bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Validation in a Novel Quantification System of Ferroptosis Patterns for the Prediction of Prognosis and Immunotherapy Response in Left- and Right-Sided Colon Cancer
Authors: Zhang Heng-Chun , Deng Shen-Hui , Pi Ya-Nan , Guo Jun-Nan , Xi Hua , Shi Xin , Yang Xue-Fei , Zhang Bo-Miao , Xue Wei-Nan , Cui Bin-Bin , Liu Yan-Long
Published: April 2022

Background

This study aimed to establish a novel quantification system of ferroptosis patterns and comprehensively analyze the relationship between ferroptosis score (FS) and the immune cell infiltration (ICI) characterization, tumor mutation burden (TMB), prognosis, and therapeutic sensitivity in left-sided and right-sided colon cancers (LCCs and RCCs, respectively).

Methods

We comprehensively evaluated the ferroptosis patterns in 444 LCCs and RCCs based on 59 ferroptosis-related genes (FRGs). The FS was constructed to quantify ferroptosis patterns by using principal component analysis algorithms. Next, the prognostic value and therapeutic sensitivities were evaluated using multiple methods. Finally, we performed weighted gene co-expression network analysis (WGCNA) to identify the key FRGs. The IMvigor210 cohort, TCGA-COAD proteomics cohort, and Immunophenoscores were used to verify the predictive abilities of FS and the key FRGs.

Results

Two ferroptosis clusters were determined. Ferroptosis cluster B demonstrated a high degree of congenital ICI and stromal-related signal enrichment with a poor prognosis. The prognosis, response of targeted inhibitors, and immunotherapy were significantly different between high and low FS groups (HSG and LSG, respectively). HSG was characterized by high TMB and microsatellite instability-high subtype with poor prognosis. Meanwhile, LSG was more likely to benefit from immunotherapy. ALOX5 was identified as a key FRG based on FS. Patients with high protein levels of ALOX5 had poorer prognoses.

Conclusion

This work revealed that the evaluation of ferroptosis subtypes will contribute to gaining insight into the heterogeneity in LCCs and RCCs. The quantification for ferroptosis patterns played a non-negligible role in predicting ICI characterization, prognosis, and individualized immunotherapy strategies.
T Helper 2-Associated Immunity in the Pathogenesis of Systemic Lupus Erythematosus
Authors: Ko Haeun , Kim Chan Johng , Im Sin-Hyeog
Published: April 2022

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that mainly affects women in their reproductive years. A complex interaction of environmental and genetic factors leads to the disruption of immune tolerance towards self, causing overt immune activation and production of autoantibodies that attack multiple organs. Kidney damage, termed lupus nephritis, is the leading cause of SLE-related morbidity and mortality. Autoantibodies are central to propagating lupus nephritis through forming immune complexes and triggering complements. Immunoglobulin G (IgG) potently activates complement; therefore, autoantibodies were mainly considered to be of the IgG isotype. However, studies revealed that over 50% of patients produce autoantibodies of the IgE isotype. IgE autoantibodies actively participate in disease pathogenesis as omalizumab treatment, a humanized anti-IgE monoclonal antibody, improved disease severity in an SLE clinical trial. IgE is a hallmark of T helper 2-associated immunity. Thus, T helper 2-associated immunity seems to play a pathogenic role in a subset of SLE patients. This review summarizes human and animal studies that illustrate type 2 immune responses involved during the pathology of SLE.
Labial Gland Mesenchymal Stem Cell Derived Exosomes-Mediated miRNA-125b Attenuates Experimental Sjogren’s Syndrome by Targeting PRDM1 and Suppressing Plasma Cells
Authors: Xing Yixiao , Li Boya , He Jing , Hua Hong
Published: April 2022

The pathogenesis of the prototypical chronic autoimmune disorder primary Sjögren syndrome (pSS) has been thought to be B-cell-centric, based on serum autoantibodies, the increased risk of B cell lymphoma, and altered B cell subsets in patients with pSS. Over the last 10 years, therapies targeting B cells have been investigated for pSS; however, current evidence for the efficacy of B cell targeted therapies in pSS is still sparse. Mesenchymal stem cells (MSCs) might represent a promising strategy for cell therapy of autoimmune diseases via regulation of immune cells. MSC-released exosomes carry various bioactive molecules and thus have been studied in MSC-based therapy. The newly discovered labial gland MSCs (LGMSCs) have exhibited enhanced performance. Herein, we aimed to determine the effects of LGMSC-derived exosomes (LGMSC-Exos) on the symptoms of a mouse model of pSS and their regulatory effect and mechanism on B cell subsets. In vivo, treatment of the spontaneous mouse model of pSS with LGMSC-Exos resulted in reduced inflammatory infiltration and restored saliva secretion in salivary glands. In vitro, coculture of LGMSC-Exos with peripheral blood mononuclear cells of patients with pSS markedly reduced the proportions of CD19+CD20-CD27+CD38+ plasma cells among peripheral blood mononuclear cells. Further investigations provided evidence that LGMSC-Exo-derived microRNA-125b affected plasma cells of pSS by directly binding to its target gene, PRDM1 (PR domain zinc finger protein 1, also known as BLIMP1), which might be developed as a target to treat pSS. Overall, these findings provided a possible exploitable therapeutic target in pSS and provide new insights into the potential therapeutic application of exosomes in pSS and other disease mediated by B-cells.
Role of Tocilizumab in Down Regulating sCD163 Plasmatic Levels in a Cohort of COVID-19 Patients
Authors: Marocco Raffaella , Carraro Anna , Zingaropoli Maria Antonella , Nijhawan Parni , Tortellini Eeva , Guardiani Mariasilvia , Mengoni Fabio , Zuccalà Paola , Belvisi Valeria , Kertusha Blerta , Parente Alberico , Del Borgo Cosmo , Vullo Vincenzo , Ciardi Maria Rosa , Mastroianni Claudio Maria , Lichtner Miriam
Published: April 2022

Background

CD163, a haptoglobin-hemoglobin scavenger receptor mostly expressed by monocytes and macrophages, is involved in the regulation of inflammatory processes. Following proteolytic cleavage after pro-inflammatory stimulation, CD163 is shed from the cell surface and its soluble form in plasma, sCD163, is a biomarker of monocyte/macrophage lineage activation.

