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As one of the main fungicides for the apple leaf disease control, thiophanate‐methyl (TM) mainly exerts its fungicidal activity in the form of its metabolite carbendazim (MBC), whose dissipation kinetics is very distinct from that of its parent but has been paid little attention. The aim of this work was to investigate the dissipation kinetics of TM and its active metabolite MBC in apple leaves using a modified QuEChERS–UPLC–MS/MS method. The results showed that TM and MBC could be quickly extracted by this modified QuEChERS procedure with recoveries of 81.7–96.5%. The method linearity was in the range of 0.01–50.0 mg kg−1 with the quantification limit of 0.01 mg kg−1. Then this method was applied to the analysis of fungicide dissipation kinetics in apple leaves. The results showed that the dissipation kinetics of TM for the test in 3 months can be described by a first‐order kinetics model with a DT50 (dissipation half‐life) range of 5.23–6.03 days and the kinetics for MBC can be described by a first‐order absorption–dissipation model with the Tmax (time needed to reach peak concentration) range of 4.78–7.09 days. These models can scientifically describe the behavior of TM and MBC in apple leaves, which provides necessary data for scientific application. [ABSTRACT FROM AUTHOR]

Glomerella cingulata is a pathogenic fungus that can cause apple Glomerella leaf spot (GLS), a new and destructive apple disease in China. Phytotoxins are important factors closely related to the disease process, but there is still no report on the phytotoxins of G. cingulata. The aim of this study was to rapidly identify the phytotoxins of this pathogen using a strategy of HRMS-based preliminary qualification, followed by targeted structure confirmation and also investigation of phytotoxicity characteristics. First, the crude toxin sample was directly analyzed by the UPLC-HRMS and GC-MS, and the data were processed to screen for possible phytotoxic compounds using MS library and the phytotoxicity-related literature. The reference standards of credible phytotoxic compounds were then subjected to targeted structure validation (signal comparison between standards and compounds in crude toxin via HPLC-DAD, UPLC-MS/MS, and GC-MS), and also the phytotoxicity assay. The results confirmed six phytotoxins produced by G. cingulata, namely 5-hydroxymethyl-2-furancarboxylic acid (HMFCA), 2,5-bis(hydroxymethyl)furan (BHMF), 2-furoic acid (FA), 2,3-butanediol, trans-aconitic acid (TAA), and cis-aconitic acid (CAA). Of these, HMFCA and TAA exhibited greater phytotoxicity. Main characteristics: All of them were non-host-selective toxins, and toxins were synergistically phytotoxic to the host when mixed. BHMF, HMFCA, FA, TAA, and CAA could be commonly produced by all tested strains, and their phytotoxicity can be significantly inhibited or even eliminated at high temperatures or high pH. The elucidation of the phytotoxins of G. cingulata in this work could provide information on the pathogenesis and control of apple GLS., (© 2024 Wiley‐VCH GmbH.)

The inflammation-related tumor microenvironment (TME) is one of the major driving forces of hepatocarcinogenesis. We aimed to investigate cell-to-cell communication among Hepatocellular Carcinoma (HCC) through re-analyzing HCC single-cell RNA-seq data, and to confirm such cellular interaction through in vitro and in vivo study. We found a subset of Regulatory B cells with PD-L1 expression (PD-L1 + Bregs), mainly located in adjacent HCC tissues. In co-localization with PD-L1 + Bregs, a subset of Tumor Associated Macrophages with high expression of CXCL12 (CXCL12 + TAMs) was also mainly located in adjacent HCC tissues. Moreover, CXCL12 + TAMs can be stimulated in vitro using an HCC conditional medium. Using CellChat analysis and Multiplex Immunohistochemistry staining (mIHC), CXCL12 + TAMs were found to be first recruited by Cancer-Associated Fibroblasts (CAFs) through a CD74/macrophage migration inhibitory factor (MIF) pattern, and further differentiated into TGF-β-enriched tissues. Furthermore, CXCL12 + TAMs recruited PD-L1 + Bregs via the CXCL12/CXCR4 axis, and CXCR4 expression was significantly positively correlated to PD-L1 expression in PD-L1 + Bregs. At last, we confirmed the communications among CAFs, Macrophages and B cells and their tumor-promoting effects by using an orthotopic mouse model of HCC. Immunosuppressive HCC TME involving cell-to-cell communications comprised MIF-secreting CAFs, CXCL12-secreting TAMs, and PD-L1-producing Bregs, and their regulation could be promising therapeutic targets in future immunotherapy for human HCC., Competing Interests: None., (AJCR Copyright © 2024.)

