bluuebunny/crossref_metadata_2025 huggingface dataset:
Trapezoid-Grid Finite-Difference Time-Domain Method for 3D Seismic Wavefield Modeling Using CPML Absorbing Boundary Condition
Authors: Wu Bangyu , Tan Wenzhuo , Xu Wenhao , Li Bo
Published: January 2022

The large computational memory requirement is an important issue in 3D large-scale wave modeling, especially for GPU calculation. Based on the observation that wave propagation velocity tends to gradually increase with depth, we propose a 3D trapezoid-grid finite-difference time-domain (FDTD) method to achieve the reduction of memory usage without a significant increase of computational time or a decrease of modeling accuracy. It adopts the size-increasing trapezoid-grid mesh to fit the increasing trend of seismic wave velocity in depth, which can significantly reduce the oversampling in the high-velocity region. The trapezoid coordinate transformation is used to alleviate the difficulty of processing ununiform grids. We derive the 3D acoustic equation in the new trapezoid coordinate system and adopt the corresponding trapezoid-grid convolutional perfectly matched layer (CPML) absorbing boundary condition to eliminate the artificial boundary reflection. Stability analysis is given to generate stable modeling results. Numerical tests on the 3D homogenous model verify the effectiveness of our method and the trapezoid-grid CPML absorbing boundary condition, while numerical tests on the SEG/EAGE overthrust model indicate that for comparable computational time and accuracy, our method can achieve about 50% reduction on memory usage compared with those on the uniform-grid FDTD method.
Spatiotemporal Dynamics of Cerebral Vascular Permeability in Type 2 Diabetes-Related Cerebral Microangiopathy
Authors: Chen Ying-Chen , Lu Bing-Ze , Shu Yu-Chen , Sun Yuan-Ting
Published: January 2022

Aims

Diabetes-related cerebral microangiopathy can manifest as cerebral small vessel disease (CSVD) and exhibit cognitive decline. To find the early change of function in advance, this study examined the spatiotemporal dynamics of cerebral vascular permeability (Ktrans) in the progression of type 2 diabetes mellitus (T2DM).

Methods

Ktrans was cross-sectionally measured in T2DM and non-diabetes groups with or without CSVD using dynamic contrast-enhanced MRI (DCE-MRI).

Results

In all patients with T2DM, the Ktrans of white matter (WM) was increased, whereas the Ktrans of gray matter (GM) was increased only in T2DM with CSVD. The involvement of WM was earlier than GM and was before the CSVD features could be visualized on MRI. Among the commonly available four CSVD items of MRI, microbleeds were the most sensitive, indicating the increased permeability in all patients. Increased Ktrans in T2DM was more associated with moderate WM hyperintensity but less with the presence of lacunae or multiple perivascular spaces, in contrast to patients without diabetes. The differential correlation suggested distinct mechanisms underlying diabetes-related CSVD and other CSVDs.

Conclusions

This study highlights the early development of cerebral microangiopathy with increased BBB leakage in T2DM, before the CSVD features can be visualized on MRI. The results may increase the proactivity of clinicians in recognizing the subsequent neurological comorbidities.
A Review: Depolymerization of Lignin to Generate High-Value Bio-Products: Opportunities, Challenges, and Prospects
Authors: Zhou Ningning , Thilakarathna W. P. D. Wass , He Quan Sophia , Rupasinghe H. P. Vasantha
Published: January 2022

Lignin is identified as a promising candidate in renewable energy and bioproduct manufacturing due to its high abundance, polymeric structure, and biochemical properties of monomers. Thus, emerging opportunities exist in generating high-value small molecules from lignin through depolymerization. This review aims at providing an overview of the major technologies of lignin depolymerization. The feasibility of large-scale implementation of these technologies, including thermal, biological, and chemical depolymerizations, are discussed in relation to potential industrial applications. Lignin as a renewable alternative to petroleum-based chemicals has been well documented. This review attempts to emphasize potential applications of lignin-derived monomers and their derivatives as bioactives in food, natural health product, and pharmaceutical sectors. The critical review of the prospects and challenges of lignin-derived bioproducts reveals that the advancement of research and development is required to explore the applications of depolymerization of lignins to their full potential.
Performance Prediction and Geometry Optimization for Application of Pump as Turbine: A Review
Authors: Liu Ming , Tan Lei , Cao Shuliang
Published: January 2022

Pump as Turbine (PAT) is a technically and economically effective technology to utilize small/mini/micro/pico hydropower, especially in rural areas. There are two main subjects that influence the selection and application of PAT. On the one hand, manufacturers of pumps will not provide their characteristics under the turbine mode, which requires performance prediction methods. On the other hand, PAT efficiency is always slightly lower than that of pump, which requires further geometry optimization. This literature review summarized published research studies related to performance prediction and geometry optimization, aimed at guiding for selection and optimization of PAT. Currently, there exist four categories of performance prediction methods, namely, using BEP (Best Efficiency Point), using specific speed, loss modeling, and polynomial fitting. The using BEP and loss modeling methods are based on theoretical analysis, while using specific speed and polynomial fitting methods require statistical fitting. The prediction errors of published methods are within ±10% mostly. For geometry optimization, investigations mainly focus on impeller diameter and blade geometry. The influence of impeller trimming, blade rounding, blade wrap angle, blade profile, blade number, blade trailing edge position, and guide vane number has been studied. Among published methods, the blade rounding and forward-curved impellers are the most effective and feasible techniques.
Numerical Analysis of a New Type of Dishwasher Pump for Different Rotation Speeds of the Volute
Authors: Ning Chao , Li Yalin , Huang Ping , Xu Hui , Zheng Feng
Published: January 2022

