle), and Compair (Yr8, Yr19) were detected in all countries. At least 80% of the isolates were virulent on YrA, Yr2, Yr6, Yr7, Yr8, Yr17, YrUkn, Yr31, YrExp2, Yr21, Stephens (Yr3a, YrS, YrSte), Lee (Yr7, Yr22, Yr23), and Fielder (Yr6, Yr20). Virulences to Yr1, Yr9, Yr25, Yr27, Yr28, Heines VII (Yr2, YrHVII), Paha (YrPa1, YrPa2, YrPa3), Druchamp (Yr3a, YrD, YrDru), Produra (YrPr1, YrPr2), Yamhill (Yr2, Yr4a, YrYam), Tyee (YrTye), Tres (YrTr1, YrTr2), Hyak (Yr17, YrTye), Express (YrExp1, YrExp2), Clement (Yr9, YrCle), and Compair (Yr8, Yr19) were moderately frequent (>20 to <80%). Virulence to Yr10, Yr24, Yr32, YrSP, and Moro (Yr10, YrMor) was low (≤20%). Virulence to Moro was absent in Algeria, Australia, Canada, Kenya, Russia, Spain, Turkey, and China, but 5% of the Chinese isolates were virulent to Yr10. None of the isolates from Algeria, Canada, China, Kenya, Russia, and Spain was virulent to Yr24; none of the isolates from Algeria, Australia, Canada, Nepal, Russia, and Spain was virulent to Yr32; none of the isolates from Australia, Canada, Chile, Hungary, Kenya, Kenya, Nepal, Pakistan, Russia, and Spain was virulent to YrSP; and none of the isolates from any country was virulent to Yr5 and Yr15. Although the frequencies of virulence factors were different, most of the P. striiformis f. sp. tritici isolates from these countries shared common virulence factors. The virulences and their frequencies and distributions should be useful in breeding stripe-rust-resistant wheat cultivars and understanding the pathogen migration and evolution.

Direct mass measurements of short-lived A=2Z-1 nuclides (63)Ge, (65)As, (67)Se, and (71)Kr and their impact on nucleosynthesis in the rp process.

Mass excesses of short-lived A=2Z-1 nuclei (63)Ge, (65)As, (67)Se, and (71)Kr have been directly measured to be -46,921(37), -46,937(85), -46,580(67), and -46,320(141) keV, respectively. The deduced proton separation energy of -90(85) keV for (65)As shows that this nucleus is only slightly proton unbound. X-ray burst model calculations with the new mass excess of (65)As suggest that the majority of the reaction flow passes through (64)Ge via proton capture, indicating that (64)Ge is not a significant rp-process waiting point.

Phosphodiesterase 4B is essential for T(H)2-cell function and development of airway hyperresponsiveness in allergic asthma.

BACKGROUND: Cyclic AMP (cAMP) signaling modulates functions of inflammatory cells involved in the pathogenesis of asthma, and type 4 cAMP-specific phosphodiesterases (PDE4s) are essential components of this pathway. Induction of the PDE4 isoform PDE4B is necessary for Toll-like receptor signaling in monocytes and macrophages and is associated with T cell receptor/CD3 in T cells; however, its exact physiological function in the development of allergic asthma remains undefined. OBJECTIVES: We investigated the role of PDE4B in the development of allergen-induced airway hyperresponsiveness (AHR) and T(H)2-driven inflammatory responses. METHODS: Wild-type and PDE4B(-/-) mice were sensitized and challenged with ovalbumin and AHR measured in response to inhaled methacholine. Airway inflammation was characterized by analyzing leukocyte infiltration and cytokine accumulation in the airways. Ovalbumin-stimulated cell proliferation and T(H)2 cytokine production were determined in cultured bronchial lymph node cells. RESULTS: Mice deficient in PDE4B do not develop AHR. This protective effect was associated with a significant decrease in eosinophils recruitment to the lungs and decreased T(H)2 cytokine levels in the bronchoalveolar lavage fluid. Defects in T-cell replication, T(H)2 cytokine production, and dendritic cell migration were evident in cells from the airway-draining lymph nodes. Conversely, accumulation of the T(H)1 cytokine IFN-γ was not affected in PDE4B(-/-) mice. Ablation of the orthologous PDE4 gene PDE4A has no impact on airway inflammation. CONCLUSION: By relieving a cAMP-negative constraint, PDE4B plays an essential role in T(H)2-cell activation and dendritic cell recruitment during airway inflammation. These findings provide proof of concept that PDE4 inhibitors with PDE4B selectivity may have efficacy in asthma treatment.

[Influential factors related to osteoradionecrosis of the mandible in oral and maxillofacial cancer patients following radiotherapy].

