bluuebunny/crossref_metadata_2025 huggingface dataset:
A meta-analysis of genome-wide gene expression differences identifies promising targets for type 2 diabetes mellitus
Authors: Huang Tao , Nazir Bisma , Altaf Reem , Zang Bolun , Zafar Hajra , Paiva-Santos Ana Cláudia , Niaz Nabeela , Imran Muhammad , Duan Yongtao , Abbas Muhammad , Ilyas Umair
Published: August 2022

Aims/introduction

Due to the heterogeneous nature of type 2 diabetes mellitus and its complex effects on hemodynamics, there is a need to identify new candidate markers which are involved in the development of type 2 diabetes mellitus (DM) and can serve as potential targets. As the global diabetes prevalence in 2019 was estimated as 9.3% (463 million people), rising to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045, the need to limit this rapid prevalence is of concern. The study aims to identify the possible biomarkers of type 2 diabetes mellitus with the help of the system biology approach using R programming.

Materials and methods

Several target proteins that were found to be associated with the source genes were further curated for their role in type 2 diabetes mellitus. The differential expression analysis provided 50 differentially expressed genes by pairwise comparison between the biologically comparable groups out of which eight differentially expressed genes were short-listed. These DEGs were as follows: MCL1, PTX3, CYP3A4, PTGS1, SSTR2, SERPINA3, TDO2, and GALNT7.

Results

The cluster analysis showed clear differences between the control and treated groups. The functional relationship of the signature genes showed a protein–protein interaction network with the target protein. Moreover, several transcriptional factors such as DBX2, HOXB7, POU3F4, MSX2, EBF1, and E4F1 showed association with these identified differentially expressed genes.

Conclusions

The study highlighted the important markers for diabetes mellitus that have shown interaction with other proteins having a role in the progression of diabetes mellitus that can serve as new targets in the management of DM.
The application of new concepts of the assessment of the thyroid state to pregnant women
Authors: Fitzgerald Stephen P. , Bean Nigel G. , Fitzgerald Samuel P. , Falhammar Henrik
Published: August 2022

Recently proposed concepts regarding the nature and assessment of the thyroid state have provided a model more consistent with empiric evidence. It now appears likely that there are no such entities as thyroid set points and individual euthyroidism. Rather than there being discrete thyroid states, peripheral organ parameters are associated with thyroid function in a continuous manner. Thyroid hormone levels and, in particular, levels of free thyroxine now appear to be superior to thyrotropin levels as indicators of the thyroid state. Complicating the assessment of the correlations of the thyroid state with pregnancy outcomes are the contribution of the placenta to maternal thyroid function, fetal thyroid development, the multiple potential pathways to any particular outcome, the likely presence of small critical periods of time, the differing genetics of fetal and maternal tissues, and the unreliability of thyroid hormone assays. Nevertheless, there is no apparent reason for there to be a change in pregnancy to the basic principles of thyroid hormone action. The relationships between mild abnormalities of the thyroid state and pregnancy outcomes and the value of treating such mild abnormalities remain uncertain and controversial. The evidence suggests that further investigation of these clinical questions might better be based on thyroid hormone, particularly free thyroxine, levels. In the investigation of borderline low thyroid states, the categories of subclinical hypothyroidism and isolated hypothyroxinemia might both be abandoned with attention being directed to low free thyroxine levels regardless of the thyroid-stimulating hormone (TSH) levels. For these changes to occur, there would ideally be improvements in the assays for free thyroxine in pregnancy. The evidence suggests that, just as in the non-pregnant situation, pregnancy guidelines based on thyrotropin levels may need revision.
Dynamic High Resolution Hydrological Status Monitoring in Real-Time: The UK Water Resources Portal
Authors: Barker Lucy J. , Fry Matt , Hannaford Jamie , Nash Gemma , Tanguy Maliko , Swain Oliver
Published: August 2022

Understanding the current hydro-meteorological situation is critical to manage extreme events and water resources. The United Kingdom Water Resources Portal (UKWRP) has been developed to enable dynamic, interactive access to hydro-meteorological data across the United Kingdom, including catchment daily rainfall (near), real-time daily mean river flows, groundwater levels, real-time soil moisture data, and standardised climate indices. The UKWRP offers a way of exploring the full range of river flow and rainfall variability, including comparing current conditions to those in the past, from droughts to floods. A variety of different plotting capabilities mean users can view and explore data in different ways depending on their requirements. Here we discuss the mechanisms and the engagement undertaken to develop the UKWRP, in addition to the technical issues and solutions of bringing multiple data sources and types together, how the data are processed, stored and published to deliver an integrated tool for water resources management. The UKWRP enables all water users–from farmers, to water companies to members of the general public–to view and explore the data used by regulators to manage water supplies. We demonstrate how the UKWRP can be used to monitor the hydrological situation, using recent examples of both floods and droughts, and enables consistent messaging and universal access to data and information. Finally, we discuss the decisions the information provided in the UKWRP can support, and possible future developments. The UKWRP is aimed at the United Kingdom water research and management community, but we envisage that the Portal (and the development pathway and technical solutions reported here) could provide a useful exemplar for similar systems in other international settings.
Genetic parameters for residual feed intake, methane emissions, and body composition in New Zealand maternal sheep
Authors: Johnson Patricia L. , Hickey Sharon , Knowler Kevin , Wing Janine , Bryson Brooke , Hall Melanie , Jonker Arjan , Janssen Peter H. , Dodds Ken G. , McEwan John C. , Rowe Suzanne J.
Published: August 2022