The interaction between impeller and volute produces a complex and unsteady water flow. It involves the interference of the non-uniform flow (such as the impeller’s jet wake and a secondary flow). In this paper, the transient flow in a new type of dishwasher pump is investigated numerically. In addition, pressure measurements are used to validate the numerical method, and the simulation results agree well with the experiment. Three schemes, 0 rpm (revolutions per minute)/30 rpm/60 rpm, of volute speeds are investigated. Multiple monitoring points are set at different positions of the new dishwasher pump to record pressure-pulse signals. In addition, frequency signals are obtained using a Fast Fourier Transform, which is then used to analyze the effect of the volute tongue and the outflow of the impeller. The radial force on the principal axis is recorded, and the schemes with different rotation speeds of volute are compared. The results show that the volute speed has only a small effect on the pump performance. In addition, the speed of the volute mainly affects the flow field in the transition section located between impeller and volute. The difference of the flow field in the impeller depends on the relative position between the impeller and the volute. The time domain curve for the pressure pulse is periodic, and there is a deviation between the peak for the schemes in the outflow region. In the frequency domain, the characteristic frequency equals the blade passing frequency. In the outflow region, the effect of the volute speeds increases with increasing volute speed. For the radial force, the rotating volute strengthens the fluctuation of the radial force, which affects the operational stability of the pump. The shape of the vector distribution is most regular for the 30 rpm scheme, which indicates that the stability of the pump is the highest. This paper can be used to improve both the control and selection of volute speeds.
Deciphering the Role of 3D Genome Organization in Breast Cancer Susceptibility
Authors: Baur Brittany , Lee Da-Inn , Haag Jill , Chasman Deborah , Gould Michael , Roy Sushmita
Published: January 2022

Cancer risk by environmental exposure is modulated by an individual’s genetics and age at exposure. This age-specific period of susceptibility is referred to as the “Window of Susceptibility” (WOS). Rats have a similar WOS for developing breast cancer. A previous study in rat identified an age-specific long-range regulatory interaction for the cancer gene, Pappa, that is associated with breast cancer susceptibility. However, the global role of three-dimensional genome organization and downstream gene expression programs in the WOS is not known. Therefore, we generated Hi-C and RNA-seq data in rat mammary epithelial cells within and outside the WOS. To systematically identify higher-order changes in 3D genome organization, we developed NE-MVNMF that combines network enhancement followed by multitask non-negative matrix factorization. We examined three-dimensional genome organization dynamics at the level of individual loops as well as higher-order domains. Differential chromatin interactions tend to be associated with differentially up-regulated genes with the WOS and recapitulate several human SNP-gene interactions associated with breast cancer susceptibility. Our approach identified genomic blocks of regions with greater overall differences in contact count between the two time points when the cluster assignments change and identified genes and pathways implicated in early carcinogenesis and cancer treatment. Our results suggest that WOS-specific changes in 3D genome organization are linked to transcriptional changes that may influence susceptibility to breast cancer.
Hsa-miR-557 Inhibits Osteosarcoma Growth Through Targeting KRAS
Authors: Qiao Zhi , Li Jinfeng , Kou Hongwei , Chen Xiangrong , Bao Deming , Shang Guowei , Chen Songfeng , Ji Yanhui , Cheng Tian , Wang Yisheng , Liu Hongjian
Published: January 2022

Objective: Osteosarcoma is the most common malignancy in the skeletal system; studies showed an important role of miRNAs in tumorigenesis, indicating miRNAs as possible therapeutic molecules. This study found abnormal hsa-miR-557 expression levels in osteosarcoma and tried to explore the potential function and the mechanism.

Methods: Differential expression genes of osteosarcoma were analyzed using GSE28423 from the GEO database. Survival analysis of miRNAs was conducted with data obtained from the TARGET-OS database. STRING and miRDIP were used to predict target genes of hsa-miR-557; KRAS was then verified using dual-luciferase reporter assay. Expression of genes was detected by qPCR, and levels of proteins were detected by Western blot. The proliferation ability of cells was detected by CCK-8 and cell cycle analysis. Tumor formation assay in nude mice was used to detect the influence of osteosarcoma by hsa-miR-557 in vivo.

Results: Analysis from the GEO and TARGET databases found 12 miRNAs that are significantly related to the osteosarcoma prognosis, 7 downregulated (hsa-miR-140-3p, hsa-miR-564, hsa-miR-765, hsa-miR-1224-5p, hsa-miR-95, hsa-miR-940, and hsa-miR-557) and 5 upregulated (hsa-miR-362-3p, hsa-miR-149, hsa-miR-96, hsa-miR-744, and hsa-miR-769-5p). CCK-8 analysis and cell cycle analysis found that hsa-miR-557 could significantly inhibit the proliferation of osteosarcoma cells. The tumor formation assay in nude mice showed that tumor sizes and weights were inhibited by hsa-miR-557 transfection. Further studies also proved that hsa-miR-557 could target the 3′UTR of KRAS and modulate phosphorylation of downstream proteins.

