Characterization of the complete mitochondrial genome of Ergasilus anchoratus Markevich, 1946 (Ergasilidae) and phylogeny of Copepoda.

The mitochondrial (mt) genome can provide data for phylogenetic analyses and evolutionary biology. Herein, we sequenced and annotated the complete mt genome of Ergasilus anchoratus. This mt genome was 13852 bp long and comprised 13 protein-coding genes (PCGs), 22 tRNAs and 2 rRNAs. All PCGs used the standard ATN start codons and complete TAA/TAG termination codons. A majority of tRNA genes exhibited standard cloverleaf secondary structures, with the exception of one tRNA that lacked the TψC arm (trnC), and three tRNAs that lacked the DHU arm (trnR, trnS1 and trnS2). Phylogenetic analyses conducted using Bayesian inference (BI) and maximum likelihood (ML) methods both supported Ergasilidae as a monophyletic family forming a sister group to Lernaea cyprinacea and Paracyclopina nana. It also supported the monophyly of orders Calanoida, Cyclopoida, and Siphonostomatoida; and the monophyly of families Harpacticidae, Ergasilidae, Diaptomidae, and Calanidae. The gene orders of E. anchoratus and Sinergasilus undulatus were identical, which represents the first instance of two identical gene orders in copepods. More mt genomes are needed to better understand the phylogenetic relationships within Copepoda in the future.

Reversibly Cross-Linked Isoporous Membranes Fabricated by the Recyclable Block Copolymer with Pendent Dithiolane Groups.

The reversible formation and cleavage of disulfide bonds under physical/chemical stimuli make it a valuable motif in constructing dynamically cross-linked materials. In the present work, the block copolymer bearing pendent dithiolanes was synthesized and fabricated into isoporous membranes by the combination of self-assembly and nonsolvent-induced phase separation strategy. The cross-linking within the membrane was realized by the thiol-initiated ring-opening cascades of cyclic disulfides. Successful formation of disulfide bond networks within the isoporous membranes was proved by the Raman spectra, UV-vis diffuse reflectance spectroscopy, differential scanning calorimetry, and rheological analysis. The cross-linking in membranes was further demonstrated by the notably improved toughness and obviously enhanced swelling resistance to acid/alkaline solution as well as organic solvents. Importantly, the cross-linked isoporous membranes were fully dissolvable in solution containing dithiothreitol, which enabled the complete cleavage of disulfide bonds and successful recovery of the block copolymer that was able to be repeatedly fabricated into isoporous membranes with pore sizes identical to membranes prepared from the freshly synthesized copolymer. Our results indicate that dynamically cross-linked isoporous membranes with improved durability and good recyclability can be custom-made by simply incorporating active dithiolane moieties into self-assembling block copolymers.

Comprehensive molecular characterisation of the complete mitogenome of Ergasilus tumidus and phylogenetic relationships of Copepoda inferred from mitogenomes.

Although parasitic copepods of the genus Ergasilus von Nordmann, 1832 are globally distributed parasites of fish, their phylogenetic relationships with other Copepoda are not clear, and the characteristics of their mitochondrial genomes (mitogenomes) are not thoroughly understood. The objective of this study was to address these knowledge gaps by sequencing the complete mitogenome of Ergasilus tumidus Markevich, 1940. The complete mitogenome (GenBank Acc. No. OQ596537) was 14,431 bp long and it comprised 13 protein-coding genes (PCGs), 22 tRNAs, two tRNAs, and two control regions (CRs). Phylogenetic analyses, conducted using concatenated nucleotide and amino acid sequences of 13 protein-coding genes, produced two partially incongruent topologies. While the order Calanoida was consistently resolved as the sister lineage to the other three orders, topological instability was observed in the relationships of the orders Cyclopoida, Siphonostomatoida and Harpacticoida. Siphonostomatoida clustered with Cyclopoida in the nucleotide-based phylogeny, but with Harpacticoida in the amino acid-based phylogeny. The latter topology conforms to the widely accepted relationships, but we speculate that the former topology is more likely to be the correct one. Our study provides a complete mitogenome sequence of E. tumidus, which helps us better understand the molecular evolution of the genus Ergasilus. Additionally, we suggest a different perspective on the controversial phylogenetic relationships among Siphonostomatoida, Cyclopoida and Harpacticoida, diverging from previously accepted views.