Objective: To identify risk factors associated with mandibular osteoradionecrosis (ORN) in oral and maxillofacial cancer patients following radiotherapty and to provide scientific basis for the etiological research and clinical prevention of mandibular ORN. Methods: A retrospective study was conducted in patients with oral and maxillofacial-head and neck cancer during the period from January 2013 to December 2015. Influential factors related to mandibular ORN were screened by single factor analysis, Lasso and Logistic regression analysis. Results: A total of 757 patients were analyzed, and the total incidence of mandibular ORN was 12.0%(91/757). There were 443 males and 314 females, aged (51.8±13.7) years. Thirty-five related factors were screened to 28 by single factor analysis. It was determined by Lasso regression analysis that, radiation doses (OR=1.135, P=0.034, 95%CI: 1.089-1.232), T classification (OR=2.586, P=0.001, 95%CI: 1.482-4.512), mandibular surgery (OR=9.101, P<0.001, 95%CI: 2.796-29.630), periodontitis (OR=6.089, P<0.001, 95%CI: 2.708-13.693), diabetes (OR=4.467, P=0.002, 95%CI: 1.705-11.704), tooth extraction after radiotherapy (OR=3.228, P=0.001, 95%CI: 1.640-6.350), dental caries (OR=2.911, P=0.009, 95%CI: 1.300-6.516), periapical periodontitis (OR=2.726, P=0.016, 95%CI: 1.209-6.145), smoking (OR=4.438, P=0.002, 95%CI: 1.702-11.571) and unilateral/bilateral radiotherapy (OR=2.225, P=0.028, 95%CI: 1.090-4.545) were significantly associated with developing mandibular ORN. Conclusions: Ten main risk factors for mandibular ORN were identified through the single center, large sample, retrospective analysis, which has a certain value for clinical prevention of mandibular ORN. Prospective, randomized controlled trials and long-term follow-up are still needed.

Silencing of miR-330-5p stimulates osteogenesis in bone marrow mesenchymal stem cells and inhibits bone loss in osteoporosis by activating Bgn-mediated BMP/Smad pathway.

OBJECTIVE: To illustrate the role of micro ribonucleic acid (miR)-330-5p in regulating osteogenesis through biglycan (Bgn)-mediated bone morphogenetic protein (BMP)/Smad pathway. MATERIALS AND METHODS: A mouse model of osteoporosis (OP) was established by ovariectomy (OVX). BMD and miR-330-5p levels in mice undergoing sham operation or OVX were determined. BMD and BV/TV in OP mice with in vivo knockdown of miR-330-5p were measured by Micro-CT. After silencing of miR-330-5p in mouse primary bone marrow stromal cells (BMSCs), expression changes in osteogenesis-associated genes, ALP activity, and mineralization ability were assessed. Subsequently, the interaction between miR-330-5p and Bgn was examined by Dual-Luciferase reporter gene assay and Western blotting. Then, Bgn levels in BMSCs undergoing osteogenesis at different time points were measured. At last, the regulatory effects of miR-330-5p/Bgn axis on the BMP/Smad pathway, ALP activity, and mineralization ability in BMSCs were evaluated. RESULTS: BMD was decreased and miR-330-5p was upregulated in OP mice. OP mice with in vivo knockdown of miNA-330-5p presented higher BMD and BV/TV than controls. Transfection with miR-330-5p inhibitor upregulated osteogenesis-associated genes, ALP activity, and mineralization ability in BMSCs. Bgn was time-dependently upregulated in BMSCs undergoing osteogenesis, which was indicated to be the target gene of miR-330-5p. Besides, Bgn level was negatively regulated by miR-330-5p. Importantly, Bgn was able to reverse the regulatory effects of miR-330-5p on the BMP/Smad pathway, ALP activity, and mineralization ability in BMSCs. CONCLUSIONS: Knockdown of miR-330-5p facilitates osteogenesis in BMSCs through the Bgn-induced BMP/Smad pathway, thus alleviating the progression of OP.

Race Dynamics, Diversity, and Virulence Evolution in Puccinia striiformis f. sp. tritici, the Causal Agent of Wheat Stripe Rust in China from 2003 to 2007.

Stripe (or yellow) rust caused by Puccinia striiformis f. sp. tritici is the most destructive foliar disease of wheat in China. The pathogen populations were analyzed for virulence evolution, complexity, phenotypic dynamics, and diversity on temporal and spatial bases. A total of 41 races were identified and characterized from 4,714 stripe rust isolates collected during 2003 through 2007 from wheat growing areas in 15 provinces in China. The races were based on avirulence/virulence patterns to 19 differential host genotypes. Chinese stripe rust population exhibited high diversity with a complex virulence structure. Comparisons using the relative Shannon's index indicated that some differences in the richness and evenness of races were present in pathogen populations within years and between regions despite a national tendency to reduced diversity over time. A noticeably increased frequency of race CYR33 (Chinese yellow rust 33) with virulence for YrSu was the major virulence change recorded in this study compared to the results on an annual basis. Isolates of Puccinia striiformis f. sp. tritici from different regions showed differences in the composition of races, distribution frequency, and diversity. The uneven distribution of major races and comparatively greater diversity in the Northwest and Southwest regions than that in the Huang-Huai-Hai region suggest that long-distance migrations of the pathogen occur from one or more over-summering areas eastward into over-wintering areas. This supports the hypothesis that southern Gansu and northwestern Sichuan comprises a "center of origin for virulence". Mutation of virulence or avirulence for host resistance in the stripe rust fungus may be the basic cause of the occurrence of new virulent types. The subsequent dominance of certain races will vary with parasitic fitness and the opportunities to be selected through large-scale cultivation of varieties with matching resistance genes. Implications of the center of origin for virulence variation and diversity in the pathogen population and an alternative strategy for limiting virulence evolution are discussed.

