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Yaling Li,1,* Kaiyang Shao,1,* Ruyi Cai,1 Yi Liu,2 Xiaojing Liu,2,3 Feihua Ni,1 Huiyan Zheng,1 Ruying Hu,1 Ting Sun1 1Department of Health Management Center, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ting Sun, Department of Health Management Center, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, People’s Republic of China, Email 1195037@zju.edu.cnBackground: The coexistence of blaNDM-1 with other resistance determinants is rarely reported for Providencia rettgeri. Therefore, this study investigates the phenotypic and genetic characteristics of a multidrug-resistant P. rettgeri strain YQ150713.Methods: P. rettgeri YQ150713 was identified as carrying blaNDM-1. S1-pulsed-field gel electrophoresis (S1-PFGE), Southern blotting, and conjugation experiments were used to determine plasmid characteristics. An antimicrobial susceptibility test was conducted. The complete genomic sequence of YQ150713 was obtained using Illumina NovaSeq 6000 and Oxford nanopore platforms. To further characterize the phylogenetic structure of P. rettgeri YQ150713, average nucleotide identity (ANI) and phylogenetic analyses were conducted.Results: The S1-PFGE, Southern blot, and conjugation assays have confirmed that the isolate P. rettgeri YQ150713 contains the blaNDM-1 gene on a conjugative plasmid pYQ150713-NDM-1. Antimicrobial susceptibility testing has indicated that strain YQ150713 was resistant to various common antibiotics, except aztreonam and fosfomycin. Bioinformatics analysis has further shown that pYQ150713-NDM-1 was a novel plasmid with a size of 265,883 bp, and blaNDM-1 and blaOXA-10 were co-located on it. Phylogenetic analysis suggesting P. rettgeri has spread widely throughout the world.Conclusion: In this study, blaNDM-1 and blaOXA-10 were co-localized on a novel plasmid pYQ150713-NDM-1 with a horizontal transfer function. To reduce the risk of the dissemination of such P. rettgeri isolates in clinical settings, more surveillance will be required in the future.Keywords: antimicrobial resistance, blaNDM-1, blaOXA-10, Providencia rettgeri, carbapenemase-producing, average nucleotide identity, phylogenetic

Yingying Shen,1,* Fanhua Yu,2,* Hangping Ge,1 Keding Shao,2 Yuhong Zhou,1 Baodong Ye,1 Yiping Shen,1 Dijiong Wu1 1Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dijiong Wu; Yiping ShenDepartment of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, #54 Youdian Road, Hangzhou, Zhejiang, 310006, People’s Republic of ChinaFax +8657187073569Email wudijiong@zcmu.edu.cn; shenyp_@126.comAbstract: Autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) can be observed in Waldenström macroglobulinemia (WM). The autoimmune disorders are primarily mediated by autoimmune monoclonal gammopathy, but drug-induced hemolysis should also be considered. Herein, we presented the case of a 63-year-old female WM patient complicated with ITP, who was admitted to our department with a complaint of abdominal pain. After first half of bortezomib/dexamethasone/rituximab (BRD) chemotherapy, her platelet level recovered, but subsequently decreased to extremely low level (around 1– 2× 109/L), and the patient suffered from platelet transfusion refractoriness. During the management of refractory thrombocytopenia, the patient developed severe hemolytic anemia, and further tests confirmed warm AIHA. FcγRIIα polymorphism test showed that the patient had FcγRIIα-131RH, which implied that the AIHA may not be WM-related. Given the effects of ibrutinib in controlling WM, secondary AITP and AIHA, ibrutinib single treatment was started, which quickly corrected the thrombocytopenia within five days, but not hemolysis. With a relatively safe platelet level, eltrombopag was stopped, and the hemolysis relieved three days after eltrombopag withdrawal. This is the first report on eltrombopag-induced AIHA in the management of WM-associated ITP.Keywords: Waldenström macroglobulinemia, immune thrombocytopenia, ibrutinib, hemolytic anemia, eltrombopag, rituximab