There is simultaneous interest in improving the feed efficiency of ruminant livestock and reducing methane (CH4) emissions. The relationship (genetic and phenotypic) between feed efficiency (characterized as residual feed intake: RFI) and greenhouse gases [methane (CH4) and carbon dioxide (CO2)] traits in New Zealand (NZ) maternal sheep has not previously been investigated, nor has their relationship with detailed estimates of body composition. To investigate these relationships in NZ maternal sheep, a feed intake facility was established at AgResearch Invermay, Mosgiel, NZ in 2015, comprising automated feeders that record individual feeding events. Individual measures of feed intake, feeding behavior (length and duration of eating events), and gas emissions (estimated using portable accumulation chambers) were generated on 986 growing maternal ewe lambs sourced from three pedigree recorded flocks registered in the Sheep Improvement Limited database (www.sil.co.nz). Additional data were generated from a subset of 591 animals for body composition (estimated using ultrasound and computed tomography scanning). The heritability estimates for RFI, CH4, and CH4/(CH4+CO2) were 0.42 ± 0.09, 0.32 ± 0.08, and 0.29 ± 0.06, respectively. The heritability estimates for the body composition traits were high for carcass lean and fat traits; for example, the heritability for visceral fat (adjusted for body weight) was 0.93 ± 0.19. The relationship between RFI and CH4 emissions was complex, and although less feed eaten will lead to a lowered absolute amount of CH4 emitted, there was a negative phenotypic and genetic correlation between RFI and CH4/(CH4+CO2) of −0.13 ± 0.03 and −0.41 ± 0.15, respectively. There were also genetic correlations, that were different from zero, between both RFI and CH4 traits with body composition including a negative correlation between the proportion of visceral fat in the body and RFI (−0.52 ± 0.16) and a positive correlation between the proportion of lean in the body and CH4 (0.54 ± 0.12). Together the results provide the first accurate estimates of the genetic correlations between RFI, CH4 emissions, and the body composition (lean and fat) in sheep. These correlations will need to be accounted for in genetic improvement programs.
Arbutin Protects Retinal Pigment Epithelium Against Oxidative Stress by Modulating SIRT1/FOXO3a/PGC-1α/β Pathway
Authors: Tang Han , Du Han , Kuang Xielan , Huang Hao , Zeng Jingshu , Long Chongde , Zhu Binbin , Fu Licheng , Wang Hua , Zhang Qingjiong , Lin Shuibin , Yan Jianhua , Shen Huangxuan
Published: August 2022

Age-related macular degeneration (AMD), which is the leading cause of blindness among the elderly in western societies, is majorly accompanied by retinal pigment epithelium (RPE) degeneration. Because of the irreversible RPE cell loss among oxidative stress, it is crucial to search for available drugs for atrophic (dry) AMD. RNA-Seq analysis revealed that genes related to aging and mitochondrial health were differentially expressed under Arbutin treatment, whereas compared to oxidative injury, our study demonstrated that Arbutin substantially abrogated oxidative stress-induced cell senescence and apoptosis linked to intracellular antioxidant enzyme system homeostasis maintenance, restored mitochondrial membrane potential (MMP), and reduced the SA-β-GAL accumulation in RPE. Furthermore, Arbutin alleviated oxidative stress-mediated cell apoptosis and senescence via activation of SIRT1, as evidenced by the increase of the downstream FoxO3a and PGC-1α/β that are related to mitochondrial biogenesis, and the suppression of NF-κB p65 inflammasome, whereas rehabilitation of oxidative stress by SIRT1 inhibitor attenuated the protective effect of Arbutin. In conclusion, we validated the results in an in vivo model constructed by NAIO3-injured mice. OCT and HE staining showed that Arbutin sustained retinal integrity in the case of oxidative damage in vivo, and the disorder of RPE cytochrome was alleviated through fundus observation. In summary, our findings identified that oxidative stress-induced mitochondrial malfunction and the subsequent senescence acceleration in RPE cells, whereas Arbutin inhibited TBHP-induced RPE degeneration via regulating the SIRT1/Foxo3a/PGC-1α/β signaling pathway. These findings suggested that Arbutin is a new agent with potential applications in the development of AMD diseases.
A homozygous variant in the GPIHBP1 gene in a child with severe hypertriglyceridemia and a systematic literature review
Authors: Sustar Ursa , Groselj Urh , Khan Sabeen Abid , Shafi Saeed , Khan Iqbal , Kovac Jernej , Bizjan Barbara Jenko , Battelino Tadej , Sadiq Fouzia
Published: August 2022

Background: Due to nonspecific symptoms, rare dyslipidaemias are frequently misdiagnosed, overlooked, and undertreated, leading to increased risk for severe cardiovascular disease, pancreatitis and/or multiple organ failures before diagnosis. Better guidelines for the recognition and early diagnosis of rare dyslipidaemias are urgently required.

Methods: Genomic DNA was isolated from blood samples of a Pakistani paediatric patient with hypertriglyceridemia, and from his parents and siblings. Next-generation sequencing (NGS) was performed, and an expanded dyslipidaemia panel was employed for genetic analysis.

