bluuebunny/crossref_metadata_2025 huggingface dataset:
Exposure to the Gram-Negative Bacteria Pseudomonas aeruginosa Influences the Lung Dendritic Cell Population Signature by Interfering With CD103 Expression
Authors: Brassard Julyanne , Roy Joanny , Lemay Anne-Marie , Beaulieu Marie-Josée , Bernatchez Emilie , Veillette Marc , Duchaine Caroline , Blanchet Marie-Renée
Published: July 2021

Lung dendritic cells (DCs) are divided into two major populations, which include CD103+XCR1+ cDC1s and CD11b+Sirpα+ cDC2s. The maintenance of their relative proportions is dynamic and lung inflammation, such as caused by exposure to lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, can have a significant impact on the local cDC signature. Alterations in the lung cDC signature could modify the capacity of the immune system to respond to various pathogens. We consequently aimed to assess the impact of the Gram-negative bacteria Pseudomonas aeruginosa on lung cDC1 and cDC2 populations, and to identify the mechanisms leading to alterations in cDC populations. We observed that exposure to P. aeruginosa decreased the proportions of CD103+XCR1+ cDC1s, while increasing that of CD11b+ DCs. We identified two potential mechanisms involved in this modulation of lung cDC populations. First, we observed an increase in bone marrow pre-DC IRF4 expression suggesting a higher propensity of pre-DCs to differentiate towards the cDC2 lineage. This observation was combined with a reduced capacity of lung XCR1+ DC1s to express CD103. In vitro, we demonstrated that GM-CSF-induced CD103 expression on cDCs depends on GM-CSF receptor internalization and RUNX1 activity. Furthermore, we observed that cDCs stimulation with LPS or P. aeruginosa reduced the proportions of intracellular GM-CSF receptor and decreased RUNX1 mRNA expression. Altogether, these results suggest that alterations in GM-CSF receptor intracellular localization and RUNX1 signaling could be involved in the reduced CD103 expression on cDC1 in response to P. aeruginosa. To verify whether the capacity of cDCs to express CD103 following P. aeruginosa exposure impacts the immune response, WT and Cd103-/- mice were exposed to P. aeruginosa. Lack of CD103 expression led to an increase in the number of neutrophils in the airways, suggesting that lack of CD103 expression on cDC1s could favor the innate immune response to this bacterium.
Probiotic Lacticaseibacillus rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 as an Adjunctive Treatment for Bacterial Vaginosis Do Not Increase the Cure Rate in a Chinese Cohort: A Prospective, Parallel‐Group, Randomized, Controlled Study
Authors: Zhang Yongke , Lyu Jinli , Ge Lan , Huang Liting , Peng Zhuobing , Liang Yiheng , Zhang Xiaowei , Fan Shangrong
Published: July 2021

The purpose of this study was to evaluate the effectiveness of metronidazole and oral probiotics adjunct to metronidazole in the treatment of bacterial vaginosis (BV). One hundred and twenty-six Chinese women with BV were enrolled in this parallel, controlled trial, and were randomly assigned into two study arms: the metronidazole group, which was prescribed metronidazole vaginal suppositories for 7 days, and the adjunctive probiotic group, which received Lacticaseibacillus rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 orally for 30 days as an adjunct to metronidazole. Clinical symptoms and Nugent scores at the initial visit, 30 days and 90 days were compared. There was no significant difference of the 30-day total cure rate between the adjunctive probiotic group (57.69%) and the metronidazole group (59.57%), with an odds ratio (OR) of 0.97 (95% confidence interval (CI), 0.70 to 1.35, p-value = 0.04), or of the 90-day total cure rate (36.54% vs. 48.94%, OR, 0.75; 95% CI, 0.47 to 1.19; p-value = 0.213). Also, no significant difference of the vaginal and faecal microbial diversity and structure between the two groups at 0, 30 or 90 days were shown based on 16S rRNA sequences. The probiotic species were rarely detected in either the vaginal microbiota or the faecal microbiota after administration which may revealed the cause of noneffective of oral probiotics. No serious adverse effects were reported in the trial. The study indicated that oral probiotic adjunctive treatment did not increase the cure rate of Chinese BV patients compared to metronidazole.
Pre-Diabetes Increases Tuberculosis Disease Severity, While High Body Fat Without Impaired Glucose Tolerance Is Protective
Authors: Sinha Roma , Ngo Minh Dao , Bartlett Stacey , Bielefeldt-Ohmann Helle , Keshvari Sahar , Hasnain Sumaira Z. , Donovan Meg L. , Kling Jessica C. , Blumenthal Antje , Chen Chen , Short Kirsty R. , Ronacher Katharina
Published: July 2021

