bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting the TLR2 Receptor With a Novel Thymopentin-Derived Peptide Modulates Immune Responses
Authors: Wei Xubiao , Zhang Lulu , Zhang Rijun , Wu Rujuan , Petitte James N. , Hou Yanfei , Si Dayong , Ahmad Baseer , Guo Henan , Zhang Manyi , Cheng Qiang , Tong Yucui
Published: May 2021

The innate and adaptive immune systems act in concert to protect us from infectious agents and other harmful substances. As a state of temporary or permanent immune dysfunction, immunosuppression can make an organism more susceptible to infection, organ injury, and cancer due to damage to the immune system. It takes a long time to develop new immunomodulatory agents to prevent and treat immunosuppressive diseases, with slow progress. Toll-like receptor 2 (TLR2) agonists have been reported as potential immunomodulatory candidates due to their effective activation of immune responses. It has been demonstrated that thymopentin (TP5) could modulate immunity by binding to the TLR2 receptor. However, the fairly short half-life of TP5 greatly reduces its pharmacological potential for immunosuppression therapy. Although peptide cathelicidin 2 (CATH2) has a long half-life, it shows poor immunomodulatory activity and severe cytotoxicity, which seriously hampers its clinical development. Peptide hybridization is an effective approach for the design and engineering of novel functional peptides because hybrid peptides combine the advantages and benefits of various native peptides. In this study, to overcome all these challenges faced by the parental peptides, six hybrid peptides (CaTP, CbTP, CcTP, TPCa, TPCb, and TPCc) were designed by combining the full-length TP5 with different active fragments of CATH2. CbTP, the most potent TLR2 agonist among the six hybrid peptides, was effectively screened through in silico analysis and in vitro experiments. The CbTP peptide exhibited lower cytotoxicity than either CATH2 or TP5. Furthermore, the immunomodulatory effects of CbTP were confirmed in a CTX-immunosuppressed mouse model, which showed that CbTP has increased immunopotentiating activity and physiological stability compared to the parental peptides. CbTP successfully inhibited immunosuppression and weight loss, increased immune organ indices, and improved CD4+/CD8+ T lymphocyte subsets. In addition, CbTP significantly increased the production of the cytokine TNF-α and IL-6, and the immunoglobulins IgA, IgM, and IgG. The immunoenhancing effects of CbTP were attributed to its TLR2-binding activity, promoting the formation of the TLR2 cluster, the activation of the TLR2 receptor, and thus activation of the downstream MyD88-NF-кB signaling pathway.
Co-Administration of Anticancer Candidate MK-2206 Enhances the Efficacy of BCG Vaccine Against Mycobacterium tuberculosis in Mice and Guinea Pigs
Authors: Bouzeyen Rania , Chugh Saurabh , Gosain Tannu Priya , Barbouche Mohamed-Ridha , Haoues Meriam , Rao Kanury V. S. , Essafi Makram , Singh Ramandeep
Published: May 2021

The failure of M. bovis BCG to induce long-term protection has been endowed to its inability to escape the phagolysosome, leading to mild activation of CD8+ mediated T cell response. Induction of apoptosis in host cells plays an important role in potentiating dendritic cells-mediated priming of CD8+ T cells, a process defined as “cross-priming.” Moreover, IL-10 secretion by infected cells has been reported to hamper BCG-induced immunity against Tuberculosis (TB). Previously, we have reported that apoptosis of BCG-infected macrophages and inhibition of IL-10 secretion is FOXO3 dependent, a transcription factor negatively regulated by the pro-survival activated threonine kinase, Akt. We speculate that FOXO3-mediated induction of apoptosis and abrogation of IL-10 secretion along with M. bovis BCG immunization might enhance the protection imparted by BCG. Here, we have assessed whether co-administration of a known anti-cancer Akt inhibitor, MK-2206, enhances the protective efficacy of M. bovis BCG in mice model of infection. We observed that in vitro MK-2206 treatment resulted in FOXO3 activation, enhanced BCG-induced apoptosis of macrophages and inhibition of IL-10 secretion. Co-administration of M. bovis BCG along with MK-2206 also increased apoptosis of antigen-presenting cells in draining lymph nodes of immunized mice. Further, MK-2206 administration improved BCG-induced CD4+ and CD8+ effector T cells responses and its ability to induce both effector and central memory T cells. Finally, we show that co-administration of MK-2206 enhanced the protection imparted by M. bovis BCG against Mtb in aerosol infected mice and guinea pigs. Taken together, we provide evidence that MK-2206-mediated activation of FOXO3 potentiates BCG-induced immunity and imparts protection against Mtb through enhanced innate immune response.
Immunosuppressive PLGA TGF-β1 Microparticles Induce Polyclonal and Antigen-Specific Regulatory T Cells for Local Immunomodulation of Allogeneic Islet Transplants
Authors: Li Ying , Frei Anthony W. , Labrada Irayme M. , Rong Yanan , Liang Jia-Pu , Samojlik Magdalena M. , Sun Chuqiao , Barash Steven , Keselowsky Benjamin G. , Bayer Allison L. , Stabler Cherie L.
Published: May 2021

