bluuebunny/crossref_metadata_2025 huggingface dataset:
Membrane Fouling in Algal Separation Processes: A Review of Influencing Factors and Mechanisms
Authors: Novoa Andres Felipe , Vrouwenvelder Johannes S. , Fortunato Luca
Published: May 2021

The use of algal biotechnologies in the production of biofuels, food, and valuable products has gained momentum in recent years, owing to its distinctive rapid growth and compatibility to be coupled to wastewater treatment in membrane photobioreactors. However, membrane fouling is considered a main drawback that offsets the benefits of algal applications by heavily impacting the operation cost. Several fouling control strategies have been proposed, addressing aspects related to characteristics in the feed water and membranes, operational conditions, and biomass properties. However, the lack of understanding of the mechanisms behind algal biofouling and control challenges the development of cost-effective strategies needed for the long-term operation of membrane photobioreactors. This paper reviews the progress on algal membrane fouling and control strategies. Herein, we summarize information in the composition and characteristics of algal foulants, namely algal organic matter, cells, and transparent exopolymer particles; and review their dynamic responses to modifications in the feedwater, membrane surface, hydrodynamics, and cleaning methods. This review comparatively analyzes (i) efficiency in fouling control or mitigation, (ii) advantages and drawbacks, (iii) technological performance, and (iv) challenges and knowledge gaps. Ultimately, the article provides a primary reference of algal biofouling in membrane-based applications.
A New Optical Fiber Probe-Based Quantum Dots Immunofluorescence Biosensors in the Detection of Staphylococcus aureus
Authors: Cui Jiewei , Zhou Minjuan , Li Ying , Liang Zhixin , Li Yanqin , Yu Ling , Liu Yang , Liang Yuan , Chen Liangan , Yang Changxi
Published: May 2021

Staphylococcus aureus (S. aureus) is one of the most common clinical pathogenic bacteria with strong pathogenicity and usually leads to various suppurative infections with high fatality. Traditional bacterial culture for the detection of S. aureus is prone to diagnosis and antimicrobial treatment delays because of its long-time consumption and low sensitivity. In this study, we successfully developed a quantum dots immunofluorescence biosensor for S. aureus detection. The biosensor combined the advantages of biosensors with the high specificity of antigen-antibody immune interactions and the high sensitivity and stability of quantum dots fluorescence. The results demonstrated that the biosensor possessed high specificity and high sensitivity for S. aureus detection. The detection limit of S. aureus reached 1 × 104 CFU/ml or even 1 × 103 CFU/ml, and moreover, the fluorescence intensity had a significant positive linear correlation relationship with the logarithm of the S. aureus concentration in the range of 103–107 CFU/ml (correlation coefficient R2 = 0.9731, P = 0.011). A specificity experiment showed that this biosensor could effectively distinguish S. aureus (1 × 104 CFU/ml and above) from other common pathogenic (non-S. aureus) bacteria in nosocomial infections, such as Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Escherichia coli. Additionally, the whole detection procedure spent only 2 h. In addition, the biosensor in this study may not be affected by the interference of the biofilm or other secretions since the clinical biological specimens are need to be fully liquefied to digest and dissolve viscous secretions such as biofilms before the detection procedure of the biosensor in this study. In conclusion, the biosensor could meet the need for rapid and accurate S. aureus detection for clinical application.
Different Effects of Endothelial Extracellular Vesicles and LPS-Induced Endothelial Extracellular Vesicles on Vascular Smooth Muscle Cells: Role of Curcumin and Its Derivatives
Authors: Xiang Debiao , Li Yamei , Cao Yuling , Huang Ying , Zhou Lili , Lin Xiulian , Qiao Yong , Li Xin , Liao Duanfang
Published: May 2021

Background: During the progression of atherosclerosis (AS), the vascular endothelial and smooth muscle cells are reciprocally regulated by extracellular vesicles (EVs). EVs have different effects on pathological and physiological processes due to the different cargoes contained in EVs.

Purpose: To study the effects of endothelial cells-derived EVs on normal and inflammatory conditions. To investigate the effects of curcumin and curcumin derivatives (Nicotinic-curcumin) on endothelial EVs.

Methods: EVs were isolated from human umbilical vein endothelial cells (HUVECs) by ultracentrifugation. To examined the effect of normal and LPS-induced endothelial cells-derived EVs on the proliferation of human aortic smooth muscle cells (HASMCs), the CCK-8 assay was performed. Transwell and wound healing assays were conducted to assess cell migration. The effects of EVs on lipid accumulation following treatment with oxidized low-density lipoprotein (Ox-LDL) were evaluated with the oil red O staining assay and HPLC. The number of EVs was calculated using the nanoparticle tracking analysis (NTA) and BCA. The expression levels of Rab27a and Rab27b that regulate the EVs secretion were measured by Western blotting assay. The differential expression of miRNAs in endothelial EVs and LPS-induced endothelial EVs was analyzed using miRNA-Sequencing (miRNA-Seq) and RT-PCR.

Results: Treatment with endothelial EVs reduced the proliferation and migration of HASMCs as well as lipid accumulation in HASMCs. However, treatment with LPS-induced endothelial EVs did not inhibit the migration of HASMCs or lipid accumulation, instead it promoted the proliferation of HASMCs. Treatment with the two types of EVs induced differential expression of several miRNAs, including miR-92a-3p, miR-126-5p, miR-125a-3p, miR-143-3p, etc. Moreover, 1 μg/mL LPS induction greatly increased secretion of endothelial EVs. Treatment with curcumin and nicotinic-curcumin reduced endothelial EVs secretion, possibly by inhibiting inflammation.

