bluuebunny/crossref_metadata_2025 huggingface dataset:
Commercial trade of wild animals: examining the use of the IUCN Red List and CITES Appendices as the basis for corporate trade policies
Authors: Green Jennah , Schmidt-Burbach Jan , Elwin Angie
Published: July 2022

Wildlife exploitation is considered a predominant factor driving global biodiversity loss and zoonotic disease transmission, in addition to a range of concerns for animal welfare and ecosystem health. One of the ways in which wild animals are exploited is for commercial trade as exotic pets, fashion products, luxury foods, traditional medicine, entertainment, ornaments and more. While the trade in some wildlife species is restricted or prohibited under various domestic and international laws, many species are not bound by legal protection and are traded in largely unmonitored numbers with the potential for severe consequences. Companies, particularly large e-commerce platforms, are increasingly adopting policies to restrict the legal trade in wild animals. Due to the absence of clear guidelines for corporate services of wildlife trade, these policies commonly adopt pre-determined species lists, such as the International Union for the Conservation of Nature’s (IUCN) Red List of Threatened Species or the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) Appendices, as the basis for ‘negative lists’ to guide which species to restrict trade in. However, these databases were not intended for this application and there has been no assessment of their use for this purpose. Here, we summarise and compare the scale and scope of species listed on the IUCN Red List and the CITES Appendices, to discuss how much additional protection these lists provide wild animals if used as policy instruments to guide corporate wildlife trade restrictions beyond the relevant legal bounds. Based on our results, we discuss why that using one list or another would likely omit taxa of conservation concern from protection, and using both lists in conjunction would still not comprehensively reflect all species vulnerable to extinction as a result of exploitation. Further, neither list can mitigate the animal welfare and public health concerns inherently associated with all commercial wildlife trade. We recommend that companies looking to develop policies relating to commercial wildlife trade consider going beyond the scope of predetermined species lists to help mitigate the harmful effects of commercial wildlife exploitation via trade for all wild animals.
No accelerated arterial aging in relatively young women after preeclampsia as compared to normotensive pregnancy
Authors: Janssen Emma B. N. J. , Hooijschuur Mieke C. E. , Lopes van Balen Veronica A. , Morina-Shijaku Erjona , Spaan Julia. J. , Mulder Eva G. , Hoeks Arnold P. , Reesink Koen D. , van Kuijk Sander M. J. , van't Hof Arnoud , van Bussel Bas C. T. , Spaanderman Marc E. A. , Ghossein-Doha Chahinda
Published: July 2022

Introduction

Preeclampsia, an endothelial disorder of pregnancy, predisposes to remote cardiovascular diseases (CVD). Whether there is an accelerated effect of aging on endothelial decline in former preeclamptic women is unknown. We investigated if the arterial aging regarding endothelial-dependent and -independent vascular function is more pronounced in women with a history of preeclampsia as compared to women with a history of solely normotensive gestation(s).

Methods

Data was used from the Queen of Hearts study (ClinicalTrials.gov Identifier NCT02347540); a large cross-sectional study on early detection of cardiovascular disease among young women (≥18 years) with a history of preeclampsia and a control group of low-risk healthy women with a history of uncomplicated pregnancies. Brachial artery flow-mediated dilation (FMD; absolute, relative and allometric) and sublingually administered nitroglycerine-mediated dilation (NGMD; absolute and relative) were measured using ultrasound. Cross-sectional associations of age with FMD and NGMD were investigated by linear regression. Models were adjusted for body mass index, smoking, antihypertensive drug use, mean arterial pressure, fasting glucose, menopausal state, family history of CVD and stress stimulus during measurement. Effect modification by preeclampsia was investigated by including an interaction term between preeclampsia and age in regression models.

Results

Of the 1,217 included women (age range 22–62 years), 66.0% had a history of preeclampsia and 34.0% of normotensive pregnancy. Advancing age was associated with a decrease in relative FMD and NGMD (unadjusted regression coefficient: FMD: −0.48%/10 years (95% CI:−0.65 to −0.30%/10 years), NGMD: −1.13%/10 years (−1.49 to −0.77%/10 years)) and increase in brachial artery diameter [regression coefficient = 0.16 mm/10 years (95% CI 0.13 to 0.19 mm/10 years)]. Similar results were found when evaluating FMD and NGMD as absolute increase or allometrically, and after confounder adjustments. These age-related change were comparable in former preeclamptic women and controls (p-values interaction ≥0.372). Preeclampsia itself was independently associated with consistently smaller brachial artery diameter, but not with FMD and NGMD.

Conclusion

In young- to middle-aged women, vascular aging in terms of FMD and NGMD was not accelerated in women after preeclampsia compared to normotensive pregnancies, even though former preeclamptic women consistently have smaller brachial arteries.
Graft preservation confers myocardial protection during coronary artery bypass grafting
Authors: Szalkiewicz Philipp , Emmert Maximilian Y. , Heinisch Paul P. , Arnold Zsuzsanna , Crailsheim Ingo , Mach Markus , Aschacher Thomas , Grabenwöger Martin , Winkler Bernhard
Published: July 2022

Background

During on-pump coronary artery bypass grafting (ONCAB), graft flushing for distal anastomoses testing also perfuses the downstream myocardium. This single-center retrospective study evaluated the impact of specific preservation solutions on myocardial protection during ONCAB.

