bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Cells Profiles In The Peripheral Blood Of Patients With Moderate To Severe COVID-19 And Healthy Subjects With and Without Vaccination With The Pfizer-BioNTech mRNA Vaccine
Authors: Al-Attiyah Raja’a , Safar Hussain A. , Botras Lotfy , Botras Marina , Al-Kandari Fatma , Chehadeh Wassim , Mustafa Abu Salim
Published: July 2022

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), has caused a global crisis. Patients with COVID-19 present with a range of clinical manifestations, from no symptoms to severe illness. However, little is known about the profiles of immune cells required to protect against SARS-CoV-2. This study was performed to determine the immune cells profiles in the peripheral blood of COVID-19 patients with moderate to severe disease (n=52), and compare the findings with those from healthy subjects vaccinated with Pfizer BioNTech mRNA vaccine (VS) (n=62), and non-vaccinated healthy subjects (HS) (n=30) from Kuwait. Absolute counts and percentages of total lymphocytes and lymphocyte subsets (CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD16+CD56+ NK cells) in the peripheral blood of the three groups were analyzed using flow cytometry. The results showed that the absolute counts of total lymphocytes, CD3+, CD4+, and CD8+ T cells, CD19+ B cells, and CD56+ NK cells, were significantly lower in COVID-19 patients than normal healthy controls and vaccinated subjects. The percentages of CD3+ and CD4+ T lymphocytes were also significantly lower in the COVID-19 patients. However, the percentage of CD16+CD56+ NK cells was significantly higher in the peripheral blood of COVID-19 patients, compared to the HS and VS groups with no detectable differences in the percentages of CD8+ T cells and CD19+ B cells between the three groups. Analysis of the monocyte subsets has showed a significantly higher percentage of CD14+HLA-DR+ monocytes in COVID-19 patients compared to HS whereas the inflammatory CD14+CD16+ HLA-DR+ monocytes, and the non-classical CD16+HLA-DR+ monocytes showed significantly lower frequency in the blood of the patients than that of HS. These findings demonstrate perturbations of both innate and adaptive immune cell subsets that reflect dysregulated host responses in COVID-19 patients with moderate to severe disease.
The Mechanisms of Effector Th Cell Responses Contribute to Treg Cell Function: New Insights into Pathogenesis and Therapy of Asthma
Authors: Chen Wenjing , Cao Yuxue , Zhong Yuanyuan , Sun Jing , Dong Jingcheng
Published: July 2022

CD4 + helper T (Th) cell subsets are critically involved in the pathogenesis of asthma. Naive Th cells differentiate into different subsets under the stimulation of different sets of cytokines, and the differentiation process is dominantly driven by lineage specific transcription factors, such as T-bet (Th1), GATA3 (Th2), RORγt (Th17) and Foxp3 (Treg). The differentiation mechanisms driven by these transcription factors are mutually exclusive, resulting in functional inhibition of these Th subsets to each other, particularly prominent between effector Th cells and Treg cells, such as Th2 versus Treg cells and Th17 versus Treg cells. Being of significance in maintaining immune homeostasis, the balance between effector Th cell response and Treg cell immunosuppression provides an immunological theoretical basis for us to understand the immunopathological mechanism and develop the therapy strategies of asthma. However, recent studies have found that certain factors involved in effector Th cells response, such as cytokines and master transcription factors (IL-12 and T-bet of Th1, IL-4 and GATA3 of Th2, IL-6 and RORγt of Th17), not only contribute to immune response of effector Th cells, but also promote the development and function of Treg cells, therefore bridging the interplay between effector Th cell immune responses and Treg cell immunosuppression. Although we have an abundant knowledge concerning the role of these cytokines and transcription factors in effector Th cell responses, our understanding on their role in Treg cell development and function is scattered thus need to be summarized. This review summarized the role of these cytokines and transcription factors involved in effector Th cell responses in the development and function of Treg cells, in the hope of providing new insights of understanding the immunopathological mechanism and seeking potential therapy strategies of asthma.
Monocytic Subsets Impact Cerebral Cortex and Cognition: Differences Between Healthy Subjects and Patients With First-Episode Schizophrenia
Authors: Chen Song , Fan Fengmei , Xuan Fang-Ling , Yan Ling , Xiu Meihong , Fan Hongzhen , Cui Yimin , Zhang Ping , Yu Ting , Yang Fude , Tian Baopeng , Hong L. Elliot , Tan Yunlong , Tian Li
Published: July 2022

