bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of Immune Checkpoint Receptors in Placentae With Infectious and Non-Infectious Chronic Villitis
Authors: Shahi Maryam , Mamber Czeresnia Ricardo , Cheek E. Heidi , Quinton Reade A. , Chakraborty Rana , Enninga Elizabeth Ann L.
Published: July 2021

Pregnancy is an immunological paradox whereby maternal immunity accepts a genetically unique fetus (or fetuses), while maintaining protective innate and adaptive responses to infectious pathogens. This close contact between the genetically diverse mother and fetus requires numerous mechanisms of immune tolerance initiated by trophoblast cell signals. However, in a placental condition known as villitis of unknown etiology (VUE), there appears to be a breakdown in this tolerance allowing maternal cytotoxic T-cells to traffic into the placenta to destroy fetal villi. VUE is associated with several gestational complications and an increased risk of recurrence in a subsequent pregnancy, making it a significant obstetrical diagnosis. The cause of VUE remains unclear, but dysfunctional signaling through immune checkpoint pathways, which have a critical role in blunting immune responses, may play an important role. Therefore, using placental tissue from normal pregnancy (n=8), VUE (n=8) and cytomegalovirus (CMV) infected placentae (n=4), we aimed to identify differences in programmed cell death 1 (PD-1), programmed death ligand-1 (PD-L1), LAG3 and CTLA4 expression between these etiologies by immunohistochemistry (IHC). Results demonstrated significantly lower expression of PD-L1 on trophoblast cells from VUE placentae compared to control and CMV infection. Additionally, we observed significantly higher counts of PD-1+ (>100 cells/image) and LAG3+ (0-120 cells/image) cells infiltrating into the villi during VUE compared to infection and control. Minimal CTLA4 staining was observed in all placentae, with only a few Hofbauer cells staining positive. Together, this suggests that a loss of tolerance through immune checkpoint signaling may be an important mechanism leading to the activation and trafficking of maternal cells into fetal villi during VUE. Further mechanistic studies are warranted to understand possible allograft rejection more clearly and in developing effective strategies to prevent this condition from occurringin utero.
Immune Equilibrium Depends on the Interaction Between Recognition and Presentation Landscapes
Authors: Shevyrev Daniil , Tereshchenko Valeriy , Kozlov Vladimir
Published: July 2021

In this review, we described the structure and organization of antigen-recognizing repertoires of B and T cells from the standpoint of modern immunology. We summarized the latest advances in bioinformatics analysis of sequencing data from T and B cell repertoires and also presented contemporary ideas about the mechanisms of clonal diversity formation at different stages of organism development. At the same time, we focused on the importance of the allelic variants of the HLA genes and spectra of presented antigens for the formation of T-cell receptors (TCR) landscapes. The main idea of this review is that immune equilibrium and proper functioning of immunity are highly dependent on the interaction between the recognition and the presentation landscapes of antigens. Certain changes in these landscapes can occur during life, which can affect the protective function of adaptive immunity. We described some mechanisms associated with these changes, for example, the conversion of effector cells into regulatory cells and vice versa due to the trans-differentiation or bystander effect, changes in the clonal organization of the general TCR repertoire due to homeostatic proliferation or aging, and the background for the altered presentation of some antigens due to SNP mutations of MHC, or the alteration of the presenting antigens due to post-translational modifications. The authors suggest that such alterations can lead to an increase in the risk of the development of oncological and autoimmune diseases and influence the sensitivity of the organism to different infectious agents.
Pathogenetic Interplay Between IL-6 and Tryptophan Metabolism in an Experimental Model of Obesity
Authors: Mondanelli Giada , Albini Elisa , Orecchini Elena , Pallotta Maria Teresa , Belladonna Maria Laura , Ricci Giovanni , Grohmann Ursula , Orabona Ciriana
Published: July 2021

Obesity is a metabolic disease characterized by a state of chronic, low-grade inflammation and dominated by pro-inflammatory cytokines such as IL-6. Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that catalyzes the first step in the kynurenine pathway by transforming l-tryptophan (Trp) into l-kynurenine (Kyn), a metabolite endowed with anti-inflammatory and immunoregulatory effects. In dendritic cells, IL-6 induces IDO1 proteasomal degradation and shuts down IDO1-mediated immunosuppressive effects. In tumor cells, IL-6 upregulates IDO1 expression and favors tumor immune escape mechanisms. To investigate the role of IDO1 and its possible relationship with IL-6 in obesity, we induced the disease by feeding mice with a high fat diet (HFD). Mice on a standard diet were used as control. Experimental obesity was associated with high IDO1 expression and Kyn levels in the stromal vascular fraction of visceral white adipose tissue (SVF WAT). IDO1-deficient mice on HFD gained less weight and were less insulin resistant as compared to wild type counterparts. Administration of tocilizumab (TCZ), an IL-6 receptor (IL-6R) antagonist, to mice on HFD significantly reduced weight gain, controlled adipose tissue hypertrophy, increased insulin sensitivity, and induced a better glucose tolerance. TCZ also induced a dramatic inhibition of IDO1 expression and Kyn production in the SVF WAT. Thus our data indicated that the IL-6/IDO1 axis may play a pathogenetic role in a chronic, low-grade inflammation condition, and, perhaps most importantly, IL-6R blockade may be considered a valid option for obesity treatment.
Coexpression of Three Odorant-Binding Protein Genes in the Foreleg Gustatory Sensilla of Swallowtail Butterfly Visualized by Multicolor FISH Analysis
Authors: Ugajin Atsushi , Ozaki Katsuhisa
Published: July 2021

