bluuebunny/crossref_metadata_2025 huggingface dataset:
FNDC5 Causes Resistance to Sorafenib by Activating the PI3K/Akt/Nrf2 Pathway in Hepatocellular Carcinoma Cells
Authors: Liu Huayuan , Zhao Lei , Wang Mengya , Yang Kexin , Jin Zhipeng , Zhao Chengjian , Shi Guangjun
Published: March 2022

In this study, we aimed to reveal the resistance mechanism of hepatocellular carcinoma (HCC) cells to sorafenib by exploring the effect of FNDC5 on sorafenib-induced ferroptosis in HCC cells. We compared the expression level of FNDC5 between sorafenib-resistant and sorafenib-sensitive HCC cell lines and the level of ferroptosis between the groups after treatment with sorafenib. We knocked down FNDC5 in drug-resistant cell lines and overexpressed it in sorafenib-sensitive HCC cell lines to further demonstrate the role of FNDC5 in sorafenib-induced ferroptosis. Using PI3K inhibitors, we revealed the specific mechanism by which FNDC5 functions. In addition, we verified our findings obtained in in vitro experiments using a subcutaneous tumorigenic nude mouse model. The findings revealed that FNDC5 inhibits sorafenib-induced ferroptosis in HCC cells. In addition, FNDC5 activated the PI3K/Akt pathway, which in turn promoted the nuclear translocation of Nrf2 and increased the intracellular antioxidant response, thereby conferring resistance to ferroptosis. Our study provides novel insights for improving the efficacy of sorafenib.
Development and External Validation of a Novel Model for Predicting Postsurgical Recurrence and Overall Survival After Cytoreductive R0 Resection of Epithelial Ovarian Cancer
Authors: Li Qiaqia , Deng Yinghong , Wei Wei , Yang Fan , Lin An , Yao Desheng , Zhu Xiaofeng , Li Jundong
Published: March 2022

Purpose

Treatment of epithelial ovarian cancer is evolving towards personalization and precision, which require patient-specific estimates of overall survival (OS) and progression-free survival (PFS).

Patients and Methods

Medical records of 1173 patients who underwent debulking surgery in our center were comprehensively reviewed and randomly allocated into a derivation cohort of 879 patients and an internal validation cohort of 294 patients. Five hundred and seventy-seven patients from the other three cancer centers served as the external validation cohort. A novel nomogram model for PFS and OS was constructed based on independent predictors identified by multivariable Cox regression analysis. The predictive accuracy and discriminative ability of the model were measured using Harrell’s concordance index (C-index) and calibration curve.

Results

The C-index values were 0.82 (95% CI: 0.76–0.88) and 0.84 (95% CI: 0.78–0.90) for the PFS and OS models, respectively, substantially higher than those obtained with the FIGO staging system and most nomograms reported for use in epithelial ovarian cancer. The nomogram score could clearly classify the patients into subgroups with different risks of recurrence or postoperative mortality. The online versions of our nomograms are available at https://eocnomogram.shinyapps.io/eocpfs/ and https://eocnomogram.shinyapps.io/eocos/.

Conclusion

A externally validated nomogram predicting OS and PFS in patients after R0 reduction surgery was established using a propensity score matching model. This nomogram may be useful in estimating individual recurrence risk and guiding personalized surveillance programs for patients after surgery, and it could potentially aid clinical decision-making or stratification for clinical trials.
Gender Specificity and Local Socioeconomic Influence on Association of GHR fl/d3 Polymorphism With Growth and Metabolism in Children and Adolescents
Authors: Chen Xiaotian , Liu Chunlan , Yang Song , Yang Yaming , Chen Yanchun , Zhao Xianghai , Zhu Weiguang , Zhao Qihui , Ni Chuan , Huang Xiangyuan , Yan Weili , Shen Chong , Gu Harvest F.
Published: March 2022

Objective

Growth hormone receptor (GHR) mediates most GH biological actions. This study is aimed to evaluate whether GHR fl/d3 polymorphism contributes to the inter-individual variability of growth and metabolism in healthy children and adolescents.

Methods

A total of 4,730 students aged 6-16 years from Yixing and Suqian City in China were included in this cross-sectional study. Height and body mass index (BMI) were transformed into the form of z-score corresponding to age and gender. Logistic regression was used to evaluate the associations of GHR fl/d3 polymorphism with height, BMI, metabolic traits, and hypertension by estimating the odds ratios (ORs) and 95% confidence intervals (CIs).

Results

GHR d3 allele was inversely associated with overweight, total cholesterol (TC) and triglyceride (TG) levels (OR [95% CI] for overweight: 0.754 [0.593-0.959], P = 0.021; OR [95% CI] for TC: 0.744 [0.614-0.902], P = 0.003; OR [95% CI] for TG: 0.812 [0.654-0.998], P = 0.047). GHR d3 allele was associated with decreased odds of pre-hypertension in boys (OR [95% CI]: 0.791 [0.645-0.971], P = 0.025), but associated with increased odds of pre-hypertension and hypertension in girls (ORs [95% CIs]: 1.379 [1.106-1.719], P = 0.004; OR [95% CI]: 1.240 [1.013-1.519], P = 0.037). Interaction of GHR fl/d3 polymorphism with gender contributed to increased odds of pre-hypertension and hypertension (interactive ORs [95% CIs]: 1.735 [1.214-2.481], P = 0.003; OR [95% CI]: 1.509 [1.092-2.086], P = 0.013). Stratification analysis showed that the correlation tendencies of GHR fl/d3 polymorphism and BMI with age were different between two cities with discrepant economic development levels.