Allogeneic islet transplantation is a promising cell-based therapy for Type 1 Diabetes (T1D). The long-term efficacy of this approach, however, is impaired by allorejection. Current clinical practice relies on long-term systemic immunosuppression, leading to severe adverse events. To avoid these detrimental effects, poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) were engineered for the localized and controlled release of immunomodulatory TGF-β1. The in vitro co-incubation of TGF-β1 releasing PLGA MPs with naïve CD4+ T cells resulted in the efficient generation of both polyclonal and antigen-specific induced regulatory T cells (iTregs) with robust immunosuppressive function. The co-transplantation of TGF-β1 releasing PLGA MPs and Balb/c mouse islets within the extrahepatic epididymal fat pad (EFP) of diabetic C57BL/6J mice resulted in the prompt engraftment of the allogenic implants, supporting the compatibility of PLGA MPs and local TGF-β1 release. The presence of the TGF-β1-PLGA MPs, however, did not confer significant graft protection when compared to untreated controls, despite measurement of preserved insulin expression, reduced intra-islet CD3+ cells invasion, and elevated CD3+Foxp3+ T cells at the peri-transplantation site in long-term functioning grafts. Examination of the broader impacts of TGF-β1/PLGA MPs on the host immune system implicated a localized nature of the immunomodulation with no observed systemic impacts. In summary, this approach establishes the feasibility of a local and modular microparticle delivery system for the immunomodulation of an extrahepatic implant site. This approach can be easily adapted to deliver larger doses or other agents, as well as multi-drug approaches, within the local graft microenvironment to prevent transplant rejection.
CcpA- and Shm2-Pulsed Myeloid Dendritic Cells Induce T-Cell Activation and Enhance the Neutrophilic Oxidative Burst Response to Aspergillus fumigatus
Authors: Page Lukas , Wallstabe Julia , Lother Jasmin , Bauser Maximilian , Kniemeyer Olaf , Strobel Lea , Voltersen Vera , Teutschbein Janka , Hortschansky Peter , Morton Charles Oliver , Brakhage Axel A. , Topp Max , Einsele Hermann , Wurster Sebastian , Loeffler Juergen
Published: May 2021

Aspergillus fumigatus causes life-threatening opportunistic infections in immunocompromised patients. As therapeutic outcomes of invasive aspergillosis (IA) are often unsatisfactory, the development of targeted immunotherapy remains an important goal. Linking the innate and adaptive immune system, dendritic cells are pivotal in anti-Aspergillus defense and have generated interest as a potential immunotherapeutic approach in IA. While monocyte-derived dendritic cells (moDCs) require ex vivo differentiation, antigen-pulsed primary myeloid dendritic cells (mDCs) may present a more immediate platform for immunotherapy. To that end, we compared the response patterns and cellular interactions of human primary mDCs and moDCs pulsed with an A. fumigatus lysate and two A. fumigatus proteins (CcpA and Shm2) in a serum-free, GMP-compliant medium. CcpA and Shm2 triggered significant upregulation of maturation markers in mDCs and, to a lesser extent, moDCs. Furthermore, both A. fumigatus proteins elicited the release of an array of key pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, IL-8, and CCL3 from both DC populations. Compared to moDCs, CcpA- and Shm2-pulsed mDCs exhibited greater expression of MHC class II antigens and stimulated stronger proliferation and IFN-γ secretion from autologous CD4+ and CD8+ T-cells. Moreover, supernatants of CcpA- and Shm2-pulsed mDCs significantly enhanced the oxidative burst in allogeneic neutrophils co-cultured with A. fumigatus germ tubes. Taken together, our in vitro data suggest that ex vivo CcpA- and Shm2-pulsed primary mDCs have the potential to be developed into an immunotherapeutic approach to tackle IA.
Exploring the Pathogenesis of Psoriasis Complicated With Atherosclerosis via Microarray Data Analysis
Authors: Su Wenxing , Zhao Ying , Wei Yuqian , Zhang Xiaoyan , Ji Jiang , Yang Shun
Published: May 2021

Background

Although more and more evidence has supported psoriasis is prone to atherosclerosis, the common mechanism of its occurrence is still not fully elucidated. The purpose of this study is to further explore the molecular mechanism of the occurrence of this complication.

Methods

The gene expression profiles of psoriasis (GSE30999) and atherosclerosis (GSE28829) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) of psoriasis and atherosclerosis, three kinds of analyses were performed, namely functional annotation, protein‐protein interaction (PPI) network and module construction, and hub gene identification and co-expression analysis.

Results

A total of 94 common DEGs (24 downregulated genes and 70 upregulated genes) was selected for subsequent analyses. Functional analysis emphasizes the important role of chemokines and cytokines in these two diseases. In addition, lipopolysaccharide-mediated signaling pathway is closely related to both. Finally, 16 important hub genes were identified using cytoHubba, including LYN, CSF2RB, IL1RN, RAC2, CCL5, IRF8, C1QB, MMP9, PLEK, PTPRC, FYB, BCL2A1, LCP2, CD53, NCF2 and TLR2.

Conclusions

Our study reveals the common pathogenesis of psoriasis and atherosclerosis. These common pathways and hub genes may provide new ideas for further mechanism research.
Loss of CD96 Expression as a Marker of HIV-Specific CD8+ T-Cell Differentiation and Dysfunction
Authors: Bunet Rémi , Nayrac Manon , Ramani Hardik , Sylla Mohamed , Durand Madeleine , Chartrand-Lefebvre Carl , Routy Jean-Pierre , Landay Alan L. , Gauchat Jean-Francois , Chomont Nicolas , Ancuta Petronela , Kaufmann Daniel E. , Bernard Nicole , Tremblay Cécile L. , El-Far Mohamed
Published: May 2021

