bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of FCER1G related to Activated Memory CD4+ T Cells Infiltration by Gene Co-expression Network and Construction of a Risk Prediction Module in Diffuse Large B-Cell Lymphoma
Authors: Xiang Xiaoyu , Gao Li-Min , Zhang Yuehua , Tang Yuan , Zhao Sha , Liu Weiping , Ye Yunxia , Zhang Wenyan
Published: June 2022

Diffuse large B cell lymphoma (DLBCL) is a group of biologically heterogeneous tumors with different prognoses. The tumor microenvironment plays a vital role in the tumorigenesis and development of DLBCL, and activated memory CD4+ T cells are an essential component of immunological cells in the lymphoma microenvironment. So far, there are few reports about activated memory CD4+T cells infiltration and related genes in the DLBCL tumor microenvironment. This study obtained the mRNA expression profile information of the testing GSE87371 dataset and another six validation datasets (GSE53786, GSE181063, GSE10846, GSE32918, GSE32018, GSE9327, GSE3892, TCGA-DLBC) from the GEO and TCGA databases. Weighted Gene Co-expression Network Analysis (WGCNA) screened gene module associated with activated memory CD4+ T cells infiltration. CIBERSORT and TIMER (immune cells infiltrating estimation analysis tools) were used to identify the relationship between activated memory CD4+ T cells and genes associated with immune infiltrating cells in the tumor microenvironment. The least absolute shrinkage and selection operator (LASSO) built the risk prediction model and verified it using nomogram and Kaplan-Meier analysis. Further functional characterization includes Gene Ontology, KEGG pathway analysis and Gene Set Enrichment Analysis (GSEA) to investigate the role and underlying mechanisms of these genes. These results suggest that the expression of FCER1G can reflect the invasion of activated memory CD4+ T cells in DLBCL, which provides a new idea for studying the tumor microenvironment and may become a potential predictive biomarker for the assessment of DLBCL.
Identification of an Endoplasmic Reticulum Stress-Related Gene Signature to Evaluate the Immune Status and Predict the Prognosis of Hepatocellular Carcinoma
Authors: Song Dingli , Zhou Zhenyu , Zhang Dai , Wu Jie , Hao Qian , Zhao Lili , Ren Hong , Zhang Boxiang
Published: June 2022

Liver cancer is the sixth most frequently diagnosed primary malignancy and ranks as the third leading cause of cancer-related death worldwide in 2020. ER stress also plays a vital role in the pathogenesis of malignancies. In the current study, we aimed to construct an endoplasmic reticulum stress-related genes (ERGs) signature to predict the overall survival (OS) of patients with HCC. Differentially expressed ERGs (DE-ERGs) were analyzed using The Cancer Genome Atlas (TCGA-LIHC cohort) and International Cancer Genome Consortium (ICGC-LIRI-JP cohort) databases. The prognostic gene signature was identified by the univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression analysis. The predictive ability of the model was evaluated by utilizing Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves. Gene set variant analysis (GSVA) was performed to explore the underlying biological processes and signaling pathways. CIBERPORT and single-sample Gene Set Enrichment Analysis (ssGSEA) were implemented to estimate the immune status between the different risk groups. A total of 113 DE-ERGs were identified between 50 normal samples and 365 HCC samples in the TCGA-LIHC cohort, and 48 DE-ERGs were associated with OS through the univariate Cox regression. A six DE-ERGs (PPARGC1A, SQSTM1, SGK1, PON1, CDK1, and G6PD) signature was constructed and classified patients into high-risk and low-risk groups. The risk score was an independent prognostic indicator for OS (HR > 1, p < 0.001). The function enrichment analysis indicated that cell cycle, RNA degradation, protein localization, and cell division were the main biological processes. The high-risk group had higher immune cell infiltration levels than those of the low-risk group. We predicted the response to targeted therapy in high- and low-risk patients with HCC and found that the high-risk patients were more sensitive to pazopanib. At last, we verified the expression of the six gene patterns in HCC tissues by qRT-PCR and immunohistochemistry. This signature may be a potential tool to provide a choice for prognosis prediction and personal management of patients with HCC.
Strategies of LncRNA DLX6-AS1 on Study and Therapeutics
Authors: Zhao Yanyan , Li Pei
Published: June 2022

Accumulating evidence has revealed the vital regulatory roles of lncRNA DLX6-AS1 in various tumors at pre-transcriptional, transcriptional, and post-transcriptional levels, which makes it a potential prognosis factor and therapeutic target. In addition, the presence of lncRNA DLX6-AS1 in the exosomes of peripheral blood of patients with tumors may also contribute to it being a possible cancer-related biomarker. However, most literature studies are devoted to studying the effect of lncRNA DLX6-AS1 as a sponging molecule of miRNAs, the research of which is likely to get stuck into a dilemma. Literature studies published already have demonstrated an exciting cell malignant phenotype inhibition with the knockdown of lncRNA DLX6-AS1 in various tumor cell lines. With the comprehensive development of delivery systems, high-throughput sequencing, and aptamers, the problems of finding novel research methods and exploring the therapeutic options which are based on lncRNA DLX6-AS1 in vivo could come into a period to deal with. This review aims to summarize the research statuses of lncRNA DLX6-AS1, discuss other study methodologies and therapeutic strategies on it, which might be of help to the deep learning of lncRNA DLX6-AS1 and its application from basic to clinical research.
The Pathogenic R3052W BRCA2 Variant Disrupts Homology-Directed Repair by Failing to Localize to the Nucleus
Authors: Jimenez-Sainz Judit , Krysztofiak Adam , Garbarino Jennifer , Rogers Faye , Jensen Ryan B.
Published: June 2022