Results: The NGS revealed the presence of a homozygous missense pathogenic variant c.230G>A (NM_178172.6) in exon 3 of the GPIHBP1 (glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1) gene resulting in amino acid change p.Cys77Tyr (NP_835466.2). The patient was 5.5 years old at the time of genetic diagnosis. The maximal total cholesterol and triglyceride levels were measured at the age of 10 months (850.7 mg/dl, 22.0 mmol/L and 5,137 mg/dl, 58.0 mmol/L, respectively). The patient had cholesterol deposits at the hard palate, eruptive xanthomas, lethargy, poor appetite, and mild splenomegaly. Both parents and sister were heterozygous for the familial variant in the GPIHBP1 gene. Moreover, in the systematic review, we present 62 patients with pathogenic variants in the GPIHBP1 gene and clinical findings, associated with hyperlipoproteinemia.

Conclusion: In a child with severe hypertriglyceridemia, we identified a pathogenic variant in the GPIHBP1 gene causing hyperlipoproteinemia (type 1D). In cases of severe elevations of plasma cholesterol and/or triglycerides genetic testing for rare dyslipidaemias should be performed as soon as possible for optimal therapy and patient management.
Deconvolution of B cell receptor repertoire in multiple sclerosis patients revealed a delay in tBreg maturation
Authors: Lomakin Yakov A. , Zvyagin Ivan V. , Ovchinnikova Leyla A. , Kabilov Marsel R. , Staroverov Dmitriy B. , Mikelov Artem , Tupikin Alexey E. , Zakharova Maria Y. , Bykova Nadezda A. , Mukhina Vera S. , Favorov Alexander V. , Ivanova Maria , Simaniv Taras , Rubtsov Yury P. , Chudakov Dmitriy M. , Zakharova Maria N. , Illarioshkin Sergey N. , Belogurov Alexey A. , Gabibov Alexander G.
Published: August 2022

Background

B lymphocytes play a pivotal regulatory role in the development of the immune response. It was previously shown that deficiency in B regulatory cells (Bregs) or a decrease in their anti-inflammatory activity can lead to immunological dysfunctions. However, the exact mechanisms of Bregs development and functioning are only partially resolved. For instance, only a little is known about the structure of their B cell receptor (BCR) repertoires in autoimmune disorders, including multiple sclerosis (MS), a severe neuroinflammatory disease with a yet unknown etiology. Here, we elucidate specific properties of B regulatory cells in MS.

Methods

We performed a prospective study of the transitional Breg (tBreg) subpopulations with the CD19+CD24highCD38high phenotype from MS patients and healthy donors by (i) measuring their content during two diverging courses of relapsing-remitting MS: benign multiple sclerosis (BMS) and highly active multiple sclerosis (HAMS); (ii) analyzing BCR repertoires of circulating B cells by high-throughput sequencing; and (iii) measuring the percentage of CD27+ cells in tBregs.

Results

The tBregs from HAMS patients carry the heavy chain with a lower amount of hypermutations than tBregs from healthy donors. The percentage of transitional CD24highCD38high B cells is elevated, whereas the frequency of differentiated CD27+ cells in this transitional B cell subset was decreased in the MS patients as compared with healthy donors.

Conclusions

Impaired maturation of regulatory B cells is associated with MS progression.
Extrahepatic factors in hepatic immune regulation
Authors: Zhang Shaoying , Lu Shemin , Li Zongfang
Published: August 2022

The liver is a site of complex immune activity. The hepatic immune system tolerates harmless immunogenic loads in homeostasis status, shelters liver function, while maintaining vigilance against possible infectious agents or tissue damage and providing immune surveillance at the same time. Activation of the hepatic immunity is initiated by a diverse repertoire of hepatic resident immune cells as well as non-hematopoietic cells, which can sense “danger signals” and trigger robust immune response. Factors that mediate the regulation of hepatic immunity are elicited not only in liver, but also in other organs, given the dual blood supply of the liverviaboth portal vein blood and arterial blood. Emerging evidence indicates that inter-organ crosstalk between the liver and other organs such as spleen, gut, lung, adipose tissue, and brain is involved in the pathogenesis of liver diseases. In this review, we present the features of hepatic immune regulation, with particular attention to the correlation with factors from extrahepatic organ. We describe the mechanisms by which other organs establish an immune association with the liver and then modulate the hepatic immune response. We discuss their roles and distinct mechanisms in liver homeostasis and pathological conditions from the cellular and molecular perspective, highlighting their potential for liver disease intervention. Moreover, we review the available animal models and methods for revealing the regulatory mechanisms of these extrahepatic factors. With the increasing understanding of the mechanisms by which extrahepatic factors regulate liver immunity, we believe that this will provide promising targets for liver disease therapy.
Identification of OTUD6B as a new biomarker for prognosis and immunotherapy by pan-cancer analysis
Authors: Zhao Guang , Song Dingli , Wu Jie , Yang Sanhu , Shi Sien , Cui Xiaohai , Ren Hong , Zhang Boxiang
Published: August 2022

Background

Ovarian-tumor (OTU) domain-containing protein 6B (OTUD6B), one of newly identified OTU deubiquitylating enzyme families, is proved to be associated with tumor progression. However, whether it plays a key role in pan-cancer still remains unknown.

Methods

The profiles of OTUD6B expression in multiple cancers were analyzed using The Cancer Genome Atlas (TCGA) database. Information of protein expression was performed based on the HPA, GeneCards, and String databases. K-M plotter and survival data analysis were used to analyze the prognostic value of OTUD6B expression, including overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). R package “clusterProfiler” was used for enrichment analysis of OTUD6B. Furthermore, we analyzed the correlation between the expression of OTUD6B, immune infiltration, and immune-related genes. Additionally, we preliminarily validated its tumorigenic effect in lung cancer cell lines.