Materials and methods

Between July 2019 and March 2020 either DuraGraft (DG) or 0.9% Saline/Biseko (SB) was applied to 272 ONCAB. Overall, 166 patients were propensity-matched into two groups. Cardiac enzymes [high-sensitive Troponin I (hs-TnI) and creatine kinase (CK)] were evaluated 7 days post-surgery.

Results

Post-surgery, hs-TnI values were significantly lower from 3 to 6 h (h) up to 4 days in the DG group: 3–6 h: 4,034 ng/L [IQR 1,853–8,654] vs. 5,532 ng/L [IQR 3,633—8,862], p = 0.05; 12–24 h: 2,420 ng/L [IQR 1,408–5,782] vs. 4,166 [IQR 2,052–8,624], p < 0.01; 2 days: 1,095 ng/L [IQR 479–2,311] vs. 1,564 ng/L [IQR 659–5,057], p = 0.02 and at 4 days: 488 ng/L [IQR 232–1,061] vs. 745 ng/L [IQR 319–1,820], p = 0.03. The maximum value: 4,151 ng/L [IQR 2,056–8,621] vs. 6,349 ng/L [IQR 4,061–12,664], p < 0.01 and the median area under the curve (AUC): 6,146 ng/L/24 h [IQR 3,121–13,248] vs. 10,735 ng/L/24 h [IQR 4,859–21,484], p = 0.02 were lower in the DG group. CK values were not significantly different between groups: maximum value 690 [IQR 417–947] vs. 631 [464–979], p = 0.61 and AUC 1,986 [1,226–2,899] vs. 2,081 [1,311–3,063], p = 0.37.

Conclusion

Repeated graft flushing with DG resulted in lower Troponin values post-surgery suggesting enhanced myocardial protection compared to SB. Additional studies are warranted to further assess the myocardial protection properties of DG.
Crosstalk between dendritic cells and T lymphocytes during atherogenesis: Focus on antigen presentation and break of tolerance
Authors: Bellini Rossella , Bonacina Fabrizia , Norata Giuseppe Danilo
Published: July 2022

Atherosclerosis is a chronic disease resulting from an impaired lipid and immune homeostasis, where the interaction between innate and adaptive immune cells leads to the promotion of atherosclerosis-associated immune-inflammatory response. Emerging evidence has suggested that this response presents similarities to the reactivity of effector immune cells toward self-epitopes, often as a consequence of a break of tolerance. In this context, dendritic cells, a heterogeneous population of antigen presenting cells, play a key role in instructing effector T cells to react against foreign antigens and T regulatory cells to maintain tolerance against self-antigens and/or to patrol for self-reactive effector T cells. Alterations in this delicate balance appears to contribute to atherogenesis. The aim of this review is to discuss different DC subsets, and their role in atherosclerosis as well as in T cell polarization. Moreover, we will discuss how loss of T cell tolerogenic phenotype participates to the immune-inflammatory response associated to atherosclerosis and how a better understanding of these mechanisms might result in designing immunomodulatory therapies targeting DC-T cell crosstalk for the treatment of atherosclerosis-related inflammation.
Epidemiology of atrial fibrillation and risk of CVD mortality among hypertensive population: A prospective cohort study in Northeast China
Authors: Du Zhi , Lin Min , Tian Yuanmeng , Jing Li , Liu Shuang , Li Guangxiao , Jia Tong , Sun Qun , Shi Lei , Sun Jixu , Tian Wen , Xing Liying
Published: July 2022

Background

Determining risk factors of cardiovascular disease (CVD)-related mortality and evaluating their influence are important for effectively reducing corresponding mortality. However, few research findings have estimated the relationship between atrial fibrillation (AF) and CVD-related mortality among hypertension individuals.

Objective

The objective of this study was to investigate the epidemiology of AF in a hypertension population and determine the relationship between AF and CVD-related mortality.

Methods

Using a multistage, stratified, and cluster random sampling method, the prospective cohort study with a median follow-up of 3.51 years enrolled 10,678 hypertensive participants at baseline. The prevalence, awareness, and anticoagulation data of AF in this focal population were carefully assessed. Stepwise logistic regression and Cox regression analysis were respectively performed to evaluate the determinants of AF and the association between AF and CVD-related mortality.

Results

The overall prevalence of AF was 1.3% (95% CI, 1.1%−1.6%) in the hypertensive population, and it was higher in men than in women (1.8% vs. 1.0%, respectively; p=0.001). The awareness of AF was 53.1%, and the rate of oral anticoagulant (OAC) therapy was only 4.2%, although all AF participants should have required according to the European Society of Cardiology guidelines. The determinants of AF included elder, male, and history of coronary heart disease in the hypertensive population. Besides, compared with individuals without AF, the risk of CVD-related mortality significantly increased in the hypertensive population with AF (HR 3.37, 95% CI 2.10–5.40).