The BRCA2 germline missense variant, R3052W, resides in the DNA binding domain and has been previously classified as a pathogenic allele. In this study, we sought to determine how R3052W alters the cellular functions of BRCA2 in the DNA damage response. The BRCA2 R3052W mutated protein exacerbates genome instability, is unable to rescue homology-directed repair, and fails to complement cell survival following exposure to PARP inhibitors and crosslinking drugs. Surprisingly, despite anticipated defects in DNA binding or RAD51-mediated DNA strand exchange, the BRCA2 R3052W protein mislocalizes to the cytoplasm precluding its ability to perform any DNA repair functions. Rather than acting as a simple loss-of-function mutation, R3052W behaves as a dominant negative allele, likely by sequestering RAD51 in the cytoplasm.
Development of a Platelet-Related Prognostic Model for Colorectal Cancer
Authors: Wang Pengcheng , Zhao Wei , Cao Hailei
Published: June 2022

Colorectal cancer (CRC) represents one of the most common malignancies with high morbidity worldwide. Growing evidence has suggested that platelets are a fundamental component of the tumor microenvironment and play crucial roles in driving tumor biological behavior. The construction of a platelet-related prognostic model that can reliably predict CRC prognosis is of great clinical significance. The 1427 CRC-specific platelet-related genes were collected and mainly enriched in the ribosome and immune-related pathways. Based on platelet-related genes, three subtypes of TCGA CRC samples were identified by consensus clustering and characterized by differences in angiogenesis, epithelial–mesenchymal transition, immune infiltration, and prognosis. A total of 100 prognostic platelet-related genes were identified by univariate Cox regression. LASSO Cox regression further shrank those genes and constructed a 10-gene prognostic model. The patients with higher risk scores had significantly worse disease-specific survival than those with lower scores in both TCGA and validation cohorts. The risk score demonstrated good predictive performance for prognosis by receiver operating characteristic (ROC) curves. Furthermore, multivariate Cox regression analysis showed that the risk score was independent of TNM stage, sex, and age, and a graphic nomogram based on the risk score and clinical factors was developed to predict survival probability of CRC patients. Patients from the high-risk group were characterized by higher infiltration of immunosuppressive cells such as MDSC and Treg and higher expression of checkpoints CTLA4, CD86, and PDCD1LG2. Taken together, we identified three platelet-related subtypes and specifically constructed a promising 10-gene prognostic model in CRC. Our results highlighted the potential survival effects of platelet-related genes and provided evidence about their roles in regulating tumor immunity.
Case Report: Preimplantation Genetic Testing for X-Linked Severe Combined Immune Deficiency Caused by IL2RG Gene Variant
Authors: Ren Jun , Peng Cuiting , Zhou Fan , Li Yutong , Keqie Yuezhi , Chen Han , Zhu Hongmei , Chen Xinlian , Liu Shanling
Published: June 2022

Preimplantation genetic testing (PGT) has been increasingly used to prevent rare inherited diseases. In this study, we report a case where PGT was used to prevent the transmission of disease-caused variant in a SCID-X1 (OMIM:300400) family. SCID-X1 is an X-linked recessive inherited disease whose major clinical manifestation of immune deficiency is the significant reduction in the number of T-cells and natural killer cells. This family gave birth to a boy who was a hemizygous proband whose IL2RG gene was mutated (c.315T > A, p(Tyr105*), NM_000206.3, CM962677). In this case, Sanger sequencing for mutated allele and linkage analysis based on single-nucleotide polymorphism (SNP) haplotype via next-generation sequencing were performed simultaneously. After PGT for monogenic disorder, we detected the aneuploidy and copy number variation (CNV) for normal and female carrier embryos. Four embryos (E02, E09, E10, and E11) were confirmed without CNVs and inherited variants at the IL2RG gene. Embryo E02 (ranking 4BB) has been transferred after considering the embryo growth rate, morphology, and PGT results. Prenatal genetic diagnosis was used to detect amniotic fluid cells, showing that this fetus did not carry the variant of the IL2RG gene (c.315T > A). Ultimately, a healthy girl who had not carried disease-causing variants of SCID-X1 confirmed by prenatal diagnosis was born, further verifying our successful application of PGT in preventing mutated allele transmission for this SCID family.
Yoga at Every Size: A Preliminary Evaluation of a Brief Online Size-Inclusive Yoga and Body Gratitude Journaling Intervention to Enhance Positive Embodiment in Higher Weight College Women
Authors: Webb Jennifer B. , Padro Meagan P. , Thomas Erin Vinoski , Davies Alexandria E. , Etzel Lena , Rogers Courtney B. , Heredia Natalia I.
Published: June 2022