Conclusion

GHR fl/d3 polymorphism is associated with growth, metabolism, and hypertension in children and adolescents with the gender specificity, and the genetic effect of GHR fl/d3 may be modified by the local socioeconomic levels.
Prediction of Retinopathy of Prematurity Using the WINROP (Weight, IGF-1, Neonatal Retinopathy of Prematurity) Algorithm in a South African Population
Authors: Kesting Samantha Jane , Nakwa Firdose Lambey
Published: March 2022

Aim

This study aimed to assess the efficacy of the WINROP (Weight, IGF-1, Neonatal Retinopathy of Prematurity) screening algorithm in a South African population.

Methods

A retrospective record review included infants born between 1 January 2013 and 1 December 2014 who underwent ROP (retinopathy of prematurity) screening. Outcomes of ophthalmology examinations were compared to alarms triggered on WINROP after gestational age, date of birth, and weekly weights were entered. Sensitivity, specificity, positive predictive, and negative predictive values and mean time of alarm were calculated.

Results

Rates of ROP were 5.9% for all stages of ROP and 2.3% for severe ROP in the 220 infants included. Mean gestation age was 29.1 ± 1.3 weeks and mean birth weight 1,115.5 ± 201 g. WINROP triggered high-risk alarms in 70.5% of infants at a mean of 30.7 weeks of gestational age. Sensitivity for severe ROP was 100 and 76.9% for all stages of ROP. Specificity was low for both severe ROP and all stages of ROP at 30.2 and 30.0%, respectively.

Conclusion

Rates of ROP are low in this population. The high number of alarms with a low negative predictive value would reduce the number of screens by 29.5%. Alarms were triggered before scheduled screening, possibly helpful in planning discharges and follow-up visits.
Immune Dysregulation in Pediatric Common Variable Immunodeficiency: Implications for the Diagnostic Approach
Authors: Szczawińska-Popłonyk Aleksandra , Ta̧polska-Jóźwiak Katarzyna , Schwartzmann Eyal , Popłonyk Natalia
Published: March 2022

Infections and infectious complications are hallmarks of common variable immunodeficiency (CVID) and the leading cause of morbidity and mortality in affected patients at any age. However, the pediatric CVID is no longer perceived as a primary immunodeficiency associated solely with infectious manifestations; autoimmune, allergic, lymphoproliferative, and malignant disorders and organ-specific immunopathology also characterize the spectrum of non-infectious complications. In this study, we sought to determine the role of immune dysregulation and frequency of non-infectious sequelae in children affected with CVID. We also aimed at providing an insight into the pathogenesis of non-infectious complications and at delineating the diagnostic approach to pediatric CVID with immune dysregulation. An in-depth retrospective analysis of clinical manifestations and their correlations with selected immune parameters was performed in a group of 39 CVID children, followed by our pediatric immunology department. Whereas recurrent sinopulmonary infections were present in all (100%) of the children studied, an unexpectedly high rate of non-infectious disorders and immune dysregulation phenotypes were observed in as many as 32 (82.05%) patients, compared with infection-only phenotypes limited to 7 (17.95%) male patients. The most common inflammatory comorbidity was asthma, diagnosed in 21 (53.85%) patients. The second most frequent immune dysregulation group was autoimmune disorders, present in 18 (46.15%) of the children studied with a high rate of autoimmune thyroiditis in as many as 10 (25.64%) of the CVID-affected children. Lymphoproliferation was seen in 14 children (35.90%), and, among them, lymphadenopathy occurred in nine (23.08%) cases and granulomatous lymphocytic interstitial lung disease in seven (17.95%) cases. Finally, malignancies occurred in two female patients (5.13%), papillary thyroid cancer in the first one and T-cell lymphoblastic leukemia in the other one. The most prominent abnormalities in the B- and T-cell compartment contributing to complex immune deficiency and immune dysregulation phenotypes were seen in the autoimmunity group, showing significant reductions in the switched memory B cell, naive T helper cell, and regulatory T-cell subsets. Herein, we document the previously unreported high rate of immune dysregulation in pediatric CVID as a clinical and diagnostic challenge with the variability of defects in the humoral and cellular immune responses.
Impact of Adolescent Intermittent Ethanol Exposure on Social Investigation, Social Preference, and Neuronal Activation in cFos-LacZ Male and Female Rats
Authors: Towner Trevor T. , Applegate Devon T. , Varlinskaya Elena I. , Werner David F.
Published: March 2022

Adolescence is a sensitive developmental period during which alcohol use is often initiated and consumed in high quantities, often at binge or even high-intensity drinking levels. Our lab has repeatedly found that adolescent intermittent ethanol (AIE) exposure in rats results in long-lasting social impairments, specifically in males, however our knowledge of the neuronal underpinnings to this sex-specific effect of AIE is limited. The present study was designed to test whether social anxiety-like alterations in AIE-exposed males would be accompanied by alterations of neuronal activation across brain regions associated with social behavior, with AIE females demonstrating no social impairments and alterations in neuronal activation. Adolescent male and female cFos-LacZ transgenic rats on a Sprague-Dawley background were exposed to ethanol (4 g/kg, 25% v/v) or water via intragastric gavage every other day during postnatal days (P) 25–45 for a total of 11 exposures (n = 13 per group). Social behavior of adult rats was assessed on P70 using a modified social interaction test, and neuronal activation in brain regions implicated in social responding was assessed via β-galactosidase (β-gal) expression. We found that AIE exposure in males resulted in a significantly lower social preference coefficient relative to water-exposed controls, with no effect evident in females. Exposure-specific relationships between social behavior and neuronal activation were identified, with AIE eliminating correlations found in water controls related to social interaction, and eliciting negative correlations mainly in limbic regions in a sex-specific manner. AIE exposure in the absence of social testing was also found to differentially affect neural activity in the orbitofrontal cortex and central amygdala in males and females. These data suggest that AIE produces sex-specific social impairments that are potentially driven by differential neuronal activation states in regions important for social behavior, including the medial prefrontal and orbitofrontal cortices, nucleus accumbens, lateral septum, and central amygdala. Future studies should be focused on identification of specific neuronal phenotypes activated by interaction with a social partner in AIE-exposed subjects and their control counterparts.
A Betulinic Acid Derivative, BA5, Induces G0/G1 Cell Arrest, Apoptosis Like-Death, and Morphological Alterations in Leishmania sp
Authors: Magalhães Tatiana Barbosa dos Santos , Silva Dahara Keyse Carvalho , Teixeira Jessica da Silva , De Lima Juliana Dizaira Teles , Barbosa-Filho José Maria , Moreira Diogo Rodrigo Magalhães , Guimarães Elisalva Teixeira , Soares Milena Botelho Pereira
Published: March 2022