Persistent immune activation and inflammation in people living with HIV (PLWH) are associated with immunosenescence, premature aging and increased risk of non-AIDS comorbidities, with the underlying mechanisms not fully understood. In this study, we show that downregulation of the T-cell immunoglobulin receptor CD96 on CD8+T cells from PLWH is associated with decreased expression of the co-stimulatory receptors CD27 and CD28, higher expression of the senescence marker CD57 and accumulation of a terminally differentiated T-cell memory phenotype. In addition, we show that CD96-low CD8+T-cells display lower proliferative potential compared to their CD96-high counterparts and that loss of CD96 expression by HIV-specific CD8+T-cells is associated with a suboptimal response to HIV antigens. In conclusion, our results suggest that CD96 marks CD8+T-cells with competent responses to HIV and the loss of its expression might be used as a biomarker for CD8+T-cell senescence and dysfunction in PLWH.
Unraveling the Underlying Interaction Mechanism Between Dabie bandavirus and Innate Immune Response
Authors: Zhou Chuan-min , Yu Xue-jie
Published: May 2021

The genus Bandavirus consists of seven tick-borne bunyaviruses, among which four are known to infect humans. Dabie bandavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), poses serious threats to public health worldwide. SFTSV is a tick-borne virus mainly reported in China, South Korea, and Japan with a mortality rate of up to 30%. To date, most immunology-related studies focused on the antagonistic role of SFTSV non-structural protein (NSs) in sequestering RIG-I-like-receptors (RLRs)-mediated type I interferon (IFN) induction and type I IFN mediated signaling pathway. It is still elusive whether the interaction of SFTSV and other conserved innate immune responses exists. As of now, no specific vaccines or therapeutics are approved for SFTSV prevention or treatments respectively, in part due to a lack of comprehensive understanding of the molecular interactions occurring between SFTSV and hosts. Hence, it is necessary to fully understand the host-virus interactions including antiviral responses and viral evasion mechanisms. In this review, we highlight the recent progress in understanding the pathogenesis of SFTS and speculate underlying novel mechanisms in response to SFTSV infection.
Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades
Authors: Wang Xiaoyan , Wu Bingchen , Yan Zhengqing , Wang Guoqiang , Chen Shiqing , Zeng Jian , Tao Feng , Xu Bichun , Ke Honggang , Li Mei
Published: May 2021

The common gamma receptor–dependent cytokines and their JAK-STAT pathways play important roles in T cell immunity and have been demonstrated to be related with response to immune checkpoint blockades (ICBs). PTPRD and PTPRT are phosphatases involved in JAK-STAT pathway. However, their clinical significance for non-small cell lung cancer (NSCLC) treated with ICBs is still unclear. Genomic and survival data of NSCLC patients administrated with anti–PD-1/PD-L1 or anti–CTLA-4 antibodies (Rizvi2015; Hellmann2018; Rizvi2018 Samstein2019) were retrieved from publicly accessible data. Genomic, survival and mRNA data of 1007 patients with NSCLC were obtained from The Cancer Genome Atlas (TCGA). PTPRD/PTPRT mutation was significantly associated with better progression-free survival (PFS) in three independent Rizvi2015, Hellmann2018 and Rizvi2018 cohorts. The median PFS for PTPRD/PTPRT mutant-type vs. wild-type NSCLC patients were not reached vs. 6.3 months (Rizvi2015, HR = 0.16; 95% CI, 0.02-1.17; P=0.03), 24.0 vs. 5.4 months (Hellmann2018, HR, 0.49; 95% CI, 0.26-0.94; P=0.03), 5.6 vs. 3.0 months (Rizvi2018, HR = 0.64; 95% CI, 0.44-0.92; P=0.01) and 6.8 vs. 3.5 months (Pooled cohort, HR, 0.54; 95% CI, 0.39-0.73; P<0.0001) respectively. PTPRD/PTPRT mutation was an independent predictive factor for PFS in pooled cohort (P = 0.01). Additionally, PTPRD/PTPRT mutation associated with better overall survival (OS) in Samstein2019 cohort (19 vs. 10 months, P=0.03). While similar clinical benefits were not observed in patients without ICBs treatment (TCGA cohort, P=0.78). In the further exploratory analysis, PTPRD/PTPRT mutation was significantly associated with increased tumor mutation burden and higher mRNA expression of JAK1 and STAT1. Gene Set Enrichment Analysis revealed prominent enrichment of signatures related to antigen processing and presentation in patients with PTPRD/PTPRT mutation. This work suggested that PTPRD/PTPRT mutation might be a potential positive predictor for ICBs in NSCLC. These results need to be further confirmed in future.
The Efficacy of Intra-Arterial Plus Intravesical Chemotherapy Versus Intravesical Chemotherapy Alone After Bladder-Sparing Surgery in High-Risk Bladder Cancer: A Systematic Review and Meta-Analysis of Comparative Study
Authors: Zhou Zhongbao , Cui Yuanshan , Huang Shuangfeng , Chen Zhipeng , Zhang Yong
Published: May 2021

Background

Due to the poor prognosis, the treatment of high-risk bladder cancer (HRBC) remains controversial. This meta-analysis aims to access the efficacy of intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IC) versus IC alone after bladder-sparing surgery in HRBC.

Methods

A systematic search of PubMed, Cochrane Library databases, EMBASE (until June 2020) was conducted. PRISMA checklist was followed. The data were analyzed by RevMan v5.3.0.