The present pilot randomized controlled trial (RCT) evaluated the feasibility, acceptability, and preliminary efficacy of a 4-week online yoga and body gratitude journaling intervention for strengthening positive embodiment among racially-diverse higher weight college women. Seventy-five participants were initially randomized to either the yoga condition (n = 36) or to a wait-list control (n = 39). Participants completed measures of positive and negative body image, weight bias internalization, self-compassion, drive for leanness, and physical activity acceptance at both baseline and post. Preliminary results among the 42 analyzed completers (mean age = 20.9, SD = 2.4; 30% Black or African American) revealed acceptable feasibility given the low-intensity nature of the intervention reflected in a 36% attrition rate. Self-reported adherence was strong for the yoga component with 81% of participants indicating that they practiced with the videos ≥3–4 times per week as suggested. Although 71% reported completing the body gratitude journal ≥1–2 times per week, daily adherence was minimal. Acceptability was also high among participants randomized to the yoga condition as indicated by 86% expressing at least moderate levels of satisfaction with the overall program. Qualitative feedback from participants further supported the acceptability of the program and pointed to important areas in further refining the protocol in the future. Preliminary efficacy was supported by significant reductions in internal body shame and gains in body appreciation, functional body appreciation, functional body satisfaction, functional body awareness, and behavioral commitment to physical activity engagement among the yoga vs. wait-list control participants. These promising findings once replicated in larger, higher-powered trials may have important implications for extending the reach and accessibility of mind-body wellness practices like yoga to benefit racially-/ethnically-diverse college women of higher weight. This research is further responsive to the growing need for efficacious remotely-delivered, and scalable behavioral health interventions in the ongoing era of the COVID-19 pandemic. However, additional research is warranted to explore ways of enhancing engagement of participants with lower levels of positive embodiment and to further incentivize the journaling component of the intervention.
Humoral and Cellular Responses to BNT162b2 as a Booster Following Two Doses of ChAdOx1 nCov-19 Determined Using Three SARS-CoV-2 Antibody Assays and an Interferon-Gamma Release Assay: A Prospective Longitudinal Study in Healthcare Workers
Authors: Jeong Seri , Lee Nuri , Lee Su Kyung , Cho Eun-Jung , Hyun Jungwon , Park Min-Jeong , Song Wonkeun , Kim Hyun Soo
Published: June 2022

Data on humoral and cellular responses to BNT162b2 as a booster dose, following two doses of ChAdOx1 nCov-19 vaccine, have seldom been reported. The aim of this study was to assess the positivity rates of three representative antibody assays targeting total, IgG, and neutralizing antibodies, and an interferon-γ release assay (IGRA), and to determine the longitudinal changes in quantitative antibody titers after each vaccination. A total of 1027 samples were collected from healthcare workers. The number of participants after the booster dose was 153, and they all completed a questionnaire on adverse reactions. All antibody assays showed 100.0% positivity at 1 month after booster vaccination. The median antibody titers of the assays were significantly increased compared with those after the second dose (22.1-fold increase for Roche total antibody, 14.0-fold increase for Abbott IgG, and 1.1-fold increase (97.5% inhibition) for GenScript neutralizing antibody). Cellular responses determined using the IGRA were positive in 92.8% of the participants. Most participants (72.5%) reported mild adverse reactions. Correlations between the three antibody assays and IGRA were weak or negligible, indicating a difference between humoral and cellular responses. Overall, our study provides information about booster vaccine strategies and laboratory settings, which could subsequently contribute to the control of the spread of coronavirus disease 2019.
Sandfly Fever Viruses Attenuate the Type I Interferon Response by Targeting the Phosphorylation of JAK-STAT Components
Authors: Moalem Yarden , Malis Yehonathan , Voloshin Konstantin , Dukhovny Anna , Hirschberg Koret , Sklan Ella H.
Published: June 2022

Sandfly fever viruses are emerging Phleboviruses typically causing mild febrile illness. Some strains, however, can cause severe and occasionally fatal neuro-invasive disease. Like most viruses, Phleboviruses have devised various strategies to inhibit the type I interferon (IFN) response to support a productive infection. Still, most of the strategies identified so far focus on inhibiting the sensing arm of the IFN response. In contrast, the effect of sandfly virus infection on signaling from the IFN receptor is less characterized. Therefore, we tested the effect of sandfly fever virus Naples (SFNV) and Sicily (SFSV) infection on IFN signaling. We found that infection with either of these viruses inhibits signaling from the IFN receptor by inhibiting STAT1 phosphorylation and nuclear localization. We show that the viral nonstructural protein NSs mediates these effects, but only NSs from SFNV was found to interact with STAT1 directly. Thus, we tested the upstream IFN signaling components and found that Janus kinase 1 (Jak1) phosphorylation is also impaired by infection.

Furthermore, the NSs proteins from both viruses directly interacted with Jak1. Last, we show that IFN inhibition by SFNV and SFSV is most likely downstream of the IFN receptor at the Jak1 level. Overall, our results reveal the multiple strategies used by these related viruses to overcome host defenses.
Nanoscale Colocalization of NK Cell Activating and Inhibitory Receptors Controls Signal Integration
Authors: Tomaz David , Pereira Pedro Matos , Guerra Nadia , Dyson Julian , Gould Keith , Henriques Ricardo
Published: June 2022