Monocytes are a highly heterogeneous population subcategorized into classical, intermediate and nonclassical subsets. How monocytes and their subsets may shape brain structures and functions in schizophrenia remains unclear. The primary goal of this cross-sectional study was to investigate monocytic subsets and their specific signature genes in regulation of cerebral cortical thickness and cognitive functions in first-episode schizophrenia (FES) patients. Whole-blood RNA sequencing of 128 FES patients and 111 healthy controls (HCs) were conducted and monocyte-specific differentially expressed genes were further analyzed. The MATRICS Consensus Cognitive Battery (MCCB) test, cortical neuroimaging and flow cytometric staining of peripheral blood monocytic subsets were performed among the participants. Significant changes in expressions of 54 monocytic signature genes were found in patients, especially for intermediate and nonclassical monocytic subsets with the most outstanding alterations being downregulated S100 Calcium Binding Protein A (S100A) and upregulated Interferon Induced Transmembrane Protein (IFITM) family members, respectively. Meanwhile, percentage of blood nonclassical monocytes was decreased in patients. Cortical thicknesses and MCCB performance were expectantly reduced and weaker intra-relationships among monocytic signature genes and cortices, respectively, were noted in patients compared to HCs. Monocytic genes were negatively associated with both cortical thicknesses and cognition in HCs, which was interestingly weakened or even reversed in patients, with nonclassical monocytic genes showing the greatest statistical significance. This study reveals that while monocytes may have negative effects on brain structure and cognition, the ameliorated phenomenon observed in schizophrenia may reflect an (mal)adaptive change of monocytes at early stage of the disorder.
Immunogenomic Characteristics of Cell-Death-Associated Genes with Prognostic Implications in Bladder Cancer
Authors: Xu Wenhao , Tang Hai-Jia , Anwaier Aihetaimujiang , Liu Wangrui , Tian Xi , Su Jiaqi , Wei Shiyin , Qu Yuanyuan , Zhang Hailiang , Ye Dingwei
Published: July 2022

Bladder cancer is one of the most common genitourinary malignant cancers worldwide. Cell death processes, including apoptosis, ferroptosis, and necrosis, provide novel clinical and immunological insights promoting the management of precision medicine. Therefore, this study aimed to evaluate the transcriptomic profile of signatures in cell death pathways with significant prognostic implications in patients with bladder cancer from multiple independent cohorts (n = 1999). First, genes involved in apoptosis (n = 19), ferroptosis (n = 31), and necrosis (n = 6) were analyzed to evaluate the prognostic implications in bladder cancer. Significant genes were included to establish the cell-death index (CDI) of 36 genes that distinguished patients according to high and low risks. Survival analysis using the Kaplan-Meier curves clustered patients based on overall survival (18.8 vs. 96.7 months; hazard model [HR] = 3.12, P<00001). Cox proportional hazard model was significantly associated with a higher risk of mortality using 10 external independent cohorts in patients with CDIhigh (HR = 1.31, 95% CI: 1.04–1.62). To explore immune parameters associated with CDI, microenvironment cell-population-counter algorithms indicated increased intratumoral heterogeneity and macrophage/monocyte infiltration and CD8+ T cells in patients with CDIhigh group. Besides, the CDIhigh group showed an increased expression of the following immune checkpoints: CD276, PD-L1, CTLA-4, and T-cell exhaustion signatures. Cytokine expression analysis revealed the highest association of IL-9R, IL-17A, IL-17F, GDF7, and IFNW1 with the high-risk group. In addition, 42 patients with BCa receiving immunotherapies were enrolled from a real-world cohort, and expression patterns of three CDI hub genes (DRD5, SCL2A14, and IGF1) were detected using immunohistochemical staining. Patients with triple-negative staining of tumor tissues had significantly higher tumor-associated macrophage abundance, PD-L1 expression, predicted immunocompromised microenvironment, and prominently progressive progression (HR = 4.316, P = 0.0028). In conclusion, this study highlights the immunoevasive tumor microenvironment characterized by the higher tumor-associated macrophage infiltration with the presence of immune checkpoint and T-cell exhaustion genes in patients with BCa at CDIhigh risk who might suffer progression and be more suitable to benefit from immune checkpoint inhibitors or other immunotherapies.
Persisting Microbiota and Neuronal Imbalance Following T. gondii Infection Reliant on the Infection Route
Authors: French Timothy , Steffen Johannes , Glas Albert , Osbelt Lisa , Strowig Till , Schott Björn H. , Schüler Thomas , Dunay Ildiko Rita
Published: July 2022

Toxoplasma gondii is a highly successful parasite capable of infecting all warm-blooded animals. The natural way of infection in intermediate hosts is the oral ingestion of parasite-contaminated water or food. In murine experimental models, oral infection (p.o.) of mice with T. gondii is applied to investigate mucosal and peripheral immune cell dynamics, whereas intraperitoneal infection (i.p.) is frequently used to study peripheral inflammation as well as immune cell – neuronal interaction in the central nervous system (CNS). However, the two infection routes have not yet been systematically compared along the course of infection. Here, C57BL/6 mice were infected p.o. or i.p. with a low dose of T. gondii cysts, and the acute and chronic stages of infection were compared. A more severe course of infection was detected following i.p. challenge, characterized by an increased weight loss and marked expression of proinflammatory cytokines particularly in the CNS during the chronic stage. The elevated proinflammatory cytokine expression in the ileum was more prominent after p.o. challenge that continued following the acute phase in both i.p. or p.o. infected mice. This resulted in sustained microbial dysbiosis, especially after p.o. challenge, highlighted by increased abundance of pathobionts from the phyla proteobacteria and a reduction of beneficial commensal species. Further, we revealed that in the CNS of i.p. infected mice CD4 and CD8 T cells displayed higher IFNγ production in the chronic stage. This corresponded with an increased expression of C1q and CD68 in the CNS and reduced expression of genes involved in neuronal signal transmission. Neuroinflammation-associated synaptic alterations, especially PSD-95, VGLUT, and EAAT2 expression, were more pronounced in the cortex upon i.p. infection highlighting the profound interplay between peripheral inflammation and CNS homeostasis.
The Coordination of mTOR Signaling and Non-Coding RNA in Regulating Epileptic Neuroinflammation
Authors: Zeng Chudai , Hu Jason , Chen Fenghua , Huang Tianxiang , Zhang Longbo
Published: July 2022