Conclusion

Our results indicated a huge burden of AF and underuse of OAC therapy for them in a community-based hypertensive population. Considering that most of the risk factors of AF were unmodifiable in hypertensive individuals, as well as its high risk of mortality, long-term interventions including AF education, timely screening, and widespread use of OACs should be emphasized in the focal populations.
Neutrophil circadian rhythm is associated with different outcomes of acute kidney injury due to cholesterol crystal embolism
Authors: Shi Chongxu , Zhao Danyang , Lyubenov Lyuben , Motrapu Manga , Li Na , Steiger Stefanie , Mammadova-Bach Elmina , Yang Luying , Liu Dong , Anders Hans-Joachim
Published: July 2022

Cholesterol crystal (CC) embolism can cause acute tissue infarction and ischemic necrosis via triggering diffuse thrombotic angiopathy occluding arterioles and arteries. Neutrophils contribute to crystal-induced immunothrombosis as well as to ischemic necrosis-related necroinflammation. We speculated that CC embolism-induced acute kidney injury (AKI) would be circadian rhythm-dependent and associated with cyclic differences in neutrophil function. Injection of CC into the left kidney induced thrombotic angiopathy progressing starting as early as 3 h after CC injection followed by a progressive ischemic cortical necrosis and AKI at 24 h. In C57BL/6J mice, circulating CD11b+Ly6G+neutrophils were higher during the day phase [Zeitgeber time (ZT) 0–12] compared to the dark phase (ZT12-24). In the time frame of thrombus formation at ZT13, more neutrophils were recruited into the injured kidney 24 h later compared to CC embolism at ZT5. This effect was associated with an increased circulating number of CXCR2+neutrophils as well as an upregulated kidney adhesion molecule and chemokine expression. These findings were associated with a significant increase in kidney necrosis, and endothelial injury at ZT13. Thus, the time of day has an effect also on CC embolism-related AKI in association with the circadian rhythm of neutrophil recruitment.
Regional differences in educational achievement: A replication study of municipality data
Authors: Boman Björn
Published: July 2022

The current study analyzed the relationships between explanatory variables such as socioeconomic status (SES), migration background (MB), and formal teacher competence, and aggregated grades in the Swedish lower-secondary school context by using aggregated municipality data from 2013, 2018, and 2019. SES indicators had larger effect sizes when data from different years were merged and when the outcome variable was changed to an alternative measure of educational achievement. In one model, the MB variable even became statistically insignificant. These results indicate that SES is an important variable which explains a substantial amount of variance in regard to school achievement indicators such as grade point average. Nonetheless, aggregated data may still suffer from omitted variable bias and biased effect size estimates.
Equational reasoning: A systematic review of the Cuisenaire–Gattegno approach
Authors: Benson Ian , Marriott Nigel , McCandliss Bruce D.
Published: July 2022

The Cuisenaire–Gattegno (Cui) approach to early mathematics uses color coded rods of unit increment lengths embedded in a systematic curriculum designed to guide learners as young as age five from exploration of integers and ratio through to formal algebraic writing. The effectiveness of this approach has been the subject of hundreds of investigations supporting positive results, yet with substantial variability in the nature of results across studies. Based on an historical analysis of one of the highest-fidelity studies (Brownell), which estimated a treatment effect on equation reasoning with an effect size of 1.66, we propose that such variability may be related to different emphases on the use of the manipulatives or on the curriculum from which they came. We conducted a systematic review and meta-analysis of Cui that sought to trace back to the earliest investigations of its efficacy. Results revealed the physical manipulatives component of the original approach (Cuisenaire Rods) have had greater adoption than efforts to retain or adopt curriculum elements from the Cuisenaire–Gattegno approach. To examine the impact of this, we extended the meta-analysis to index the degree to which each study of Cuisenaire Rods included efforts to align or incorporate curricular elements, practices, or goals with the original curriculum. Curriculum design fidelity captured a significant portion of the variability of efficacy results in the meta-analysis.
Case Report: Artifactual Hypoglycemia: A Condition That Should Not Be Forgotten
Authors: Amaral Sara , Palha Ana , Bernardino Vera , Silva-Nunes José
Published: July 2022

Background

Hypoglycemia is uncommon in people who are not being treated for diabetes mellitus and, when present, the differential diagnosis is broad. Artifactual hypoglycemia describes discrepancy between low capillary and normal plasma glucose levels regardless of symptoms and should be considered in patients with Raynaud’s phenomenon.

Case Presentation

A 46-year-old female patient with a history of a sleeve gastrectomy started complaining about episodes of lipothymias preceded by sweating, nausea, and dizziness. During one of these episodes, a capillary blood glucose was obtained with a value of 24 mg/dl. She had multiple emergency admissions with low-capillary glycemia. An exhaustive investigation for possible causes of hypoglycemia was made for 18 months. The 72h fasting test was negative for hypoglycemia. A Raynaud’s phenomenon was identified during one appointment.

Conclusion

Artifactual hypoglycemia has been described in various conditions including Raynaud’s phenomenon, peripheral arterial disease, Eisenmenger syndrome, acrocyanosis, or hypothermia. With this case report, we want to reinforce the importance of being aware of this diagnosis to prevent anxiety, unnecessary treatment, and diagnostic tests.
Modified acupuncture therapy, long-term acupoint stimulation versus sham control for weight control: a multicenter, randomized controlled trial
Authors: Dai Liang , Wang Miao , Zhang Ke-Pei , Wang Lin , Zheng Hui-Min , Li Chun-Bo , Zhou Wen-Jun , Zhou Shi-Gao , Ji Guang
Published: July 2022

Objective

Long-term acupoint stimulation (LAS), also called embedding acupuncture, is a modified acupuncture technique. The preliminary results have demonstrated its efficacy in body-weight control. However, the low quality of available trials limited its application. This study aimed to evaluate the efficacy and safety of LAS in body-weight control by using a randomized, parallel, sham-controlled clinical trial design.