Lepidopteran insects are mostly monophagous or oligophagous. Female butterflies distinguish their host plants by detecting a combination of specific phytochemicals through the gustatory sensilla densely distributed on their foreleg tarsi, thereby ensuring oviposition on appropriate host plants. In this study, to gain insight into the molecular mechanism underlying host plant recognition by the gustatory sensilla, using Asian swallowtail, Papilio xuthus, we focused on a family of small soluble ligand-binding molecules, odorant-binding proteins (OBPs), and found that three OBP genes showed enriched expression in the foreleg tarsus. Multicolor fluorescence in situ hybridization analyses demonstrated the coexpression of these three OBP genes at the bases of the foreleg gustatory sensilla. Further analyses on other appendages revealed that PxutOBP3 was exclusively expressed in the tissues which could have direct contact with the leaf surface, suggesting that this OBP gene specifically plays an important role in phytochemicals perception.
Effects of Dietary Protein and Lipid Levels on Growth, Body Composition, Blood Biochemistry, Antioxidant Capacity and Ammonia Excretion of European Grayling (Thymallus thymallus)
Authors: Rahimnejad Samad , Dabrowski Konrad , Izquierdo Marisol , Malinovskyi Oleksandr , Kolářová Jitka , Policar Tomas
Published: July 2021

This study evaluated growth, body composition, antioxidant capacity, innate immunity and ammonia excretion of European grayling (Thymallus thymallus) fed diets containing different protein and lipid contents. Six diets were produced to contain 30, 40, or 50% protein and 10 or 20% lipid. Juvenile fish averaging 25.2 ± 0.28 g were stocked into eighteen 450-L circular tanks in a recirculating aquaculture system (RAS) and fed the test diets to satiation twice daily for 12 weeks. Fish weight gain (WG) was enhanced (P < 0.05) as dietary protein increased from 30% (229% WG) to 40% (262% WG) and plateaued thereafter. Enhancing protein and lipid content of diet led to reduced feed intake. Also, feed efficiency was improved by increasing dietary protein (by 40.8%) and lipid (by 16.5%) levels. An interaction of protein and lipid was found on whole-body lipid, and muscle lipid content increased as dietary lipid level increased. Muscle arachidonic acid (ARA), eicosapentaenoic acid (EPA, 20:5n-3) and total n-6 long-chain polyunsaturated fatty acids (LC-PUFA) contents enhanced by increasing dietary protein level. Moreover, increasing fat content of diet led to enhanced muscle linoleic acid, linolenic acid, total monounsaturated fatty acids (MUFA), total n-6, ratio of docosahexaenoic acid (DHA, 22:6n-3) to EPA and n-6/n-3. However, EPA, DHA, total n-6 LC-PUFA, total n-3, total n-3 LC-PUFA, and EPA/ARA ratio decreased at higher dietary lipid level. Serum triglyceride (TG) level and lactate dehydrogenase (LDH) activity decreased as dietary protein level increased. Increasing fat content of diet led to enhanced serum TG, cholesterol and glucose concentrations and reduced alanine aminotransferase, aspartate amino transferase and LDH activities. Serum malondialdehyde concentration was enhanced by increasing both dietary protein and lipid. Furthermore, serum myeloperoxidase activity was enhanced at higher dietary lipid level. Water ammonium nitrogen (NH4+-N) concentration was measured after 5 and 24 h of last feeding, and the results indicated the reduction of ammonia excretion as dietary lipid content increased. These findings suggest that 40% dietary protein can support optimal growth of juvenile European grayling reared in RAS and increasing lipid content from 10 to 20% can improve feed utilization and reduce ammonia excretion to the rearing water.
Length-Based Assessment of Fish Stocks in a Data-Poor, Jointly Exploited (China and Vietnam) Fishing Ground, Northern South China Sea
Authors: Zhang Kui , Li Jiajun , Hou Gang , Huang Zirong , Shi Dengfu , Chen Zuozhi , Qiu Yongsong
Published: July 2021

The Beibu Gulf is one of the most important fishing grounds in the South China Sea (SCS), and the fisheries resources in this area are exploited by both China and Vietnam. In recent decades, some indications of overfishing have appeared, including declining catch rates, frequently changing catch composition, and shrinking body sizes in main commercial fish species. Due to limited data availability, only a small subset of exploited fish stocks in this area has been assessed. Here, we applied two length-based methods, electronic length frequency analysis (ELEFAN) and length-based Bayesian biomass estimation (LBB), to stock assessment of nine exploited fish species in the Beibu Gulf. There were total 53, 652 length records of 30 target stocks used in this study during the survey period from 1960 to 2015. The results showed that the two length-based methods presented different ability in estimating exploitation rate (E), and the estimatedEranged from 0.34 to 0.87 using ELEFAN method while ranged from 0.26 to 0.86 using LBB method. The prior information from ELEFAN method was effective for LBB method, as there were significant differences in 66.7% of the 30 target stocks in estimatedLinf, and 93.3% in estimatedB/BMSY, using LBB method with and without prior information. The estimatedLc/Lc_optandB/BMSYof LBB method suggest a pressing situation for the fisheries in the Beibu Gulf, as 86.7% of the 30 target stocks had been suffering from growth overfishing (Lc/Lc_opt< 1), and 83.3% had been overexploited or fully exploited (B/BMSY≤ 1.2). In addition, we suggest using both ELEFAN and LBB methods to fit length-frequency data of data-poor fish stocks because they are complementary in estimating management reference points. We also emphasize collaboration mechanism should be established by China and Vietnam for the sustainability and recovery of fishery resources in the Beibu Gulf.
An Approach of the Maximum Curvature Measurement of Dynamic Umbilicals Using OFDR Technology in Fatigue Tests
Authors: Yin Yuanchao , Yu Peng , Jia Ziguang , Wu Shanghua , Lu Qingzhen , Yan Jun , Yue Qianjin
Published: July 2021