Epilepsy accounts for a significant proportion of the burden of neurological disorders. Neuroinflammation acting as the inflammatory response to epileptic seizures is characterized by aberrant regulation of inflammatory cells and molecules, and has been regarded as a key process in epilepsy where mTOR signaling serves as a pivotal modulator. Meanwhile, accumulating evidence has revealed that non-coding RNAs (ncRNAs) interfering with mTOR signaling are involved in neuroinflammation and therefore articipate in the development and progression of epilepsy. In this review, we highlight recent advances in the regulation of mTOR on neuroinflammatory cells and mediators, and feature the progresses of the interaction between ncRNAs and mTOR in epileptic neuroinflammation.
Development of Live Attenuated Salmonella Typhimurium Vaccine Strain Using Radiation Mutation Enhancement Technology (R-MET)
Authors: Ji Hyun Jung , Jang A-Yeung , Song Joon Young , Ahn Ki Bum , Han Seung Hyun , Bang Seok Jin , Jung Ho Kyoung , Hur Jin , Seo Ho Seong
Published: July 2022

Salmonella enterica is a leading cause of food-borne diseases in humans worldwide, resulting in severe morbidity and mortality. They are carried asymptomatically in the intestine or gallbladder of livestock, and are transmitted predominantly from animals to humans via the fecal-oral route. Thus, the best preventive strategy is to preemptively prevent transmission to humans by vaccinating livestock. Live attenuated vaccines have been mostly favored because they elicit both cellular and humoral immunity and provide long-term protective immunity. However, developing these vaccines is a laborious and time-consuming process. Therefore, most live attenuated vaccines have been mainly used for phenotypic screening using the auxotrophic replica plate method, and new types of vaccines have not been sufficiently explored. In this study, we used Radiation-Mutation Enhancement Technology (R-MET) to introduce a wide variety of mutations and attenuate the virulence of Salmonella spp. to develop live vaccine strains. The Salmonella Typhimurium, ST454 strain (ST WT) was irradiated with Cobalt60 gamma-irradiator at 1.5 kGy for 1 h to maximize the mutation rate, and attenuated daughter colonies were screened using in vitro macrophage replication capacity and in vivo mouse infection assays. Among 30 candidates, ATOMSal-L6, with 9,961-fold lower virulence than the parent strain (ST454) in the mouse LD50 model, was chosen. This vaccine candidate was mutated at 71 sites, and in particular, lost one bacteriophage. As a vaccine, ATOMSal-L6 induced a Salmonella-specific IgG response to provide effective protective immunity upon intramuscular vaccination of mice. Furthermore, when mice and sows were orally immunized with ATOMSal-L6, we found a strong protective immune response, including multifunctional cellular immunity. These results indicate that ATOMSal-L6 is the first live vaccine candidate to be developed using R-MET, to the best of our knowledge. R-MET can be used as a fast and effective live vaccine development technology that can be used to develop vaccine strains against emerging or serotype-shifting pathogens.
Novel Findings in Teleost TRAF4, a Protein Acts as an Enhancer in TRIF and TRAF6 Mediated Antiviral and Inflammatory Signaling
Authors: Chen Ying , Li Ying , Li Peng Tian , Luo Zi Hao , Zhang Zi Ping , Wang Yi Lei , Zou Peng Fei
Published: July 2022

Tumor necrosis factor receptor-associated factors (TRAFs) are important adaptor molecules that play important roles in host immune regulation and inflammatory responses. Compared to other members of TRAFs, the function of TRAF4 in vertebrate immunity remains unclear, especially in teleosts. In the present study, TRAF4 ortholog was cloned and identified in large yellow croaker (Larimichthys crocea), named as Lc-TRAF4. The open reading frame (ORF) of Lc-TRAF4 is 1,413 bp and encodes a protein of 470 amino acids (aa), which is consisted of a RING finger domain, two zinc finger domains, and a MATH domain. The genome organization of Lc-TRAF4 is conserved in teleosts, amphibians, birds, and mammals, with 7 exons and 6 introns. Quantitative real-time PCR analysis revealed that Lc-TRAF4 was broadly distributed in various organs/tissues of healthy large yellow croakers and could be significantly up-regulated in the gill, intestine, spleen, head kidney, and blood under poly I:C, LPS, PGN, and Pseudomonas plecoglossicida stimulations. Notably, luciferase assays showed that overexpression of Lc-TRAF4 could significantly induce the activation of IRF3, IRF7, and type I IFN promoters, with the RING finger and zinc finger domains function importantly in such promoter activation. Confocal microscopy revealed that Lc-TRAF4 is located in the cytoplasm, whereas the deletion of the RING finger, zinc finger or MATH domain showed little effect on the subcellular localization of Lc-TRAF4. Interestingly, Lc-TRAF4 overexpression could significantly enhance Lc-TRIF and Lc-TRAF6 medicated IRF3 and IRF7 promoter activation. In addition, co-expression of Lc-TRAF4 with Lc-TRIF or Lc-TRAF6 could significantly induce the expression of antiviral and inflammation-related genes, including IRF3, IRF7, ISG15, ISG56, Mx, RSAD2, TNF-α, and IL-1β compared to the only overexpression of Lc-TRAF4, Lc-TRIF or Lc-TRAF6. These results collectively imply that Lc-TRAF4 functions as an enhancer in Lc-TRIF and Lc-TRAF6 mediated antiviral and inflammatory signaling.
Volume and Heat Transports by North Brazil Current Rings
Authors: Bueno Luana F. , Costa Vladimir S. , Mill Guilherme N. , Paiva Afonso M.
Published: July 2022