Type 2 diabetes (T2D) is a well-known risk factor for tuberculosis (TB), but little is known about pre-diabetes and the relative contribution of impaired glucose tolerance vs. obesity towards susceptibility to TB. Here, we developed a preclinical model of pre-diabetes and TB. Mice fed a high fat diet (HFD) for 12 weeks presented with impaired glucose tolerance and hyperinsulinemia compared to mice fed normal chow diet (NCD). Infection with M. tuberculosis (Mtb) H37Rv after the onset of dysglycemia was associated with significantly increased lung pathology, lower concentrations of TNF-α, IFN-γ, IFN-β and IL-10 and a trend towards higher bacterial burden at 3 weeks post infection. To determine whether the increased susceptibility of pre-diabetic mice to TB is reversible and is associated with dysglycemia or increased body fat mass, we performed a diet reversal experiment. Pre-diabetic mice were fed a NCD for 10 additional weeks (HFD/NCD) at which point glucose tolerance was restored, but body fat mass remained higher compared to control mice that consumed NCD throughout the entire experiment (NCD/NCD). Upon Mtb infection HFD/NCD mice had significantly lower bacterial burden compared to NCD/NCD mice and this was accompanied by restored IFN-γ responses. Our findings demonstrate that pre-diabetes increases susceptibility to TB, but a high body mass index without dysglycemia is protective. This murine model offers the opportunity to further study the underlying immunological, metabolic and endocrine mechanisms of this association.
De Novo Sequencing and High-Contiguity Genome Assembly of Moniezia expansa Reveals Its Specific Fatty Acid Metabolism and Reproductive Stem Cell Regulatory Network
Authors: Liu Yi , Wang Zhengrong , Huang Wanlong , Pang Shuai , Qian Lingxiao , Zhang Yanyan , Meng Jimeng , Xu Mengfei , Wang Weiyi , Wang Yunfei , Lu Baoyan , Zhao Yiyue , Xian Jinwen , Bo Xinwen , Yue Bisong
Published: July 2021

Moniezia expansa (M. expansa) parasitizes the small intestine of sheep and causes inhibited growth and development or even death. Being globally distributed, it causes considerable economic losses to the animal husbandry industry. Here, using Illumina, PacBio and BioNano techniques, we obtain a high-quality genome assembly of M. expansa, which has a total length of 142 Mb, a scaffold N50 length of 7.27 Mb and 8,104 coding genes. M. expansa has a very high body fat content and a specific type of fatty acid metabolism. It cannot synthesize any lipids due to the loss of some key genes involved in fatty acid synthesis, and it may can metabolize most lipids via the relatively complete fatty acid β-oxidation pathway. The M. expansa genome encodes multiple lipid transporters and lipid binding proteins that enable the utilization of lipids in the host intestinal fluid. Although many of its systems are degraded (with the loss of homeobox genes), its reproductive system is well developed. PL10, AGO, Nanos and Pumilio compose a reproductive stem cell regulatory network. The results suggest that the high body lipid content of M. expansa provides an energy source supporting the high fecundity of this parasite. Our study provides insight into host interaction, adaptation, nutrient acquisition, strobilization, and reproduction in this parasite and this is also the first genome published in Anoplocephalidae.
Lacidipine Ameliorates the Endothelial Senescence and Inflammatory Injury Through CXCR7/P38/C/EBP-β Signaling Pathway
Authors: Liu Xing , Huang Zhuoshan , Zhang Yuanyuan , Shui Xing , Liu Fanmao , Wu Zhen , Xu Shiyue
Published: July 2021

Background: Lacidipine, a third-generation calcium channel blocker, exerts beneficial effects on the endothelium of hypertensive patients in addition to blood pressure lowering. However, the detailed mechanism underlying Lacidipine-related endothelial protection is still elusive.

Methods: Sixteen spontaneous hypertensive rats (SHRs) were randomly divided into two groups: Lacidipine-treated SHR group and saline-treated control group. Tail systolic blood pressure was monitored for four consecutive weeks. Endothelial cells (ECs) were pretreated with Lacidipine prior to being stimulated with H2O2, bleomycin, or Lipopolysaccharides (LPS) in vitro. Then, cell activity, migration, and senescence were measured by Cell Counting Kit-8 assay, transwell assay, and β-galactosidase staining, respectively. The fluorescent probe 2′, 7′-dichlorofluorescein diacetate (DCFH-DA) was used to assess the intracellular reactive oxygen species (ROS). Related protein expression was detected by Western blotting and immunofluorescence.

Results: Our data showed that Lacidipine treatment lowered the blood pressure of SHRs accompanied by the elevation of CXCR7 expression and suppression of P38 and CCAAT/enhancer-binding protein beta (C/EBP-β) compared with the control group. In vitro experiments further demonstrated that Lacidipine increased the cell viability and function of ECs under oxidative stress, cell senescence, and inflammatory activation via the CXCR7/P38/signaling pathway.

Conclusions: Our results suggested that Lacidipine plays a protective role in EC senescence, oxidative stress, and inflammatory injury through the regulation of CXCR7/P38/C/EBP-β signaling pathway.
Mild Therapeutic Hypothermia Alters Hemostasis in ST Elevation Myocardial Infarction Patients
Authors: Scherz Thomas , Hofbauer Thomas M. , Ondracek Anna S. , Simon Daniel , Sterz Fritz , Testori Christoph , Lang Irene M. , Mangold Andreas
Published: July 2021

Background and Rationale: Mild therapeutic hypothermia (MTH) is a concept to reduce infarct size and improve outcome after ST-segment elevation myocardial infarction (STEMI). In the STATIM trial, we investigated MTH as an additional therapy for STEMI patients. In the intention-to-treat set, 101 patients were included. No difference in primary and secondary endpoints measured by cardiac magnetic resonance imaging was found. Platelet activation and plasmatic coagulation are key in the pathophysiology of STEMI. In the present study, we investigated the effect of MTH on primary and secondary hemostasis in STEMI patients.

