bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Monoclonal Antibody Blockade of Long Fragment Neurotensin on Weight Loss, Behavior, and Metabolic Traits After High-Fat Diet Induced Obesity
Authors: Wu Zherui , Stadler Nicolas , Abbaci Amazigh , Liu Jin , Boullier Agnès , Marie Nicolas , Biondi Olivier , Moldes Marthe , Morichon Romain , Feve Bruno , Melander Olle , Forgez Patricia
Published: October 2021

Background

Obesity is a major public health problem of our time as a risk factor for cardiometabolic disease and the available pharmacological tools needed to tackle the obesity pandemic are insufficient. Neurotensin (NTS) is a 13 amino acid peptide, which is derived from a larger precursor hormone called proneurotensin or Long Form NTS (LF NTS). NTS modulates neuro-transmitter release in the central system nervous, and facilitates intestinal fat absorption in the gastrointestinal tract. Mice lacking LF NTS are protected from high fat diet (HFD) induced obesity, hepatic steatosis and glucose intolerance. In humans, increased levels of LF NTS strongly and independently predict the development of obesity, diabetes mellitus, cardiovascular disease and mortality. With the perspective to develop therapeutic tools to neutralize LF NTS, we developed a monoclonal antibody, specifically inhibiting the function of the LF NTS (LF NTS mAb). This antibody was tested for the effects on body weight, metabolic parameters and behavior in mice made obese by high-fat diet.

Methods

C57bl/6j mice were subjected to high-fat diet (HFD) until they reached an obesity state, then food was switched to chow. Mice were treated with either PBS (control therapy) or LF NTS mAb at the dose of 5 mg/kg once a week (i.v.). Mice weight, plasma biochemical analysis, fat and muscle size and distribution and behavioral tests were performed during the losing weight period and the stabilization period.

Results

Obese mice treated with the LF NTS mAb lost weight significantly faster than the control treated group. LF NTS mAb treatment also resulted in smaller fat depots, increased fecal cholesterol excretion, reduced liver fat and larger muscle fiber size. Moreover, mice on active therapy were also less stressed, more curious and more active, providing a possible explanation to their weight loss.

Conclusion

Our results demonstrate that in mice subjected to HFD-induced obesity, a blockade of LF NTS with a monoclonal antibody results in reduced body weight, adipocyte volume and increased muscle fiber size, possibly explained by beneficial effects on behavior. The underlying mechanisms as well as any future role of LF NTS mAb as an anti-obesity agent warrants further studies.
The Origins of Ion Conductivity in MOF-Ionic Liquids Hybrid Solid Electrolytes
Authors: Zettl Roman , Hanzu Ilie
Published: October 2021

Fast Li+solid ion conductors are a key component of all-solid-state batteries, a technology currently under development. The possible use of metallic lithium as active material in solid-state batteries warrants a quantum step improvement of battery specific energy, enabling further electric vehicles application. Hereby, we report the synthesis and ion conduction properties of a new solid hybrid electrolyte based on the MIL-121 metal organic framework (MOF) structure. After an ion exchange procedure that introduces Li+in the structure, a known quantity of a soaking electrolyte is incorporated. The soaking electrolyte is based on the EMIM-TFSI ionic liquid, thus we can classify our formulation as a MOF–ionic liquid hybrid solid electrolyte. Electrical conductivity is investigated by impedance spectroscopy and preliminary studies of ion dynamics are conducted by7Li NMR. The field of MOF-based ion conductors remains in incipient stages of research. Our report paves the way towards the rational design of new solid-state ion conductors.
Financial Innovation, Sustainable Economic Growth, and Credit Risk: A Case of the ASEAN Banking Sector
Authors: Khan Ali Burhan , Fareed Muhammad , Salameh Anas A. , Hussain Haroon
Published: October 2021

A dynamic and rapidly changing global financial environment is posing various risks for the banking sector. Therefore, the future of the Association of Southeast Asian Nations (ASEAN) banks depends on how efficiently and effectively they manage these risks. Among these risks, a credit risk is the most crucial risk for the banking sector. Thus, the current study aims to analyze the impact of financial innovation and sustainable economic growth on the credit risk of ASEAN banks. For this purpose, a sample of 4 ASEAN countries from 2011 to 2018 is selected, and by applying a panel-corrected standard error (PCSE) approach, both variables were found to be a significant contributor toward the credit risk. Current research will not only be beneficial for the management of ASEAN countries’ banks but also provide help to the overall financial industry and their respective regulatory bodies to understand the behavior of ASEAN banks’ credit risk regarding financial innovation and economic growth. Thus, this study will play an essential role concerning the stability of the banking sector in the ASEAN region.
Tree–Crop Ecological and Physiological Interactions Within Climate Change Contexts: A Mini-Review
Authors: Gonçalves Berta , Morais Maria Cristina , Pereira Sandra , Mosquera-Losada Maria Rosa , Santos Mário
Published: October 2021