A methodology that combines a 24-year long (January 1993 to December 2016) global dataset of eddy trajectories, derived from altimetry, with vertical temperature and salinity profiles from the EN4.2.0 database, derived from XBTs/MBTs, CTDs and Argo floats, was used to reconstruct the mean vertical structure of North Brazil Current (NBC) rings, and to calculate some of their properties. The number of NBC rings formed each year varied from 2 to 8, with an annual-mean formation of 5.3 ± 1.5. During the analyzed period, 112 rings were sampled at least once, at various distances from the center of the rings, leading to a total of 1323 (604) temperature (salinity) profiles available to compute the mean NBC ring, depicting a large, surface intensified, and relatively shallow ring, with intense temperature and salinity anomalies. The meridional volume transport was estimated in 1.3 Sv (1Sv = 106 m3s-1) per ring, leading to an annualized transport of ~7 ± 2 Sv. The amount of South Atlantic Water (SAW) within the mean ring was estimated in ~40 to 60% of the ring volume. According to these estimates, NBC rings may be responsible in different years for approximately 20 to 80% of the northward volume transport associated with the upper limb of the Atlantic Meridional Overturning Circulation (AMOC), and approximately 15 to 55% of the meridional heat transport in the tropical Atlantic.
Review of Structure Types and New Development Prospects of Artificial Reefs in China
Authors: Pan Yun , Tong Huanhuan , Wei Dongze , Xiao Weiqi , Xue Dawen
Published: July 2022

Artificial reefs are beneficial to restore fishery resources and increase fishery production. Meanwhile, they play a significant role in improving ocean ecology and accelerating the evolution of fishery industries. Since they are generally affected by currents, waves, and other hydrological factors, the flow field around artificial reefs and their stabilities have become a research hotspot in recent years. Research on artificial reefs is a systematic process consisting of four aspects: Firstly, the significance, the definition, the mechanism, and the present research progress were introduced for artificial reefs in detail. Secondly, the development trend of the sit-bottom artificial reef and that of the floating artificial reef were summarized, respectively. Thirdly, it was found that the combination of traditional artificial reefs and emerging ocean engineering has a great development potential in practical engineering. Finally, the existing problems related to the hydrodynamic characteristics of the artificial reefs in China were summarized, and the prospects of artificial reefs were proposed. The purpose of this study is to provide a scientific reference for the ecological and sustainable development of the large-scale construction of artificial reefs in the ocean.
Climate-Change Refugia for the Bubblegum Coral Paragorgia arborea in the Northwest Atlantic
Authors: Wang Shuangqiang , Murillo F. Javier , Kenchington Ellen
Published: July 2022

The large, habitat-forming bubblegum coral,Paragorgia arborea, is a vulnerable marine ecosystem indicator with an antitropical distribution. Dense aggregations of the species have been protected from bottom-contact fishing in the Scotian Shelf bioregion off Nova Scotia, Canada in the northwest Atlantic Ocean. Recently, basin-scale habitat suitability ensemble modeling has projected an alarming loss of 99% of suitable habitat for this species across the North Atlantic by 2100. Here, a regional reassessment of the predicted distribution of this species in the bioregion, using both machine learning (random forest) and generalized additive model (GAM) frameworks, including projection to 2046−2065, was undertaken. Extrapolation diagnostics were applied to determine the degree to which the models projected into novel covariate space (i.e., extrapolation) in order to avoid erroneous inferences. The best predictors of the species’ distribution were a suite of temporally-invariant terrain variables that identified suitable habitat along the upper continental slope. Additional predictors, projected to vary with future ocean climatologies, identified areas of the upper slope in the eastern portion of the study area that will remain within suitable ranges forP. arboreaat least through to the mid-century. Additionally, 3-D Lagrangian particle tracking simulations indicated potential for both connectivity among known occurrence sites and existing protected areas, and for colonization of unsurveyed areas predicted to have suitable habitat, from locations of known occurrence. These results showed that extirpation of this iconic species from the Scotian Shelf bioregion is unlikely over the next decades. Potential climate refugia were identified and results presented in the context of protected area network design properties of representativity, connectivity, adequacy, viability and resilience.
Why and How is Burrow Ventilation Initiated? A Case Study of Polychaete Behavior in the Burrow at Different Temperatures
Authors: Fang Jinghui , Meng Shan , Lux Rosa Helena Escobar , Jiang Weiwei , Jiang Zengjie , Mao Yuze , Jansen Henrice , Fang Jianguang , Strand Øivind
Published: July 2022