Conclusion: This study showed that hsa-miR-557 could inhibit osteosarcoma growth both in vivo and in vitro, by modulating KRAS expression.
Prenatal Cadmium Exposure Alters Proliferation in Mouse CD4+ T Cells via LncRNA Snhg7
Authors: McCall Jamie L. , Varney Melinda E. , Rice Emily , Dziadowicz Sebastian A. , Hall Casey , Blethen Kathryn E. , Hu Gangqing , Barnett John B. , Martinez Ivan
Published: January 2022

Objective

Prenatal cadmium (Cd) exposure leads to immunotoxic phenotypes in the offspring affecting coding and non-coding genes. Recent studies have shown that long non-coding RNAs (lncRNAs) are integral to T cell regulation. Here, we investigated the role of long non-coding RNA small nucleolar RNA host gene 7 (lncSnhg7) in T cell proliferation.

Methods

RNA sequencing was used to analyze the expression of lncRNAs in splenic CD4+ T cells with and without CD3/CD28 stimulation. Next, T cells isolated from offspring exposed to control or Cd water throughout mating and gestation were analyzed with and without stimulation with anti-CD3/CD28 beads. Quantitative qPCR and western blotting were used to detect RNA and protein levels of specific genes. Overexpression of a miR-34a mimic was achieved using nucleofection. Apoptosis was measured using flow cytometry and luminescence assays. Flow cytometry was also used to measure T cell proliferation in culture. Finally, lncSnhg7 was knocked down in splenic CD4+ T cells with lentivirus to assess its effect on proliferation.

Results

We identified 23 lncRNAs that were differentially expressed in stimulated versus unstimulated T cells, including lncSnhg7. LncSnhg7 and a downstream protein, GALNT7, are upregulated in T cells from offspring exposed to Cd during gestation. Overexpression of miR-34a, a regulator of lncSnhg7 and GALNT7, suppresses GALNT7 protein levels in primary T cells, but not in a mouse T lymphocyte cell line. The T cells isolated from Cd-exposed offspring exhibit increased proliferation after activation in vitro, but Treg suppression and CD4+ T cell apoptosis are not affected by prenatal Cd exposure. Knockdown on lncSnhg7 inhibits proliferation of CD4+ T cells.

Conclusion

Prenatal Cd exposure alters the expression of lncRNAs during T cell activation. The induction of lncSnhg7 is enhanced in splenic T cells from Cd offspring resulting in the upregulation of GALNT7 protein and increased proliferation following activation. miR-34a overexpression decreased GALNT7 expression and knockdown of lncSnhg7 inhibited proliferation suggesting that the lncSnhg7/miR-34a/GALNT7 is an important pathway in primary CD4+ T cells. These data highlight the need to understand the consequences of environmental exposures on lncRNA functions in non-cancerous cells as well as the effects in utero.
High Dimensional Analyses of Circulating Immune Cells in Psoriatic Arthritis Detects Elevated Phosphorylated STAT3
Authors: Macaubas Claudia , Rahman Shamma S. , Lavi Idit , Haddad Amir , Elias Muna , Sengupta Deepanwita , Zisman Devy , Mellins Elizabeth D.
Published: January 2022

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis, affecting up to 40% of patients with psoriasis. Constitutive expression by CD4+ T cells of an active form of STAT3, a signal transducer and transcription factor, has been shown to induce many of the major features of PsA in an animal model. We used high dimensional mass cytometry (CyTOF) to probe ex-vivo levels of phosphorylated STAT3 (pSTAT3) in circulating immune cell subpopulations from PsA patients during active and inactive states. We evaluated the frequency of 16 immune cell populations and the levels of the activated forms of STAT3 (pSTAT3) and, for comparison, STAT1 (pSTAT1) and Src (pSrc) in whole blood fixed shortly after collection. In addition to PsA patients, we studied active rheumatoid arthritis (RA) patients. Increased levels of pSTAT3 were found in all the CD4+ T cell subsets analyzed, specifically, Th1, Th2, Th17, T follicular helper (Tfh) and T regulatory (Treg) as well as in CD14+CD16- (classical) monocytes from active PsA patients compared to inactive patients. After correcting for body mass index (BMI), smoking and conventional disease modifying antirheumatic drugs (c-DMARDs), levels of pSTAT3 levels remained increased in Th1 and Tfh CD4+ T cells, and in CD14+CD16- monocytes from active patients compared to inactive patients. No differences between the patient groups were observed for pSTAT1 or pSrc. No differences were found between the active PsA and active RA groups after correction for multiple testing. During active PsA, circulating Th1 and Tfh CD4+ T cells, and CD14+CD16- monocytes expressing high levels of pSTAT3 may play a role in PsA pathophysiology, perhaps by migration to inflamed sites.
Epitope-Specific Anti-C1q Autoantibodies in Systemic Lupus Erythematosus
Authors: Kleer Jessica S. , Rabatscher Pascal A. , Weiss Jessica , Leonardi Joel , Vogt Severin B. , Kieninger-Gräfitsch Andrea , Chizzolini Carlo , Huynh-Do Uyen , Ribi Camillo , Trendelenburg Marten
Published: January 2022

Objective

In patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients.

Methods

First, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP®microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models.

Results

The epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p < 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q.