The effects of climate change are increasingly noticed worldwide, and crops are likely to be impacted in direct and indirect ways. Thus, it is urgent to adopt pliable strategies to reduce and/or mitigate possible adverse effects to meet the growing demand for sustainable and resilient food production. Monoculture cropping is globally the most common production system. However, adaptation to ongoing climate change, namely, to more extreme environmental conditions, has renewed the interest in other practices such as agroforestry, agroecology, and permaculture. This article provides an overview of ecological and physiological interactions between trees and crops in Mediterranean agroforestry systems and compares them with those from monocultures. The advantages and disadvantages of both systems are explored. The added value of modeling in understanding the complexity of interactions within agroforestry systems, supporting decision-making under current and future weather conditions, is also pinpointed. Several interactions between trees and crops might occur in agroforestry systems, leading to mutual positive and/or negative effects on growth, physiology, and yield. In this sense, selecting the most suitable combination of tree/crop species in mixtures may be best be indicated by complementary traits, which are crucial to maximizing trade-offs, improving productivity, ecosystem services, and environmental sustainability.
Flight Altitudes of Raptors in Southern Africa Highlight Vulnerability of Threatened Species to Wind Turbines
Authors: McClure Christopher J. W. , Dunn Leah , McCabe Jennifer D. , Rolek Brian W. , Botha André , Virani Munir Z. , Buij Ralph , Katzner Todd E.
Published: October 2021

Energy infrastructure, particularly for wind power, is rapidly expanding in Africa, creating the potential for conflict with at-risk wildlife populations. Raptor populations are especially susceptible to negative impacts of fatalities from wind energy because individuals tend to be long-lived and reproduce slowly. A major determinant of risk of collision between flying birds and wind turbines is the altitude above ground at which a bird flies. We examine 18,710 observations of flying raptors recorded in southern Africa and we evaluate, for 49 species, the frequency with which they were observed to fly at the general height of a wind turbine rotor-swept zone (50–150 m). Threatened species, especially vultures, were more likely to be observed at turbine height than were other species, suggesting that these raptors are most likely to be affected by wind power development across southern Africa. Our results highlight that threatened raptor species, particularly vultures, might be especially impacted by expanded wind energy infrastructure across southern Africa.
Metabolome and Transcriptome Analysis of Liver and Oocytes of Schizothorax o’connori Raised in Captivity
Authors: Zhou Jianshe , Wang Wanliang , Li Zhichao , Zhang Chi , Wan Zhiyi , Sun Shuaijie , Zeng Benhe , Li Ming , Sun Guirong
Published: October 2021

Schizothorax o’connori (S. o’connori) is a representative tetraploid species in the subfamily Schizothoracinae and an important endemic fish in the Qinghai-Tibet Plateau. However, the domestication of S. o’connori remains challenging due to the lack of basic research. Here, we investigated the effects of artificial feeding on the oocytes and liver of S. o’connori by comparing the histological, metabolomic, and transcriptomic data. Histological results showed that the oocytes and liver of captive-reared S. o’connori had abnormal cell morphology. After comparison with the self-built database, a total of 233 metabolites were annotated. In oocytes, a total of 37 differentially accumulated metabolites (DAMs) were detected and two pathways were significantly enriched. There were obvious differences in the metabolites related to ovarian development, including pregnenolone and arachidonic acid. In liver, a total of 70 DAMs were detected and five pathways were significantly enriched. Based on the transcriptomic data, a total of 159 differentially expressed genes (DEGs) were significantly related with cell growth and death pathway in oocytes, while a total of 2841 DEGs were significantly related with 102 pathways in liver. Comparing the metabolomic and transcriptomic data showed that there were three common significant enrichment pathways in liver, including biosynthesis of unsaturated fatty acids, starch and sucrose metabolism, and fatty acid biosynthesis. These results showed that special attention should be given to the composition and intake of fatty acids during the artificial breeding of S. o’connori. In addition, many of metabolite-gene pairs were related to adenosine 5′-diphosphate, adenosine monophosphate, and pregnenolone. In summary, these data provide an overview of global metabolic and transcriptomic resources and broaden our understanding of captive-reared S. o’connori.
First Detection in West Africa of a Mutation That May Contribute to Artemisinin Resistance Plasmodium falciparum
Authors: Zhao Hui , Pi Liang , Zhao Luyi , Qin Yucheng , Zeng Weilin , Xiang Zheng , Yang Qi , Pan Maohua , Li Xinxin , Zou Chunyan , Chen Xi , Zhao Wei , Lu Yuxin , Wu Yanrui , Duan Mengxi , Wang Xun , Li Xiaosong , Mazier Dominique , Huang Yaming , Yang Zhaoqing
Published: October 2021

Background: The spread of drug resistance has seriously impacted the effective treatment of infection with the malaria parasite, Plasmodium falciparum. Continuous monitoring of molecular marker polymorphisms associated with drug resistance in parasites is essential for malaria control and elimination efforts. Our study describes mutations observed in the resistance genes Pfkelch13, Pfcrt, and Pfmdr1 in imported malaria and identifies additional potential drug resistance-associated molecular markers.

Methods: Chinese patients infected in Africa with P. falciparum were treated with intravenous (IV) injections of artesunate 240–360 mg for 3–5 days while hospitalized and treated with oral dihydroartemisinin-piperaquine (DHP) for 3 days after hospital discharge. Blood samples were collected and PCR sequencing performed on genes Pfkelch13, Pfcrt, and Pfmdr1 from all isolates.

Results: We analyzed a total of 225 patients from Guangxi, China with P. falciparum malaria acquired in Africa between 2016 and 2018. All patients were cured completely after treatment. The F446I mutation of the Pfkelch13 gene was detected for the first time from samples of West African P. falciparum, with a frequency of 1.0%. Five haplotypes of Pfcrt that encode residues 72–76 were found, with the wild-type CVMNK sequence predominating (80.8% of samples), suggesting that the parasites might be chloroquine sensitive. For Pfmdr1, N86Y (13.1%) and Y184F (58.8%) were the most prevalent, suggesting that artemether-lumefantrine may not, in general, be a suitable treatment for the group.