Methods

This was a randomized, single-blind, sham-controlled clinical trial including 84 adult participants (18–60 years) with a body mass index (BMI) of ≥ 24 kg/m2 conducted in three general hospitals in Shanghai, China. Participants were equally assigned to receive LAS or sham LAS (SLAS) once per 10 days, eight times in total. After completion, an additional intervention with a 3-month follow-up period was set to examine the continued effect of LAS. The primary outcome was the change in body weight from baseline to treatment endpoint within the intention-to-treat (ITT) analysis. Secondary outcomes contained changes in waist-to-hip ratio (WHR), lipid metabolism, and visceral and subcutaneous adipose tissues.

Results

From 14 May 2018 to 03 November 2019, 84 participants out of 201 screened individuals met the eligibility criteria, were randomized, and were analyzed (42 participants in each group). From baseline to treatment endpoint, the body-weight reduction in the LAS group was significantly larger than in the sham control (net difference: 1.57 kg, 95% CI: 0.29–2.86, p = 0.012). The superior weight reduction effect persisted in the follow-up period (net difference: 3.20 kg, 95% CI: 1.17–5.21, p = 0.001). LAS therapy also showed improvement in triglyceride and subcutaneous adipose tissue (SAT) compared with sham control. One participant in the LAS group reported a slightly uncomfortable and tingling sensation after the additional intervention. No other adverse events (AEs) were documented.

Conclusion

LAS, a modified acupuncture technique, is safe and effective in body-weight control. It could be used as an alternative choice to classical acupuncture for obesity management.

Clinical Trial Registration

[www.chictr.org.cn], identifier [ChiCTR1800015498].
Fear of hypoglycemia and quality of life in young people with type 1 diabetes and their parents in the era of sensor glucose monitoring
Authors: Glocker Vivien , Bachmann Sara , Hess Melanie , Szinnai Gabor , Burckhardt Marie-Anne
Published: July 2022

Introduction

It is crucial to understand psychosocial outcomes in children and adolescents with type 1 diabetes (T1D) and their families to provide optimal family-centered care. Hence, the aim of this study was to explore psychosocial outcomes in young people with T1D and their parents using currently available glucose monitoring devices in a real-life clinic setting.

Methods

Children and adolescents aged 2-18 years with T1D for more than 6 months and their parents were recruited into a cross-sectional study to complete the Hypoglycemia Fear Survey (HFS) and the Pediatric Quality of Life Inventory (PedsQL) Generic Score Scales, Diabetes Module and Family Impact Module. Demographics and diabetes-specific parameters were obtained from medicals records.

Results

Fifty-nine children and adolescents (mean age 15.1 ± 3.0 years) and 49 parents of children (mean age of children 12.5± 3.3 years) of which 44 were child-parent dyads completed the questionnaires. Parents had a higher mean (SD) FOH total and worry subscore than children, total score was 37.9 (14.6) vs. 32.2 (11.9), p = 0.047 and worry subscore was 17.8 (10.4) vs. 12.8 (9.0), p = 0.01. Furthermore, lower parental diabetes-specific QoL score was observed in parents, 78.8 (12.2) vs. 82.7 (10.3), p=0.02. No difference in FOH and QoL between real-time continuous glucose monitoring (rtCGM) and intermittently scanned glucose monitoring (isCGM) users and users of devices with and without alerts was observed. In isCGM users (n=36 completing the child questionnaires, n=33 completing parent questionnaires), higher parental FOH and lower parental diabetes-specific QoL correlated with higher scanning frequency, r = 0.399, p = 0.021, and r = -0.464, p = 0.007 respectively. No significant correlation was documented between scanning frequency and child questionnaire scores.

Conclusions

Parents are more likely to perceive higher levels of psychosocial burden related to their child’s diabetes than children and adolescents with T1D, especially parents of younger children. This highlights the need for family-based education and treatment resources to support parents in diabetes management in addition to rapidly advancing diabetes technology. In isCGM users, higher parental FOH and lower parent-perceived QoL correlated with a higher scanning frequency, indicating the potential impact of glucose monitoring modality on psychosocial outcomes or vice versa.
Multifaceted fish diversities respond differently to impounding age and longitudinal location along a reservoir cascade
Authors: Liao Chuansong , Wang Jiacheng , Ye Shaowen , Li Wei , Correa Sandra Bibiana , Zhang Tanglin , Liu Jiashou
Published: July 2022

Damming usually modifies riverine habitats, which affects various aspects of fish diversity, especially in a reservoir cascade. Their influence on fish assemblage has been studied widely, but a lack of data from the diversity perspective remains. The Gezhouba Reservoir and Three Gorges Reservoir are two of the largest cascaded reservoirs located on the upper Yangtze River. In this study, we investigated the current fish assemblages in 2020∼2021 and retrieved 22 previous investigations in different sections of this cascade system to analyze how fish taxonomic, functional, and phylogenetic alpha- and beta-diversity change with the distance from the dams and the impounding age during 1998∼2021, and all sampling sites are located in the upper section of the dams. The total species richness and phylogenetic diversity increased significantly with the distance from the dams, but the functional diversity did not change substantially. No significant difference was found in the influence of impounding age on the three aspects of fish diversity. We observed a noticeable increase in non-indigenous fish species richness, functional diversity, and phylogenetic diversity over time, these effects were similar in areas at different distances from the dams. The species richness and phylogenetic diversity of lotic fish decreased from the lotic to lentic zones, whereas the functional and phylogenetic diversities decreased significantly with impounding age. The taxonomic beta-diversity was remarkably higher than the functional and phylogenetic beta-diversities. The differences among the three facets of beta-diversity were driven by a lower functional turnover than the taxonomic and phylogenetic turnovers, and their nestedness components were low without exception. The present study suggests that trade-offs should be considered when designing policies to protect fish diversity based on different objectives.
Emerging concepts regarding pro- and anti tumor properties of B cells in tumor immunity
Authors: Qin You , Lu Furong , Lyu Kexing , Chang Alfred E. , Li Qiao
Published: July 2022

