Search

Longlong Wang,1,2 Qiong Ou,1,2 Guangliang Shan,3 Miaochan Lao,2 Guo Pei,2 Yanxia Xu,2 Jinhuan Huang,4 Jiaoying Tan,1,2 Weiping Chen,1,2 Bing Lu1,2 1The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 2Sleep Center, Department of Pulmonary and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, People’s Republic of China; 3Department of Epidemiology & Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences/School of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, People’s Hospital of Chenghai, Shantou, People’s Republic of ChinaCorrespondence: Qiong Ou, Sleep Center, Department of Pulmonary and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute, Guangzhou, 510080, People’s Republic of China, Tel +86 13609717251, Email ouqiong2776@hotmail.comPurpose: Non-sleepy sleep-disordered breathing (SDB) is increasingly recognized as an important clinical subtype. The association between non-sleepy SDB and cardiovascular disease (CVD) is not well understood. Our objectives were to investigate the relationship between non-sleepy SDB and CVD and determine which nocturnal hypoxia parameter most strongly reflects this association in a large community population.Patients and Methods: Cross-sectional data from 3626 randomly-selected Chinese community-dwelling participants who underwent overnight type IV sleep monitoring were analyzed. Parameters of nocturnal hypoxemia were extracted from sleep monitoring devices, including mean nocturnal oxygen saturation, lowest oxygen saturation, oxygen desaturation index (ODI), and time with oxygen saturation < 90%. An ODI ≥ 7.0 events/h was considered to signify SDB. An Epworth Sleepiness Scale score of 10 or less indicated no sleepiness.Results: The SDB rate was 30.7% (1114/3626), of which 96.5% (1075/1114) were considered the non-sleepy SDB subtype. ODI, typical nocturnal intermittent hypoxia indicator for SDB, was independently related to CVD, regardless of whether excessive daytime sleepiness was present. After adjusting for confounders, ODI most strongly reflected the association between non-sleepy SDB and CVD (OR:1.023; 95% CI:1.003– 1.043). We observed a nonlinear association between ODI and the prevalence of CVD, where the likelihood of CVD increased with ODI≥ 10 events/h and a markedly increasing trend was observed with ODI ≥ 20 events/h (reference ODI = 7.0 events/h). Metabolic parameters, Pittsburgh Sleep Quality Index, and inflammatory marker did not mediate the association between ODI and CVD in the non-sleepy SDB subtype.Conclusion: In the Chinese community-dwelling population, non-sleepy SDB was highly prevalent. ODI, an easily extracted indicator from a type IV sleep monitor, most strongly reflected the association between non-sleepy SDB and CVD.Keywords: oxygen desaturation index, cardiovascular disease, non-sleepy, sleep-disordered breathing, community-based general population