Conclusions: For the first time, this study detected the F446I mutation of the Pfkelch13 gene from Africa parasites that lacked clinical evidence of resistance. This study provides the latest data for molecular marker surveillance related to antimalarial drug resistance genes Pfkelch13, Pfcrt, and Pfmdr1 imported from Africa, in Guangxi, China from Chinese migrate workers.

Clinical Trial Registration: ChiCTROPC17013106.
MiR-124-3p Suppresses the Dysfunction of High Glucose-Stimulated Endothelial Cells by Targeting G3BP2
Authors: Zhao Haijun , He Yanhui
Published: October 2021

Background: Diabetic retinopathy (DR) is the most important manifestation of diabetic microangiopathy. MicroRNAs (miRNAs), members of non-coding RNAs, have been frequently reported to regulate various diseases including DR. MiR-124-3p is involved in DR based on bioinformatics. The current study aimed to investigate the role of miR-124-3p in high glucose (HG)-treated human retinal microvascular endothelial cells (HRMECs), an in vitro model of DR.

Methods: Bioinformatics analysis was applied to reveal the targets downstream miR-124-3p. A series of assays including CCK-8, luciferase reporter, western blot, and tube formation assays were used to explore the function and mechanism of miR-124-3p in HG-stimulated HRMECs.

Results: We found out that miR-124-3p was downregulated in HG-stimulated HRMECs. Functionally, miR-124-3p overexpression restrained the HG-induced cell injury of HRMECs. Mechanistically, we predicted 5 potential target mRNAs of miR-124-3p. G3BP stress granule assembly factor 2 (G3BP2) was validated to bind with miR-124-3p. Rescue assays showed that miR-124-3p suppressed cell injury of HG-stimulated HRMECs through G3BP2. In addition, miR-124-3p regulated the p38MAPK signaling pathway by G3BP2, and G3BP2 promoted injury of HG-treated HRMECs through the activation of the p38MAPK signaling pathway.

Conclusion: MiR-124-3p suppressed the dysfunctions of HG-treated HRMECs by targeting G3BP2 and activating the p38MAPK signaling. This new discovery provided a potential biomarker for DR treatment.
Pathogenic Mechanism of Der p 38 as a Novel Allergen Homologous to RipA and RipB Proteins in Atopic Dermatitis
Authors: Jeon Hyang , Kim Geunyeong , Kashif Ayesha , Hong Min Hwa , Lee Ji-Sook , Hong Yujin , Park Beom Seok , Yang Eun Ju , Kim In Sik
Published: October 2021

Atopic dermatitis (AD) is a chronic relapsing pruritic disease encompassing skin inflammation and barrier dysfunction. House dust mites are key allergens that augment the development of atopic dermatitis. We aimed to investigate the pathogenic mechanism of AD due to Der p 38, recently identified by us. The frequency of IgE reactivity to Der p 38 in AD subjects was 52.6% (10/19) in the skin prick test and 57.9% (11/19) in the dot blot assay. In human keratinocyte HaCaT cells, Der p 38 triggered the impairment of filaggrin expression and induced pro-inflammatory cytokines such as IL-6, IL-8 and MCP-1 through TLR4, PI3K, AKT, c−Jun N−terminal kinase (JNK) and NF-κB pathway. Supernatants from Der p 38-treated cells blocked filaggrin expression and neutrophil apoptosis. The anti-apoptotic effect of the Der p 38-released molecules on neutrophils was accomplished by inhibition of the caspase 9/3 pathway, and by increased MCL-1 expression and BCL-2/BAX expression ratio. In C57BL/6 wild type (WT) mice, Der p 38 induced a dose-dependent increase of AD-like skin lesions, with enhanced expressions of total and Der p 38-specific IgE. Der p 38 also diminished the expressions of skin barrier proteins and induced JNK activation. However, the AD-like features following cutaneous Der p 38 exposure were observed to be reduced in the TLR4 knockout (KO) group, as compared to the WT group. Skin infiltration of neutrophils, eosinophils and mast cells was increased in the WT mice, but was not portrayed in the TLR4 KO mice. These findings indicate that Der p 38 is a novel mite allergen that triggers AD by lowering skin barrier proteins and increasing inflammatory cells. Results of this study have thereby paved the way to unveil the pathogenic mechanisms of AD.
Pleiotropic Effects of Glucocorticoids on the Immune System in Circadian Rhythm and Stress
Authors: Shimba Akihiro , Ejima Aki , Ikuta Koichi
Published: October 2021

Glucocorticoids (GCs) are a class of steroid hormones secreted from the adrenal cortex. Their production is controlled by circadian rhythm and stress, the latter of which includes physical restraint, hunger, and inflammation. Importantly, GCs have various effects on immunity, metabolism, and cognition, including pleiotropic effects on the immune system. In general, GCs have strong anti-inflammatory and immunosuppressive effects. Indeed, they suppress inflammatory cytokine expression and cell-mediated immunity, leading to increased risks of some infections. However, recent studies have shown that endogenous GCs induced by the diurnal cycle and dietary restriction enhance immune responses against some infections by promoting the survival, redistribution, and response of T and B cellsviacytokine and chemokine receptors. Furthermore, although GCs are reported to reduce expression of Th2 cytokines, GCs enhance type 2 immunity and IL-17-associated immunity in some stress conditions. Taken together, GCs have both immunoenhancing and immunosuppressive effects on the immune system.
Plasma EVs Display Antigen-Presenting Characteristics in Patients With Allergic Rhinitis and Promote Differentiation of Th2 Cells
Authors: Fang Shu-Bin , Zhou Zhi-Rou , Peng Ya-Qi , Liu Xiao-Qing , He Bi-Xin , Chen De-Hua , Chen Dong , Fu Qing-Ling
Published: October 2021

Background

Allergic rhinitis (AR) is characterized by IgE-mediated mucosa response after exposure to allergens. Extracellular vesicles (EVs) are nano-size vesicles containing biological cargos for intercellular communications. However, the role of plasma EVs in pathogenesis of AR remains largely unknown.