Natural killer (NK) cell responses depend on the balance of signals from inhibitory and activating receptors. However, how the integration of antagonistic signals occurs upon NK cell–target cell interaction is not fully understood. Here we provide evidence that NK cell inhibitionviathe inhibitory receptor Ly49A is dependent on its relative colocalization at the nanometer scale with the activating receptor NKG2D upon immune synapse (IS) formation. NKG2D and Ly49A signal integration and colocalization were studied using NKG2D-GFP and Ly49A-RFP-expressing primary NK cells, forming ISs with NIH3T3 target cells, with or without the expression of single-chain trimer (SCT) H2-Dd and an extended form of SCT H2-Dd-CD4 MHC-I molecules. Nanoscale colocalization was assessed by Förster resonance energy transfer between NKG2D-GFP and Ly49A-RFP and measured for each synapse. In the presence of their respective cognate ligands, NKG2D and Ly49A colocalize at the nanometer scale, leading to NK cell inhibition. However, increasing the size of the Ly49A ligand reduced the nanoscale colocalization with NKG2D, consequently impairing Ly49A-mediated inhibition. Thus, our data shows that NK cell signal integration is critically dependent on the dimensions of NK cell ligand–receptor pairs by affecting their relative nanometer-scale colocalization at the IS. Our results together suggest that the balance of NK cell signals and NK cell responses is determined by the relative nanoscale colocalization of activating and inhibitory receptors in the immune synapse.
Priming With Rhinovirus Protects Mice Against a Lethal Pulmonary Coronavirus Infection
Authors: Cox Garrison , Gonzalez Andres J. , Ijezie Emmanuel C. , Rodriguez Andres , Miller Craig R. , Van Leuven James T. , Miura Tanya A.
Published: June 2022

Rhinoviruses (RV) have been shown to inhibit subsequent infection by heterologous respiratory viruses, including influenza viruses and severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). To better understand the mechanisms whereby RV protects against pulmonary coronavirus infection, we used a native murine virus, mouse hepatitis virus strain 1 (MHV-1), that causes severe disease in the lungs of infected mice. We found that priming of the respiratory tract with RV completely prevented mortality and reduced morbidity of a lethal MHV-1 infection. Replication of MHV-1 was reduced in RV-primed mouse lungs although expression of antiviral type I interferon, IFN-β, was more robust in mice infected with MHV-1 alone. We further showed that signaling through the type I interferon receptor was required for survival of mice given a non-lethal dose of MHV-1. RV-primed mice had reduced pulmonary inflammation and hemorrhage and influx of leukocytes, especially neutrophils, in the airways upon MHV-1 infection. Although MHV-1 replication was reduced in RV-primed mice, RV did not inhibit MHV-1 replication in coinfected lung epithelial cells in vitro. In summary, RV-mediated priming in the respiratory tract reduces viral replication, inflammation, and tissue damage, and prevents mortality of a pulmonary coronavirus infection in mice. These results contribute to our understanding of how distinct respiratory viruses interact with the host to affect disease pathogenesis, which is a critical step in understanding how respiratory viral coinfections impact human health.
COVID-19 and Preexisting Comorbidities: Risks, Synergies, and Clinical Outcomes
Authors: Bigdelou Banafsheh , Sepand Mohammad Reza , Najafikhoshnoo Sahar , Negrete Jorge Alfonso Tavares , Sharaf Mohammed , Ho Jim Q. , Sullivan Ian , Chauhan Prashant , Etter Manina , Shekarian Tala , Liang Olin , Hutter Gregor , Esfandiarpour Rahim , Zanganeh Steven
Published: June 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated symptoms, named coronavirus disease 2019 (COVID-19), have rapidly spread worldwide, resulting in the declaration of a pandemic. When several countries began enacting quarantine and lockdown policies, the pandemic as it is now known truly began. While most patients have minimal symptoms, approximately 20% of verified subjects are suffering from serious medical consequences. Co-existing diseases, such as cardiovascular disease, cancer, diabetes, and others, have been shown to make patients more vulnerable to severe outcomes from COVID-19 by modulating host–viral interactions and immune responses, causing severe infection and mortality. In this review, we outline the putative signaling pathways at the interface of COVID-19 and several diseases, emphasizing the clinical and molecular implications of concurring diseases in COVID-19 clinical outcomes. As evidence is limited on co-existing diseases and COVID-19, most findings are preliminary, and further research is required for optimal management of patients with comorbidities.
Differential Regulation of Allergic Airway Inflammation by Acetylcholine
Authors: Roberts Luke B. , Berkachy Rita , Wane Madina , Patel Dhiren F. , Schnoeller Corinna , Lord Graham M. , Gounaris Kleoniki , Ryffel Bernhard , Quesniaux Valerie , Darby Matthew , Horsnell William G. C. , Selkirk Murray E.
Published: June 2022