Conclusion

In this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE.
Transmembrane Helices Are an Over-Presented and Evolutionarily Conserved Source of Major Histocompatibility Complex Class I and II Epitopes
Authors: Bilderbeek Richèl J. C. , Baranov Maksim V. , van den Bogaart Geert , Bianchi Frans
Published: January 2022

Cytolytic T cell responses are predicted to be biased towards membrane proteins. The peptide-binding grooves of most alleles of histocompatibility complex class I (MHC-I) are relatively hydrophobic, therefore peptide fragments derived from human transmembrane helices (TMHs) are predicted to be presented more often as would be expected based on their abundance in the proteome. However, the physiological reason of why membrane proteins might be over-presented is unclear. In this study, we show that the predicted over-presentation of TMH-derived peptides is general, as it is predicted for bacteria and viruses and for both MHC-I and MHC-II, and confirmed by re-analysis of epitope databases. Moreover, we show that TMHs are evolutionarily more conserved, because single nucleotide polymorphisms (SNPs) are present relatively less frequently in TMH-coding chromosomal regions compared to regions coding for extracellular and cytoplasmic protein regions. Thus, our findings suggest that both cytolytic and helper T cells are more tuned to respond to membrane proteins, because these are evolutionary more conserved. We speculate that TMHs are less prone to mutations that enable pathogens to evade T cell responses.
Clinical Courses of IKAROS and CTLA4 Deficiencies: A Systematic Literature Review and Retrospective Longitudinal Study
Authors: Hoshino Akihiro , Toyofuku Etsushi , Mitsuiki Noriko , Yamashita Motoi , Okamoto Keisuke , Yamamoto Michio , Kanda Kenji , Yamato Genki , Keino Dai , Yoshimoto-Suzuki Yuri , Kamizono Junji , Onoe Yasuhiro , Ichimura Takuya , Nagao Mika , Yoshimura Masaru , Tsugawa Koji , Igarashi Toru , Mitsui-Sekinaka Kanako , Sekinaka Yujin , Doi Takehiko , Yasumi Takahiro , Nakazawa Yozo , Takagi Masatoshi , Imai Kohsuke , Nonoyama Shigeaki , Morio Tomohiro , Latour Sylvain , Kanegane Hirokazu
Published: January 2022

IKAROS and CTLA4 deficiencies are inborn errors of immunity and show similar clinical phenotypes, including hypogammaglobulinemia and autoimmune diseases (ADs). However, the differences in clinical features and pathogenesis of these are not fully understood. Therefore, we performed systematic literature reviews for IKAROS and CTLA4 deficiencies. The reviews suggested that patients with IKAROS deficiency develop AD earlier than hypogammaglobulinemia. However, no study assessed the detailed changes in clinical manifestations over time; this was likely due to the cross-sectional nature of the studies. Therefore, we conducted a retrospective longitudinal study on IKAROS and CTLA4 deficiencies in our cohort to evaluate the clinical course over time. In patients with IKAROS deficiency, AD and hypogammaglobulinemia often develop in that order, and AD often resolves before the onset of hypogammaglobulinemia; these observations were not found in patients with CTLA4 deficiency. Understanding this difference in the clinical course helps in the clinical management of both. Furthermore, our results suggest B- and T-cell-mediated ADs in patients with IKAROS and CTLA4 deficiencies, respectively.
LncRNA GAS5/miR-137 Is a Hypoxia-Responsive Axis Involved in Cardiac Arrest and Cardiopulmonary Cerebral Resuscitation
Authors: Jing Wang , Tuxiu Xie , Xiaobing Long , Guijun Jiang , Lulu Kang , Jie Jiang , Lu Ye , Liying Zhan , Xiaoxing Xiong , Jingjun Lyu
Published: January 2022

Background

Cardiac arrest/cardiopulmonary resuscitation (CA/CPR) represents one of the devastating medical emergencies and is associated with high mortality and neuro-disability. Post-cardiac arrest syndrome (PCAS) is mechanistically ascribed to acute systemic ischemia/reperfusion(I/R) injury. The lncRNA/microRNA/mRNA networks have been found to play crucial roles in the pathogenesis of the hypoxia-responsive diseases. Nonetheless, the precise molecular mechanisms by which lncRNA/miRNA/mRNA axes are involved in the astrocyte–microglia crosstalk in CA/CPR have not been fully elucidated.

Methods

We collected and purified the exosomes from the blood of CA/CPR patients and supernatant of OGD/R-stimulated astrocytes. On the basis of microarray analysis, bioinformatic study, and luciferase activity determination, we speculated that lncRNA GAS5/miR-137 is implicated in the astrocyte–microglia crosstalk under the insult of systemic I/R injury. The regulation of lncRNA GAS5/miR-137 on INPP4B was examined by cellular transfection in OGD/R cell culture and by lateral ventricle injection with miR-137 agomir in CA/CPR mice model. Flow cytometry and immunofluorescence staining were performed to detect the microglial apoptosis, M1/M2 phenotype transformation, and neuroinflammation. Neurological scoring and behavior tests were conducted in CA/CPR group, with miR-137 agomir lateral-ventricle infusion and in their controls.

Results

In all the micRNAs, miR-137 was among the top 10 micRNAs that experienced greatest changes, in both the blood of CA/CPR patients and supernatant of OGD/R-stimulated astrocytes. Bioinformatic analysis revealed that miR-137 was sponged by lncRNA GAS5, targeting INPP4B, and the result was confirmed by Luciferase activity assay. qRT-PCR and Western blotting showed that lncRNA GAS5 and INPP4B were over-expressed whereas miR-137 was downregulated in the blood of CA/CPR patients, OGD/R-stimulated astrocytes, and brain tissue of CA/CPR mice. Silencing lncRNA GAS5 suppressed INPP4B expression, but over-expression of miR-137 negatively modulated its expression. Western blotting exhibited that PI3K and Akt phosphorylation was increased when lncRNA GAS5 was silenced or miR-137 was over-expressed. However, PI3K and Akt phosphorylation was notably suppressed in the absence of miR-137, almost reversing their phosphorylation in the silencing lncRNA GAS5 group. Then we found that GAS5 siRNA or miR-137 mimic significantly increased cell viability and alleviated apoptosis after OGD/R injury. Furthermore, over-expression of miR-137 attenuated microglial apoptosis and neuroinflammation in CA/CPR mice model, exhibiting significantly better behavioral tests after CA/CPR.