Findings

OTUD6B expression was upregulated in most cancers, such as COAD, CHOL, and LUAD, and predicted poor prognosis in most cancers in TCGA. Results showed that OTUD6B expression was positively correlated with memory CD4+ T cells, Th1 CD4+ T cells, and CD8+ T cells. In terms of the immune-related genes, OTUD6B was found to be associated with most types of genes, such as immunostimulatory genes KDR, TGFBR1, and IL-10. Moreover, for most types of tumors, the immune score was found to be negatively correlated with OTUD6B expression. In addition, lung cancer cell lines with OTUD6B knockdown significantly inhibited proliferation and invasion ability of lung cancer cells.

Conclusions

The study indicated that OTUD6B is an oncogene and may serve as a new potential biomarker in various tumors. OTUD6B may play a part in TIME, which could be applied as a new target for cancer therapy.
Association of Hashimoto’s thyroiditis and anti-thyroid antibodies with oral lichen planus: A cross-sectional study
Authors: Zhang Tianyu , Hou Feifei , Liu Dan , Zhou Hangfan , Sun Yutong , Deng Xiaoting , Xu Yiming , Xiao Yanxuan , Wang Xianwen , Wu Chuanji , Meng Yang , Yuan Peiyang , Qiu Xuemei , Ye Lu , Liang Yuye , Wei Wei , Jiang Lu
Published: August 2022

Hashimoto’s thyroiditis (HT) and its autoantibodies may be associated with oral lichen planus (OLP). In this cross-sectional study, we aimed to assess the relationship among HT, auto-anti-thyroid antibodies, and OLP in a Chinese population of 247 patients with oral lichen planus. Clinical manifestations of OLP were evaluated using the Thongprasom scoring system and clinical type. The diagnosis of HT was based on thyroid function, anti-thyroid peroxidase antibody (anti-TPOAb) and anti-thyroglobulin antibody (anti-TgAb) detection, and ultrasonography. The prevalence of HT in all patients with OLP was 39.68% (98/247); the prevalence in females with OLP was 46.24% (86/186), which was higher than that in males with OLP 19.67% (12/61) (P < 0.01). The titers of the two HT autoantibodies in females with OLP were higher than those in males (P < 0.01). The clinical manifestations of OLP, regardless of being evaluated using the Thongprasom system or clinical type, were not significantly associated with HT development or TPOAb (P = 0.864) or TgAb titers (P = 0.745). In this population-based southern Chinese cohort, the prevalence of HT in patients with OLP, particularly in female patients with OLP, was significantly higher than that in the general population. Female patients had higher HT autoantibody titers than male patients. However, the clinical manifestations of OLP were not significantly correlated with either HT development or auto-anti-thyroid antibody levels. The findings could help further elucidate the factors involved in the relationship between oral lichen planus and Hashimoto’s thyroiditis.
MiR-150 in HTLV-1 infection and T-cell transformation
Authors: D’Agostino Donna M. , Raimondi Vittoria , Silic-Benussi Micol , Ciminale Vincenzo
Published: August 2022

Human T-cell leukemia virus-1 (HTLV-1) is a retrovirus that persistently infects CD4+ T-cells, and is the causative agent of adult T-cell leukemia/lymphoma (ATLL), tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) and several inflammatory diseases. T-cell transformation by HTLV-1 is driven by multiple interactions between viral regulatory proteins and host cell pathways that govern cell proliferation and survival. Studies performed over the last decade have revealed alterations in the expression of many microRNAs in HTLV-1-infected cells and ATLL cells, and have identified several microRNA targets with roles in the viral life cycle and host cell turnover. This review centers on miR-150-5p, a microRNA whose expression is temporally regulated during lymphocyte development and altered in several hematological malignancies. The levels of miR-150-5p are reduced in many HTLV-1-transformed- and ATLL-derived cell lines. Experiments in these cell lines showed that downregulation of miR-150-5p results in activation of the transcription factor STAT1, which is a direct target of the miRNA. However, data on miR-150-5p levels in freshly isolated ATLL samples are suggestive of its upregulation compared to controls. These apparently puzzling findings highlight the need for more in-depth studies of the role of miR-150-5p in HTLV-1 infection and pathogenesis based on knowledge of miR-150-5p-target mRNA interactions and mechanisms regulating its function in normal leukocytes and hematologic neoplasms.
Clinical application of the CO2 laser in Ab externo Schlemm's canal surgery
Authors: Zhang Liu , Yao Yihua , Lin Qingxia , Li Yanhong , Zhang Jianhui
Published: August 2022

Purpose

This study aimed to investigate the clinical application of laser as a knife in Ab externo Schlemm's canal (SC) surgery and compare the efficacy and safety of the CO2 laser with the conventional procedure using a surgical knife.

Methods

Patients who underwent either canaloplasty or trabeculotomy with CO2 laser system which was used to locate and ablate the outer wall of SC at the time interval between May 2020 and May 2021 were identified, their medical files were reviewed, and their results were compared with conventional surgery group who underwent canaloplasty or trabeculotomy with conventional surgical knife at the same time period. The following datas were conducted and compared: age, sex, intraocular pressure (IOP), number of drugs, best-corrected visual acuity (BCVA), mean deviation and pattern standard deviation of visual field examination, SC opening related complications.