Acetylcholine (ACh) from neuronal and non-neuronal sources plays an important role in the regulation of immune responses and is associated with the development of several disease pathologies. We have previously demonstrated that group 2 innate lymphoid cell (ILC2)-derived ACh is required for optimal type 2 responses to parasitic infection and therefore sought to determine whether this also plays a role in allergic inflammation. RoraCre+ChatLoxP mice (in which ILC2s cannot synthesize ACh) were exposed to an allergenic extract of the fungus Alternaria alternata, and immune responses in the airways and lung tissues were analyzed. Airway neutrophilia and expression of the neutrophil chemoattractants CXCL1 and CXCL2 were enhanced 24 h after exposure, suggesting that ILC2-derived ACh plays a role in limiting excessive pulmonary neutrophilic inflammation. The effect of non-selective depletion of ACh was examined by intranasal administration of a stable parasite-secreted acetylcholinesterase. Depletion of airway ACh in this manner resulted in a more profound enhancement of neutrophilia and chemokine expression, suggesting multiple cellular sources for the release of ACh. In contrast, depletion of ACh inhibited Alternaria-induced activation of ILC2s, suppressing the expression of IL-5, IL-13, and subsequent eosinophilia. Depletion of ACh reduced macrophages with an alternatively activated M2 phenotype and an increase in M1 macrophage marker expression. These data suggest that ACh regulates allergic airway inflammation in several ways, enhancing ILC2-driven eosinophilia but suppressing neutrophilia through reduced chemokine expression.
Peripheral Organ Injury After Stroke
Authors: Wang Jin , Zhang Jiehua , Ye Yingze , Xu Qingxue , Li Yina , Feng Shi , Xiong Xiaoxing , Jian Zhihong , Gu Lijuan
Published: June 2022

Stroke is a disease with high incidence, mortality and disability rates. It is also the main cause of adult disability in developed countries. Stroke is often caused by small emboli on the inner wall of the blood vessels supplying the brain, which can lead to arterial embolism, and can also be caused by cerebrovascular or thrombotic bleeding. With the exception of recombinant tissue plasminogen activator (rt-PA), which is a thrombolytic drug used to recanalize the occluded artery, most treatments have been demonstrated to be ineffective. Stroke can also induce peripheral organ damage. Most stroke patients have different degrees of injury to one or more organs, including the lung, heart, kidney, spleen, gastrointestinal tract and so on. In the acute phase of stroke, severe inflammation occurs in the brain, but there is strong immunosuppression in the peripheral organs, which greatly increases the risk of peripheral organ infection and aggravates organ damage. Nonneurological complications of stroke can affect treatment and prognosis, may cause serious short-term and long-term consequences and are associated with prolonged hospitalization and increased mortality. Many of these complications are preventable, and their adverse effects can be effectively mitigated by early detection and appropriate treatment with various medical measures. This article reviews the pathophysiological mechanism, clinical manifestations and treatment of peripheral organ injury after stroke.
Genome Wide Identification and Expression Profiling Indicate Expansion of Family I84 Protease Inhibitor via Gene Tandem Duplication and Divergence in Razor Clam Sinonovacula constricta
Authors: Liu Sheng , Liu Youli , Lu Jiali , Mao Jinxia , Lin Zhihua , Xue Qinggang
Published: June 2022

Family I84 protease inhibitors represent a novel family in the MEROPS peptidase database and are likely unique for molluscan host defense. Two Family I84 members, scSI-1 and scSI-2, were reported from the razor clam Sinonovacula constricta in a previous research. In the present study, 12 additional genes, named scSI-3 to scSI-14, were identified via genome wide sequence analyses. Among them, 10 genes were predicted to have a signal sequence, but one (scSI-7) was not. Besides, one sequence (scSI-14) was likely to encode a prematurely terminated peptide. The predicted mature peptides shared characteristics including 12 conserved cysteine residues, isoelectric points of 4.98 to 6.11, and molecular weights of 7.1 to 9.3 kDa with previously reported family members. Four motifs were characterized in 13 predicted mature peptides (with exception of scSI-14), which shared two to four conserved cysteine residues, are possibly to form two functional domain comprised 6 cysteine residues, respectively. At genomic level, all the 14 razor clam Family I84 genes were organized into 3 exons and 2 introns; 13 of them clustered in 3 regions of 100 kb on 3 separate chromosomes, suggesting tandem duplications of related genes. The promoter region of all the 14 genes was predicted to share some transcription factor binding sites, in particular those responsive to pathological and physiological stimuli, but no shared motifs were identified. Analyses also revealed differences in expression patterns among the genes. One gene in a tandem duplicated gene pairs usually showed a higher expression level than the other whereas non-tandem duplicated genes exhibited a higher degree of correlation in expression level. In addition, 8 of the 14 genes demonstrated higher level of expression in Vibrio tolerant clams than in non-tolerant clams following challenges with Vibrio parahaemolyticus. These results generated important information about the evolution of Family I84 protease inhibitors in S. constricta.
Vaccination With Oral Polio Vaccine Reduces COVID-19 Incidence
Authors: Yagovkina Nadezhda V. , Zheleznov Lev M. , Subbotina Ksenia A. , Tsaan Andrey A. , Kozlovskaya Liubov I. , Gordeychuk Ilya V. , Korduban Anastasia K. , Ivin Yury Y. , Kovpak Anastasia A. , Piniaeva Anastasia N. , Shishova Anna A. , Shustova Elena Y. , Khapchaev Yusuf K. , Karganova Galina G. , Siniugina Alexandra A. , Pomaskina Tatiana V. , Erovichenkov Aleksandr A. , Chumakov Konstantin , Ishmukhametov Aydar A.
Published: June 2022

Background

Effective response to emerging pandemic threats is complicated by the need to develop specific vaccines and other medical products. The availability of broadly specific countermeasures that could be deployed early in the pandemic could significantly alter its course and save countless lives. Live attenuated vaccines (LAVs) were shown to induce non-specific protection against a broad spectrum of off-target pathogens by stimulating innate immune responses. The purpose of this study was to evaluate the effect of immunization with bivalent Oral Poliovirus Vaccine (bOPV) on the incidence of COVID-19 and other acute respiratory infections (ARIs).