Bioirrigation is a process corresponding to animal-induced transport of porewater solute or exchange between interstitial and overlying waters. How and why the burrowing macrobenthos complete this process remain unclear. Here, we used two infaunal-behavior observation devices to investigate the ventilation behaviors of the benthic polychaete Perinereis aibuhitensis Grube, a species that is widespread along the Asian coast with a wide temperature range, at various temperatures (5°C, 10°C, 15°C, 20°C, and 25°C). The two typical movement behaviors of P. aibuhitensis, axial crawling and radial undulation, as well as associated parameters, were delimited and quantified. We found that the radial undulation frequency of P. aibuhitensis and the associated pumping rate (PR) increased significantly with temperature (T, 5-25°C); this relationship can be described by the regression equation PR = −0.0067T2 + 0.29T - 0.52 (R2 = 0.749, P < 0.05; n = 15). The relationship between axial crawling velocity (ACV) and temperature (T, 5-25°C) can be expressed by the regression equation ACV = -0.0001T3 + 0.0059T2 - 0.063T + 0.28 (R2 = 0.997, P<0.05; n = 15). In general, pumping efficiency increased as temperature decreased, implying that the polychaete increasingly conserved energy at lower temperatures. Peak pumping volume (4.36 L d-1) was observed at 25°C, as a result of radial undulations. Thus, we concluded that radial undulation was the primary movement that led to bioirrigation. The dissolved oxygen demand was the key factor driving the initiation of radial undulation, and the specific aim of radial undulation was to increase oxygen availability by pumping new seawater into the burrow. Thus, radial undulation is critical for polychaete survival. The dissolved oxygen threshold level at which pumping was initiated increased with temperature, suggesting more energy conserved at lower temperatures. This pumping strategy of P. aibuhitensis is consistent with optimality theory, and is here designated the “optimal dissolved oxygen obtainment strategy”.
Cargo and Functional Profile of Saliva-Derived Exosomes Reveal Biomarkers Specific for Head and Neck Cancer
Authors: Hofmann Linda , Medyany Valentin , Ezić Jasmin , Lotfi Ramin , Niesler Beate , Röth Ralph , Engelhardt Daphne , Laban Simon , Schuler Patrick J. , Hoffmann Thomas K. , Brunner Cornelia , Jackson Edwin K. , Theodoraki Marie-Nicole
Published: July 2022

Background

Exosomes contribute to immunosuppression in head and neck squamous cell carcinoma (HNSCC), a tumor entity which lacks specific tumor biomarkers. Plasma-derived exosomes from HNSCC patients correlate with clinical parameters and have potential as liquid biopsy. Here, we investigate the cargo and functional profile of saliva-derived exosomes from HNSCC patients and their potential as non-invasive biomarkers for disease detection and immunomodulation.

Methods

Exosomes were isolated from saliva of HNSCC patients (n = 21) and healthy donors (HD, n = 12) by differential ultracentrifugation. Surface values of immune checkpoints and tumor associated antigens on saliva-derived exosomes were analyzed by bead-based flow cytometry using CD63 capture. Upon co-incubation with saliva-derived exosomes, activity and proliferation of T cells were assessed by flow cytometry (CD69 expression, CFSE assay). Adenosine levels were measured by mass spectrometry after incubation of saliva-derived exosomes with exogenous ATP. miRNA profiling of saliva-derived exosomes was performed using the nCounter® SPRINT system.

Results

Saliva-derived, CD63-captured exosomes from HNSCC patients carried high amounts of CD44v3, PDL1 and CD39. Compared to plasma, saliva was rich in tumor-derived, CD44v3+ exosomes and poor in hematopoietic cell-derived, CD45+ exosomes. CD8+ T cell activity was attenuated by saliva-derived exosomes from HNSCC patients, while proliferation of CD4+ T cells was not affected. Further, saliva-derived exosomes produced high levels of immunosuppressive adenosine. 62 HD- and 31 HNSCC-exclusive miRNAs were identified. Samples were grouped in “Healthy” and “Cancer” based on their saliva-derived exosomal miRNA profile, which was further found to be involved in RAS/MAPK, NF-κB complex, Smad2/3, and IFN-α signaling.

Conclusions

Saliva-derived exosomes from HNSCC patients were enriched in tumor-derived exosomes whose cargo and functional profile reflected an immunosuppressive TME. Surface values of CD44v3, PDL1 and CD39 on CD63-captured exosomes, adenosine production and the miRNA cargo of saliva-derived exosomes emerged as discriminators of disease and emphasized their potential as liquid biomarkers specific for HNSCC.
Effects of Taurine on Primary Metabolism and Transcription in a Coral Symbiodinium sp.
Authors: Huang Aiyou , Shi Hejing , Cui Ruoxuan , Cai Xiaoni , Xie Zhenyu
Published: July 2022

Coral reefs belong to the marine ecosystems and host the richest biodiversity of marine organisms. Coral reefs are formed as a result of the symbiotic relationship between the host coral animal and photosynthetic dinoflagellates, namely Symbiodinium sp. Coral animals induce the release of carbon fixation products of symbiotic Symbiodinium sp. through secreting host release factors (HRFs) such as taurine. To study the potential effect of taurine on photosynthesis and release of carbon fixation products of Symbiodinium sp., we compared the growth of Symbiodinium sp. under control and taurine-stimulated conditions. Photosynthesis parameters were detected to monitor the photosynthetic efficiency. Biomass and the contents of total soluble sugar, total insoluble sugar, total protein, total lipids, chlorophyll a were analyzed. Metabolome and transcriptome analyses were performed to analyze the potential effect of taurine on primary metabolism and mRNA transcription. The results revealed that taurine significantly increased the growth, photosynthesis efficiency, total soluble sugar, chlorophyll a, and chlorophyll b and free amino acid content of Symbiodinium sp. while decreased the content of total insoluble sugar. Results of metabolome and transcriptome analyses suggested that taurine might affect metabolic pathways in Symbiodinium sp. by altering the permeability of the algal cell membrane, diverting photosynthetically fixed carbon from storage compounds to translocated compounds, releasing a signal of low concentrations of nitrogen to initiate a series of response mechanisms, and controlling the density of Symbiodinium sp. through the quorum sensing effect. These results help to explore how corals control carbon metabolism in Symbiodinium sp. and to provide theoretical guidance for furthering our understanding of Symbiodinium sp. biology and coral-algal symbiosis.
Microbiomes Associated With the Surfaces of Northern Argentinian Fruits Show a Wide Species Diversity
Authors: Vermote Louise , Verce Marko , Mozzi Fernanda , De Vuyst Luc , Weckx Stefan
Published: July 2022