Ke Huang,1,2 Kewu Huang,3 Jianying Xu,4 Lan Yang,5 Jianping Zhao,6 Xiangyan Zhang,7 Chunxue Bai,8 Jian Kang,9 Pixin Ran,10 Huahao Shen,11 Fuqiang Wen,12 Yahong Chen,13 Tieying Sun,14 Guangliang Shan,15 Yingxiang Lin,3 Sinan Wu,2,16 Ting Yang,1,2,17 Chen Wang1,2,17,18 1Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, National Clinical Research Center for Respiratory Diseases, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Shanxi Dayi Hospital, Taiyuan, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of China; 8Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 9Department of Pulmonary and Critical Care Medicine, First Hospital of China Medical University, Shenyang, People’s Republic of China; 10State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 11Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People’s Republic of China; 12State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 13Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 14Department of Respiratory and Critical Care Medicine, Beijing Hospital, Beijing, People’s Republic of China; 15Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 16Institute of Clinical Medical Sciences, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 17Department of Respiratory Medicine, Capital Medical University, Beijing, People’s Republic of China; 18Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Chen Wang; Ting YangDepartment of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Chaoyang District, Beijing, 100029, People’s Republic of ChinaTel +86 10 65105565; +86 10 84206276Email cyh-birm@263.net; dryangting@qq.comPurpose: Anxiety and depression are often underdiagnosed and affect the prognosis of patients with chronic obstructive pulmonary disease (COPD). We analyzed data from the China Pulmonary Health (CPH) study to assess the prevalence of anxiety and depression in COPD patients and their relationship with disease severity.Patients and Methods: A total of 57,779 subjects aged 20 years or older were recruited in the CPH study. All participants were assessed using a standard questionnaire and underwent pulmonary function tests before and after the use of a bronchodilator in local health centers. The Hospital Anxiety and Depression Scale (HADS) questionnaire with a cutoff score of 8 was used to define anxiety and depression. The prevalence of anxiety and depression in patients of COPD were investigated. Multivariate logistic regression was used to investigate the effects of COPD and lung function on anxiety and depression.Results: A total of 49,053 participants (20,661 men and 28,392 women) completed the questionnaire with reliable post-bronchodilator pulmonary function test results and were included in the final analysis, of which 4686 (9.55%) were diagnosed with COPD. Of the patients with COPD, 10.79% had anxiety, 13.65% had depression, and 7.08% had anxiety and depression concomitantly. In the multivariate logistic regression analysis, COPD was not significantly associated with anxiety, depression, or both. After adjusting for confounders in model 1, patients in the GOLD III–IV group had a significantly higher risk of anxiety, depression, and their coincidence. After further adjusting for respiratory symptoms in model 2, lung function impairment in the GOLD III–IV group was only significantly associated with a higher risk of depression or at least one of anxiety and depression.Conclusion: Anxiety and depression are prevalent in patients with COPD in China. More severe lung function impairment is significantly associated with a higher risk of depression.Keywords: anxiety, COPD, depression, Hospital Anxiety and Depression Scale, HADS

Our understanding of interactions among intestinal helminths, gut microbiota and host is still in its infancy in fish. In this study, the effects of Schyzocotyle acheilognathi infection on the intestinal microbiota, growth and immune reactions of grass carp were explored under laboratory conditions. 16S rDNA amplification sequencing results showed that S. acheilognathi infection altered the composition of intestinal microbiota only at the genus level, with a significant increase in the relative abundance of Turicibacter and Ruminococcus (P < 0.05) and a significant decrease in the relative abundance of Gordonia, Mycobacterium and Pseudocanthomonas (P < 0.05). Schyzocotyle acheilognathi infection had no significant effect (P > 0.05) on the alpha diversity indices (including Chao1, ACE, Shannon, Simpson index) of intestinal microbiota in grass carp, but PERMANOVA analysis showed that microbial structure significantly (P < 0.01) differed between hindgut and foregut. PICRUST prediction showed that some metabolism-related pathways were significantly changed after S. acheilognathi infection. The relative abundance of Turicibacter was positively correlated with the fresh weight of tapeworm (foregut: r = 0.48, P = 0.044; hindgut: r = 0.63, P = 0.005). There was no significant difference in the body condition of grass carp between the S. acheilognathi infected group and the uninfected group (P > 0.05). Intestinal tissue section with HE staining showed that S. acheilognathi infection severely damaged the intestinal villi, causing serious degeneration, necrosis and shedding of intestinal epithelial cells. The real-time fluorescent quantitative PCR results showed that S. acheilognathi infection upregulated the mRNA expression of the immune-related genes: Gal1-L2, TGF-β1 and IgM.