Conclusion: Endothelial EVs may confer beneficial effects on atherosclerosis by regulating vascular smooth muscle cell (VSMCs), whereas pro-inflammatory factors may disrupt this effect.
Coronary Arteries: Normal Anatomy With Historical Notes and Embryology of Main Stems
Authors: Thiene Gaetano , Frescura Carla , Padalino Massimo , Basso Cristina , Rizzo Stefania
Published: May 2021

Anatomy of subepicardial coronary arteries became a topic of investigation at autopsy in Florence (Italy) by Banchi in the early twentieth century, with the discovery of dominant and balanced patterns. Thereafter, in the 60's of the same century Baroldi in Milan did post-mortem injection with spectacular three-dimensional casts. Later Sones at the Cleveland Clinic introduced selective coronary arteriography for in vivo visualization of coronary arteries. In the present chapter we show these patterns, as well as normal variants of origin and course with questionable risk of ischemia, like myocardial bridge as well as origin of the left circumflex coronary artery from the right sinus with retroaortic course. As far as embryology, the coronary arteries and veins are epicardial in origin and finally connect the former with the aorta, and the latter with the sinus venosus. At the time of spongy myocardium, intramural blood supply derives directly by the ventricular cavities, whereas later, at the time of myocardial compaction, vascularization originates from the subepicardial network. The connection of the subepicardial plexus with the aorta occurs with prongs of the peritruncal ring, which penetrate the facing aortic sinuses. Septation of truncus arteriosus is not responsible for the final position of the coronary orifices. Infact in transposition of the great arteries coronary ostia are regularly located within facing sinuses of the anterior aorta.
Case Report: Pericardial Effusion Treated With Pericardiectomy Plus Right Atrial Mass Resection: A 2-Year Follow-Up of Cardiac Rosai-Dorfman Disease
Authors: Conte Edoardo , Brucato Antonio , Petrella Francesco , Passoni Emanuela , Lauri Gianfranco , Bigliardi Mauro , Elisa De Camilli , Ricciardi Gabriella , Selmi Carlo , Agostoni Piergiuseppe , Alamanni Francesco , Andreini Daniele
Published: May 2021

Background: Rosai-Dorfman disease (RDD) is rare a sinus histiocytosis typically causing lymphadenopathy. Heart involvement is anecdotal, and <30 cases of cardiac RDD (cRDD) have been reported so far.

Case Presentation: A 46-year old woman with positive clinical history for RDD was admitted to our cardiology department with transthoracic echocardiography diagnosis of severe pericardial effusion and right atrial masses. Pericardiocentesis with catheter insertion was performed 3 days after the admission due to clinical evidence of cardiac tamponade. After 10 weeks of maximal medical therapy for inflammatory pericarditis, including non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, steroids, and anakinra, at least 100 ml of pericardial citric liquid has been daily drained suggesting no clinical improvement. Pericardial liquid analysis demonstrated no malignant cells, but immunohistochemical analysis resulted positive for AE1–AE3, D2–40, S100, and CD68 consistent with an RDD diagnosis. Surgical management was judged clinically indicated, and 2 months after admission, the patient underwent pericardiectomy and debulking of atrial mass with freezing of remaining atrial neoformation. Regular clinical and echocardiography evaluation was performed without pericardial effusion recurrence after 2 years of follow-up.

Conclusions: This is the first case ever reported of cRDD who survived after 2 years of follow-up. Pericardiectomy could be feasible and effective for recurrent pericardial effusion in cRDD. Close follow-up and a multidisciplinary environment is needed to take care of cRDD patients.
The Role of Lipid Profile as an Independent Predictor of Non-alcoholic Steatosis and Steatohepatitis in Morbidly Obese Patients
Authors: Ganjooei Narges Ashraf , Jamialahmadi Tannaz , Nematy Mohsen , Jangjoo Ali , Goshayeshi Ladan , Khadem-Rezaiyan Majid , Reiner Željko , Alidadi Mona , Markin Alexander M. , Sahebkar Amirhossein
Published: May 2021

Background and Aims: Obesity is one of the major health problems worldwide. Morbid obesity (body mass index >40 kg/m2 or over 35 with a comorbidity) is associated, apart from other diseases, with an increased risk of non-alcoholic fatty liver disease (NAFLD). Moreover, dyslipidemia is an important comorbidity that is frequently found in NAFLD patients. The aim of this study was to analyze whether serum lipids in morbidly obese patients are associated with the spectrum of NAFLD.

Methods: Total serum cholesterol, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, VLDL, and triglycerides were analyzed in 90 morbidly obese patients. The association of lipid profile parameters with histopathological, elastographic, and sonographic indices of NAFLD, non-alcoholic steatohepatitis (NASH), and liver fibrosis were explored.

Results: The mean levels of serum total cholesterol, LDL-C, and non-HDL cholesterol in patients with positive histology for liver steatosis and NASH were significantly higher than those in patients with negative histology. None of the indices showed a strong association with NAFLD, NASH, or liver fibrosis after adjustment for potential confounders.