Methods

Plasma EVs from patients with AR were isolated, quantified, and characterized. The expression of Der p 1 and antigen-presenting molecules on EVs was determined by Western blot, flow cytometry, or ELISA. PKH26- and CFSE (carboxyfluorescein succinimidyl ester)-stained AR-EVs were used to determine the uptake of EVs by CD4+T cells and their effects on CD4+T cell proliferation, respectively.

Results

Plasma EVs in healthy control (HC) and AR patients were similar in the concentration of particles, expression for specific EV markers, and both had structural lipid bilayer. However, the levels of Der p 1 on plasma EVs from both mild and moderate-severe AR patients were significantly higher than that on HC. The levels of antigen-presenting molecules on plasma EVs were similar from three subjects. Moreover, levels of Der p 1 on EVs in plasma, but not nasal secretion, were significantly associated with the symptom score of AR patients and level of plasma IL-13. Additionally, plasma EVs from patients with AR promoted the development of Th2 cells, while no effect was found on CD4+ T-cell proliferation.

Conclusions

Plasma EVs derived from patients with AR exhibited antigen-presenting characteristics and promoted differentiation of Th2 cells, thus providing novel understanding of the pathogenesis of AR.
Targeting Microglial α-Synuclein/TLRs/NF-kappaB/NLRP3 Inflammasome Axis in Parkinson’s Disease
Authors: Li Yunna , Xia Yun , Yin Sijia , Wan Fang , Hu Junjie , Kou Liang , Sun Yadi , Wu Jiawei , Zhou Qiulu , Huang Jinsha , Xiong Nian , Wang Tao
Published: October 2021

According to emerging studies, the excessive activation of microglia and the subsequent release of pro-inflammatory cytokines play important roles in the pathogenesis and progression of Parkinson’s disease (PD). However, the exact mechanisms governing chronic neuroinflammation remain elusive. Findings demonstrate an elevated level of NLRP3 inflammasome in activated microglia in the substantia nigra of PD patients. Activated NLRP3 inflammasome aggravates the pathology and accelerates the progression of neurodegenerative diseases. Abnormal protein aggregation of α-synuclein (α-syn), a pathologically relevant protein of PD, were reported to activate the NLRP3 inflammasome of microglia through interaction with toll-like receptors (TLRs). This eventually releases pro-inflammatory cytokines through the translocation of nuclear factor kappa-B (NF-κB) and causes an impairment of mitochondria, thus damaging the dopaminergic neurons. Currently, therapeutic drugs for PD are primarily aimed at providing relief from its clinical symptoms, and there are no well-established strategies to halt or reverse this disease. In this review, we aimed to update existing knowledge on the role of the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis and microglial activation in PD. In addition, this review summarizes recent progress on the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis of microglia as a potential target for PD treatment by inhibiting microglial activation.
γδT Cells Are Required for CD8+ T Cell Response to Vaccinia Viral Infection
Authors: Dai Rui , Huang Xiaopei , Yang Yiping
Published: October 2021

Vaccinia virus (VV) is the most studied member of the poxvirus family, is responsible for the successful elimination of smallpox worldwide, and has been developed as a vaccine vehicle for infectious diseases and cancer immunotherapy. We have previously shown that the unique potency of VV in the activation of CD8+T cell response is dependent on efficient activation of the innate immune system through Toll-like receptor (TLR)-dependent and -independent pathways. However, it remains incompletely defined what regulate CD8+T cell response to VV infection. In this study, we showed that γδT cells play an important role in promoting CD8+T cell response to VV infection. We found that γδT cells can directly present viral antigens in the context of MHC-I for CD8+T cell activation to VVin vivo, and we further demonstrated that cell-intrinsic MyD88 signaling in γδT cells is required for activation of γδT cells and CD8+T cells. These results illustrate a critical role for γδT cells in the regulation of adaptive T cell response to viral infection and may shed light on the design of more effective vaccine strategies based on manipulation of γδT cells.
Alternative Complement Pathway Inhibition Does Not Abrogate Meningococcal Killing by Serum of Vaccinated Individuals
Authors: Ispasanie Emma , Muri Lukas , Schubart Anna , Thorburn Christine , Zamurovic Natasa , Holbro Thomas , Kammüller Michael , Pluschke Gerd
Published: October 2021

Dysregulation of complement activation causes a number of diseases, including paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. These conditions can be treated with monoclonal antibodies (mAbs) that bind to the complement component C5 and prevent formation of the membrane attack complex (MAC). While MAC is involved in uncontrolled lysis of erythrocytes in these patients, it is also required for serum bactericidal activity (SBA), i.e. clearance of encapsulated bacteria. Therefore, terminal complement blockage in these patients increases the risk of invasive disease by Neisseria meningitidis more than 1000-fold compared to the general population, despite obligatory vaccination. It is assumed that alternative instead of terminal pathway inhibition reduces the risk of meningococcal disease in vaccinated individuals. To address this, we investigated the SBA with alternative pathway inhibitors. Serum was collected from adults before and after vaccination with a meningococcal serogroup A, C, W, Y capsule conjugate vaccine and tested for meningococcal killing in the presence of factor B and D, C3, C5 and MASP-2 inhibitors. B meningococci were not included in this study since the immune response against protein-based vaccines is more complex. Unsurprisingly, inhibition of C5 abrogated killing of meningococci by all sera. In contrast, both factor B and D inhibitors affected meningococcal killing in sera from individuals with low, but not with high bactericidal anti-capsular titers. While the anti-MASP-2 mAb did not impair SBA, inhibition of C3 impeded meningococcal killing in most, but not in all sera. These data provide evidence that vaccination can provide protection against invasive meningococcal disease in patients treated with alternative pathway inhibitors.
Speed and Location Both Matter: Antigen Stimulus Dynamics Controls CAR-T Cell Response
Authors: Liu Can , Qi Timothy , Milner J. Justin , Lu Yong , Cao Yanguang
Published: October 2021