Ding Ye,1 Bin Liu,1 Zhixing He,2 Lin Huang,2 Yu Qian,1 Keding Shao,2 Chengping Wen,2 Yingying Mao1 1Department of Epidemiology and Biostatistics, Zhejiang Chinese Medical University School of Public Health, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Institute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University School of Basic Medical Sciences, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaCorrespondence: Yingying MaoDepartment of Epidemiology and Biostatistics, Zhejiang Chinese Medical University School of Public Health, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaTel +86-571-8661-3536Email myy@zcmu.edu.cnChengping WenInstitute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University School of Basic Medical Sciences, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaTel +86-571-8663-3377Email wengcp@163.comObjective: To investigate the potential causal associations of circulating levels of growth differentiation factor 15 (GDF-15) with the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) using a Mendelian randomization (MR) design.Methods: A genome-wide association study (GWAS) of GDF-15 among 5,440 individuals of European ancestry was used to identify genetic instruments. Summary statistics of SLE, RA and IBD were obtained from publicly available GWASs. We conducted an MR study using the inverse-variance weighted (IVW) method, supplemented with simple-median and weighted-median methods. Cochran Q test and MR-Egger regression were used to detect potential heterogeneity and directional pleiotropy. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.Results: We found that genetically predicted high circulating GDF-15 levels were associated with a decreased risk of SLE (OR 0.80, 95% CI 0.68– 0.92 by IVW), with similar results in sensitivity analyses. In replication analysis using summary data from another SLE GWAS, the results were consistent (OR 0.82, 95% CI 0.71– 0.93 by IVW). Moreover, no evidence of heterogeneity or pleiotropy was detected. However, genetically determined circulating levels of GDF-15 were not associated with risk of RA or IBD in the primary analysis and subsequent sensitivity analyses.Conclusions: Our study suggested an inverse association between circulating GDF-15 levels and risk of SLE, and further studies are warranted to elucidate the underlying biological mechanisms. There was limited evidence supporting a causal association of circulating GDF-15 levels with risk of RA and IBD.Keywords: growth differentiation factor 15, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Mendelian randomization, single nucleotide polymorphism

Li-Li Xia,1,* Su-Fen Li,2,* Kan Shao,1 Xin Zhang,3 Shan Huang1 1Department of Endocrinology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Neurology, Huai’an Second People’s Hospital and The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, People’s Republic of China; 3Department of Radiology, The Fourth People’s Hospital of Huai’an, Huai’an, People’s Republic of China *These authors contributed equally to this work Abstract: To investigate the correlation between computed tomography (CT) features and glycosylated hemoglobin (HbAlc) levels in patients with type 2 diabetes mellitus (T2DM) complicated with primary pulmonary tuberculosis (PTB). One hundred and eighty untreated PTB patients complicated with T2DM were selected. Based on the HbAlc level, the patients were divided into three groups: HbAlc level 9% (Group III: 100 patients). The changes of CT manifestations and HbAlc were analyzed after TB and T2DM treatment. In the three groups, the detection rate of large segmented leafy shadow was 50%, 56.2%, and 87%; the air bronchogram sign detection rate was 40.6%, 47.9%, and 77%; the discovery rate of mouth-eaten cavity was 31.2%, 45.8%, and 65%; thick wall cavity detection rate was 25%, 31.2%, and 52%; the rate of multiple cavities was 34.3%, 50%, and 73%; and bronchial TB was found in 33.3%, 21.8%, and 46%, respectively. The detection rates of lesions in Group III were significantly higher than in Group II and Group I (p