Conclusion: A slight predictive value of lipid profile is not sufficiently enough to use solely as a non-invasive test in predicting NASH or liver fibrosis.
Therapeutic Exosomes in Prognosis and Developments of Coronary Artery Disease
Authors: Chen Ai-Qun , Gao Xiao-Fei , Wang Zhi-Mei , Wang Feng , Luo Shuai , Gu Yue , Zhang Jun-Jie , Chen Shao-Liang
Published: May 2021

Exosomes, with an diameter of 30~150 nm, could be released from almost all types of cells, which contain diverse effective constituent, such as RNAs, proteins, lipids, and so on. In recent years, exosomes have been verified to play an important role in mechanism, diagnosis, treatment, and prognosis of cardiovascular disease, especially coronary artery disease (CAD). Moreover, it has also been shown that exosomes derived from different cell types have various biological functions based on the cell stimulation and microenvironment. However, therapeutic exosomes are currently far away from clinical translation, despite it is full of hope. In this review, we summarize an update of the recent studies and systematic knowledge of therapeutic exosomes in atherosclerosis, myocardial infarction, and in-stent restenosis, which might provide a novel insight into the treatment of CAD and promote the potential clinical application of therapeutic exosomes.
Himalayan Blue Pine Deduced Precipitation Record from Cold Arid Lahaul–Spiti, Himachal Pradesh, India
Authors: Misra Krishna G. , Singh Vikram , Yadava Akhilesh K. , Misra Sandhya , Maurya Ravi S. , Vishwakarma Sadhana
Published: May 2021

Ecologically Himalayan blue pine (Pinus wallichiana A. B. Jackson) is the most sensitive tree-species found across the high mountain ranges of Himalaya with deciphering tree-line for the region. Earlier studies showed the potential of Himalayan blue pine to reconstruct the past climate for extending observational data back to the centuries from orography-dominated Himalaya. However, tree-growth of the blue pine is largely found modulated by temperature in the western Himalayan region. In the present study, we attempted the first time to develop precipitation records using Himalayan blue pine chronology from cold arid Lahaul–Spiti, Himachal Pradesh, India. The blue pine chronology extends back to AD 1578 and showed significant relationship with the climatic variables. The bootstrap correlation analyses revealed previous year December to current year July precipitation plays significant role in tree-growth advancements. The previous year December to current year July (pDcJuly) precipitation has been reconstructed back to the AD 1730 for the Lahaul–Spiti region. The recorded individual and multi-year periods of low and high precipitation are consistent with existing hydro-climatic records from the western Himalaya. The five driest and wettest individual years are 1732, 1737, 1970, 2008, 1785, and 1730, 1771, 1758, 1734, 1736, respectively. The spatial correlation between gridded precipitation and reconstructed pDcJuly precipitation is significant for the region close to the sampling site. The study based on the Himalayan blue pine tree-ring chronology addressed its dendroclimatic utility for the semi-arid Lahaul–Spiti region and would be valuable to understand climatic variability over the past three centuries. The strong resemblance of the species with the Himalayan cedar growth patterns showed its promising viability to develop a network of multispecies for more robust climatic reconstruction in the future.
Clinical, Biological, Radiological Pathological and Immediate Post-Operative Remission of Sparsely and Densely Granulated Corticotroph Pituitary Tumors: A Retrospective Study of a Cohort of 277 Patients With Cushing’s Disease
Authors: Rak Beata , Maksymowicz Maria , Pękul Monika , Zieliński Grzegorz
Published: May 2021

Purpose

Cushing’s disease is the most common cause of endogenous hypercortisolemia due to a corticotroph pituitary tumor. Up-to-date there is no reliable biomarker of invasiveness among corticotroph tumors, while it is well established in the literature that sparsely granulated somatotroph tumors are characterized by poorer prognosis. The aim of the study was to correlate multiple data including clinical, biochemical, radiological, and pathological findings (including granulation pattern) as well as immediate post-operative remission status among patients operated on due to corticotroph tumors.

Methods

We enrolled all patients consecutively operated on for planned transsphenoidal neurosurgery due to corticotroph PitNETs in years 2010–2018. We excluded from analysis silent corticotroph tumors, plurihormonal PitNETs, and the Crooke’s cell adenomas.

Results

We recorded 348 hormonally active corticotroph PitNETs. The results of the analysis showed the female predominance 79.88% (n = 278), with the mean age of Cushing’s disease occurrence 43.27 years of age. The mean time from the first signs and symptoms to the operation was 2 years. The women were diagnosed earlier (20–40 years of agevs.50–60 years of age among men). We performed a detailed analysis of 277 cases classified by granularity pattern as DG or SG corticotroph PitNETs. Densely granulated tumors (DG) occurred four times more frequently than sparsely granulated (SG) (n = 225vs. n = 52), at similar age (mean 42.94; median 40vs.mean 45.46; median 45.5; p = 0.3896), but were characterized by lower Knosp’s scale grades (p = 0.0147*), smaller preoperative tumors’ volumes measured at MRI, and more commonly exhibited lower Ki-67 labeling index (<3%) (p = 0.0168*). What is more, DG adenomas more frequently achieved an immediate remission status (measured as postoperative cortisol concentration <2 µg/dl; p = 0.0180*), and the mean postoperative cortisol concentration in DG group was lower than in SG group (mean 5.375 µg/dlvs. 10.47 µg/dl; median 2.49 µg/dlvs. 6.52 µg/dl; p = 0.0028**).

Conclusions

Our study indicates that DG corticotroph adenomas occurred at younger age, more commonly were microadenomas as compared to SG tumors, less frequently had invasive features in comparison to SG corticotroph adenomas (p = 0.0019**), and more commonly achieved an immediate postsurgical hormonal remission (p = 0.0180*). We highlight the need for an accurate differentiation of DG and SG subtypes in the pathomorphological diagnosis of corticotropic tumors, especially in invasive PitNETs.
The Risk Threshold for Hemoglobin A1c Associated With Albuminuria: A Population-Based Study in China
Authors: Lian Hong , Wu Hongshi , Ning Jie , Lin Diaozhu , Huang Chulin , Li Feng , Liang Ying , Qi Yiqin , Ren Meng , Yan Li , You Lili , Xu Mingtong
Published: May 2021

Background

Diabetic kidney disease (DKD) is a kind of common microvascular complication of diabetes. This study aims to explore the possible links between blood sugar level and albuminuria, providing the exact cut point of the “risk threshold” for blood glucose with DKD.