Despite the success in B-cell malignancies, chimeric antigen receptor (CAR)-T cell therapies have not yet demonstrated consistent efficacy across all patients and tumor types, particularly against solid tumors. Higher rates of T cell exhaustion are associated with inferior clinical outcomes following CAR-T cell therapy, which is prevalent in solid tumors. T cell exhaustion may originate from persistent and chronic antigen stimulation by tumor cells that resist and/or evade T cell-mediated killing. We exploited CAR-T exhaustion with a classic negative feedback model (incoherent feedforward loop, IFFL) to investigate the balance between CAR-T cell activation and exhaustion under different antigen presentation dynamics. Built upon the experimental and clinical data, we hypothesize that the speed and anatomical location of antigenic stimulation are both crucial to CAR-T cell response. Chronic antigenic stimulation as well as the harsh tumor microenvironment present multiple barriers to CAR-T cell efficacy in solid tumors. Many therapeutic strategies are individually insufficient to improve of CAR-T responses against solid tumors, as they clear but one of the many barriers CAR-T cells face in solid tumors. A combination strategy targeting multiple barriers holds promise to improve CAR-T therapy in solid tumors.
Non-Invasive Antibody Assessment in Saliva to Determine SARS-CoV-2 Exposure in Young Children
Authors: Heinzel Constanze , Pinilla Yudi T. , Elsner Käthe , Friessinger Evelyn , Mordmüller Benjamin , Kremsner Peter G. , Held Jana , Fendel Rolf , Kreidenweiss Andrea
Published: October 2021

Saliva is a body fluid with hitherto unused potential for the assessment of SARS-CoV-2 antibodies. Specific antibodies can indicate a past SARS-CoV-2 infection and allow to estimate the proportion of individuals with a potential protective immunity. First, we carefully characterized plasma samples obtained from adult control groups with and without prior SARS-CoV-2 infection using certified reference ELISAs. Simultaneously collected saliva samples of confirmed convalescent and negative individuals where then used to validate the herein newly developed ELISA for the detection of SARS-CoV-2 IgG antibodies in saliva. The saliva ELISA was applied to assess SARS-CoV-2 exposure in young children (N = 837) in the age between 1 and 10 years in Tübingen, Germany, towards the end of the first pandemic year 2020. Sensitivity and specificity of the new saliva ELISA was 87% and 100%, respectively. With 12% of all Tübingen children sampled via their respective educational institutions, estimates of SARS-CoV-2 antibody prevalence was 1.6%. Interestingly, only 0.4% preschool kids were positive compared to 3.0% of primary school children. Less than 20% of positive children self-reported symptoms within two months prior to saliva sampling that could be associated - but not exclusively - with a SARS-CoV-2 infection. The saliva ELISA is a valid and suitable protocol to enable population-based surveys for SARS-CoV-2 antibodies. Using non-invasive sampling and saliva ELISA testing, we found that prevalence of SARS-CoV-2 antibodies was significantly lower in young children than in primary school children.
Serum LAG-3 Predicts Outcome and Treatment Response in Hepatocellular Carcinoma Patients With Transarterial Chemoembolization
Authors: Guo Mengzhou , Qi Feng , Rao Qianwen , Sun Jialei , Du Xiaojing , Qi Zhuoran , Yang Biwei , Xia Jinglin
Published: October 2021

Background

Transarterial chemoembolization (TACE) stands for the most commonly utilized therapy for hepatocellular carcinoma (HCC) worldwide. This study was to explore the potential predictive and prognostic roles of LAG-3 and PD-L1 as serum biomarkers in HCC patients underwent TACE treatment.

Methods

A total of 100 HCC patients receiving TACE as well as 30 healthy controls were enrolled in the study. Serum LAG-3 and PD-L1 levels were determined at baseline and 3 day after TACE using enzyme-linked immunosorbent assay (ELISA).

Results

We found serum levels of LAG-3 and PD-L1 were significantly elevated in HCC patients compared with healthy controls. Interestingly, patients with low pre-TACE and post-TACE levels of LAG-3 but not PD-L1 had a high probability of achieving an objective response (OR) after TACE treatment. Additionally, high pre-TACE LAG-3 level was correlated with poor disease outcome, and the patients with both high serum LAG-3 and PD-L1 level had the shorter overall survival (OS) than patients who are either PD-L1 or LAG-3 high or both PD-L1 and LAG-3 low. High pre-TACE serum LAG-3 level was positively associated with more cirrhosis pattern, advanced BCLC stage, pre-TACE alanine aminotransferase (ALT) level, and pre-TACE aspartate aminotransferase (AST) level. Furthermore, in 50 patients who underwent TACE, the serum LAG-3 level was significantly decreased at 3 day after TACE.