ABSTRACT The gut microbiota plays an essential role in the health of bees. To elucidate the effect of feed and Nosema ceranae infection on the gut microbiota of honey bee (Apis cerana), we used 16S rRNA sequencing to survey the gut microbiota of honey bee workers fed with sugar water or beebread and inoculated with or without N. ceranae. The gut microbiota of A. cerana is dominated by Serratia, Snodgrassella, and Lactobacillus genera. The overall gut microbiota diversity was show to be significantly differential by feeding type. N. ceranae infection significantly affects the gut microbiota only in bees fed with sugar water. Higher abundances of Lactobacillus, Gluconacetobacter, and Snodgrassella and lower abundances of Serratia were found in bees fed with beebread than in those fed with sugar water. N. ceranae infection led to a higher abundance of Snodgrassella and a lower abundance of Serratia in sugar-fed bees. Imputed bacterial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed the significant metagenomics functional differences by feeding and N. ceranae infections. Furthermore, A. cerana workers fed with sugar water showed lower N. ceranae spore loads but higher mortality than those fed with beebread. The cumulative mortality was strongly positive correlated (rho = 0.61) with the changes of overall microbiota dissimilarities by N. ceranae infection. Both feeding types and N. ceranae infection significantly affect the gut microbiota in A. cerana workers. Beebread not only provides better nutrition but also helps establish a more stable gut microbiota and therefore protects bees in response to N. ceranae infection. IMPORTANCE The gut microbiota plays an essential role in the health of bees. Scientific evidence suggests that diet and infection can affect the gut microbiota and modulate the health of the gut; however, the interplay between those two factors and the bee gut microbiota is not well known. In this study, we used a high-throughput sequencing method to monitor the changes of gut microbiota associated with both feeding types and Nosema ceranae infection. Our results showed that the gut microbiota composition and diversity of Asian honey bee were significantly associated with both feeding types and the N. ceranae infection. More interestingly, bees fed with beebread showed higher microbiota stability and lower mortality rates than those fed with sugar water when infected by N. ceranae. Those data suggest that beebread has the potential not only to provide better nutrition but also help to establish a more stable gut microbiota to protect bees against N. ceranae infection.

Catastrophic brittle failure prevents the application of bulk metallic glasses (BMGs).The brittle La69Co17Al14 BMG shows large compressive plasticity when compressed in constrained conditions. Here the compressive plasticity of this BMG was systematically studied by decreasing aspect ratio (height/diameter) of the samples in uniaxial compression and the brittle-ductile transition occurs at an aspect ratio of 0.36. With the increase of the plasticity (decrease of the aspect ratio), the hardness decreases firstly and then increases, however, the relaxation enthalpy indicating its structure increases monotonically. Our findings provide a powerful experimental support for the application of brittle La-based BMGs. [ABSTRACT FROM AUTHOR]

To improve the performance of laser selective melted 316L stainless steel products, this paper studies the effect of laser power on the mechanical properties. The results of the study showed that when the laser power is 180 W, the surface morphology and tensile fracture of the specimen are best, and the mechanical properties of formed parts can be improved by laser selective melting of 316L stainless steel. [ABSTRACT FROM AUTHOR]

Introduction: Honey bees provides valuable pollination services for world food crops and wild flowering plants which are habitats of many animal species and remove carbon dioxide from the atmosphere, a powerful tool in the fight against climate change. Nevertheless, the honey bee population has been declining and the majority of colony losses occur during the winter. Objectives: The goal of this study was to understand the mechanisms underlying overwinter colony losses and develop novel therapeutic strategies for improving bee health. Methods: First, pathogen prevalence in overwintering bees were screened between 2015 and 2018. Second, RNA sequencing (RNA-Seq) for transcriptional profiling of overwintering honey bees was conducted and qRT-PCR was performed to confirm the results of the differential expression of selected genes. Lastly, laboratory bioassays were conducted to measure the effects of cold challenges on bee survivorship and stress responses and to assess the effect of a novel medication for alleviating cold stress in honey bees. Results: We identified that sirtuin signaling pathway is the most significantly enriched pathway among the down-regulated differentially expressed genes (DEGs) in overwintering diseased bees. Moreover, we showed that the expression of SIRT1 gene, a major sirtuin that regulates energy and immune metabolism, was significantly downregulated in bees merely exposed to cold challenges, linking cold stress with altered gene expression of SIRT1. Furthermore, we demonstrated that activation of SIRT1 gene expression by SRT1720, an activator of SIRT1 expression, could improve the physiology and extend the lifespan of cold-stressed bees. Conclusion: Our study suggests that increased energy consumption of overwintering bees for maintaining hive temperature reduces the allocation of energy toward immune functions, thus making the overwintering bees more susceptible to disease infections and leading to high winter colony losses. The novel information gained from this study provides a promising avenue for the development of therapeutic strategies for mitigating colony losses, both overwinter and annually.