1T-VS2@V2O3 Synergistic Nanoarchitecture-Based Lamellar Clusters as the High Conductivity Cathodes of Thermal Batteries.

Thermal batteries are solid-state, thermally activated batteries with long storage times and high reliability. FeS2 is used as a cathode material commonly, but the high internal resistance and low voltage platform limit the improvement of battery performance. Herein, the 1T-phase vanadium disulfide (VS2) is prepared via the scalable hydrothermal method and applied to thermal battery cathode materials for the first time. 1T-VS2 lamellar flower clusters have high electronic conductivity (1.583 S cm-1) at room temperature, which is 75 times higher than FeS2 (0.021 S cm-1). Mechanism analysis shows that 1T-VS2@V2O3 can be formed based on the part of 1T-VS2 being oxidized to V2O3 at the discharge temperature. Benefiting from the synergistic effect of vanadium sulfide and vanadium oxide as a cathode for thermal batteries enhanced specific capacity (292.4 mA h g-1) and mass energy density (572.5 W h kg-1) when cutoff voltage is 1 V. Additionally, the discharge results indicate that the cells utilizing 1T-VS2 cathodes provided a higher voltage platform of 2.11 V than 1.84 V for FeS2. This impressive work can offer a good strategy for boosting cathode materials for a high-performance thermal battery.

Postoperative blood glucose increase is associated with futile recanalization in patients with successful thrombectomy: a retrospective study.

BACKGROUND: Timely recognition of futile recanalization might enable a prompt response and an improved outcome in post-thrombectomy patients. This study aims to evaluate whether postoperative blood glucose increase (BGI) could act as an indicator of futile recanalization in patients receiving a successful thrombectomy. METHODS: This is a single-center, retrospective analysis of patients with anterior circulation large-vessel occlusion and successful thrombectomy between February 2019 and June 2022. BGI was defined as a higher level of blood glucose at the first postoperative morning than at admission. Futile recanalization was defined as patients with a modified Rankin Scale score of 3-6 at 90 days after onset. Multivariable binary logistic regression was used to assess the association of BGI with futile recanalization. RESULTS: A total of 276 patients were enrolled, amongst which 120 patients (43.5%) had BGI. Futile recanalization was more prevalent among patients with BGI compared to those without (70.0 vs. 49.4%, P = 0.001). After adjusting for potential confounders, BGI was associated with a higher likelihood of futile recanalization (adjusted OR: 2.97, 95%CI: 1.50-5.86, P = 0.002). This association was consistently observed regardless of diabetes history, occlusion site, time from symptom onset to groin puncture, or reperfusion status. CONCLUSION: Our findings support BGI serving as an indicator of futile recanalization in patients with anterior circulation large-vessel occlusion and successful thrombectomy.

Evaluation of SARS-CoV-2 RNA Rebound After Nirmatrelvir/Ritonavir Treatment in Randomized, Double-Blind, Placebo-Controlled Trials - United States and International Sites, 2021-2022.

Rebound of SARS-CoV-2 shedding or COVID-19 signs and symptoms has been described after treatment with nirmatrelvir/ritonavir (Paxlovid). The direct association of nirmatrelvir/ritonavir to COVID-19 rebound remains unclear because most reports are based on individual cases or nonrandomized studies. Viral RNA shedding data from two phase 2/3, randomized, double-blind, placebo-controlled clinical trials of nirmatrelvir/ritonavir (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients [EPIC-HR] and Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients [EPIC-SR]) were analyzed to investigate the role of nirmatrelvir/ritonavir treatment in COVID-19 rebound. Rates of rebound of SARS-CoV-2 RNA shedding, identified based on an increase in nasopharyngeal viral RNA levels from day 5 (end-of-treatment) to day 10 or day 14, were similar between nirmatrelvir/ritonavir and placebo recipients. Among subjects with a virologic response through day 5, viral RNA rebound occurred in 6.4%-8.4% of nirmatrelvir/ritonavir recipients and 5.9%-6.5% of placebo recipients across EPIC-HR and the 2021/pre-Omicron and 2022/Omicron enrollment periods of EPIC-SR. Viral RNA rebound after nirmatrelvir/ritonavir treatment was not associated with COVID-19-related hospitalization or death. Data from randomized trials demonstrated that SARS-CoV-2 rebound can occur with or without antiviral treatment, supporting the Food and Drug Administration's determination of safety and efficacy of nirmatrelvir/ritonavir in eligible patients at high risk for severe COVID-19.