Conclusion

Both pre-TACE and post-TACE serum LAG-3 levels could serve as powerful predictors for tumor response of TACE, and high pre-TACE serum LAG-3 level was an indicator for poor prognosis in HCC.
Partners in Crime: Beta-Cells and Autoimmune Responses Complicit in Type 1 Diabetes Pathogenesis
Authors: Toren Eliana , Burnette KaLia S. , Banerjee Ronadip R. , Hunter Chad S. , Tse Hubert M.
Published: October 2021

Type 1 diabetes (T1D) is an autoimmune disease characterized by autoreactive T cell-mediated destruction of insulin-producing pancreatic beta-cells. Loss of beta-cells leads to insulin insufficiency and hyperglycemia, with patients eventually requiring lifelong insulin therapy to maintain normal glycemic control. Since T1D has been historically defined as a disease of immune system dysregulation, there has been little focus on the state and response of beta-cells and how they may also contribute to their own demise. Major hurdles to identifying a cure for T1D include a limited understanding of disease etiology and how functional and transcriptional beta-cell heterogeneity may be involved in disease progression. Recent studies indicate that the beta-cell response is not simply a passive aspect of T1D pathogenesis, but rather an interplay between the beta-cell and the immune system actively contributing to disease. Here, we comprehensively review the current literature describing beta-cell vulnerability, heterogeneity, and contributions to pathophysiology of T1D, how these responses are influenced by autoimmunity, and describe pathways that can potentially be exploited to delay T1D.
Detection of Ecological Thresholds and Selection of Indicator Taxa for Epibenthic Communities Exposed to Multiple Pressures
Authors: Isabel Laurie , Beauchesne David , McKindsey Chris , Archambault Philippe
Published: October 2021

The estuary and the Gulf of St. Lawrence (EGSL), eastern Canada form a vast inland sea that is subjected to numerous anthropogenic pressures. Management tools are needed to detect and quantify their effect on benthic communities. The aims of this study are to analyze the spatial distribution of epibenthic communities in the EGSL and quantify the impact of important pressures on them to identify indicator taxa. Epibenthic communities were sampled at 1314 EGSL sites between 2011 and 2018 by bottom trawling. Cluster analyses revealed the presence of six distinct epibenthic communities that seem to be strongly influenced by oxygen concentration. Threshold analyses confirm that oxygen is an important predictor of epibenthic community composition and distribution. A major oxygen threshold is observed around 50–100 μmol O2 L–1, resulting in a shift of community type. At these concentrations and below, opportunistic taxa dominate the community while sensitive taxa are absent or present at very low abundance. Biomass of the latter only starts to increase when oxygen concentrations reach 150 μmol O2 L–1. The species Actinostola callosa, Actinauge cristata, Ctenodiscus crispatus, and Brisaster fragilis were identified as good indicators for detecting this impact threshold forepibenthic communities. This study provides threshold-based indicator species that help to establish and monitor the ecological state of epibenthic communities in a marine ecosystem exposed to multiple pressures.
Protandric Transcriptomes to Uncover Parts of the Crustacean Sex-Differentiation Puzzle
Authors: Levy Tom , Zupo Valerio , Mutalipassi Mirko , Somma Emanuele , Ruocco Nadia , Costantini Maria , Abehsera Shai , Manor Rivka , Chalifa-Caspi Vered , Sagi Amir , Aflalo Eliahu D.
Published: October 2021

Hermaphrodite systems offer unique opportunities to study sexual differentiation, due to their high degree of sexual plasticity and to the fact that, unlike gonochoristic systems, the process is not confined to an early developmental stage. In protandric shrimp species, such as Hippolyte inermis and Pandalus platyceros, male differentiation is followed by transformation to femaleness during adulthood. The mechanisms controlling sexual differentiation have not been fully elucidated in crustaceans, but a key role has been attributed to the insulin-like hormone (IAG) produced by the androgenic gland (AG), a crustacean masculine endocrine organ. To uncover further transcriptomic toolkit elements affecting the sexual differentiation of H. inermis, we constructed eye and whole body RNA libraries of four representative stages during its protandric life cycle (immature, male, young female and mature female). The body libraries contained transcripts related to the reproductive system, among others, while the eye libraries contained transcripts related to the X-organ-sinus gland, a central endocrine complex that regulates crustacean reproduction. Binary pattern analysis, performed to mine for genes expressed differentially between the different life stages, yielded 19,605 and 6,175 transcripts with a specific expression pattern in the eye and body, respectively. Prominent sexually biased transcriptomic patterns were recorded for the IAG and vitellogenin genes, representing, respectively, a key factor within the masculine IAG-switch, and a precursor of the yolk protein, typical of feminine reproductive states. These patterns enabled the discovery of novel putative protein-coding transcripts exhibiting sexually biased expression in the H. inermis body and eye transcriptomes of males and females. Homologs to the above novel genes have been found in other decapod crustaceans, and a comparative study, using previously constructed transcriptomic libraries of another protandric shrimp, P. platyceros, showed similar sexually biased results, supporting the notion that such genes, mined from the H. inermis transcriptome, may be universal factors related to reproduction and sexual differentiation and their control in other crustaceans. This study thus demonstrates the potential of transcriptomic studies in protandric species to uncover unexplored layers of the complex crustacean sex-differentiation puzzle.
Polyol-Made Spinel Ferrite Nanoparticles—Local Structure and Operating Conditions: NiFe2O4 as a Case Study
Authors: Gaudisson T. , Nowak S. , Nehme Z. , Menguy N. , Yaacoub N. , Grenèche J.-M. , Ammar S.
Published: October 2021