Conclusion

LncRNA GAS5/miR-137 may be involved in the astrocyte–microglia communication that inhibits PI3K/Akt signaling activation via regulation of INPP4B during CA/CPR.
Human Brain Organoids as an In Vitro Model System of Viral Infectious Diseases
Authors: Su Xuan , Yue Peng , Kong Jing , Xu Xin , Zhang Yu , Cao Wenjing , Fan Yuxin , Liu Meixiao , Chen Jingjing , Liu Aihua , Bao Fukai
Published: January 2022

Brain organoids, or brainoids, have shown great promise in the study of central nervous system (CNS) infection. Modeling Zika virus (ZIKV) infection in brain organoids may help elucidate the relationship between ZIKV infection and microcephaly. Brain organoids have been used to study the pathogenesis of SARS-CoV-2, human immunodeficiency virus (HIV), HSV-1, and other viral infections of the CNS. In this review, we summarize the advances in the development of viral infection models in brain organoids and their potential application for exploring mechanisms of viral infections of the CNS and in new drug development. The existing limitations are further discussed and the prospects for the development and application of brain organs are prospected.
Paramylon from Euglena gracilis Prevents Lipopolysaccharide-Induced Acute Liver Injury
Authors: Xie Yunhao , Li Jin , Qin Huan , Wang Qing , Chen Zixi , Liu Chengyu , Zheng Ling , Wang Jiangxin
Published: January 2022

Acute liver injury (ALI) is a life-threatening syndrome with high mortality and lacks effective therapies. Rodents under LPS (lipopolysaccharide)/D-Gal (D-galactosamine) stress mimic ALI by presenting dramatically increased inflammation and cell death in the liver. Euglena gracilis, functioning like dietary fiber, is commonly used as a paramylon (Pa)-rich nutritional supplement that has various biological effects such as regulating immune system, anti-obesity, and anti-tumor. Here, we found that Pa or sonicated and alkalized paramylon (SA-Pa) alleviated the LPS/D-Gal-induced hepatic histopathological abnormalities in mice. Compared with Pa, SA-Pa had lower molecular weights/sizes and showed better efficacy in alleviating injury-induced hepatic functions, as well as the transcriptional levels of inflammatory cytokines. Moreover, SA-Pa treatment promoted M2 macrophage activation that enhanced the anti-inflammatory function in the liver, and downregulated STAT3 target genes, such as Fos, Jun, and Socs3 upon the injury. Meanwhile, SA-Pa treatment also alleviated apoptosis and necroptosis caused by the injury. Our results demonstrated that SA-Pa efficiently protected the liver from LPS/D-Gal-induced ALI by alleviating inflammation and cell death.
The Anti-DNA Antibodies: Their Specificities for Unique DNA Structures and Their Unresolved Clinical Impact—A System Criticism and a Hypothesis
Authors: Rekvig Ole Petter
Published: January 2022

Systemic lupus erythematosus (SLE) is diagnosed and classified by criteria, or by experience, intuition and traditions, and not by scientifically well-defined etiology(ies) or pathogenicity(ies). One central criterion and diagnostic factor is founded on theoretical and analytical approaches based on our imperfect definition of the term “The anti-dsDNA antibody”. “The anti-dsDNA antibody” holds an archaic position in SLE as a unique classification criterium and pathogenic factor. In a wider sense, antibodies to unique transcriptionally active or silent DNA structures and chromatin components may have individual and profound nephritogenic impact although not considered yet – not in theoretical nor in descriptive or experimental contexts. This hypothesis is contemplated here. In this analysis, our state-of-the-art conception of these antibodies is probed and found too deficient with respect to their origin, structural DNA specificities and clinical/pathogenic impact. Discoveries of DNA structures and functions started with Miescher’s Nuclein (1871),viaChargaff, Franklin, Watson and Crick, and continues today. The discoveries have left us with a DNA helix that presents distinct structures expressing unique operations of DNA. All structures are proven immunogenic! Unique autoimmune antibodies are described against e.g. ssDNA, elongated B DNA, bent B DNA, Z DNA, cruciform DNA, or individual components of chromatin. In light of the massive scientific interest in anti-DNA antibodies over decades, it is an unexpected observation that the spectrum of DNA structures has been known for decades without being implemented in clinical immunology. This leads consequently to a critical analysis of historical and contemporary evidence-based data and of ignored and one-dimensional contexts and hypotheses: i.e. “one antibody - one disease”. In this study radical viewpoints on the impact of DNA and chromatin immunity/autoimmunity are considered and discussed in context of the pathogenesis of lupus nephritis.
l-Isoleucine Administration Alleviates DSS-Induced Colitis by Regulating TLR4/MyD88/NF-κB Pathway in Rats
Authors: Mao Xiangbing , Sun Rui , Wang Qingxiang , Chen Daiwen , Yu Bing , He Jun , Yu Jie , Luo Junqiu , Luo Yuheng , Yan Hui , Wang Jianping , Wang Huifen , Wang Quyuan
Published: January 2022