Methods

The relationship between blood glucose and albuminuria was modeled using linear and logistic regression in the REACTION study cohorts (N= 8932). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. Two-slope linear regression was used to simulate associations between blood glucose and ACR.

Results

We found that the increase in ACR was accompanied by increased HbA1c, with a turning point at 5.5%. The positive correlation remained highly significant (P<0.001) when adjusted for age, sex, marital status, education, smoking status, drinking status, BMI, waistline, SBP and DBP. In subgroup analyses including gender, obesity, hypertension, and smoking habits, the relationship was significant and stable.

Conclusions

We determined a risk threshold for HbA1c associated with albuminuria in a Chinese population over the age of 40. HbA1c ≥ 5.5% was positively and independently associated with ACR. These results suggest the necessity of early blood glucose control and renal function screening for DKD in at-risk populations.
Quotient of Waist Circumference and Body Mass Index: A Valuable Indicator for the High-Risk Phenotype of Obesity
Authors: Liu Xiao-cong , Huang Yu , Lo Kenneth , Huang Yu-qing , Chen Ji-yan , Feng Ying-qing
Published: May 2021

Objective

Measuring the body mass index (BMI) or waist circumference (WC) alone is insufficient for assessing possible health risks due to obesity. This study aimed to investigate whether the quotient of WC and BMI can be used as a proxy of the high-risk phenotype of obesity.

Methods

Data for analysis were derived from the National Health and Nutrition Examination Survey (NHANES 1999-2014). The Waist-BMI Ratio was defined as WC divided by BMI. The associations between Waist-BMI Ratio and mortality were estimated using Cox regression models. Restricted cubic spline and two-piecewise linear regression models were used to identify non-linear relationships. The discriminative abilities of different anthropometric measures were compared using receiver operating characteristic curves (ROC).

Results

This study is based on data from 35557 adults (51.1% female, mean age 44.9 years). During an average follow-up of 101.8 months, 3680 participants died, including 807 of cardiovascular causes. In fully adjusted models, Waist-BMI Ratio was independently associated with overall (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.48-2.13) and cardiovascular (HR, 1.77; 95% CI, 1.25-2.52) mortality. Spline analyses revealed that dose-response relationships existed between Waist-BMI Ratio and death. The mortality risk rises dramatically above the cut-off point of the Waist-BMI Ratio (HR, 3.22; 95% CI, 2.43-4.26 for overall mortality and HR, 3.07; 95% CI, 1.71-5.52 for cardiovascular mortality). ROC curve analysis suggested that Waist-BMI Ratio was a better discriminator of mortality (AUC 0.637 for overall and 0.639 for cardiovascular mortality) than BMI, WC, and waist-to-height ratio (Delong’s test all P <0.001).

Conclusions

Waist-BMI Ratio was independently associated with overall and cardiovascular mortality in a J-shaped pattern, offering an immense potential risk marker for obesity in the clinical setting.
Machine Intelligence in Single-Cell Data Analysis: Advances and New Challenges
Authors: Liu Jiajia , Fan Zhiwei , Zhao Weiling , Zhou Xiaobo
Published: May 2021

The rapid development of single-cell technologies allows for dissecting cellular heterogeneity at different omics layers with an unprecedented resolution. In-dep analysis of cellular heterogeneity will boost our understanding of complex biological systems or processes, including cancer, immune system and chronic diseases, thereby providing valuable insights for clinical and translational research. In this review, we will focus on the application of machine learning methods in single-cell multi-omics data analysis. We will start with the pre-processing of single-cell RNA sequencing (scRNA-seq) data, including data imputation, cross-platform batch effect removal, and cell cycle and cell-type identification. Next, we will introduce advanced data analysis tools and methods used for copy number variance estimate, single-cell pseudo-time trajectory analysis, phylogenetic tree inference, cell–cell interaction, regulatory network inference, and integrated analysis of scRNA-seq and spatial transcriptome data. Finally, we will present the latest analyzing challenges, such as multi-omics integration and integrated analysis of scRNA-seq data.
Elastic Net Models Based on DNA Copy Number Variations Predicts Clinical Features, Expression Signatures, and Mutations in Lung Adenocarcinoma
Authors: Xiang Yi , Zou Xiaohuan , Shi Huaqiu , Xu Xueming , Wu Caixia , Zhong Wenjuan , Wang Jinfeng , Zhou Wenting , Zeng Xiaoli , He Miao , Wang Ying , Huang Li , Wang Xiangcai
Published: May 2021

In the precision medicine of lung adenocarcinoma, the identification and prediction of tumor phenotypes for specific biomolecular events are still not studied in depth. Various earlier researches sheds light on the close correlation between genetic expression signatures and DNA copy number variations (CNVs), for which analysis of CNVs provides valuable information about molecular and phenotypic changes in tumorigenesis. In this study, we propose a comprehensive analysis combining genome-wide association analysis and an Elastic Net Regression predictive model, focus on predicting the levels of many gene expression signatures in lung adenocarcinoma, based upon DNA copy number features alone. Additionally, we predicted many other key phenotypes, including clinical features (pathological stage), gene mutations, and protein expressions. These Elastic Net prediction methods can also be applied to other gene sets, thereby facilitating their use as biomarkers in monitoring therapy.
Excellent Response to Atezolizumab After Clinically Defined Hyperprogression Upon Previous Treatment With Pembrolizumab in Metastatic Triple-Negative Breast Cancer: A Case Report and Review of the Literature
Authors: Feng Dongfeng , Guan Yaping , Liu Mingguo , He Shuqian , Zhao Weipeng , Yin Beibei , Liang Jing , Li Yan , Wang Jun
Published: May 2021