Apple rust caused by Gymnosporangium yamadae is a significant disease in China's main apple production areas. We evaluated the effects of temperature, moisture, and ultraviolet (UV) light on the germination, infection, and survival of teliospore horns and basidiospores under artificially controlled environmental conditions. The temperature required for the germination and infection of teliospores and basidiospores of G. yamadae ranged from 5 to 25°C, with an optimum temperature of approximately 17°C. The teliospore horns germinated after soaking in distilled water for 5 min and required at least 2.3 h of development to produce basidiospores under the most favorable conditions. The basidiospores germinated only in free water and produced germ tubes 0.8 h after being placed in the water. The half-life of the basidiospore was 72.5 h in the dark and only 9.5 h when exposed to intense UV light. The basidiospores inoculated on the host leaves required at least 2.3 h of water exposure to cause rust lesions. A revised Weibull model could describe the relationships between the germination and infection of teliospore horns and basidiospores with temperature and wetness duration. Collectively, these results can serve as a valuable guide for developing a model to predict future apple rust epidemics and establish a method for effective control strategies., Competing Interests: The author(s) declare no conflict of interest.

Sodium-rich anti-perovskites have unique advantages in terms of composition tuning and electrochemical stability when used as solid-state electrolytes in sodium-ion batteries. However, their Na + transport mechanism is not clear and Na + conductivity needs to be improved. In this paper, we investigate the stability, elastic properties and Na + transport mechanisms of both the double anti-perovskite Na 3 S 0.5 O 0.5 I and anti-perovskite Na 3 OI. The results indicate that the NaI Schottky defect is the most favorable intrinsic defect for Na + transport and due to the substitution of S 2- for O 2- , Na 3 S 0.5 O 0.5 I has stronger ductility and higher Na + conductivity compared to Na 3 OI, despite the electrochemical window being slightly narrower. Divalent alkaline earth metal dopants can increase the Na + vacancy concentration, while impeding Na + migration. Among the dopants, Sr 2+ and Ca 2+ are the optimal dopants for Na 3 S 0.5 O 0.5 I and Na 3 OI, respectively. Notably, the Na + conductivity of the non-stoichiometric Na 3 S 0.5 O 0.5 I at room temperature is 1.2 × 10 -3 S cm -1 , indicating its great potential as a solid-state electrolyte. Moreover, strain effect calculations show that biaxial tensile strain is beneficial for Na + transport. Our work reveals the sodium-ion transport mechanism and elastic properties of double anti-perovskites, which is of great significance for the development of solid-state electrolytes.