Inflammatory bowel disease (namely, colitis) severely impairs human health. Isoleucine is reported to regulate immune function (such as the production of immunoreactive substances). The aim of this study was to investigate whether l-isoleucine administration might alleviate dextran sulfate sodium (DSS)-induced colitis in rats. In the in vitro trial, IEC-18 cells were treated by 4 mmol/L l-isoleucine for 12 h, which relieved the decrease of cell viability that was induced by TNF-α (10 ng/ml) challenge for 24 h (P <0.05). Then, in the in vivo experiment, a total of 44 Wistar rats were allotted into 2 groups that were fed l-isoleucine-supplemented diet and control diet for 35 d. From 15 to 35 d, half of the rats in the 2 groups drank the 4% DSS-adding water. Average daily gain, average daily feed intake and feed conversion of rats were impaired by DSS challenge (P <0.05). Drinking the DSS-supplementing water also increased disease activity index (DAI) and serum urea nitrogen level (P <0.05), shortened colonic length (P <0.05), impaired colonic enterocyte apoptosis, cell cycle, and the ZO-1 mRNA expression (P <0.05), increased the ratio of CD11c-, CD64-, and CD169-positive cells in colon (P <0.05), and induced extensive ulcer, infiltration of inflammatory cells, and collagenous fiber hyperplasia in colon. However, dietary l-isoleucine supplementation attenuated the negative effect of DSS challenge on growth performance (P <0.05), DAI (P <0.05), colonic length and enterocyte apoptosis (P <0.05), and dysfunction of colonic histology, and downregulated the ratio of CD11c-, CD64-, and CD169-positive cells, pro-inflammation cytokines and the mRNA expression of TLR4, MyD88, and NF-κB in the colon of rats (P <0.05). These results suggest that supplementing l-isoleucine in diet improved the DSS-induced growth stunting and colonic damage in rats, which could be associated with the downregulation of inflammation via regulating TLR4/MyD88/NF-κB pathway in colon.
Responses of Bloom-Forming Heterosigma akashiwo to Allelochemical Linoleic Acid: Growth Inhibition, Oxidative Stress and Apoptosis
Authors: Wang Renjun , Liu Qian
Published: January 2022

Algal blooms have been occurring in many regions worldwide, and allelochemicals are important algaecides used to control harmful algal blooms (HABs). The allelopathic effects of linoleic acid (LA) on the harmful raphidophyte Heterosigma akashiwo were studied, and the possible mechanisms were investigated through analyses of population growth dynamics, cellular ultrastructure and the physiological levels of H. akashiwo. The results showed that the inhibitory effect of LA on H. akashiwo cells increased with an increasing LA concentration. The levels of ROS and MDA were significantly elevated, indicating oxidative stress and lipid peroxidation due to LA exposure. At the same time, LA also activated the antioxidant system, including superoxide dismutase (SOD), catalase (CAT), and POD, and non-enzymatic antioxidants such as reduced AsA and glutathione (GSH). Transmission electron microscopy (TEM) revealed that the morphology of the algal cells was impaired in an LA-dependent manner. Annexin V-FITC/PI double staining and flow cytometric analysis revealed that LA exposure decreased the cellular mitochondrial membrane potential (MMP), increased the rate of apoptosis. LA modulated bcl-2/bax homeostasis and increased the expressions of cytochrome c and caspases-3 and -9, proving that LA induced cell death via the mitochondria-mediated apoptotic pathway. It was suggested that LA had allelopathic effects on H. akashiwo, inducing physiological and morphological changes and finally triggering the apoptosis of H. akashiwo. All of these results showed that LA might have the potential as an algaecide to control harmful algae.
Novel Findings of Retinal and Choroidal Features Utilizing Optical Coherence Tomography Angiography Analysis in Patients With Autoimmune Posterior Uveitis
Authors: Shen Junhui , Kong Jinfeng , Chen Si , Liu Xin , Teng Yan , Wu Hailan , Wang Lijuan , Wu Manman , Su Zhaoan , Feng Lei
Published: January 2022

Purpose: To analyze the quantitative parameters acquired by optical coherence tomography angiography (OCTA) in patients with autoimmune posterior uveitis.

Methods: OCTA images of 65 eyes affected with uveitis and 65 normal control (NC) eyes were obtained. The central macular thickness (CMT), retinal thicknesses, foveal avascular zone (FAZ) area, foveal density 300 μm (FD300), and vascular density (VD) were compared among acute uveitic eyes, chronic uveitic eyes, and NC eyes. VDs were evaluated in the choriocapillaris, outer retina, optic disk, whole and parafovea superficial capillary plexus (SCP), and whole and parafovea deep capillary plexus (DCP). Correlation analysis was used to analyze the relationship between LogMAR best-corrected visual acuity (BCVA) and quantitative parameters from OCTA.

Results: Compared with NC eyes, the CMT and retinal thicknesses were increased significantly in eyes with uveitis (p < 0.05, respectively). No significant difference was observed in the FAZ area. FD300, VDs in the optic disk, SCP, and DCP both in whole image and parafovea, choriocapillaris were significantly decreased in uveitis eyes (p < 0.05, respectively) compared with NC eyes, only the acute group had decreased VD of the outer retina and choriocapillaris compared with the NC group (p < 0.05). Moreover, quantitative parameters of OCTA showed a significant correlation with LogMAR BCVA in the patients with uveitis. Whole VD DCP was the best predictive factor for BCVA in the patients with uveitis.