The assessment of sCD163 plasmatic levels in an early stage of the disease could have clinical utility in predicting the severity of COVID-19 pneumonia. The use of tocilizumab (monoclonal antibody anti-IL-6 receptor) in COVID-19 patients reduces lethality rate at 30 days. The aim of the study was to investigate the effect of tocilizumab on sCD163 plasmatic levels in a cohort of COVID-19 patients.

Methods

In COVID-19 patients, on hospital admission (T0), after 7 days from hospitalization (T7) and after 45 days from discharge (T45) sCD163 plasmatic levels were evaluated, along with other laboratory parameters. COVID-19 patients were stratified into tocilizumab (TCZ) and non-tocilizumab (non-TCZ) groups. TCZ group was further divided into responder (R) and non-responder (NR) groups. Patients who died or required mechanical ventilation were defined as NR. As control group, healthy donors (HD) were enrolled.

Results

Seventy COVID-19 patients and 47 HD were enrolled. At T0, sCD163 plasmatic levels were higher in COVID-19 patients compared to HD (p<0.0001) and the longitudinal evaluation showed a reduction in sCD163 plasmatic levels at T7 compared to T0 (p=0.0211). At T0, both TCZ and non-TCZ groups showed higher sCD163 plasmatic levels compared to HD (p<0.0001 and p=0.0147, respectively). At T7, the longitudinal evaluation showed a significant reduction in sCD163 plasmatic levels (p=0.0030) only in the TCZ group, reaching levels comparable to those of HD. Conversely, not statistically significance in non-TCZ group was observed and, at T7, a statistically significance was found comparing non-TCZ group to HD (p=0.0019). At T0, R and NR groups showed not statistically significance in sCD163 plasmatic levels and both groups showed higher levels compared to HD (p=0.0001 and p=0.0340, respectively). The longitudinal evaluation showed significant reductions in both groups (R: p=0.0356; NR: p=0.0273) independently of the outcome. After 45 days of follow-up sCD163 plasmatic levels remain stable.

Conclusion

sCD163 plasmatic levels are increased in COVID-19 pneumonia and is efficiently down-regulated by tocilizumab treatment regardless of the clinical outcome.
N6-Methyladenosine-Modified circRNA in the Bovine Mammary Epithelial Cells Injured by Staphylococcus aureus and Escherichia coli
Authors: Xu Haojun , Lin Changjie , Li Ting , Zhu Yifan , Yang Jinghan , Chen Sijie , Chen Jianguo , Chen Xi , Chen Yingyu , Guo Aizhen , Hu Changmin
Published: April 2022

Mastitis is a common disease that hinders the development of dairy industry and animal husbandry. It leads to the abuse of antibiotics and the emergence of super drug-resistant bacteria, and poses a great threat to human food health and safety. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) are the most common pathogens of mastitis in dairy cows and usually cause subclinical or clinical mastitis. CircRNAs and N6-methyladenosine (m6A) play important roles in immunological diseases. However, the mechanisms by which m6A modifies circRNA in bovine mammary epithelial cells remain poorly understood. The aim of our study was to investigate m6A-modified circRNAs in bovine mammary epithelial cells (MAC-T cells) injured by S. aureus and E. coli. The profile of m6A-modified circRNA showed a total of 1,599 m6A peaks within 1,035 circRNAs in the control group, 35 peaks within 32 circRNAs in the S. aureus group, and 1,016 peaks within 728 circRNAs in the E. coli group. Compared with the control group, 67 peaks within 63 circRNAs were significantly different in the S. aureus group, and 192 peaks within 137 circRNAs were significantly different in the E. coli group. Furthermore, we found the source genes of these differentially m6A-modified circRNAs in the S. aureus and E. coli groups with similar functions according to GO and KEGG analyses, which were mainly associated with cell injury, such as inflammation, apoptosis, and autophagy. CircRNA–miRNA–mRNA interaction networks predicted the potential circRNA regulation mechanism in S. aureus- and E. coli-induced cell injury. We found that the mRNAs in the networks, such as BCL2, MIF, and TNFAIP8L2, greatly participated in the MAPK, WNT, and inflammation pathways. This is the first report on m6A-modified circRNA regulation of cells under S. aureus and E. coli treatment, and sheds new light on potential mechanisms and targets from the perspective of epigenetic modification in mastitis and other inflammatory diseases.
Early-Life Lung and Gut Microbiota Development and Respiratory Syncytial Virus Infection
Authors: Yagi Kazuma , Asai Nobuhiro , Huffnagle Gary B. , Lukacs Nicholas W. , Fonseca Wendy
Published: April 2022