Due to high ion conductivity, low cost, and adjustable composition, antiperovskite has attracted much attention as a potentially useful material in solid-state batteries. Compared with simple antiperovskite, Ruddlesden-Popper (R-P) antiperovskite is an updated material, which is not only more stable but also reported to significantly enhance conductivity when added to simple antiperovskite. However, systematic theoretical research on R-P antiperovskite is scarce, hindering its further development. In this study, the recently reported easily synthesized R-P antiperovskite LiBr(Li2OHBr)2 is calculated for the first time. Comparative calculations were conducted on the transport performance, thermodynamic properties, and mechanical properties of H-rich LiBr(Li2OHBr)2 and H-free LiBr(Li3OBr)2. Our results indicate that due to the presence of protons, LiBr(Li2OHBr)2 is more prone to defects, and synthesizing more LiBr Schottky defects can improve its Li-ion conductivity. Young's modulus of the LiBr(Li2OHBr)2 is as low as 30.61 GPa, which is beneficial for its application as a sintering aid. However, the calculated Pugh's ratio (B/G) of 1.28 and 1.50, respectively, indicates that R-P antiperovskites LiBr(Li2OHBr)2 and LiBr(Li3OBr)2 exhibit mechanical brittleness, which is not conducive to its application as solid electrolytes. Through quasi-harmonic approximation, we found that the linear thermal expansion coefficient of LiBr(Li2OHBr)2 is 2.07 × 10-5 K-1, which is more advantageous in matching electrodes than LiBr(Li3OBr)2 and even simple antiperovskites. Overall, our research provides comprehensive insights into the practical application of R-P antiperovskite in solid-state batteries., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Although the perovskite (Nd,Sr)CoO 3 (NSC 113 )/Ruddlesden-Popper (R-P) oxide (Nd,Sr) 2 CoO 4 (NSC 214 ) heterostructure is reported to improve the oxygen reduction reaction (ORR) activity by 2-3 orders of magnitude, the enhancement mechanism remains unclear. For the first time, we conclude that there are two main factors that can enhance the ORR activity: (1) Oxygen adsorbed on such heterostructures would gain more electrons, promoting the oxygen adsorption. (2) The more distant rock-salt layers on the heterointerfaces can facilitate the insertion of interstitial oxygen and form a high-speed transport channel of interstitial oxygen. Moreover, the perovskite/double-layered R-P oxide heterostructure, which has not been reported yet, is predicted to have better ORR performance than the perovskite/single-layered R-P oxide heterostructure. Our work elucidates the ORR enhancement mechanism on perovskite/R-P oxide heterostructures from the atomic level, which is demonstrated by experiments and, thus, is very meaningful for the development of high-performance electrochemical devices.

Until recently, the causal agent of Botryosphaeria canker was assumed to differ from that causing ring rot on fruit and warts on branches on apple trees in China and East Asia. However, recent research documented that Botryosphaeria dothidea caused both disease symptoms on apple. Inoculations with strains isolated from cankers and warts on branches were conducted to investigate symptom progression caused by B. dothidea and conditions inducing the two symptom types. The results confirmed that both cankers and warts are caused by B. dothidea. Warts are the results of hyperplasia and suberization of bark tissues induced by fungal infection, whereas cankers result from the rapid growth of hyphae from inside warts, lenticels, or wounds. Resistance to B. dothidea exists in living apple branches. When a living branch is infected via lenticels, the pathogen induces proliferation and suberization of cortical cells that restricts the growth and expansion of the hyphae, leading to warts. However, under certain stress conditions such as drought, the hyphae inside host tissues expand rapidly and kill cortical cells, leading to canker development. Host resistance may recover during active growth periods, which suppresses or even stops rapid expansion of the hyphae, leading to the intermediate symptom of canker warts. Abiotic factors, such as drought or high temperature in early spring, can result in rapid extension of colonized hyphae in branches and conversion of warts to cankers. Preventing this transition can be an important measure in managing Botryosphaeria canker on apple.

Botryosphaeria dothidea is a fungal pathogen causing canker, dieback, and fruit rot of apple trees worldwide. Ascospores are an important source of inoculum of Botryosphaeria canker in China. Experiments were conducted under both controlled and natural conditions to study perithecium formation in relation to environmental conditions. Perithecia of B. dothidea were detected on cankered lesions throughout the apple growing season except in July and in some years including August under natural conditions. On newly formed canker lesions, the first perithecium was detected as early as August, about 1 week after rainfall. Perithecia matured successively, lasting from early August to June of the next year, with a peak in late September or early October. Temperature and rainfall are two key environmental factors affecting perithecium formation. Under controlled conditions, perithecia were produced only on cankered shoots incubated at test temperatures of 20 and 25°C and wetted by >3 days of simulated rainfall per week. The number of perithecia produced on canker lesions increased with the increase in rainfall duration. Perithecia were formed on canker shoots exposed to rainfall only in June, July, and August but not in September. Rainfall of >3 days per week can be used to predict the initial formation of perithecia in the main apple production areas in China to assist disease management.