Conclusion: Quantitative measurement by OCTA is a promising strategy for objective assessment of autoimmune posterior uveitis.
Long-Term Amelioration Practices Reshape the Soil Microbiome in a Coastal Saline Soil and Alter the Richness and Vertical Distribution Differently Among Bacterial, Archaeal, and Fungal Communities
Authors: Sun Ruibo , Wang Xiaogai , Tian Yinping , Guo Kai , Feng Xiaohui , Sun Hongyong , Liu Xiaojing , Liu Binbin
Published: January 2022

Globally soil salinity is one of the most devastating environmental stresses affecting agricultural systems and causes huge economic losses each year. High soil salinity causes osmotic stress, nutritional imbalance and ion toxicity to plants and severely affects crop productivity in farming systems. Freezing saline water irrigation and plastic mulching techniques were successfully developed in our previous study to desalinize costal saline soil. Understanding how microbial communities respond during saline soil amelioration is crucial, given the key roles soil microbes play in ecosystem succession. In the present study, the community composition, diversity, assembly and potential ecological functions of archaea, bacteria and fungi in coastal saline soil under amelioration practices of freezing saline water irrigation, plastic mulching and the combination of freezing saline water irrigation and plastic mulching were assessed through high-throughput sequencing. These amelioration practices decreased archaeal and increased bacterial richness while leaving fungal richness little changed in the surface soil. Functional prediction revealed that the amelioration practices, especially winter irrigation with saline water and film mulched in spring, promoted a community harboring heterotrophic features. β-null deviation analysis illustrated that amelioration practices weakened the deterministic processes in structuring coastal saline soil microbial communities. These results advanced our understanding of the responses of the soil microbiome to amelioration practices and provided useful information for developing microbe-based remediation approaches in coastal saline soils.
Oligomerization of the FliF Domains Suggests a Coordinated Assembly of the Bacterial Flagellum MS Ring
Authors: Mariano Giuseppina , Faba-Rodriguez Raquel , Bui Soi , Zhao Weilong , Ross James , Tzokov Svetomir B. , Bergeron Julien R. C.
Published: January 2022

The bacterial flagellum is a complex, self-assembling macromolecular machine that powers bacterial motility. It plays diverse roles in bacterial virulence, including aiding in colonization and dissemination during infection. The flagellum consists of a filamentous structure protruding from the cell, and of the basal body, a large assembly that spans the cell envelope. The basal body is comprised of over 20 different proteins forming several concentric ring structures, termed the M- S- L- P- and C-rings, respectively. In particular, the MS rings are formed by a single protein FliF, which consists of two trans-membrane helices anchoring it to the inner membrane and surrounding a large periplasmic domain. Assembly of the MS ring, through oligomerization of FliF, is one of the first steps of basal body assembly. Previous computational analysis had shown that the periplasmic region of FliF consists of three structurally similar domains, termed Ring-Building Motif (RBM)1, RBM2, and RBM3. The structure of the MS-ring has been reported recently, and unexpectedly shown that these three domains adopt different symmetries, with RBM3 having a 34-mer stoichiometry, while RBM2 adopts two distinct positions in the complex, including a 23-mer ring. This observation raises some important question on the assembly of the MS ring, and the formation of this symmetry mismatch within a single protein. In this study, we analyze the oligomerization of the individual RBM domains in isolation, in the Salmonella enterica serovar Typhimurium FliF ortholog. We demonstrate that the periplasmic domain of FliF assembles into the MS ring, in the absence of the trans-membrane helices. We also report that the RBM2 and RBM3 domains oligomerize into ring structures, but not RBM1. Intriguingly, we observe that a construct encompassing RBM1 and RBM2 is monomeric, suggesting that RBM1 interacts with RBM2, and inhibits its oligomerization. However, this inhibition is lifted by the addition of RBM3. Collectively, this data suggest a mechanism for the controlled assembly of the MS ring.
yggS Encoding Pyridoxal 5′-Phosphate Binding Protein Is Required for Acidovorax citrulli Virulence
Authors: Wang Yuanjie , Zhao Yuqiang , Xia Liming , Chen Lin , Liao Yajie , Chen Baohui , Liu Yiyang , Gong Weirong , Tian Yanli , Hu Baishi
Published: January 2022

Bacterial fruit blotch, caused by seed-borne pathogen Acidovorax citrulli, poses a serious threat to the production of cucurbits globally. Although the disease can cause substantial economic losses, limited information is available about the molecular mechanisms of virulence. This study identified that, a random transposon insertion mutant impaired in the ability to elicit a hypersensitive response on tobacco. The disrupted gene in this mutant was determined to be Aave_0638, which is predicted to encode a YggS family pyridoxal phosphate-dependent enzyme. YggS is a highly conserved protein among multiple organisms, and is responsible for maintaining the homeostasis of pyridoxal 5′-phosphate and amino acids in cells. yggS deletion mutant of A. citrulli strain XjL12 displayed attenuated virulence, delayed hypersensitive response, less tolerance to H2O2 and pyridoxine, increased sensitivity to antibiotic β-chloro-D-alanine, and reduced swimming. In addition, RNA-Seq analysis demonstrated that yggS was involved in regulating the expression of certain pathogenicity-associated genes related to secretion, motility, quorum sensing and oxidative stress response. Importantly, YggS significantly affected type III secretion system and its effectors in vitro. Collectively, our results suggest that YggS is indispensable for A.citrulli virulence and expands the role of YggS in the biological processes.
GAL08, an Uncultivated Group of Acidobacteria, Is a Dominant Bacterial Clade in a Neutral Hot Spring
Authors: Ruhl Ilona A. , Sheremet Andriy , Furgason Chantel C. , Krause Susanne , Bowers Robert M. , Jarett Jessica K. , Tran Triet M. , Grasby Stephen E. , Woyke Tanja , Dunfield Peter F.
Published: January 2022