We report the effect of a polyol-mediated annealing on nickel ferrite nanoparticles. By combining X-ray fluorescence spectroscopy, X-ray diffraction, and 57Fe Mössbauer spectrometry, we showed that whereas the as-prepared nanoparticles (NFO) are stoichiometric, the annealed ones (a-NFO) are not, since Ni0-based crystals precipitate. Nickel depletion from the spinel lattice and reduction in the polyol solvent are accompanied with an important cation migration. Indeed, thanks to Mössbauer hyperfine structure analysis, we evidenced that the cation distribution in NFO departs from the thermodynamically stable inverse spinel structure with a concentration of tetrahedrally coordinated Ni2+ of 20 wt-% (A sites). After annealing, and nickel demixing, originated very probably from the A sites of NFO lattice, the spinel phase accommodates with cation and anion vacancies, leading to the (Fe3+0.84□0.16)A[Ni2+0.80Fe3+1.16□0.04]BO4-0.20 formula, meaning that the applied polyol-mediated treatment is not so trivial.
The Value of 18F-FDG PET/CT in Diagnosing Pancreatic Lesions: Comparison With CA19-9, Enhanced CT or Enhanced MR
Authors: Huang Shengyun , Chong Huanhuan , Sun Xun , Wu Zhijian , Jia Qing , Zhang Yongxue , Lan Xiaoli
Published: October 2021

Objective: To investigate the value of 18F-FDG PET/CT in diagnosing pancreatic lesions, and compare it with CA19-9, contrast-enhanced CT (CECT), and contrast-enhanced MRI (CEMR).

Methods: Cases of patients with suspected pancreatic lesions examined between January 1, 2011 and June 30, 2017 were retrospectively analyzed. CA19-9, CECT and CEMR within 2 weeks of PET/CT were evaluated. We compared the diagnostic efficacy of PET/CT with CA19-9, CECT and CEMR as well as combined tests.

Results: A total of 467 cases were examined in this study, including 293 males and 174 females, with an average age of 57.79 ± 12.68 y (16–95 y). Cases in the malignant group (n = 248) had significantly higher SUVmax (7.34 ± 4.17 vs. 1.70 ± 2.68, P < 0.001) and CA19-9 (663.21 ± 531.98 vs. 87.80 ± 218.47, P < 0.001) than those in the benign group (n = 219). The sensitivity, specificity and accuracy of PET/CT were 91.9, 96.3, and 94.0%, respectively. Those for CECT were 83.6, 77.8, 81.2%, respectively; and 91.2, 75.0, 81.7% were for CEMR. PET/CT corrected 14.7% (28/191) CECT diagnoses and 12.2% (10/82) CEMR diagnoses. Although the diagnostic efficiency of CA19-9 was acceptable (80.0, 69.0, 74.9% respectively), the joint application of PET/CT and CA19-9 could significantly enhance the diagnostic efficiency compared with PET/CT alone (sen 97.4 vs. 90.5%, P = 0.0003; spe 100.0 vs. 95.2%, P = 0.0047).

Conclusions: PET/CT has sensitivity similar to CECT, CEMR and significantly higher specificity and accuracy, helping reduce false diagnoses of morphological images. Combining PET/CT with CA19-9 could enhance diagnostic efficiency.
Association of Cytomegalovirus Infection With Anti-MDA5 Antibody-Positive Dermatomyositis: A Prospective Cohort Study
Authors: Huang Linlin , Zhu Wenbo , Ye Yan , Wu Xiaoping , Yan Qingran , Wang Zhiqing , Lin Yanwei , Chen Sheng
Published: October 2021

Objectives: To investigate whether cytomegalovirus (CMV) infection plays a role in the pathogenesis and prognosis of idiopathic inflammatory myopathy (IIM), particularly in anti-MDA5 antibody-positive (anti-MDA5+) dermatomyositis (DM).

Methods: A prospective cohort of 204 newly diagnosed IIM patients and 50 healthy individuals were enrolled in the study. CMV-IgM and CMV-IgG antibody concentrations and lymphocyte counts were analyzed. Differences in categorical data were compared using Fisher's exact test and the chi-square test. One-year survival rates were analyzed in MDA5+ DM patients with and without CMV infection.

Results: In IIM patients, the median CMV-IgM level was significantly higher than in healthy controls (6 U/mL vs. 0 U/mL, p < 0.05) as was the median CMV-IgG level (114 U/mL vs. 105 U/mL, p < 0.05). The percentage of recent CMV infections in the MDA5+ DM group was much higher than it was in the MDA5− IIM group (19.1% vs. 7.0%, p = 0.009). MDA5+ DM patients with CMV DNA-emia had poorer 1 year survival than the CMV-DNA− group (33.3% vs. 86.3%, p = 0.010). CMV-IgM-positive (CMV-IgM+) MDA5+ DM patients had lower CD4+ T cell counts (245.7 cells/μL vs. 420.5 cells/μL, p < 0.05) and CD19+ B cell counts (97.3 cells/μL vs. 240.6 cells/μL, p < 0.05).

Conclusion: The number of CMV infections was significantly higher in IIM patients, particularly in MDA5+ DM patients. Lower CD4+ T cells and CD19+ B cells were observed in CMV-IgM+ MDA5+ DM patients. CMV infection may have an important role in the pathogenesis and prognosis of MDA5+ DM by disrupting immunity.
Heat Shock Proteins in Urine as Cancer Biomarkers
Authors: Albakova Zarema , Norinho Diogo Dubart , Mangasarova Yana , Sapozhnikov Alexander
Published: October 2021