Circular RNAs (circRNAs) are circularized, single-stranded RNAs that are covalently linked. With their abundance in tissues and developmental stage-specific expression, circRNAs participate in a variety of physiological and pathological processes. In this review, we discuss the development of circRNAs used as biomarkers and therapeutic targets for cardiovascular diseases (CVDs), focusing on recent discoveries and applications of exosomal circRNAs that highlight opportunities and challenges. Some studies have identified a spectrum of circRNAs that are differentially expressed in CVDs, while other studies further manipulated specific circRNA expression and showed an ameliorated pathogenic state such as ischemic injury, hypertrophy, and cardiac fibrosis. Studies and applications of circRNAs are being rapidly developed. We expect to see clinical use of circRNAs as biomarkers and targets for disease treatment in the near future., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aberrant expression of urokinase-type plasminogen activator receptor (uPAR) has been observed in human gastric cancers. Prostaglandin E 2 (PGE 2 ), whose biosynthesis is catalyzed by cyclooxygenase-2 (COX-2), is implicated in cancer metastasis; however, the cellular and molecular mechanisms of PGE 2 -driven uPAR expression are yet to be elucidated in human gastric cancer AGS cells. In this study, we showed that PGE 2 induces uPAR expression in concentration- and time-dependent manners. Furthermore, using antagonists and siRNA, we found that among the four subtypes of PGE 2 receptors, EP2 receptors are involved in PGE 2 -induced uPAR expression. PGE 2 induced the activation of Src, epidermal growth factor receptor (EGFR), c-Jun NH 2 -terminal kinase (JNK), extracellular signal-regulated kinase (Erk), and p38 mitogen activated protein kinase (p38 MAPK). Specific inhibitor and mutagenesis studies showed that Src, EGFR, JNK1/2, and Erk1/2 are involved in PGE 2 -induced uPAR expression. PGE 2 induces EP2-dependent phosphorylation of Src, while the activation of Src-dependent EGFR leads to the phosphorylation of JNK1/2 and Erk1/2. Deletion and site-directed mutagenesis studies demonstrated the involvement of transcription factor activator protein (AP)-1 and nuclear factor-kappa B (NF-κB) in PGE 2 -induced uPAR expression. EGFR-dependent MAPKs (JNK1/2 and Erk1/2) function as the upstream signaling molecules in the activation of AP-1 and NF-κB, respectively. AGS cells pre-treated with PGE 2 showed remarkably enhanced invasiveness, which was partially abrogated by uPAR-neutralizing antibodies. To the best of our knowledge, this is the first report that PGE 2 -induced uPAR expression, which stimulates invasiveness of human gastric cancer AGS cells, is mediated by the EP2 receptor-dependent Src/EGFR/JNK1/2, Erk1/2/AP-1, and Src/EGFR/JNK1/2, Erk1/2/NF-κB cascades. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

To investigate the epidemiology of hand, foot, and mouth disease (HFMD) and the genetic characteristics of enterovirus A71 (EV-A71) in Linyi of Shandong Province, China during 2007-2012. The number of reported HFMD cases were obtained from the National Notifiable Disease Reporting System (NNDRS) were analyzed by descriptive epidemiology method; the VP1 region of EV-A71 isolated from HFMD patients in Linyi was amplified and sequenced. Finally, the genetic variability and phylogenecity of VP1 sequences of EV-A71 were analyzed by MEGA 5.0. The results showed that HFMD incidence was reported in each year from 2007 to 2012 in Linyi, and the highest incidence and mortality were reported in 2009, when there were total 14697 cases and 9 of death. The reported incidence was 140.28/100000, and the mortality was 0.086/100000. The peak incidence usually occurred between April and July, and the summit occurred in May. Scattered children accounted for 77.37%-92.00% of all cases. The peak age was 2.5 years during 2007-2009 and 1.5 years during 2010-2012. A total of 1365 laboratory-confirmed HFMD cases were reported in the 6 consecutive years, accounting for 2.98% of the gross number. Among these reports, the ratio of EV-A71 was 44.18%, and the ratio of coxsackievirus A16 (CVA16) was 46.59%. All EV-A71 strains isolated in Linyi during 2007-2012 belonged to the C4a evolutionary branch of C4 genotype. In conclusion, HFMD outbreaks occurred every year in Linyi during 2007-2012. Incidence varied significantly among different counties. The peak incidence in each year lasted from April to July. Most of the patients were children under 3 years of age, and scattered children took the highest proportion. Co-circulation of EV-A71 and CVA16 was the major cause of HFMD in each year. Since the first report of HFMD prevalence caused by EV-A71 (C4a) in 2007, the virus has been prevalent continuously in Linyi for 6 years.