Postoperative fibrinogen-to-albumin ratio acting as an indicator of futile recanalization in patients with successful thrombectomy.

BACKGROUND: Timely recognition of futile recanalization might enable a prompter response and thus improve outcomes in patients receiving successful thrombectomy. This study aims to evaluate whether postoperative fibrinogen-to-albumin ratio (FAR) could act as an indicator of futile recanalization. METHODS: This is a single-center, retrospective analysis of patients with acute anterior circulation large-vessel occlusion and successful thrombectomy between May 2019 and June 2022. FAR was defined as postoperative blood levels of fibrinogen divided by those of albumin, and dichotomized into high and low levels based on the Youden index. Futile recanalization was defined as patients achieving a successful recanalization with a modified Rankin Scale score of 3-6 at 90 days. Multivariable logistic regression was used to assess the association of FAR with futile recanalization. RESULTS: A total of 255 patients were enrolled, amongst which 87 patients (34.1%) had high postoperative FAR. Futile recanalization was more prevalent among patients with high FAR compared to those with low FAR (74.7% vs. 53.0%, p = .001). After adjusting for potential confounders, high postoperative FAR was found to independently correspond with the occurrence of futile recanalization (adjusted OR 2.40, 95%CI 1.18-4.87, p = .015). This association was consistently observed regardless of prior antithrombotic therapy, treatment of intravenous thrombolysis, occlusion site, time from symptom onset to groin puncture, and reperfusion status. CONCLUSION: Our findings support high postoperative FAR serving as an indicator of futile recanalization in patients with anterior circulation large-vessel occlusion and successful thrombectomy.

[Analysis of O3 Sources in Yulin City in Summer Based on WRF-CMAQ/ISAM Model].

In order to have a clearer understanding of the sources of ozone pollution in Yulin City in summer and put forward scientific governance suggestions, the WRF-CMAQ model was used to simulate the O3 concentration in Yulin City and surrounding areas (including Taiyuan City, Xi'an City, Yinchuan City, Hohhot City, and other provincial capital cities) in July 2019. Using the ISAM module, the sources of O3 and its precursors NOx and VOCs in a heavy pollution process in Yulin City were quantified. The results showed that on heavy pollution days, the O3 in Yulin City mainly came from the long-distance transmission outside the simulation area (55.5%), followed by the photochemical reaction of precursors in the simulation area (20.6%, 10.0%, 5.0%, 2.3%, and 2.1%, respectively, in Yulin City, Shanxi Province, Inner Mongolia Autonomous Region, and Shaanxi Province, 1.2% in Gansu Province, Ningxia Hui Autonomous Region, and Henan Province in total), and initial conditions (0.3%); the remaining sources (23.6%) could not be successfully labeled. Yulin City is in the VOCs control area, and its VOCs were composed of paraffin (76.5%), ketones (9.2%), and other types of VOCs (14.3%). The VOCs came from the emission of pollution sources in the simulation area (45.6%, 22.0%, 11.4%, 6.3%, and 5.1%, respectively, in Yulin City, Shanxi Province, Inner Mongolia Autonomous Region, and Shaanxi Province, 0.8% in Gansu Province, Ningxia Hui Autonomous Region, and Henan Province in total) and the long-distance transmission outside the simulation area (27.9%); the remaining 26.5% were not successfully marked. This research showed that to control the O3 pollution in Yulin, not only should the local VOCs emissions be controlled, but the overall planning of VOCs emissions in the peripheral areas should also be done well.

PRDX1 negatively regulates bleomycin-induced pulmonary fibrosis via inhibiting the epithelial-mesenchymal transition and lung fibroblast proliferation in vitro and in vivo.