Immunotherapy with immune checkpoint inhibitors (ICIs), including programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors, has revolutionized the systematic treatment of advanced and metastatic solid tumors. However, the response rate to ICIs is unsatisfactory, and unexpected hyperprogressive disease (HPD) is even observed in a small subgroup of patients. Patients with HPD usually have worsening clinical symptoms and poorer survival, and therapeutic strategies are extremely limited. Here, we presented a patient with HPD who had used a PD-L1 inhibitor and was highly responsive to the sequential use of a PD-1 inhibitor. A 67-year-old woman with metastatic triple-negative breast cancer was treated with pembrolizumab plus chemotherapy after progression on previous multiple-line chemotherapy treatments. After 2 cycles of treatments, she rapidly developed HPD, as confirmed by radiological evaluation and worsening symptoms. At that time, pembrolizumab was discontinued, and she switched to the PD-L1 inhibitor atezolizumab plus chemotherapy. This patient partially responded to atezolizumab plus chemotherapy without experiencing severe drug-related adverse effects. This is the first reported case of metastatic breast cancer in a patient with radiologically confirmed HPD after pembrolizumab therapy in which successful rechallenge with atezolizumab relieved clinical symptoms. Further studies with larger sample sizes involving a deeper translational investigation of HPD are needed to confirm the efficacy and mechanism of sequential application of different ICIs for the clinical management of HPD.
Metabolic Interdependency of Th2 Cell-Mediated Type 2 Immunity and the Tumor Microenvironment
Authors: Schreiber Simon , Hammers Christoph M. , Kaasch Achim J. , Schraven Burkhart , Dudeck Anne , Kahlfuss Sascha
Published: May 2021

The function of T cells is critically dependent on their ability to generate metabolic building blocks to fulfil energy demands for proliferation and consecutive differentiation into various T helper (Th) cells. Th cells then have to adapt their metabolism to specific microenvironments within different organs during physiological and pathological immune responses. In this context, Th2 cells mediate immunity to parasites and are involved in the pathogenesis of allergic diseases including asthma, while CD8+T cells and Th1 cells mediate immunity to viruses and tumors. Importantly, recent studies have investigated the metabolism of Th2 cells in more detail, while others have studied the influence of Th2 cell-mediated type 2 immunity on the tumor microenvironment (TME) and on tumor progression. We here review recent findings on the metabolism of Th2 cells and discuss how Th2 cells contribute to antitumor immunity. Combining the evidence from both types of studies, we provide here for the first time a perspective on how the energy metabolism of Th2 cells and the TME interact. Finally, we elaborate how a more detailed understanding of the unique metabolic interdependency between Th2 cells and the TME could reveal novel avenues for the development of immunotherapies in treating cancer.
STING Contributes to Host Defense Against Staphylococcus aureus Pneumonia Through Suppressing Necroptosis
Authors: Liu Zhen-Zhen , Yang Yong-Jun , Zhou Cheng-Kai , Yan Shi-Qing , Ma Ke , Gao Yu , Chen Wei
Published: May 2021

STING (Stimulator of interferon genes) is known as an important adaptor protein or direct sensor in the detection of nucleotide originating from pathogens or the host. The implication of STING during pulmonary microbial infection remains unknown to date. Herein, we showed that STING protected against pulmonary S.aureus infection by suppressing necroptosis. STING deficiency resulted in increased mortality, more bacteria burden in BALF and lungs, severe destruction of lung architecture, and elevated inflammatory cells infiltration and inflammatory cytokines secretion. STING deficiency also had a defect in bacterial clearance, but did not exacerbate pulmonary inflammation during the early stage of infection. Interestingly, TUNEL staining and LDH release assays showed that STING-/- mice had increased cell death than WT mice. We further demonstrated that STING-/- mice had decreased number of macrophages accompanied by increased dead macrophages. Our in vivo and in vitro findings further demonstrated this cell death as necroptosis. The critical role of necroptosis was detected by the fact that MLKL-/- mice exhibited decreased macrophage death and enhanced host defense to S.aureus infection. Importantly, blocking necroptosis activation rescued host defense defect against S.aureus pneumonia in STING-/- mice. Hence, these results reveal an important role of STING in suppressing necroptosis activation to facilitate early pathogen control during pulmonary S.aureus infection.
The GABAA Receptor Influences Pressure Overload-Induced Heart Failure by Modulating Macrophages in Mice
Authors: Bu Jin , Huang Shiyuan , Wang Jue , Xia Tong , Liu Hui , You Ya , Wang Zhaohui , Liu Kun
Published: May 2021

Background

Myocardial macrophages have key roles in cardiac remodeling and dysfunction. The gamma-aminobutyric acid subtype A (GABAA) receptor was recently found to be distributed in macrophages, allowing regulation of inflammatory responses to various diseases. This study aimed to clarify the role of GABAA receptor-mediated macrophage responses in pressure overload-induced heart failure.