Results

A total of 49 patients (49 eyes) were included in this study, including 23 in the Laser surgery group and 26 in the conventional surgery group. Time for SC opening was 49.33 ± 25.23 s and 116.50 ± 31.79 s for laser surgery group and conventional surgery group, respectively. This difference between the two groups was statistically significant (P < 0.01). Hemorrhage occurred in five eyes during ablation for the laser surgery group and in 24 eyes for the conventional surgery group. In addition, anterior chamber penetration occurred in two cases for the laser surgery group and in six cases for the conventional surgery group. The success rate of identifying and opening outer wall of SC was 91.30% (21 eyes) for the laser surgery group and 76.92% (20 eyes) for the conventional surgery group. The difference between preoperative and postoperative intraocular pressure for each group was statistically significant (P < 0.01), and there were no statistically significant differences across the two groups in terms of postoperative IOP (P = 0.238) and BCVA (P = 0.389).

Conclusion

Compared with the conventional procedure using a surgical knife, CO2 laser-assisted ablation of the outer wall of SC was less time-consuming and less technically challenging. CO2 laser-assisted ablation also resulted in fewer complications. Furthermore, it had a shorter learning curve and a higher success rate of identifying and opening SC.
Emerging microfluidic technologies for microbiome research
Authors: Yu Yue , Wen Hui , Li Sihong , Cao Haojie , Li Xuefei , Ma Zhixin , She Xiaoyi , Zhou Lei , Huang Shuqiang
Published: August 2022

The importance of the microbiome is increasingly prominent. For example, the human microbiome has been proven to be strongly associated with health conditions, while the environmental microbiome is recognized to have a profound influence on agriculture and even the global climate. Furthermore, the microbiome can serve as a fascinating reservoir of genes that encode tremendously valuable compounds for industrial and medical applications. In the past decades, various technologies have been developed to better understand and exploit the microbiome. In particular, microfluidics has demonstrated its strength and prominence in the microbiome research. By taking advantage of microfluidic technologies, inherited shortcomings of traditional methods such as low throughput, labor-consuming, and high-cost are being compensated or bypassed. In this review, we will summarize a broad spectrum of microfluidic technologies that have addressed various needs in the field of microbiome research, as well as the achievements that were enabled by the microfluidics (or technological advances). Finally, how microfluidics overcomes the limitations of conventional methods by technology integration will also be discussed.
Whole-genome sequence of a high-temperature edible mushroom Pleurotus giganteus (zhudugu)
Authors: Yu Hailong , Zhang Meiyan , Sun Yating , Li Qiaozhen , Liu Jianyu , Song Chunyan , Shang Xiaodong , Tan Qi , Zhang Lujun , Yu Hao
Published: August 2022

Most of the sequenced wood-rotting edible mushroom produce fruiting body at relatively low temperatures. Little information has been known about the high-temperature wood-rotting mushroom. Here, we performed de novo sequencing and assembly of the genome of a high-temperature edible mushroom Pleurotus giganteus from a monokaryotic strain zhudugu2 using the Illumina and Pac-Bio CLR sequencing technologies. P. giganteus, also known as Zhudugu in China, is a well-known culinary edible mushroom that has been widely distributed and cultivated in China, Southeast Asia, and South Asia. The genome consists of 40.00 Mb in 27 contigs with a contig N50 of 4.384 Mb. Phylogenetic analysis reveals that P. giganteus and other strains in Pleurotus clustered in one clade. Phylogenetic analysis and average nucleotide identity analysis indicated that the P. giganteus genome showed a closer relationship with other Pleurotus species. Chromosome collinearity analysis revealed a high level of collinearity between P. ostreatus and P. giganteus. There are 12,628 protein-coding genes annotated in this monoploid genome. A total of 481 enzymes accounting for 514 carbohydrate-active enzymes (CAZymes) terms were identified in the P. giganteus genome, including 15 laccases and 10 class II peroxidases predicted in the genome, which revealed the robustness of lignocellulose degradation capacity of P. giganteus. The mating-A type locus of P. giganteus consisted of a pair of homeodomain mating-type genes HD1 and HD2. The mating-B type locus of P. giganteus consisted of at least four pheromone receptor genes and three pheromone genes. The genome is not only beneficial for the genome-assisted breeding of this mushroom but also helps us to understand the high-temperature tolerance of the edible mushroom.
A putative siderophore receptor of Gallibacterium anatis 12656-12 under Fur control also binds hemoglobin
Authors: Chantes-Guerra Alberto , Maldonado-Puga Samantha , Rojas-Ruiz Norma , Rea-Hernandez Ismael , Montes-Garcia Fernando J. , Trujillo-Ruiz Hector , Yañez-Aguilar Ivan E. , Vazquez-Cruz Candelario , Sanchez-Alonso Patricia , Negrete-Abascal Erasmo
Published: August 2022