Results

A total of five articles including 843 patients were studied. The analysis demonstrated that the IAC + IC group had a greater improvement of overall survival (P = 0.02) and significant reduction in terms of tumor recurrence rate (P = 0.0006) and tumor progression rate (P = 0.008) compared with the IC group. The recurrence-free survival in the IAC + IC group was significantly higher than that in the IC group (P = 0.004), but there was no significant difference in progression-free survival between the two groups (P = 0.32). In addition, the combination of IAC and IC significantly extended tumor recurrence interval (P = 0.0001) and reduced tumor-specific death rate (P = 0.01) for patients with HRBC compared with IC alone. For side effects related with IAC, although about half of the patients experienced some toxicities, most of them were mild and reversible (grades 1–2, 22.3% vs. grade 3–4, 2.7%), mainly including nausea/vomiting (P = 0.0001), neutropenia (P = 0.002), and alanine aminotransferase (P = 0.0001).

Conclusion

Patients with HRBC treated with IAC + IC after bladder-sparing surgery had a marked improvement in the overall survival, recurrence-free survival, time interval to first recurrence, tumor recurrence rate, tumor progression rate, and tumor-specific death rate than patients treated with IC alone. However, progression-free survival was not significantly correlated with treatment strategy. In addition, patients seemed to tolerate well the toxicities related with IAC.

Systematic Review Registration

PROSPERO, identifier CRD42021232679.
Targeting Treatment Resistance in Head and Neck Squamous Cell Carcinoma – Proof of Concept for CT Radiomics-Based Identification of Resistant Sub-Volumes
Authors: Bogowicz Marta , Pavic Matea , Riesterer Oliver , Finazzi Tobias , Garcia Schüler Helena , Holz-Sapra Edna , Rudofsky Leonie , Basler Lucas , Spaniol Manon , Ambrusch Andreas , Hüllner Martin , Guckenberger Matthias , Tanadini-Lang Stephanie
Published: May 2021

Purpose

Radiomics has already been proposed as a prognostic biomarker in head and neck cancer (HNSCC). However, its predictive power in radiotherapy has not yet been studied. Here, we investigated a local radiomics approach to distinguish between tumor sub-volumes with different levels of radiosensitivity as a possible target for radiation dose intensification.

Materials and Methods

Of 40 patients (n=28 training and n=12 validation) with biopsy confirmed locally recurrent HNSCC, pretreatment contrast-enhanced CT images were registered with follow-up PET/CT imaging allowing identification of controlled (GTVcontrol) vs non-controlled (GTVrec) tumor sub-volumes on pretreatment imaging. A bi-regional model was built using radiomic features extracted from pretreatment CT in the GTVrec and GTVcontrol to differentiate between those regions. Additionally, concept of local radiomics was implemented to perform detection task. The original tumor volume was divided into sub-volumes with no prior information on the location of recurrence. Radiomic features from those sub-volumes were then used to detect recurrent sub-volumes using multivariable logistic regression.

Results

Radiomic features extracted from non-controlled regions differed significantly from those in controlled regions (training AUC = 0.79 CI 95% 0.66 - 0.91 and validation AUC = 0.88 CI 95% 0.72 – 1.00). Local radiomics analysis allowed efficient detection of non-controlled sub-volumes both in the training AUC = 0.66 (CI 95% 0.56 – 0.75) and validation cohort 0.70 (CI 95% 0.53 – 0.86), however performance of this model was inferior to bi-regional model. Both models indicated that sub-volumes characterized by higher heterogeneity were linked to tumor recurrence.

Conclusion

Local radiomics is able to detect sub-volumes with decreased radiosensitivity, associated with location of tumor recurrence in HNSCC in the pre-treatment CT imaging. This proof of concept study, indicates that local CT radiomics can be used as predictive biomarker in radiotherapy and potential target for dose intensification.
Mechanisms of Neoantigen-Targeted Induction of Pyroptosis and Ferroptosis: From Basic Research to Clinical Applications
Authors: Yu Jie , Wang Qing , Zhang Xiaoyun , Guo Zhiliang , Cui Xiaodong
Published: May 2021

Neoantigens are tumor-specific antigens (TSAs) that are only expressed in tumor cells. They are ideal targets enabling T cells to recognize tumor cells and stimulate a potent antitumor immune response. Pyroptosis and ferroptosis are newly discovered types of programmed cell death (PCD) that are different from apoptosis, cell necrosis, and autophagy. Studies of ferroptosis and pyroptosis of cancer cells are increasing, and strategies to modify the tumor microenvironment (TME) through ferroptosis to inhibit the occurrence and development of cancer, improve prognosis, and increase the survival rate are popular research topics. In addition, adoptive T cell therapy (ACT), including chimeric antigen receptor T cell (CAR-T) technology and T cell receptor engineered T cell (TCR-T) technology, and checkpoint blocking tumor immunotherapies (such as anti-PD- 1 and anti-PD-L1 agents), tumor vaccines and other therapeutic technologies that rely on tumor neoantigens are rapidly being developed. In this article, the relationship between neoantigens and pyroptosis and ferroptosis as well as the clinical role of neoantigens is reviewed.
Regulation of Actin Bundle Mechanics and Structure by Intracellular Environmental Factors
Authors: Castaneda Nicholas , Park Jinho , Kang Ellen Hyeran
Published: May 2021

The mechanical and structural properties of actin cytoskeleton drive various cellular processes, including structural support of the plasma membrane and cellular motility. Actin monomers assemble into double-stranded helical filaments as well as higher-ordered structures such as bundles and networks. Cells incorporate macromolecular crowding, cation interactions, and actin-crosslinking proteins to regulate the organization of actin bundles. Although the roles of each of these factors in actin bundling have been well-known individually, how combined factors contribute to actin bundle assembly, organization, and mechanics is not fully understood. Here, we describe recent studies that have investigated the mechanisms of how intracellular environmental factors influence actin bundling. This review highlights the effects of macromolecular crowding, cation interactions, and actin-crosslinking proteins on actin bundle organization, structure, and mechanics. Understanding these mechanisms is important in determining in vivo actin biophysics and providing insights into cell physiology.
The Impacts of COVID-19 on US Maternity Care Practices: A Followup Study
Authors: Gutschow Kim , Davis-Floyd Robbie
Published: May 2021