Prototype fatigue tests simulate in-place working conditions of dynamic umbilicals that are usually conducted to verify fatigue life. The fatigue failure hot spot locates on the top segment of the umbilical. The umbilical reaches a maximum curvature at the hot spot. The hot spot position of the umbilical is always inside or near the bend stiffener. The radial gap between the umbilical and the bend stiffener is very small, making it difficult to put traditional sensors in the gap. In this work, a prototype umbilical tension-bending test is conducted, and the optic frequency domain reflectometer (OFDR) technology is utilized to measure the distributed strain of the umbilical inside the bend stiffener. The curvature of the umbilical is obtained to locate the fatigue hot spot in order to verify the feasibility of this approach. The test results show that the umbilical curvature can be measured well with the use of OFDR technology. The influence of tension and swing angle on the position of the maximum curvature is studied. The method proposed in this article provides a valuable approach for curvature monitoring in the application of dynamic umbilical fatigue tests.
A Complete Two-Dimensional Avalanche Photodiode Based on MoTe2−WS2−MoTe2 Heterojunctions With Ultralow Dark Current
Authors: Ouyang Tenghui , Wang Ximiao , Liu Shaojing , Chen Huanjun , Deng Shaozhi
Published: July 2021

Two-dimensional (2D)-material-based photodetectors have recently received great attention due to their potentials in developing ultrathin and highly compact devices. Avalanche photodiodes (APDs) are widely used in a variety of fields such as optical communications and bioimaging due to their fast responses and high sensitivities. However, conventional APDs based on bulk materials are limited by their relatively high dark current. One solution to tackle this issue is by employing nanomaterials and nanostructures as the active layers for APDs. In this study, we proposed and fabricated an atomically-thick APD based on heterojunctions formed by 2D transition metal dichalcogenides (TMDs). A typical device structure was formed by stacking a semiconducting monolayer WS2 onto two metallic few-layer MoTe2 flakes. Due to the Schottky barrier formed between the TMD layers and their atomic thicknesses, the dark current of the APD is greatly reduced down to 93 pA. In addition, the APD can operate through a broad spectral range from visible to near-infrared region, with a responsivity of 6.02 A/W, an external quantum eﬃciency of 1,406%, and an avalanche gain of 587. We believe that the 2D APD demonstrated here provides a feasible approach for developing all-2D optoelectronic devices with simultaneous high-sensitivity and low noise.
Whole-Genome Sequencing Reveals Exonic Variation of ASIC5 Gene Results in Recurrent Pregnancy Loss
Authors: Al Qahtani Nourah H. , AbdulAzeez Sayed , Almandil Noor B. , Fahad Alhur Norah , Alsuwat Hind Saleh , Al Taifi Hatoon Ahmed , Al-Ghamdi Ahlam A. , Rabindran Jermy B. , Abouelhoda Mohamed , Subhani Shazia , Al Asoom Lubna , Borgio J. Francis
Published: July 2021

Family trio next-generation sequencing-based variant analysis was done to identify the genomic reason on unexplained recurrent pregnancy loss (RPL). A family (dead fetus and parents) from Saudi Arabia with an earlier history of three unexplained RPLs at the ninth week of pregnancy was included in the study. Whole-genome sequencing (WGS) of a dead fetus and the parents was done to identify the pathogenic variation and confirmed through Sanger sequencing. WGS of dead fetus identifies a novel homozygous exonic variation (NM_017419.3:c.680G>T) in ASIC5 (acid-sensing ion channel subunit family member 5) gene; the parents are heterozygous. Newly designed ARMS PCR followed by direct sequencing confirms the presence of heterozygous in one subject and absence of homozygous novel mutation among randomly selected healthy Saudis. The second family with heterozygous was confirmed with three unexplained RPLs. Pathogenicity analysis of R227I amino acid substitution in ASIC5 protein through molecular docking and interaction analysis revealed that the mutations are highly pathogenic, decrease the stability of the protein, and prevent binding of amiloride, which is an activator to open the acid-sensing ion channel of ASIC5. The identified rare and novel autosomal recessive mutation, c.680G>T:p.R227I (ASIC5Saudi), in two families confirm the ASIC5 gene association with RPL and can be fatal to the fetus.
Therapeutic Hypothermia Reduces Peritoneal Dialysis Induced Myocardial Blood Flow Heterogeneity and Arrhythmia
Authors: Kharche Sanjay R. , Lemoine Sandrine , Tamasi Tanya , Hur Lisa , So Aaron , McIntyre Christopher W.
Published: July 2021

Background: Moderate therapeutic hypothermia (TH) is a well-recognized cardio-protective strategy. The instillation of fluid into the peritoneum provides an opportunity to deliver moderate hypothermia as primary prevention against cardiovascular events. We aimed to to investigate both cardiac perfusion consequences (overall blood flow and detailed assessment of perfusion heterogeneity) and subsequently simulate the associated arrhythmic risk for patients undergoing peritoneal dialysis (PD) induced TH.

Methods: Patients underwent high resolution myocardial perfusion scanning using high resolution 256 slice CT scanning, at rest and with adenosine stress. The first visit using the patient's usual PD regimen, on the second visit the same regime was utilized but with cooled peritoneal dialysate at 32°C. Myocardial blood flow (MBF) was quantified from generated perfusion maps, reconstructed in 3D. MBF heterogeneity was assessed by fractal dimension (FD) measurement on the 3D left ventricular reconstruction. Arrhythmogenicity was quantified from a sophisticated computational simulation using a multi-scale human 3D ventricle wedge electrophysiological computational model.