Leishmaniasis are endemic diseases caused by different species of intracellular parasites of the genus Leishmania. Due to the high toxicity and drug resistance of current antileishmanial drugs, it is necessary to identify new and more effective drugs. Previously, we investigated the immunomodulatory and anti-Trypanosoma cruzi action of BA5, a derivative of betulinic acid. In the present study, we investigated the in vitro activity of BA5 against different species of Leishmania and their action mechanism. BA5 exhibited low cytotoxicity against macrophages and inhibited the proliferation of promastigote forms of Leishmania amazonensis (IC50 = 4.5 ± 1.1 μM), Leishmania major (IC50 = 3.0 ± 0.8 μM), Leishmania braziliensis (IC50 = 0.9 ± 1.1 μM) and Leishmania infantum (IC50 = 0.15 ± 0.05 μM). Incubation with BA5 reduced the percentage of Leishmania amazonensis-infected macrophages and the number of intracellular parasites (IC50 = 4.1 ± 0.7 μM). To understand the mechanism of action underlying BA5 antileishmanial activity (incubation at IC50/2, IC50 or 2xIC50 values of the drug), we investigated ultrastructural changes by scanning electron microscopy and evaluated cell cycle, membrane mitochondrial potential, and cell death against promastigote forms of Leishmania amazonensis by flow cytometry. Promastigotes incubated with BA5 presented membrane blebbing, flagella damage, increased size, and body deformation. Flow cytometry analysis showed that parasite death is mainly caused by apoptosis-like death, arrested cell cycle in G0/G1 phase and did not alter the membrane mitochondrial potential of Leishmania amazonensis. Surprisingly, the combination of BA5 and amphotericin B, an assay used to determine the degree of drug interaction, revealed synergistic effects (CI = 0.15 ± 0.09) on promastigotes forms of Leishmania amazonensis. In conclusion, BA5 compound is an effective and selective antileishmanial agent.
The Botanical Drug PBI-05204, a Supercritical CO2 Extract of Nerium Oleander, Is Synergistic With Radiotherapy in Models of Human Glioblastoma
Authors: Colapietro Alessandro , Yang Peiying , Rossetti Alessandra , Mancini Andrea , Vitale Flora , Chakraborty Sharmistha , Martellucci Stefano , Marampon Francesco , Mattei Vincenzo , Gravina Giovanni Luca , Iorio Roberto , Newman Robert A. , Festuccia Claudio
Published: March 2022

Glioblastoma multiforme (GBM) is the most common as well as one of the most malignant types of brain cancer. Despite progress in development of novel therapies for the treatment of GBM, it remains largely incurable with a poor prognosis and a very low life expectancy. Recent studies have shown that oleandrin, a unique cardiac glycoside from Nerium oleander, as well as a defined extract (PBI-05204) that contains this molecule, inhibit growth of human glioblastoma, and modulate glioblastoma patient-derived stem cell-renewal properties. Here we demonstrate that PBI-05204 treatment leads to an increase in vitro in the sensitivity of GBM cells to radiation in which the main mechanisms are the transition from autophagy to apoptosis, enhanced DNA damage and reduced DNA repair after radiotherapy (RT) administration. The combination of PBI-05204 with RT was associated with reduced tumor progression evidenced by both subcutaneous as well as orthotopic implanted GBM tumors. Collectively, these results reveal that PBI-05204 enhances antitumor activity of RT in preclinical/murine models of human GBM. Given the fact that PBI-05204 has already been examined in Phase I and II clinical trials for cancer patients, its efficacy when combined with standard-of-care radiotherapy regimens in GBM should be explored.
C1QTNF6 is a Prognostic Biomarker and Related to Immune Infiltration and Drug Sensitivity: A Pan-Cancer Analysis
Authors: Liu Wei , Zhang Jian , Xie Tao , Huang Xiaoting , Wang Baiyao , Tian Yunhong , Yuan Yawei
Published: March 2022

Background: The discovery of reliable cancer biomarkers could tune a diagnosis and improve the way patients are treated. However, many cancers lack robust biomarkers. C1QTNF6 has been preliminarily elucidated for its role in some tumors. However, no pan-cancer analysis has been performed to comprehensively explore the value of C1QTNF6.