Controversial views regarding the roles of B cells in tumor immunity have existed for several decades. However, more recent studies have focused on its positive properties in antitumor immunity. Many studies have demonstrated a close association of the higher density of intratumoral B cells with favorable outcomes in cancer patients. B cells can interact with T cells as well as follicular dendritic cells within tertiary lymphoid structures, where they undergo a series of biological events, including clonal expansion, somatic hypermutation, class switching, and tumor-specific antibody production, which may trigger antitumor humoral responses. After activation, B cells can function as effector cellsviadirect tumor-killing, antigen-presenting activity, and production of tumor-specific antibodies. At the other extreme, B cells can obtain inhibitory functions by relevant stimuli, converting to regulatory B cells, which serve as an immunosuppressive arm to tumor immunity. Here we summarize our current understanding of the bipolar properties of B cells within the tumor immune microenvironment and propose potential B cell-based immunotherapeutic strategies, which may help promote cancer immunotherapy.
Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2
Authors: Wines Bruce D. , Kurtovic Liriye , Trist Halina M. , Esparon Sandra , Lopez Ester , Chappin Klasina , Chan Li-Jin , Mordant Francesca L. , Lee Wen Shi , Gherardin Nicholas A. , Patel Sheila K. , Hartley Gemma E. , Pymm Phillip , Cooney James P. , Beeson James G. , Godfrey Dale I. , Burrell Louise M. , van Zelm Menno C. , Wheatley Adam K. , Chung Amy W. , Tham Wai-Hong , Subbarao Kanta , Kent Stephen J. , Hogarth P. Mark
Published: July 2022

Joining a function-enhanced Fc-portion of human IgG to the SARS-CoV-2 entry receptor ACE2 produces an antiviral decoy with strain transcending virus neutralizing activity. SARS-CoV-2 neutralization and Fc-effector functions of ACE2-Fc decoy proteins, formatted with or without the ACE2 collectrin domain, were optimized by Fc-modification. The different Fc-modifications resulted in distinct effects on neutralization and effector functions. H429Y, a point mutation outside the binding sites for FcγRs or complement caused non-covalent oligomerization of the ACE2-Fc decoy proteins, abrogated FcγR interaction and enhanced SARS-CoV-2 neutralization. Another Fc mutation, H429F did not improve virus neutralization but resulted in increased C5b-C9 fixation and transformed ACE2-Fc to a potent mediator of complement-dependent cytotoxicity (CDC) against SARS-CoV-2 spike (S) expressing cells. Furthermore, modification of the Fc-glycan enhanced cell activation via FcγRIIIa. These different immune profiles demonstrate the capacity of Fc-based agents to be engineered to optimize different mechanisms of protection for SARS-CoV-2 and potentially other viral pathogens.
Neuroinflammation in neurodegeneration via microbial infections
Authors: Tran Van Thi Ai , Lee Luke P. , Cho Hansang
Published: July 2022

Recent epidemiological studies show a noticeable correlation between chronic microbial infections and neurological disorders. However, the underlying mechanisms are still not clear due to the biological complexity of multicellular and multiorgan interactions upon microbial infections. In this review, we show the infection leading to neurodegeneration mediated by multiorgan interconnections and neuroinflammation. Firstly, we highlight three inter-organ communications as possible routes from infection sites to the brain: nose-brain axis, lung-brain axis, and gut-brain axis. Next, we described the biological crosstalk between microglia and astrocytes upon pathogenic infection. Finally, our study indicates how neuroinflammation is a critical player in pathogen-mediated neurodegeneration. Taken together, we envision that antibiotics targeting neuro-pathogens could be a potential therapeutic strategy for neurodegeneration.
Systematic identification of key extracellular proteins as the potential biomarkers in lupus nephritis
Authors: Zhou Xue , Zhang Yuefeng , Wang Ning
Published: July 2022

Background

Lupus nephritis (LN) is the most common and severe clinical manifestation of systemic lupus erythematosus (SLE) with considerable morbidity/mortality and limited treatment options. Since kidney biopsy is a relative hysteretic indicator, it is indispensable to investigate potential biomarkers for early diagnosis and predicting clinical outcomes of LN patients. Extracellular proteins may become the promising biomarkers by the secretion into body fluid. Our study linked extracellular proteins with lupus nephritis to identify the emerging biomarkers.

Methods

The expression profiling data were acquired from the Gene Expression Omnibus (GEO) database. Meanwhile, the two gene lists encoding extracellular proteins were collected from the Human Protein Atlas (HPA) and UniProt database. Subsequently, the extracellular protein-differentially expressed genes (EP-DEGs) were screened out, and the key EP-DEGs were determined by MCODE, MCC, and Degree methods via the protein–protein interaction (PPI) network. The expression level, immune characteristics, and diagnostic value of these candidate biomarkers were investigated. Finally, the Nephroseq V5 tool was applied to evaluate the clinical significance of the key EP-DEGs.