This article extends the findings of a rapid response article researched in April 2020 to illustrate how providers’ practices and attitudes toward COVID-19 had shifted in response to better evidence, increased experience, and improved guidance on how SARS-CoV-2 and COVID-19 impacted maternity care in the United States. This article is based on a review of current labor and delivery guidelines in relation to SARS-CoV-2 and COVID-19, and on an email survey of 28 community-based and hospital-based maternity care providers in the United State, who discuss their experiences and clients’ needs in response to a rapidly shifting landscape of maternity care during the COVID-19 pandemic. One-third of our respondents are obstetricians, while the other two-thirds include midwives, doulas, and labor and delivery nurses. We present these providers’ frustrations and coping mechanisms in shifting their practices in relation to COVID-19. The primary lessons learned relate to improved testing and accessing PPE for providers and clients; the need for better integration between community- and hospital-based providers; and changes in restrictive protocols concerning labor support persons, rooming-in with newborns, immediate skin-to-skin contact, and breastfeeding. We conclude by suggesting that the COVID-19 pandemic offers a transformational moment to shift maternity care in the United States toward a more integrated and sustainable model that might improve provider and maternal experiences as well as maternal and newborn outcomes.
A Novel Canine Mammary Cancer Cell Line: Preliminary Identification and Utilization for Drug Screening Studies
Authors: Li Rifei , Wu Haoxian , Sun Yue , Zhu Jingru , Tang Jun , Kuang Yu , Li Gebin
Published: May 2021

Canine malignant mammary tumor is a dangerously fatal neoplastic disease with poor survival in female dogs. The aim of this study was to preliminary characterize a novel canine mammary cancer cell line, B-CMT, from canine primary mammary gland tumor, and to utilize it as a cell model for in vitro screening of possible therapeutic drugs. The successfully established cell line, B-CMT, was cultured over 50 passages. B-CMT has a fast proliferation rate, and a population doubling time (PDT) of 33.6 h. The B-CMT cell line lacked human epidermal growth factor receptor-2 (HER-2), estrogen receptors (ER) and progesterone receptors (PR) expression by qRT-PCR. Compared with MDCK cells, CDH1 expression of CMT cell line was significantly decreased or even absent, but GATA3 expression dramatically increased, while TGF-β expression was at a similar level. Interestingly, the B-CMT cell line from canine primary tumor also showed positive hypoxia inducible factor-1α (HIF-1α) results in immunofluorescence (IF), western blot, and qRT-PCR analysis. Ten days post inoculation with EGFP-B-CMT (B-CMT cells stably expressing EGFP), the experimental mice developed palpable soft tissue masses which histologically resembled the canine primary tumor, and was approved to be derived from B-CMT cell line through detection of EGFP by immunohistochemical (IHC) analysis. Moreover, we investigated the cytotoxicity of five drugs to B-CMT cells, and the results showed that rapamycin and imatinib significantly inhibited the proliferation of the cells in vitro within a certain range of concentration. They also induced cell cycle arrest of B-CMT cells at G1 and G2 phase, respectively. In summary, the results of this report showed that B-CMT cell line might serve as a tool for future studies on tumor microenvironment and drug resistance.
Threatened Woody Plants of Georgia and Micropropagation as a Tool for In Vitro Conservation
Authors: Gaidamashvili Mariam , Benelli Carla
Published: May 2021

Georgia is the major part of the Caucasus; it is considered as one of the distinguished regions of the world with respect to biodiversity. The majority of Georgia’s biodiversity is connected with forest ecosystems, which cover about 38% of the country’s territories. In Georgia, as in other countries, many unique species of forest phytocenosis are threatened by extinction and/or genetic pollution due to the negative impact of various environmental and anthropogenic factors. Implementation of biotechnological approaches in practice for in vitro conservation of species can significantly speed up the processes of protection, thus guaranteeing the sustainability of the phytogenetic pool of the country. The present review summarizes the current status of several threatened woody perennials of the Red List of Georgia belonging to the genera Castanea, Quercus, and Betula, which are the dominant or edificatory species of forest phytocenosis. The feasibility for their in vitro propagation for conservation purposes is discussed.
Effects of Phosphorus Ensembled Nanomaterials on Nutrient Uptake and Distribution in Glycine max L. under Simulated Precipitation
Authors: Li Qingqing , Ma Chuanxin , White Jason C. , Xing Baoshan
Published: May 2021