Methods: Data from the TCGA database, GTEx database stored in the USUC Xena were used for analyzing the profiles of C1QTNF6 expression in normal and tumor tissues in pan-cancer. Subsequently, the gene alteration rates of C1QTNF6 were acquired on the online web cBioportal. With the aid of the TCGA data, the association between C1QTNF6 mRNA expression and copy number alterations (CNA) and methylation was determined. Survival analyses of C1QTNF6 were carried out. Moreover, the tumor biological and immunological characteristics of C1QTNF6 were clarified in the forms of the correlation between C1QTNF6 expression and hallmark Pathway scores in MsigDB database, immune cell infiltration, immune-related genes. We conducted a GSEA of C1QTNF6 to illustrate its potential biological functions. In addition, GDSC2 data with 198 drugs were adopted to explore drug sensitivity with the change of C1QTNF6 expression.

Result:C1QTNF6 was overexpressed in many types of cancer, Survival analysis showed that C1QTNF6 independently served as a prognostic indicator for poor survival in many tumors. Besides, we also identified a positive correlation between C1QTNF6 and cancer hallmark pathway score, tumor microenvironment related pathways score (TMEp score), and immune characteristic. In terms of drug sensitivity analysis, we found higher expression level of C1QTNF6 predicts a high IC50 value for most of 198 drugs which predicts drug resistance.

Conclusions: Our study provides a new biological marker for pan-cancer, which is beneficial to the diagnosis and treatment of cancer, which bring a new therapeutic target for tumors.
Investigating the Implications of CFTR Exon Skipping Using a Cftr Exon 9 Deleted Mouse Model
Authors: Martinovich Kelly M. , Kicic Anthony , Stick Stephen M. , Johnsen Russell D. , Fletcher Sue , Wilton Steve D.
Published: March 2022

Introduction: Severity and disease progression in people with Cystic Fibrosis (CF) is typically dependent on their genotype. One potential therapeutic strategy for people with specific mutations is exon skipping with antisense oligonucleotides (AO). CFTR exon 9 is an in-frame exon and hence the exclusion of this exon would excise only 31 amino acids but not alter the reading frame of the remaining mRNA. Splice mutations 1209 + 1 G > C and 1209 + 2 T > G were documented to cause CFTR exon 9 skipping and these variants were reported to manifest as a milder CF disease, therefore exon 9 skipping could be beneficial for people with class I mutations that affect exon 9 such as p.Trp401X. While the impact of exon 9 skipping on gene expression and cellular pathways can be studied in cells in vitro, trace amount of full-length normal or mutated material could confound the evaluation. To overcome this limitation, the impact of CFTR exon 9 skipping on disease phenotype and severity is more effectively evaluated in a small animal model. It was hypothesised that antisense oligonucleotide-mediated skipping this particular exon could result in a “mild mouse CF phenotype”.

Methods:Cftr exon 9 deleted mice were generated using homologous recombination. Survival of homozygous (CftrΔ9/Δ9) and heterozygous (CftrΔ9/+) mice was compared to that of other CF mouse models, and lung and intestinal organ histology examined for any pathologies. Primary airway epithelial cells (pAECs) were harvested from CftrΔ9/Δ9 mice and cultured at the Air Liquid Interface for CFTR functional assessment using Ussing Chamber analysis.

Results: A CftrΔ9/Δ9 mouse model presented with intestinal obstructions, and at time of weaning (21 days). CftrΔ9/Δ9 mice had a survival rate of 83% that dropped to 38% by day 50. Histological sections of the small intestine from CftrΔ9/Δ9 mice showed more goblet cells and mucus accumulation than samples from the CftrΔ9/+ littermates. Airway epithelial cell cultures established from CftrΔ9/Δ9 mice were not responsive to forskolin stimulation.

Summary: The effect of Cftr exon 9 deletion on Cftr function was assessed and it was determined that the encoded Cftr isoform did not result in a milder “mouse CF disease phenotype,” suggesting that Cftr exon 9 is not dispensable, although further investigation in human CF pAECs would be required to confirm this observation.
Therapeutic Targeting of Endosome and Mitochondrial Reactive Oxygen Species Protects Mice From Influenza Virus Morbidity
Authors: To Eunice E. , Erlich Jonathan R. , Liong Felicia , Liong Stella , Luong Raymond , Oseghale Osezua , Miles Mark A. , Papagianis Paris C. , Quinn Kylie M. , Bozinovski Steven , Vlahos Ross , Brooks Robert D. , O’Leary John J. , Brooks Doug A. , Selemidis Stavros
Published: March 2022

There is an urgent need to develop effective therapeutic strategies including immunomodulators to combat influenza A virus (IAV) infection. Influenza A viruses increase ROS production, which suppress anti-viral responses and contribute to pathological inflammation and morbidity. Two major cellular sites of ROS production are endosomes via the NOX2-oxidase enzyme and the electron transport chain in mitochondria. Here we examined the effect of administration of Cgp91ds-TAT, an endosome-targeted NOX2 oxidase inhibitor, in combination with mitoTEMPO, a mitochondrial ROS scavenger and compared it to monotherapy treatment during an established IAV infection. Mice were infected with IAV (Hkx31 strain; 104PFU/mouse) and 24 h post infection were treated with Cgp91ds-TAT (0.2 mg/kg), mitoTEMPO (100 μg) or with a combination of these inhibitors [Cgp91ds-TAT (0.2 mg/kg)/mitoTEMPO (100 μg)] intranasally every day for up to 2 days post infection (pi). Mice were euthanized on Days 3 or 6 post infection for analyses of disease severity. A combination of Cgp91ds-TAT and mitoTEMPO treatment was more effective than the ROS inhibitors alone at reducing airway and neutrophilic inflammation, bodyweight loss, lung oedema and improved the lung pathology with a reduction in alveolitis following IAV infection. Dual ROS inhibition also caused a significant elevation in Type I IFN expression at the early phase of infection (day 3 pi), however, this response was suppressed at the later phase of infection (day 6 pi). Furthermore, combined treatment with Cgp91ds-TAT and mitoTEMPO resulted in an increase in IAV-specific CD8+ T cells in the lungs. In conclusion, this study demonstrates that the reduction of ROS production in two major subcellular sites, i.e. endosomes and mitochondria, by intranasal delivery of a combination of Cgp91ds-TAT and mitoTEMPO, suppresses the severity of influenza infection and highlights a novel immunomodulatory approach for IAV disease management.
Multidimensional Diffusion MRI Methods With Confined Subdomains
Authors: Boito Deneb , Yolcu Cem , Özarslan Evren
Published: March 2022