Results: We studied 7 PD patients, mean age of 60 ± 7 and mean vintage dialysis of 23.6 ± 17.6 months. There were no significant different in overall segmental MBF between normothermic condition (NT) and TH. MBF heterogeneity was significantly decreased (−14%, p = 0.03) at rest and after stress (−14%, p = 0.03) when cooling was applied. Computational simulation showed that TH allowed a normalization of action potential, QT duration and T wave.

Conclusion: TH-PD results in moderate hypothermia leading to a reduction in perfusion heterogeneity and simulated risk of non-terminating malignant ventricular arrhythmias.
Profiling of Oral Microbiota and Cytokines in COVID-19 Patients
Authors: Iebba Valerio , Zanotta Nunzia , Campisciano Giuseppina , Zerbato Verena , Di Bella Stefano , Cason Carolina , Luzzati Roberto , Confalonieri Marco , Palamara Anna Teresa , Comar Manola
Published: July 2021

The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recently demonstrated in the sputum or saliva, suggesting how the shedding of viral RNA outlasts the end of symptoms. Recent data from transcriptome analysis show that the oral cavity mucosa harbors high levels of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2), highlighting its role as a double-edged sword for SARS-CoV-2 body entrance or interpersonal transmission. Here, we studied the oral microbiota structure and inflammatory profile of 26 naive severe coronavirus disease 2019 (COVID-19) patients and 15 controls by 16S rRNA V2 automated targeted sequencing and magnetic bead-based multiplex immunoassays, respectively. A significant diminution in species richness was observed in COVID-19 patients, along with a marked difference in beta-diversity. Species such as Prevotella salivae and Veillonella infantium were distinctive for COVID-19 patients, while Neisseria perflava and Rothia mucilaginosa were predominant in controls. Interestingly, these two groups of oral species oppositely clustered within the bacterial network, defining two distinct Species Interacting Groups (SIGs). COVID-19-related pro-inflammatory cytokines were found in both oral and serum samples, along with a specific bacterial consortium able to counteract them. We introduced a new parameter, named CytoCOV, able to predict COVID-19 susceptibility for an unknown subject at 71% of power with an Area Under Curve (AUC) equal to 0.995. This pilot study evidenced a distinctive oral microbiota composition in COVID-19 subjects, with a definite structural network in relation to secreted cytokines. Our results would be usable in clinics against COVID-19, using bacterial consortia as biomarkers or to reduce local inflammation.
Production, Storage Stability, and Susceptibility Testing of Reuterin and Its Impact on the Murine Fecal Microbiome and Volatile Organic Compound Profile
Authors: Castellani Christoph , Obermüller Beate , Kienesberger Bernhard , Singer Georg , Peterbauer Clemens , Grabherr Reingard , Mayrhofer Sigrid , Klymiuk Ingeborg , Horvath Angela , Stadlbauer Vanessa , Russmayer Hannes , Miekisch Wolfram , Fuchs Patricia , Till Holger , Heinl Stefan
Published: July 2021

Background: Probiotics are generally considered as safe, but infections may rarely occur in vulnerable patients. Alternatives to live microorganisms to manage dysbiosis may be of interest in these patients. Reuterin is a complex component system exhibiting broad spectrum antimicrobial activity and a possible candidate substance in these cases.

Methods: Reuterin supernatant was cultured from Lentilactobacillus diolivorans in a bioreactor in a two-step process. Storage stability at −20°C and effect of repeated freeze-thaw cycles were assessed by high performance liquid chromatography (HPLC). Antimicrobial activity was tested against Clostridium difficile, Listeria monocytogenes, Escherichia coli, Enterococcus faecium, Staphylococcus (S.) aureus, Staphylococcus epidermidis, Streptococcus (S.) agalactiae, Propionibacterium acnes, and Pseudomonas aeruginosae. Male BALBc mice were gavage fed with reuterin supernatant (n = 10) or culture medium (n = 10). Fecal volatile organic compounds (VOC) were assessed by gas chromatography mass spectroscopy; the microbiome was examined by 16S rRNA gene sequencing.

Results: The supernatant contained 13.4 g/L reuterin (3-hydroxypropionaldehyde; 3-HPA). 3-HPA content remained stable at −20°C for 35 days followed by a slow decrease of its concentration. Repeated freezing/thawing caused a slow 3-HPA decrease. Antimicrobial activity was encountered against S. aureus, S. epidermidis, and S. agalactiae. Microbiome analysis showed no differences in alpha and beta diversity markers. Linear discriminant effect size (LEfSe) analysis identified Lachnospiraceae_bacterium_COE1 and Ruminoclostridium_5_uncultured_Clostridiales_ bacterium (in the reuterin medium group) and Desulfovibrio_uncultured_ bacterium, Candidatus Arthromitus, Ruminococcae_NK4A214_group, and Eubacterium_xylanophilum_group (in the reuterin group) as markers for group differentiation. VOC analysis showed a significant decrease of heptane and increase of 3-methylbutanal in the reuterin group.