BACKGROUND: Pulmonary fibrosis is a major category of end-stage changes in lung diseases, characterized by lung epithelial cell damage, proliferation of fibroblasts, and accumulation of extracellular matrix. Peroxiredoxin 1 (PRDX1), a member of the peroxiredoxin protein family, participates in the regulation of the levels of reactive oxygen species in cells and various other physiological activities, as well as the occurrence and development of diseases by functioning as a chaperonin. METHODS: Experimental methods including MTT assay, morphological observation of fibrosis, wound healing assay, fluorescence microscopy, flow cytometry, ELISA, western blot, transcriptome sequencing, and histopathological analysis were used in this study. RESULTS: PRDX1 knockdown increased ROS levels in lung epithelial cells and promoted epithelial-mesenchymal transition (EMT) through the PI3K/Akt and JNK/Smad signalling pathways. PRDX1 knockout significantly increased TGF-ß secretion, ROS production, and cell migration in primary lung fibroblasts. PRDX1 deficiency also increased cell proliferation, cell cycle circulation, and fibrosis progression through the PI3K/Akt and JNK/Smad signalling pathways. BLM treatment induced more severe pulmonary fibrosis in PRDX1-knockout mice, mainly through the PI3K/Akt and JNK/Smad signalling pathways. CONCLUSIONS: Our findings strongly suggest that PRDX1 is a key molecule in BLM-induced lung fibrosis progression and acts through modulating EMT and lung fibroblast proliferation; therefore, it may be a therapeutic target for the treatment of BLM-induced lung fibrosis.

[Analysis of Causes and Sources of Summer Ozone Pollution in Rizhao Based on CMAQ and HYSPLIT Models].

As a typical coastal city, O3 pollution in Rizhao has become increasingly serious in recent years. In order to explore the causes and sources of O3 pollution, IPR process analysis and ISAM source tracking tools based on the CMAQ model were used, respectively, to quantify the contributions of different physicochemical processes and different source tracking areas to O3 in Rizhao. Additionally, by comparing the differences between O3-exceeding days and non-exceeding days, combined with the HYSPLIT model, the regional transportation path of O3 in Rizhao was explored. The results showed that the concentrations of O3, NOx, and VOCs near the coastal areas of Rizhao and Lianyungang were significantly increased on O3 exceedance days compared with those on non-exceedance days. This was mainly because Rizhao was the convergence zone of western, southwestern, and eastern winds on exceedance days, which facilitated the transport and accumulation of pollutants. Process analysis showed that the transport process (TRAN) contribution to the near-surface O3 near the coastal areas of Rizhao and Lianyungang increased significantly on the exceedance days, whereas the contribution to most areas to the west of Linyi decreased. Photochemical reaction (CHEM) had a positive contribution to the O3 concentration in Rizhao during the daytime at all heights, and TRAN had a positive contribution at 0-60 m above the ground, and mainly had a negative contribution above 60 m. The contributions of CHEM and TRAN at 0-60 m above the ground would increase significantly on exceedance days, which was approximately twice that on the non-exceedance days. Source analysis showed that the local sources in Rizhao were the main contribution sources of NOx and VOCs, with the contribution rates of 47.5% and 58.0%, respectively. O3 mainly came from the contribution outside the simulation area (67.5%). The O3 and precursor contributions of the western cities of Rizhao (Weifang, Linyi, etc.) and the southern cities (Lianyungang, etc.) would increase significantly on the days of exceeding the standard. The transportation path analysis showed that the number of exceedances accounted for the largest proportion (11.8%) in the path from the west of Rizhao, which was the main transportation channel of O3 and precursors in Rizhao. This was verified through process analysis and source tracking results, and such trajectories accounted for 13.0% of the total number of trajectories, and their main routes were in the Shaanxi, Shanxi, Hebei, and Shandong regions.

Efficacy and safety evaluation of complete intrafascial prostatectomy in suspected prostate cancer patients with dysuria: a retrospective cohort study.