Abstract Background Species belonging to the genus Lernaea are cosmopolitan parasites that can infect many different freshwater fish hosts. Due to a high degree of morphological intraspecific variability and high levels of interspecific similarities, their classification is extremely difficult and controversial. Although the suitability of the shape of cephalic horns has been questioned decades ago by some experimental infection studies, this character still plays the central role in the identification of Lernaea spp. Methods We used the nominal species Lernaea cyprinacea and Lernaea cruciata to test the hypothesis that the shape of the anchor can exhibit host-induced morphological variability, and that the two taxa may be synonymous. Results We examined 517 wild or farmed specimens of five host fish species (four cyprinids and a mosquitofish), and found that all 16 parasite specimens collected from mosquitofish could be morphologically identified as L. cruciata, whereas the remaining 25 parasite specimens were all identified as L. cyprinacea. We experimentally infected goldfish and mosquitofish specimens with offspring (copepodids) of a single L. cyprinacea specimen: the adult parasites from goldfish were morphologically identified as L. cyprinacea, and those from mosquitofish as L. cruciata. We then used molecular data to corroborate that all these specimens are conspecific. Conclusions Our results suggest that L. cyprinacea and L. cruciata may be synonyms, misidentified as different species as a result of host-induced morphological variation. Given the current shortage of molecular data for the genus Lernaea, in order to resolve the taxonomy of this genus (determine the exact number of species), future studies should aim to sequence as much molecular data as possible, and conduct further experimental infections.

Abstract Background Parasitic protozoans, helminths, alter the gut microbiota in mammals, yet little is known about the influence of intestinal cestodes on gut microbiota in fish. In the present study, the composition and diversity of the hindgut microbiota were determined in the intestine of common carp (Cyprinus carpio) infected with two tapeworm species, Khawia japonensis and Atractolytocestus tenuicollis. Results The intestine contained a core microbiota composed of Proteobacteria, Fusobacteria and Tenericutes. Infection with the two cestode species had no significant effect on the microbial diversity and richness, but it altered the microbial composition at the genus level. PCoA analysis indicated that microbial communities in the infected and uninfected common carp could not be distinguished from each other. However, a Mantel test indicated that the abundance of K. japonensis was significantly correlated with the microbial composition (P = 0.015), while the abundance of A. tenuicollis was not (P = 0.954). According to Pearsonʼs correlation analysis, the abundance of K. japonensis exhibited an extremely significant (P

Abstract Background Isopoda is a highly diverse order of crustaceans with more than 10,300 species, many of which are parasitic. Taxonomy and phylogeny within the order, especially those of the suborder Cymothoida Wägele, 1989, are still debated. Mitochondrial (mt) genomes are a useful tool for phylogenetic studies, but their availability for isopods is very limited. To explore these phylogenetic controversies on the mt genomic level and study the mt genome evolution in Isopoda, we sequenced mt genomes of two parasitic isopods, Tachaea chinensis Thielemann, 1910 and Ichthyoxenos japonensis Richardson, 1913, belonging to the suborder Cymothoida, and conducted comparative and phylogenetic mt genomic analyses across Isopoda. Results The complete mt genomes of T. chinensis and I. japonensis were 14,616 bp and 15,440 bp in size, respectively, with the A+T content higher than in other isopods (72.7 and 72.8%, respectively). Both genomes code for 13 protein-coding genes, 21 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and possess a control region (CR). Both are missing a gene from the complete tRNA set: T. chinensis lacks trnS1 and I. japonensis lacks trnI. Both possess unique gene orders among isopods. Within the CR of I. japonensis (284 bp), we identified a repetitive region with four tandem repeats. Phylogenetic analysis based on concatenated nucleotide sequences of 13 protein-coding genes showed that the two parasitic cymothoids clustered together and formed a basal clade within Isopoda. However, another parasitic cymothoid, Gyge ovalis Shiino, 1939, formed a sister group with the suborder Limnoriidea Brandt & Poore in Poore, 2002, whereas two free-living cymothoid species were located in the derived part of the phylogram: Bathynomus sp. formed a sister group with the suborder Sphaeromatidea Wägele, 1989, and Eurydice pulchra Leach, 1815 with a clade including Bathynomus sp., Sphaeromatidea and Valvifera G. O. Sars, 1883. Conclusions Our results did not recover the suborders Cymothoida and Oniscidea Latreille, 1802 as monophyletic, with parasitic and free-living cymothoidans forming separate clades. Furthermore, two parasitic cymothoidans formed the sister-clade to all other isopods, separated from Epicaridea Latreille, 1825, which challenges currently prevalent isopod phylogeny. Additional mt genomes of parasitic and free-living isopods might confer a sufficient phylogenetic resolution to enable us to resolve their relationships, and ultimately allow us to better understand the evolutionary history of the entire isopod order.