Methods and Results

C57BL/6J mice underwent transverse aortic constriction for pressure-overload hypertrophy (POH) and were intraperitoneally treated with a specific GABAA receptor agonist (topiramate) or antagonist (bicuculline). Echocardiography, histology, and flow cytometry were performed to evaluate the causes and effects of myocardial hypertrophy and fibrosis. Activation of the GABAA receptor by topiramate reduced ejection fraction and fractional shortening, enlarged the end-diastolic and end-systolic left ventricular internal diameter, aggravated myocardial hypertrophy and fibrosis, and accelerated heart failure in response to pressure overload. Mechanistically, topiramate increased the number of Ly6Clow macrophages in the heart during POH and circulating Ly6Chigh classic monocyte infiltration in late-phase POH. Further, topiramate drove Ly6Clow macrophages toward MHCIIhigh macrophage polarization. As a result, Ly6Clow macrophages activated the amphiregulin-induced AKT/mTOR signaling pathway, and Ly6ClowMHCIIhigh macrophage polarization increased expression levels of osteopontin and TGF-β, which led to myocardial hypertrophy and fibrosis. Conversely, GABAA receptor blockage with bicuculline reversed these effects.

Conclusions

Control of the GABAA receptor activity in monocytes/macrophages plays an important role in myocardial hypertrophy and fibrosis after POH. Blockade of the GABAA receptor has the potential to improve pressure overload-induced heart failure.
Defective Neutrophil Transendothelial Migration and Lateral Motility in ARPC1B Deficiency Under Flow Conditions
Authors: Kempers Lanette , Sprenkeler Evelien G. G. , van Steen Abraham C. I. , van Buul Jaap D. , Kuijpers Taco W.
Published: May 2021

The actin-related protein (ARP) 2/3 complex, essential for organizing and nucleating branched actin filaments, is required for several cellular immune processes, including cell migration and granule exocytosis. Recently, genetic defects in ARPC1B, a subunit of this complex, were reported. Mutations in ARPC1B result in defective ARP2/3-dependent actin filament branching, leading to a combined immunodeficiency with severe inflammation. In vitro, neutrophils of these patients showed defects in actin polymerization and chemotaxis, whereas adhesion was not altered under static conditions. Here we show that under physiological flow conditions human ARPC1B-deficient neutrophils were able to transmigrate through TNF-α-pre-activated endothelial cells with a decreased efficiency and, once transmigrated, showed definite impairment in subendothelial crawling. Furthermore, severe locomotion and migration defects were observed in a 3D collagen matrix and a perfusable vessel-on-a-chip model. These data illustrate that neutrophils employ ARP2/3-independent steps of adhesion strengthening for transmigration but rely on ARP2/3-dependent modes of migration in a more complex multidimensional environment.
Expression of the Carbohydrate Lewis Antigen, Sialyl Lewis A, Sialyl Lewis X, Lewis X, and Lewis Y in the Placental Villi of Patients With Unexplained Miscarriages
Authors: Ma Zhi , Yang Huixia , Peng Lin , Kuhn Christina , Chelariu-Raicu Anca , Mahner Sven , Jeschke Udo , von Schönfeldt Viktoria
Published: May 2021

Background

Lewis antigens such as Sialyl Lewis A (sLeA), Sialyl Lewis X (sLeX), Lewis X (LeX), and Lewis Y (LeY) are a class of carbohydrate molecules that are known to mediate adhesion between tumor cells and endothelium by interacting with its selectin ligands. However, their potential role in miscarriage remains enigmatic. This study aims to analyze the expression pattern of sLeA, sLeX, LeX, and LeY in the placental villi tissue of patients with a medical history of unexplained miscarriages.

Methods

Paraffin-embedded slides originating from placental tissue were collected from patients experiencing a miscarriage early in their pregnancy (6–13 weeks). Tissues collected from spontaneous (n = 20) and recurrent (n = 15) miscarriages were analyzed using immunohistochemical and immunofluorescent staining. Specimens obtained from legally terminated normal pregnancies were considered as control group (n = 18). Assessment of villous vessel density was performed in another cohort (n = 10 each group) of gestation ages-paired placenta tissue. Protein expression was evaluated with Immunoreactive Score (IRS). Statistical analysis was performed by using Graphpad Prism 8.

Results

Expression of sLeA, sLeX, LeX, and LeY in the syncytiotrophoblast was significantly upregulated in the control group compared with spontaneous and recurrent miscarriage groups. However, no prominent differences between spontaneous and recurrent miscarriage groups were identified. Potential key modulators ST3GAL6 and NEU1 were found to be significantly downregulated in the recurrent miscarriage group and upregulated in the spontaneous group, respectively. Interestingly, LeX and LeY expression was also detected in the endothelial cells of villous vessels in the control group but no significant expression in miscarriage groups. Furthermore, assessment of villous vessel density using CD31 found significantly diminished vessels in all size groups of villi (small villi <200 µm, P = 0.0371; middle villi between 200 and 400 µm, P = 0.0010 and large villi >400 µm, P = 0.0003). Immunofluorescent double staining also indicated the co-localization of LeX/Y and CD31.