The fiber, vitamin, and antioxidant contents of fruits contribute to a balanced human diet. In countries such as Argentina, several tropical fruits are witnessing a high yield in the harvest season, with a resulting surplus. Fruit fermentation using autochthonous starter cultures can provide a solution for food waste. However, limited knowledge exists about the microbiota present on the surfaces of fruits and the preceding flowers. In the present exploratory study, the microbiomes associated with the surfaces of tropical fruits from Northern Argentina, such as white guava, passion fruit and papaya were investigated using a shotgun metagenomic sequencing approach. Hereto, one sample composed of 14 white guava fruits, two samples of passion fruits with each two to three fruits representing the almost ripe and ripe stage of maturity, four samples of papaya with each two to three fruits representing the unripe, almost ripe, and ripe stage of maturity were processed, as well as a sample of closed and a sample of open Japanese medlar flowers. A considerable heterogeneity was found in the composition of the fruits’ surface microbiota at the genus and species level. While bacteria dominated the microbiota of the fruits and flowers, a small number of the metagenomic sequence reads corresponded with yeasts and filamentous fungi. A minimal abundance of bacterial species critical in lactic acid and acetic acid fermentations was found. A considerable fraction of the metagenomic sequence reads from the fruits’ surface microbiomes remained unidentified, which suggested that intrinsic species are to be sequenced or discovered.
Recombinant Family 1 Carbohydrate-Binding Modules Derived From Fungal Cellulase Enhance Enzymatic Degradation of Lignocellulose as Novel Effective Accessory Protein
Authors: Jia Hexue , Feng Xiaoting , Huang Jiamin , Guo Yingjie , Zhang Daolei , Li Xuezhi , Zhao Jian
Published: July 2022

Fungal cellulases usually contain a family 1 carbohydrate-binding module (CBM1), and its role was considered to recognize the substrate specifically. This study testified that the CBM1s derived from cellobiohydrolase I of Trichoderma reesei, Penicillium oxalicum, and Penicillium funiculosum could be used as an effective accessory protein in cellulase cocktails to enhance the saccharification of lignocellulose, and its enhancement effect was significantly superior to some reported accessory proteins, such as bovine serum albumin (BSA). The promoting effects of the CBM1s were related to not only the CBM1 sources and protein dosages, but also the substrate characteristics and solid consistency during enzymatic hydrolysis. The adsorption capacity of the CBM1s, the adsorption kinetic of TrCBM from T. reesei and cellobiohydrolase, endoglucanase, and β-glucosidase from P. oxalicum, and the effect of adding TrCBM on enzyme activities of free cellulases in the hydrolysis system were investigated, and the binding conformations and affinities of CBM1s to cellulose and lignin were predicted by molecular docking. It was speculated that the higher affinity of the CBM1s to lignin than cellulases could potentially enable the CBM1s to displace cellulase adsorbed on lignin or to preferentially adsorb onto lignin to avoid ineffective adsorption of cellulase onto lignin, which enhanced cellulase system efficiency during enzymatic hydrolysis of lignocellulose.
Establishing Sterility Assurance for Bacillus canaveralius 29669 Spores Under High Heat Exposure
Authors: Dean Zachary Steven , DiNicola Michael , Klonicki Emily , Roberts Scott , Clement Brian Gregory , Guan Lisa
Published: July 2022

The ever-increasing complexity in critical spacecraft hardware and materials has led to the development of new microbial reduction procedures as well as to changes in established processes such as heat microbial reduction (HMR). In the space biology field of Planetary Protection, 500°C for 0.5 s is the current HMR recommendation to reduce microorganisms from flight hardware. However, more studies are needed to effectively determine the microbial reduction capability of high-temperature (more than 200°C), short-duration (under 30 s) heat exposures. One of the many recent microbial reduction bioengineering research avenues harnesses electromagnetic energy for microbial reduction, with previous investigations demonstrating that infrared heaters are capable of the short temperature ramp time required for rapid heating investigations above 200°C. Therefore, this study employed a 6 kW infrared heater to determine the survivability of heat resistant Bacillus canaveralius 29669 to high-temperature, short-duration infrared temperatures. While B. canaveralius 29669 spores can survive microbial heat reduction processes above 200°C, we found evidence suggesting that the 500°C for 0.5 s temperature sterilization specification for Planetary Protection should be updated. This research presents spore survival data and a corresponding model pointing to a re-evaluation of the recommended HMR exposure of 500°C for 0.5 s, while simultaneously meeting requirements on the forward biological contamination of solar system bodies and opening up design possibilities for future spacecraft hardware.
Bacterial Proprioception: Can a Bacterium Sense Its Movement?
Authors: Gupta Rachit , Yuan Junhua , Lele Pushkar P.
Published: July 2022