Methods and Results: Platelet function and morphology were assessed by routine blood count, aggregometry testing, and flow cytometry. Soluble platelet markers were determined by enzyme-linked immunosorbent assay (ELISA) testing. Plasmatic coagulation was measured throughout the study. Platelet count remained unchanged, irrespective of treatment, whereas platelet size decreased in both patient groups. Platelet aggregometry indicated increased platelet reactivity in the MTH group. Furthermore, higher adenosine diphosphate (ADP) plasma levels were found in MTH patients. Expression of glycoprotein IIb/IIIa was increased on platelets of STEMI patients treated with MTH. Lower patient temperatures correlated with longer clotting times and resulted in reduced pH. Lower pH values were positively correlated with longer clotting times.

Conclusion: Present data indicate longer clotting times and higher platelet reactivity in STEMI patients treated with MTH. These changes did not correspond to clinical bleeding events or larger infarct size.
Trends in COVID-19 Publications: Streamlining Research Using NLP and LDA
Authors: Gupta Akash , Aeron Shrey , Agrawal Anjali , Gupta Himanshu
Published: July 2021

Background: Research publications related to the novel coronavirus disease COVID-19 are rapidly increasing. However, current online literature hubs, even with artificial intelligence, are limited in identifying the complexity of COVID-19 research topics. We developed a comprehensive Latent Dirichlet Allocation (LDA) model with 25 topics using natural language processing (NLP) techniques on PubMed® research articles about “COVID.” We propose a novel methodology to develop and visualise temporal trends, and improve existing online literature hubs.

Our results for temporal evolution demonstrate interesting trends, for example, the prominence of “Mental Health” and “Socioeconomic Impact” increased, “Genome Sequence” decreased, and “Epidemiology” remained relatively constant. Applying our methodology to LitCovid, a literature hub from the National Center for Biotechnology Information, we improved the breadth and depth of research topics by subdividing their pre-existing categories. Our topic model demonstrates that research on “masks” and “Personal Protective Equipment (PPE)” is skewed toward clinical applications with a lack of population-based epidemiological research.
Electroacupuncture Alleviates Diabetic Peripheral Neuropathy by Regulating Glycolipid-Related GLO/AGEs/RAGE Axis
Authors: Wang Xuan , Li Qian , Han Xu , Gong Meirong , Yu Zhi , Xu Bin
Published: July 2021

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus (DM) and affects over one-third of all patients. Neuropathic pain and nerve dysfunction induced by DM is related to the increase of advanced glycation end products (AGEs) produced by reactive dicarbonyl compounds in a hyperglycemia environment. AGEs induce the expression of pro-inflammatory cytokines via the main receptor (RAGE), which has been documented to play a crucial role in the pathogenesis of diabetic peripheral neuropathy. Electroacupuncture (EA) has been reported to have a positive effect on paralgesia caused by various diseases, but the mechanism is unclear. In this study, we used high-fat-fed low-dose streptozotocin-induced rats as a model of type 2 diabetes (T2DM). Persistent metabolic disorder led to mechanical and thermal hyperalgesia, as well as intraepidermal nerve fiber density reduction and nerve demyelination. EA improved neurological hyperalgesia, decreased the pro-inflammatory cytokines, reduced the generation of AGEs and RAGE, and regulated the glyoxalase system in the EA group. Taken together, our study suggested that EA plays a role in the treatment of T2DM-induced DPN, and is probably related to the regulation of metabolism and the secondary influence on the GLO/AGE/RAGE axis.
Impact of a Single 36 Hours Prolonged Fasting Period in Adults With Type 1 Diabetes – A Cross-Over Controlled Trial
Authors: Moser Othmar , Eckstein Max L. , Mueller Alexander , Tripolt Norbert J. , Yildirim Hakan , Abbas Farah , Pferschy Peter N. , Goswami Nandu , Aberer Felix , Obermayer Anna , Pieber Thomas R. , Kojzar Harald , Sourij Caren , Brunner Martina , Niedrist Tobias , Herrmann Markus , Sourij Harald
Published: July 2021

Prolonged fasting has shown beneficial effects in healthy individuals and in people with chronic diseases. In type 1 diabetes, the effect or even the feasibility of fasting is unclear. We aimed to assess the impact and safety of prolonged fasting in adults with type 1 diabetes. Glycemia was assessed during overnight fasting (12 hours) vs. prolonged fasting (36 hours) via an intermittently-scanned continuous glucose monitoring system. Anthropometric data, metabolic and hormonal markers were compared between both trial arms. After each fasting period, a 75 g oral glucose tolerance test was performed and plasma glucose levels and hormones were assessed. Data were compared via paired t-tests and mixed-model regressions (p ≤ 0.05). Twenty individuals with type 1 diabetes (7 females) with a mean ± SD age of 35 ± 11 years, body mass index (BMI) 24.8 ± 2.8 kg/m2 and HbA1c 54 ± 7 mmol/mol were included. Hypoglycemia/hour (70 mg/dL; <3.9 mmol/L) was similar in both trial arms (12 hrs: 0.07 ± 0.06 vs. 36 hrs: 0.05 ± 0.03, p=0.21). Glycemic excursions during the oral glucose tolerance test were not different after the two fasting periods. Beta-hydroxybutyrate levels were higher after prolonged fasting (p=0.0006). Our study showed that people with type 1 diabetes can safely perform a 36 hours fasting period with a low risk of hypoglycemia and ketoacidosis.