Diffusion Magnetic Resonance Imaging (dMRI) is an imaging technique with exquisite sensitivity to the microstructural properties of heterogeneous media. The conventionally adopted acquisition schemes involving single pulsed field gradients encode the random motion of water molecules into the NMR signal, however typically conflating the effects of different sources contributing to the water motion. Time-varying magnetic field gradients have recently been considered for disentangling such effects during the data encoding phase, opening to the possibility of adding specificity to the recovered information about the medium’s microstructure. Such data is typically represented via a diffusion tensor distribution (DTD) model, thus assuming the existence of several non-exchanging compartments in each of which diffusion is unrestricted. In this work, we consider a model that takes confinement into account and possesses a diffusion time-dependence closer to that of restricted diffusion, to replace the free diffusion assumption in multidimensional diffusion MRI methods. We first demonstrate how the confinement tensor model captures the relevant signal modulations impressed by water diffusing in both free and closed spaces, for data simulated with a clinically feasible protocol involving time-varying magnetic field gradients. Then, we provide the basis for incorporating this model into two multidimensional dMRI methods, and attempt to recover a confinement tensor distribution (CTD) on a human brain dataset.
The Case for, and Challenges of, Human Cardiac Tissue in Advancing Phosphoprotein Research
Authors: Huang Amanda W. , Janssen Paul M. L.
Published: March 2022

Cardiovascular disease (CVD) and stroke affect over 92 million Americans and account for nearly 1 out of 3 deaths in the US. The use of animal models in cardiovascular research has led to considerable advances in treatment and in our understanding of the pathophysiology of many CVDs. Still, animals may not fully recapitulate human disease states; species differences have long been postulated to be one of the main reasons for a failure of translation between animals and humans in drug discovery and development. Indeed, it has become increasingly clear over the past few decades that to answer certain biomedical questions, like the physiological mechanisms that go awry in many human CVDs, animal tissues may not always be the best option to use. While human cardiac tissue has long been used for laboratory research, published findings often contradict each other, leading to difficulties in interpretation. Current difficulties in utilizing human cardiac tissue include differences in acquisition time, varying tissue procurement protocols, and the struggle to define a human “control” sample. With the tremendous emphasis on translational research that continues to grow, research studies using human tissues are becoming more common. This mini review will discuss advantages, disadvantages, and considerations of using human cardiac tissue in the study of CVDs, paying specific attention to the study of phosphoproteins.
A Comprehensive Approach to Evaluate Durum Wheat–Faba Bean Mixed Crop Performance
Authors: Tavoletti Stefano , Merletti Ariele
Published: March 2022

Plant breeding for intercropping is lagging because most varieties currently available in the market are selected for sole cropping systems. The present study analyzed the response of durum wheat (12 varieties) and faba bean (3 varieties) in pure and mixed cropping. Field trials were conducted in 2019 and 2020. The performance of each variety in mixed and pure cropping was evaluated using both univariate and multivariate analyses of the grain yield and land equivalent ratio (LER). For durum wheat, grain protein content was also evaluated. Durum wheat varieties were characterized by good performance in both years, whereas faba bean varieties were more affected by the growing season, suggesting that much breeding effort is warranted to improve the latter as a pure and mixed crop. Moreover, the relative performance of all varieties was affected by their combination in mixed cropping, as evaluated based on the ratio (LERratio) between LER for wheat (LERw) and LER for faba bean (LERfb). To further evaluate the overall performance of wheat and faba bean in mixed cropping, total yield, LERtotal (LERw + LERfb), and ln(LERratio) were subjected to principal component and cluster analyses. The first principal component combined the total yield and LERtotal in a single index of the overall performance of each mixed crop combination. The second principal component, based on ln(LERratio), highlighted the relative performance of varieties in each mixed crop combination. The proposed multivariate approach can be applied in the breeding programs for intercropping to identify variety combinations based on crop performance and the relative importance of the proportion of cereal and legume grains in the total harvest.
Genomic Analysis and Delineation of the Tan Spot Susceptibility Locus Tsc1 in Wheat
Authors: Running Katherine L. D. , Momotaz Aliya , Kariyawasam Gayan K. , Zurn Jason D. , Acevedo Maricelis , Carter Arron H. , Liu Zhaohui , Faris Justin D.
Published: March 2022