Background: Suspected localized prostate cancer (PCa) patients with dysuria Complete intrafascial prostatectomy (CIP) can remove the whole prostate gland with the maximal retain of adjacent normal tissues around the prostate, and can be applied in some suspected localized prostate cancer (PCa) patients with dysuria. However, precious few studies have assessed the efficacy and safety of CIP in these patients without preoperative needle biopsies. Methods: In this retrospective single-arm cohort study, all 22 suspected PCa patients with dysuria who underwent CIP at our hospital were enrolled. The clinical data including age, prostate-specific antigen (PSA), free-serum PSA, prostate volume, perioperative and postoperative complications were collected. The PSA level at 6 weeks after CIP and recoveries of urinary continence and erectile function were acquired in the follow-up procedures, and were used as the main measurements of efficacy and safety for CIP respectively. Results: The patients had an average age of 71.91±8.29 years and an average preoperative PSA level of 10.75±4.25 ng/mL. The operations for all 22 patients were successfully completed. The average operation time was 135.20±41.44 min (range, 40.0-215.0 min), and the average blood loss volume was 128.64±145.09 mL. In total, 17 patients (77.27%) had PCa confirmed by postoperative pathology, and 5 patients (22.73%) had benign prostatic hyperplasia. The PSA level dropped to 0.010±0.004 ng/mL at 6 weeks after surgery. According to the loose criteria to assess urinary incontinence, the patients achieved continence rates of 63.6% immediately after the operation, 95.5% at 1 month, and 100% at 3 months. According to the strict criteria, the continence rates immediately, and at 1, 3, 6, and 9 months after surgery were 27.3%, 63.6%, 90.9%, 95.5%, and 100%, respectively. None of the patients complained of urinary obstruction symptoms after surgery. Before CIP, all the patients had erectile dysfunction and an International Index of Erectile Function 5 (IIEF-5) score of 9.64±5.91. After surgery, the patients had IIEF-5 scores at 3, 6, and 12 months of 5.45±4.43, 6.95±5.30, and 7.57±5.69, respectively. Conclusions: Although the study had some limitations, CIP may be a prudent option for patients with suspected localized PCa who also present with dysuria.

[Gene Polymorphisms of Patients with Lymphoma-Associated Hemophagocytic Syndrome in Longyan area, Fujian Province].

OBJECTIVE: To analyze the gene polymorphisms of patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. METHODS: A total of 125 patients with lymphoma-associated hemophagocytic syndrome in Longyan, Fujian province, admitted to Longyan First Hospital from May 2017 to November 2020 were selected. Peripheral venous blood was collected from all the patients, and the genotypes of perforin 1 (PRF1) and interleukin-10 (IL-10) gene loci were detected by PCR-fluorescence probe method, and the correlation between PRF1 and IL-10 gene polymorphisms and lymphoma-associated hemophagocytic syndrome was analyzed. RESULTS: The mutation frequencies of PRF1 gene loci rs885821 (C>T), rs885822 (C>T), rs1889490 (G>A) in patients with lymphoma-associated hemophagocytic syndrome were 10.40%, 78.8% and 64.4%, respectively. The mutation frequencies of rs1800872 (A>C), rs1800871 (C>T) and rs1800896 (G>A) of IL-10 loci were 56.0%, 45.2% and 77.6%, respectively. CONCLUSION: PRF1 and IL-10 gene loci were polymorphic in patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. Alleles C and G of PRF1 and IL-10 were risk factors, and alleles T and A were protective factors.

Metformin attenuates multiple myeloma cell proliferation and encourages apoptosis by suppressing METTL3-mediated m6A methylation of THRAP3, RBM25, and USP4.