Several environmental factors can influence the development and establishment of the early-life microbiota. For example, exposure to different environmental factors from birth to childhood will shape the lung and gut microbiota and the development of the immune system, which will impact respiratory tract infection and widespread disease occurrence during infancy and later in life. Respiratory syncytial virus (RSV) infects most infants by the age of two and is the primary cause of bronchiolitis in children worldwide. Approximately a third of infants hospitalized with bronchiolitis develop asthma later in life. However, it is unclear what factors increase susceptibility to severe RSV-bronchiolitis and the subsequent asthma development. In recent years, the role of the gut and lung microbiota in airway diseases has received increased interest, and more studies have focused on this field. Different epidemiological studies and experimental animal models have associated early-life gut microbiota dysbiosis with an increased risk of lung disease later in life. This work will review published evidence that correlated environmental factors that affect the early-life microbiota composition and their role in developing severe RSV infection.
A Multiparametric Approach to Unravelling the Geoenvironmental Conditions in Sediments of Bay of Koper (NE Adriatic Sea): Indicators of Benthic Foraminifera and Geochemistry
Authors: Žvab Rožič Petra , Vidović Jelena , Ćosović Vlasta , Hlebec Ana , Rožič Boštjan , Dolenec Matej
Published: April 2022

The Bay of Koper is influenced by agricultural, urban, and port activities, therefore pollution from trace metals is a concern. A total of 20 sediment samples obtained from four 10-cm sediment cores were analyzed. Element concentration in the sediment of the bay was determined spatially and temporally from the recent surface to depth. The results were correlated with the composition and diversity of the benthic foraminiferal assemblages. Major element concentrations indicate natural lithogenic origin (which is also confirmed by mineralogical features). The benthic foraminiferal assemblages in sediment samples, although mainly composed of representatives of the Rotaliida, show moderate to high species diversity and are dominated by the pollution tolerant speciesAmmonia pakinsoniana,Haynesinasp.,Valvulineria bradyanaand the non-keelElphidiumsp. and subordinated byAmmonia tepidaandHaynesina depressula. Canonical correspondence analysis (CCA) on foraminiferal species and trace element concentrations shows a possible control of some potential toxic elements (i.e., Cu, Ni, Pb, Zr, Cr, As) on the diversity and taxonomic composition of foraminiferal assemblages. Nevertheless, foraminiferal diversity and dominance in the bay are related to sediment characteristics such as sediment grain size, and the amount of terrigenous inflow rather than to the element concentrations of sediments. This study evaluated ecological conditions by using the Foram-AMBi and EcoQS indices. The values of the Foram-AMBI index reflect the good to moderate quality of ecological conditions, whereas high to poor ecological statuses were interpreted by calculating EcoQS.
Untargeted Metabolomics Yields Insights Into the Lipidome of Botrylloides niger Herdman, 1886, An Ascidian Invading the Mediterranean Sea
Authors: Della Sala Gerardo , Coppola Daniela , Virgili Riccardo , Vitale Giovanni Andrea , Tanduo Valentina , Teta Roberta , Crocetta Fabio , de Pascale Donatella
Published: April 2022

Human-mediated dispersal of alien species in new biogeographic realms is one of the major drivers of biodiversity change in marine ecosystems. Among others, ascidians are invasive species spreading worldwide, thus causing ecological and economic harms in the recipient environments. An integrated taxonomic approach on selected samples allowed the identification of Botrylloides niger Herdman 1886 as a non-indigenous ascidian forming large aggregates and outcompeting native species in the Fusaro Lake (central-western Mediterranean Sea). This led to the opportunity to investigate in deep its metabolome for the first time. Untargeted mass spectrometry-based metabolomics unveiled B. niger to be a source of nutraceuticals and bioactive natural products, such as lysophospholipids, sulfonolipids, polyunsaturated fatty acids, sphingolipids, monoacylglycerols, and alkaloids. Even if causing ecosystem alterations, our results suggest that B. niger could be exploited for nutritional and/or pharmaceutical purposes, thereby turning a treat in a resource.
LncRNA TUG1 Promotes Apoptosis, Invasion, and Angiogenesis of Retinal Endothelial Cells in Retinopathy of Prematurity via MiR-145-5p
Authors: Wang Yuexia , Wang Yue , Wang Xue , Ma Yuan , Li Zhaojin , Di Yu
Published: April 2022

Purpose

Retinopathy of prematurity (ROP) is a common retinal vascular disease in premature neonates. In recent years, there is increasing evidence that the long non-coding RNA taurine upregulated gene 1 (TUG1) plays a regulatory role in vascular diseases, suggesting a potential role for TUG1 in vascular endothelial cells. We hypothesized that TUG1 may be associated with ROP. Our aim, therefore, was to explore the biological functions of TUG1 in aberrant retinal development.

Methods

We used the mouse oxygen-induced retinopathy (OIR) model to simulate the pathological changes of retinal in ROP. Quantitative real-time polymerase chain reaction was used to detect the expression of TUG1, miR-145-5p and cellular communication network factor 1 (CCN1). Human retinal endothelial cells (HRECs) were treated with CoCl2 to mimic hypoxia conditions. Cellular functional changes were observed after transfection with RNA interference (RNAi)-TUG1 and miR-145-5p mimics. The apoptosis of HRECs was detected by flow cytometry, the migration ability was detected by wound healing and transwell migration assays, and the ability of angiogenesis was detected by tube formation assay. The potential binding sites between TUG1, miR-145-5p, and CCN1 were verified by dual-luciferase reporter assays. The degree of retinopathy was evaluated by staining retinal sections with hematoxylin and eosin, and the expression of CCN1, HIF-1α, VEGF, caspase-3, Bcl-2, IL-1β, and TNF-α protein was analyzed by Western blotting and immunohistochemistry.