Abstract Background Recent mitochondrial phylogenomics studies have reported a sister-group relationship of the orders Capsalidea and Dactylogyridea, which is inconsistent with previous morphology- and molecular-based phylogenies. As Dactylogyridea mitochondrial genomes (mitogenomes) are currently represented by only one family, to improve the phylogenetic resolution, we sequenced and characterized two dactylogyridean parasites, Lamellodiscus spari and Lepidotrema longipenis, belonging to a non-represented family Diplectanidae. Results The L. longipenis mitogenome (15,433 bp) contains the standard 36 flatworm mitochondrial genes (atp8 is absent), whereas we failed to detect trnS1, trnC and trnG in L. spari (14,614 bp). Both mitogenomes exhibit unique gene orders (among the Monogenea), with a number of tRNA rearrangements. Both long non-coding regions contain a number of different (partially overlapping) repeat sequences. Intriguingly, these include putative tRNA pseudogenes in a tandem array (17 trnV pseudogenes in L. longipenis, 13 trnY pseudogenes in L. spari). Combined nucleotide diversity, non-synonymous/synonymous substitutions ratio and average sequence identity analyses consistently showed that nad2, nad5 and nad4 were the most variable PCGs, whereas cox1, cox2 and cytb were the most conserved. Phylogenomic analysis showed that the newly sequenced species of the family Diplectanidae formed a sister-group with the Dactylogyridae + Capsalidae clade. Thus Dactylogyridea (represented by the Diplectanidae and Dactylogyridae) was rendered paraphyletic (with high statistical support) by the nested Capsalidea (represented by the Capsalidae) clade. Conclusions Our results show that nad2, nad5 and nad4 (fast-evolving) would be better candidates than cox1 (slow-evolving) for species identification and population genetics studies in the Diplectanidae. The unique gene order pattern further suggests discontinuous evolution of mitogenomic gene order arrangement in the Class Monogenea. This first report of paraphyly of the Dactylogyridea highlights the need to generate more molecular data for monogenean parasites, in order to be able to clarify their relationships using large datasets, as single-gene markers appear to provide a phylogenetic resolution which is too low for the task.

Abstract Background As the topologies produced by previous molecular and morphological studies were contradictory and unstable (polytomy), evolutionary relationships within the Diplozoidae family and the Monogenea class (controversial relationships among the Discocotylinea, Microcotylinea and Gastrocotylinea suborders) remain unresolved. Complete mitogenomes carry a relatively large amount of information, sufficient to provide a much higher phylogenetic resolution than traditionally used morphological traits and/or single molecular markers. However, their implementation is hampered by the scarcity of available monogenean mitogenomes. Therefore, we sequenced and characterized mitogenomes belonging to three Diplozoidae family species, and conducted comparative genomic and phylogenomic analyses for the entire Monogenea class. Results Taxonomic identification was inconclusive, so two of the species were identified merely to the genus level. The complete mitogenomes of Sindiplozoon sp. and Eudiplozoon sp. are 14,334 bp and 15,239 bp in size, respectively. Paradiplozoon opsariichthydis (15,385 bp) is incomplete: an approximately 2000 bp-long gap within a non-coding region could not be sequenced. Each genome contains the standard 36 genes (atp8 is missing). G + T content and the degree of GC- and AT-skews of these three mitogenome (and their individual elements) were higher than in other monogeneans. nad2, atp6 and nad6 were the most variable PCGs, whereas cox1, nad1 and cytb were the most conserved. Mitochondrial phylogenomics analysis, conducted using concatenated amino acid sequences of all PCGs, indicates that evolutionary relationships of the three genera are: (Eudiplozoon, (Paradiplozoon, Sindiplozoon)); and of the three suborders: (Discocotylinea, (Microcotylinea, Gastrocotylinea)). These intergeneric relationships were also supported by the skewness and principal component analyses. Conclusions Our results show that nad2, atp6 and nad6 (fast-evolving) would be better candidates than cox1 (slow-evolving) for species identification and population genetics studies in Diplozoidae. Nucleotide bias and codon and amino acid usage patterns of the three diplozoid mitogenomes are more similar to cestodes and trematodes than to other monogenean flatworms. This unusual mutational bias was reflected in disproportionately long branches in the phylogram. Our study offsets the scarcity of molecular data for the subclass Polyopisthocotylea to some extent, and might provide important new insights into the evolutionary history of the three genera and three suborders.