Based on the results of epidemiological and preclinical studies, metformin can improve the prognosis of patients with malignant tumors. Studies have confirmed that metformin inhibits multiple myeloma (MM) cell proliferation and promotes apoptosis. Nevertheless, the specific mechanism remains to be elucidated. MM cells were intervened with different doses of metformin to detect cell proliferation and apoptosis. Western blotting and RT-qPCR were employed to assess the expression of METTL3, METTL14, WTAP, FTO, and ALKBH5 after metformin intervention. The microarray dataset GSE29023 was retrieved from the Gene Expression Omnibus (GEO) database and calculated using the R language (limma package) to authenticate differentially expressed genes (DEGs). The database for annotation, visualization, and integrated discovery (David) was applied for GO annotation analysis of DEGs. Subsequently, the string database and Cytoscape software were applied to construct protein-protein interaction (PPI) and DEM hub gene networks. Bioinformatics analysis and MeRIP were applied to predict and test METTL3-mediated m6A levels on mRNA of THRAP3, RBM25, and USP4 in METTL3 knocked-down cells. Then rescue experiments were performed to explore effects of METTL3 and THRAP3, RBM25, or USP4 on cell proliferation and apoptosis. The effect on MM cell xenograft tumor growth was observed by injection of metformin or/and overexpression of METTL3 in in vivo experiments. Metformin decreased cell proliferation and encouraged cell apoptosis in a dose-dependent manner. Global m6A modification was elevated in MM cells compared to normal cells, which was counteracted by metformin treatment. Furthermore, THRAP3, RBM25, and USP4 were identified as possible candidate genes for metformin treatment by GSE29023 data mining. METTL3 interference impaired m6A modification on mRNA of THRAP3, RBM25, and USP4 as well as expression levels. The mRNA stability and expression of THRAP3, RBM25, and USP4 was decreased after metformin treatment, which was reversed by METTL3 overexpression. THRAP3, RBM25 or USP4 knockdown reversed the assistance of METTL3 overexpression on the malignant behavior of MM cells. Finally, upregulation of METTL3 was shown to exert facilitative effects on xenograft tumor growth by blocking metformin injection. The present study demonstrates that metformin can repress the expression of THRAP3, RBM25, and USP4 by inhibiting METTL3-mediated m6A modification, which in turn hamper cell proliferation and promotes cell apoptosis.Abbreviations: multiple myeloma (MM), Gene Expression Omnibus (GEO), differentially expressed genes (DEGs), database for annotation, visualization and integrated discovery (David), protein-protein interaction (PPI), epithelial­mesenchymal transition (EMT), methyltransferase like 3 (METTL3), methyltransferase like 14 (METTL14), wilms tumor 1-associated protein (WTAP), methyltransferase like 16 (METTL16), acute myeloid leukemia (AML), non-small lung cancer (NSCLC), glioma stem cells (GSCs), normal bone marrow-derived plasma cells (nPCs), false discovery rate (FDR), biological process (BP), optical density (OD), horseradish peroxidase (HRP), M6A RNA immunoprecipitation assay (MeRIP).

Synthesis of cellulose nanofiber/polysiloxane-polyurea composite materials with self-healing and reprocessing properties.

Inspired by the self-recoverability ability of organisms, various self-healing materials have been developed. However, most reinforced fillers are faced with the problem that mechanical strength and self-healing efficiency of materials cannot be improved simultaneously. Here we first prepared new polysiloxane-polyurea (PDMS-PU) and used it as matrix resin to prepare cellulose nanofiber (CNF)/PDMS-PU composite materials with high mechanical properties. CNFs increased the tensile strength of PDMS-PU by 38.87 % and CNF/PDMS-PU composite materials maintained the great bending resistance, transparency and reprocessing properties of PDMS-PU. Moreover, the introduction of CNFs did not reduce the self-healing efficiency of PDMS-PU, and PDMS-PU containing disulfide bonds with CNF content of 1 % (CNF/PDMS-IPDI-S-1 %) with healing efficiency of 95.58 %, and the tensile strength after three recycling processing was still as high as 92.55 % of the original. CNFs reinforced PDMS-PU composite materials are expected to replace PDMS materials in advanced engineering fields that require high strength durability and good formability.

Gene Polymorphisms of Patients with Lymphoma-Associated Hemophagocytic Syndrome in Longyan area, Fujian Province / 中国实验血液学杂志

OBJECTIVE@#To analyze the gene polymorphisms of patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province.@*METHODS@#A total of 125 patients with lymphoma-associated hemophagocytic syndrome in Longyan, Fujian province, admitted to Longyan First Hospital from May 2017 to November 2020 were selected. Peripheral venous blood was collected from all the patients, and the genotypes of perforin 1 (PRF1) and interleukin-10 (IL-10) gene loci were detected by PCR-fluorescence probe method, and the correlation between PRF1 and IL-10 gene polymorphisms and lymphoma-associated hemophagocytic syndrome was analyzed.@*RESULTS@#The mutation frequencies of PRF1 gene loci rs885821 (C>T), rs885822 (C>T), rs1889490 (G>A) in patients with lymphoma-associated hemophagocytic syndrome were 10.40%, 78.8% and 64.4%, respectively. The mutation frequencies of rs1800872 (A>C), rs1800871 (C>T) and rs1800896 (G>A) of IL-10 loci were 56.0%, 45.2% and 77.6%, respectively.@*CONCLUSION@#PRF1 and IL-10 gene loci were polymorphic in patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. Alleles C and G of PRF1 and IL-10 were risk factors, and alleles T and A were protective factors.