Pasteurellaceae family members obtain iron directly from host proteins or through siderophore-dependent mechanisms. Although Gallibacterum anatis expresses different virulence factors, its response to growth under iron restriction is unknown. G. anatis cultured in the presence of 2,2′-dipyridyl, up-expressed an approximately 65 kDa protein and repressed the expression of a 70 kDa protein. MALDI-TOF analysis of those proteins indicated homology with CirA (65 kDa), a protein involved in iron-siderophore acquisition in Mannheimia succinoproducens and a TonB-dependent receptor (70 kDa protein), a protein that binds chicken hemoglobin; however, G. anatis siderophore production was not detected by chromo azurol S (CAS)-BHI agar determination. This putative G. anatis siderophore receptor is under Fur control, but not the hemoglobin binding protein, as observed in G. anatis 12656-12 fur mutant (Ω fur 126.13) grown in the presence or not of 2,2′-dipyridyl. The addition of FeCl3 to the culture medium diminished the growth and biofilm production in approximately 30% and 35%, respectively, in the wild-type strain, but the growth of Ω fur 126.13 strain was not affected and biofilm production increased in 35%. G. anatis Ω fur 126.13 presented lower virulence when it was inoculated to 35-day-old chickens in comparison to the wild-type strain. The induction of more than one iron uptake mechanism could benefit pathogenic microorganisms such as Gallibacterium.
Characterization of toxin-antitoxin systems from public sequencing data: A case study in Pseudomonas aeruginosa
Authors: Dai Zehan , Wu Tianzhi , Xu Shuangbin , Zhou Lang , Tang Wenli , Hu Erqian , Zhan Li , Chen Meijun , Yu Guangchuang
Published: August 2022

The toxin-antitoxin (TA) system is a widely distributed group of genetic modules that play important roles in the life of prokaryotes, with mobile genetic elements (MGEs) contributing to the dissemination of antibiotic resistance gene (ARG). The diversity and richness of TA systems in Pseudomonas aeruginosa, as one of the bacterial species with ARGs, have not yet been completely demonstrated. In this study, we explored the TA systems from the public genomic sequencing data and genome sequences. A small scale of genomic sequencing data in 281 isolates was selected from the NCBI SRA database, reassembling the genomes of these isolates led to the findings of abundant TA homologs. Furthermore, remapping these identified TA modules on 5,437 genome/draft genomes uncovers a great diversity of TA modules in P. aeruginosa. Moreover, manual inspection revealed several TA systems that were not yet reported in P. aeruginosa including the hok-sok, cptA-cptB, cbeA-cbtA, tomB-hha, and ryeA-sdsR. Additional annotation revealed that a large number of MGEs were closely distributed with TA. Also, 16% of ARGs are located relatively close to TA. Our work confirmed a wealth of TA genes in the unexplored P. aeruginosa pan-genomes, expanded the knowledge on P. aeruginosa, and provided methodological tips on large-scale data mining for future studies. The co-occurrence of MGE, ARG, and TA may indicate a potential interaction in their dissemination.
P25 and P37 proteins encoded by firespike leafroll-associated virus are viral suppressors of RNA silencing
Authors: Wang Yaqin , Liu Hui , Wang Zhanqi , Guo Yushuang , Hu Tao , Zhou Xueping
Published: August 2022

Firespike leafroll-associated virus (FLRaV) is a major pathogen associated with firespike (Odontonema tubaeforme) leafroll disease. Phylogenetic analysis showed that FLRaV possesses typical traits of subgroup II members of ampeloviruses, but encodes two additional proteins, P25 and P37. Here, we determined the microfilament localization of P25 protein. Posttranscriptional gene silencing (PTGS) assay showed that both FLRaV P25 and P37 were able to suppress the local and systemic PTGS and FLRaV P25 was capable of suppressing the green fluorescent protein (GFP) gene silencing triggered by both sense RNA-induced PTGS (S-PTGS) and inverted repeat RNA-induced PTGS (IR-PTGS). In contrast, FLRaV P37 was only able to inhibit the GFP silencing triggered by the S-PTGS but not the IR-PTGS. In the transcriptional gene silencing (TGS) assay, only FLRaV P25 was found to be able to reverse established TGS-mediated silencing of GFP in 16-TGS plants. We also found that FLRaV P25 could aggravate the disease symptom and viral titer of potato virus X in N. benthamiana. These results suggest that FLRaV P25 and P37 may have crucial roles in overcoming host RNA silencing, which provides key insights into our understanding of the molecular mechanisms underlying FLRaV infection.
Obligately aerobic human gut microbe expresses an oxygen resistant tungsten-containing oxidoreductase for detoxifying gut aldehydes
Authors: Thorgersen Michael P. , Schut Gerrit J. , Poole Farris L. , Haja Dominik K. , Putumbaka Saisuki , Mycroft Harriet I. , de Vries Willem J. , Adams Michael W. W.
Published: August 2022

Brevibacillus massiliensis strain phR is an obligately aerobic microbe that was isolated from human feces. Here, we show that it readily takes up tungsten (W), a metal previously associated only with anaerobes. The W is incorporated into an oxidoreductase enzyme (BmWOR) that was purified from native biomass. BmWOR consists of a single 65 kDa subunit and contains a single W-pyranopterin cofactor and a single [4Fe-4S] cluster. It exhibited high aldehyde-oxidizing activity with very high affinities (apparent Km < 6 μM) for aldehydes common in the human gut and in cooked foods, including furfural, propionaldehyde, benzaldehyde and tolualdehyde, suggesting that BmWOR plays a key role in their detoxification. B. massiliensis converted added furfural to furoic acid when grown in the presence of W, but not in the presence of the analogous element molybdenum. B. massiliensis ferredoxin (BmFd) served as the electron acceptor (apparent Km < 5 μM) for BmWOR suggesting it is the physiological electron carrier. Genome analysis revealed a Fd-dependent rather than NADH-dependent Complex I, suggesting that WOR not only serves a detoxification role but its aldehyde substrates could also serve as a source of energy. BmWOR is the first tungstoenzyme and the first member of the WOR family to be obtained from a strictly aerobic microorganism. Remarkably, BmWOR oxidized furfural in the presence of air (21% O2, v/v) but only if BmFd was also present. BmWOR is the first characterized member of the Clade 83 WORs, which are predominantly found in extremely halophilic and aerobic archaea (Clade 83A), with many isolated from food sources, while the remaining bacterial members (Clade 83B) include both aerobes and anaerobes. The potential advantages for microbes found in foods and involved in human gut health that harbor O2-resistant WORs, including in Bacillus and Brevibacillus based-probiotics, are discussed.
Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects
Authors: Wang Ruihan , Gao Hui , Xie Hongsheng , Jia Zhiyun , Chen Qin
Published: August 2022