Results

In the retina tissue of OIR mice, TUG1, miR-145-5p, and CCN1 were differentially expressed. Knocking down TUG1 attenuated apoptosis, migration, and angiogenesis induced by hypoxia on HRECs, as did miR-145-5p overexpression. Results from reporter assays indicate direct interactions between TUG1, miR-145-5p, and CCN1. Intravitreal injection of miR-145-5p mimics reduced the degree of retinopathy.

Conclusion

TUG1 acts as a molecular sponge of miR-145-5p to regulate CCN1 expression and thus regulate the development of retinal neovascularization. This regulatory mechanism may provide a new theoretical basis for the prevention and treatment of ROP.
Immediate Ocular Changes After Light-Emitting Diode Displays Exposure—A Preliminary Study
Authors: Lin Chia-Chen , Hung Jia-Horung , Huang Yi-Hsun
Published: April 2022

Purpose

Computer vision syndrome (CVS) is one of the most frequently encountered problems among video display terminals (VDT) users, but little is known regarding the short-term effect after exposure to light-emitting diodes (LED). The purpose of this study was to determine if short-term exposure to LED leads to changes in corrected distance visual acuity (CDVA), lipid layer thickness (LLT), blink rates, partial blink ratio, and computer vision syndrome questionnaire (CVS-Q) score.

Design

Prospective, cross-sectional study.

Methods

In this study, participants were recruited at the National Cheng-Kung University Hospital, a tertiary referral center in southern Taiwan, for examination. Participants were asked to complete the CVS-Q and undergo a series of ocular examinations, including CDVA, LLT, blink rates and partial blink ratio before and after watching an LED display for 15 min. Main Outcome Measures were changes in CDVA, LLT, blink rates, partial blink ratio, and CVS-Q measurements.

Results

In total, 120 eyes from 60 participants (mean age: 35.7 ± 9.4 years) were included; 31 participants were men (51.7%), and 29 were women (48.3%). The CDVA, LLT, blink rates, and partial blink ratio did not change after watching the LED display. The CVS-Q score significantly improved after short-term LED exposure (P < 0.001). A subgroup analysis of subjects with a baseline LLT of <60 nm or ≥60 nm determined that LLT significantly decreased in individuals with a baseline LLT of ≥60 nm (P = 0.016).

Conclusion

Short-term use of LED displays reduced LLT in individuals with a baseline LLT of ≥60 nm, despite the visual symptoms of CVS improved subjectively. Therefore, digital device users should be aware of the potential negative effects of LED exposure on the eyes.
B Cells on the Stage of Inflammation in Juvenile Idiopathic Arthritis: Leading or Supporting Actors in Disease Pathogenesis?
Authors: Moura Rita A. , Fonseca João Eurico
Published: April 2022

Juvenile idiopathic arthritis (JIA) is a term that collectively refers to a group of chronic childhood arthritides, which together constitute the most common rheumatic condition in children. The International League of Associations for Rheumatology (ILAR) criteria define seven categories of JIA: oligoarticular, polyarticular rheumatoid factor (RF) negative (RF-), polyarticular RF positive (RF+), systemic, enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. The ILAR classification includes persistent and extended oligoarthritis as subcategories of oligoarticular JIA, but not as distinct categories. JIA is characterized by a chronic inflammatory process affecting the synovia that begins before the age of 16 and persists at least 6 weeks. If not treated, JIA can cause significant disability and loss of quality of life. Treatment of JIA is adjusted according to the severity of the disease as combinations of non-steroidal anti-inflammatory drugs (NSAIDs), synthetic and/ or biological disease modifying anti-rheumatic drugs (DMARDs). Although the disease etiology is unknown, disturbances in innate and adaptive immune responses have been implicated in JIA development. B cells may have important roles in JIA pathogenesis through autoantibody production, antigen presentation, cytokine release and/ or T cell activation. The study of B cells has not been extensively explored in JIA, but evidence from the literature suggests that B cells might have indeed a relevant role in JIA pathophysiology. The detection of autoantibodies such as antinuclear antibodies (ANA), RF and anti-citrullinated protein antibodies (ACPA) in JIA patients supports a breakdown in B cell tolerance. Furthermore, alterations in B cell subpopulations have been documented in peripheral blood and synovial fluid from JIA patients. In fact, altered B cell homeostasis, B cell differentiation and B cell hyperactivity have been described in JIA. Of note, B cell depletion therapy with rituximab has been shown to be an effective and well-tolerated treatment in children with JIA, which further supports B cell intervention in disease development.
Risk of Pleural Empyema in Adult Patients With Asthma: A Nationwide Retrospective Cohort Study
Authors: Liao Wei-Chih , Lin Cheng-Li , Shen Te-Chun , Tu Chih-Yen , Hsia Te-Chun , Hsu Wu-Huei
Published: April 2022

Background

Respiratory system infections commonly occur among individuals with asthma. However, whether asthma patients have a higher risk of pleural empyema development remains unclear.

Methods

This is a retrospective cohort study based on data from the National Health Insurance Research Database of Taiwan. The asthma cohort consisted of 48,360 newly diagnosed adult individuals from 2000 to 2012. The comparison cohort consisted of the same number of adults who did not have asthma and was matched for age, gender, comorbidity, and the year of diagnosis. The development of pleural empyema was followed up to 2013.