Abstract Background After observing differences in the number of reproductive complexes per proglottid within the genus Ligula, the genus Digramma was erected. However, the validity of Digramma has been previously questioned due to a low variability in the cox1, nad1 and ITS rDNA sequences between the two genera. We undertook a study to greatly increase the amount of sequence data available for resolution of this question by sequencing and characterizing the complete mitogenomes of Digramma interrupta and Ligula intestinalis. Results The circular mtDNA molecules of Digramma interrupta and Ligula intestinalis are 13,685 bp and 13,621 bp in size, respectively, both comprising 12 PCGs, 22 tRNA genes, two rRNA genes, and two mNCRs. Both mitogenomes exhibit the same gene order and share 92.7% nucleotide identity, compared with 85.8–86.5% to the most closely related genus Dibothriocephalus. Each gene from D. interrupta and L. intestinalis is almost of the same size, and the sequence identity ranges from 87.5% (trnD) to 100% (trnH, trnQ and trnV). NCR2 sequences of D. interrupta and L. intestinalis are 249 bp and 183 bp in length, respectively, which contributes to the main difference in length between their complete mitogenomes. A sliding window analysis of the 12 PCGs and two rRNAs indicated nucleotide diversity to be higher in nad5, nad6, nad2, nad4 and cox3, whereas the most conserved genes were rrnL and rrnS. Lower sequence identity was also found in nad2, nad4, nad5, nad6 and cox3 genes between the two diphyllobothriids. Within the Diphyllobothriidae, phylogenetic analysis indicated Ligula and Digramma to be most closely related to one another, forming a sister group with Dibothriocephalus. Conclusions Owing to higher nucleotide diversity, the genes nad2, nad4, nad5, nad6 and cox3 should be considered optimal candidates to use as molecular markers for population genetics and species identification between the two closely related species. The phylogenetic results in combination with the comparative analysis of the two mitogenomes, consistently support the congeneric status of L. intestinalis and D. interrupta.

Abstract Background Paratetraonchoides inermis (Monogenea: Tetraonchoididae) is a flatworm parasitising the gills of uranoscopid fishes. Its morphological characteristics are ambiguous, and molecular data have never been used to study its phylogenetic relationships, which makes its taxonomic classification controversial. Also, several decades of unsuccessful attempts to resolve the relationships within the Monogenea present a strong indication that morphological datasets may not be robust enough to be used to infer evolutionary histories. As the use of molecular data is currently severely limited by their scarcity, we have sequenced and characterized the complete mitochondrial (mt) genome of P. inermis. To investigate its phylogenetic position, we performed phylogenetic analyses using Bayesian inference and maximum likelihood approaches using concatenated amino acid sequences of all 12 protein-coding genes on a dataset containing all available monogenean mt genomes. Results The circular mt genome of P. inermis (14,654 bp) contains the standard 36 genes: 22 tRNAs, two rRNAs, 12 protein-encoding genes (PCGs; Atp8 is missing) and a major non-coding region (mNCR). All genes are transcribed from the same strand. The A + T content of the whole genome (82.6%), as well as its elements, is the highest reported among the monogeneans thus far. Three tRNA-like cloverleaf structures were found in mNCR. Several results of the phylogenomic analysis are in disagreement with previously proposed relationships: instead of being closely related to the Gyrodactylidea, Tetraonchidea exhibit a phylogenetic affinity with the Dactylogyridea + Capsalidea clade; and the order Capsalidea is neither basal within the subclass Monopisthocotylea, nor groups with the Gyrodactylidea, but instead forms a sister clade with the Dactylogyridea. The mt genome of P. inermis exhibits a unique gene order, with an extensive reorganization of tRNAs. Monogenea exhibit exceptional gene order plasticity within the Neodermata. Conclusions This study shows that gene order within monopisthocotylid mt genomes is evolving at uneven rates, which creates misleading evolutionary signals. Furthermore, our results indicate that all previous attempts to resolve the evolutionary history of the Monogenea may have produced at least partially erroneous relationships. This further corroborates the necessity to generate more molecular data for this group of parasitic animals.