Methods and Findings

A randomized parallel-group comparative study was conducted in Kirov Medical University. 1115 healthy volunteers aged 18 to 65 were randomized into two equal groups, one of which was immunized orally with a single dose of bOPV “BiVac Polio” and another with placebo. The study participants were monitored for three months for respiratory illnesses including COVID-19. The endpoint was the incidence of acute respiratory infections and laboratory confirmed COVID-19 in both groups during 3 months after immunization. The number of laboratory-confirmed cases of COVID-19 was significantly lower in the vaccinated group than in placebo (25 cases vs. 44, p=0.036). The difference between the overall number of clinically diagnosed respiratory illnesses in the two groups was not statistically significant.

Conclusions

Immunization with bOPV reduced the number of laboratory-confirmed COVID-19 cases, consistent with the original hypothesis that LAVs induce non-specific protection against off-target infections. The findings are in line with previous observations of the protective effects of OPV against seasonal influenza and other viral and bacterial pathogens. The absence of a statistically significant effect on the total number of ARIs may be due to the insufficient number of participants and heterogeneous etiology of ARIs. OPV could be used to complement specific coronavirus vaccines, especially in regions of the world where the vaccines are unavailable, and as a stopgap measure for urgent response to future emerging infections. Clinical trial registration number NCT05083039 at clinicaltrals.gov https://clinicaltrials.gov/ct2/show/NCT05083039?term=NCT05083039&draw=2&rank=1
Immune Microenvironment in Osteosarcoma: Components, Therapeutic Strategies and Clinical Applications
Authors: Zhu Tianyi , Han Jing , Yang Liu , Cai Zhengdong , Sun Wei , Hua Yingqi , Xu Jing
Published: June 2022

Osteosarcoma is a primary malignant tumor that tends to threaten children and adolescents, and the 5-year event-free survival rate has not improved significantly in the past three decades, bringing grief and economic burden to patients and society. To date, the genetic background and oncogenesis mechanisms of osteosarcoma remain unclear, impeding further research. The tumor immune microenvironment has become a recent research hot spot, providing novel but valuable insight into tumor heterogeneity and multifaceted mechanisms of tumor progression and metastasis. However, the immune microenvironment in osteosarcoma has been vigorously discussed, and the landscape of immune and non-immune component infiltration has been intensively investigated. Here, we summarize the current knowledge of the classification, features, and functions of the main infiltrating cells, complement system, and exosomes in the osteosarcoma immune microenvironment. In each section, we also highlight the complex crosstalk network among them and the corresponding potential therapeutic strategies and clinical applications to deepen our understanding of osteosarcoma and provide a reference for imminent effective therapies with reduced adverse effects.
Glycoprotein B Antibodies Completely Neutralize EBV Infection of B Cells
Authors: Hong Junping , Wei Dongmei , Zhong Ling , Wu Qian , Chen Kaiyun , Zhang Wanlin , Yang Yanbo , Chen Junyu , Xia Ningshao , Zhang Xiao , Chen Yixin
Published: June 2022

The Epstein–Barr virus (EBV) is the first reported oncogenic herpesvirus that establishes persistent infection in B lymphocytes in 95% of adults worldwide. Glycoprotein B (gB) plays a predominant role in the fusion of the viral envelope with the host cell membrane. Hence, it is of great significance to isolate gB-specific fusion-inhibiting neutralizing antibodies (NAbs). AMMO5 is the only gB NAb but fails to antagonize B-cell infection. It is essential to isolate potent NAbs that can completely block EBV infection of B cells. Using hybridoma technology and neutralization assay, we isolate two gB NAbs 8A9 and 8C12 that are capable of completely neutralizing B-cell infection in vitro. In addition, 8A9 shows cross-reactivity with rhesus lymphocryptovirus (rhLCV) gB. Competitive binding experiments demonstrate that 8A9 and 8C12 recognize novel epitopes that are different from the AMMO5 epitope. The epitopes of 8A9 and 8C12 are mapped to gB D-II, and the AMMO5 epitope is located precisely at gB aa 410–419. We find that 8A9 and 8C12 significantly inhibit gB-derived membrane fusion using a virus-free fusion assay. In summary, this study identifies two gB-specific NAbs that potently block EBV infection of B cells. Our work highlights the importance of gB D-II as a predominant neutralizing epitope, and aids in the rational design of therapeutics or vaccines based on gB.
Consideration of Genetic Structure in the Ecologically or Biologically Significant Marine Areas Criteria: A Review of Convention on Biological Diversity Regional Workshops and A Case Study of Coral Reef Conservation Planning
Authors: Yamakita Takehisa , Sodeyama Fumiaki , Iguchi Akira , Kitano Yuko F. , Teshima Kosuke M. , Shimura Akifumi , Nakabayashi Aki , Nagai Satoshi , Nakamura Takashi , Aizawa Hiroaki , Yasuda Nina
Published: June 2022