Conclusion: The supernatant produced in this study contained acceptable amounts of 3-HPA remaining stable for 35 days at −20°C and exhibiting an antimicrobial effect against S. aureus, S. agalactiae, and S. epidermidis. Under in vivo conditions, the reuterin supernatant caused alterations of the fecal microbiome. In the fecal, VOC analysis decreased heptane and increased 3-methylbutanal were encountered. These findings suggest the high potential of the reuterin system to influence the intestinal microbiome in health and disease, which needs to be examined in detail in future projects.
Comparison of Antimicrobial Resistance, Virulence Genes, Phylogroups, and Biofilm Formation of Escherichia coli Isolated From Intensive Farming and Free-Range Sheep
Authors: Zhao Xueliang , Lv Yunyang , Adam Fathalrhman Eisa Addoma , Xie Qingfang , Wang Bin , Bai Xindong , Wang Xiaoyuan , Shan Honghu , Wang Xinglong , Liu Haijin , Dang Ruyi , Wang Juan , Yang Zengqi
Published: July 2021

Pathogenic E. coli are among the most frequently isolated bacterial pathogens on large-scale sheep farms in China. Antibiotic use in wool sheep production is a risk factor for promoting the emergence of resistant E. coli. To reveal the differences of E. coli populations in sheep from different farming systems the antimicrobial resistance, virulence genes, biofilm formation, and phylogroups of 500 E. coli isolates obtained between September 2019 and December 2020 in northwest China from diarrheic infections of intensive farming and free-range sheep were analyzed. The antimicrobial susceptibility test for 12 classes of antimicrobial agents was determined using the broth microdilution susceptibility method, and PCR was used to detect the differences in virulence genes and phylogroups. Additionally, biofilm formation was determined using microtiter plate and slide agglutination methods. Among the 500 E. coli isolates, the majority of the isolates were multidrug resistant (75.4%) and carried at least one virulence gene (94.8%). We observed that 412 (82.4%), 360 (72.0%), and 266 (53.2%) are found to be resistant to sulfisoxazole, florfenicol, and tetracyclines, respectively. Resistance was also observed to mequindox (46.8%), ampicillin (43.6%), spectinomycin (38.6%), enrofloxacin (34.2%), ceftiofur (21.0%), gentamycin (20.4%), ceftazidime (17.8%), and polymyxin B (7.8%) but no resistance was found to meropenem. These results showed that strains from free-range subjects had fewer antibiotic resistance strains rather than sheep that were intensively farmed (P < 0.05). We observed fifteen virulence genes, of which etrA (n = 401, 80.2%) is the most common. In addition, EAEC (86.4%) is dominant among free-range sheep and EHEC (80.1%) is dominant among intensive farming. Among all virulence genes, the strongest correlation was found between etrA and papC gene (P < 0.001, OR = 455.68). Similarly, the strongest correlation was also found between eltA and sulfisoxazole (P < 0.001, OR = 877). Furthermore, the majority of the E. coli isolates belonged to phylogroup B1 (50.6%), followed by phylogroup C (20.6%), A (7.4%), E (7.4%), D (5.8%), B2 (1.6%), and F (1%). Interestingly, phylogroup B2 and D were all distributed in intensive farms. In addition, 33 (6.6%), 373 (74.6%), and 94 (18.8%) showed moderate, weak, and no connection biofilm formation ability, respectively. These data uncovered that wool sheep serve as a reservoir of pathogenic E. coli harboring multiple resistance phenotypes and virulence genes. The overlapping virulence-associated traits between IPEC and ExPEC indicated the zoonotic potential and safety threats of sheep food products. It is urgent to improve the proper use of antimicrobials in China as well as other countries.
Temporal, Spatial, and Genomic Analyses of Enterobacteriaceae Clinical Antimicrobial Resistance in Companion Animals Reveals Phenotypes and Genotypes of One Health Concern
Authors: Singleton David A. , Pongchaikul Pisut , Smith Shirley , Bengtsson Rebecca J. , Baker Kate , Timofte Dorina , Steen Stephen , Jones Matthew , Roberts Larry , Sánchez-Vizcaíno Fernando , Dawson Susan , Noble P.-J. M. , Radford Alan D. , Pinchbeck Gina L. , Williams Nicola J.
Published: July 2021

Background

Antimicrobial resistance (AMR) is a globally important one health threat. The impact of resistant infections on companion animals, and the potential public health implications of such infections, has not been widely explored, largely due to an absence of structured population-level data.

Objectives

We aimed to efficiently capture and repurpose antimicrobial susceptibility test (AST) results data from several veterinary diagnostic laboratories (VDLs) across the United Kingdom to facilitate national companion animal clinical AMR surveillance. We also sought to harness and genotypically characterize isolates of potential AMR importance from these laboratories.

Methods

We summarized AST results for 29,330 canine and 8,279 feline Enterobacteriaceae isolates originating from companion animal clinical practice, performed between April 2016 and July 2018 from four VDLs, with submissions from 2,237 United Kingdom veterinary practice sites.

Results

Escherichia coli (E. coli) was the most commonly isolated Enterobacteriaceae in dogs (69.4% of AST results, 95% confidence interval, CI, 68.7–70.0) and cats (90.5%, CI 89.8–91.3). Multi-drug resistance was reported in 14.1% (CI 13.5–14.8) of canine and 12.0% (CI 11.1–12.9) of feline E. coli isolates. Referral practices were associated with increased E. coli 3rd generation ≤ cephalosporin resistance odds (dogs: odds ratio 2.0, CI 1.2–3.4). We selected 95 E. coli isolates for whole genome analyses, of which seven belonged to sequence type 131, also carrying the plasmid-associated extended spectrum β-lactamase gene blaCTX–M–15. The plasmid-mediated colistin resistance gene mcr-9 was also identified for the first time in companion animals.