The necrotrophic fungal pathogen Pyrenophora tritici-repentis (Ptr) causes the foliar disease tan spot in both bread wheat and durum wheat. Wheat lines carrying the tan spot susceptibility gene Tsc1 are sensitive to the Ptr-produced necrotrophic effector (NE) Ptr ToxC. A compatible interaction results in leaf chlorosis, reducing yield by decreasing the photosynthetic area of leaves. Developing genetically resistant cultivars will effectively reduce disease incidence. Toward that goal, the production of chlorosis in response to inoculation with Ptr ToxC-producing isolates was mapped in two low-resolution biparental populations derived from LMPG-6 × PI 626573 (LP) and Louise × Penawawa (LouPen). In total, 58 genetic markers were developed and mapped, delineating the Tsc1 candidate gene region to a 1.4 centiMorgan (cM) genetic interval spanning 184 kb on the short arm of chromosome 1A. A total of nine candidate genes were identified in the Chinese Spring reference genome, seven with protein domains characteristic of resistance genes. Mapping of the chlorotic phenotype, development of genetic markers, both for genetic mapping and marker-assisted selection (MAS), and the identification of Tsc1 candidate genes provide a foundation for map-based cloning of Tsc1.
Quantitative Trait Locus Analysis and Identification of Candidate Genes Affecting Seed Size and Shape in an Interspecific Backcross Inbred Line Population of Gossypium hirsutum × Gossypium barbadense
Authors: Wu Luyao , Jia Bing , Pei Wenfeng , Wang Li , Ma Jianjiang , Wu Man , Song Jikun , Yang Shuxian , Xin Yue , Huang Li , Feng Pan , Zhang Jinfa , Yu Jiwen
Published: March 2022

Seed size and shape are key agronomic traits affecting seedcotton yield and seed quality in cotton (Gossypium spp.). However, the genetic mechanisms that regulate the seed physical traits in cotton are largely unknown. In this study, an interspecific backcross inbred line (BIL) population of 250 BC1F7 lines, derived from the recurrent parent Upland CRI36 (Gossypium hirsutum) and Hai7124 (Gossypium barbadense), was used to investigate the genetic basis of cotton seed physical traits via quantitative trait locus (QTL) mapping and candidate gene identification. The BILs were tested in five environments, measuring eight seed size and shape-related traits, including 100-kernel weight, kernel length width and their ratio, kernel area, kernel girth, kernel diameter, and kernel roundness. Based on 7,709 single nucleotide polymorphic (SNP) markers, a total of 49 QTLs were detected and each explained 2.91–35.01% of the phenotypic variation, including nine stable QTLs mapped in at least three environments. Based on pathway enrichment, gene annotation, genome sequence, and expression analysis, five genes encoding starch synthase 4, transcription factor PIF7 and MYC4, ubiquitin-conjugating enzyme E27, and THO complex subunit 4A were identified as candidate genes that might be associated with seed size and shape. Our research provides valuable information to improve seed physical traits in cotton breeding.
Plant Salinity Stress Response and Nano-Enabled Plant Salt Tolerance
Authors: Li Zengqiang , Zhu Lan , Zhao Fameng , Li Jiaqi , Zhang Xin , Kong Xiangjun , Wu Honghong , Zhang Zhiyong
Published: March 2022

The area of salinized land is gradually expanding cross the globe. Salt stress seriously reduces the yield and quality of crops and endangers food supply to meet the demand of the increased population. The mechanisms underlying nano-enabled plant tolerance were discussed, including (1) maintaining ROS homeostasis, (2) improving plant’s ability to exclude Na+and to retain K+, (3) improving the production of nitric oxide, (4) increasing α-amylase activities to increase soluble sugar content, and (5) decreasing lipoxygenase activities to reduce membrane oxidative damage. The possible commonly employed mechanisms such as alleviating oxidative stress damage and maintaining ion homeostasis were highlighted. Further, the possible role of phytohormones and the molecular mechanisms in nano-enabled plant salt tolerance were discussed. Overall, this review paper aims to help the researchers from different field such as plant science and nanoscience to better understand possible new approaches to address salinity issues in agriculture.
The MIK2/SCOOP Signaling System Contributes to Arabidopsis Resistance Against Herbivory by Modulating Jasmonate and Indole Glucosinolate Biosynthesis
Authors: Stahl Elia , Fernandez Martin Angel , Glauser Gaétan , Guillou Marie-Charlotte , Aubourg Sébastien , Renou Jean-Pierre , Reymond Philippe
Published: March 2022

Initiation of plant immune signaling requires recognition of conserved molecular patterns from microbes and herbivores by plasma membrane-localized pattern recognition receptors. Additionally, plants produce and secrete numerous small peptide hormones, termed phytocytokines, which act as secondary danger signals to modulate immunity. In Arabidopsis, the Brassicae-specific SERINE RICH ENDOGENOUS PEPTIDE (SCOOP) family consists of 14 members that are perceived by the leucine-rich repeat receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR LIKE KINASE 2 (MIK2). Recognition of SCOOP peptides elicits generic early signaling responses but knowledge on how and if SCOOPs modulate specific downstream immune defenses is limited. We report here that depletion of MIK2 or the single PROSCOOP12 precursor results in decreased Arabidopsis resistance against the generalist herbivore Spodoptera littoralis but not the specialist Pieris brassicae. Increased performance of S. littoralis on mik2-1 and proscoop12 is accompanied by a diminished accumulation of jasmonic acid, jasmonate-isoleucine and indolic glucosinolates. Additionally, we show transcriptional activation of the PROSCOOP gene family in response to insect herbivory. Our data therefore indicate that perception of endogenous SCOOP peptides by MIK2 modulates the jasmonate pathway and thereby contributes to enhanced defense against a generalist herbivore.
Anthocyanin and Flavonol Glycoside Metabolic Pathways Underpin Floral Color Mimicry and Contrast in a Sexually Deceptive Orchid
Authors: Wong Darren C. J. , Perkins James , Peakall Rod
Published: March 2022