In this study we reviewed the use of genetic information in the Ecologically or Biologically Significant Marine Areas (EBSA) of Convention on Biological Diversity (CBD). We also evaluated genetic indicators for each criterion of important marine areas. We proposed five genetic indices, mainly based on microsatellite analysis (e.g., private allele frequency and number of cryptic species), then selected EBSAs in tropical and temperate zones of Japan based on eight coral species as a case study. Finally, we compared the results with the findings from conventional species-based EBSAs. In the EBSAs genetic information was mainly used in the Northern Hemisphere, particularly in the Baltic Sea; it was rarely applied in the Southern Hemisphere and Asian regions. Although typically applied to large organisms, genetic information is used to various organisms, including benthic and bacterial communities. Genetic data are used as indicators of diversity and endemism. Genetic indices were available for all seven EBSA criteria, but only five indices of three criteria were used. Examination of important areas of corals in the temperate zone using these indices showed that the indices without genetic indicators extracted a large number of important areas in the tropics; however, the use of genetic indicators identified important locations, including in temperate zones. Comparison with conventional, mainly species-based non-genetic methods showed less than 50% agreement, although particularly important sites in marine protected areas were identified by both methods. While there is still more work to be done, such as consideration of the number of survey sites or target species, one reason is that species-based methods tend to evaluate tropical areas higher. Therefore, these genetic indices are useful for examining important regions, particularly in temperate zones; they revealed cryptic lineages, indicating that many unknown marine taxa should be considered in vulnerable marine areas. Some indicators could be extracted with additional effort, such as population size estimation, immigration, or the use of next-generation sequencing, thus guiding future studies. Because limited genetic information was available in the early stages of EBSA selection, there is a need for systematic surveys and evaluations, particularly in the Southern hemisphere, Asian region, and in small organisms.
REE Anomalies Changes in Bottom Sediments Applied in the Western Equatorial Atlantic Since the Last Interglacial
Authors: Sousa Thiago A. , Venancio Igor Martins , Marques Eduardo Duarte , Figueiredo Thiago S. , Nascimento Rodrigo Azevedo , Smoak Joseph M. , Albuquerque Ana Luiza S. , Valeriano Claudio Morisson , Silva-Filho Emmanoel Vieira
Published: June 2022

We reconstruct paleoredox conditions in the Western Equatorial Atlantic (WEA) over the glacial-interglacial cycle (~130 ka) by using new high-resolution REEs data and their anomalies from a marine sediment core (GL-1248) collected from the equatorial margin off the continental shelf of NE Brazil. This approach aims to improve the understanding of the dynamics of paleoclimatic and sedimentary inputs on the coast of northeastern Brazil. Marine sediments were analyzed via Mass Spectrometry (ICP-MS) after total digestion with HF/HNO3. REEs proxies are a useful tool in understanding the transport and origin of sediments due to their physicochemical properties. Our data showed the Parnaíba River was the main source of REEs content in the western South Atlantic. Fe minerals (Fe-oxyhydroxides) produced via weathering of continental and tropical soils were the principal REE-carrier phase during transportation and ultimate deposition at core site GL-1248. Several regional climatic factors mainly rainfall changes contributed significantly to continental-REEs erosion of sedimentary layers of the Parnaíba Basin, and transport and deposition of the mobilized REEs from the continent to the study site. Furthermore, changes in the negative Ce-anomaly showed low variation along the core indicating a reduction in deep ocean oxygenation during the interglacial relative to the last glacial period. That variation, probably, was associated with glacial-interglacial variations in sea level with the exposure of the continental shelf. The origin of positive Eu anomalies in siliciclastic sediment, also observed in the core, was explained by preferential retention by feldspars such as plagioclases and potassium feldspars mostly from the assimilation of felspar during fractionation crystallization of felsic magma in the Parnaíba basin since the Last Interglacial.
Seagrass Thermal Limits and Vulnerability to Future Warming
Authors: Marbà Núria , Jordà Gabriel , Bennett Scott , Duarte Carlos M.
Published: June 2022

Seagrasses have experienced major losses globally mostly attributed to human impacts. Recently they are also associated with marine heat waves. The paucity of information on seagrass mortality thermal thresholds prevents the assessment of the risk of seagrass loss under marine heat waves. We conducted a synthesis of reported empirically- or experimentally-determined seagrass upper thermal limits (Tlimit) and tested the hypothesis that they increase with increasing local annual temperature. We found that Tlimit increases 0.42± 0.07°C per°C increase in in situ annual temperature (R2 = 0.52). By combining modelled seagrass Tlimit across global coastal areas with current and projected thermal regimes derived from an ocean reanalysis and global climate models (GCMs), we assessed the proximity of extant seagrass meadows to their Tlimit and the time required for Tlimit to be met under high (RCP8.5) and moderate (RCP4.5) emission scenarios of greenhouse gases. Seagrass meadows worldwide showed a modal difference of 5°C between present Tmax and seagrass Tlimit. This difference was lower than 3°C at the southern Red Sea, the Arabian Gulf, the Gulf of Mexico, revealing these are the areas most in risk of warming-derived seagrass die-off, and up to 24°C at high latitude regions. Seagrasses could meet their Tlimit regularly in summer within 50-60 years or 100 years under, respectively, RCP8.5 or RCP4.5 scenarios for the areas most at risk, to more than 200 years for the Arctic under both scenarios. This study shows that implementation of the goals under the Paris Agreement would safeguard much of global seagrass from heat-derived mass mortality and identifies regions where actions to remove local anthropogenic stresses would be particularly relevant to meet the Target 10 of the Aichi Targets of the Convention of the Biological Diversity.
Cholesterol Accumulation in Livers of Indian Medaka, Oryzias dancena, Acclimated to Fresh Water and Seawater
Authors: Ranasinghe Naveen , Lin Chia-Hao , Lee Tsung-Han
Published: June 2022