Results

Pleural empyema incidence was 2.03-fold higher in the asthma cohort compared to the comparison cohort (8.65 vs. 4.25 per 10,000 person-years), with an adjusted hazard ratio (HR) of 2.12 [95% confidence interval (CI) = 1.76–2.56]. Stratified analyses by age, gender, comorbidity, and corticosteroid use revealed that the crude and adjusted HRs of pleural empyema associated with asthma were all significant. Among patients with asthma, the risk of pleural empyema elevated with increased frequency of annual asthma-related emergency room visits and hospital admissions (≥1 vs. <1, aHR = 8.07, 95% CI = 4.31–15.1 and aHR = 9.31, 95% CI = 5.56–15.6).

Conclusion

An increased risk of pleural empyema occurrence was observed in adult patients with asthma than those without asthma. Furthermore, the risk of pleural empyema may increase with poor control of asthma.
Wearable Smart Contact Lenses for Continual Glucose Monitoring: A Review
Authors: Elsherif Mohamed , Moreddu Rosalia , Alam Fahad , Salih Ahmed E. , Ahmed Israr , Butt Haider
Published: April 2022

Diabetes mellitus is a chronic disease requiring a careful management to prevent its collateral complications, such as cardiovascular and Alzheimer's diseases, retinopathy, nephropathy, foot and hearing impairment, and neuropathy. Self-monitoring of blood glucose at point-of-care settings is an established practice for diabetic patients. However, current technologies for glucose monitoring are invasive, costly, and only provide single snapshots for a widely varying parameter. On the other hand, tears are a source of physiological information that mirror the health state of an individual by expressing different concentrations of metabolites, enzymes, vitamins, salts, and proteins. Therefore, the eyes may be exploited as a sensing site with substantial diagnostic potential. Contact lens sensors represent a viable route for targeting minimally-invasive monitoring of disease onset and progression. Particularly, glucose concentration in tears may be used as a surrogate to estimate blood glucose levels. Extensive research efforts recently have been devoted to develop smart contact lenses for continual glucose detection. The latest advances in the field are reviewed herein. Sensing technologies are described, compared, and the associated challenges are critically discussed.
Case Report: 18F-FDG PET/CT Demonstrating Malignant Spread of a Pulmonary Epithelioid Hemangioendothelioma
Authors: Wu Ruolin , Xia Xiaotian , Hu Fan , Zhang Yajing , Wang Jingjing , He Yong , Gao Zairong
Published: April 2022

Pulmonary epithelioid hemangioendothelioma (EHE) is a rare vascular malignancy that is typically low-to-intermediate grade. We report a 47-year-old man with a rapidly progressive pulmonary EHE who initially presented with asymptomatic pulmonary nodules. One nodule was mildly hypermetabolic on initial 18F-FDG PET/CT. 10 months later, the patient developed severe bone pain and night sweats. Repeat imaging revealed several lung lesions, diffuse pleural thickening, and multiple skeletal metastases with considerably increased tracer uptake. The patient underwent vertebral, pleural, and pulmonary biopsies and a diagnosis of advanced pulmonary EHE was made. His disease progressed despite four courses of antineoplastic therapy, after which he began palliative care. Pulmonary EHE can be aggressive and spread rapidly. Biopsy of hypermetabolic lung lesions using PET/CT guidance might enable early definitive diagnosis.
Functional Optical Coherence Tomography for Intrinsic Signal Optoretinography: Recent Developments and Deployment Challenges
Authors: Kim Tae-Hoon , Ma Guangying , Son Taeyoon , Yao Xincheng
Published: April 2022

Intrinsic optical signal (IOS) imaging of the retina, also termed as optoretinogram or optoretinography (ORG), promises a non-invasive method for the objective assessment of retinal function. By providing the unparalleled capability to differentiate individual retinal layers, functional optical coherence tomography (OCT) has been actively investigated for intrinsic signal ORG measurements. However, clinical deployment of functional OCT for quantitative ORG is still challenging due to the lack of a standardized imaging protocol and the complication of IOS sources and mechanisms. This article aims to summarize recent developments of functional OCT for ORG measurement, OCT intensity- and phase-based IOS processing. Technical challenges and perspectives of quantitative IOS analysis and ORG interpretations are discussed.
Effect of Patent Expiry on the Performance of Innovator Multinational Pharmaceutical Companies in a Low Middle Income Country
Authors: Khalil Farrukh , Onyango Joseph Odhiambo
Published: April 2022

Patent expiry or loss of exclusivity exposes innovator pharmaceutical companies to changes in the market dynamics brought about by increased production of generics by rival companies after patent expiration. This current study focused on the effect of generic products manufacturing and competitive market pressures, price changes, and changes in sales volumes and profitability of innovator multinational pharmaceutical companies after patent expiry. The methodology of this study involved a descriptive survey design and utilized both qualitative and quantitative techniques for data collection, analysis, and presentation. Primary data were collected using the key informants' in-depth interviews and survey questionnaires. The top management, including regional managers, general managers, and directors of each of the eight companies participating in this study, were interviewed to gather the qualitative data. Thirty-six respondents comprising of Product Development Managers and Business Supervising Managers responded to a survey questionnaire through purposive sampling. Findings depicted a significant effect of patent expiry on the generic production and subsequent decline in the performance of multinational innovator companies in the pharmaceutical industry. This study recommends that multinational innovator companies operating in low-income countries, such as Kenya, develop strategic policies to tap into the market by leveraging generic production through collaborative manufacturing with generic companies to share revenues.
Phylogenetic and Spatiotemporal Analyses of the Complete Genome Sequences of Avian Coronavirus Infectious Bronchitis Virus in China During 1985–2020: Revealing Coexistence of Multiple Transmission Chains and the Origin of LX4-Type Virus
Authors: Fan Wensheng , Chen Jiming , Zhang Yu , Deng Qiaomu , Wei Lanping , Zhao Changrun , Lv Di , Lin Liting , Zhang Bingsha , Wei Tianchao , Huang Teng , Wei Ping , Mo Meilan
Published: April 2022