The Coupling Between Cell Wall Integrity Mediated by MAPK Kinases and SsFkh1 Is Involved in Sclerotia Formation and Pathogenicity of Sclerotinia sclerotiorum.

The plant pathogenic fungus Sclerotinia sclerotiorum can survive on a wide range of hosts and cause significant losses on crop yields. FKH, a forkhead box (FOX)-containing protein, functions to regulate transcription and signal transduction. As a transcription factor (TF) with multiple biological functions in eukaryotic organisms, little research has been done on the role of FKH protein in pathogenic fungi. SsFkh1 encodes a protein which has been predicted to contain FOX domain in S. sclerotiorum. In this study, the deletion mutant of SsFkh1 resulted in severe defects in hyphal development, virulence, and sclerotia formation. Moreover, knockout of SsFkh1 lead to gene functional enrichment in mitogen-activated protein kinase (MAPK) signaling pathway in transcriptome analysis and SsFkh1 was found to be involved in the maintenance of the cell wall integrity (CWI) and the MAPK signaling pathway. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that SsFkh1 interacts with SsMkk1. In addition, we explored the conserved MAPK signaling pathway components, including Bck1, Mkk1, Pkc1, and Smk3 in S. sclerotiorum. ΔSsmkk1, ΔSspkc1, ΔSsbck1, and ΔSssmk3knockout mutant strains together with ΔSsmkk1 com, ΔSspkc1 com, ΔSsbck1 com, and ΔSssmk3 com complementation mutant strains were obtained. The results indicated that ΔSsmkk1, ΔSspkc1, ΔSsbck1, and ΔSssmk3 displayed similar phenotypes to ΔSsfkh1 in sclerotia formation, compound appressorium development, and pathogenicity. Taken together, SsFkh1 may be the downstream substrate of SsMkk1 and involved in sclerotia formation, compound appressorium development, and pathogenicity in S. sclerotiorum.

Pterostilbene pre-treatment reduces LPS-induced acute lung injury through activating NR4A1.

CONTEXT: Pterostilbene (PTE), a common polyphenol compound, exerts an anti-inflammatory effect in many diseases, including acute lung injury (ALI). OBJECTIVE: This study explores the potential mechanism of PTE pre-treatment against lipopolysaccharide (LPS)-induced ALI. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were divided into control, ALI, 10 mg/kg PTE + LPS, 20 mg/kg PTE + LPS, and 40 mg/kg PTE + LPS groups. At 24 h before LPS instillation, PTE was administered orally. At 2 h before LPS instillation, PTE was again administered orally. After 24 h of LPS treatment, the rats were euthanized. The levels of inflammatory cells and inflammatory factors in the bronchoalveolar lavage fluid (BALF), the expression of nuclear receptor subfamily 4 group A member 1 (NR4A1), and the nuclear factor (NF)-κB pathway-related protein levels were detected. NR4A1 agonist was used to further investigate the mechanism of PTE pre-treatment. RESULTS: After PTE pre-treatment, the LPS induced inflammation was controlled and the survival rate was increased to 100% from 70% after LPS treatment 24 h. For lung injury score, it decreased to 1.5 from 3.5 after treating 40 mg/kg PTE. Compared with the control group, the expression of NR4A1 in the ALI group was decreased by 20-40%. However, the 40 mg/kg PTE pre-treatment increased the NR4A1 expression by 20-40% in the lung tissue. The results obtained with pre-treatment NR4A1 agonist were similar to those obtained by pre-treatment 40 mg/kg PTE. CONCLUSIONS: PTE pre-treatment might represent an appropriate therapeutic target and strategy for preventing ALI induced by LPS.

An engineered abcb4 expression model reveals the central role of NF-κB in the regulation of drug resistance in zebrafish.