Abstract Background External segmentation and internal proglottization are important evolutionary characters of the Eucestoda. The monozoic caryophyllideans are considered the earliest diverging eucestodes based on partial mitochondrial genes and nuclear rDNA sequences, yet, there are currently no complete mitogenomes available. We have therefore sequenced the complete mitogenomes of three caryophyllideans, as well as the polyzoic Schyzocotyle acheilognathi, explored the phylogenetic relationships of eucestodes and compared the gene arrangements between unsegmented and segmented cestodes. Results The circular mitogenome of Atractolytocestus huronensis was 15,130 bp, the longest sequence of all the available cestodes, 14,620 bp for Khawia sinensis, 14,011 bp for Breviscolex orientalis and 14,046 bp for Schyzocotyle acheilognathi. The A-T content of the three caryophyllideans was found to be lower than any other published mitogenome. Highly repetitive regions were detected among the non-coding regions (NCRs) of the four cestode species. The evolutionary relationship determined between the five orders (Caryophyllidea, Diphyllobothriidea, Bothriocephalidea, Proteocephalidea and Cyclophyllidea) is consistent with that expected from morphology and the large fragments of mtDNA when reconstructed using all 36 genes. Examination of the 54 mitogenomes from these five orders, revealed a unique arrangement for each order except for the Cyclophyllidea which had two types that were identical to that of the Diphyllobothriidea and the Proteocephalidea. When comparing gene order between the unsegmented and segmented cestodes, the segmented cestodes were found to have the lower similarities due to a long distance transposition event. All rearrangement events between the four arrangement categories took place at the junction of rrnS-tRNA Arg (P1) where NCRs are common. Conclusions Highly repetitive regions are detected among NCRs of the four cestode species. A long distance transposition event is inferred between the unsegmented and segmented cestodes. Gene arrangements of Taeniidae and the rest of the families in the Cyclophyllidea are found be identical to those of the sister order Proteocephalidea and the relatively basal order Diphyllobothriidea, respectively.

Abstract IS630/Tc1/mariner (ITm) represents the most widely distributed superfamily of DNA transposons in nature. Currently, bioinformatics research on ITm members primarily involves collecting data of existing and emerging members and organizing them into new groups or families. In the present study, our survey revealed that Tc1 and IS630 members have a broad host range, spanning across all six biological kingdoms (bacteria, fungi, plantae, animalia, archaea and protista) and viruses. The primary discoveries include the first Tn630 member—Tn630-NC1 and the closest homolog of IS630 from viruses—Tc1-C#1. By incorporating our discoveries into existing knowledge, we proposed a model to elucidate the formation of composite transposons. Organization of Tc1 and IS630 members into groups across biological kingdoms facilitates data collection for future research, particularly on their horizontal transfer between different kingdoms. The formation of composite transposons may result from asymmetric of terminal inverted repeats. IS630 should be merged with Tc1 into a single family IS630/Tc1. Furthermore, IS630 and its homologs constitute a valuable resource for studying horizontal gene transfer between gut bacteria and phages, opening up new avenues for research in this field.