Results

A total of 164 DEGs were acquired by comparing LN samples with healthy controls based on GSE32591 datasets. Then, 38 EP-DEGs were screened out through the intersection between DEGs and extracellular protein gene lists. Function enrichment analysis indicated that these EP-DEGs might participate in immune response and constitute the extracellular matrix. Four key EP-DEGs (LUM, TGFBI, COL1A2, and POSTN) were eventually identified as candidate biomarkers, and they were all overexpressed in LN samples. Except that LUM expression was negatively correlated with most of the immune regulatory genes, there was a positive correlation between the remaining three biomarkers and the immune regulatory genes. In addition, these biomarkers had high diagnostic value, especially the AUC value of the LUM–TGFBI combination which reached almost 1 (AUC = 0.973), demonstrating high accuracy in distinguishing LN from controls. Finally, we found a meaningful correlation of these biomarkers with sex, WHO class, and renal function such as glomerular filtration rate (GFR), serum creatinine level, and proteinuria.

Conclusion

In summary, our study comprehensively identified four key EP-DEGs exerting a vital role in LN diagnosis and pathogenesis and serving as promising therapeutic targets.
The DCMU Herbicide Shapes T-cell Functions By Modulating Micro-RNA Expression Profiles
Authors: Autin Pierre , Deshayes Sophie , Lea Juliette , Boisgerault Nicolas , Dupré Emilie , Labarrière Nathalie , Leguevel Rémy , Fonteneau Jean-François , Blanquart Christophe , Fradin Delphine
Published: July 2022

DCMU [N-(3,4-dichlorophenyl)-N-dimethylurea] or diuron is a widely used herbicide, which can cause adverse effects on human, especially on immune cells, due to their intrinsic properties and wide distribution. These cells are important for fighting not only against virus or bacteria but also against neoplastic cell development. We developed an approach that combines functional studies and miRNA and RNA sequencing data to evaluate the effects of DCMU on the human immune response against cancer, particularly the one carried out by CD8+ T cells. We found that DCMU modulates the expression of miRNA in a dose-dependent manner, leading to a specific pattern of gene expression and consequently to a diminished cytokine and granzyme B secretions. Using mimics or anti-miRs, we identified several miRNA, such as hsa-miR-3135b and hsa-miR-21-5p, that regulate these secretions. All these changes reduce the CD8+ T cells’ cytotoxic activity directed against cancer cells, in vitro and in vivo in a zebrafish model. To conclude, our study suggests that DCMU reduces T-cell abilities, participating thus to the establishment of an environment conducive to cancer development.
Current status of xenotransplantation research and the strategies for preventing xenograft rejection
Authors: Zhou Qiao , Li Ting , Wang Kaiwen , Zhang Qi , Geng Zhuowen , Deng Shaoping , Cheng Chunming , Wang Yi
Published: July 2022

Transplantation is often the last resort for end-stage organ failures, e.g., kidney, liver, heart, lung, and pancreas. The shortage of donor organs is the main limiting factor for successful transplantation in humans. Except living donations, other alternatives are needed, e.g., xenotransplantation of pig organs. However, immune rejection remains the major challenge to overcome in xenotransplantation. There are three different xenogeneic types of rejections, based on the responses and mechanisms involved. It includes hyperacute rejection (HAR), delayed xenograft rejection (DXR) and chronic rejection. DXR, sometimes involves acute humoral xenograft rejection (AHR) and cellular xenograft rejection (CXR), which cannot be strictly distinguished from each other in pathological process. In this review, we comprehensively discussed the mechanism of these immunological rejections and summarized the strategies for preventing them, such as generation of gene knock out donors by different genome editing tools and the use of immunosuppressive regimens. We also addressed organ-specific barriers and challenges needed to pave the way for clinical xenotransplantation. Taken together, this information will benefit the current immunological research in the field of xenotransplantation.
Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis
Authors: Liu Yiying , Lu Taoyuan , Liu Zaoqu , Ning Wenhua , Li Siying , Chen Yanru , Ge Xiaoyong , Guo Chunguang , Zheng Youyang , Wei Xiangyang , Wang Haiming
Published: July 2022

Background

Synovial macrophages play important roles in the formation and progression of osteoarthritis (OA). This study aimed to explore the biological and clinical significance of macrophage-associated genes (MAGs) in OA.

Methods

The OA synovial gene expression profiles GSE89408 and GSE82107 were obtained from the GEO database. Single-sample gene set enrichment analysis (ssGSEA) and GSEA were employed to decipher differences in immune infiltration and macrophage-associated biological pathways, respectively. Protein–protein interaction (PPI) network analysis and machine learning were utilized to establish a macrophage-associated gene diagnostic signature (MAGDS). RT-qPCR was performed to test the expression of key MAGs in murine models.

Results

OA synovium presented high levels of immune infiltration and activation of macrophage-associated biological pathways. A total of 55 differentially expressed MAGs were identified. Using PPI analysis and machine learning, a MAGDS consisting of IL1B, C5AR1, FCGR2B, IL10, IL6, and TYROBP was established for OA diagnosis (AUC = 0.910) and molecular pathological evaluation. Patients with high MAGDS scores may possess higher levels of immune infiltration and expression of matrix metalloproteinases (MMPs), implying poor biological alterations. The diagnostic value of MAGDS was also validated in an external cohort (AUC = 0.886). The expression of key MAGs was validated in a murine model using RT-qPCR. Additionally, a competitive endogenous RNA network was constructed to reveal the potential posttranscriptional regulatory mechanisms.