The evolution of the bacterial flagellum gave rise to motility and repurposing of a signaling network, now termed the chemotaxis network, enabled biasing of cell movements. This made it possible for the bacterium to seek out favorable chemical environments. To enable chemotaxis, the chemotaxis network sensitively detects extracellular chemical stimuli and appropriately modulates flagellar functions. Additionally, the flagellar motor itself is capable of detecting mechanical stimuli and adapts its structure and function in response, likely triggering a transition from planktonic to surface-associated lifestyles. Recent work has shown a link between the flagellar motor’s response to mechanical stimuli and the chemotactic output. Here, we elaborate on this link and discuss how it likely helps the cell sense and adapt to changes in its swimming speeds in different environments. We discuss the mechanism whereby the motor precisely tunes its chemotaxis output under different mechanical loads, analogous to proprioception in higher order organisms. We speculate on the roles bacterial proprioception might play in a variety of phenomena including the transition to surface-associated lifestyles such as swarming and biofilms.
Isolation of Bioactive Compounds, Antibacterial Activity, and Action Mechanism of Spore Powder From Aspergillus niger xj
Authors: Wei Longfeng , Zhang Qinyu , Xie Ailin , Xiao Yang , Guo Kun , Mu Shuzhen , Xie Yudan , Li Zhu , He Tengxia
Published: July 2022

Aspergillus fungi can produce a wide range of secondary metabolites, and they have represented a potential resource of novel bioactive compounds. Bacterial plant diseases have a serious impact on the sustainable development of agriculture worldwide, so it is necessary to use natural antibacterial compounds in microorganisms to control plant pathogens. This study was conducted to investigate the bioactive compounds of Aspergillus niger xj, three plant pathogens (Agrobacterium tumefaciens T-37, Erwinia carotovora EC-1, and Ralstonia solanacearum RS-2) were used as indicator bacteria, according to the biological activity tracking, five compounds were isolated from A. niger xj spore powder, and characterization of compounds was done by NMR (1H-NMR and 13C-NMR) and EI-MS and was identified as ergosterol (1), β-sitosterol (2), 5-pentadecylresorcinol (3), 5-hydroxymethyl-2-furancarboxylic acid (4), and succinimide (5). Compounds 3 and 5 were isolated from A. niger xj for the first time. The minimum inhibitory concentration (MIC) of five compounds against three plant pathogens was evaluated, the results showed that compound 4 exhibited the strongest antibacterial activity against tested bacteria, and RS-2 was the most sensitive to compound 4, showing the lowest MIC of 15.56 μg/ml. We concluded that the mechanism of action of the compound 4 against RS-2 might be described as compound 4 acting on bacterial protein synthesis and intracellular metabolism according to the results of the scanning electron microscopy observation, permeability of cell membrane and SDS-PAGE. These results indicated that compound 4 has good potential to be as a biocontrol agent. In conclusion, the results from this study demonstrated that the compounds with antibacterial activity are of great significance of the prevention and control of plant phytopathogenic bacteria, and they may be applicable to exploring alternative approaches to integrated control of phytopathogens.
Decoding the Role of Epigenetics in Breast Cancer Using Formal Modeling and Machine-Learning Methods
Authors: Asim Ayesha , Kiani Yusra Sajid , Saeed Muhammad Tariq , Jabeen Ishrat
Published: July 2022

Breast carcinogenesis is known to be instigated by genetic and epigenetic modifications impacting multiple cellular signaling cascades, thus making its prevention and treatments a challenging endeavor. However, epigenetic modification, particularly DNA methylation-mediated silencing of key TSGs, is a hallmark of cancer progression. One such tumor suppressor gene (TSG) RUNX3 (Runt-related transcription factor 3) has been a new insight in breast cancer known to be suppressed due to local promoter hypermethylation mediated by DNA methyltransferase 1 (DNMT1). However, the precise mechanism of epigenetic-influenced silencing of the RUNX3 signaling resulting in cancer invasion and metastasis remains inadequately characterized. In this study, a biological regulatory network (BRN) has been designed to model the dynamics of the DNMT1–RUNX3 network augmented by other regulators such as p21, c-myc, and p53. For this purpose, the René Thomas qualitative modeling was applied to compute the unknown parameters and the subsequent trajectories signified important behaviors of the DNMT1–RUNX3 network (i.e., recovery cycle, homeostasis, and bifurcation state). As a result, the biological system was observed to invade cancer metastasis due to persistent activation of oncogene c-myc accompanied by consistent downregulation of TSG RUNX3. Conversely, homeostasis was achieved in the absence of c-myc and activated TSG RUNX3. Furthermore, DNMT1 was endorsed as a potential epigenetic drug target to be subjected to the implementation of machine-learning techniques for the classification of the active and inactive DNMT1 modulators. The best-performing ML model successfully classified the active and least-active DNMT1 inhibitors exhibiting 97% classification accuracy. Collectively, this study reveals the underlined epigenetic events responsible for RUNX3-implicated breast cancer metastasis along with the classification of DNMT1 modulators that can potentially drive the perception of epigenetic-based tumor therapy.
Cations Do Not Alter the Membrane Structure of POPC—A Lipid With an Intermediate Area
Authors: Kurakin Sergei , Ivankov Oleksandr , Skoi Vadim , Kuklin Alexander , Uhríková Daniela , Kučerka Norbert
Published: July 2022