Conclusions

Linking clinical AMR data with genotypic characterization represents an efficient means of identifying important resistance trends in companion animals on a national scale.
Generation of a Sleeping Beauty Transposon-Based Cellular System for Rapid and Sensitive Screening for Compounds and Cellular Factors Limiting SARS-CoV-2 Replication
Authors: Widera Marek , Wilhelm Alexander , Toptan Tuna , Raffel Johanna M. , Kowarz Eric , Roesmann Fabian , Grözinger Finn , Siemund Anna Lena , Luciano Vanessa , Külp Marius , Reis Jennifer , Bracharz Silvia , Pallas Christiane , Ciesek Sandra , Marschalek Rolf
Published: July 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the acute respiratory disease COVID-19, which has become a global concern due to its rapid spread. The common methods to monitor and quantitate SARS-CoV-2 infectivity in cell culture are so far time-consuming and labor-intensive. Using the Sleeping Beauty transposase system, we generated a robust and versatile cellular infection model that allows SARS-CoV-2 infection experiments compatible for high-throughput and live cell imaging. The model is based on lung derived A549 cells, which show a profound interferon response and convenient cell culture characteristics. ACE2 and TMPRSS2 were introduced for constitutive expression (A549-AT). Subclones with varying levels of ACE2/TMPRSS2 were screened for optimal SARS-CoV-2 susceptibility. Furthermore, extensive evaluation demonstrated that SARS-CoV-2 infected A549-AT cells were distinguishable from mock-infected cells and already showed approximately 12 h post infection a clear signal to noise ratio in terms of cell roughness, fluorescence and a profound visible cytopathic effect. Moreover, due to the high transfection efficiency and proliferation capacity, Sleeping Beauty transposase-based overexpression cell lines with a second inducible fluorescence reporter cassette (eGFP) can be generated in a very short time, enabling the investigation of host and restriction factors in a doxycycline-inducible manner. Thus, the novel model cell line allows rapid and sensitive monitoring of SARS-CoV-2 infection and the screening for host factors essential for viral replication.
Mucosa-Associated Microbial Profile Is Altered in Small Intestinal Bacterial Overgrowth
Authors: Li Jia , Zhang Ru , Ma Jinxia , Tang Shuai , Li Yuan , Li Yi , Wan Jun
Published: July 2021

The overall gut microbial profile of patients with small intestinal bacterial overgrowth (SIBO) has not been thoroughly investigated. We investigated the microbial communities of mucosal specimens from the duodenum, ileum, sigmoid colon, and feces of patients with and without SIBO, as diagnosed by lactulose breath testing. The bacteria present in the mucosal and fecal samples were identified using 16S rRNA gene sequencing. Further analysis was performed using the linear discriminant analysis (LDA) effect size method, random forest analysis, and receiver operating characteristic analysis. The microbial diversities of the fecal samples were significantly lower than those of the mucosal samples from the duodenum, ileum, and sigmoid colon (P < 0.001, P < 0.001, and P < 0.001, respectively), while the bacterial compositions of the ileac mucosal samples and sigmoid mucosal samples were similar. The bacterial composition of either the fecal or duodenal mucosal samples were significantly different from those of the other three groups (ANOSIM R = 0.305, P = 0.001). The bacterial compositions of the mucosal samples of the duodenum, ileum, and sigmoid colon in the SIBO + subjects were significantly different from those of the SIBO− subjects (ANOSIM P = 0.039, 0.002, and 0.007, respectively). The relative abundances of 7, 18, and 8 genera were significantly different (LDA score > 3) in the mucosal samples of the duodenum, ileum, and sigmoid colon between the SIBO + and SIBO− groups. Four genera (Lactobacillus, Prevotella_1, Dialister, and norank_f__Ruminococcaceae) showed similar changes among the mucosal samples of the duodenum, ileum, and sigmoid colon in the SIBO + subjects. A signature consisting of four genera in the duodenal mucosa, three genera in the ileac mucosa, or six genera in the mucosa of the sigmoid colon exhibited predictive power for SIBO (area under the curve = 0.9, 0.93, and 0.87, respectively). This study provides a comprehensive profile of the gut microbiota in patients with SIBO. Dysbiosis was observed in the mucosa-associated gut microbiome but not in the fecal microbiome of patients with SIBO. Furthermore, we identified mucosa-associated taxa that may be potential biomarkers or therapeutic targets of SIBO. Further investigation is needed on their mechanisms and roles in SIBO.
A Comprehensive Review on the Impact of Edible Coatings, Essential Oils, and Their Nano Formulations on Postharvest Decay Anthracnose of Avocados, Mangoes, and Papayas
Authors: Sivakumar Dharini , Tuna Gunes Nurdan , Romanazzi Gianfranco
Published: July 2021

Subtropical fruit such as avocados (Persea americana), mangoes (Mangifera indica L.), and papayas (Carica papaya L.) are economically important in international trade and predominantly exported to European destinations. These fruits are highly consumed due to their health benefits. However, due to long-distance shipping and the time required to reach the retail department stores, postharvest losses, due to postharvest decay occurring during the supply chain, affect the fruit quality on arrival at the long-distance distribution points. Currently, the use of synthetic fungicide, Prochloraz®, is used at the packing line to reduce postharvest decay and retain the overall quality of mangoes and avocados. Due to the ban imposed on the use of synthetic fungicides on fresh fruit, several studies have focused on the development of alternative technologies to retain the overall quality during marketing. Among the developed alternative technologies for commercial adoption is the use of edible coatings, such as chitosan biocontrol agents and essential oil vapors. The objective of this review is to summarize and analyze the recent advances and trends in the use of these alternative postharvest treatments on anthracnose decay in avocados, mangoes, and papayas.
Identification of a Gene Set Correlated With Immune Status in Ovarian Cancer by Transcriptome-Wide Data Mining
Authors: Fan Lili , Lei Han , Lin Ying , Zhou Zhengwei , Shu Guang , Yan Zhipeng , Chen Haotian , Zhang Tianxiang , Yin Gang
Published: July 2021