Conclusions

We developed and validated a MAGDS model with the ability to accurately diagnose and characterize biological alterations in OA. The six key MAGs may also be latent targets for immunoregulatory therapy.
Notes on syphilis vaccine development
Authors: Kojima Noah , Konda Kelika A. , Klausner Jeffrey D.
Published: July 2022

The quest for a syphilis vaccine to provide protection from infection or disease began not long after the isolation of the first Treponema pallidum subspecies pallidum (T. pallidum) strain in 1912. Yet, a practical and effective vaccine formulation continues to elude scientists. Over the last few years, however, efforts toward developing a syphilis vaccine have increased thanks to an improved understanding of the repertoire of T. pallidum outer membrane proteins (OMPs), which are the most likely syphilis vaccine candidates. More has been also learned about the molecular mechanisms behind pathogen persistence and immune evasion. Published vaccine formulations based on a subset of the pathogen’s OMPs have conferred only partial protection upon challenge of immunized laboratory animals, primarily rabbits. Nonetheless, those experiments have improved our approach to the choice of immunization regimens, adjuvants, and vaccine target selection, although significant knowledge gaps remain. Herein, we provide a brief overview on current technologies and approaches employed in syphilis vaccinology, and possible future directions to develop a vaccine that could be pivotal to future syphilis control and elimination initiatives.
Glycyrrhetinic acid regulates impaired macrophage autophagic flux in the treatment of non-alcoholic fatty liver disease
Authors: Fan Yadong , Dong Wenjin , Wang Ying , Zhu Shan , Chai Rundong , Xu Zhe , Zhang Xiaoyu , Yan Yiqi , Yang Long , Bian Yuhong
Published: July 2022

Macrophages are involved in hepatocyte steatosis and necroinflammation and play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Impaired autophagy function (decreased autophagy or blocked autophagic flow) leads to cell damage and death and promotes NAFLD progression. The experimental and clinical research of glycyrrhetinic acid (GA) in the treatment of NAFLD has gradually attracted attention with clear pharmacological activities such as immune regulation, antiviral, antitumor, antioxidant, liver protection, and anti-inflammatory. However, the effects of GA on the STAT3-HIF-1α pathway and autophagy in macrophages are still unclear, and its mechanism of action in the treatment of NAFLD remains to be further elucidated. We constructed a NAFLD mouse model through a high-fat and high-sugar diet to investigate the therapeutic effects of GA. The results showed that GA reduced weight, improved the pathological changes and hepatic lipid deposition of liver, and abnormally elevated the levels of serum biochemical (AST, ALT, TG, T-CHO, LDL-C, and HDL-C) and inflammatory indexes (IL-1β, IL-4, IL-6, MCP-1, and TNF-α) in NAFLD mice. Further examination revealed that GA ameliorates excessive hepatic macrophage infiltration and hepatocyte apoptosis. The results of the cell experiments further elaborated that GA modulated the PA-induced macrophage STAT3-HIF-1α pathway and ameliorated impaired autophagic flux (blockade of autophagosome–lysosome fusion) and overactivation of inflammation. Excessive hepatocyte apoptosis caused by the uncontrolled release of inflammatory cytokines was also suppressed by GA.

Conclusion

This study demonstrated that GA could regulate the STAT3-HIF-1α pathway of macrophages, ameliorate the impaired autophagy flux, and reduce the excessive production of inflammatory cytokines to improve the excessive apoptosis of liver cells, thus playing a therapeutic role on NAFLD.
Reduced binding activity of vaccine serum to omicron receptor-binding domain
Authors: Li Mingzhi , Weng Shiqi , Wang Quansheng , Yang Zibing , Wang Xiaoling , Yin Yanjun , Zhou Qiuxiang , Zhang Lirong , Tao Feifei , Li Yihan , Jia Mengle , Yang Lingdi , Xin Xiu , Li Hanguang , Kang Lumei , Wang Yu , Wang Ting , Li Sha , Kong Lingbao
Published: July 2022

Coronavirus disease 2019 (COVID-19) vaccination regimens contribute to limiting the spread of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). However, the emergence and rapid transmission of the SARS-CoV-2 variant Omicron raise a concern about the efficacy of the current vaccination strategy. Here, we expressed monomeric and dimeric receptor-binding domains (RBDs) of the spike protein of prototype SARS-CoV-2 and Omicron variant in E. coli and investigated the reactivity of anti-sera from Chinese subjects immunized with SARS-CoV-2 vaccines to these recombinant RBDs. In 106 human blood samples collected from 91 participants from Jiangxi, China, 26 sera were identified to be positive for SARS-CoV-2 spike protein antibodies by lateral flow dipstick (LFD) assays, which were enriched in the ones collected from day 7 to 1 month post-boost (87.0%) compared to those harvested within 1 week post-boost (23.8%) (P < 0.0001). A higher positive ratio was observed in the child group (40.8%) than adults (13.6%) (P = 0.0073). ELISA results showed that the binding activity of anti-SARS-CoV-2 antibody-positive sera to Omicron RBDs dropped by 1.48- to 2.07-fold compared to its homogeneous recombinant RBDs. Thus, our data indicate that current SARS-CoV-2 vaccines provide restricted humoral protection against the Omicron variant.
Human surfactant protein D facilitates SARS-CoV-2 pseudotype binding and entry in DC-SIGN expressing cells, and downregulates spike protein induced inflammation
Authors: Beirag Nazar , Kumar Chandan , Madan Taruna , Shamji Mohamed H. , Bulla Roberta , Mitchell Daniel , Murugaiah Valarmathy , Neto Martin Mayora , Temperton Nigel , Idicula-Thomas Susan , Varghese Praveen M. , Kishore Uday
Published: July 2022