Combining small-angle neutron scattering (SANS), small-angle X-ray scattering (SAXS), and densitometric measurements, we have studied the interactions of the divalent cations Ca2+ and Mg2+ with the lipid vesicles prepared of a mixed-chain palmitoyl-oleoyl-phosphatidylcholine (POPC) at 25°C. The structural parameters of the POPC bilayer, such as the bilayer thickness, lateral area, and volume per lipid, displayed no changes upon the ion addition at concentrations up to 30 mM and minor changes at > 30 mM Ca2+ and Mg2+, while some decrease in the vesicle radius was observed over the entire concentration range studied. This examination allows us to validate the concept of lipid–ion interactions governed by the area per lipid suggested previously and to propose the mixed mode of those interactions that emerge in the POPC vesicles. We speculate that the average area per POPC lipid that corresponds to the cutoff length of lipid–ion interactions generates an equal but opposite impact on ion bridges and separate lipid–ion pairs. As a result of the dynamic equilibrium, the overall structural properties of bilayers are not affected. As the molecular mechanism proposed is affected by the structural properties of a particular lipid, it might help us to understand the fundamentals of processes occurring in complex multicomponent membrane systems.
Recent Advances in Transistor-Based Bionic Perceptual Devices for Artificial Sensory Systems
Authors: Yu Hongli , Zhu Yixin , Zhu Li , Lin Xinhuang , Wan Qing
Published: July 2022

The sensory nervous system serves as the window for human beings to perceive the outside world by converting external stimuli into distinctive spiking trains. The sensory neurons in this system can process multimodal sensory signals with extremely low power consumption. Therefore, new-concept devices inspired by the sensory neuron are promising candidates to address energy issues in nowadays’ robotics, prosthetics and even computing systems. Recent years have witnessed rapid development in transistor-based bionic perceptual devices, and it is urgent to summarize the research and development of these devices. In this review, the latest progress of transistor-based bionic perceptual devices for artificial sense is reviewed and summarized in five aspects, i.e., vision, touch, hearing, smell, and pain. Finally, the opportunities and challenges related to these areas are also discussed. It would have bright prospects in the fields of artificial intelligence, prosthetics, brain-computer interface, robotics, and medical testing.
Case Report: Rapid Progression of Cognitive Dysfunction as an Initial Feature of Systemic Lupus Erythematosus With Leukoencephalopathy: A Case Report and Literature Review
Authors: Feng Yukun , Yu Teng , Xiao Qin , Yang Xiaodong
Published: July 2022

Neuropsychiatric systemic lupus erythematosus (NPSLE) has been considered to have high morbidity and mortality. Thus, earlier recognition and treatment are of great importance. However, the rapid progression of cognitive dysfunction with leukoencephalopathy as an initial presentation in SLE is rarely described. We report a case in which an elderly man experienced rapidly progressive cognitive impairment with bilateral, symmetric, and diffuse leukoencephalopathy with lasting diffusion-weighted image hyperintensity. An immunological workup showed low complement levels and positivity for antinuclear antibody -speckle and Coombs tests in the patient's serum samples. He had an appropriate improvement in cognitive function after receiving a combination of various immunotherapies. Long-term follow-up showed clinical improvement, including rheumatological labs and neuroimaging. A review of the literature on NPSLE with leukoencephalopathy and a summary of all reported cases to date are also presented. Our case indicated that isolated leukoencephalopathy in NPSLE, as an indicator of severe NPSLE, can be recognized early. Immunotherapy is warranted given the possibility of clinical improvement.
Alterations of Cerebral Blood Flow and Its Connectivity in Olfactory-Related Brain Regions of Type 2 Diabetes Mellitus Patients
Authors: Luo Wei , Wang Jie , Chen Mimi , Zhou Shanlei , Deng Datong , Liu Fujun , Yu Yongqiang
Published: July 2022

To investigate the alteration of cerebral blood flow (CBF) and its connectivity patterns in olfactory-related regions of type 2 diabetes mellitus (T2DM) patients using arterial spin labeling (ASL). Sixty-nine patients with T2DM and 63 healthy controls (HCs) underwent ASL scanning using 3.0T magnetic resonance imaging. We compared the CBF values of the olfactory-related brain regions between the two groups and analyzed the correlation between their changes and clinical variables. We also used these regions as seeds to explore the differences in CBF connectivity patterns in olfactory-related brain regions between the T2DM patients and HCs. Compared with the HC group, the CBF of the right orbital part of the inferior frontal gyrus (OIFG), right insula, and bilateral olfactory cortex was decreased in the T2DM patients. Moreover, the duration of the patients was negatively correlated with the CBF changes in the right OIFG, right insula, and right olfactory cortex. The CBF changes in the right OIFG were positively correlated with the Self-Rating Depression Scale scores, those in the right insula were negatively correlated with the max blood glucose of continuous glucose, and those in the right olfactory cortex were negatively correlated with the mean blood glucose of continuous glucose. In addition, the T2DM patients also showed decreased CBF connectivity between the right OIFG and the left temporal pole of the middle temporal gyrus and increased CBF connectivity between the right medial orbital part of the superior frontal gyrus and the right orbital part of the superior frontal gyrus and between the right olfactory cortex and the bilateral caudate and the left putamen. Patients with T2DM have decreased CBF and altered CBF connectivity in multiple olfactory-related brain regions. These changes may help explain why olfactory dysfunction occurs in patients with T2DM, thus providing insights into the neuropathological mechanism of olfactory dysfunction and cognitive decline in T2DM patients.