Immune checkpoint blocking (ICB) immunotherapy has achieved great success in the treatment of various malignancies. Although not have been approved for the treatment of ovarian cancer (OC), it has been actively tested for the treatment of OC. However, biomarkers that could indicate the immune status of OC and predict the response to ICB are rare. We downloaded RNAseq and clinical data of OC from The Cancer Genome Atlas (TCGA). Data analysis revealed both TMBhighand immunityhighwere significantly related to better survival of OC. Up-regulated differentially expressed genes (Up-DEGs) were identified by analyzing the gene expression levels. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in the “GSVA” and “limma” package in R software. The correlation of genes with overall survival was also analyzed by conducted Kaplan-Meier survival analysis. Four genes, CXCL13, FCRLA, MS4A1, and PLA2G2D were found positively correlated with better prognosis of OC and mainly involved in immune response-related pathways. Finally, TIMER and TIDE were used to predict gene immune function and its association with immunotherapy. We found that these four genes were positively correlated with better response to immune checkpoint blockade-based immunotherapy. Altogether, CXCL13, FCRLA, MS4A1, and PLA2G2D may be used as potential therapeutic genes for reflecting OC immune status and predicting response to immunotherapy.
Prognostic Prediction, Immune Microenvironment, and Drug Resistance Value of Collagen Type I Alpha 1 Chain: From Gastrointestinal Cancers to Pan-Cancer Analysis
Authors: Liu Yi , Xue Jinmin , Zhong Maoxi , Wang Zhi , Li Jie , Zhu Yuxi
Published: July 2021

Background: Gastrointestinal cancers patients might experience multiple primary tumors in the digestive tract. Therefore, identifying potential biomarkers can help us better understand the underlying mechanism. From the GEO database, four profiles of gastrointestinal cancers were gathered for the screening process, and six hub genes were found by bioinformatics analysis. Collagen type I alpha 1 chain (COL1A1), one of the hub genes, is a component of the extracellular matrix and is critical for tumor microenvironment. However, the expression level, signaling pathway, prognostic prediction, and immunological value of COL1A1 in different cancers remain unclear.

Methods: We comprehensively analyzed gene expression and genetic alteration patterns of COL1A1 among 33 types of malignancies from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression projects. Besides, we explored the correlation of COL1A1 with cancer prognosis, immune infiltrates, PD-L1, tumor mutational burden (TMB)/microsatellite instability status (MSI), and the pathway and drug sensitivity of co-expressed genes.

Results: The results showed that COL1A1 was highly expressed and associated with poor prognosis in the majority of cancers. The most common alteration type of COL1A1 was missense mutation, and COL1A1 was associated with poor prognosis in KIRP, LGG, MESO, SKCM, and STAD. For the immunologic significance, COL1A1 expression was closely related to high TMB in THYM, LAML, ACC, KICH, PRAD, and LGG, and high MSI in TGCT, MESO, PRAD, COAD, SARC, and CESC. In addition, COL1A1 was positively correlated with the abundance of CAFs, macrophages, and tumor-infiltrating lymphocytes. However, it was negatively correlated with CD8+ T cells mainly in CESC, HNSC-HPV+, and SKCM. Besides, as a component of the extracellular matrix, COL1A1 was involved in the activation of epithelial-mesenchymal transition (EMT), and high expression of HTRA1 was resistant to multiple drugs.

Conclusion:COL1A1 can serve as a prognostic and immunological biomarker in different cancers.
Ferroptosis-Related Gene Signature and Patterns of Immune Infiltration Predict the Overall Survival in Patients With Lung Adenocarcinoma
Authors: Wang Yuxuan , Chen Weikang , Zhu Minqi , Xian Lei
Published: July 2021

Background:Lung adenocarcinoma (LUAD) is a malignant tumor with high heterogeneity and poor prognosis. Ferroptosis, a form of regulated cell-death–related iron, has been proven to trigger inflammation-associated immunosuppression in the tumor microenvironment, which promotes tumor growth. Therefore, the clinical prognostic value of ferroptosis-related genes in LUAD needs to be further explored.

Method:In this study, we downloaded the mRNA expression profiles and corresponding clinical data of LUAD patients from the Cancer Genome Atlas database. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct ferroptosis-related gene signature. Based on these, we established the nomograms for prognosis prediction and validated the model in the GSE72094 dataset. The cell type was identified using the CIBERSORT algorithm for estimating relative subsets of RNA transcripts, which was then used to screen significant tumor immune-infiltrating cells associated with the LUAD prognosis prediction model. Subsequently, we applied co-expression analysis to reveal the relationship between ferroptosis-related genes and significant immune cells.

Results:The univariate COX regression analysis showed that 20 genes were associated with the overall survival (OS) as prognostic differentially expressed genes (DEGs) (FDR <0.05). Patients were divided into two risk groups using a 13-gene signature, with the high-risk group having a significantly worse OS than their low-risk counterparts (p< 0.001). We used receiver operating characteristic (ROC) curve analysis to confirm the predictive capacity of the signature. Besides, we identified seven pairs of ferroptosis-related genes and tumor-infiltrating immune cells associated with the prognosis of LUAD patients.