Clinical Trial Registration

DRKS.de, identifier DRKS00016148.
Assessment for Voltage Violations considering Reactive Power Compensation Provided by Smart Inverters in Distribution Network
Authors: Hu Jindi , Yin Weibin , Ye Chengjin , Bao Weidong , Wu Jiajia , Ding Yi
Published: July 2021

Due to the high proportion of renewable energies, traditional voltage regulation methods such as on-load tap changers (OLTCs) and switching capacitors (SCs) are currently facing the challenge of providing fast, step-less, and low-cost reactive power to reduce the increasing risks of voltage violations in distribution networks (DNs). To meet such increasing demand for voltage regulation, smart inverters, including photovoltaics (PVs) and electric vehicle (EV) chargers, stand out as a feasible approach for reactive power compensation. This paper aims to assess the voltage violation risks in DNs considering the reactive power response of smart inverters. Firstly, reactive power compensation models of PVs and EV chargers are investigated and voltage deviation indexes of the regulation results are proposed. Moreover, kernel density estimation (KDE) and slice sampling are adopted to provide the PV output and EV charging demand samples. Then, the risk assessment is carried out with a voltage regulation model utilizing OLTCs, SCs, and available smart inverters. Numerical studies demonstrate that the reactive power support from smart inverters can significantly mitigate the voltage violation risks and reduce the switching and cost of OLTCs and capacitors in DNs.
Searching for Function: Reconstructing Adaptive Niche Changes Using Geochemical and Morphological Data in Planktonic Foraminifera
Authors: Kearns Lorna E. , Bohaty Steven M. , Edgar K. M. , Nogué Sandra , Ezard Thomas H. G.
Published: July 2021

Dead species remain dead. The diversity record of life is littered with examples of declines and radiations, yet no species has ever re-evolved following its true extinction. In contrast, functional traits can transcend diversity declines, often develop iteratively and are taxon-free allowing application across taxa, environments and time. Planktonic foraminifera have an unrivaled, near continuous fossil record for the past 200 million years making them a perfect test organism to understand trait changes through time, but the functional role of morphology in determining habitat occupation has been questioned. Here, we use single specimen stable isotopes to reconstruct the water depth habitat of individual planktonic foraminifera in the genus Subbotina alongside morphological measurements of the tests to understand trait changes through the Middle Eocene Climatic Optimum [MECO: ∼40 Myr ago (mega annum, Ma)]. The MECO is a geologically transient global warming interval that marks the beginning of widespread biotic reorganizations in marine organisms spanning a size spectrum from diatoms to whales. In contrast to other planktonic foraminiferal genera, the subbotinids flourished through this interval despite multiple climatic perturbations superimposed on a changing background climate. Through coupled trait and geochemical analysis, we show that Subbotina survival through this climatically dynamic interval was aided by trait plasticity and a wider ecological niche than previously thought for a subthermocline dwelling genus supporting a generalist life strategy. We also show how individually resolved oxygen isotopes can track shifts in depth occupancy through climatic upheaval. During and following the MECO, temperature changes were substantial in the thermocline and subthermocline in comparison to the muted responses of the surface ocean. In our post-MECO samples, we observe restoration of planktonic foraminifera depth stratification. Despite these changing temperatures and occupied depths, we do not detect a contemporaneous morphological response implying that readily available traits such as test size and shape do not have a clear functional role in this generalist genus. Modern imaging measurement technologies offer a promising route to gather more informative morphological traits for functional analysis, rather than the traditional candidates that are most easily measured.
A Fast and Efficient Approach to Obtaining High-Purity Glioma Stem Cell Culture
Authors: Han Xin-Xin , Cai Chunhui , Yu Li-Ming , Wang Min , Hu Dai-Yu , Ren Jie , Zhang Meng-Han , Zhu Lu-Ying , Zhang Wei-Hua , Huang Wei , He Hua , Gao Zhengliang
Published: July 2021

Glioma is the most common and malignant primary brain tumor. Patients with malignant glioma usually have a poor prognosis due to drug resistance and disease relapse. Cancer stem cells contribute to glioma initiation, progression, resistance, and relapse. Hence, quick identification and efficient understanding of glioma stem cells (GSCs) are of profound importance for therapeutic strategies and outcomes. Ideally, therapeutic approaches will only kill cancer stem cells without harming normal neural stem cells (NSCs) that can inhibit GSCs and are often beneficial. It is key to identify the differences between cancer stem cells and normal NSCs. However, reports detailing an efficient and uniform protocol are scarce, as are comparisons between normal neural and cancer stem cells. Here, we compared different protocols and developed a fast and efficient approach to obtaining high-purity glioma stem cell by tracking observation and optimizing culture conditions. We examined the proliferative and differentiative properties confirming the identities of the GSCs with relevant markers such as Ki67, SRY-box containing gene 2, an intermediate filament protein member nestin, glial fibrillary acidic protein, and s100 calcium-binding protein (s100-beta). Finally, we identified distinct expression differences between GSCs and normal NSCs including cyclin-dependent kinase 4 and tumor protein p53. This study comprehensively describes the features of GSCs, their properties, and regulatory genes with expression differences between them and normal stem cells. Effective approaches to quickly obtaining high-quality GSCs from patients should have the potential to not only help understand the diseases and the resistances but also enable target drug screening and personalized medicine for brain tumor treatment.
Common Variable Immunodeficiency and Autoimmune Diseases: A Retrospective Study of 95 Adult Patients in a Single Tertiary Care Center
Authors: Mormile Ilaria , Punziano Alessandra , Riolo Carlo Alberto , Granata Francescopaolo , Williams Michela , de Paulis Amato , Spadaro Giuseppe , Rossi Francesca Wanda
Published: July 2021