Familial frontotemporal lobar degeneration (FTLD) is a pathologically heterogeneous group of neurodegenerative diseases with diverse genotypes and clinical phenotypes. Three major mutations were reported in patients with familial FTLD, namely, progranulin (GRN), microtubule-associated protein tau (MAPT), and the chromosome 9 open reading frame 72 (C9orf72) repeat expansion, which could cause neurodegenerative pathological changes years before symptom onset. Noninvasive quantitative molecular imaging with PET or single-photon emission CT (SPECT) allows for selective visualization of the molecular targets in vivo to investigate brain metabolism, perfusion, neuroinflammation, and pathophysiological changes. There was increasing evidence that several molecular imaging biomarkers tend to serve as biomarkers to reveal the early brain abnormalities in familial FTLD. Tau-PET with 18F-flortaucipir and 11C-PBB3 demonstrated the elevated tau position in patients with FTLD and also showed the ability to differentiate patterns among the different subtypes of the mutations in familial FTLD. Furthermore, dopamine transporter imaging with the 11C-DOPA and 11C-CFT in PET and the 123I-FP-CIT in SPECT revealed the loss of dopaminergic neurons in the asymptomatic and symptomatic patients of familial FTLD. In addition, PET imaging with the 11C-MP4A has demonstrated reduced acetylcholinesterase (AChE) activity in patients with FTLD, while PET with the 11C-DAA1106 and 11C-PK11195 revealed an increased level of microglial activation associated with neuroinflammation even before the onset of symptoms in familial FTLD. 18F-fluorodeoxyglucose (FDG)-PET indicated hypometabolism in FTLD with different mutations preceded the atrophy on MRI. Identifying molecular imaging biomarkers for familial FTLD is important for the in-vivo assessment of underlying pathophysiological changes with disease progression and future disease-modifying therapy. We review the recent progress of molecular imaging in familial FTLD with focused on the possible implication of these techniques and their prospects in specific mutation types.
Infra-low frequency neurofeedback in application to Tourette syndrome and other tic disorders: A clinical case series
Authors: Solberg Bodil , Solberg Erlend
Published: August 2022

We describe our clinical experience in treating patients with Tourette syndrome and other tic disorders using infra-low frequency neurofeedback (ILF NF), often in conjunction with cognitive behavior therapy. Following a narrative description of our approach, we present outcome data for 100 successive cases. Many of the children and adolescents that we have treated since 2005 did not derive sufficient benefit from standard treatment for Tourette syndrome and other tic disorders. In our clinical experience, based on extensive before- and after- testing and symptom tracking, this patient group derived significant additive benefit from complementary neurofeedback treatment. The majority of trainees attained a higher level of functioning and were able to live up to their potential in a way they were not able to prior to neurofeedback treatment.
Heterotypic neutrophil-in-tumor structure: A novel pathological feature first discovered in the tissues of OPSCC
Authors: Fan Jie , Li Peng , Fang Qigen , Yang Yang , Zhang He , Du Wei , Liu Shanting , Luo Ruihua
Published: August 2022

Objective

To reveal a novel pathological feature: heterotypic neutrophil-in-tumor structure (hNiT) first discovered in patients with oropharyngeal squamous cell carcinoma (OPSCC), to analyze the prognostic role of hNiT in OPSCC patients and to explore the role of p16 in the formation of hNiT structures.

Methods

Clinically, 197 patients were enrolled. Clinicopathological information was extracted and analyzed. All pathologic sections made from primary tumors were re-evaluated by immunohistochemistry and immunostaining. In vitro, we cocultured OPSCC cell line SCC-15 with neutrophils to form hNiT structures, which were then subject to fluorescence staining. By RNAi and overexpression techniques, we investigated the role of CDKN2A in the formation of hNiTs. We validated the two techniques by qPCR and Western Blot.

Results

The hNiT as a novel pathological feature was first discovered in the tissues of OPSCC. The FNiT was significantly associated with tumor stage, disease stage, p16 and tumor grade. A total of 119 patients died of the disease, and the 5-year disease-specific survival (DSS) rate was 36%. The median survival time was 52.6 months. In patients with an FNiT<0.5%, the 5-year DSS rate was 40%; in patients with an FNiT>=0.5%, the 5-year DSS was 28%, and the difference was significant (p=0.001). Cox model analysis showed that FNiT along with disease stage, p16 and tumor grade was an independent prognostic factor for DSS. Immunostaining results of p16 expression showed hNiT formation was negatively correlated to p16 in OPSCC as well as in the hNiT formation assays in vitro indicated by fluorescent staining. Function assays of CDKN2A implied that reduce CDKN2A promoted the formation of hNiT while elevated CDKN2A impeded the hNiT formation.