Nanoscale hydroxyapatite (nHA) was synthesized to investigate its potential as a phosphorus (P) ensembled nanofertilizer, using soybean (Glycine max L.) as a model plant. The conventional analogue phosphate (pi) was used for comparison with the synthesized nHA. Varied precipitation intensities (0%, 30%, 60%, and 100%) were simulated by adding selected volumes of the P fertilizers (nHA or pi) via foliar spray and soil amendment. The total amounts of added P were the same across all the treatments. The importance of a wash-off effect was investigated on foliar-treated seedlings by evaluating different watering heights (20, 120, and 240 cm above the seedlings). Fresh weight, pigment content, macro-, and micronutrient contents were measured in soybean tissues across all the treatments after 4 weeks of greenhouse cultivation. The synthesized nHA showed superior effects on plant nutrient content upon high precipitation intensities. For example, at 100% precipitation intensity, there was 32.6% more P and 33.2% more Ca in shoots, 40.6% more P and 45.4% more Ca in roots, and 37.9% more P and 82.3% more Ca in pods, as compared to those with pi treatment, respectively. No impact on soybean biomass was evident upon the application of nHA or pi. Further investigation into customizing nHA to enhance its affinity with crop leaves and to extend retention time on the leaf surface is warranted given that the present study did not show significant positive impacts of nHA on soybean growth under the effects of precipitation. Taken together, our findings increase understanding of the potential application of nHA as a nano-enabled fertilizer in sustainable agriculture.
Tillage Intensity Influences Insect-Pest and Predator Dynamics of Wheat Crop Grown under Different Conservation Agriculture Practices in Rice-Wheat Cropping System of Indo-Gangetic Plain
Authors: Jasrotia Poonam , Bhardwaj Ajay Kumar , Katare Subhash , Yadav Jayant , Kashyap Prem Lal , Kumar Sudheer , Singh Gyanendra Pratap
Published: May 2021

Tillage can alter the soil habitats wherein many insect pests and their natural enemies reside during at least part of their life cycle. To enhance crop productivity and reduce climate change effects, conservation agriculture (CA) with reduced-tillage or no-tillage practices have been advocated to farmers. However, information relating to the effect of CA on insect pests and their natural enemies is very scarce, at least in the Indo-Gangetic region. In this study, the effect of tillage on the abundance of, and damage by, major insect pests (foliar aphids, root aphids, termites, and pink stem borer) and their natural enemies in wheat managed under three tillage practices, i.e., zero-till (ZT), reduced tillage (RT), and conventional tillage (CT) with (protected) and without (unprotected) insecticide protection scenarios, was investigated. Foliar aphid and termite numbers were lowest in the ZT-protected system, and highest in the CT-unprotected system. Pink stem borer damage was significantly higher in the ZT-unprotected system, whereas the root aphid number was maximum in the RT-unprotected system. The natural enemies of these four major insect pests of wheat showed variable trends under the studied tillage systems. The abundance and damage of these major insect pests showed a positive correlation with the normalized difference vegetative index (NDVI) and canopy temperature. The dynamics of the insect pests and their predators were driven by soil habitat-related changes (direct) as well as crop growth-related effects (indirect). A fine-tuning of insect-pest management tactics based on these relations would enhance the success of CA systems.
Acute and Subchronic Toxicity Studies of Aristolochic Acid A in Tianfu Broilers
Authors: Xu Dan , Ran Chonglin , Yin Lizi , Lin Juchun , Fu Hualin , Peng Xi , Zhao Xiaoling , Shu Gang
Published: May 2021

Aristolochic acid (AA) is one of the components of some traditional Chinese medicines, which has high toxic potential in animals, leading to huge economic losses in the breeding industry. The purpose of this study is to evaluate the toxicology of AA on Tianfu broilers through acute and subchronic toxicity tests. The results showed that the median lethal dose of AA to Tianfu broilers was 14.52 mg/kg. After continuous intraperitoneal injection of AA solution (1.452 mg/kg) for 28 days, the swollen and necrotic renal tubular epithelial cells were histologically observed; in addition, blood urea nitrogen (BUN) and creatinine (Cre) were significantly increased, indicating AA could induce serious kidney lesions in broilers. Moreover, the ROS, the apoptosis rate and the depolarization rate of the mitochondrial membrane potential of broilers’ renal cells increased. The results of QRT-PCR showed that AA reduced the mRNA expressions of HO-1, NQO1, Raf-1 and Bcl-2, while the expressions of Bax and Caspase-3 increased, which show that AA aroused oxidative stress and promoted the apoptosis of renal cells. In conclusion, AA has been found to damage broilers’ kidneys by breaking the redox balance to form oxidative stress, along with promoting apoptosis of renal cells.
Optimization of Sperm Management and Fertilization in Zebrafish (Danio rerio (Hamilton))
Authors: Cheng Yu , Franěk Roman , Rodina Marek , Xin Miaomiao , Cosson Jacky , Zhang Songpei , Linhart Otomar
Published: May 2021

The aim of the present study was to investigate the spontaneous motility of spermatozoa and to optimize sperm collection, short-term sperm storage, and fertilization in zebrafish Danio rerio. The movement of spermatozoon in water was propagated along the flagellum at 16 s after sperm activation then damped from the end of the flagellum for 35 s and fully disappeared at 61 s after activation. For artificial fertilization, milt must be added to an immobilizing solution, which stops the movement of sperm and keeps the sperm motionless until fertilization. E400 and Kurokura as isotonic solutions were shown to be suitable extenders to store sperm for fertilization for 6 h. E400 stored sperm for 12 h at 0–2 °C. Sperm motility decreased only to 36% at 12 h post stripping for the E400 extender and to 19% for the Kurokura extender. To achieve an optimal level of fertilization and swim-up larvae rates, a test tube with a well-defined amount of 6,000,000 spermatozoa in E400 extender per 100 eggs and 100 µL of activation solution has proven to be more successful than using a Petri dish. The highest fertilization and swim-up larvae rates reached 80% and 40–60%, respectively, with milt stored for 1.5 h in the E400 extender at 0–2 °C.
Untargeted Metabolomics Reveals Intestinal Pathogenesis and Self-Repair in Rabbits Fed an Antibiotic-Free Diet
Authors: Tang Tao , Li Ya , Wang Jie , Elzo Mauricio A. , Shao Jiahao , Li Yanhong , Xia Siqi , Fan Huimei , Jia Xianbo , Lai Songjia
Published: May 2021