Rice stripe virus (RSV), which belongs to the genus Tenuivirus, is an emergent virus problem. The RSV genome is composed of four single-strand RNAs (RNA1-RNA4) and encodes seven proteins. We investigated interactions between six of the RSV proteins by yeast-two hybrid (Y2H) assay in vitro and by bimolecular fluorescence complementation (BiFC) in planta. Y2H identified self-interaction of the nucleocapsid protein (NP) and NS3, while BiFC revealed self-interaction of NP, NS3, and NCP. To identify regions(s) and/or crucial amino acid (aa) residues required for NP self-interaction, we generated various truncated and aa substitution mutants. Y2H assay showed that the N-terminal region of NP (aa 1-56) is necessary for NP self-interaction. Further analysis with substitution mutants demonstrated that additional aa residues located at 42-47 affected their interaction with full-length NP. These results indicate that the N-terminal region (aa 1-36 and 42-47) is required for NP self-interaction. BiFC and co-localization studies showed that the region required for NP self-interaction is also required for NP localization at the nucleus. Overall, our results indicate that the N-terminal region (aa 1-47) of the NP is important for NP self-interaction and that six aa residues (42-47) are essential for both NP self-interaction and nuclear localization., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To understand the clinical features of death from hand, foot and mouth disease (HFMD) and to explore the early warning index of HFMD death., Methods: A total of 41 HFMD death cases were collected as case group in Shandong province between 2009 and 2011, and another 123 serious HFMD cases were selected as control group according to the similar gender, place of origin and hospital level, with the ratio at 1:3. We investigated the general situation, clinical treatment, past medical history, clinical symptoms and signs of the ill children, and applied the conditional logistic regression to explore early warning index of HFMD death., Results: The rate of patients who had symptoms in nervous system, digestive system, circulatory system and respiratory system were separately 90.2% (37/41), 58.5% (24/41), 53.7% (22/41) and 90.2% (37/41) in case group; and the proportions were 44.7% (55/123), 13.8% (17/123), 10.6% (13/123) and 12.2% (15/123) respectively in control group. The difference between the two groups showed statistical significance (χ(2) = 25.881, 32.791, 34.011, 86.505, P < 0.05). In case group, 37 patients had neurogenic pulmonary edema, 26 patients got encephalitis, 15 patients had respiratory and circulatory failure, 7 patients got pulmonary hemorrhage, 4 patients had multiple organ failure, 4 patients got myocarditis and 1 patient had cerebral hernia. According to multi-factor logistic regression analysis, the early warning indicators of HFMD death included neck resistance (case group: 34.1% (14/41), control group: 4.1% (5/123); OR = 7.145, 95%CI: 1.748 - 29.204), vomiting (case group: 58.5% (24/41), control group: 13.8% (17/123); OR = 5.632, 95%CI: 1.793 - 17.685) and increase of heart rate (case group: 53.7% (22/41), control group: 10.6% (14/123), OR = 6.370, 95%CI: 1.517 - 26.743)., Conclusion: In the process of clinical treatment and care, we should interfere the serious HFMD patients with neck resistance, vomiting and increase of heart rate, and thereby reduce the death from HFMD.