Common variable immunodeficiency (CVID) is the most common clinically significant primary immunodeficiency in adulthood, which presents a broad spectrum of clinical manifestations, often including non-infectious complications in addition to heightened susceptibility to infections. These protean manifestations may significantly complicate the differential diagnosis resulting in diagnostic delay and under-treatment with increased mortality and morbidity. Autoimmunity occurs in up to 30% of CVID patients, and it is an emerging cause of morbidity and mortality in this type of patients. 95 patients (42 males and 53 females) diagnosed with CVID, basing on ESID diagnostic criteria, were enrolled in this retrospective cohort study. Clinical phenotypes were established according to Chapel 2012: i) no other disease-related complications, ii) cytopenias (thrombocytopenia/autoimmune hemolytic anemia/neutropenia), iii) polyclonal lymphoproliferation (granuloma/lymphoid interstitial pneumonitis/persistent unexplained lymphadenopathy), and iv) unexplained persistent enteropathy. Clinical items in the analysis were age, gender, and clinical features. Laboratory data included immunoglobulin (Ig)G, IgM and IgA levels at diagnosis, flow-cytometric analysis of peripheral lymphocytes (CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD4+CD25highCD127low, CD19hiCD21loCD38lo, and follicular T helper cell counts). Comparisons of continuous variables between groups were performed with unpaired t-test, when applicable. 39 patients (41%) showed autoimmune complications. Among them, there were 21 females (53.8%) and 18 males (46.2%). The most prevalent autoimmune manifestations were cytopenias (17.8%), followed by arthritis (11.5%), psoriasis (9.4%), and vitiligo (6.3%). The most common cytopenia was immune thrombocytopenia, reported in 10 out of 95 patients (10.5%), followed by autoimmune hemolytic anemia (n=3, 3.1%) and autoimmune neutropenia (n=3, 3.1%). Other autoimmune complications included thyroiditis, coeliac disease, erythema nodosum, Raynaud’s phenomenon, alopecia, recurring oral ulcers, autoimmune gastritis, and primary biliary cholangitis. There were no statistically significant differences comparing immunoglobulin levels between CVID patients with or without autoimmune manifestations. There was no statistical difference in CD3+, CD8+, CD4+CD25highCD127low T, CD19, CD19hiCD21loCD38lo, and follicular T helper cell counts in CVID patients with or without autoimmune disorders. In conclusion, autoimmune manifestations often affect patients with CVID. Early recognition and tailored treatment of these conditions are pivotal to ensure a better quality of life and the reduction of CVID associated complications.
HLA Class I Molecules as Immune Checkpoints for NK Cell Alloreactivity and Anti-Viral Immunity in Kidney Transplantation
Authors: Duygu Burcu , Olieslagers Timo I. , Groeneweg Mathijs , Voorter Christina E. M. , Wieten Lotte
Published: July 2021

Natural killer (NK) cells are innate lymphocytes that can kill diseased- or virally-infected cells, mediate antibody dependent cytotoxicity and produce type I immune-associated cytokines upon activation. NK cells also contribute to the allo-immune response upon kidney transplantation either by promoting allograft rejection through lysis of cells of the transplanted organ or by promoting alloreactive T cells. In addition, they protect against viral infections upon transplantation which may be especially relevant in patients receiving high dose immune suppression. NK cell activation is tightly regulated through the integrated balance of signalingviainhibitory- and activating receptors. HLA class I molecules are critical regulators of NK cell activation through the interaction with inhibitory- as well as activating NK cell receptors, hence, HLA molecules act as critical immune checkpoints for NK cells. In the current review, we evaluate how NK cell alloreactivity and anti-viral immunity are regulated by NK cell receptors belonging to the KIR family and interacting with classical HLA class I molecules, or by NKG2A/C and LILRB1/KIR2DL4 engaging non-classical HLA-E or -G. In addition, we provide an overview of the methods to determine genetic variation in these receptors and their HLA ligands.
The Enhanced Immune Protection in Small Abalone Haliotis diversicolor Against a Secondary Infection With Vibrio harveyi
Authors: Yao Tuo , Lu Jie , Bai Changming , Xie Zhilv , Ye Lingtong
Published: July 2021

In recent years, more and more studies have shown that early pathogenic bacterial infection in invertebrates can enhance immunity and significantly reduce mortality when reinfected with the same pathogen. There are mechanisms to explain this phenomenon, but they are relatively few. In addition, dose-dependent primary infection is also associated with increased immunity. In the present study, the initial infection dose and mortality of abalone Haliotis diversicolor after reinfection with Vibrio harveyi were recorded, and the mechanism of immune enhancement was investigated by the transcriptomic response of abalone after two successive stimuli with V. harveyi. Priming with different concentrations of pathogen can enhance immunity; however, higher concentration is not always better. Compared with the first exposure, more genes were up-regulated after the second exposure. Among the commonly expressed genes, the immune related genes were significantly or persistently highly expressed after two infections and included pattern recognition receptors as well as immune effectors, such as toll-like receptors, perlucin 4, scavenger receptor class B-like protein, cytochrome P450 1B1-like, glutathione S-transferase 6, lysozyme and so on; in addition, these immune-related genes were mainly distributed in the pathways related to phagocytosis and calcium signaling. Among the specifically expressed genes, compared with the first infection, more genes were involved in the immune, metabolic and digestive pathways after the second infection, which would be more conducive to preventing the invasion of pathogens. This study outlined the mechanism of immune enhancement in abalone after secondary infection at the global molecular level, which is helpful for a comprehensive understanding of the mechanism of immune priming in invertebrates.
Multi-Omics Analysis Showed the Clinical Value of Gene Signatures of C1QC+ and SPP1+ TAMs in Cervical Cancer
Authors: Li Xiong , Zhang Qinghua , Chen Gang , Luo Danfeng
Published: July 2021

Purpose

To evaluate the value of C1QC+ and SPP1+ TAMs gene signatures in patients with cervical cancer.