Infectious bronchitis (IB) virus (IBV) causes considerable economic losses to poultry production. The data on transmission dynamics of IBV in China are limited. The complete genome sequences of 212 IBV isolates in China during 1985–2020 were analyzed as well as the characteristics of the phylogenetic tree, recombination events, dN/dS ratios, temporal dynamics, and phylogeographic relationships. The LX4 type (GI-19) was found to have the highest dN/dS ratios and has been the most dominant genotype since 1999, and the Taiwan-I type (GI-7) and New type (GVI-1) showed an increasing trend. A total of 59 recombinants were identified, multiple recombination events between the field and vaccine strains were found in 24 isolates, and the 4/91-type (GI-13) isolates were found to be more prone to being involved in the recombination. Bayesian phylogeographic analyses indicated that the Chinese IBVs originated from Liaoning province in the early 1900s. The LX4-type viruses were traced back to Liaoning province in the late 1950s and had multiple transmission routes in China and two major transmission routes in the world. Viral phylogeography identified three spread regions for IBVs (including LX4 type) in China: Northeastern China (Heilongjiang, Liaoning, and Jilin), north and central China (Beijing, Hebei, Shanxi, Shandong, and Jiangsu), and Southern China (Guangxi and Guangdong). Shandong has been the epidemiological center of IBVs (including LX4 type) in China. Overall, our study highlighted the reasons why the LX4-type viruses had become the dominant genotype and its origin and transmission routes, providing more targeted strategies for the prevention and control of IB in China.
Crops Change the Morphology, Abundance, and Mass of Microplastics in Mollisols of Northeast China
Authors: Wang Jiuqi , Yan Pengke , Wang Wan , Hao Xinhua , Xu Bing , Aurangzeib Muhammad , Zhang Shaoliang
Published: April 2022

Degradation of microplastics (MPs) by both physicochemical and biological processes in the natural environment is determined by the enzymes inside the soil, and which was severely influenced by crop growth and straw amendment (SA). However, it is still unclear how crop growth and SA influence degradation of MPs in soils. In this study, both catalase and sucrase were measured, and the stereomicroscope combined with microscopic infrared spectroscopy and scanning electron microscope (SEM) was used to detect the morphology and quantity of low-density polyethylene microplastic (LDPE-MP) and low-density polypropylene microplastic (LDPP-MP), after crop growth (maize and soybean, with and without SA, 1 and 2% MP) in an outdoor pot experiment, in the Mollisols. The results showed that the growth of the crops changed the morphology, functional groups (e.g., methylene, carbonyl), total mass, and abundance ratio of MPs of different sizes. These were possibly caused by enzymes that were significantly influenced by crop types, abundance, and types of MPs in the soils. Maize growth decreased the mass of LDPE-MP and LDPP-MP by 28.7 and 32.7%, respectively, and 2% (w/w) of LDPP-MP addition in soil decreased mass of 9%, which was higher than that in 1% (w/w) LDPP-MP addition in soil. Soybean growth with SA decreased the mass of LDPE-MP and LDPP-MP by 36.6 and 20.7%, respectively, than the control treatment (CK). Compared with CK, both crop growth and SA changed the abundance of MPs of different sizes and decreased the mean size of MPs. The LDPE-MP could be more easily degraded by enzymes in the soils compared to LDPP-MP when the MP size was smaller with surface roughness. Generally, both maize and soybean growth can accelerate MP change in soils, and MP change process was mainly determined by SA, MP types, and the dose effect of MP.
Microbiologically Influenced Corrosion of Copper and Its Alloys in Anaerobic Aqueous Environments: A Review
Authors: Amendola Roberta , Acharjee Amit
Published: April 2022

Regardless of the long record of research works based on microbiologically influenced corrosion (MIC), its principle and mechanism, which lead to accelerated corrosion, is yet to be fully understood. MIC is observed on different metallic substrates and can be caused by a wide variety of microorganisms with sulfate-reducing bacteria (SRB) being considered the most prominent and economically destructive one. Copper and its alloys, despite being used as an antimicrobial agent, are recorded to be susceptible to microbial corrosion. This review offers a research overview on MIC of copper and its alloys in anaerobic aqueous environments. Proposed MIC mechanisms, recent work and developments as well as MIC inhibition techniques are presented focusing on potable water systems and marine environment. In the future research perspectives section, the importance and possible contribution of knowledge about intrinsic properties of substrate material are discussed with the intent to bridge the knowledge gap between microbiology and materials science related to MIC.
Stability of the Microbiome of the Sponge Mycale (Oxymycale) acerata in the Western Antarctic Peninsula
Authors: Happel Lea , Rondon Rodolfo , Font Alejandro , González-Aravena Marcelo , Cárdenas César A.
Published: April 2022