Conclusions

The expression of four mentioned carbohydrate Lewis antigens and their potential modulators, ST3GAL6 and NEU1, in the placenta of patients with miscarriages was significantly different from the normal pregnancy. For the first time, their expression pattern in the placenta was illustrated, which might shed light on a novel understanding of Lewis antigens’ role in the pathogenesis of miscarriages.
Single-Cell Profiling Reveals Transcriptional Signatures and Cell-Cell Crosstalk in Anti-PLA2R Positive Idiopathic Membranous Nephropathy Patients
Authors: Xu Jie , Shen Chanjuan , Lin Wei , Meng Ting , Ooi Joshua D. , Eggenhuizen Peter J. , Tang Rong , Xiao Gong , Jin Peng , Ding Xiang , Tang Yangshuo , Peng Weisheng , Nie Wannian , Ao Xiang , Xiao Xiangcheng , Zhong Yong , Zhou Qiaoling
Published: May 2021

Idiopathic membranous nephropathy (IMN) is an organ-specific autoimmune disease of the kidney glomerulus. It may gradually progress to end-stage renal disease (ESRD) characterized by increased proteinuria, which leads to serious consequences. Although substantial advances have been made in the understanding of the molecular bases of IMN in the last 10 years, certain questions remain largely unanswered. To define the transcriptomic landscape at single-cell resolution, we analyzed kidney samples from 6 patients with anti-PLA2R positive IMN and 2 healthy control subjects using single-cell RNA sequencing. We then identified distinct cell clusters through unsupervised clustering analysis of kidney specimens. Identification of the differentially expressed genes (DEGs) and enrichment analysis as well as the interaction between cells were also performed. Based on transcriptional expression patterns, we identified all previously described cell types in the kidney. The DEGs in most kidney parenchymal cells were primarily enriched in genes involved in the regulation of inflammation and immune response including IL-17 signaling, TNF signaling, NOD-like receptor signaling, and MAPK signaling. Moreover, cell-cell crosstalk highlighted the extensive communication of mesangial cells, which infers great importance in IMN. IMN with massive proteinuria displayed elevated expression of genes participating in inflammatory signaling pathways that may be involved in the pathogenesis of the progression of IMN. Overall, we applied single-cell RNA sequencing to IMN to uncover intercellular interactions, elucidate key pathways underlying the pathogenesis, and identify novel therapeutic targets of anti-PLA2R positive IMN.
Preservation of Gastrointestinal Mucosal Barrier Function and Microbiome in Patients With Controlled HIV Infection
Authors: Mak Gerald , Zaunders John J. , Bailey Michelle , Seddiki Nabila , Rogers Geraint , Leong Lex , Phan Tri Giang , Kelleher Anthony D. , Koelsch Kersten K. , Boyd Mark A. , Danta Mark
Published: May 2021

Background

Despite successful ART in people living with HIV infection (PLHIV) they experience increased morbidity and mortality compared with HIV-negative controls. A dominant paradigm is that gut-associated lymphatic tissue (GALT) destruction at the time of primary HIV infection leads to loss of gut integrity, pathological microbial translocation across the compromised gastrointestinal barrier and, consequently, systemic inflammation. We aimed to identify and measure specific changes in the gastrointestinal barrier that might allow bacterial translocation, and their persistence despite initiation of antiretroviral therapy (ART).

Method

We conducted a cross-sectional study of the gastrointestinal (GIT) barrier in PLHIV and HIV-uninfected controls (HUC). The GIT barrier was assessed as follows: in vivo mucosal imaging using confocal endomicroscopy (CEM); the immunophenotype of GIT and circulating lymphocytes; the gut microbiome; and plasma inflammation markers Tumour Necrosis Factor-α (TNF-α) and Interleukin-6 (IL-6); and the microbial translocation marker sCD14.

Results

A cohort of PLHIV who initiated ART early, during primary HIV infection (PHI), n=5), and late (chronic HIV infection (CHI), n=7) infection were evaluated for the differential effects of the stage of ART initiation on the GIT barrier compared with HUC (n=6). We observed a significant decrease in the CD4 T-cell count of CHI patients in the left colon (p=0.03) and a trend to a decrease in the terminal ileum (p=0.13). We did not find evidence of increased epithelial permeability by CEM. No significant differences were found in microbial translocation or inflammatory markers in plasma. In gut biopsies, CD8 T-cells, including resident intraepithelial CD103+ cells, did not show any significant elevation of activation in PLHIV, compared to HUC. The majority of residual circulating activated CD38+HLA-DR+ CD8 T-cells did not exhibit gut-homing integrins α4ß7, suggesting that they did not originate in GALT. A significant reduction in the evenness of species distribution in the microbiome of CHI subjects (p=0.016) was observed, with significantly higher relative abundance of the genus Spirochaeta in PHI subjects (p=0.042).

Conclusion

These data suggest that substantial, non-specific increases in epithelial permeability may not be the most important mechanism of HIV-associated immune activation in well-controlled HIV-positive patients on antiretroviral therapy. Changes in gut microbiota warrant further study.
Impacts of Pervasive Climate Change and Extreme Events on Rocky Intertidal Communities: Evidence From Long-Term Data
Authors: Mieszkowska Nova , Burrows Michael T. , Hawkins Stephen J. , Sugden Heather
Published: May 2021