Sexually deceptive plants secure pollination by luring specific male insects as pollinators using a combination of olfactory, visual, and morphological mimicry. Flower color is a key component to this attraction, but its chemical and genetic basis remains poorly understood.Chiloglottis trapeziformisis a sexually deceptive orchid which has predominantly dull green-red flowers except for the central black callus projecting from the labellum lamina. The callus mimics the female of the pollinator and the stark color contrast between the black callus and dull green or red lamina is thought to enhance the visibility of the mimic. The goal of this study was to investigate the chemical composition and genetic regulation of temporal and spatial color patterns leading to visual mimicry, by integrating targeted metabolite profiling and transcriptomic analysis. Even at the very young bud stage, high levels of anthocyanins were detected in the dark callus, with peak accumulation by the mature bud stage. In contrast, anthocyanin levels in the lamina peaked as the buds opened and became reddish-green. Coordinated upregulation of multiple genes, including dihydroflavonol reductase and leucoanthocyanidin dioxygenase, and the downregulation of flavonol synthase genes (FLS) in the callus at the very young bud stage underpins the initial high anthocyanin levels. Conversely, within the lamina, upregulatedFLSgenes promote flavonol glycoside over anthocyanin production, with the downstream upregulation of flavonoid O-methyltransferase genes further contributing to the accumulation of methylated flavonol glycosides, whose levels peaked in the mature bud stage. Finally, the peak anthocyanin content of the reddish-green lamina of the open flower is underpinned by small increases in gene expression levels and/or differential upregulation in the lamina in select anthocyanin genes whileFLSpatterns showed little change. Differential expression of candidate genes involved in specific transport, vacuolar acidification, and photosynthetic pathways may also assist in maintaining the distinct callus and contrasting lamina color from the earliest bud stage through to the mature flower. Our findings highlight that flower color in this sexually deceptive orchid is achieved by complex tissue-specific coordinated regulation of genes and biochemical pathways across multiple developmental stages.
International Students’ Motivation to Study Abroad: An Empirical Study Based on Expectancy-Value Theory and Self-Determination Theory
Authors: Yue Yun , Lu Jinjin
Published: March 2022

Push-pull theory, consumer decision-making models and rational choice theory are commonly used to explain international student mobility (ISM). Despite their merits, the individual’s motivation to study abroad is ignored. Based on two motivation theories—expectancy-value theory (EVT) and self-determination theory (SDT), this study examines whether students’ intention to study abroad originates from the students themselves or compromises social pressure and how the external factors defined in push-pull theory work with these motivations to affect their decision-making. A quantitative study was conducted with a sample size of 736 international students in China. The findings show that the decision to study abroad is a highly subjective and intrinsically driven behavior in which realizing one’s self-worth or fulfilling one’s purpose of life plays the most significant role. Making a decision needs a “cost-benefits calculus,” but the utility value of study abroad was positioned behind attainment value and identified motivation. The heterogeneity of international students’ motivation was also differentiated by both their gender and their parents’ educational backgrounds.
Long-Term Posttraumatic Growth in Victims of Terrorism in Spain
Authors: Fausor Rocío , Sanz Jesús , Navarro-McCarthy Ashley , Gesteira Clara , Morán Noelia , Cobos-Redondo Beatriz , Altungy Pedro , Marqueses José M. S. , Sanz-García Ana , García-Vera María P.
Published: March 2022

Background

Scientific literature on posttraumatic growth (PTG) after terrorist attacks has primarily focused on persons who had not been directly exposed to terrorist attacks or persons who had been directly exposed to them, but who were assessed few months or years after the attacks.

Methods

We examined long-term PTG in 210 adults directly exposed to terrorist attacks in Spain a mean of 29.6 years after the attacks (range: 2–47 years). The participants had been injured by a terrorist attack (38.6%) or were first-degree relatives of people who had been killed or injured by a terrorist attack (41.4% and 20%, respectively). They completed diagnostic measures of emotional disorders and measures of PTSD and depression symptomatology, optimism, and PTG.

Results

Multiple regression analyses revealed gender differences (women reported higher levels of PTG than did men) and a positive linear relationship between PTG and cumulative trauma after the terrorist attack. Some PTG dimensions were significantly associated with PTSD symptomatology, these associations being linear, not curvilinear. However, PTG was not associated with depression symptomatology, diagnosis of emotional disorders, age, elapsed time since the attack, or optimism. In comparison with survivors assessed 18 years after the 1995 Oklahoma City bombing, Spanish victims of terrorism showed higher levels of appreciation of life, but lower levels of relating to others and spiritual change.

Conclusion

The findings underscore the influence of gender on PTG and provide support to the hypothesis that some emotional distress may be a necessary condition of PTG. Future studies on PTG after terrorist attacks should take into consideration the characteristics of the terrorist attack itself and the contexts of violence and threat in which it occurred. The political, social, and cultural characteristics of the community affected by it and the profile and characteristics of other traumatic events suffered after the attack should also be taken into account in further research.
The Associations Between Parental Burnout and Mental Health Symptoms Among Chinese Parents With Young Children During the COVID-19 Pandemic
Authors: Chen Minglong , Bai Yashuang , Fu Mingqi , Huang Ning , Ahmed Farooq , Shahid Muhammad , Wang Xiaohua , Liu Chengbin , Feng Xing Lin , Guo Jing
Published: March 2022