Methods

We compare the C1QC+ and SPP1+ TAMs gene signatures with the M1/M2 gene signatures at single cell level and bulk RNA-seq level and evaluate which gene signature can clearly divide TAMs and patients with cervical cancer into distinct clinical subclusters better.

Results

At single-cell level, C1QC+ and SPP1+ TAMs gene signatures, but not M1 and M2 gene signatures, could clearly divided TAMs into two subclusters in a colon cancer data set and an advanced basal cell data set. For cervical cancer data from TCGA, patients with C1QChigh and SPP1low TAMs gene signatures have the best prognosis, lowest proportion (34.21%) of locally advanced cervical cancer (LACC), and highest immune cell infiltration, whereas patients with C1QClow and SPP1high TAMs gene signatures have the worst prognosis, highest proportion (71.79%) of LACC and lowest immune cell infiltration. Patients with C1QChigh and SPP1low TAMs gene signature have higher expression of most of the Immune checkpoint molecules (ICMs) than patients with C1QClow and SPP1high TAMs gene signatures. The GSEA results suggested that subgroups of patients divided by C1QC+ and SPP1+ TAMs gene signatures showed different anti- or pro-tumor state.

Conclusion

C1QC+ and SPP1+ TAMs gene signatures, but not M1/M2 gene signatures, can divide cervical patients into subgroups with different prognosis, tumor stage, different immune cell infiltration, and ICMs expression. Our findings may help to find suitable treatment strategy for cervical cancer patients with different TAMs gene signatures.
Non-HLA Antibodies and Epitope Mismatches in Kidney Transplant Recipients With Histological Antibody-Mediated Rejection
Authors: Crespo Marta , Llinàs-Mallol Laura , Redondo-Pachón Dolores , Butler Carrie , Gimeno Javier , Pérez-Sáez María José , Burballa Carla , Buxeda Anna , Arias-Cabrales Carlos , Folgueiras Montserrat , Sanz-Ureña Sara , Valenzuela Nicole M. , Reed Elaine F. , Pascual Julio
Published: July 2021

Background

Correlation between antibody-mediated rejection (ABMR) and circulating HLA donor-specific antibodies (HLA-DSA) is strong but imperfect in kidney transplant (KT) recipients, raising the possibility of undetected HLA-DSA or non-HLA antibodies contributing to ABMR. Detailed evaluation of the degree of HLA matching together with the identification of non-HLA antibodies in KT may help to decipher the antibody involved.

Methods

We retrospectively assessed patients with transplant biopsies scored following Banff’15 classification. Pre- and post-transplant serum samples were checked for HLA and non-HLA antibodies [MICA-Ab, angiotensin-II type-1-receptor (AT1R)-Ab, endothelin-1 type-A-receptor (ETAR)-Ab and crossmatches with primary aortic endothelial cells (EC-XM)]. We also analyzed HLA epitope mismatches (HLA-EM) between donors and recipients to explore their role in ABMR histology (ABMRh) with and without HLA-DSA.

Results

One-hundred eighteen patients with normal histology (n = 19), ABMRh (n = 52) or IFTA (n = 47) were studied. ABMRh patients were HLA-DSApos (n = 38, 73%) or HLA-DSAneg (n = 14, 27%). Pre-transplant HLA-DSA and AT1R-Ab were more frequent in ABMRh compared with IFTA and normal histology cases (p = 0.006 and 0.003), without differences in other non-HLA antibodies. Only three ABMRhDSAneg cases showed non-HLA antibodies. ABMRhDSAneg and ABMRhDSApos cases showed similar biopsy changes and graft-survival. Both total class II and DRB1 HLA-EM were associated with ABMRhDSApos but not with ABMRhDSAneg. Multivariate analysis showed that pre-transplant HLA-DSA (OR: 3.69 [1.31–10.37], p = 0.013) and AT1R-Ab (OR: 5.47 [1.78–16.76], p = 0.003) were independent predictors of ABMRhDSApos.

Conclusions

In conclusion, pre-transplant AT1R-Ab is frequently found in ABMRhDSApos patients. However, AT1R-Ab, MICA-Ab, ETAR-Ab or EC-XM+ are rarely found among ABMRhDSAneg patients. Pre-transplant AT1R-Ab may act synergistically with preformed or de novo HLA-DSA to produce ABMRhDSApos but not ABMRhDSAneg. HLA epitope mismatch associates with ABMRhDSApos compared with ABMRhDSAneg, suggesting factors other than HLA are responsible for the damage.
Improved Calibration and Data Processing Procedures of OPUS Optical Sensor for High-Resolution in situ Monitoring of Nitrate in Seawater
Authors: Nehir Münevver , Esposito Mario , Begler Christian , Frank Carsten , Zielinski Oliver , Achterberg Eric P.
Published: July 2021