Multi-drug resistance (MDR) is a phenomenon that tumor cells are exposed to a chemotherapeutic drug for a long time and then develop resistance to a variety of other anticancer drugs with different structures and different mechanisms. The in vitro studies of tumor cell lines cannot systematically reflect the role of MDR gene in vivo, and the cost of in vivo studies of transgenic mice as animal models is high. Given the myriad merits of zebrafish relative to other animal models, we aimed to establish a screening system using zebrafish stably expressing ATP-binding cassette (ATP-cassette) superfamily transporters and unveil the potential regulatory mechanism. We first used the Tol2-mediated approach to construct a Tg (abcb4:EGFP) transgenic zebrafish line with ATP-binding cassette (ABC) subfamily B member 4 (abcb4) gene promoter to drive EGFP expression. The expression levels of abcb4 and EGFP were significantly increased when Tg(abcb4:EGFP) transgenic zebrafish embryos were exposed to doxorubicin (DOX) or vincristine (VCR), and the increases were accompanied by a marked decreased accumulation of rhodamine B (RhB) in embryos, indicating a remarkable increase in DOX or VCR efflux. Mechanistically, Akt and Erk signalings were activated upon the treatment with DOX or VCR. With the application of Akt and Erk inhibitors, drug resistance was reversed with differing responsive effects. Notably, downstream NF-κB played a central role in the regulation of abcb4-mediated drug resistance. Taken together, the data indicate that the engineered Tg(abcb4:EGFP) transgenic zebrafish model is a new platform for screening drug resistance in vivo, which may facilitate and accelerate the process of drug development.

Starchy vegetable intake in the first trimester is associated with a higher risk of gestational diabetes mellitus: a prospective population-based study.

OBJECTIVE: The purpose of this study was to evaluate the association between starchy vegetable consumption and subgroup consumption in the first trimester and the risk of gestational diabetes mellitus (GDM). METHODS: A prospective study (n = 1444) was conducted in China. Dietary information was assessed by 24-hour dietary recalls for three days and then we calculated the consumption of total starchy vegetable and its subgroups, including (1) potato and (2) other starchy vegetable (pumpkin, lotus root, yam, taro, water chestnut, pea, and cowpea). GDM was diagnosed according to the results of 75-g two-hour oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. A modified log-binomial regression was used to estimate RRs and 95% CIs of GDM risk. RESULTS: Among the 1444 participants in our study, 520 were diagnosed with GDM. The adjusted RRs (95% CIs) for GDM from the lowest to the highest quartiles of total starchy vegetable consumption were 1.00 (reference), 1.29 (1.06, 1.57), 1.13 (0.93, 1.40), and 1.26 (1.02, 1.56), respectively; p for trend = .032. For potato, the RR of GDM risk was 1.32 for the highest potato intake quartile compared with the lowest quartile (95% CI 1.07-1.64, p for trend = .003). In addition, we did not observe an association between other starchy vegetable intakes and GDM risk. CONCLUSIONS: A higher consumption of total starchy vegetables and potatoes in the first trimester is associated with a greater risk of GDM.

Transcription factor SsFoxE3 activating SsAtg8 is critical for sclerotia, compound appressoria formation, and pathogenicity in Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum, the notorious necrotrophic phytopathogenic fungus with wide distribution, is responsible for sclerotium disease in more than 600 plant species, including many economic crops such as soybean, oilseed rape, and sunflower. The compound appressorium is a crucial multicellular infection structure that is a prerequisite for infecting healthy tissues. Previously, the Forkhead-box family transcription factors (FOX TFs) SsFoxE2 and SsFKH1 were shown to play a key regulatory role in the hyphae growth, sexual reproduction, and pathogenicity of S. sclerotiorum. However, little is known about the roles of SsFoxE3 regulating growth and development and pathogenicity. Here, we report SsFoxE3 contributes to sclerotium formation and deletion of SsFoxE3 leads to reduced formation of compound appressoria and developmental delays. Transcripts of SsFoxE3 were greatly increased during the initial stage of infection and SsFoxE3 deficiency reduced virulence on the host, while stabbing inoculation could partially restore pathogenicity. The SsFoxE3 mutant showed sensitivity to H2 O2 , and the expression of reactive oxygen species detoxification and autophagy-related genes were reduced. Moreover, expression of SsAtg8 was also decreased during the infection process of the SsFoxE3 mutant. Yeast 1-hybrid tests suggested that SsFoxE3 interacted with the promoter of SsAtg8. Disruption of SsAtg8 resulted in a phenotype similar to that of the SsFoxE3 mutant. Comparative analysis of the level of autophagy in the wild type and SsFoxE3 mutant showed that N starvation-induced autophagy was reduced in the SsFoxE3 mutant. Taken together, our findings indicate that SsFoxE3 plays an important role in compound appressorium formation and is involved in transcriptional activation of SsAtg8 during infection by S. sclerotiorum.