The Coronavirus Disease 2019 (COVID-19) pandemic has caused numerous unexpected changes for families and societies, which have likely contributed to higher amounts of stress for most parents. This study aimed to examine the relationship between burnout and mental health among parents during the COVID-19. Pandemic exposure and household factors (e.g., family structure, family function) were examined as moderators. An online cross-sectional survey recruiting 1,209 adults was conducted from April 21st to April 28th, 2020 during the COVID-19 lockdown in China. The multivariable linear regression analysis was employed to test the association between burnout, household factors, and mental health among parents. Findings suggested that for parents with a young child, poorer mental health was related to a higher level of burnout (β = 0.220, P < 0.001) and greater exposure to the pandemic. Mothers of a single and/or young child had considerably poorer mental health. Moreover, the relationship between mental health and burnout among parents was significantly moderated by epidemic exposure (β = 2.561, P < 0.001), family structure (number of children: β = −1.257, P < 0.001; first child age: β=-1.116, P < 0.001) and family function (β = −0.574, P < 0.05). This study indicated that burnout symptoms were significantly associated with worse mental health among parents in China. Besides, exposure to the pandemic, family structure, and family function was found to moderate the association between burnout and mental health among parents. Therefore, the present study stressed enhanced access to mental health resources and emotional supports for parents during a public crisis to reduce the deleterious effects of burnout.
Immune-Related lncRNAs Pairs to Construct a Novel Signature for Predicting Prognosis in Gastric Cancer
Authors: Bao Tianshang , Wang Zeyu , Xu Jia
Published: March 2022

Background

Immune-related long non-coding RNAs (irlncRNAs) appear valuable in predicting prognosis in patients with cancer. In this study, we used a fresh modeling algorithm to construct irlncRNAs signature and then assessed its predictive value for prognosis, tumor immune infiltration, and chemotherapy efficacy in gastric cancer (GC) patients.

Materials and Methods

The raw transcriptome data were extracted from the Cancer Genome Atlas (TCGA). Patients were randomly divided into the training and testing cohort. irlncRNAs were identified through co-expression analysis, after which differentially expressed irlncRNA (DEirlncRNA) pairs were identified. Next, we developed a model to distinguish between high- or low-risk groups in GC patients through univariate and LASSO regression analyses. A ROC curve was used to verify this model. After subgrouping patients according to the median risk score, we investigated the connection between the risk score of GC and clinicopathological characteristics. Functional enrichment analysis was also performed.

Results

We find that the results indicate that immune-related lncRNA signaling has essential value in predicting prognosis, and it may be potential to measure the Efficacy for immunotherapy. This feature may be a guide to the selection of GC immunotherapy.

Conclusion

Our data revealed that immune-related lncRNA signaling had essential value in predicting prognosis, and it may be potentially used to measure the efficacy for immunotherapy. This feature may also be used to guide the selection of GC immunotherapy.
Paracetamol (Acetaminophen) and its Effect on the Developing Mouse Brain
Authors: Philippot Gaëtan , Hosseini Kimia , Yakub Armine , Mhajar Yasser , Hamid Mariam , Buratovic Sonja , Fredriksson Robert
Published: March 2022

Paracetamol, or acetaminophen (AAP), is the most commonly used analgesic during pregnancy and early life. While therapeutic doses of AAP are considered harmless during these periods, recent findings in both humans and rodents suggest a link between developmental exposure to AAP and behavioral consequences later in life. The aim of this study is to evaluate the impact of neonatal exposure to clinically relevant doses of AAP on adult spontaneous behavior, habituation, memory, learning, and cognitive flexibility later in life using a mouse model. Markers of oxidative stress, axon outgrowth, and glutamatergic transmission were also investigated in the hippocampus during the first 24 h after exposure. In addition, potential long-term effects on synaptic density in the hippocampus have been investigated. In a home cage setting, mice neonatally exposed to AAP (30 + 30 mg/kg, 4 h apart) on postnatal day 10 displayed altered spontaneous behavior and changed habituation patterns later in life compared to controls. These mice also displayed reduced memory, learning and cognitive flexibility compared to control animals in the Morris water maze. An increase of markers for oxidative stress was observed in the hippocampus 6 h after AAP exposure. As AAP is the first choice treatment for pain and/or fever during pregnancy and early life, these results may be of great importance for risk assessment. Here we show that AAP can have persistent negative effects on brain development and suggest that AAP, despite the relatively low doses, is capable to induce acute oxidative stress in the hippocampus.
Genetic Effects of Indica Lineage Introgression on Amylopectin Chain Length Distribution in Japonica Milled Rice
Authors: Cui Juan , Zhao Xue , Yu Yuejiao , Zhang Wenxing , Kong Ximan , Sun Jian , Chen Wenfu
Published: March 2022

The fine structure of amylopectin affects rice quality; in particular, the amylopectin chain length distribution (ACLD) in milled rice differs between subspecies of Oryza sativa L. However, the correlation between ACLD and quality trait factors, and the genetic basis of ACLD phenotypic variation, are still unknown. Here, the correlations of ACLD with cooking and eating quality and with the rapid viscosity analysis (RVA) index were studied using chromosome segment substitution lines (CSSLs). Clear variations in ACLD were observed in introgression lines: introgression of indica segments of chromosome 3 and 7 increased the proportion of amylopectin Fa, and another segment of chromosome 3 reduced the proportion of amylopectin Fb2. A segment of chromosome 11 decreased the proportion of amylopectin Fa but increased that of Fb3. Correlation analysis with the RVA index further showed that the breakdown viscosity (BDV) was negatively correlated with the proportion of amylopectin Fb1, Fb2, and Fb3 chains, and positively correlated with Fa. Consistency viscosity (CSV) values were negatively correlated with the proportion of amylopectin Fb1, Fb2, and Fb3 chains. We thus clarified the quality trait factors determined by variation in ACLD, and provide key information for pyramiding inter-subspecific genetic superiority in molecular design breeding for rice quality.