Nitrate, an essential nutrient for primary production in natural waters, is optically detectable in the ultraviolet spectral region of 217–240 nm, with no chemical reagents required. Optical nitrate sensors allow monitoring at high temporal and spatial resolutions that are difficult to achieve with traditional approaches involving collection of discrete water samples followed by wet-chemical laboratory analysis. The optical nitrate measurements are however subject to matrix interferences in seawater, including bromide, at the spectral range of interest. Significant progress has been made over the last 10 years in improving data quality for seawater nitrate analysis using the ISUS and SUNA (Seabird Scientific, United States) optical sensors. Standardization of sensor calibration and data processing procedures are important for ensuring comparability of marine nitrate data reported in different studies. Here, we improved the calibration and data processing of the OPUS sensor (TriOS GmbH, Germany), and tested five OPUS sensors simultaneously deployed under identical conditions in the laboratory in terms of inter-sensor similarities and differences. We also improved the sampling interval of the OPUS to 3 s in a continuous mode by a custom-built controller, which facilitates the integration of the sensor into autonomous profiling systems. Real-time, high-resolution, in situ measurements were conducted through (1) underway surface measurements in the southeastern North Sea and (2) depth profiles on a conductivity–temperature–depth frame in the tropical Atlantic Ocean. The nitrate data computed from the optical measurements of the sensor agreed with data from discrete water samples analyzed via conventional wet-chemical methods. This work demonstrates that the OPUS sensor, with improved calibration and data processing procedures, allows in situ quantification of nitrate concentrations in dynamic coastal waters and the open ocean, with an accuracy better than ∼2 μM and short-term precision of 0.4 μM NO3–. The OPUS has a unique depth rating of 6,000 m and is a good and cost-effective nitrate sensor for the research community.
The Effect of Antibacterial and Waterproof Coating Prepared From Hexadecyltrimethoxysilane and Nano-Titanium Dioxide on Wood Properties
Authors: Yang Lechen , Wu Yan , Yang Feng , Wang Wenhao
Published: July 2021

As one of the most sustainable resources, wood has been widely used in the fields of construction, decoration, flooring and furniture. However, the micron-scale porous structure of wood makes it have strong moisture absorption capacity and is susceptible to bacterial adhesion. In order to expand its utility in more applications of wood products, it is necessary to make the wood have a certain antibacterial and waterproof properties. This study demonstrates a method of using hexadecyltrimethoxysilane and nano-titanium dioxide to prepare antibacterial and waterproof coating and apply it to wood surfaces. Studies have shown that this kind of wood coated with an antibacterial waterproof coating has excellent antibacterial properties (antibacterial rate as high as 99%) and waterproof properties. In addition, this antibacterial and waterproof coating does not cause a major change in the color of the wood, and at the same time increase the tensile strength and hardness to a certain extent. The above-mentioned properties of this antibacterial and waterproof coating provide a new idea for the preparation of wood coatings.
Is 70Zn(d,x)67Cu the Best Way to Produce 67Cu for Medical Applications?
Authors: Nigron Etienne , Guertin Arnaud , Haddad Ferid , Sounalet Thomas
Published: July 2021

The pair of copper radionuclides 64Cu/67Cu (T1/2 = 12. 7 h/61.8 h) allows, respectively, PET imaging and targeted beta therapy. An analysis of the different production routes of 67Cu with charged particles was performed and the reaction 70Zn(d,x) route was identified as a promising one. It may allow the production of 67Cu without 64Cu. The production cross section has been measured up to 28.7 MeV. Measurements were done using the well-known stacked-foils technique using 97.5% enriched 70Zn homemade electroplated targets. These measurements complement at higher incident energies the only set of data available in nuclear databases. The results show that using a 26 MeV deuteron beam and a highly enriched 70Zn target, it is possible to produce high purity 67Cu comparable to that obtained using photoproduction. This production route can be of interest for future linear accelerators under development where mA deuteron beams can be available if adequate targetry is developed.
Whole Genome Sequence of Bacillus velezensis Strain GUMT319: A Potential Biocontrol Agent Against Tobacco Black Shank Disease
Authors: Ding Haixia , Mo Weidi , Yu Shui , Cheng Huanhuan , Peng Lijuan , Liu Zuoyi
Published: July 2021

Phytophthora nicotianae causes black shank, a serious soil-borne disease, in tobacco. In this study, the Bacillus strain GUMT319 was isolated from the rhizosphere of healthy tobacco plants grown in a field in Guizhou with a high incidence of tobacco black shank. Genome sequencing revealed that GUMT319 contained a single circular chromosome 3,940,023 bp in length, with 4,053 predicted genes and an average GC content of 46.6%. Based on phylogenomic analyses, GUMT319 was designated as Bacillus velezensis. The genome of GUMT319 contained more than 60 genes and 13 gene clusters that have previously been found to be active in antifungal mechanisms, biofilm formation, and chemotaxis motility. Additionally, confocal laser scanning microscopy and scanning electron microscopy showed that GUMT319 formed a spatially organized biofilm in vivo. In addition, lauric acid negatively regulated biofilm formation. This is the first study to report that nicotine in tobacco root exudates was a chemoattractant for biocontrol Bacillus strains. In this study, we identified new interactions between beneficial microorganisms and tobacco roots in the rhizosphere. Moreover, dual culture tests in vitro showed that GUMT319 inhibited the growth of P. nicotianae and also displayed inhibitory effects against eight other plant pathogens, namely, Colletotrichum scovillei, Colletotrichum capsici, Fusarium carminascens, Sclerotinia sclerotiorum, Alternaria alternata, Phomopsis sp., Phyllosticta sorghina, and Exserohilum turcicum. Furthermore, GUMT319 exhibited > 70% control efficiency against tobacco black shank in field experiments conducted in 2018–2020. Thus, GUMT319 was more effective in controlling the incidence of tobacco black shank than other treatments including fungicide application. Overall, these results suggested that GUMT319 (B. velezensis) could be used as a potential biocontrol agent against tobacco black shank.
Co-infections as Modulators of Disease Outcome: Minor Players or Major Players?
Authors: Devi Priti , Khan Azka , Chattopadhyay Partha , Mehta Priyanka , Sahni Shweta , Sharma Sachin , Pandey Rajesh
Published: July 2021