Lung surfactant protein D (SP-D) and Dendritic cell-specific intercellular adhesion molecules-3 grabbing non-integrin (DC-SIGN) are pathogen recognising C-type lectin receptors. SP-D has a crucial immune function in detecting and clearing pulmonary pathogens; DC-SIGN is involved in facilitating dendritic cell interaction with naïve T cells to mount an anti-viral immune response. SP-D and DC-SIGN have been shown to interact with various viruses, including SARS-CoV-2, an enveloped RNA virus that causes COVID-19. A recombinant fragment of human SP-D (rfhSP-D) comprising of α-helical neck region, carbohydrate recognition domain, and eight N-terminal Gly-X-Y repeats has been shown to bind SARS-CoV-2 Spike protein and inhibit SARS-CoV-2 replication by preventing viral entry in Vero cells and HEK293T cells expressing ACE2. DC-SIGN has also been shown to act as a cell surface receptor for SARS-CoV-2 independent of ACE2. Since rfhSP-D is known to interact with SARS-CoV-2 Spike protein and DC-SIGN, this study was aimed at investigating the potential of rfhSP-D in modulating SARS-CoV-2 infection. Coincubation of rfhSP-D with Spike protein improved the Spike Protein: DC-SIGN interaction. Molecular dynamic studies revealed that rfhSP-D stabilised the interaction between DC-SIGN and Spike protein. Cell binding analysis with DC-SIGN expressing HEK 293T and THP- 1 cells and rfhSP-D treated SARS-CoV-2 Spike pseudotypes confirmed the increased binding. Furthermore, infection assays using the pseudotypes revealed their increased uptake by DC-SIGN expressing cells. The immunomodulatory effect of rfhSP-D on the DC-SIGN: Spike protein interaction on DC-SIGN expressing epithelial and macrophage-like cell lines was also assessed by measuring the mRNA expression of cytokines and chemokines. RT-qPCR analysis showed that rfhSP-D treatment downregulated the mRNA expression levels of pro-inflammatory cytokines and chemokines such as TNF-α, IFN-α, IL-1β, IL- 6, IL-8, and RANTES (as well as NF-κB) in DC-SIGN expressing cells challenged by Spike protein. Furthermore, rfhSP-D treatment was found to downregulate the mRNA levels of MHC class II in DC expressing THP-1 when compared to the untreated controls. We conclude that rfhSP-D helps stabilise the interaction between SARS- CoV-2 Spike protein and DC-SIGN and increases viral uptake by macrophages via DC-SIGN, suggesting an additional role for rfhSP-D in SARS-CoV-2 infection.
The impact of antibiotic use on clinical features and survival outcomes of cancer patients treated with immune checkpoint inhibitors
Authors: Zhou Jiaxin , Huang Guowei , Wong Wan-Ching , Hu Da-hai , Zhu Jie-wen , Li Ruiman , Zhou Hong
Published: July 2022

Background

Nowadays, immune checkpoint inhibitors (ICIs) have become one of the essential immunotherapies for cancer patients. However, the impact of antibiotic (ATB) use on cancer patients treated with ICIs remains controversial.

Methods

Our research included retrospective studies and a randomized clinical trial (RCT) with cancer patients treated with ICIs and ATB, from the public database of PubMed, Web of Science, Embase, Cochrane, clinical trials, and JAMA. The survival outcomes included progression-free survival (PFS) and overall survival (OS). Meanwhile, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and subgroup analyses were performed to determine the concrete association between ATB use and the prognosis of cancer patients treated in ICIs.

Results

Our results revealed that ATB use was associated with poor survival outcomes, including OS (HR: 1.94, 95% CI: 1.68–2.25, p <0.001) and PFS (HR: 1.83, 95% CI: 1.53–2.19, p <0.001). The subgroup analysis learned about the association between ATB use and the prognosis of cancer patients with ICI treatment, including 5 cancer types, 3 kinds of ICI, 5 different ATP windows, broad-spectrum ATB class, and ECOG score. ATB treatment was associated with poor OS of non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), esophageal cancer (EC), and melanoma (MEL) in patients treated in ICIs, while non-small-cell lung cancer (NSCLC) and renal cell carcinoma (RCC) were associated with poor PFS. Meanwhile, it was strongly related to the ICI type and ATB window. Furthermore, it is firstly mentioned that the use of broad-spectrum ATB class was strongly associated with poor PFS.

Conclusion

In conclusion, our meta-analysis indicated that ATB use was significantly associated with poor OS and PFS of cancer patients treated with ICI immunotherapy, especially for patients with ATB use in the period of (−60 days; +30 days) near the initiation of ICI treatment. Also, different cancer types and the ICI type can also impact the survival outcome. This first reveals the strong relationship between the broad-spectrum ATB class and poor PFS. Still, more studies are needed for further study.