The sponge microbiome, especially in Low Microbial Abundance (LMA) species, is expected to be influenced by the local environment; however, contrasting results exist with evidence showing that host specificity is also important, hence suggesting that the microbiome is influenced by host-specific and environmental factors. Despite sponges being important members of Southern Ocean benthic communities, their relationships with the microbial communities they host remain poorly studied. Here, we studied the spatial and temporal patterns of the microbiota associated with the ecologically important LMA sponge M. acerata at sites along ∼400 km of the Western Antarctic Peninsula (WAP) to assess patterns in the core and variable microbial components of the symbiont communities of this sponge species. The analyses of 31 samples revealed that the microbiome of M. acerata is composed of 35 prokaryotic phyla (3 Archaea, 31 Bacteria, and one unaffiliated), being mainly dominated by Proteobacteria with Gammaproteobacteria as the most dominant class. The core community was composed of six prokaryotic OTUs, with gammaproteobacterial OTU (EC94 Family), showing a mean abundance over 65% of the total abundance. Despite some differences in rare OTUs, the core community did not show clear patterns in diversity and abundance associated with specific sites/environmental conditions, confirming a low variability in community structure of this species along the WAP. The analysis at small scale (Doumer Island, Palmer Archipelago) showed no differences in space and time in the microbiome M. acerata collected at sites around the island, sampled in three consecutive years (2016–2018). Our results highlight the existence of a low spatial and temporal variability in the microbiome of M. acerata, supporting previous suggestions based on limited studies on this and other Antarctic sponges.
Impact of SARS-CoV-2 on Host Factors Involved in Mental Disorders
Authors: Rhoades Raina , Solomon Sarah , Johnson Christina , Teng Shaolei
Published: April 2022

COVID-19, caused by SARS-CoV-2, is a systemic illness due to its multiorgan effects in patients. The disease has a detrimental impact on respiratory and cardiovascular systems. One early symptom of infection is anosmia or lack of smell; this implicates the involvement of the olfactory bulb in COVID-19 disease and provides a route into the central nervous system. However, little is known about how SARS-CoV-2 affects neurological or psychological symptoms. SARS-CoV-2 exploits host receptors that converge on pathways that impact psychological symptoms. This systemic review discusses the ways involved by coronavirus infection and their impact on mental health disorders. We begin by briefly introducing the history of coronaviruses, followed by an overview of the essential proteins to viral entry. Then, we discuss the downstream effects of viral entry on host proteins. Finally, we review the literature on host factors that are known to play critical roles in neuropsychiatric symptoms and mental diseases and discuss how COVID-19 could impact mental health globally. Our review details the host factors and pathways involved in the cellular mechanisms, such as systemic inflammation, that play a significant role in the development of neuropsychological symptoms stemming from COVID-19 infection.
A Novel Acyl-AcpM-Binding Protein Confers Intrinsic Sensitivity to Fatty Acid Synthase Type II Inhibitors in Mycobacterium smegmatis
Authors: Li Mengmiao , Huang Qian , Zhang Weidi , Cao Yinghua , Wang Zhanxin , Zhao Zhenwen , Zhang Xiaotian , Zhang Junjie
Published: April 2022

The fatty acid synthase type II (FAS-II) multienzyme system is the main target of drugs to inhibit mycolic acid synthesis in mycobacterium. Meromycolate extension acyl carrier protein (AcpM) serves as the carrier of fatty acyl chain shuttling among the individual FAS-II components during the progression of fatty acid elongation. In this paper, MSMEG_5634 in Mycobacterium smegmatis was determined to be a helix-grip structure protein with a deep hydrophobic pocket, preferring to form a complex with acyl-AcpM containing a fatty acyl chain at the C36-52 length, which is the medium product of FAS-II. MSMEG_5634 interacted with FAS-II components and presented relative accumulation at the cellular pole. By forming the MSMEG_5634/acyl-AcpM complex, which is free from FAS-II, MSMEG_5634 could transport acyl-AcpM away from FAS-II. Deletion of the MSMEG_5634 gene in M. smegmatis resulted in a mutant with decreased sensitivity to isoniazid and triclosan, two inhibitors of the FAS-II system. The isoniazid and triclosan sensitivity of this mutant could be restored by the ectopic expression of MSMEG_5634 or Rv0910, the MSMEG_5634 homologous protein in Mycobacterium tuberculosis H37Rv. These results suggest that MSMEG_5634 and its homologous proteins, forming a novel acyl-AcpM-binding protein family in mycobacterium, confer intrinsic sensitivity to FAS-II inhibitors.
Variation in Bacterial Community Structure Under Long-Term Fertilization, Tillage, and Cover Cropping in Continuous Cotton Production
Authors: Duan Ning , Li Lidong , Liang Xiaolong , Fine Aubrey , Zhuang Jie , Radosevich Mark , Schaeffer Sean M.
Published: April 2022

Agricultural practices alter the structure and functions of soil microbial community. However, few studies have documented the alterations of bacterial communities in soils under long-term conservation management practices for continuous crop production. In this study, we evaluated soil bacterial diversity using 16S rRNA gene sequencing and soil physical and chemical properties within 12 combinations of inorganic N fertilization, cover cropping, and tillage throughout a cotton production cycle. Soil was collected from field plots of the West Tennessee Agriculture Research and Education Center in Jackson, TN, United States. The site has been under continuous cotton production for 38 years. A total of 38,038 OTUs were detected across 171 soil samples. The dominant bacterial phyla wereProteobacteria,Acidobacteria,Actinobacteria,Verrucomicrobia, andChloroflexi, accounting for ∼70% of the total bacterial community membership. Conventional tillage increased alpha diversity in soil samples collected in different stages of cotton production. The effects of inorganic N fertilization and conventional tillage on the structure of bacterial communities were significant at all four sampling dates (p< 0.01). However, cover cropping (p< 0.05) and soil moisture content (p< 0.05) only showed significant influence on the bacterial community structure after burn-down of the cover crops and before planting of cotton (May). Nitrate-N appeared to have a significant effect on the structure of bacterial communities after inorganic fertilization and at the peak of cotton growth (p< 0.01). Structural equation modeling revealed that the relative abundances of denitrifying and nitrifying bacteria were higher when conventional tillage and vetch cover crop practices were applied, respectively. Our results indicate that long-term tillage and fertilization are key factors increasing the diversity and restructuring the composition of bacterial communities, whereas cover cropping may have shorter-term effects on soil bacteria community structure. In this study, management practices might positively influence relative abundances of bacterial functional groups associated with N cycling. The bacteria functional groups may build a network for providing N and meet microbial N needs in the long term.
Comparative Genomics Assisted Functional Characterization of Rahnella aceris ZF458 as a Novel Plant Growth Promoting Rhizobacterium
Authors: Xu Shuai , Zhao Yurong , Peng Yue , Shi Yanxia , Xie Xuewen , Chai Ali , Li Baoju , Li Lei
Published: April 2022