Human host and pathogen interaction is dynamic in nature and often modulated by co-pathogens with a functional role in delineating the physiological outcome of infection. Co-infection may present either as a pre-existing pathogen which is accentuated by the introduction of a new pathogen or may appear in the form of new infection acquired secondarily due to a compromised immune system. Using diverse examples of co-infecting pathogens such as Human Immunodeficiency Virus,Mycobacterium tuberculosisand Hepatitis C Virus, we have highlighted the role of co-infections in modulating disease severity and clinical outcome. This interaction happens at multiple hierarchies, which are inclusive of stress and immunological responses and together modulate the disease severity. Already published literature provides much evidence in favor of the occurrence of co-infections during SARS-CoV-2 infection, which eventually impacts the Coronavirus disease-19 outcome. The availability of biological models like 3D organoids, mice, cell lines and mathematical models provide us with an opportunity to understand the role and mechanism of specific co-infections. Exploration of multi-omics-based interactions across co-infecting pathogens may provide deeper insights into their role in disease modulation.
Microbiome Structure of the Aphid Myzus persicae (Sulzer) Is Shaped by Different Solanaceae Plant Diets
Authors: He Baoyu , Chen Xiaoyulong , Yang Hong , Cernava Tomislav
Published: July 2021

Myzus persicae (Sulzer) is an important insect pest in agriculture that has a very broad host range. Previous research has shown that the microbiota of insects has implications for their growth, development, and environmental adaptation. So far, there is little detailed knowledge about the factors that influence and shape the microbiota of aphids. In the present study, we aimed to investigate diet-induced changes in the microbiome of M. persicae using high-throughput sequencing of bacterial 16S ribosomal RNA gene fragments in combination with molecular and microbiological experiments. The transfer of aphids to different plants from the Solanaceae family resulted in a substantial decrease in the abundance of the primary symbiont Buchnera. In parallel, a substantial increase in the abundance of Pseudomonas was observed; it accounted for up to 69.4% of the bacterial community in M. persicae guts and the attached bacteriocytes. In addition, we observed negative effects on aphid population dynamics when they were transferred to pepper plants (Capsicum annuum L.). The microbiome of this treatment group showed a significantly lower increase in the abundance of Pseudomonas when compared with the other Solanaceae plant diets, which might be related to the adaptability of the host to this diet. Molecular quantifications of bacterial genera that were substantially affected by the different diets were implemented as an additional verification of the microbiome-based observations. Complementary experiments with bacteria isolated from aphids that were fed with different plants indicated that nicotine-tolerant strains occur in Solanaceae-fed specimens, but they were not restricted to them. Overall, our mechanistic approach conducted under controlled conditions provided strong indications that the aphid microbiome shows responses to different plant diets. This knowledge could be used in the future to develop environmentally friendly methods for the control of insect pests in agriculture.
Dysbiosis of Gut Microbiota in Patients With Acute Myocardial Infarction
Authors: Han Ying , Gong Zhaowei , Sun Guizhi , Xu Jing , Qi Changlu , Sun Weiju , Jiang Huijie , Cao Peigang , Ju Hong
Published: July 2021

Acute myocardial infarction (AMI) continues as the main cause of morbidity and mortality worldwide. Interestingly, emerging evidence highlights the role of gut microbiota in regulating the pathogenesis of coronary heart disease, but few studies have systematically assessed the alterations and influence of gut microbiota in AMI patients. As one approach to address this deficiency, in this study the composition of fecal microflora was determined from Chinese AMI patients and links between gut microflora and clinical features and functional pathways of AMI were assessed. Fecal samples from 30 AMI patients and 30 healthy controls were collected to identify the gut microbiota composition and the alterations using bacterial 16S rRNA gene sequencing. We found that gut microflora in AMI patients contained a lower abundance of the phylum Firmicutes and a slightly higher abundance of the phylum Bacteroidetes compared to the healthy controls. Chao1 (P = 0.0472) and PD-whole-tree (P = 0.0426) indices were significantly lower in the AMI versus control group. The AMI group was characterized by higher levels of the genera Megasphaera, Butyricimonas, Acidaminococcus, and Desulfovibrio, and lower levels of Tyzzerella 3, Dialister, [Eubacterium] ventriosum group, Pseudobutyrivibrio, and Lachnospiraceae ND3007 group as compared to that in the healthy controls (P < 0.05). The common metabolites of these genera are mostly short-chain fatty acids, which reveals that the gut flora is most likely to affect the occurrence and development of AMI through the short-chain fatty acid pathway. In addition, our results provide the first evidence revealing remarkable differences in fecal microflora among subgroups of AMI patients, including the STEMI vs. NSTEMI, IRA-LAD vs. IRA-Non-LAD and Multiple (≥2 coronary stenosis) vs. Single coronary stenosis groups. Several gut microflora were also correlated with clinically significant characteristics of AMI patients, including LVEDD, LVEF, serum TnI and NT-proBNP, Syntax score, counts of leukocytes, neutrophils and monocytes, and fasting serum glucose levels. Taken together, the data generated enables the prediction of several functional pathways as based on the fecal microfloral composition of AMI patients. Such information may enhance our comprehension of AMI pathogenesis.