Correction: USP17 mediates macrophage-promoted inflammation and stemness in lung cancer cells by regulating TRAF2/TRAF3 complex formation.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Anxiogenic-like behavioral phenotype of mice deficient in phosphodiesterase 4B (PDE4B).

Phosphodiesterase-4 (PDE4), an enzyme that catalyzes the hydrolysis of cyclic AMP and plays a critical role in controlling its intracellular concentration, has been implicated in depression- and anxiety-like behaviors. However, the functions of the four PDE4 subfamilies (PDE4A, PDE4B, PDE4C, and PDE4D) remain largely unknown. In animal tests sensitive to anxiolytics, antidepressants, memory enhancers, or analgesics, we examined the behavioral phenotype of mice deficient in PDE4B (PDE4B-/-). Immunoblot analysis revealed loss of PDE4B expression in the cerebral cortex and amygdala of PDE4B-/- mice. The reduction of PDE4B expression was accompanied by decreases in PDE4 activity in the brain regions of PDE4B-/- mice. Compared to PDE4B+/+ littermates, PDE4B-/- mice displayed anxiogenic-like behavior, as evidenced by decreased head-dips and time spent in head-dipping in the holeboard test, reduced transitions and time on the light side in the light-dark transition test, and decreased initial exploration and rears in the open-field test. Consistent with anxiogenic-like behavior, PDE4B-/- mice displayed increased levels of plasma corticosterone. In addition, these mice also showed a modest increase in the proliferation of neuronal cells in the hippocampal dentate gyrus. In the forced-swim test, PDE4B-/- mice exhibited decreased immobility; however, this was not supported by the results from the tail-suspension test. PDE4B-/- mice did not display changes in memory, locomotor activity, or nociceptive responses. Taken together, these results suggest that the PDE4B subfamily is involved in signaling pathways that contribute to anxiogenic-like effects on behavior.

Synergistic effect of phosphodiesterase 4 inhibitor and serum on migration of endotoxin-stimulated macrophages.

Macrophage migration is an essential step in host defense against infection and wound healing. Elevation of cAMP by inhibiting phosphodiesterase 4 (PDE4), enzymes that specifically degrade cAMP, is known to suppress various inflammatory responses in activated macrophages, but the role of PDE4 in macrophage migration is poorly understood. Here we show that the migration of Raw 264.7 macrophages stimulated with LPS was markedly and dose-dependently induced by the PDE4 inhibitor rolipram as assessed by scratch wound healing assay. Additionally, this response required the involvement of serum in the culture medium as serum starvation abrogated the effect. Further analysis revealed that rolipram and serum exhibited synergistic effect on the migration, and the influence of serum was independent of PDE4 mRNA expression in LPS-stimulated macrophages. Moreover, the enhanced migration by rolipram was mediated by activating cAMP/exchange proteins directly activated by cAMP (Epac) signaling, presumably via interaction with LPS/TLR4 signaling with the participation of unknown serum components. These results suggest that PDE4 inhibitors, together with serum components, may serve as positive regulators of macrophage recruitment for more efficient pathogen clearance and wound repair.

USP17 mediates macrophage-promoted inflammation and stemness in lung cancer cells by regulating TRAF2/TRAF3 complex formation.

Macrophage accumulation and inflammation in the lung owing to stresses and diseases is a cause of lung cancer development. However, molecular mechanisms underlying the interaction between macrophages and cancer cells, which drive inflammation and stemness in cancers, are poorly understood. In this study, we investigated the expression of ubiquitin-specific peptidase 17 (USP17) in lung cancers, and role of elevated USP17 in the interaction between macrophages and lung cancer cells. USP17 expression in lung cancers was associated with poor prognosis, macrophage, and inflammatory marker expressions. Macrophages promoted USP17 expression in cancer cells. TNFR-associated factor (TRAF) 2-binding and TRAF3-binding motifs were identified in USP17, through which it interacted with and disrupted the TRAF2/TRAF3 complex. This stabilized its client proteins, enhanced inflammation and stemness in cancer cells, and promoted macrophage recruitment. In different animal studies, co-injection of macrophages with cancer cells promoted USP17 expression in tumors and tumor growth. Conversely, depletion of macrophages in host animals by clodronate liposomes reduced USP17 expression and tumor growth. In addition, overexpression of USP17 in cancer cells promoted tumor growth and inflammation-associated and stemness-associated gene expressions in tumors. These results suggested that USP17 drives a positive-feedback interaction between macrophages and cancer cells to enhance inflammation and stemness in cancer cells, and promotes lung cancer growth.