Abstract The function of PD-1/PD-L1 axis have been intensively studied for immune escape of various cancers. However, the underlying function of PD-L2 remains poorly understood. Here, we demonstrate that PD-L2 is majorly expressed in exosomes with surface localization by clear cell renal cell carcinoma (ccRCC) cells. Tumor cell-derived exosome PD-L2 (TDE-PD-L2) exhibits high expression compared with TDE-PD-L1 in various cancers. In the absence of adaptive immune, TDE-PD-L2 suppresses tumor growth and metastasis. Under immune competence condition, TDE-PD-L2 is hijacked by immune cells in a PD-1-dependent manner to systematically dampen function of T cells via the increased proportion of the regulatory T cells and the decreased proportion of cytotoxic CD8+ T cells in both tumor-infiltrating T cells and spleen. The effects of TDE-PD-L2 on tumor is restored by antibodies targeting PD-L2. Collectively, we demonstrate that PD-1/TDE-PD-L2 axis systematically suppresses T cell functions, representing a potentially therapeutic strategy for ccRCC treatment.

Abstract Background Obesity has emerged as a growing global public health concern over recent decades. Obesity prevalence exhibits substantial global variation, ranging from less than 5% in regions like China, Japan, and Africa to rates exceeding 75% in urban areas of Samoa. Aim To examine the involvement of metabolism-related genes. Methods Gene expression datasets GSE110729 and GSE205668 were accessed from the GEO database. DEGs between obese and lean groups were identified through DESeq2. Metabolism-related genes and pathways were detected using enrichment analysis, WGCNA, Random Forest, and XGBoost. The identified signature genes were validated by real-time quantitative PCR (qRT-PCR) in mouse models. Results A total of 389 genes exhibiting differential expression were discovered, showing significant enrichment in metabolic pathways, particularly in the propanoate metabolism pathway. The orangered4 module, which exhibited the highest correlation with propanoate metabolism, was identified using Weighted Correlation Network Analysis (WGCNA). By integrating the DEGs, WGCNA results, and machine learning methods, the identification of two metabolism-related genes, Storkhead Box 1 (STOX1), NACHT and WD repeat domain-containing protein 2(NWD2) was achieved. These signature genes successfully distinguished between obese and lean individuals. qRT-PCR analysis confirmed the downregulation of STOX1 and NWD2 in mouse models of obesity. Conclusion This study has analyzed the available GEO dataset in order to identify novel factors associated with obesity metabolism and found that STOX1 and NWD2 may serve as diagnostic biomarkers.

Abstract Background There is a growing interest in utilizing a combination of brain radiotherapy (RT) and tyrosine kinase inhibitors (TKIs) for patients diagnosed with brain metastases (BM) in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma (LAC). The current status of this treatment strategy remains a subject of debate. Methods We initiated our study by conducting a comprehensive literature search using the SCI-expanded database of Web of Science Core Collection (WoSCC). We utilized the VOSPviewer software to analyze various aspects of the research, including the year of publication, authorship, keywords, and country.Subsequently, we performed an extensive and systematic literature search on popular online databases. Our primary outcome measures were overall survival (OS) and intracranial progression-free survival (iPFS), both quantified by hazard ratios (HRs). Additionally, for data verification, we included data from patients in non-small cell lung cancer with brain metastasis who underwent therapeutic intervention at the Cancer Prevention and Treatment Center of Sun Yat-sen University and the Radiotherapy Department of Hanzhong Central Hospital between August 2012 and November 2021. Results The bibliometric analysis revealed an increasing trend in research focused on the combination of RT and TKIs for the management of lung cancer brain metastases over the previous decade. Then, nine studies consistent with the research direction were included for meta-analysis. The meta-analysis showed that the OS (HR = 0.81, 95% confidence interval: 0.69–0.94; P = 0.007) and iPFS (HR = 0.71, 95% confidence interval: 0.61–0.82; P