The prohibition of the use of growth-promoting drug additives in feeds was implemented in China in 2020. However, rabbits can experience symptoms of intestinal disease, such as diarrhea and flatulence, when switching from standard normal diets with antibiotics to antibiotic-free diets. The molecular mechanisms related to the occurrence of these diseases as well as associated physiological and metabolic changes in the intestine are unclear. Thus, the objectives of this study were to study the pathogenesis of intestinal inflammation using untargeted metabolomics. This was done to identify differential metabolites between a group of antibiotic-free feed Hyplus rabbits (Dia) whose diet was abruptly changed from a standard normal diet with antibiotics to an antibiotic-free diet, and an antibiotic diet group Hyplus rabbits (Con) that was fed a standard normal diet with antibiotics. Morphological damage to the three intestinal tissues was determined through visual microscopic examination of intestinal Dia and Con tissue samples stained with hematoxylin and eosin (HE). A total of 1969 different metabolites were identified in the three intestinal tissues from Dia and Con rabbits. The level of 1280 metabolites was significantly higher and the level of 761 metabolites was significantly lower in the Dia than in the Con group. These differential metabolites were involved in five metabolic pathways associated with intestinal inflammation (tryptophan metabolism, pyrimidine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, lysine degradation, and bile secretion). Rabbits in the Dia group developed metabolic disorders that affected the intestinal microbiota and changed the permeability of the intestinal tract, thereby triggering intestinal inflammation, affecting feed utilization, reducing production performance, and activating the intestinal tract self-repair mechanism. Thus, the abrupt transition from a diet with antibiotics to an antibiotic-free diet affected the structure and metabolism of the intestinal tract in Hyplus rabbits. Consequently, to avoid these problems, the antibiotic content in a rabbit diet should be changed gradually or alternative antibiotics should be found.
Expression Characteristics of microRNA in Pig Umbilical Venous Blood and Umbilical Arterial Blood
Authors: Gan Mailin , Liu Lin , Zhang Shunhua , Guo Zongyi , Tan Ya , Luo Jia , Yang Qiong , Pan Hongmei , Li Xuewei , Wang Jinyong , Shen Linyuan , Zhu Li
Published: May 2021

As the medium of material exchange between mother and fetus, umbilical cord blood is closely connected with fetal development. microRNA (miRNA) has a wide range of biological functions and has high flow characteristics. Small RNA sequencing of pig umbilical venous blood (UVB) and umbilical arterial blood (UAB) revealed that a total of 302 miRNAs were identified, and 106 and 22 miRNAs were specifically expressed in the UVB and UAB, respectively. Using the two methods of differential expression multiple and differential expression percentage, it is found that only 35% of the highly expressed miRNAs in the UVB by the two analysis modes overlap, but 56.25% of the enriched signal pathways are the same. Only 20% of the highly expressed miRNAs in the UAB overlap, but 62.07% of the signal pathways are the same. Further analysis revealed that miR-423 can be used as a characteristic miRNA of UVB and has the potential to treat muscle-related diseases. miR-122-5p can be used as a characteristic miRNA of UAB and may help to improve liver- and brain-related diseases. In summary, these results enrich understanding of miRNA in mother–fetal communication and provide a reference for the development and application of porcine cord blood products.
Effectiveness and Efficiency of Corral Traps, Drop Nets and Suspended Traps for Capturing Wild Pigs (Sus scrofa)
Authors: Gaskamp Joshua A. , Gee Kenneth L. , Campbell Tyler A. , Silvy Nova J. , Webb Stephen L.
Published: May 2021

Strategic control and eradication programs for wild pigs (Sus scrofa) are being developed to help curtail the expanding populations of this invasive, alien species. Drop nets and corral traps have a long history of capturing a multitude of wildlife species, so we evaluated the effectiveness and efficiency of these traps for controlling wild pigs in southern Oklahoma. We also developed and evaluated a suspended metal trap that provided real-time monitoring and deployment to capture animals. Effectiveness of each trap type was estimated as the proportion of pigs removed from the total population, whereas efficiency was calculated based on catch per unit effort (CPUE) (i.e., the number of person hours per pig removal). During 3 years of study (2010–2012), we removed 601 pigs, 296 using drop nets, 60 using corral traps, and 245 using suspended traps. Suspended traps removed 88.1% of the estimated population, whereas drop nets removed 85.7% and corral traps removed 48.5%. CPUE was 0.64 person hours/pig using suspended traps followed by 1.9 person hours/pig for drop nets and 2.3 person hours/pig for corral traps. Drop nets and suspended traps were more effective at removing a large proportion of the population (>85%), mainly through whole sounder removal, but the suspended trap with real-time notifications was the most efficient trap type, requiring fewer person hours to operate.
Single Fixed-Time Post-Cervical Insemination in Gilts with Buserelin
Authors: Suárez-Usbeck Andrés , Mitjana Olga , Tejedor María Teresa , Bonastre Cristina , Sistac Jorge , Ubiergo Antonio , Falceto María Victoria
Published: May 2021