Conclusion

The hNiT as a novel pathological feature is associated with the adverse prognosis of OPSCC patients with p16 inhibiting the formation of hNiT structures.
Whole transcriptome sequencing reveals a TCF4-ZNF384 fusion in acute lymphoblastic leukemia
Authors: Wu Zhengyu , Zhang Fang , Liu Chengzhu , Shen Shuhong , Chu Jinhua , Yang Linhai , Xie Zhiwei , Liu Yu , Liu Kangkang , Wang Ningling
Published: August 2022

Previous studies have shown that, the clinical features and prognosis of ZNF384-rearranged pediatric acute lymphoblastic leukemia (ALL) depend on its translocation partners. We report two cases of TCF4-ZNF384 fusion, one 6-year-old girl and one 10-year-old boy, both diagnosed by whole-transcriptome sequencing, and TCF4 is the newest fusion partner of ZNF384. As illustrated in this first report of TCF4-ZNF384 fusion in ALL patients, the identification of patients with ZNF384 rearrangement in ALL patients is critical to elucidate outcomes associated with a specific rearrangement and to develop appropriate treatment strategies. In addition, the development of other methods to detect ZNF384 specific translocation partners and leukemia specific targeting agents is of great significance to further improve the prognosis of ALL with ZNF384-rearrangement.
Adjuvant chemotherapy can benefit the survival of stage I lung adenocarcinoma patients with tumour spread through air spaces after resection: Propensity-score matched analysis
Authors: Xie Shaonan , Liu Qingyi , Han Yaqing , Wang Shize , Deng Huiyan , Liu Guangjie
Published: August 2022

Background

It is still unclear whether stage I lung adenocarcinoma patients with tumour spread through air spaces (STAS) can benefit from postoperative adjuvant chemotherapy (ACT) after lobectomy. This study investigated the effect of ACT on the postoperative survival of patients with stage I (STAS+) lung adenocarcinoma.

Methods

We retrospectively analysed the clinical data of stage I (STAS+) invasive lung adenocarcinoma patients who underwent lobectomy in the Department of Thoracic Surgery of our hospital from January 1, 2013 to January 1, 2016. Propensity score matching (PSM) was performed to group patients to investigate whether ACT could lead to better prognosis of patients.

Results

A total of 593 patients with stage I (STAS+) lung adenocarcinoma were enrolled. The study after PSM included 406 patients. Kaplan–Meier survival analysis showed the experimental group had a better 3-year recurrence-free survival (RFS) rate (p = 0.037) and the 5-year RFS rate (p = 0.022) than the control group. It also had higher 5-year overall survival (p = 0.017). The multivariate analysis by Cox proportional hazard regression model showed that stage I STAS+ lung adenocarcinoma patients with lymphatic vessel invasion (HR: 1.711, 95% CI: 1.052-2.784; p = 0.045), vascular invasion (HR: 5.014, 95% CI: 3.154-7.969; p < 0.001), and visceral pleural invasion (HR: 2.086, 95% CI: 1.162-3.743; p = 0.014), and without ACT (HR: 1.675, 95% CI: 1.043-2.689; p = 0.033) had a significant survival disadvantage.

Conclusion

ACT can boost the postoperative survival of patients with stage I (STAS+) lung adenocarcinoma.
Effectiveness of PARP inhibition in enhancing the radiosensitivity of 3D spheroids of head and neck squamous cell carcinoma
Authors: Zhou Chumin , Fabbrizi Maria Rita , Hughes Jonathan R. , Grundy Gabrielle J. , Parsons Jason L.
Published: August 2022

A critical risk factor for head and neck squamous cell carcinoma (HNSCC), particularly of the oropharynx, and the response to radiotherapy is human papillomavirus (HPV) type-16/18 infection. Specifically, HPV-positive HNSCC display increased radiosensitivity and improved outcomes, which has been linked with defective signalling and repair of DNA double-strand breaks (DSBs). This differential response to radiotherapy has been recapitulated in vitro using cell lines, although studies utilising appropriate 3D models that are more reflective of the original tumour are scarce. Furthermore, strategies to enhance the sensitivity of relatively radioresistant HPV-negative HNSCC to radiotherapy are still required. We have analysed the comparative response of in vitro 3D spheroid models of oropharyngeal squamous cell carcinoma to x-ray (photon) irradiation and provide further evidence that HPV-positive cells, in this case now grown as spheroids, show greater inherent radiosensitivity compared to HPV-negative spheroids due to defective DSB repair. We subsequently analysed these and an expanded number of spheroid models, with a particular focus on relatively radioresistant HPV-negative HNSCC, for impact of poly(ADP-ribose) polymerase (PARP) inhibitors (olaparib and talazoparib) in significantly inhibiting spheroid growth in response to photons but also proton beam therapy. We demonstrate that in general, PARP inhibition can further radiosensitise particularly HPV-negative HNSCC spheroids to photons and protons leading to significant growth suppression. The degree of enhanced radiosensitivity was observed to be dependent on the model and on the tumour site (oropharynx, larynx, salivary gland, or hypopharynx) from which the cells were derived. We also provide evidence suggesting that PARP inhibitor effectiveness relates to homologous recombination repair proficiency. Interestingly though, we observed significantly enhanced effectiveness of talazoparib versus olaparib specifically in response to proton irradiation. Nevertheless, our data generally support that PARP inhibition in combination with radiotherapy (photons and protons) should be considered further as an effective treatment for HNSCC, particularly for relatively radioresistant HPV-negative tumours.