Sterol regulatory-element binding proteins (SREBPs), sirtuin (SIRT1), and liver X receptor α (LXRα) play important roles in regulating cholesterol metabolism in mammals. However, little is known about the relationship between cholesterol metabolism and SIRT1, LXRα, and SREBP-1 in fish. In addition, knowledge of the effects of salinity on hepatic cholesterol metabolism in euryhaline teleosts is fragmented. This study revealed that hepatic cholesterol content was significantly different between fresh water (FW)- and seawater (SW)-acclimated Indian medaka. Gene expression analysis indicated srebp-1, lxrα, and sirt1 transcripts were not affected by changes in ambient salinity. However, SREBP-1, but not LXRα and SIRT1 protein expression, was significantly induced in the liver of FW-acclimated medaka. When SREBP-1 Vivo-MO inhibited SREBP-1 translation, hepatic cholesterol content was predominantly downregulated in FW- and SW-acclimated medaka. This is the first study to show that SREBP-1 is involved in cholesterol biosynthesis in fish. Furthermore, SREBP-1 knockdown had different effects on the expression of hmgcr and fdps, which encode the key enzymes involved in cholesterol biosynthesis. This study further enhances our knowledge of cholesterol metabolism in the livers of euryhaline teleosts during salinity acclimation.
Experimental Study on Aspect Ratio and Velocity Intensity of Scour Around Submerged Pile Groups
Authors: Lu Youxiang , Wang Zhenlu , Yin Zegao , Du Shengtao , Pan Xinying , Liang Bingchen
Published: June 2022

Submerged pile groups are important components of complex piers in hydraulic engineering and are analogs for a range of subsea structures. These may sustain severe damages from local scour. The velocity intensity (U / Uc, the ratio of critical velocity to mean velocity) and aspect ratio (H / Dp, the ratio of pile height to pile diameter) are critical variables in this scour process. However, previous studies on scour around submerged pile groups were conducted in clear-water conditions (U / Uc < 1). In addition, many research studies are being conducted in shallow water flow conditions, which cannot eliminate the effect of the water depth on the scour process. Thus, these research studies cannot directly be applied to live-bed scour around submerged structures. To expand the velocity intensity and aspect ratio of scour around submerged pile groups, flume experiments were conducted with uniform quartz sand in both clear-water and live-bed conditions. Pile groups with different heights are adopted as experimental models. An improved time factor for both clear-water and live-bed scour around submerged structures is determined with the present experiments to extrapolate the scour depth of the present work to the equilibrium scour depth. This new time factor is then tested with experimental data from the literature. The tests demonstrate that this new time factor can reliably predict the scour process and equilibrium scour depth for submerged structures. Empirical relationships to demonstrate the effects of the studied variables including the equilibrium scour depth, scour area, and scour volume are presented. Different methods to predict the effects of the velocity intensity and aspect ratio on the scour depth are compared based on the present work. Furthermore, a correction coefficient is proposed to illustrate the effect of aspect ratio on scour depth. Then, equations of scour area and volume are derived according to the present experiments.
A Discontinuous Individual Growth Model of Swimming Crab Portunus trituberculatus and Its Application in the Nutrient Dynamic Simulation in an Intensive Mariculture Pond
Authors: Dong Shipeng , Xu Xian , Lin Fan , Yu Liye , Shan Hongwei , Wang Fang
Published: June 2022

Environmental problems such as organic pollution and eutrophication caused by highly intensive mariculture activities constrain the sustainable and healthy development of industry. Therefore, it is necessary to quantify the nutrient dynamics of aquaculture animals in order to reduce the risk of environmental pollution. In this study, a discontinuous individual growth model of Portunus trituberculatus in an intensive mariculture pond of P. trituberculatus–Penaeus japonicus–Sinonovacula constricta was constructed based on a dynamic energy budget theory combined with the index of condition factor. This model better predicted the growth and molting behavior of P. trituberculatus, and an acceptable fit was obtained through model parameterization using the Add-my-Pet (AmP) method (mean relative error = 0.058, symmetric mean squared error = 0.007). Ten molts were simulated over 180 days and generally coincided with the recorded molt time points. Based on this model and P. trituberculatus populations, the dynamic processes of carbon, nitrogen, and phosphorus in ingestion, respiration, excretion, feces, residual feed, dead crabs, seeding, molt, and harvest were simulated. The carbon, nitrogen, and phosphorus ingested during the 180-day culture period were 4,938.57 kg ha-1, 1,255.88 kg ha-1, and 244.16 kg ha-1, respectively. Carbon, nitrogen, and phosphorus removal by harvest accounted for 1.06%, 1.03% and 0.62% of the total ingestion, respectively, while carbon, nitrogen, and phosphorus removal by dead crabs accounted for 6.84%, 6.63%, and 4.04%, respectively, and carbon, nitrogen, and phosphorus released from residual feed into the water accounted for 41.43% of the total feed. The accurate simulation of molting behavior and nutrient dynamics in this study provides a theoretical basis for molting risk prevention and environmental stress assessment of P. trituberculatus and provides basic modules and data support for the construction of the integrated mariculture ecosystem model.