Conclusion:In this study, we construct a ferroptosis-related gene signature that can be used for prognostic prediction in LUAD. In addition, we reveal a potential connection between ferroptosis and tumor-infiltrating immune cells.
Combined Support Vector Machine Classifier and Brain Structural Network Features for the Individual Classification of Amnestic Mild Cognitive Impairment and Subjective Cognitive Decline Patients
Authors: Huang Weijie , Li Xuanyu , Li Xin , Kang Guixia , Han Ying , Shu Ni
Published: July 2021

Objective

Individuals with subjective cognitive decline (SCD) or amnestic mild cognitive impairment (aMCI) represent important targets for the early detection and intervention of Alzheimer’s disease (AD). In this study, we employed a multi-kernel support vector machine (SVM) to examine whether white matter (WM) structural networks can be used for screening SCD and aMCI.

Methods

A total of 138 right-handed participants [51 normal controls (NC), 36 SCD, 51 aMCI] underwent MRI brain scans. For each participant, three types of WM networks with different edge weights were constructed with diffusion MRI data: fiber number-weighted networks, mean fractional anisotropy-weighted networks, and mean diffusivity (MD)-weighted networks. By employing a multiple-kernel SVM, we seek to integrate information from three weighted networks to improve classification performance. The accuracy of classification between each pair of groups was evaluated via leave-one-out cross-validation.

Results

For the discrimination between SCD and NC, an area under the curve (AUC) value of 0.89 was obtained, with an accuracy of 83.9%. Further analysis revealed that the methods using three types of WM networks outperformed other methods using single WM network. Moreover, we found that most of discriminative features were from MD-weighted networks, which distributed among frontal lobes. Similar classification performance was also reported in the differentiation between subjects with aMCI and NCs (accuracy = 83.3%). Between SCD and aMCI, an AUC value of 0.72 was obtained, with an accuracy of 72.4%, sensitivity of 74.5% and specificity of 69.4%. The highest accuracy was achieved with features only selected from MD-weighted networks.

Conclusion

White matter structural network features help machine learning algorithms accurately identify individuals with SCD and aMCI from NCs. Our findings have significant implications for the development of potential brain imaging markers for the early detection of AD.
To Regulate or Not to Regulate: Emotion Regulation in Participants With Low and High Impulsivity
Authors: Maier Moritz Julian , Schiel Julian Elias , Rosenbaum David , Hautzinger Martin , Fallgatter Andreas Jochen , Ehlis Ann-Christine
Published: July 2021

Successful emotion regulation plays a key role in psychological health and well-being. This study examines (1) whether cognitive control and corresponding neural connectivity are associated with emotion regulation and (2) to what extent external instructions can improve emotion regulation in individuals with low vs. high cognitive control capacity. For this, emotion regulation capabilities and the impact of emotion regulation on a subsequent emotional Stroop task was tested in participants with low (N = 25) vs. high impulsivity (N = 32). The classification according to impulsivity is based upon the stable correlation between high impulsivity and reduced cognitive control capacity. A negative emotion inducing movie scene was presented with the instruction to either suppress or allow all emotions that arose. This was followed by an emotional Stroop task. Electromyography (EMG) over the corrugator supercilii was used to assess the effects of emotion regulation. Neurophysiological mechanisms were measured using functional near-infrared spectroscopy over frontal brain areas. While EMG activation was low in the low-impulsive group independent of instruction, high-impulsive participants showed increased EMG activity when they were not explicitly instructed to suppress arising emotions. Given the same extent of functional connectivity within frontal lobe networks, the low-impulsive participants controlled their emotions better (less EMG activation) than the high-impulsive participants. In the Stroop task, the low-impulsive subjects performed significantly better. The emotion regulation condition had no significant effect on the results. We conclude that the cognitive control network is closely associated with emotion regulation capabilities. Individuals with high cognitive control show implicit capabilities for emotion regulation. Individuals with low cognitive control require external instructions (= explicit emotion regulation) to achieve similarly low expressions of emotionality. Implications for clinical applications aiming to improve emotion regulation are discussed.
Neurocognitive Effects of Preceding Facial Expressions on Perception of Subsequent Emotions
Authors: Kim Shin Ah , Kim Sang Hee
Published: July 2021

In everyday life, individuals successively and simultaneously encounter multiple stimuli that are emotionally incongruent. Emotional incongruence elicited by preceding stimuli may alter emotional experience with ongoing stimuli. However, the underlying neural mechanisms of the modulatory influence of preceding emotional stimuli on subsequent emotional processing remain unclear. In this study, we examined self-reported and neural responses to negative and neutral pictures whose emotional valence was incongruent with that of preceding images of facial expressions. Twenty-five healthy participants performed an emotional intensity rating task inside a brain scanner. Pictures of negative and neutral scenes appeared, each of which was preceded by a pleasant, neutral, or unpleasant facial expression to elicit a degree of emotional incongruence. Behavioral results showed that emotional incongruence based on preceding facial expressions did not influence ratings of subsequent pictures’ emotional intensity. On the other hand, neuroimaging results revealed greater activation of the right dorsomedial prefrontal cortex (dmPFC) in response to pictures that were more emotionally incongruent with preceding facial expressions. The dmPFC had stronger functional connectivity with the right ventrolateral prefrontal cortex (vlPFC) during the presentation of negative pictures that followed pleasant facial expressions compared to those that followed unpleasant facial expressions. Interestingly, increased functional connectivity of the dmPFC was associated with the reduced modulatory influence of emotional incongruence on the experienced intensity of negative emotions. These results indicate that functional connectivity of the dmPFC contributes to the resolution of emotional incongruence, reducing the emotion modulation effect of preceding information on subsequent emotional processes.