Heat shock proteins (HSPs) are a large family of molecular chaperones, which have shown to be implicated in various hallmarks of cancer such as resistance to apoptosis, invasion, angiogenesis, induction of immune tolerance, and metastasis. Several studies reported aberrant expression of HSPs in liquid biopsies of cancer patients and this has opened new perspectives on the use of HSPs as biomarkers of cancer. However, no specific diagnostic, predictive, or prognostic HSP chaperone-based urine biomarker has been yet discovered. On the other hand, divergent expression of HSPs has also been observed in other pathologies, including neurodegenerative and cardiovascular diseases, suggesting that new approaches should be employed for the discovery of cancer-specific HSP biomarkers. In this study, we propose a new strategy in identifying cancer-specific HSP-based biomarkers, where HSP networks in urine can be used to predict cancer. By analyzing HSPs present in urine, we could predict cancer with approximately 90% precision by machine learning approach. We aim to show that coupling the machine learning approach and the understanding of how HSPs operate, including their functional cycles, collaboration with and within networks, is effective in defining patients with cancer, which may provide the basis for future discoveries of novel HSP-based biomarkers of cancer.
Prognostic Significance of Ultrasound Findings of Acute Acalculous Cholecystitis for Elderly Long-Term Bedridden Patients
Authors: Lin Qian , Shen Lei , Chen Cheng , Yang Zhen , Que Yifan , Liu Yani , Yin Ming , Xu Guogang , Li Junlai
Published: October 2021

Background: Acute acalculous cholecystitis (AAC) is characterized by the development of cholecystitis in the gallbladder without gallstones or with small gallstones unrelated to inflammatory diseases. This disease is not rare in the elderly bedridden patients with co-morbidities and prone to develop life-threatening gangrene or perforation of gallbladder. Early imaging is essential for detecting and effectively treating AAC. This study aimed to evaluate the use of ultrasound diagnostic criteria for the diagnosis and prognosis of elderly long-term bedridden patients with suspected AAC.

Methods: We retrospectively studied 374 elderly bedridden patients with clinical manifestations of AC at the acute stage of the disease. Gallbladder anomalies were found in 92 patients by ultrasound examination, which correlated with the duration time of clinical manifestations, complications, as well as therapeutic prognosis. The major and minor ultrasound criteria of AAC were made according to the Tokyo Guidelines 2018. Ultrasound results were thought to be AAC positive when they met two major criteria or one major and two minor criteria.

Results: Forty-three (46.7%) of the 92 patients presented with AAC (+) test results based on the ultrasound criteria, with a higher incidence of complications (27.9%) than AAC (–) patients (0%; P < 0.001). The median length of symptoms (8 vs. 4 days, P < 0.001) and duration of antibiotic therapy (13 vs. 5 days, P < 0.001) were longer in the AAC (+) group.

Conclusions: The ultrasound-based AAC (+) group often had a worse prognosis than the AAC (–) group. Therefore, patients from the AAC (+) group should receive a follow-up ultrasound examination to detect disease progression early.
Feasibility of Droplet Digital PCR Analysis of Plasma Cell-Free DNA From Kidney Transplant Patients
Authors: Jerič Kokelj Barbara , Štalekar Maja , Vencken Sebastian , Dobnik David , Kogovšek Polona , Stanonik Matjaž , Arnol Miha , Ravnikar Maja
Published: October 2021

Increasing research demonstrates the potential of donor-derived cell-free DNA (dd-cfDNA) as a biomarker for monitoring the health of various solid organ transplants. Several methods have been proposed for cfDNA analysis, including real-time PCR, digital PCR, and next generation sequencing-based approaches. We sought to revise the droplet digital PCR (ddPCR)-based approach to quantify relative dd-cfDNA in plasma from kidney transplant (KTx) patients using a novel pilot set of assays targeting single nucleotide polymorphisms that have a very high potential to distinguish cfDNA from two individuals. The assays are capable of accurate quantification of down to 0.1% minor allele content when analyzing 165 ng of human DNA. We found no significant differences in the yield of extracted cfDNA using the three different commercial kits tested. More cfDNA was extracted from the plasma of KTx patients than from healthy volunteers, especially early after transplantation. The median level of donor-derived minor alleles in KTx samples was 0.35%. We found that ddPCR using the evaluated assays within specific range is suitable for analysis of KTx patients' plasma but recommend prior genotyping of donor DNA and performing reliable preamplification of cfDNA.
A Patched-Like Protein PsPTL Is Not Essential for the Growth and Response to Various Stresses in Phytophthora sojae
Authors: Xue Zhaolin , Wang Weizhen , Shen Jinghuan , Zhang Jinhui , Zhang Xitao , Liu Xili
Published: October 2021

Patched (Ptc) and Patched-related (Ptr) proteins containing sterol-sensing domains (SSD) and Patched domains are highly conserved in eukaryotes for lipid transport and metabolism. Four proteins containing predicted SSD and Patched domains were simultaneously found by searching thePhytophthora sojaegenome database, and one of them was identified as a Patched-like (PTL) protein. Here, we investigated the biological function ofPsPTL. The expression level ofPsPTLwas higher during mycelial and sporulation stages, compared to zoospore (ZO), cyst, and germinated-cyst stages, without significant change during infection. However, deletion ofPsPTLusing CRISPR/Cas9 had no significant effect on the growth, development, or virulence ofP. sojae. Further investigations showed thatPsPTLis not essential forP. sojaeto cope with external stresses such as temperature, pH, oxidative and osmotic pressure. In addition, this gene did not appear to play an essential role inP. sojae’s response to exogenous sterols. The transcript levels of the other three proteins containing predicted SSD and Patched domains were also not significantly upregulated inPsPTLdeletion transformants. Our studies demonstrated that PsPTL is not an essential protein forP. sojaeunder the tested conditions, and more in-depth research is required for revealing the potential functions ofPsPTLunder special conditions or in other signaling pathways.