Annual surveys of the abundance of intertidal invertebrates and macroalgae have been made at between 70 and 100 rocky intertidal time-series sites around the United Kingdom coastline since 2002 under the MarClim project. The data provide a unique opportunity to investigate the impacts of both pervasive climate change and their punctuation by extreme events on intertidal species. After the extreme storm events in the 2013/2014 winter season and the record heatwaves in the summers of 2018 and 2020, MarClim surveys recorded both physical and biological changes to rocky shore habitats. Subsequent surveys reassessed the effects on community structure via analysis of those species that resisted storm damage, those species that returned after the extreme storm events, and species that opportunistically occupied vacant habitat after storm-induced species loss. In addition, biannual storm damage surveys documenting communities recovery were carried out in the spring and winter of each year from 2014 to 2020 at three MarClim sites in north Cornwall (Crackington Haven, Trevone, and St. Ives), which experienced different types of abiotic and biotic damage resulting from these storms. Impacts of heatwaves and cold spells on the abundance of species were determined by regression on frequencies of event per year. Species of invertebrates and macroalgae generally declined in years of more frequent winter cold spells and summer heatwaves, while winter heatwaves and summer cold spells had similar numbers of positive and negative effects across species. Winter warm spells tended to have a more negative effect on cold-affinity species than on warm-affinity species. No abrupt shift was recorded after the 2013/2014 storms. Whilst a short-term change in some species was recorded in quantitative quadrat surveys, the biological communities returned to the long-term species composition and abundance within 2 years. The heatwave events caused sublethal heat damage in macroalgae, evidenced as dried areas of tissue on many individuals, with mortality-induced reductions in the abundance of only a few invertebrate species, recorded in Scotland and southwest England after the heatwave events in 2018 and 2020. MarClim and storm-damage surveys indicate that there have been no sustained impacts from either extreme thermal or storm events across the rocky intertidal communities, and biodiversity has not been significantly altered as a result. The abundance and biogeographical distributions of rocky intertidal species and communities around the United Kingdom are being driven by longer-term, large scale, pervasive change in environmental conditions, with a gradual shift towards dominance of Lusitanian species from the early 2000s in responses to warming of the marine climate.
Community Assembly Processes as a Mechanistic Explanation of the Predator-Prey Diversity Relationship in Marine Microbes
Authors: Chang Feng-Hsun , Yang Jinny Wu , Liu Ariana Chih-Hsien , Lu Hsiao-Pei , Gong Gwo-Ching , Shiah Fuh-Kwo , Hsieh Chih-hao
Published: May 2021

Predator and prey α-diversities are often positively associated; yet, understandings of the underlying mechanisms require manipulative experiments and thus remain unclear. We attempt to address this issue by deciphering how α-diversity of predator and prey influences each other’s community assembly processes, which subsequently determine theirα-diversity. The occurrence of assembly processes was indicated by the mean pairwise taxonomic index within a community (αMPTI), assuming assembly processes left traceable imprints on species’ phylogeny. Specifically,αMPTIquantifies deviations of observed phylogenetic distances from that of random, so that it can be used to hint at the occurrence of non-random/deterministic assembly processes. LargerαMPTIof a community implies the occurrence of weaker homogenizing deterministic assembly processes, which suggests that this community might be comprised of less similar species and thus has higher α-diversity. We hypothesize that higher predator and prey α-diversity would be positively associated with each other’sαMPTI, which would then be positively associated with theirα-diversity. To test the hypothesis, we calculated Shannon diversity andαMPTIfor heterotrophic nanoflagellates (HNF; predator) and bacteria (prey) communities in the East China Sea (ECS). The HNF Shannon diversity was found to be positively associated withαMPTIof bacteria, which was then positively associated with bacterial Shannon diversity. In contrast, bacterial Shannon diversity did not correlate with HNF’sαMPTI. We argue that top-down control is one of the explanations to the positiveα-diversity association among trophic levels in microbes of the ECS.
Interaction Between Dietary Lipid Level and Seasonal Temperature Changes in Gilthead Sea Bream Sparus aurata: Effects on Growth, Fat Deposition, Plasma Biochemistry, Digestive Enzyme Activity, and Gut Bacterial Community
Authors: Pelusio Nicole Francesca , Scicchitano Daniel , Parma Luca , Dondi Francesco , Brini Elisa , D’Amico Federica , Candela Marco , Yúfera Manuel , Gilannejad Neda , Moyano Francisco Javier , Gatta Pier Paolo , Bonaldo Alessio
Published: May 2021

A 121-day feeding trial was undertaken to test the effects of two dietary lipid levels (16 and 21% L16, L21) in triplicated gilthead sea bream groups (initial weight: 67.5 g) reared at two different water temperatures (high, H 23°C and low, L 17°C) in the same recirculation system but exposed to a switch in temperature after 58 days. Fish kept at H were transferred to L (HL transition, autumn shift), and the fish kept at L were exposed to H (LH transition, summer shift), while continuing to receive the same diet to apparent satiation in each group. At the end of the trial, no significant diet effect on specific growth rate (SGR), feed intake (FI), and feed conversion rate (FCR) were detected in fish exposed to HL transition compared with those exposed to LH transition, while gross lipid efficiency (GLE) and lipid efficiency ratio (LER) were higher in L16. After temperature changes, L16 displayed higher SGR, FI, GLE, and LER, while mesenteric fat index was reduced. After temperature changes, the combined effects of low lipid diet and low temperature conditions resulted in higher pepsin activity, while trypsin, chymotrypsin, and lipase activities were generally higher at high lipid content. The combined effect of diet and temperature did not alter the metabolic plasma profile, except for the observed final higher aspartate aminotransferase (AST) and alkaline phosphatase (ALP) values when combining high dietary lipid (L21) and temperature changes. Different diets showed a significantly different gut microbiome layout, only at high temperature with L16 diet resulting in a higher load of Lactobacillus. On the contrary, no dietary impact on ecosystem diversity was observed, independently from the temperature. In addition, L16 diet in the HL transition favored an increase in Weissella and Bradyrhizobium genera in the gut microbiome, while in the final condition of LH transition, L21 diet favored a significant increase in Streptococcus and Bacillus. According to the results, the utilization of 16% dietary lipid levels in gilthead sea bream should be preferred during seasonal temperature changes in order to optimize feed utilization and gut health.