Current protocols for gilts recommend the deposit of multiple semen doses in the cervix each 12–24 h after estrus detection. Our objectives were: (1) to determine the effect of buserelin and a single fixed-time artificial insemination using the new post-cervical artificial insemination technique (FTAI-PCAI) on reproductive and productive performance in gilts, and (2) to compare this protocol with conventional estrus detection and double PCAI without hormonal induction. In the control group (C; n = 240), gilts were inseminated twice (8 and 12 h from estrus onset). Gilts in the treatment group (T; n = 226) received buserelin (10 μg, intramuscular) 120 h after altrenogest treatment (18 d) and one single PCAI 30–33 h after buserelin administration. The groups did not differ in reproductive and production performance (p > 0.05). The T group showed greater piglet birth weight and shorter estrus duration (p < 0.001). Delivery batch length differed significantly depending on the season (p < 0.05); the shortest length corresponded to autumn. Both groups only differed significantly in spring (p = 0.018), with a shorter length in the T group. This new FTAI-PCAI protocol with buserelin is recommended in gilts, helping with optimization of genetic diffusion, boars, and semen doses.
The Effect of Single and Triple Testicular Biopsy Using Biopty Gun on Spermatogenesis in Pubertal Rats
Authors: Šušnjar Tomislav , Kuzmić Prusac Ivana , Švagelj Ivan , Jurišić Anđela , Šušnjar Tomislav , Jurišić Antonija , Jukić Miro , Pogorelić Zenon
Published: May 2021

Background: The aim of this study was to compare consequences in single and triple testicular biopsy by biopty gun in pubertal rats using histological and immunohistochemical analysis. Methods: Thirty-two Sprague-Dawley male rats were used as the experimental model. The rats were randomly divided into three study groups. The rats from the first group (n = 12) received a single-biopsy of upper pole of the left testis, while the rats from the second group (n = 10) received triple-biopsy of upper and lower poles and lateral surface of left testis. The third group (n = 10) was a control group. On the eightieth day after the biopsy in all rats bilateral orchiectomy and funiculectomy were performed to obtain testicular tissue and sperm for analysis. The consequences of the puncture were observed by pathohistology, immunohistochemistry and semen analysis. Results: The results of the study showed lower percentage of sperm count (14.5 mill/mL vs. 16 mill/mL, p = 0.130), sperm motility (24.6% vs. 32.7%, p > 0.05), abnormal sperm (30% vs. 27%, p > 0.05), atrophic tubules (21% vs. 6%, p < 0.001), volume (1.7 mL vs. 2.28 mL, p < 0.01) and apoptotic index (1.56 vs. 1.19, p = 0.650) in the testes with a triple-biopsy compared to the testes with a single-biopsy. Semen analysis showed a borderline significant difference between the group with triple-biopsy where sperm count was lower than it in the control group (14.5 mill/mL vs. 17.5 mill/mL, p = 0.05). A single-biopsy has little effect on the testis, especially on overall fertility. A triple-biopsy showed higher degree of the testicular damage but without a significant impact on overall fertility. Semen analysis showed that single- and triple-biopsies did not have a significant effect on sperm count, motility and morphology. Conclusion: Biopty gun procedure is a cheap, simple and reliable method for testicular biopsy in rats without a significant effect on sperm count, motility and morphology.
Performance Evaluation of IMERG GPM Products during Tropical Storm Imelda
Authors: Sakib Salman , Ghebreyesus Dawit , Sharif Hatim O.
Published: May 2021

Tropical Storm Imelda struck the southeast coastal regions of Texas from 17–19 September, 2019, and delivered precipitation above 500 mm over about 6000 km2. The performance of the three IMERG (Early-, Late-, and Final-run) GPM satellite-based precipitation products was evaluated against Stage-IV radar precipitation estimates. Basic and probabilistic statistical metrics, such as CC, RSME, RBIAS, POD, FAR, CSI, and PSS were employed to assess the performance of the IMERG products. The products captured the event adequately, with a fairly high POD value of 0.9. The best product (Early-run) showed an average correlation coefficient of 0.60. The algorithm used to produce the Final-run improved the quality of the data by removing systematic errors that occurred in the near-real-time products. Less than 5 mm RMSE error was experienced in over three-quarters (ranging from 73% to 76%) of the area by all three IMERG products in estimating the Tropical Storm Imelda. The Early-run product showed a much better RBIAS relatively to the Final-run product. The overall performance was poor, as areas with an acceptable range of RBIAS (i.e., between −10% and 10%) in all the three IMERG products were only 16% to 17% of the total area. Overall, the Early-run product was found to be better than Late- and Final-run.
The Association between Difficulties with Speech Fluency and Language Skills in a National Age Cohort of Children with Down Syndrome
Authors: Næss Kari-Anne , Nygaard Egil , Hofslundsengen Hilde , Yaruss J.
Published: May 2021

The present study (a) addressed difficulties in speech fluency in children with Down syndrome and typically developing children at a similar non-verbal level and (b) examined the association between difficulties with speech fluency and language skills in children with Down syndrome. Data from a cross-sectional parent survey that included questions about children’s difficulties with speech fluency, as well as clinical tests from a national age cohort of 43 six-year-olds with Down syndrome and 57 young typically developing children, were collected. Fisher’s exact test, Student’s t-test, linear regression, and density ellipse scatter plots were used for analysis. There was a significantly higher occurrence of parent-reported difficulties with speech fluency in the children with Down syndrome. Higher language scores were significantly associated with a lower degree of difficulties; this association was strongest for vocabulary and phonological skills. Although difficulties with speech fluency were not reported for all children with Down syndrome, a substantially higher occurrence of such difficulties was reported compared to that for typically developing children. The significant association between difficulties with speech fluency and the level of language functioning suggests that speech fluency and language skills should be taken into consideration when planning treatment for children with Down syndrome.