GAL08 are bacteria belonging to an uncultivated phylogenetic cluster within the phylum Acidobacteria. We detected a natural population of the GAL08 clade in sediment from a pH-neutral hot spring located in British Columbia, Canada. To shed light on the abundance and genomic potential of this clade, we collected and analyzed hot spring sediment samples over a temperature range of 24.2–79.8°C. Illumina sequencing of 16S rRNA gene amplicons and qPCR using a primer set developed specifically to detect the GAL08 16S rRNA gene revealed that absolute and relative abundances of GAL08 peaked at 65°C along three temperature gradients. Analysis of sediment collected over multiple years and locations revealed that the GAL08 group was consistently a dominant clade, comprising up to 29.2% of the microbial community based on relative read abundance and up to 4.7 × 105 16S rRNA gene copy numbers per gram of sediment based on qPCR. Using a medium quality threshold, 25 single amplified genomes (SAGs) representing these bacteria were generated from samples taken at 65 and 77°C, and seven metagenome-assembled genomes (MAGs) were reconstructed from samples collected at 45–77°C. Based on average nucleotide identity (ANI), these SAGs and MAGs represented three separate species, with an estimated average genome size of 3.17 Mb and GC content of 62.8%. Phylogenetic trees constructed from 16S rRNA gene sequences and a set of 56 concatenated phylogenetic marker genes both placed the three GAL08 bacteria as a distinct subgroup of the phylum Acidobacteria, representing a candidate order (Ca. Frugalibacteriales) within the class Blastocatellia. Metabolic reconstructions from genome data predicted a heterotrophic metabolism, with potential capability for aerobic respiration, as well as incomplete denitrification and fermentation. In laboratory cultivation efforts, GAL08 counts based on qPCR declined rapidly under atmospheric levels of oxygen but increased slightly at 1% (v/v) O2, suggesting a microaerophilic lifestyle.
Positive Interactions Between Lactic Acid Bacteria Could Be Mediated by Peptides Containing Branched-Chain Amino Acids
Authors: Canon Fanny , Briard-Bion Valérie , Jardin Julien , Thierry Anne , Gagnaire Valérie
Published: January 2022

Lactic acid bacteria (LAB) are responsible for the sanitary, organoleptic, and health properties of most fermented products. Positive interactions between pairs of LAB strains, based on nitrogen dependencies, were previously demonstrated. In a chemically defined medium, using milk and lupin proteins as sole nitrogen source, two proteolytic strains were able to sustain the growth of non-proteolytic strains, but one did not. The objective of the present study was, thus, to determine which specific peptides were implicated in the positive interactions observed. Peptides produced and involved in the bacterial interactions were quantified using tandem mass spectrometry (LC-MS/MS). About 2,000 different oligopeptides ranging from 6 to more than 50 amino acids in length were identified during the time-course of the experiment. We performed a clustering approach to decipher the differences in peptide production during fermentation by the three proteolytic strains tested. We also performed sequence alignments on parental proteins and identified the cleavage site profiles of the three bacterial strains. Then, we characterized the peptides that were used by the non-proteolytic strains in monocultures. Hydrophobic and branched-chain amino acids within peptides were identified as essential in the interactions. Ultimately, better understanding how LAB can positively interact could be useful in multiple food-related fields, e.g., production of fermented food products with enhanced functional properties, or fermentation of new food matrices.
Antibacterial Activity and Multi-Targeting Mechanism of Dehydrocorydaline From Corydalis turtschaninovii Bess. Against Listeria monocytogenes
Authors: Kim Gowoon , Xu Yijuan , Zhang Jiarong , Sui Zhongquan , Corke Harold
Published: January 2022

Listeria monocytogenes is a foodborne pathogen, with relatively low incidence but high case-fatality. Phytochemicals have been recognized as a promising antimicrobial agent as an alternative to synthetic chemicals due to their safety and high efficacy with multi-target sites. This study identified and characterized a novel antibacterial agent, dehydrocorydaline, in the Corydalis turschaninovii rhizome using HPLC-LTQ-Orbitrap-HRMS, and its antibacterial effect with lowest MIC (1 mg/mL) and MBC (2 mg/mL) values. In addition, an in vitro growth kinetic assay, cytoplasmic nucleic acid and protein leakage assay, and observation of morphological changes in bacterial cells supported the strong antibacterial activity. Dehydrocorydaline also displayed effective inhibitory effects on biofilm formation and bacterial motility. In order to investigate the potential antibacterial mechanism of action of dehydrocorydaline against L. monocytogenes, label-free quantitative proteomics was used, demonstrating that dehydrocorydaline has multiple targets for combating L. monocytogenes including dysregulation of carbohydrate metabolism, suppression of cell wall synthesis, and inhibition of bacterial motility. Overall, this study demonstrated that dehydrocorydaline has potential as a natural and effective antibacterial agent with multi-target sites in pathogenic bacteria, and provides the basis for development of a new class of antibacterial agent.