Many Rahnella strains have been widely described as plant growth-promoting rhizobacteria with the potential to benefit plant growth and protect plants from pathogens. R. aceris ZF458 is a beneficial plant bacterium isolated from swamp soil with the potential for biocontrol. Strain ZF458 has shown broad-spectrum antagonistic activities against a variety of plant pathogens and exhibited a dramatic effect on controlling Agrobacterium tumefaciens in sunflowers. The R. aceris ZF458 genome sequence contained a 4,861,340-bp circular chromosome and two plasmids, with an average G + C content of 52.20%. Phylogenetic analysis demonstrated that R. aceris ZF458 was closely related to R. aceris SAP-19. Genome annotation and comparative genomics identified the conservation and specificity of large numbers of genes associated with nitrogen fixation, plant growth hormone production, organic acid biosynthesis and pyrroloquinoline quinone production that specific to benefiting plants in strain ZF458. In addition, numerous conserved genes associated with environmental adaption, including the bacterial secretion system, selenium metabolism, two-component system, flagella biosynthesis, chemotaxis, and acid resistance, were also identified in the ZF458 genome. Overall, this was the first study to systematically analyze the genes linked with plant growth promotion and environmental adaption in R. aceris. The aim of this study was to derive genomic information that would provide an in-depth insight of the mechanisms of plant growth-promoting rhizobacteria, and could be further exploited to improve the application of R. aceris ZF458 in the agriculture field.
Picorna-Like Viruses of the Havel River, Germany
Authors: Zell Roland , Groth Marco , Selinka Lukas , Selinka Hans-Christoph
Published: April 2022

To improve the understanding of the virome diversity of riverine ecosystems in metropolitan areas, a metagenome analysis was performed with water collected in June 2018 from the river Havel in Berlin, Germany. After enrichment of virus particles and RNA extraction, paired-end Illumina sequencing was conducted and assignment to virus groups and families was performed. This paper focuses on picorna-like viruses, the most diverse and abundant group of viruses with impact on human, animal, and environmental health. Here, we describe altogether 166 viral sequences ranging in size from 1 to 11.5 kb. The 71 almost complete genomes are comprised of one candidate iflavirus, one picornavirus, two polycipiviruses, 27 marnaviruses, 27 dicistro-like viruses, and 13 untypeable viruses. Many partial picorna-like virus sequences up to 10.2 kb were also investigated. The sequences of the Havel picorna-like viruses represent genomes of seven of eight so far known Picornavirales families. Detection of numerous distantly related dicistroviruses suggests the existence of additional, yet unexplored virus groups with dicistronic genomes, including few viruses with unusual genome layout. Of special interest is a clade of dicistronic viruses with capsid protein-encoding sequences at the 5′-end of the genome. Also, monocistronic viruses with similarity of their polymerase and capsid proteins to those of dicistroviruses are interesting. A second protein with NTP-binding site present in the polyprotein of solinviviruses and related viruses needs further attention. The results underline the importance to study the viromes of fluvial ecosystems. So far acknowledged marnaviruses have been isolated from marine organisms. However, the present study and available sequence data suggest that rivers and limnic habitats are relevant ecosystems with circulation of marnaviruses as well as a plethora of unknown picorna-like viruses.
Structural and Enzymological Evidence for an Altered Substrate Specificity in Okur-Chung Neurodevelopmental Syndrome Mutant CK2αLys198Arg
Authors: Werner Christian , Gast Alexander , Lindenblatt Dirk , Nickelsen Anna , Niefind Karsten , Jose Joachim , Hochscherf Jennifer
Published: April 2022

Specific de novo mutations in the CSNK2A1 gene, which encodes CK2α, the catalytic subunit of protein kinase CK2, are considered as causative for the Okur-Chung neurodevelopmental syndrome (OCNDS). OCNDS is a rare congenital disease with a high phenotypic diversity ranging from neurodevelopmental disabilities to multi-systemic problems and characteristic facial features. A frequent OCNDS mutation is the exchange of Lys198 to Arg at the center of CK2α′s P+1 loop, a key element of substrate recognition. According to preliminary data recently made available, this mutation causes a significant shift of the substrate specificity of the enzyme. We expressed the CK2αLys198Arg recombinantly and characterized it biophysically and structurally. Using isothermal titration calorimetry (ITC), fluorescence quenching and differential scanning fluorimetry (Thermofluor), we found that the mutation does not affect the interaction with CK2β, the non-catalytic CK2 subunit, and that the thermal stability of the protein is even slightly increased. However, a CK2αLys198Arg crystal structure and its comparison with wild-type structures revealed a significant shift of the anion binding site harboured by the P+1 loop. This observation supports the notion that the Lys198Arg mutation causes an alteration of substrate specificity which we underpinned here with enzymological data.